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Chang XQ, Yue RS. Therapeutic Potential of Luteolin for Diabetes Mellitus and Its Complications. Chin J Integr Med 2025; 31:566-576. [PMID: 39302570 DOI: 10.1007/s11655-024-3917-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2023] [Indexed: 09/22/2024]
Abstract
The global prevalence of diabetes mellitus (DM) and its complications has been showing an upward trend in the past few decades, posing an increased economic burden to society and a serious threat to human life and health. Therefore, it is urgent to investigate the effectiveness of complementary and alternative therapies for DM and its complications. Luteolin is a kind of polyphenol flavonoid with widely existence in some natural resources, as a safe dietary supplement, it has been widely studied and reported in the treatment of DM and its complications. This review demonstrates the therapeutic potential of luteolin in DM and its complications, and elucidates the action mode of luteolin at the molecular level. It is characterized by anti-inflammatory, antioxidant, and neuroprotective effects. In detail, luteolin can not only improve endothelial function, insulin resistance and β-cell dysfunction, but also inhibit the activities of dipeptidyl peptidase-4 and α-glucosidase. However, due to the low water solubility and oral bioavailability of luteolin, its application in the medical field is limited. Therefore, great importance should be attached to the joint application of luteolin with current advanced science and technology. And more high-quality human clinical studies are needed to clarify the effects of luteolin on DM patients.
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Affiliation(s)
- Xiao-Qin Chang
- Endocrinology Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China
| | - Ren-Song Yue
- Endocrinology Department, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
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2
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Liang Q, Liu X, Xu X, Chen Z, Luo T, Su Y, Xie C. Molecular mechanisms and therapeutic perspectives of luteolin on diabetes and its complications. Eur J Pharmacol 2025; 1000:177691. [PMID: 40311831 DOI: 10.1016/j.ejphar.2025.177691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 04/13/2025] [Accepted: 04/29/2025] [Indexed: 05/03/2025]
Abstract
BACKGROUND Extensive preclinical studies have established luteolin, a flavonoid with potent antidiabetic activity, as a therapeutic candidate for preventing and managing various diabetic complications including cardiomyopathy, nephropathy, and osteopathy. This systematic review evaluates current evidence regarding luteolin's antidiabetic potential. AIM OF THE STUDY This study evaluates luteolin's efficacy in diabetes management through evidence synthesis, while critically assessing current research challenges and translational opportunities. METHODS A comprehensive literature search was conducted across Pubmed, Embase, Web of Science, and Google Scholar databases, encompassing articles published between 2000 and 2024. RESULTS Luteolin is a naturally occurring flavonoid that has strong antidiabetic properties. It regulates intestinal microenvironmental homeostasis, lipogenesis and catabolism, and the absorption of carbohydrates. It also modulates nine diabetic complications by reducing inflammation, oxidative stress, apoptosis, and autophagy. Luteolin's potential nutritional and physiological benefits notwithstanding, attention must be directed immediately to its bioavailability, innovative formulations, safety assessment, synergistic effects, and optimal dosage and time for supplementation. In particular, clinical studies are needed to validate efficacy and safety and provide a reliable scientific basis. CONCLUSION Luteolin may act as a pleiotropic molecule targeting multiple signaling cascades to exert antidiabetic bioactivity.
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Affiliation(s)
- Qingzhi Liang
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, China
| | - Xiaoqin Liu
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, China
| | - Xin Xu
- Department of Emergency, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, China
| | - Zhengtao Chen
- Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, 330006, China
| | - Ting Luo
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, China
| | - Yi Su
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, China
| | - Chunguang Xie
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, 610072, China; Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610072, China.
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Sabarathinam S, Jayaraman A, Venkatachalapathy R. Gut microbiome-derived metabolites and their impact on gene regulatory networks in gestational diabetes. J Steroid Biochem Mol Biol 2025; 247:106674. [PMID: 39793933 DOI: 10.1016/j.jsbmb.2025.106674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 01/07/2025] [Accepted: 01/07/2025] [Indexed: 01/13/2025]
Abstract
This study explored the therapeutic potential of gut microbiota metabolites in managing Gestational Diabetes Mellitus (GDM). Using network pharmacology, molecular docking, and dynamics simulations, we identified key targets and pathways involved in GDM. We screened 135 gut-derived metabolites, with 8 meeting drug-likeness and pharmacokinetic criteria. Analysis revealed significant overlap with GDM-related targets, including AKT1, IL6, TNF, and STAT3. Functional enrichment analysis highlighted the AGE-RAGE signaling and inflammatory pathways as crucial in GDM pathogenesis. Molecular docking and dynamics simulations showed strong binding affinities and stable interactions between two metabolites, luteolin and naringenin chalcone, and the target protein AKT1. These findings suggest that gut microbiota-derived metabolites, particularly luteolin and naringenin chalcone, may effectively modulate key pathways in GDM, offering promising avenues for novel treatment strategies.
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Affiliation(s)
- Sarvesh Sabarathinam
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, Tamil Nadu 602105, India.
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Li X, Xie E, Sun S, Shen J, Ding Y, Wang J, Peng X, Zheng R, Farag MA, Xiao J. Flavonoids for gastrointestinal tract local and associated systemic effects: A review of clinical trials and future perspectives. J Adv Res 2025:S2090-1232(25)00033-5. [PMID: 39798849 DOI: 10.1016/j.jare.2025.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 01/06/2025] [Accepted: 01/06/2025] [Indexed: 01/15/2025] Open
Abstract
BACKGROUND Flavonoids are naturally occurring dietary phytochemicals with significant antioxidant effects aside from several health benefits. People often consume them in combination with other food components. Compiling data establishes a link between bioactive flavonoids and prevention of several diseases in animal models, including cardiovascular diseases, diabetes, gut dysbiosis, and metabolic dysfunction-associated steatotic liver disease (MASLD). However, numerous clinical studies have demonstrated the ineffectiveness of flavonoids contradicting rodent models, thereby challenging the validity of using flavonoids as dietary supplements. AIM OF REVIEW This review provides a clinical perspective to emphasize the effective roles of dietary flavonoids as well as to summarize their specific mechanisms in animals briefly. KEY SCIENTIFIC CONCEPTS OF REVIEW First, this review offers an in-depth elucidation of the metabolic processes of flavonoids within human, encompassing the small, large intestine, and the liver. Furthermore, the review provides a comprehensive overview of the various functions of flavonoids in the gastrointestinal tract, including hindering the breakdown and assimilation of macronutrients, such as polysaccharides and lipids, regulating gut hormone secretion as well as inhibition of mineral iron absorption. In the large intestine, an unabsorbed major portion of flavonoids interact with the gut flora leading to their biotransformation. Once absorbed and circulated in the bloodstream, bioactive flavonoids or their metabolites exert numerous beneficial systemic effects. Lastly, we examine the protective effects of flavonoids in several metabolic disorders, including endothelial dysfunction, MASLD, cardiovascular disease, obesity, hyperlipidemia, and insulin resistance. In conclusion, this review outlines the safety and future prospects of flavonoids in the field of health, especially in the prevention of metabolic syndrome (MetS).
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Affiliation(s)
- Xiaopeng Li
- Center of Nutrition and Food Sciences Hunan Agricultural Products Processing Institute Hunan Academy of Agricultural Sciences Changsha China.
| | - Enjun Xie
- School of Public Health Zhejiang University School of Medicine Hangzhou China
| | - Shumin Sun
- School of Public Health Zhejiang University School of Medicine Hangzhou China
| | - Jie Shen
- School of Public Health Zhejiang University School of Medicine Hangzhou China
| | - Yujin Ding
- National Clinical Research Center for Metabolic Diseases Metabolic Syndrome Research Center Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University Changsha China
| | - Jiaqi Wang
- Ausnutria Dairy Co., Ltd., Changsha 410200 China
| | - Xiaoyu Peng
- Ausnutria Dairy Co., Ltd., Changsha 410200 China
| | - Ruting Zheng
- Ausnutria Dairy Co., Ltd., Changsha 410200 China
| | - Mohamed A Farag
- Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo 11562 Egypt
| | - Jianbo Xiao
- Universidade de Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Instituto de Agroecoloxía e Alimentación (IAA) - CITEXVI 36310 Vigo, Spain; Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Isabel Torres 21 39011 Santander, Spain.
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Fikry H, Saleh LA, Sadek DR, Alkhalek HAA. The possible protective effect of luteolin on cardiovascular and hepatic changes in metabolic syndrome rat model. Cell Tissue Res 2025; 399:27-60. [PMID: 39514020 DOI: 10.1007/s00441-024-03927-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 10/21/2024] [Indexed: 11/16/2024]
Abstract
The metabolic syndrome, or MetS, is currently a global health concern. The anti-inflammatory, anti-proliferative, and antioxidant properties of luteolin are some of its advantageous pharmacological characteristics. This research was designed to establish a MetS rat model and investigate the possible protective effect of luteolin on cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. Forty adult male albino rats were split into four groups: a negative control group, a group treated with luteolin, a group induced MetS (fed 20% fructose), and a group treated with luteolin (fed 20% fructose and given luteolin). Following the experiment after 8 weeks, biochemical, histological (light and electron), and immunohistochemistry analyses were performed on liver and heart tissues. Serum levels of cTnI, CK-MB, and LDH were significantly elevated in response to the cardiovascular effect of MetS. Furthermore, compared to the negative control group, the MetS group showed a marked increase in lipid peroxidation in the cardiac and hepatic tissues, as evidenced by elevated levels of MDA and a decline in the antioxidant defense system, as demonstrated by lower activities of GSH and SOD. The fatty liver-induced group exhibited histological alterations, including disrupted hepatic architecture, dilated and congested central veins, blood sinusoids, and portal veins. In addition to nuclear structural alterations, most hepatocytes displayed varying degrees of cytoplasmic vacuolation, mitochondrial alterations, and endoplasmic reticulum dilatation. These alterations were linked to inflammatory cellular infiltrations, collagen fiber deposition, active hepatic stellate cells, and scattered hypertrophied Kupffer cells, as demonstrated by electron microscopy and validated by immunohistochemical analysis. It is interesting to note that eosinophils were seen between the liver cells and in dilated blood sinusoids. Moreover, the biochemical (hepatic and cardiac) and histological (liver) changes were significantly less severe in luteolin-treated rat on a high-fructose diet. These results suggested that luteolin protects against a type of metabolic syndrome that is produced experimentally.
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Affiliation(s)
- Heba Fikry
- Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Khalifa El-Maamon St, Abbasiya Sq., Cairo, Egypt.
| | - Lobna A Saleh
- Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Khalifa El-Maamon St, Abbasiya Sq., Cairo, Egypt
| | - Doaa Ramadan Sadek
- Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Khalifa El-Maamon St, Abbasiya Sq., Cairo, Egypt
| | - Hadwa Ali Abd Alkhalek
- Department of Histology and Cell Biology, Faculty of Medicine, Ain Shams University, Khalifa El-Maamon St, Abbasiya Sq., Cairo, Egypt
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Zhang Y, Luo C, Huang P, Cheng Y, Ma Y, Gao J, Ding H. Luteolin alleviates muscle atrophy, mitochondrial dysfunction and abnormal FNDC5 expression in high fat diet-induced obese rats and palmitic acid-treated C2C12 myotubes. J Nutr Biochem 2025; 135:109780. [PMID: 39395694 DOI: 10.1016/j.jnutbio.2024.109780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 09/22/2024] [Accepted: 10/07/2024] [Indexed: 10/14/2024]
Abstract
Obesity is associated with a series of skeletal muscle impairments and dysfunctions, which are characterized by metabolic disturbances and muscle atrophy. Luteolin is a phenolic phytochemical with broad pharmacological activities. The present study aimed to evaluate the protective effects of Luteolin on muscle function and explore the potential mechanisms in high-fat diet (HFD)-induced obese rats and palmitic acid (PA)-treated C2C12 myotubes. Male Sprague-Dawley (SD) rats were fed with a control diet or HFD and orally administrated 0.5% sodium carboxymethyl cellulose (vehicle) or Luteolin (25, 50, and 100 mg/kg, respectively) for 12 weeks. The results showed that Luteolin ameliorated HFD-induced body weight gain, glucose intolerance and hyperlipidemia. Luteolin also alleviated muscle atrophy, decreased ectopic lipid deposition and prompted muscle-fiber-type conversion in the skeletal muscle. Meanwhile, we observed an evident improvement in mitochondrial quality control and respiratory capacity, accompanied by reduced oxidative stress. Mechanistic studies indicated that AMPK/SIRT1/PGC-1α signaling pathway plays a key role in the protective effects of Luteolin on skeletal muscle in the obese states, which was further verified by using specific inhibitors of AMPK and SIRT1. Moreover, the mRNA expression levels of markers in brown adipocyte formation were significantly up-regulated post Luteolin supplementation in different adipose depots. Taken together, these results revealed that Luteolin supplementation might be a promising strategy to prevent obesity-induced loss of mass and biological dysfunctions of skeletal muscle.
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Affiliation(s)
- Yiyuan Zhang
- Department of Pharmaceutical Science, Wuhan University, Wuhan 430000, China
| | - Chunyun Luo
- Department of Pharmaceutical Science, Wuhan University, Wuhan 430000, China
| | - Puxin Huang
- Department of Pharmaceutical Science, Wuhan University, Wuhan 430000, China
| | - Yahong Cheng
- Department of Pharmaceutical Science, Wuhan University, Wuhan 430000, China
| | - Yufang Ma
- Department of Pharmaceutical Science, Wuhan University, Wuhan 430000, China
| | - Jiefang Gao
- Department of Pharmaceutical Science, Wuhan University, Wuhan 430000, China
| | - Hong Ding
- Department of Pharmaceutical Science, Wuhan University, Wuhan 430000, China.
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Fukuda T, Kawakami K, Toyoda M, Hayashi C, Sanui T, Uchiumi T. Luteolin, chemical feature and potential use for oral disease. CURRENT ORAL HEALTH REPORTS 2024; 11:290-296. [DOI: 10.1007/s40496-024-00389-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 08/13/2024] [Indexed: 01/05/2025]
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Najafi N, Barangi S, Moosavi Z, Aghaee-Bakhtiari SH, Mehri S, Karimi G. Melatonin Attenuates Arsenic-Induced Neurotoxicity in Rats Through the Regulation of miR-34a/miR-144 in Sirt1/Nrf2 Pathway. Biol Trace Elem Res 2024; 202:3163-3179. [PMID: 37853305 DOI: 10.1007/s12011-023-03897-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 09/29/2023] [Indexed: 10/20/2023]
Abstract
Arsenic (As) exposure is known to cause several neurological disorders through various molecular mechanisms such as oxidative stress, apoptosis, and autophagy. In the current study, we assessed the effect of melatonin (Mel) on As-induced neurotoxicity. Thirty male Wistar rat were treated daily for 28 consecutive days. As (15 mg/kg, gavage) and Mel (10 and 20 mg/kg, i.p.) were administered to rats. Morris water maze test was done to evaluate learning and memory impairment in training days and probe trial. Oxidative stress markers including MDA and GSH levels, SOD activity, and HO-1 levels were measured. Besides, the levels of apoptosis (caspase 3, Bax/Bcl2 ratio) and autophagy markers (Sirt1, Beclin-1, and LC3 II/I ratio) as well as the expression of miR-144 and miR-34a in cortex tissue were determined. As exposure disturbed learning and memory in animals and Mel alleviated these effects. Also, Mel recovered cortex pathological damages and oxidative stress induced by As. Furthermore, As increased the levels of apoptosis and autophagy proteins in cortex, while Mel (20 mg/kg) decreased apoptosis and autophagy. Also, Mel increased the expression of miR-144 and miR-34a which inhibited by As. In conclusion, Mel administration attenuated As-induced neurotoxicity through anti-oxidative, anti-apoptotic, and anti-autophagy mechanisms, which may be recommended as a therapeutic target for neurological disorders.
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Affiliation(s)
- Nahid Najafi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Samira Barangi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Moosavi
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Seyed Hamid Aghaee-Bakhtiari
- Bioinformatics Research Group, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Soghra Mehri
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Gholamreza Karimi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
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Sun S, Zhang R, Chen Y, Xu Y, Li X, Liu C, Chen G, Wei X. E4bp4-Cyp3a11 axis in high-fat diet-induced obese mice with weight fluctuation. Nutr Metab (Lond) 2024; 21:30. [PMID: 38802929 PMCID: PMC11131204 DOI: 10.1186/s12986-024-00803-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 05/01/2024] [Indexed: 05/29/2024] Open
Abstract
OBJECTIVE Weight regain after weight loss is a challenge in obesity management. The metabolic changes and underlying mechanisms in obese people with weight fluctuation remain to be elucidated. In the present study, we aimed to profile the features and clinical significance of liver transcriptome in obese mice with weight regain after weight loss. METHODS The male C57BL/6J mice were fed with standard chow diet or high-fat diet (HFD). After 9 weeks, the HFD-induced obese mice were randomly divided into weight gain (WG), weight loss (WL) and weight regain (WR) group. After 10 weeks of dietary intervention, body weight, fasting blood glucose (FBG), intraperitoneal glucose tolerance, triglycerides (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C) were measured. Morphological structure and lipid droplet accumulation in the liver were observed by H&E staining and oil red O staining, respectively. The liver transcriptome was detected by RNA sequencing. Protein expressions of liver cytochrome P450 3a11 (Cyp3a11) and E4 promoter-binding protein 4 (E4bp4) were determined by Western blot. RESULTS After 10 weeks of dietary intervention, the body weight, FBG, glucose area under the curve, T-CHO and LDL-C in WL group were significantly lower than those in WG group (P < 0.05). At 4 weeks of HFD re-feeding, the mice in WR group presented body weight and T-CHO significantly lower than those in WG group, whereas higher than those in WL group (P < 0.05). Hepatic vacuolar degeneration and lipid droplet accumulation in the liver were significantly alleviated in WL group and WR group, compared to those in WG group. The liver transcriptome associated with lipid metabolism was significantly altered during weight fluctuation in obese mice. Compared with those in WG group, Cyp3a11 in the liver was significantly upregulated, and E4bp4 was significantly downregulated in WL and WR groups. CONCLUSION Obese mice experience weight regain after weight loss by HFD re-feeding, but their glucose and lipid metabolism disorders are milder than those induced by the persistence of obesity. Downregulated E4bp4 and upregulated Cyp3a11 are detected in obese mice after weight loss, suggesting that the E4bp4-Cyp3a11 axis may involved in metabolic mechanisms underlying weight regulation.
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Affiliation(s)
- Shuoshuo Sun
- Department of Endocrinology, Affiliated Hospital of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China
- The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People's Republic of China
| | - Ruixiang Zhang
- Department of Endocrinology, Affiliated Hospital of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China
| | - Yu Chen
- Department of Endocrinology, Affiliated Hospital of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China
| | - Yijiao Xu
- Department of Endocrinology, Affiliated Hospital of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China
| | - Xingjia Li
- Department of Endocrinology, Affiliated Hospital of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China
| | - Chao Liu
- Department of Endocrinology, Affiliated Hospital of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China
| | - Guofang Chen
- Department of Endocrinology, Affiliated Hospital of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.
- Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People's Republic of China.
| | - Xiao Wei
- Department of Endocrinology, Affiliated Hospital of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.
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Wang Y, Luo M, Che L, Wu Q, Li J, Ma Y, Wang J, Liu C. Enhanced detection of ligand-PPARγ binding based on surface plasmon resonance through complexation with SRC1- or NCOR2-related polypeptide. Int J Biol Macromol 2024; 268:131865. [PMID: 38670200 DOI: 10.1016/j.ijbiomac.2024.131865] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Revised: 03/12/2024] [Accepted: 04/23/2024] [Indexed: 04/28/2024]
Abstract
A previous study reported the use of a biosensing technique based on surface plasmon resonance (SPR) for the ligand binding detection of peroxisome proliferator activator receptor gamma (PPARγ). This detection was designed based on the structural properties of PPARγ. Because of cross-linked protein inactivation and the low molecular weight of conventional ligands, direct ligand binding detection based on SPR has low stability and repeatability. In this study, we report an indirect response methodology based on SPR technology in which anti-His CM5 chip binds fresh PPARγ every cycle, resulting in more stable detection. We developed a remarkable improvement in ligand-protein binding detectability in vitro by introducing two coregulator-related polypeptides into this system. In parallel, a systematic indirect response methodology can reflect the interaction relationship between ligands and proteins to some extent by detecting the changes in SA-SRC1 and GST-NCOR2 binding to PPARγ. Rosiglitazone, a PPARγ agonist with strong affinity, is a potent insulin-sensitizing agent. Some ligands may be competitively exerted at the same sites of PPARγ (binding rosiglitazone). We demonstrated using indirect response methodology that selective PPARγ modulator (SPPARM) candidates of PPARγ can be found by competing for the binding of the rosiglitazone site on PPARγ, although they may have no effect on polypeptides and PPARγ binding.
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Affiliation(s)
- Yiting Wang
- Experimental Research Center of China Academy of Chinese Medical Sciences, Beijing, China
| | - Mingzhu Luo
- Experimental Research Center of China Academy of Chinese Medical Sciences, Beijing, China
| | - Luyang Che
- Department of Vascular and Endovascular Surgery, People's Liberation Army General Hospital Hainan Hospital, Sanya, Hainan Province, China
| | - Qixin Wu
- Experimental Research Center of China Academy of Chinese Medical Sciences, Beijing, China
| | - Jingzhe Li
- Experimental Research Center of China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanyan Ma
- Experimental Research Center of China Academy of Chinese Medical Sciences, Beijing, China
| | - Jingyi Wang
- Experimental Research Center of China Academy of Chinese Medical Sciences, Beijing, China
| | - Changzhen Liu
- Experimental Research Center of China Academy of Chinese Medical Sciences, Beijing, China.
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Shin J, Lee Y, Ju SH, Jung YJ, Sim D, Lee SJ. Unveiling the Potential of Natural Compounds: A Comprehensive Review on Adipose Thermogenesis Modulation. Int J Mol Sci 2024; 25:4915. [PMID: 38732127 PMCID: PMC11084502 DOI: 10.3390/ijms25094915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 04/19/2024] [Accepted: 04/23/2024] [Indexed: 05/13/2024] Open
Abstract
The process of adipocyte browning has recently emerged as a novel therapeutic target for combating obesity and obesity-related diseases. Non-shivering thermogenesis is the process of biological heat production in mammals and is primarily mediated via brown adipose tissue (BAT). The recruitment and activation of BAT can be induced through chemical drugs and nutrients, with subsequent beneficial health effects through the utilization of carbohydrates and fats to generate heat to maintain body temperature. However, since potent drugs may show adverse side effects, nutritional or natural substances could be safe and effective as potential adipocyte browning agents. This review aims to provide an extensive overview of the natural food compounds that have been shown to activate brown adipocytes in humans, animals, and in cultured cells. In addition, some key genetic and molecular targets and the mechanisms of action of these natural compounds reported to have therapeutic potential to combat obesity are discussed.
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Affiliation(s)
- Jaeeun Shin
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Yeonho Lee
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Seong Hun Ju
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Young Jae Jung
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Daehyeon Sim
- Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea; (J.S.); (Y.L.); (S.H.J.); (Y.J.J.); (D.S.)
| | - Sung-Joon Lee
- Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul 02855, Republic of Korea
- Interdisciplinary Program in Precision Public Health, BK21 Four Institute of Precision Public Health, Korea University, Seoul 02846, Republic of Korea
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Park YJ, Seo DW, Gil TY, Kim HJ, Jin JS, Cha YY, An HJ. Sipyimigwanjung-tang, a traditional herbal medication, alleviates weight gain in a high-fat diet-induced obese mice model. Heliyon 2024; 10:e27463. [PMID: 38495187 PMCID: PMC10943437 DOI: 10.1016/j.heliyon.2024.e27463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 02/27/2024] [Accepted: 02/29/2024] [Indexed: 03/19/2024] Open
Abstract
Obesity leads to the development of metabolic syndrome and comorbidities. Overweight and obesity continue to be a relentless global issue. Sipyimigwanjung-tang (SGT), a traditional herbal medication, was first mentioned in Dongui Sasang Shinpyun and has been used to treat edema, meteorism, and jaundice, which are common findings associated with obesity. The main physiological feature of obesity is expanded adipose tissue, which causes several impairments in liver metabolism. Therefore, this study aimed to investigate the anti-obesity effects of SGT in the epididymal white adipose tissue (eWAT) and livers of high-fat diet (HFD)-induced obese mice. SGT significantly blocked HFD-induced weight gain in C57BL/6N mice. In addition, SGT effectively reduced the increased weight and adipocyte size in eWAT of HFD-induced obese C57BL/6 N mice. Moreover, SGT significantly decreased the elevated gene expression of Peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein α, and Sterol regulatory element-binding protein 1 in the eWAT of HFD-induced obese mice. Furthermore, SGT significantly decreased lipid accumulation in the livers of HFD-induced obese mice and differentiated 3T3-L1 adipocytes. Hence, the present study provides substantial evidence that SGT has potential therapeutic effects on obesity.
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Affiliation(s)
- Yea-Jin Park
- Department of Rehabilitative Medicine of Korean Medicine and Neuropsychiatry, College of Korean Medicine, Sangji University, Wonju, Gangwon-do, 26339, Republic of Korea
- Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Dong-Wook Seo
- Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Tae-Young Gil
- Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Hyo-Jung Kim
- Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
| | - Jong-Sik Jin
- Department of Oriental Medicine Resources, Jeonbuk National University, Iksan, 54596, Republic of Korea
| | - Yun-Yeop Cha
- Department of Rehabilitative Medicine of Korean Medicine and Neuropsychiatry, College of Korean Medicine, Sangji University, Wonju, Gangwon-do, 26339, Republic of Korea
| | - Hyo-Jin An
- Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 02447, Republic of Korea
- Department of Integrated Drug Development and Natural Products, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea
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13
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Laouani A, Nasrallah H, Sassi A, Ferdousi F, Kalai FZ, Hasni Y, Isoda H, Saguem S. Antiobesity and Hypolipidemic Potential of Nitraria retusa Extract in Overweight/Obese Women: A Randomized, Double-Blind, Placebo-Controlled Pilot Study. Nutrients 2024; 16:317. [PMID: 38276555 PMCID: PMC10818277 DOI: 10.3390/nu16020317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Revised: 01/12/2024] [Accepted: 01/17/2024] [Indexed: 01/27/2024] Open
Abstract
This study aimed to assess the efficacy of Nitraria retusa extract (NRE) in reducing weight, body mass index (BMI), body fat composition (BF), and anthropometric parameters among overweight/obese women, comparing the results with those of a placebo group. Overweight/obese individuals participated in a 12-week, double-blind, randomized, placebo-controlled trial. Body weight, BMI, body composition, and anthropometric parameters were assessed. Additionally, lipid profile and safety evaluation parameters were evaluated. Compared to the placebo group, the NRE group exhibited a mean weight loss difference of 2.27 kg (p < 0.001) at the trial's conclusion. Interestingly, the most significant weight reduction, amounting to 3.34 kg ± 0.93, was observed in younger participants with a BMI > 30.0. Similarly, BMI and BF% significantly decreased in the NRE group, contrary to the placebo group (p = 0.008 and p = 0.005, respectively). The percentage of body water (BW) (p = 0.006) as well as the ratio of LBM/BF (p = 0.039) showed a significant increase after the NRE intervention compared to the placebo. After age adjustment, all variables, except LBM/BF, retained statistical significance. Additionally, all anthropometric parameters were significantly reduced only in the NRE group. Most importantly, a significant reduction in Triglyceride (TG) levels in the NRE group was revealed, in contrast to the placebo group (p = 0.011), and the significance was still observed after age adjustment (p = 0.016). No side effects or adverse changes in kidney and liver function tests were observed in both groups. In conclusion, NRE demonstrated potent antiobesity effects, suggesting that NRE supplementation may represent an effective alternative for treating obesity compared to antiobesity synthetic drugs.
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Affiliation(s)
- Aicha Laouani
- Laboratory of Metabolic Biophysics and Applied Pharmacology, Faculty of Medicine, University of Sousse, Sousse 4002, Tunisia; (A.L.); (H.N.); (A.S.)
- USCR Analytical Platform UHPLC-MS & Research in Medicine and Biology, Faculty of Medicine, University of Sousse, Sousse 4023, Tunisia
| | - Hana Nasrallah
- Laboratory of Metabolic Biophysics and Applied Pharmacology, Faculty of Medicine, University of Sousse, Sousse 4002, Tunisia; (A.L.); (H.N.); (A.S.)
- USCR Analytical Platform UHPLC-MS & Research in Medicine and Biology, Faculty of Medicine, University of Sousse, Sousse 4023, Tunisia
| | - Awatef Sassi
- Laboratory of Metabolic Biophysics and Applied Pharmacology, Faculty of Medicine, University of Sousse, Sousse 4002, Tunisia; (A.L.); (H.N.); (A.S.)
- USCR Analytical Platform UHPLC-MS & Research in Medicine and Biology, Faculty of Medicine, University of Sousse, Sousse 4023, Tunisia
| | - Farhana Ferdousi
- Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan;
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8572, Japan;
| | - Feten Zar Kalai
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8572, Japan;
- Japan Laboratory of Aromatic and Medicinal Plants, Center of Biotechnology, Technopark of Borj Cedria, BP 901, Hammam-Lif, Tunis 2050, Tunisia
| | - Yosra Hasni
- Endocrinology-Diabetology Department, Farhat Hached Hospital, Sousse 4003, Tunisia;
| | - Hiroko Isoda
- Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba 305-8572, Japan;
- Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba 305-8572, Japan;
- Open Innovation Laboratory for Food and Medicinal Resource Engineering (FoodMed-OIL), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8577, Japan
| | - Saad Saguem
- Laboratory of Metabolic Biophysics and Applied Pharmacology, Faculty of Medicine, University of Sousse, Sousse 4002, Tunisia; (A.L.); (H.N.); (A.S.)
- USCR Analytical Platform UHPLC-MS & Research in Medicine and Biology, Faculty of Medicine, University of Sousse, Sousse 4023, Tunisia
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Wang T, Wang YY, Shi MY, Liu L. Mechanisms of action of natural products on type 2 diabetes. World J Diabetes 2023; 14:1603-1620. [DOI: 10.4239/wjd.v14.i11.1603] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/14/2023] [Accepted: 10/23/2023] [Indexed: 11/14/2023] Open
Abstract
Over the past several decades, type 2 diabetes mellitus (T2DM) has been considered a global public health concern. Currently, various therapeutic modalities are available for T2DM management, including dietary modifications, moderate exercise, and use of hypoglycemic agents and lipid-lowering medications. Although the curative effect of most drugs on T2DM is significant, they also exert some adverse side effects. Biologically active substances found in natural medicines are important for T2DM treatment. Several recent studies have reported that active ingredients derived from traditional medicines or foods exert a therapeutic effect on T2DM. This review compiled important articles regarding the therapeutic effects of natural products and their active ingredients on islet β cell function, adipose tissue inflammation, and insulin resistance. Additionally, this review provided an in-depth understanding of the multiple regulatory effects on different targets and signaling pathways of natural medicines in the treatment of T2DM as well as a theoretical basis for clinical effective application.
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Affiliation(s)
- Tao Wang
- Clinical Molecular Immunology Center, Yangtze University, Jingzhou 434023, Hubei Province, China
| | - Yang-Yang Wang
- Clinical Molecular Immunology Center, Yangtze University, Jingzhou 434023, Hubei Province, China
| | - Meng-Yue Shi
- Clinical Molecular Immunology Center, Yangtze University, Jingzhou 434023, Hubei Province, China
| | - Lian Liu
- Department of Pharmacology, Yangtze University, Jingzhou 434023, Hubei Province, China
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15
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Kim HJ, Jung DW, Williams DR. Age Is Just a Number: Progress and Obstacles in the Discovery of New Candidate Drugs for Sarcopenia. Cells 2023; 12:2608. [PMID: 37998343 PMCID: PMC10670210 DOI: 10.3390/cells12222608] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 11/08/2023] [Accepted: 11/09/2023] [Indexed: 11/25/2023] Open
Abstract
Sarcopenia is a disease characterized by the progressive loss of skeletal muscle mass and function that occurs with aging. The progression of sarcopenia is correlated with the onset of physical disability, the inability to live independently, and increased mortality. Due to global increases in lifespan and demographic aging in developed countries, sarcopenia has become a major socioeconomic burden. Clinical therapies for sarcopenia are based on physical therapy and nutritional support, although these may suffer from low adherence and variable outcomes. There are currently no clinically approved drugs for sarcopenia. Consequently, there is a large amount of pre-clinical research focusing on discovering new candidate drugs and novel targets. In this review, recent progress in this research will be discussed, along with the challenges that may preclude successful translational research in the clinic. The types of drugs examined include mitochondria-targeting compounds, anti-diabetes agents, small molecules that target non-coding RNAs, protein therapeutics, natural products, and repositioning candidates. In light of the large number of drugs and targets being reported, it can be envisioned that clinically approved pharmaceuticals to prevent the progression or even mitigate sarcopenia may be within reach.
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Affiliation(s)
| | - Da-Woon Jung
- New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea;
| | - Darren Reece Williams
- New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea;
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Yao C, Dai S, Wang C, Fu K, Wu R, Zhao X, Yao Y, Li Y. Luteolin as a potential hepatoprotective drug: Molecular mechanisms and treatment strategies. Biomed Pharmacother 2023; 167:115464. [PMID: 37713990 DOI: 10.1016/j.biopha.2023.115464] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 09/04/2023] [Accepted: 09/07/2023] [Indexed: 09/17/2023] Open
Abstract
Luteolin is a flavonoid widely present in various traditional Chinese medicines. In recent years, luteolin has received more attention due to its impressive liver protective effect, such as metabolic associated fatty liver disease, hepatic fibrosis and hepatoma. This article summarizes the pharmacological effects, pharmacokinetic characteristics, and toxicity of luteolin against liver diseases, and provides prospect. The results indicate that luteolin improves liver lesions through various mechanisms, including inhibiting inflammatory factors, reducing oxidative stress, regulating lipid balance, slowing down excessive aggregation of extracellular matrix, inducing apoptosis and autophagy of liver cancer cells. Pharmacokinetics research manifested that due to metabolic effects, the bioavailability of luteolin is relatively low. It is worth noting that appropriate modification, new delivery systems, and derivatives can enhance its bioavailability. Although many studies have shown that the toxicity of luteolin is minimal, strict toxicity experiments are still needed to evaluate its safety and promote its reasonable development. In addition, this study also discussed the clinical applications related to luteolin, indicating that it is a key component of commonly used liver protective drugs in clinical practice. In view of its excellent pharmacological effects, luteolin is expected to become a potential drug for the treatment of various liver diseases.
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Affiliation(s)
- Chenhao Yao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Shu Dai
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Cheng Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Ke Fu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Rui Wu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xingtao Zhao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yuxin Yao
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yunxia Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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17
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Shehnaz SI, Roy A, Vijayaraghavan R, Sivanesan S, Pazhanivel N. Modulation of PPAR-γ, SREBP-1c and inflammatory mediators by luteolin ameliorates β-cell dysfunction and renal damage in a rat model of type-2 diabetes mellitus. Mol Biol Rep 2023; 50:9129-9142. [PMID: 37749346 DOI: 10.1007/s11033-023-08804-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 09/06/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND Natural products have been recommended as a complementary therapy for type 2 diabetes mellitus (T2DM) due to constraints of safety and tolerability of existing anti-diabetic agents. Luteolin exhibits anti-diabetic and anti-inflammatory effects. Hence, the impact of luteolin on glucose homoeostasis and organ damage was investigated in high-fat diet (HFD) and streptozotocin (STZ) induced T2DM in rats. METHODS AND RESULTS Male Wistar rats were maintained on HFD (provided 55% energy as fat) for 10 days. Subsequently, a single dose of 40 mg/kg STZ was injected intraperitoneally on the 11th day. Seventy-two hours after STZ administration, diabetic rats with established hyperglycemia (fasting serum glucose > 200 mg/dL) were randomized into different groups having six rats each and orally administered either 0.5% hydroxy propyl cellulose or pioglitazone (10 mg/kg) or luteolin (50 mg/kg or 100 mg/kg) once daily for 28 days, while continuing HFD for respective groups. Luteolin significantly reduced hyperglycaemia, homoeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) levels, and improved hypoinsulinemia and HOMA of b-cell function (HOMA-B) in a dose-dependent manner. Increased TNF-α, IL-6 and NFκB levels in diabetic rats were significantly regulated. Additionally, luteolin significantly augmented PPAR-γ expression while attenuating sterol regulatory element binding protein-1c (SREBP-1c) expression. Histopathological scrutiny validated that luteolin effectively attenuated HFD-STZ-induced injury in pancreatic β-cells and kidneys to near normalcy. CONCLUSION Our study showed that luteolin ameliorated hyperglycemia and improved hypoinsulinemia, β-cell dysfunction, and renal impairment in HFD-STZ-induced diabetic rats by attenuating inflammation and dysregulated cytokine secretion through modulation of PPAR-γ, TNF-α, IL-6 and NF-kB expression and down-regulation of SREBP-1c.
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Affiliation(s)
- Syed Ilyas Shehnaz
- Department of Pharmacology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha Nagar, Thandalam, Chennai, Tamil Nadu, 602105, India.
| | - Anitha Roy
- Department of Pharmacology, Center for Transdisciplinary Research, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, 600077, India
| | - Rajagopalan Vijayaraghavan
- Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, 602105, India
| | - Senthilkumar Sivanesan
- Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, 602105, India
- Department of Biosciences, Institute of Biotechnology, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, 602105, India
| | - Natesan Pazhanivel
- Department of Veterinary Pathology, Madras Veterinary College, Chennai, Tamil Nadu, 600 007, India
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18
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Han Y, Choi JY, Kwon EY. Mentha canadensis attenuates adiposity and hepatic steatosis in high-fat diet-induced obese mice. Nutr Res Pract 2023; 17:870-882. [PMID: 37780219 PMCID: PMC10522806 DOI: 10.4162/nrp.2023.17.5.870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 08/07/2023] [Accepted: 08/14/2023] [Indexed: 10/03/2023] Open
Abstract
BACKGROUND/OBJECTIVES Obesity is a major risk factor for metabolic syndrome, a global public health problem. Mentha canadensis (MA), a traditional phytomedicine and dietary herb used for centuries, was the focus of this study to investigate its effects on obesity. MATERIALS/METHODS Thirty-five male C57BL/6J mice were randomly divided into 2 groups and fed either a normal diet (ND, n = 10) or a high-fat diet (HFD, n = 25) for 4 weeks to induce obesity. After the obesity induction period, the HFD-fed mice were randomly separated into 2 groups: one group continued to be fed HFD (n = 15, HFD group), while the other group was fed HFD with 1.5% (w/w) MA ethanol extract (n = 10, MA group) for 13 weeks. RESULTS The results showed that body and white adipose tissue (WAT) weights were significantly decreased in the MA-supplemented group compared to the HFD group. Additionally, MA supplementation enhanced energy expenditure, leading to improvements in plasma lipids, cytokines, hepatic steatosis, and fecal lipids. Furthermore, MA supplementation regulated lipid-metabolism-related enzyme activity and gene expression, thereby suppressing lipid accumulation in the WAT and liver. CONCLUSIONS These findings indicate that MA has the potential to improve diet-induced obesity and its associated complications, including adiposity, dyslipidemia, hepatic steatosis, and inflammation.
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Affiliation(s)
- Youngji Han
- Biological Clock-based Anti-aging Convergence Regional Leading Research Center of National Research Foundation of Korea, Korea University, Sejong 30019, Korea
| | - Ji-Young Choi
- Department of Food and Nutrition, Chosun University, Gwangju 61452, Korea
| | - Eun-Young Kwon
- Department of Food Science and Nutrition, Kyungpook National University, Daegu 41566, Korea
- Center for Food and Nutritional Genomics Research, Kyungpook National University, Daegu 41566, Korea
- Center for Beautiful Aging, Kyungpook National University, Daegu 41566, Korea
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19
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Cao Y, Fang X, Sun M, Zhang Y, Shan M, Lan X, Zhu D, Luo H. Preventive and therapeutic effects of natural products and herbal extracts on nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Phytother Res 2023; 37:3867-3897. [PMID: 37449926 DOI: 10.1002/ptr.7932] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 06/21/2023] [Accepted: 06/21/2023] [Indexed: 07/18/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common condition that is prevalent in patients who consume little or no alcohol, and is characterized by excessive fat accumulation in the liver. The disease is becoming increasingly common with the rapid economic development of countries. Long-term accumulation of excess fat can lead to NAFLD, which represents a global health problem with no effective therapeutic approach. NAFLD is a complex, multifaceted pathological process that has been the subject of extensive research over the past few decades. Herbal medicines have gained attention as potential therapeutic agents to prevent and treat NAFLD due to their high efficacy and low risk of side effects. Our overview is based on a PubMed and Web of Science database search as of Dec 22 with the keywords: NAFLD/NASH Natural products and NAFLD/NASH Herbal extract. In this review, we evaluate the use of herbal medicines in the treatment of NAFLD. These natural resources have the potential to inform innovative drug research and the development of treatments for NAFLD in the future.
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Affiliation(s)
- Yiming Cao
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Xiaoxue Fang
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Mingyang Sun
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Yegang Zhang
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Mengyao Shan
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Xintian Lan
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Difu Zhu
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
| | - Haoming Luo
- College of Pharmacy, Changchun University of Chinese Medicine, Changchun, China
- Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China
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20
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Shehnaz SI, Roy A, Vijayaraghavan R, Sivanesan S. Luteolin Mitigates Diabetic Dyslipidemia in Rats by Modulating ACAT-2, PPARα, SREBP-2 Proteins, and Oxidative Stress. Appl Biochem Biotechnol 2023; 195:4893-4914. [PMID: 37103741 DOI: 10.1007/s12010-023-04544-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/11/2023] [Indexed: 04/28/2023]
Abstract
Diabetic dyslipidemia is a crucial link between type-2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular diseases (ASCVD). Natural biologically active substances have been advocated as complementary remedies for ASCVD and T2DM. Luteolin, a flavonoid, exhibits antioxidant, hypolipidemic, and antiatherogenic effects. Hence, we aimed to determine influence of luteolin on lipid homeostasis and hepatic damage in rats with T2DM induced by high-fat-diet (HFD) and streptozotocin (STZ). After being fed HFD for 10 days, male Wistar rats received 40 mg/kg STZ intraperitoneal injection on 11th day. Seventy-two hours later, hyperglycemic rats (fasting glucose > 200 mg/dL) were randomized into groups, and oral hydroxy-propyl-cellulose, atorvastatin (5 mg/kg), or luteolin (50 mg/kg or 100 mg/kg) administered daily, while continuing HFD for 28 days. Luteolin significantly ameliorated dyslipidemia levels and concomitantly improved atherogenic index of plasma in a dose-dependent manner. Increased levels of malondialdehyde and diminished levels of superoxide dismutase, catalase, and glutathione in HFD-STZ-diabetic rats were significantly regulated by luteolin. Luteolin significantly intensified PPARα expression while decreasing expression of acyl-coenzyme A:cholesterol acyltransferase-2 (ACAT-2) and sterol regulatory element binding protein-2 (SREBP-2) proteins. Moreover, luteolin effectively alleviated hepatic impairment in HFD-STZ-diabetic rats to near-normal control levels. The findings of the present study expound mechanisms by which luteolin mitigated diabetic dyslipidemia and alleviated hepatic impairment in HFD-STZ-diabetic rats by amelioration of oxidative stress, modulation of PPARα expression, and downregulation of ACAT-2 and SREBP-2. In conclusion, our results imply that luteolin may be efficacious in management of dyslipidemia in T2DM, and future research may be essential to substantiate our findings.
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Affiliation(s)
- Syed Ilyas Shehnaz
- Department of Pharmacology, Saveetha Medical College & Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, 602105, Tamil Nadu, India.
| | - Anitha Roy
- Centre for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, 600077, Tamil Nadu, India
| | - Rajagopalan Vijayaraghavan
- Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Chennai, 602105, Tamil Nadu, India
| | - Senthilkumar Sivanesan
- Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Chennai, 602105, Tamil Nadu, India
- Department of Biosciences, Institute of Biotechnology, Saveetha Institute of Medical and Technical Sciences, Chennai, 602105, Tamil Nadu, India
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21
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V G, K N C, Ramkumar S, Halami PM, G SK. In vitro fermentation of glycosaminoglycans from mackerel fish waste and its role in modulating the antioxidant status and gut microbiota of high fat diet-fed C57BL/6 mice. Food Funct 2023; 14:7130-7145. [PMID: 37461843 DOI: 10.1039/d2fo03603g] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/01/2023]
Abstract
Bioactive polysaccharides such as glycosaminoglycans (GAGs) exhibit potential health benefits for several health complications including obesity. The gut microbiota plays a key role in regulating host metabolism, nutrition and immunity. The present work assessed the potential of extracted GAGs (e-GAGs) in maintaining the gut microbiota and ameliorating the effects of high fat diet in in vitro and in vivo models. The in vitro fermentability of e-GAGs extracted from mackerel fish waste was analyzed with Lactobacillus plantarum (LP) and Bifidobacterium bifidum (BB); e-GAGs at 0.5 and 1% proved their prebiotic nature up to 48 h. The pH value decreased from 6.23 to 3.32, the cell density increased from 1.70 to 2.32, the viable cell count increased from 8 to 12 log CFU mL-1, and short chain fatty acid (SCFA) production was ≈33, 31 and 36% for LP and ≈37, 29 and 34% for BB in terms of acetic acid, propionic acid and butyric acid, respectively. In vivo studies on high fat diet (HFD)-fed C57BL/6 mice with e-GAGs (380 and 760 mg kg-1 diet) showed ameliorated gut microbiome and tissue/plasma antioxidant enzyme activities, and also the e-GAG-fed group showed significantly (P < 0.05) decreased lipid peroxidation. Cecal microbial analysis showed the health-promoting effects of e-GAGs in reducing (P < 0.05) the obesity ratio of Firmicutes to Bacteroidetes (F/B) within the range (5.32 and 5.26) compared with HFD (6.23). Hence, e-GAGs can be a potential molecule for the treatment of obesity by restoring the redox status under oxidative stress and ameliorating the gut microbes that produce SCFAs which are known to have health beneficial effects.
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Affiliation(s)
- Geetha V
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru - 570 020, India.
- Department of Biosciences, Mangalore University, Mangalagangothri, Mangalore - 574199, Karnataka, India
| | - Chathur K N
- Department of Food Protectants & Infestation Control, CSIR-Central Food Technological Research Institute, Mysuru - 570 020, India
| | - Smita Ramkumar
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru - 570 020, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Prakash M Halami
- Department of Microbiology & Fermentation Technology, CSIR-Central Food Technological Research Institute, Mysuru - 570 020, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
| | - Suresh Kumar G
- Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysuru - 570 020, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India
- Department of Biosciences, Mangalore University, Mangalagangothri, Mangalore - 574199, Karnataka, India
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22
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Li L, Qin Y, Xin X, Wang S, Liu Z, Feng X. The great potential of flavonoids as candidate drugs for NAFLD. Biomed Pharmacother 2023; 164:114991. [PMID: 37302319 DOI: 10.1016/j.biopha.2023.114991] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 06/05/2023] [Accepted: 06/06/2023] [Indexed: 06/13/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of approximately 25 % and is associated with high morbidity and high mortality. NAFLD is a leading cause of cirrhosis and hepatocellular carcinoma. Its pathophysiology is complex and still poorly understood, and there are no drugs used in the clinic to specifically treat NAFLD. Its pathogenesis involves the accumulation of excess lipids in the liver, leading to lipid metabolism disorders and inflammation. Phytochemicals with the potential to prevent or treat excess lipid accumulation have recently received increasing attention, as they are potentially more suitable for long-term use than are traditional therapeutic compounds. In this review, we summarize the classification, biochemical properties, and biological functions of flavonoids and how they are used in the treatment of NAFLD. Highlighting the roles and pharmacological uses of these compounds will be of importance for enhancing the prevention and treatment of NAFLD.
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Affiliation(s)
- Liangge Li
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Yiming Qin
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Xijian Xin
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Shendong Wang
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Zhaojun Liu
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China
| | - Xiujing Feng
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China; School of Clinical and Basic Medical Sciences, Shandong First Medical University& Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China.
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23
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Tehrani SS, Goodarzi G, Panahi G, Zamani-Garmsiri F, Meshkani R. The combination of metformin with morin alleviates hepatic steatosis via modulating hepatic lipid metabolism, hepatic inflammation, brown adipose tissue thermogenesis, and white adipose tissue browning in high-fat diet-fed mice. Life Sci 2023; 323:121706. [PMID: 37075944 DOI: 10.1016/j.lfs.2023.121706] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/12/2023] [Accepted: 04/14/2023] [Indexed: 04/21/2023]
Abstract
AIM The valuable effects of metformin (MET) and morin (MOR) in the improvement of NAFLD have been proposed, nevertheless, their combination impacts were not investigated so far. We determined the therapeutic effects of combined MET and MOR treatment in high-fat diet (HFD)-induced Non-alcoholic fatty liver disease (NAFLD) mice. METHODS C57BL/6 mice were fed on an HFD for 15 weeks. Animals were allotted into various groups and supplemented with MET (230 mg/kg), MOR (100 mg/kg), and MET + MOR (230 mg/kg + 100 mg/kg). KEY FINDINGS MET in combination with MOR reduced body and liver weight in HFD-fed mice. A significant decrease in fasting blood glucose and improvement in glucose tolerance was observed in HFD mice treated with MET + MOR. Supplementation with MET + MOR led to a decline in hepatic triglyceride levels and this impact was associated with diminished expression of fatty-acid synthase (FAS) and elevated expression of carnitine palmitoyl transferase 1 (CPT1) and phospho-Acetyl-CoA Carboxylase (p-ACC). Moreover, MET combined with MOR alleviates hepatic inflammation through the polarization of macrophages to the M2 phenotype, decreasing the infiltration of macrophages and lowering the protein level of NF-kB. MET and MOR in combination reduce the size and weight of epididymal white adipose tissue (eWAT), and subcutaneous WAT (sWAT), whereas improves cold tolerance, BAT activity, and mitochondrial biogenesis. Combination therapy results in stimulating brown-like adipocyte (beige) formation in the sWAT of HFD mice. SIGNIFICANCE These results suggest that the combination of MET and MOR has a protective effect on hepatic steatosis, which may use as a candidate therapeutic for the improvement of NAFLD.
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Affiliation(s)
- Sadra Samavarchi Tehrani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Golnaz Goodarzi
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghodratollah Panahi
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Fahimeh Zamani-Garmsiri
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Meshkani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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24
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Samec M, Mazurakova A, Lucansky V, Koklesova L, Pecova R, Pec M, Golubnitschaja O, Al-Ishaq RK, Caprnda M, Gaspar L, Prosecky R, Gazdikova K, Adamek M, Büsselberg D, Kruzliak P, Kubatka P. Flavonoids attenuate cancer metabolism by modulating Lipid metabolism, amino acids, ketone bodies and redox state mediated by Nrf2. Eur J Pharmacol 2023; 949:175655. [PMID: 36921709 DOI: 10.1016/j.ejphar.2023.175655] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/20/2023] [Accepted: 03/09/2023] [Indexed: 03/14/2023]
Abstract
Metabolic reprogramming of cancer cells is a common hallmark of malignant transformation. The preference for aerobic glycolysis over oxidative phosphorylation in tumors is a well-studied phenomenon known as the Warburg effect. Importantly, metabolic transformation of cancer cells also involves alterations in signaling cascades contributing to lipid metabolism, amino acid flux and synthesis, and utilization of ketone bodies. Also, redox regulation interacts with metabolic reprogramming during malignant transformation. Flavonoids, widely distributed phytochemicals in plants, exert various beneficial effects on human health through modulating molecular cascades altered in the pathological cancer phenotype. Recent evidence has identified numerous flavonoids as modulators of critical components of cancer metabolism and associated pathways interacting with metabolic cascades such as redox balance. Flavonoids affect lipid metabolism by regulating fatty acid synthase, redox balance by modulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activity, or amino acid flux and synthesis by phosphoglycerate mutase 1. Here, we discuss recent preclinical evidence evaluating the impact of flavonoids on cancer metabolism, focusing on lipid and amino acid metabolic cascades, redox balance, and ketone bodies.
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Affiliation(s)
- Marek Samec
- Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Alena Mazurakova
- Department of Anatomy, Comenius University in Bratislava, Martin, Slovakia
| | - Vincent Lucansky
- Biomedical Centre Martin, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovakia
| | - Lenka Koklesova
- Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01, Martin, Slovakia
| | - Renata Pecova
- Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Martin Pec
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia
| | - Olga Golubnitschaja
- Predictive, Preventive, Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany
| | | | - Martin Caprnda
- 1(st) Department of Internal Medicine, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovakia
| | - Ludovit Gaspar
- Faculty of Health Sciences, University of Ss. Cyril and Methodius in Trnava, Trnava, Slovakia
| | - Robert Prosecky
- 2(nd) Department of Internal Medicine, Faculty of Medicine, Masaryk University and St. Anne´s University Hospital, Brno, Czech Republic; International Clinical Research Centre, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic
| | - Katarina Gazdikova
- Department of Nutrition, Faculty of Nursing and Professional Health Studies, Slovak Medical University, Bratislava, Slovakia; Department of General Medicine, Faculty of Medicine, Slovak Medical University, Bratislava, Slovakia.
| | - Mariusz Adamek
- Department of Thoracic Surgery, Medical University of Silesia, Katowice, Poland
| | | | - Peter Kruzliak
- 2(nd) Department of Surgery, Faculty of Medicine, Masaryk University and St. Anne´s University Hospital, Brno, Czech Republic.
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.
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25
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Chen LY, Cheng HL, Liao CK, Kuan YH, Liang TJ, Tseng TJ, Lin HC. Luteolin improves nephropathy in hyperglycemic rats through anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms. J Funct Foods 2023. [DOI: 10.1016/j.jff.2023.105461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/26/2023] Open
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26
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Kim JW, Shin SK, Kwon EY. Luteolin Protects Against Obese Sarcopenia in Mice with High-Fat Diet-Induced Obesity by Ameliorating Inflammation and Protein Degradation in Muscles. Mol Nutr Food Res 2023; 67:e2200729. [PMID: 36708177 DOI: 10.1002/mnfr.202200729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 01/04/2023] [Indexed: 01/29/2023]
Abstract
SCOPE Although sarcopenia is mainly caused by aging, sarcopenia due to obesity has become an emerging issue given the increase in obesity among people of various ages. There are studies on obesity or sarcopenia, our understanding of obesity-mediated sarcopenia is insufficient. Luteolin (LU) has exhibited antiobesity effects, but no studies have investigated the LU effects on antisarcopenia. This study therefore investigated the effects of LU on obese sarcopenia in mice with high-fat diet (HFD)-induced obesity. METHODS AND RESULTS To evaluate its inhibitory efficacy against obese sarcopenia, 5-week-old mice are fed an HFD supplemented with LU for 20 weeks. LU exerts suppressive effects on obesity, inflammation, and protein degradation in the HFD-fed obese mice. It also inhibits lipid infiltration into the muscle and decreases p38 activity and the mRNA expression of inflammatory factors, including TNF-α, Tlr2, Tlr4, MCP1, and MMP2, in the muscle. The suppression of muscle inflammation by LU leads to the inhibition of myostatin, FoxO, atrogin, and MuRF expression. These effects of LU affect inhibition of protein degradation and improvement of muscle function. CONCLUSION Here, it demonstrates that LU's antiobesity and antiinflammatory functionality affect inhibition of muscle protein degradation, and consequently, these interactions by LU exerts a protective effect against obese sarcopenia.
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Affiliation(s)
- Ji-Won Kim
- Department of Food Science and Nutrition, Kyungpook National University, 80, Daehak-ro, Buk-Ku, Daegu, 41566, Republic of Korea
- Center for Food and Nutritional Genomics Research, Kyungpook National University, 80, Daehak-ro, Buk-Ku, Daegu, 41566, Republic of Korea
| | - Su-Kyung Shin
- Department of Food Science and Nutrition, Kyungpook National University, 80, Daehak-ro, Buk-Ku, Daegu, 41566, Republic of Korea
- Center for Food and Nutritional Genomics Research, Kyungpook National University, 80, Daehak-ro, Buk-Ku, Daegu, 41566, Republic of Korea
| | - Eun-Young Kwon
- Department of Food Science and Nutrition, Kyungpook National University, 80, Daehak-ro, Buk-Ku, Daegu, 41566, Republic of Korea
- Center for Food and Nutritional Genomics Research, Kyungpook National University, 80, Daehak-ro, Buk-Ku, Daegu, 41566, Republic of Korea
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27
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Pan L, Yu Z, Liang X, Yao J, Fu Y, He X, Ren X, Chen J, Li X, Lu M, Lan T. Sodium cholate ameliorates nonalcoholic steatohepatitis by activation of FXR signaling. Hepatol Commun 2023; 7:e0039. [PMID: 36706173 PMCID: PMC9988322 DOI: 10.1097/hc9.0000000000000039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 11/25/2022] [Indexed: 01/29/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) has become a major cause of liver transplantation and liver-associated death. The gut-liver axis is a potential therapy for NASH. Sodium cholate (SC) is a choleretic drug whose main component is bile acids and has anti-inflammatory, antifibrotic, and hepatoprotective effects. This study aimed to investigate whether SC exerts anti-NASH effects by the gut-liver axis. Mice were fed with an high-fat and high-cholesterol (HFHC) diet for 20 weeks to induce NASH. Mice were daily intragastric administrated with SC since the 11th week after initiation of HFHC feeding. The toxic effects of SC on normal hepatocytes were determined by CCK8 assay. The lipid accumulation in hepatocytes was virtualized by Oil Red O staining. The mRNA levels of genes were determined by real-time quantitative PCR assay. SC alleviated hepatic injury, abnormal cholesterol synthesis, and hepatic steatosis and improved serum lipid profile in NASH mice. In addition, SC decreased HFHC-induced hepatic inflammatory cell infiltration and collagen deposition. The target protein-protein interaction network was established through Cytoscape software, and NR1H4 [farnesoid x receptor (FXR)] was identified as a potential target gene for SC treatment in NASH mice. SC-activated hepatic FXR and inhibited CYP7A1 expression to reduce the levels of bile acid. In addition, high-dose SC attenuated the abnormal expression of cancer markers in NASH mouse liver. Finally, SC significantly increased the expression of FXR and FGF15 in NASH mouse intestine. Taken together, SC ameliorates steatosis, inflammation, and fibrosis in NASH mice by activating hepatic and intestinal FXR signaling so as to suppress the levels of bile acid in NASH mouse liver and intestine.
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Affiliation(s)
- Linyu Pan
- Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Ze Yu
- Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xiaolin Liang
- Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Jiyou Yao
- Department of HBP Surgery II, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Yanfang Fu
- Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xu He
- Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xiaoling Ren
- Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Jiajia Chen
- Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
| | - Xuejuan Li
- Shenzhen Children’s Hospital of China Medical University, Shenzhen, Guangdong, China
| | - Minqiang Lu
- Department of HBP Surgery II, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China
| | - Tian Lan
- Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
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28
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Tognolli K, Silva V, Sousa-Filho CPB, Cardoso CAL, Gorjão R, Otton R. Green tea beneficial effects involve changes in the profile of immune cells in the adipose tissue of obese mice. Eur J Nutr 2023; 62:321-336. [PMID: 35994086 DOI: 10.1007/s00394-022-02963-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 07/08/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE During obesity, the adipose tissue is usually infiltrated by immune cells which are related to hallmarks of obesity such as systemic inflammation and insulin resistance (IR). Green tea (GT) has been widely studied for its anti-inflammatory actions, including the modulation in the proliferation and activity of immune cells, in addition to preventing cardiovascular and metabolic diseases. METHODS The aim of the present study was to analyze the population of immune cells present in the subcutaneous and epididymal white adipose tissue (WAT) of mice kept at thermoneutrality (TN) and fed with a high-fat diet (HFD) for 16 weeks, supplemented or not with GT extract (500 mg/kg/12 weeks). RESULTS The HFD in association with TN has induced chronic inflammation, and IR in parallel with changes in the profile of immune cells in the subcutaneous and epidydimal WAT, increasing pro-inflammatory cytokines release, inflammatory cells infiltration, and fibrotic aspects in WAT. On the other hand, GT prevented body weight gain, in addition to avoiding IR and inflammation, and the consequent tissue fibrosis, maintaining a lower concentration of cytokines and a profile of immune cells similar to the control mice, preventing the harmful modulations induced by both HFD and TN. CONCLUSIONS GT beneficial effects in WAT abrogated the deleterious effects triggered by HFD and TN, maintaining all immune cells and fibrotic markers at the same level as in lean mice. These results place WAT immune cells population as a potential target of GT action, also highlighting the positive effects of GT in obese mice housed at TN.
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Affiliation(s)
- Kaue Tognolli
- Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, Regente Feijó Avenue, 1295, Sao Paulo, SP, 03342-000, Brazil
| | - Victoria Silva
- Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, Regente Feijó Avenue, 1295, Sao Paulo, SP, 03342-000, Brazil
| | - Celso Pereira Batista Sousa-Filho
- Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, Regente Feijó Avenue, 1295, Sao Paulo, SP, 03342-000, Brazil
| | | | - Renata Gorjão
- Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, Regente Feijó Avenue, 1295, Sao Paulo, SP, 03342-000, Brazil
| | - Rosemari Otton
- Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, Regente Feijó Avenue, 1295, Sao Paulo, SP, 03342-000, Brazil.
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29
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Gu W, Wang R, Cai Z, Lin X, Zhang L, Chen R, Li R, Zhang W, Ji X, Shui G, Sun Q, Liu C. Hawthorn total flavonoids ameliorate ambient fine particulate matter-induced insulin resistance and metabolic abnormalities of lipids in mice. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2023; 249:114456. [PMID: 38321675 DOI: 10.1016/j.ecoenv.2022.114456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 12/16/2022] [Accepted: 12/18/2022] [Indexed: 02/08/2024]
Abstract
Recent studies have shown a strong correlation between ambient fine particulate matter (PM2.5) exposure and diabetes risk, including abnormal lipid accumulation and systemic insulin resistance (IR). Hawthorn total flavonoids (HF) are the main groups of active substances in Hawthorn, which showed anti-hyperlipidemic and anti-hyperglycemic effects. Therefore, we hypothesized that HF may attenuate PM2.5-induced IR and abnormal lipid accumulation. Female C57BL/6 N mice were randomly assigned to the filtered air exposure (FA) group, concentrated PM2.5 exposure (PM) group, PM2.5 exposure maintained on a low-dose HF diet (LHF) group, and PM2.5 exposure maintained on a high-dose HF diet (HHF) group for an 8-week PM2.5 exposure using a whole-body exposure device. Body glucose homeostasis, lipid profiles in the liver and serum, and enzymes responsible for hepatic lipid metabolism were measured. We found that exposure to PM2.5 impaired glucose tolerance and insulin sensitivity. In addition, triacylglycerol (TAG) in serum elevated, whereas hepatic TAG levels were decreased after PM2.5 exposure, accompanied by inhibited fatty acid uptake, lipogenesis, and lipolysis in the liver. HF administration, on the other hand, balanced the hepatic TAG levels by increasing fatty acid uptake and decreasing lipid export, leading to alleviated systemic IR and hyperlipidemia in PM2.5-exposed mice. Therefore, HF administration may be an effective strategy to protect against PM2.5-induced IR and metabolic abnormalities of lipids.
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Affiliation(s)
- Weijia Gu
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou, China
| | - Ruiqing Wang
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China
| | - Ziwei Cai
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China
| | - Xiujuan Lin
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China
| | - Lu Zhang
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou, China
| | - Rucheng Chen
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou, China
| | - Ran Li
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou, China
| | - Wenhui Zhang
- Department of Environmental and Occupational health, Hangzhou Center for Disease Control and Prevention, Hangzhou, Zhejiang, China
| | - Xuming Ji
- School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
| | - Guanghou Shui
- State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
| | - Qinghua Sun
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou, China.
| | - Cuiqing Liu
- School of Public Health, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang International Science and Technology Cooperation Base of Air Pollution and Health, Hangzhou, China.
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30
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Kim Y, Lee Y, Lee MN, Nah J, Yun N, Wu D, Pae M. Time-restricted feeding reduces monocyte production by controlling hematopoietic stem and progenitor cells in the bone marrow during obesity. Front Immunol 2022; 13:1054875. [PMID: 36569870 PMCID: PMC9771705 DOI: 10.3389/fimmu.2022.1054875] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 11/15/2022] [Indexed: 12/12/2022] Open
Abstract
Time-restricted feeding (TRF) has emerged as a promising dietary approach in improving metabolic parameters associated with obesity, but its effect on immune cells under obesogenic condition is poorly understood. We conducted this study to determine whether TRF exerts its therapeutic benefit over obesity-induced myeloid cell production by analyzing hematopoietic stem and progenitor cells in bone marrow (BM) and immune cell profile in circulation. Male C57BL/6 mice were fed a low-fat diet (LFD) or high-fat diet (HFD) ad libitum for 6 weeks and later a subgroup of HFD mice was switched to a daily 10 h-TRF schedule for another 6 weeks. Mice on HFD ad libitum for 12 weeks had prominent monocytosis and neutrophilia, associated with expansion of BM myeloid progenitors, such as multipotent progenitors, pre-granulocyte/macrophage progenitors, and granulocyte/macrophage progenitors. TRF intervention in overweight and obese mice diminished these changes to a level similar to those seen in mice fed LFD. While having no effect on BM progenitor cell proliferation, TRF reduced expression of Cebpa, a transcription factor required for myeloid differentiation. These results indicate that TRF intervention may help maintain immune cell homeostasis in BM and circulation during obesity, which may in part contribute to health benefits associated with TRF.
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Affiliation(s)
- Yelim Kim
- Department of Food and Nutrition, Chungbuk National University, Cheongju, Republic of Korea
| | - Youngyoon Lee
- Department of Food and Nutrition, Chungbuk National University, Cheongju, Republic of Korea
| | - Mi Nam Lee
- Department of Biological Sciences, Chonnam National University, Gwangju, Republic of Korea
| | - Jiyeon Nah
- Department of Food and Nutrition, Chungbuk National University, Cheongju, Republic of Korea
| | - Narae Yun
- Department of Food and Nutrition, Chungbuk National University, Cheongju, Republic of Korea
| | - Dayong Wu
- Nutritional Immunology Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, United States
| | - Munkyong Pae
- Department of Food and Nutrition, Chungbuk National University, Cheongju, Republic of Korea,*Correspondence: Munkyong Pae,
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31
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Li X, Geng-Ji JJ, Quan YY, Qi LM, Sun Q, Huang Q, Jiang HM, Sun ZJ, Liu HM, Xie X. Role of potential bioactive metabolites from traditional Chinese medicine for type 2 diabetes mellitus: An overview. Front Pharmacol 2022; 13:1023713. [PMID: 36479195 PMCID: PMC9719995 DOI: 10.3389/fphar.2022.1023713] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 11/07/2022] [Indexed: 11/14/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a metabolic disease with persistent hyperglycemia primarily caused by insulin resistance (IR). The number of diabetic patients globally has been rising over the past decades. Although significant progress has been made in treating diabetes mellitus (DM), existing clinical drugs for diabetes can no longer fully meet patients when they face complex and huge clinical treatment needs. As a traditional and effective medical system, traditional Chinese medicine (TCM) has a unique understanding of diabetes treatment and has developed many classic and practical prescriptions targeting DM. With modern medicine and pharmacy advancements, researchers have discovered that various bioactive metabolites isolated from TCM show therapeutic on DM. Compared with existing clinical drugs, these bioactive metabolites demonstrate promising prospects for treating DM due to their excellent biocompatibility and fewer adverse reactions. Accordingly, these valuable metabolites have attracted the interest of researchers worldwide. Despite the abundance of research works and specialized-topic reviews published over the past years, there is a lack of updated and systematic reviews concerning this fast-growing field. Therefore, in this review, we summarized the bioactive metabolites derived from TCM with the potential treatment of T2DM by searching several authoritative databases such as PubMed, Web of Science, Wiley Online Library, and Springer Link. For the convenience of readers, the content is divided into four parts according to the structural characteristics of these valuable compounds (flavonoids, terpenoids, alkaloids, and others). Meanwhile, the detailed mechanism and future directions of these promising compounds curing DM are also summarized in the related sections. We hope this review inspires increasingly valuable and significant research focusing on potential bioactive metabolites from TCM to treat DM in the future.
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Affiliation(s)
- Xiang Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, State Administration of Traditional Chinese Medicine Key Laboratory of Traditional Chinese Medicine Regimen and Health, School of Pharmacy and College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jia-Jia Geng-Ji
- State Key Laboratory of Southwestern Chinese Medicine Resources, State Administration of Traditional Chinese Medicine Key Laboratory of Traditional Chinese Medicine Regimen and Health, School of Pharmacy and College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yun-Yun Quan
- Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Academy of Chinese Medicine Sciences, Sichuan Institute for Translational Chinese Medicine, Chengdu, Sichuan, China
| | - Lu-Ming Qi
- State Key Laboratory of Southwestern Chinese Medicine Resources, State Administration of Traditional Chinese Medicine Key Laboratory of Traditional Chinese Medicine Regimen and Health, School of Pharmacy and College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiang Sun
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qun Huang
- Department of Ophthalmology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hai-Mei Jiang
- State Key Laboratory of Southwestern Chinese Medicine Resources, State Administration of Traditional Chinese Medicine Key Laboratory of Traditional Chinese Medicine Regimen and Health, School of Pharmacy and College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zi-Jian Sun
- Sichuan Ant Recommendation Biotechnology Co., Ltd., Chengdu, Sichuan, China
| | - Hong-Mei Liu
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xin Xie
- State Key Laboratory of Southwestern Chinese Medicine Resources, State Administration of Traditional Chinese Medicine Key Laboratory of Traditional Chinese Medicine Regimen and Health, School of Pharmacy and College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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Ahmed ES, Mohamed HE, Farrag MA. Luteolin loaded on zinc oxide nanoparticles ameliorates non-alcoholic fatty liver disease associated with insulin resistance in diabetic rats via regulation of PI3K/AKT/FoxO1 pathway. Int J Immunopathol Pharmacol 2022; 36:3946320221137435. [PMID: 36319192 PMCID: PMC9630902 DOI: 10.1177/03946320221137435] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
OBJECTIVE Non-alcoholic fatty liver disease (NAFLD) is a worldwide health problem with high prevalence and morbidity associated with obesity, insulin resistance, type 2 diabetes mellitus (T2DM), and dyslipidemia. Nano-formulation of luteolin with Zn oxide in the form of Lut/ZnO NPs may improve the anti-diabetic property of each alone and ameliorate the insulin resistance thus management of NAFLD. This study aimed to measure the efficiency of Lut/ZnO NPs against insulin resistance coupled with NAFLD and T2DM. METHODS A diabetic rat model with NAFLD was induced by a high-fat diet and streptozotocin (30 mg/kg I.P). Serum diabetogenic markers levels, lipid profile, and activity of liver enzymes were measured beside liver oxidative stress markers. Moreover, the hepatic expressions of PI3K/AKT/FoxO1/SERBP1c as well as heme oxygenase-1 were measured beside the histopathological examination. RESULTS Lut/ZnO NPs treatment effectively reduced hyperglycemia, hyperinsulinemia, and ameliorated insulin resistance. Additionally, Lut/ZnO NPs improved the hepatic functions, the antioxidant system, and reduced the oxidative stress markers. Furthermore, the lipid load in the liver, as well as the circulating TG and TC, was minified via the suppression of lipogenesis and gluconeogenesis. Moreover, Lut/ZnO NPs activated the PI3K/AKT signaling pathway, hence inactivating FoxO1, therefore enhancing the hepatic cells' insulin sensitivity. CONCLUSION Lut/ZnO NPs have a hepatoprotective effect and may relieve the progression of NAFLD by alleviating insulin resistance, ameliorating the antioxidant status, and regulating the insulin signal pathway.
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Affiliation(s)
- Esraa Sa Ahmed
- Radiation Biology Research, National Center for Radiation Research and Technology, 68892Egyptian Atomic Energy Authority, Cairo, Egypt
| | - Hebatallah E Mohamed
- Radiation Biology Research, National Center for Radiation Research and Technology, 68892Egyptian Atomic Energy Authority, Cairo, Egypt
| | - Mostafa A Farrag
- Radiation Biology Research, National Center for Radiation Research and Technology, 68892Egyptian Atomic Energy Authority, Cairo, Egypt
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Zhang S, Chai X, Hou G, Zhao F, Meng Q. Platycodon grandiflorum (Jacq.) A. DC.: A review of phytochemistry, pharmacology, toxicology and traditional use. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 106:154422. [PMID: 36087526 DOI: 10.1016/j.phymed.2022.154422] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 07/01/2022] [Accepted: 08/26/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND The traditional Chinese medicine Platycodon grandiflorum (Jacq.) A. DC. (PG, balloon flower) has medicinal and culinary value. It consists of a variety of chemical components including triterpenoid saponins, polysaccharides, flavonoids, polyphenols, polyethylene glycols, volatile oils and mineral components, which have medicinal and edible value. PURPOSE The ultimate goal of this review is to summarize the phytochemistry, pharmacological activities, safety and uses of PG in local and traditional medicine. METHODS A comprehensive search of published literature up to March 2022 was conducted using the PubMed, China Knowledge Network and Web of Science databases to identify original research related to PG, its active ingredients and pharmacological activities. RESULTS Triterpene saponins are the primary bioactive compounds of PG. To date, 76 triterpene saponin compounds have been isolated and identified from PG. In addition, there are other biological components, such as flavonoids, polyacetylene and phenolic acids. These extracts possess antitussive, immunostimulatory, anti-inflammatory, antioxidant, antitumor, antiobesity, antidepressant, and cardiovascular system activities. The mechanisms of expression of these pharmacological effects include inhibition of the expression of proteins such as MDM and p53, inhibition of the activation of enzymes, such as AKT, the secretion of inflammatory factors, such as IFN-γ, TNF-α, IL-2 and IL-1β, and activation of the AMPK pathway. CONCLUSION This review summarizes the chemical composition, pharmacological activities, molecular mechanism, toxicity and uses of PG in local and traditional medicine over the last 12 years. PG contains a wide range of chemical components, among which triterpene saponins, especially platycoside D (PD), play a strong role in pharmacological activity, representing a natural phytomedicine with low toxicity that has applications in food, animal feed and cosmetics. Therefore, PG has value for exploitation and is an excellent choice for treating various diseases.
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Affiliation(s)
- Shengnan Zhang
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China
| | - Xiaoyun Chai
- Department of Organic Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
| | - Guige Hou
- School of Pharmacy, Binzhou Medical University, Yantai 264003, China
| | - Fenglan Zhao
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China
| | - Qingguo Meng
- School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.
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Zhang Z, Wang J, Lin Y, Chen J, Liu J, Zhang X. Nutritional activities of luteolin in obesity and associated metabolic diseases: an eye on adipose tissues. Crit Rev Food Sci Nutr 2022; 64:4016-4030. [PMID: 36300856 DOI: 10.1080/10408398.2022.2138257] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Obesity is characterized by excessive body fat accumulation and is a high-risk factor for metabolic comorbidities, including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. In lean individuals, adipose tissue (AT) is not only an important regulatory organ for energy storage and metabolism, but also an indispensable immune and endocrine organ. The sustained energy imbalance induces adipocyte hypotrophy and hyperplasia as well as AT remodeling, accompanied by chronic low-grade inflammation and adipocytes dysfunction in AT, ultimately leading to systemic insulin resistance and ectopic lipid deposition. Luteolin is a natural flavonoid widely distributed in fruits and vegetables and possesses multifold biological activities, such as antioxidant, anticancer, and anti-inflammatory activities. Diet supplementation of this flavonoid has been reported to inhibit AT lipogenesis and inflammation as well as the ectopic lipid deposition, increase AT thermogenesis and systemic energy expenditure, and finally improve obesity and associated metabolic diseases. The purpose of this review is to reveal the nutritional activities of luteolin in obesity and its complications with emphasis on its action on AT energy metabolism, immunoregulation, and endocrine intervention.
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Affiliation(s)
- Zhixin Zhang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
| | - Jiahui Wang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
| | - Yan Lin
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
| | - Juan Chen
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
| | - Jian Liu
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
- Engineering Research Center of Bioprocess, Ministry of Education, Hefei University of Technology, Hefei, Anhui, China
| | - Xian Zhang
- School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, China
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Wang S, Du Q, Meng X, Zhang Y. Natural polyphenols: a potential prevention and treatment strategy for metabolic syndrome. Food Funct 2022; 13:9734-9753. [PMID: 36134531 DOI: 10.1039/d2fo01552h] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Metabolic syndrome (MS) is the term for a combination of hypertension, dyslipidemia, insulin resistance, and central obesity as factors leading to cardiovascular and metabolic disease. Epidemiological investigation has shown that polyphenol intake is negatively correlated with the incidence of MS. Natural polyphenols are widely found in cocoa beans, tea, vegetables, fruits, and some Chinese herbal medicines; they are a class of plant compounds containing a variety of phenolic structural units, which are potent antioxidants and anti-inflammatory agents in plants. Polyphenols are composed of flavonoids (such as flavanols, anthocyanidins, anthocyanins, isoflavones, etc.) and non-flavonoids (such as phenolic acids, stilbenes, and lignans). Modern pharmacological studies have proved that polyphenols can reduce blood pressure, improve lipid metabolism, lower blood glucose, and reduce body weight, thereby preventing and improving MS. Due to the unique characteristics and potential development and application value of polyphenols, this review summarizes some natural polyphenols that could treat MS, including their chemical properties, plant sources, and pharmacological action against MS, to provide a basis for the further study of polyphenols in MS.
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Affiliation(s)
- Shaohui Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Qinyun Du
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xianli Meng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Yi Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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Wang Y, Lin ZJ, Huang J, Chu MZ, Ding XL, Li WJ, Mao QY, Zhang B. An integrated study of Shenling Baizhu San against hyperuricemia: Efficacy evaluation, core target identification and active component discovery. JOURNAL OF ETHNOPHARMACOLOGY 2022; 295:115450. [PMID: 35688256 DOI: 10.1016/j.jep.2022.115450] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/20/2022] [Accepted: 06/06/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Shenling Baizhu San (SLBZ) is a famous Traditional Chinese Medicine (TCM) formula that strengthens the spleen for replenishing qi, removing dampness, and inducing diuresis to relieve diarrhea. Combining the TCM interpretation that dampness is a vital pathogenesis factor in hyperuricemia occurrence and development, SLBZ has excellent potential against hyperuricemia from the perspective of TCM theories. AIM OF THE STUDY This study aimed to investigate the efficacy of SLBZ against hyperuricemia and its possible mechanism with emphasis on the active components and the core targets. MATERIALS AND METHODS In the present study, we employed meta-analysis and a hyperuricemia quail model to evaluate the uric acid-lowering effect of SLBZ. Bodyweight, serum uric acid, and excreta uric acid levels in quails were assessed. Subsequently, we analyzed the potential active components and core targets of SLBZ against hyperuricemia by network pharmacology and calculated their interaction using molecular docking. Furthermore, the hyperuricemia rats treated with interfering agents of core targets were established to determine the central role of selected targets in hyperuricemia progression. Besides, we isolated and characterized the primary renal tubular epithelial cells of quails to verify the active components and core targets of SLBZ against hyperuricemia. Western blotting was used to observe the expression of core targets treated with active components under the stimulation of interfering agents. RESULTS Data from meta-analysis and animal experiments showed that SLBZ could work effectively against hyperuricemia. Hyperuricemia quails treated with SLBZ displayed significantly reduced serum uric acid levels accompanied by increased excretion of uric acid. According to network pharmacology and molecular docking results, 34 potential active components and the core target peroxisome proliferator-activated receptor gamma (PPARγ) for SLBZ against hyperuricemia were identified. The decreased serum uric acid levels in hyperuricemia rats treated with rosiglitazone, an agonist of PPARγ, confirms the essential role of PPARγ in the pathological process of hyperuricemia. Moreover, we first successfully isolated and characterized the primary renal tubular epithelial cells of quails and observed enhanced phosphorylation of PPARγ at Ser273 in cells handled with high-level uric acid. Whereas, the enhanced expression of p-PPARγ Ser273 could be down-regulated by luteolin and naringenin, two active components of SLBZ against hyperuricemia. CONCLUSION In summary, SLBZ is a promising anti-hyperuricemia agent, and luteolin and naringenin are the active components for SLBZ against hyperuricemia by down-regulating phosphorylation of PPARγ at Ser273.
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Affiliation(s)
- Yu Wang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Zhi-Jian Lin
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Jing Huang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Meng-Zhen Chu
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Xue-Li Ding
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Wen-Jing Li
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Qiu-Yue Mao
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Bing Zhang
- Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
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Ferro Y, Pujia R, Mazza E, Lascala L, Lodari O, Maurotti S, Pujia A, Montalcini T. A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease. Lab Invest 2022; 20:377. [PMID: 35986358 PMCID: PMC9392294 DOI: 10.1186/s12967-022-03579-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 08/07/2022] [Indexed: 11/10/2022]
Abstract
Abstract
Background
Currently, there is no approved medication for non-alcoholic fatty liver disease management. Pre-clinical and clinical studies showed that several bioactive molecules in plants or foods (i.e., curcumin complex, bergamot polyphenol fraction, artichoke leaf extract, black seed oil, concentrate fish oil, picroliv root, glutathione, S-adenosyl-l-methionine and other natural ingredients) have been associated with improved fatty liver disease. Starting from these evidences, our purpose was to evaluate the effects of a novel combination of abovementioned nutraceuticals as a treatment for adults with fatty liver disease.
Methods
A total of 140 participants with liver steatosis were enrolled in a randomized, double-blind, placebo controlled clinical trial. The intervention group received six softgel capsules daily of a nutraceutical (namely Livogen Plus®) containing a combination of natural bioactive components for 12 weeks. The control group received six softgel capsules daily of a placebo containing maltodextrin for 12 weeks. The primary outcome measure was the change in liver fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, transaminases, and cytokines were measured at baseline and after intervention.
Results
After adjustment for confounding variables (i.e., CAP score and triglyceride at baseline, and changes of serum γGT, and vegetable and animal proteins, cholesterol intake at the follow-up), we found a greater CAP score reduction in the nutraceutical group rather than placebo (− 34 ± 5 dB/m vs. − 20 ± 5 dB/m, respectively; p = 0.045). The CAP score reduction (%) was even greater in those with aged 60 or less, low baseline HDL-C, AST reduction as well as in men.
Conclusion
Our results showed that a new combination of bioactive molecules as nutraceutical was safe and effective in reducing liver fat content over 12 weeks in individuals with hepatic steatosis.
Trial registration ISRCTN, ISRCTN70887063. Registered 03 August 2021—retrospectively registered, https://doi.org/10.1186/ISRCTN70887063
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Kim JW, Yang YM, Kwon EY, Choi JY. Novel Plant Extract Ameliorates Metabolic Disorder through Activation of Brown Adipose Tissue in High-Fat Diet-Induced Obese Mice. Int J Mol Sci 2022; 23:ijms23169295. [PMID: 36012561 PMCID: PMC9409404 DOI: 10.3390/ijms23169295] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/11/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Abstract
Obesity is characterized by excessive body fat accumulation due to unbalanced energy intake and expenditure. Potential therapeutic targets for anti-obesity include the inhibition of white adipose tissue (WAT) hypertrophy and hyperplasia and the activation of brown adipose tissue (BAT). Not only the activation of BAT but also the browning of WAT have gained increasing attention in research fields as an alternative method in the prevention and treatment of obesity. Here, we investigated possible mechanisms underlying the anti-obesity effect of Phlomis umbrosa Turcz. root ethanol extract (PUE) in an obesogenic animal model. PUE treatment can reduce diet-induced obesity and modulate obesity-associated metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation. In the liver, PUE improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption while increasing biliary sterol excretion and hepatic fatty acid oxidation compared to the high-fat group. Moreover, PUE increased energy expenditure and regulated fecal lipid excretion, leading to reduced body weight gain. In particular, PUE remarkably activated the browning of subWAT via upregulation of the browning-related protein and gene expression and promoted BAT activation. In conclusion, these findings provide the potential therapeutic usefulness into the effects of PUE in the treatment of obesity and metabolic disorders. Furthermore, it suggests that PUE treatment can regulate energy metabolism via activating BAT and browning subWAT.
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Affiliation(s)
- Ji-Won Kim
- Department of Food Sciences and Nutrition, Kyungpook National University, Daegu 41566, Korea
| | - Young-Mo Yang
- Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju 61452, Korea
| | - Eun-Young Kwon
- Department of Food Sciences and Nutrition, Kyungpook National University, Daegu 41566, Korea
| | - Ji-Young Choi
- Department of Food and Nutrition, College of Natural Science and Public Health and Safety, Chosun University, Gwangju 61452, Korea
- Correspondence: ; Tel.: +82-62-230-7723; Fax: +82-62-225-7726
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Huang Q, Xin X, Sun Q, An Z, Gou X, Feng Q. Plant-derived bioactive compounds regulate the NLRP3 inflammasome to treat NAFLD. Front Pharmacol 2022; 13:896899. [PMID: 36016562 PMCID: PMC9396216 DOI: 10.3389/fphar.2022.896899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 06/29/2022] [Indexed: 11/29/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by abnormal accumulation of hepatic fat and inflammatory response with complex pathogenesis. Over activation of the pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the secretion of interleukin (IL)-1β and IL-18, induces pyroptosis, and promotes the release of a large number of pro-inflammatory proteins. All of which contribute to the development of NAFLD. There is a great deal of evidence indicating that plant-derived active ingredients are effective and safe for NAFLD management. This review aims to summarize the research progress of 31 active plant-derived components (terpenoids, flavonoids, alkaloids, and phenols) that alleviate lipid deposition, inflammation, and pyroptosis by acting on the NLRP3 inflammasome studied in both in vitro and in vivo NAFLD models. These studies confirmed that the NLRP3 inflammasome and its related genes play a key role in NAFLD amelioration, providing a starting point for further study on the correlation of plant-derived compounds treatment with the NLRP3 inflammasome and NAFLD.
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Affiliation(s)
- Qian Huang
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xin Xin
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - QinMei Sun
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ziming An
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaojun Gou
- Central Laboratory, Baoshan District Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai, Shanghai, China
| | - Qin Feng
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China
- Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai, China
- *Correspondence: Qin Feng,
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Ji L, Li Q, He Y, Zhang X, Zhou Z, Gao Y, Fang M, Yu Z, Rodrigues RM, Gao Y, Li M. Therapeutic potential of traditional Chinese medicine for the treatment of NAFLD: a promising drug Potentilla discolor Bunge. Acta Pharm Sin B 2022; 12:3529-3547. [PMID: 36176915 PMCID: PMC9513494 DOI: 10.1016/j.apsb.2022.05.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/09/2022] [Accepted: 03/23/2022] [Indexed: 11/29/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and metabolic stress-induced liver injury. There are currently no approved effective pharmacological treatments for NAFLD. Traditional Chinese medicine (TCM) has been used for centuries to treat patients with chronic liver diseases without clear disease types and mechanisms. More recently, TCM has been shown to have unique advantages in the treatment of NAFLD. We performed a systematic review of the medical literature published over the last two decades and found that many TCM formulas have been reported to be beneficial for the treatment of metabolic dysfunctions, including Potentilla discolor Bunge (PDB). PDB has a variety of active compounds, including flavonoids, terpenoids, organic acids, steroids and tannins. Many compounds have been shown to exhibit a series of beneficial effects for the treatment of NAFLD, including anti-oxidative and anti-inflammatory functions, improvement of lipid metabolism and reversal of insulin resistance. In this review, we summarize potential therapeutic effects of TCM formulas for the treatment of NAFLD, focusing on the medicinal properties of natural active compounds from PDB and their underlying mechanisms. We point out that PDB can be classified as a novel candidate for the treatment and prevention of NAFLD.
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Affiliation(s)
- Longshan Ji
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shanghai Key Laboratory of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China
| | - Qian Li
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shanghai Key Laboratory of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China
| | - Yong He
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Xin Zhang
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shanghai Key Laboratory of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China
| | - Zhenhua Zhou
- Department of Hepatopathy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yating Gao
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shanghai Key Laboratory of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China
| | - Miao Fang
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shanghai Key Laboratory of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China
| | - Zhuo Yu
- Department of Hepatopathy, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Robim M. Rodrigues
- Department of in Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels 1000, Belgium
- Corresponding authors.
| | - Yueqiu Gao
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shanghai Key Laboratory of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China
- Corresponding authors.
| | - Man Li
- Laboratory of Cellular Immunity, Institute of Clinical Immunology, Shanghai Key Laboratory of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, Shanghai 201203, China
- Corresponding authors.
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Liu JJ, Liang Y, Zhang Y, Wu RX, Song YL, Zhang F, Shi JS, Liu J, Xu SF, Wang Z. GC-MS Profile of Hua-Feng-Dan and RNA-Seq Analysis of Induced Adaptive Responses in the Liver. Front Pharmacol 2022; 13:730318. [PMID: 35355721 PMCID: PMC8959110 DOI: 10.3389/fphar.2022.730318] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 01/19/2022] [Indexed: 01/17/2023] Open
Abstract
Background: Hua-Feng-Dan is a patent Chinese medicine for stroke recovery and various diseases. This study used GC-MS to profile its ingredients and RNA-Seq to analyze the induced adaptive response in the liver. Methods: Hua-Feng-Dan was subjected to steam distillation and solvent extraction, followed by GC-MS analysis. Mice were orally administered Hua-Feng-Dan and its "Guide drug" Yaomu for 7 days. Liver pathology was examined, and total RNA isolated for RNA-Seq, followed by bioinformatic analysis and quantitative real-time PCR (qPCR). Results: Forty-four volatile and fifty liposoluble components in Hua-Feng-Dan were profiled and analyzed by the NIST library and their concentrations quantified. The major components (>1%) in volatile (5) and liposoluble (10) were highlighted. Hua-Feng-Dan and Yaomu at hepatoprotective doses did not produce liver toxicity as evidenced by histopathology and serum enzyme activities. GO Enrichment revealed that Hua-Feng-Dan affected lipid homeostasis, protein folding, and cell adhesion. KEGG showed activated cholesterol metabolism, bile secretion, and PPAR signaling pathways. Differentially expressed genes (DEGs) were identified by DESeq2 with p < 0.05 compared to controls. Hua-Feng-Dan produced more DEGs than Yaomu. qPCR on selected genes largely verified RNA-Seq results. Ingenuity Pathways Analysis of the upstream regulator revealed activation of MAPK and adaptive responses by Hua-Feng-Dan, and Yaomu was less effective. Hua-Feng-Dan-induced DEGs were highly correlated with the Gene Expression Omnibus database of chemical-induced adaptive transcriptome changes in the liver. Conclusion: GC-MS primarily profiled volatile and liposoluble components in Hua-Feng-Dan. Hua-Feng-Dan at the hepatoprotective dose did not produce liver pathological changes but induced metabolic and signaling pathway activations. The effects of Hua-Feng-Dan on liver transcriptome changes point toward induced adaptive responses to program the liver to produce hepatoprotective effects.
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Affiliation(s)
- Jia-Jia Liu
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, China
| | - Yan Liang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ya Zhang
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, China
| | - Rui-Xia Wu
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ying-Lian Song
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Feng Zhang
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, China
| | - Jing-Shan Shi
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, China
| | - Jie Liu
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, China
| | - Shang-Fu Xu
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnocentric of Ministry of Education, Zunyi Medical University, Zunyi, China
| | - Zhang Wang
- College of Ethnomedicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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42
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Bardelčíková A, Miroššay A, Šoltýs J, Mojžiš J. Therapeutic and prophylactic effect of flavonoids in post-COVID-19 therapy. Phytother Res 2022; 36:2042-2060. [PMID: 35302260 PMCID: PMC9111001 DOI: 10.1002/ptr.7436] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 02/16/2022] [Accepted: 02/21/2022] [Indexed: 12/17/2022]
Abstract
The high incidence of post-covid symptoms in humans confirms the need for effective treatment. Due to long-term complications across several disciplines, special treatment programs emerge for affected patients, emphasizing multidisciplinary care. For these reasons, we decided to look at current knowledge about possible long-term complications of COVID-19 disease and then present the effect of flavonoids, which could help alleviate or eliminate complications in humans after overcoming the COVID-19 infection. Based on articles published from 2003 to 2021, we summarize the flavonoids-based molecular mechanisms associated with the post-COVID-19 syndrome and simultaneously provide a complex view regarding their prophylactic and therapeutic potential. Review clearly sorts out the outcome of post-COVID-19 syndrome according particular body systems. The conclusion is that flavonoids play an important role in prevention of many diseases. We suggest that flavonoids as critical nutritional supplements, are suitable for the alleviation and shortening of the period associated with the post-COVID-19 syndrome. The most promising flavonoid with noteworthy therapeutic and prophylactic effect appears to be quercetin.
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Affiliation(s)
- Annamária Bardelčíková
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Košice, Slovak Republic
| | - Andrej Miroššay
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Košice, Slovak Republic
| | - Jindřich Šoltýs
- Institute of Parasitology, Slovak Academy of Science, Košice, Slovak Republic
| | - Ján Mojžiš
- Department of Pharmacology, Medical Faculty of University of Pavol Jozef Šafárik in Košice, Košice, Slovak Republic
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43
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Zhang Y, Pan H, Ye X, Chen S. Proanthocyanidins from Chinese bayberry leaves reduce obesity and associated metabolic disorders in high-fat diet-induced obese mice through a combination of AMPK activation and an alteration in gut microbiota. Food Funct 2022; 13:2295-2305. [PMID: 35142317 DOI: 10.1039/d1fo04147a] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Regulating host energy metabolism and re-shaping gut microbiota are effective strategies against high-fat diet (HFD)-induced obesity and related metabolic disorders. A special type of proanthocyanidin extracted from Chinese bayberry leaves (BLPs) was studied for its effects and mechanisms in preventing HFD-induced obesity in mice. BLPs significantly reduced body weight, ameliorated inflammation and regulated gut dysbiosis in HFD-fed mice. BLPs activated AMP-activated protein kinase (AMPK) in the liver and white adipose tissue (WAT), which led to the downregulation of genes related to lipogenesis (ACC, FAS and SREBP-1c), and the upregulation of genes related to β-oxidation. Furthermore, BLPs improved HFD-induced gut dysbiosis by sharply decreasing the percentage of an endotoxin-producing bacteria - Desulfovibrionaceae, and enabling some distinct bacteria, such as Peptococcaceae, Clostridiaceae and Desulfovibrio. BLPs also reduced the circulated endotoxin and maintained the gut barrier's integrity. Further antibiotic treatment revealed that depleting the gut microbiota abrogated the anti-obesogenic effects of BLPs, yet did not affect AMPK activation. Collectively, these results suggest that BLPs reduce obesity and associated metabolic disorders in HFD-fed mice through a combination of AMPK activation and an alteration in gut microbiota.
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Affiliation(s)
- Yu Zhang
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, 200093, China.,National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, Shanghai, 200093, China
| | - Haibo Pan
- Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, Zhejiang R&D Center for Food Technology and Equipment, Zhejiang University, Hangzhou, 310058, China.
| | - Xingqian Ye
- Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, Zhejiang R&D Center for Food Technology and Equipment, Zhejiang University, Hangzhou, 310058, China.
| | - Shiguo Chen
- Department of Food Science and Nutrition, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, Zhejiang R&D Center for Food Technology and Equipment, Zhejiang University, Hangzhou, 310058, China.
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Ye L, Xin Y, Wu ZY, Sun HJ, Huang DJ, Sun ZQ. A Newly Synthesized Flavone from Luteolin Escapes from COMT-Catalyzed Methylation and Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages via JNK, p38 and NF-κB Signaling Pathways. J Microbiol Biotechnol 2022; 32:15-26. [PMID: 34099595 PMCID: PMC9628824 DOI: 10.4014/jmb.2104.04027] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 05/13/2021] [Accepted: 05/25/2021] [Indexed: 12/15/2022]
Abstract
Luteolin is a common dietary flavone possessing potent anti-inflammatory activities. However, when administrated in vivo, luteolin becomes methylated by catechol-O-methyltransferases (COMT) owing to the catechol ring in the chemical structure, which largely diminishes its anti-inflammatory effect. In this study, we made a modification on luteolin, named LUA, which was generated by the chemical reaction between luteolin and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Without a catechol ring in the chemical structure, this new flavone could escape from the COMT-catalyzed methylation, thus affording the potential to exert its functions in the original form when administrated in the organism. Moreover, an LPS-stimulated RAW cell model was applied to detect the anti-inflammatory properties. LUA showed much more superior inhibitory effect on LPS-induced production of NO than diosmetin (a major methylated form of luteolin) and significantly suppressed upregulation of iNOS and COX-2 in macrophages. LUA treatment dramatically reduced LPS-stimulated reactive oxygen species (ROS) and mRNA levels of pro-inflammatory mediators such as IL-1β, IL-6, IL-8 and IFN-β. Furthermore, LUA significantly reduced the phosphorylation of JNK and p38 without affecting that of ERK. LUA also inhibited the activation of NF-κB through suppression of p65 phosphorylation and nuclear translocation.
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Affiliation(s)
- Lin Ye
- School of Pharmacy, Changzhou University, Changzhou 213164, P.R. China,Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Yang Xin
- Food Science and Technology Program, Department of Chemistry, Faculty of Science, National University of Singapore, Singapore 117597, Singapore
| | - Zhi-yuan Wu
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Hai-jian Sun
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - De-jian Huang
- Food Science and Technology Program, Department of Chemistry, Faculty of Science, National University of Singapore, Singapore 117597, Singapore,National University of Singapore (Suzhou) Research Institute, Suzhou, Jiangsu 215123, P.R. China
| | - Zhi-qin Sun
- School of Pharmacy, Changzhou University, Changzhou 213164, P.R. China,Changzhou Second People's Hospital, Changzhou 213000, P.R. China,Corresponding author Phone: +13861285688 E-mail:
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45
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Queiroz M, Leandro A, Azul L, Figueirinha A, Seiça R, Sena CM. Luteolin Improves Perivascular Adipose Tissue Profile and Vascular Dysfunction in Goto-Kakizaki Rats. Int J Mol Sci 2021; 22:13671. [PMID: 34948468 PMCID: PMC8706309 DOI: 10.3390/ijms222413671] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Revised: 12/03/2021] [Accepted: 12/14/2021] [Indexed: 11/25/2022] Open
Abstract
UNLABELLED We investigated the effects of luteolin on metabolism, vascular reactivity, and perivascular adipose tissue (PVAT) in nonobese type 2 diabetes mellitus animal model, Goto-Kakizaki (GK) rats. METHODS Wistar and GK rats were divided in two groups: (1) control groups treated with vehicle; (2) groups treated with luteolin (10 mg/kg/day, for 2 months). Several metabolic parameters such as adiposity index, lipid profile, fasting glucose levels, glucose and insulin tolerance tests were determined. Endothelial function and contraction studies were performed in aortas with (PVAT+) or without (PVAT-) periaortic adipose tissue. We also studied vascular oxidative stress, glycation and assessed CRP, CCL2, and nitrotyrosine levels in PVAT. RESULTS Endothelial function was impaired in diabetic GK rats (47% (GK - PVAT) and 65% (GK + PVAT) inhibition of maximal endothelial dependent relaxation) and significantly improved by luteolin treatment (29% (GK - PVAT) and 22% (GK + PVAT) inhibition of maximal endothelial dependent relaxation, p < 0.01). Vascular oxidative stress and advanced glycation end-products' levels were increased in aortic rings (~2-fold, p < 0.05) of diabetic rats and significantly improved by luteolin treatment (to levels not significantly different from controls). Periaortic adipose tissue anti-contractile action was significantly rescued with luteolin administration (p < 0.001). In addition, luteolin treatment significantly recovered proinflammatory and pro-oxidant PVAT phenotype, and improved systemic and metabolic parameters in GK rats. CONCLUSIONS Luteolin ameliorates endothelial dysfunction in type 2 diabetes and exhibits therapeutic potential for the treatment of vascular complications associated with type 2 diabetes.
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MESH Headings
- Adipose Tissue/drug effects
- Adipose Tissue/metabolism
- Animals
- Carrier Proteins/metabolism
- Chemokine CCL2/metabolism
- Diabetes Mellitus, Experimental/chemically induced
- Diabetes Mellitus, Experimental/drug therapy
- Diabetes Mellitus, Experimental/metabolism
- Diabetes Mellitus, Type 2/chemically induced
- Diabetes Mellitus, Type 2/drug therapy
- Diabetes Mellitus, Type 2/metabolism
- Disease Models, Animal
- Drug Administration Schedule
- Endothelium, Vascular/drug effects
- Endothelium, Vascular/metabolism
- Luteolin/administration & dosage
- Luteolin/pharmacology
- Male
- Oxidative Stress/drug effects
- Rats
- Rats, Wistar
- Tyrosine/analogs & derivatives
- Tyrosine/metabolism
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Affiliation(s)
- Marcelo Queiroz
- Institute of Physiology, iCBR, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (M.Q.); (A.L.); (L.A.); (R.S.)
| | - Adriana Leandro
- Institute of Physiology, iCBR, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (M.Q.); (A.L.); (L.A.); (R.S.)
| | - Lara Azul
- Institute of Physiology, iCBR, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (M.Q.); (A.L.); (L.A.); (R.S.)
| | - Artur Figueirinha
- LAQV, REQUIMTE, Faculty of Farmacy, University of Coimbra, 3000-548 Coimbra, Portugal;
| | - Raquel Seiça
- Institute of Physiology, iCBR, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (M.Q.); (A.L.); (L.A.); (R.S.)
| | - Cristina M. Sena
- Institute of Physiology, iCBR, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (M.Q.); (A.L.); (L.A.); (R.S.)
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Lemon Balm and Corn Silk Extracts Mitigate High-Fat Diet-Induced Obesity in Mice. Antioxidants (Basel) 2021; 10:antiox10122015. [PMID: 34943118 PMCID: PMC8698494 DOI: 10.3390/antiox10122015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/14/2021] [Accepted: 12/15/2021] [Indexed: 12/31/2022] Open
Abstract
Lemon balm and corn silk are valuable medicinal herbs, which exhibit variety of beneficial effects for human health. The present study explored the anti-obesity effects of a mixture of lemon balm and corn silk extracts (M-LB/CS) by comparison with the effects of single herbal extracts in high-fat diet (HFD)-induced obesity in mice. HFD supplementation for 84 days increased the body weight, the fat mass density, the mean diameter of adipocytes, and the thickness of fat pads. However, oral administration of M-LB/CS significantly alleviated the HFD-mediated weight gain and adipocyte hypertrophy without affecting food consumption. Of the various combination ratios of M-LB/CS tested, the magnitude of the decreases in weight gain and adipocyte hypertrophy by administration of 1:1, 1:2, 2:1, and 4:1 (w/w) M-LB/CS was more potent than that by single herbal extracts alone. In addition, M-LB/CS reduced the HFD-mediated increases in serum cholesterol, triglyceride, and low-density lipoprotein, prevented the reduction in serum high-density lipoprotein, and facilitated fecal excretion of cholesterol and triglyceride. Moreover, M-LB/CS mitigated the abnormal changes in specific mRNAs associated with lipogenesis and lipolysis in the adipose tissue. Furthermore, M-LB/CS reduced lipid peroxidation by inhibiting the HFD-mediated reduction in glutathione, catalase, and superoxide dismutase. Therefore, M-LB/CS is a promising herbal mixture for preventing obesity.
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47
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Hadrich F, Chamkha M, Sayadi S. Protective effect of olive leaves phenolic compounds against neurodegenerative disorders: Promising alternative for Alzheimer and Parkinson diseases modulation. Food Chem Toxicol 2021; 159:112752. [PMID: 34871668 DOI: 10.1016/j.fct.2021.112752] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 11/24/2021] [Accepted: 12/01/2021] [Indexed: 02/07/2023]
Abstract
The main objective of this work was to review literature on compounds extracted from olive tree leaves, such as simple phenols (hydroxytyrosol) and flavonoids (Apigenin, apigenin-7-O-glucoside, luteolin.) and their diverse pharmacological activities as antioxidant, antimicrobial, anti-viral, anti-obesity, anti-inflammatory and neuroprotective properties. In addition, the study discussed the key mechanisms underlying their neuroprotective effects. This study adopted an approach of collecting data through the databases provided by ScienceDirect, SCOPUS, MEDLINE, PubMed and Google Scholar. This review revealed that there was an agreement on the great impact of olive tree leaves phenolic compounds on many metabolic syndromes as well as on the most prevalent neurodegenerative diseases such as Alzheimer and Parkinson. These findings would be of great importance for the use of olive tree leaves extracts as a food supplement and/or a source of drugs for many diseases. In addition, this review would of great help to beginning researchers in the field since it would offer them a general overview of the studies undertaken in the last two decades on the topic.
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Affiliation(s)
- Fatma Hadrich
- Environmental Bioprocesses Laboratory, Center of Biotechnology of Sfax, P.O. Box 1177, 3038, Sfax, Tunisia.
| | - Mohamed Chamkha
- Environmental Bioprocesses Laboratory, Center of Biotechnology of Sfax, P.O. Box 1177, 3038, Sfax, Tunisia
| | - Sami Sayadi
- Biotechnology Program, Center of Sustainable Development, College of Arts and Sciences, Qatar University, Doha, 2713, Qatar.
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48
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Zhou Y, Wang C, Kou J, Wang M, Rong X, Pu X, Xie X, Han G, Pang X. Chrysanthemi Flos extract alleviated acetaminophen-induced rat liver injury via inhibiting oxidative stress and apoptosis based on network pharmacology analysis. PHARMACEUTICAL BIOLOGY 2021; 59:1378-1387. [PMID: 34629029 PMCID: PMC8510625 DOI: 10.1080/13880209.2021.1986077] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/02/2023]
Abstract
CONTEXT Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury. Bianliang ziyu, a variety of Chrysanthemum morifolium Ramat. (Asteraceae), has potential hepatoprotective effect. However, the mechanism is not clear yet. OBJECTIVE To investigate the hepatoprotective activity and mechanism of Bianliang ziyu flower ethanol extract (BZE) on APAP-induced rats based on network pharmacology. MATERIALS AND METHODS Potential pathways of BZE were predicted by network pharmacology. Male Sprague-Dawley rats were pre-treated with BZE (110, 220 and 440 mg/kg, i.g.) for eight days, and then APAP (800 mg/kg, i.g.) was used to induce liver injury. After 24 h, serum and liver were collected for biochemical detection and western blot measurement. RESULTS Network pharmacology indicated that liver-protective effect of BZE was associated with its antioxidant and anti-apoptotic efficacy. APAP-induced liver pathological change was alleviated, and elevated serum AST and ALT were reduced by BZE (440 mg/kg) (from 66.45 to 22.64 U/L and from 59.59 to 17.49 U/L, respectively). BZE (440 mg/kg) reduced the ROS to 65.50%, and upregulated SOD and GSH by 212.92% and 175.38%, respectively. In addition, BZE (440 mg/kg) increased levels of p-AMPK, p-GSK3β, HO-1 and NQO1, ranging from 1.66- to 10.29-fold compared to APAP group, and promoted nuclear translocation of Nrf2. BZE also inhibited apoptosis induced by APAP through the PI3K-Akt pathway and restored the ability of mitochondrial biogenesis. DISCUSSION AND CONCLUSIONS Our study demonstrated that BZE protected rats from APAP-induced liver injury through antioxidant and anti-apoptotic pathways, suggesting BZE could be further developed as a potential liver-protecting agent.
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Affiliation(s)
- Yunfeng Zhou
- Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China
| | - Chunli Wang
- Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China
| | - Jiejian Kou
- Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China
| | - Minghui Wang
- Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China
| | - Xuli Rong
- Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China
| | - Xiaohui Pu
- Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China
| | - Xinmei Xie
- Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China
- CONTACT Xinmei Xie
| | - Guang Han
- Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China
- Kaifeng Key Lab for Application of Local Dendranthema morifolium in Food & Drug, Kaifeng, China
- Guang Han
| | - Xiaobin Pang
- Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng, China
- Institutes of Traditional Chinese Medicine, Henan University, Kaifeng, China
- Xiaobin Pang Pharmaceutical Institute, School of Pharmacy, Henan University, Kaifeng475004, China
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Bayliak MM, Dmytriv TR, Melnychuk AV, Strilets NV, Storey KB, Lushchak VI. Chamomile as a potential remedy for obesity and metabolic syndrome. EXCLI JOURNAL 2021; 20:1261-1286. [PMID: 34602925 PMCID: PMC8481792 DOI: 10.17179/excli2021-4013] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 07/21/2021] [Indexed: 12/26/2022]
Abstract
Obesity is an increasing health concern related to many metabolic disorders, including metabolic syndrome, diabetes type 2 and cardiovascular diseases. Many studies suggest that herbal products can be useful dietary supplements for weight management due to the presence of numerous biologically active compounds, including antioxidant polyphenols that can counteract obesity-related oxidative stress. In this review we focus on Matricaria chamomilla, commonly known as chamomile, and one of the most popular medicinal plants in the world. Thanks to a high content of phenolic compounds and essential oils, preparations from chamomile flowers demonstrate a number of pharmacological effects, including antioxidant, anti-inflammatory, antimicrobial and sedative actions as well as improving gastrointestinal function. Several recent studies have shown certain positive effects of chamomile preparations in the prevention of obesity and complications of diabetes. These effects were associated with modulation of signaling pathways involving the AMP-activated protein kinase, NF-κB, Nrf2 and PPARγ transcription factors. However, the potential of chamomile in the management of obesity seems to be underestimated. This review summarizes current data on the use of chamomile and its individual components (apigenin, luteolin, essential oils) to treat obesity and related metabolic disorders in cell and animal models and in human studies. Special attention is paid to molecular mechanisms that can be involved in the anti-obesity effects of chamomile preparations. Limitation of chamomile usage is also analyzed.
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Affiliation(s)
- Maria M Bayliak
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine
| | - Tetiana R Dmytriv
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine
| | - Antonina V Melnychuk
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine
| | - Nadia V Strilets
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine
| | - Kenneth B Storey
- Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada
| | - Volodymyr I Lushchak
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk, 76018, Ukraine.,I. Horbachevsky Ternopil National Medical University, 46002, Ternopil, Ukraine.,Research and Development University, Shota Rustaveli Str., 76018, Ivano-Frankivsk, Ukraine
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50
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El-Asfar RK, El-Derany MO, Sallam AAM, Wahdan SA, El-Demerdash E, Sayed SA, El-Mesallamy HO. Luteolin mitigates tamoxifen-associated fatty liver and cognitive impairment in rats by modulating beta-catenin. Eur J Pharmacol 2021; 908:174337. [PMID: 34265292 DOI: 10.1016/j.ejphar.2021.174337] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 06/12/2021] [Accepted: 07/11/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND AND AIM Tamoxifen (TAM) therapy has been associated with fatty liver diseases. Recently, multiple reports have also shown that TAM is related to cognitive impairment in patients with breast cancer. Luteolin, a natural flavonoid, has been traditionally used to treat various inflammatory disorders, such as chronic liver diseases, cognitive impairments, and cancers. This study aimed to evaluate the potential protective effects of luteolin against the cognitive defects and liver steatosis induced by TAM in rats. EXPERIMENTAL APPROACH The diseased group was subcutaneously (s.c) injected with TAM at a dose of 1 mg/kg daily for 7 days. The cotreated groups were given luteolin via oral gavage at a dose of 20 or 40 mg/kg concomitantly with s.c injection of TAM at a dose of 1 mg/kg for 7 days. All the groups were subjected to behavioral tests 24 h after the last TAM injection. Then, the rats were sacrificed 3 days after the last TAM injection. RESULTS Luteolin cotreatment significantly alleviated the behavioral defects in rats with TAM-induced cognitive impairment. This finding was supported by the reversal of neurodegeneration in the cortex and in the hippocampal regions of the brain. Furthermore, luteolin attenuated hepatic steatosis and decreased the levels of serum aminotransferases and hypertriglyceridemia. As an anti-inflammatory agent, luteolin cotreatment similarly decreased the levels of hepatic inflammatory markers and increased the levels of hepatic β-catenin in TAM-induced fatty liver. CONCLUSIONS Luteolin improved the TAM-induced cognitive impairment and hepatic steatosis in rats by alleviating inflammation and modulating hepatic β-catenin levels.
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Affiliation(s)
- Rana K El-Asfar
- Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Marwa O El-Derany
- Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Al-Aliaa M Sallam
- Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Department of Biochemistry, School of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Entertainment Area, Badr City, Cairo, 11829, Egypt
| | - Sara A Wahdan
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Ebtehal El-Demerdash
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Sayed A Sayed
- Department of Pathology, Al-Azhar Faculty of Medicine, Cairo, Egypt
| | - Hala O El-Mesallamy
- Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Department of Biochemistry, School of Pharmacy, Sinai University, Sinai, Egypt.
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