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1
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Wang W, Liu X, Gao X, Zhou X, Gao W, Sang Y, Yang B. Characterization, digestive properties and glucose metabolism regulation of curcumin-loaded Pickering emulsion. Carbohydr Polym 2025; 356:123408. [PMID: 40049978 DOI: 10.1016/j.carbpol.2025.123408] [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: 11/13/2024] [Revised: 01/27/2025] [Accepted: 02/14/2025] [Indexed: 05/13/2025]
Abstract
Curcumin, a polyphenolic compound with antioxidant and hypoglycemic properties, has limited applications due to low stability and poor oral bioavailability. This study aimed to overcome these challenges by developing stable oil-in-water Pickering emulsions with curcumin and evaluating their stability and digestive characteristics. Using a T2DM mouse model, we further examined the effects of curcumin-loaded Pickering emulsions on glucose metabolism. The emulsions demonstrated high curcumin encapsulation efficiency (96.72 % ± 2.15 %) and minimal average droplet size. Both emulsions showed stable zeta potential, favorable rheological properties, and strong environmental and storage stability, lasting up to 60 days. In vitro digestion studies indicated that the Pickering emulsion substantially improved curcumin bioavailability (25.48 %-36.43 %) and increased antioxidant and hypoglycemic activity compared to oil-soluble curcumin, both before and after digestion. In animal experiments, the curcumin-loaded Pickering emulsion enhanced fasting blood glucose, glucose tolerance, and insulin resistance in T2DM mice, compared to the untreated model group. It also supported tissue repair in the pancreas, liver, and colon, reduced oxidative stress in the liver, activated the PI3K/Akt signaling pathway, and favorably influenced gut microbiota and short-chain fatty acids. These findings suggest that Pickering emulsions are an effective delivery system for curcumin in functional foods, supporting their application in curcumin-based product development.
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Affiliation(s)
- Wanjia Wang
- College of Food Science and Technology, Hebei Agricultural University, Baoding, China
| | - Xinghua Liu
- Hebei Livestock Breeding Station, Shijiazhuang, China
| | - Xingchen Gao
- College of Food Science and Technology, Hebei Agricultural University, Baoding, China
| | - Xingxing Zhou
- College of Food Science and Technology, Hebei Agricultural University, Baoding, China
| | - Wei Gao
- Chen Guang Biotechnology Group Co., Ltd., Handan, China
| | - Yaxin Sang
- College of Food Science and Technology, Hebei Agricultural University, Baoding, China.
| | - Bing Yang
- College of Food Science and Technology, Hebei Agricultural University, Baoding, China.
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Guney C, Alcigir ME, Akar F. Excess Fructose Intake Activates Hyperinsulinemia and Mitogenic MAPK Pathways in Association With Cellular Stress, Inflammation, and Apoptosis in the Pancreas of Rats. Mol Nutr Food Res 2025; 69:e70048. [PMID: 40152093 PMCID: PMC12087730 DOI: 10.1002/mnfr.70048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 03/04/2025] [Accepted: 03/12/2025] [Indexed: 03/29/2025]
Abstract
The increase in sugar consumption has been associated with current metabolic disease epidemics. This study aimed to investigate the pancreatic molecular mechanisms involved in cellular stress, inflammation, mitogenesis, and apoptosis in metabolic disease induced by high-fructose diet. Here, we used biochemical, histopathological, Western blot, and immunohistochemistry methods to determine the metabolic and pancreatic alterations in male Wistar rats fed 20% fructose in drinking water for 15 weeks. High-fructose consumption in rats increased the immunopositivity and protein expression of glucose transporter 2 (GLUT2) and insulin in the pancreatic tissue, in association with abdominal adiposity, hyperglycemia, and hypertriglyceridemia. The expressions of cellular stress markers, glucose-regulated protein-78 (GRP78) and PTEN-induced putative kinase 1 (PINK1), were increased in the pancreas. The levels of interleukin (IL)-6, nuclear factor kappa B (NFκB), tumor necrosis factor α (TNFα), and IL-1β and components of the Nod-like receptor protein 3 (NLRP3) inflammasome were elevated. Excess fructose intake stimulated the activation of mitogenic extracellular signal-regulated kinases 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK)1 as well as the apoptotic p53 and Fas pathways in the pancreas of rats. There was also an increase in caspase-8 and caspase-3 cleavage. Our findings revealed that dietary high-fructose in the pancreas causes hyperinsulinemia due to the upregulation of GLUT2 together with cellular stress and inflammatory markers, thereby stimulates mitogenic mitogen-activated protein kinase (MAPK) and apoptosis pathways, resulting in a complex pathological situation.
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Affiliation(s)
- Ceren Guney
- Department of Pharmacology, Faculty of PharmacyGazi UniversityAnkaraTurkey
- Department of Pharmacology, Faculty of PharmacyDüzce UniversityDüzceTurkey
| | - Mehmet Eray Alcigir
- Department of Pathology, Faculty of Veterinary MedicineKırıkkale UniversityKırıkkaleTurkey
| | - Fatma Akar
- Department of Pharmacology, Faculty of PharmacyGazi UniversityAnkaraTurkey
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Comi L, Giglione C, Tolaj Klinaku F, Da Dalt L, Ullah H, Daglia M, Magni P. Evaluation of Metabolic Dysfunction-Associated Fatty Liver Disease-Related Pathogenic Mechanisms in Human Steatotic Liver Cell-Based Model: Beneficial Effects of Prunus domestica L. subsp. syriaca Extract. Nutrients 2025; 17:1249. [PMID: 40219006 PMCID: PMC11990314 DOI: 10.3390/nu17071249] [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: 03/03/2025] [Revised: 03/29/2025] [Accepted: 04/01/2025] [Indexed: 04/14/2025] Open
Abstract
Background/Objectives: Disrupted glucose uptake, oxidative stress, and increased de novo lipogenesis are some of the key features of metabolic dysfunction-associated fatty liver disease (MASLD). The modulation of these pathogenic mechanisms using extracts from natural and sustainable sources is a promising strategy to mitigate disease progression. This study aimed to evaluate the effects of Prunus domestica L. subsp. syriaca extract on these processes, taking advantage of a cell-based model of steatotic hepatocytes (HepG2-OA) that recapitulates some key pathophysiological features of MASLD. Methods: The HepG2-OA cell model was generated by treating cells for 7 days with 100 μM oleic acid (OA). The effect of different concentrations (0.01, 0.1, 0.5, and 1 mg/mL) of P. domestica extract was assessed through MTT assay (cell viability), flow cytometry (glucose uptake and reactive oxygen species, ROS, production), spectrophotometry (lipid accumulation), and qRT-PCR (expression of selected genes). Results: P. domestica extract exhibited no cytotoxicity at any tested concentration after 24 and 48 h in the HepG2-OA cells. The extract increased glucose uptake in a dose-dependent fashion after both 6 and 24 h. Additionally, the extract reduced lipid accumulation and downregulated the expression of key lipogenic genes (DGAT1 and FASN). Furthermore, in the HepG2-OA cells, P. domestica extract reduced ROS production and downregulated the expression of oxidative stress-related genes (SOD and CAT). Conclusions: P. domestica extract positively modulated some key molecular mechanisms associated with glucose metabolism, lipogenesis, and oxidative stress, supporting its potential as a nutraceutical candidate for MASLD management.
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Affiliation(s)
- Laura Comi
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy; (L.C.); (C.G.); (F.T.K.); (L.D.D.)
| | - Claudia Giglione
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy; (L.C.); (C.G.); (F.T.K.); (L.D.D.)
| | - Fationa Tolaj Klinaku
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy; (L.C.); (C.G.); (F.T.K.); (L.D.D.)
| | - Lorenzo Da Dalt
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy; (L.C.); (C.G.); (F.T.K.); (L.D.D.)
| | - Hammad Ullah
- School of Pharmacy, University of Management and Technology, Lahore 54000, Pakistan;
| | - Maria Daglia
- Department of Pharmacy, University of Naples Federico II, 80168 Naples, Italy;
- International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China
| | - Paolo Magni
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy; (L.C.); (C.G.); (F.T.K.); (L.D.D.)
- IRCCS MultiMedica, 20099 Sesto San Giovanni, Milan, Italy
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Ni D, Liu K, Wu N, You B, Yang B, Wu W, Dai Y. Curcumin administration alleviates seminal vesicle damage in type 1 diabetic rats by promoting AQP8 expression through AR activation. Sci Rep 2025; 15:3804. [PMID: 39885225 PMCID: PMC11782618 DOI: 10.1038/s41598-024-74750-5] [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: 04/14/2024] [Accepted: 09/30/2024] [Indexed: 02/01/2025] Open
Abstract
Diabetes is a detriment to male reproductive health, notably through its capacity to diminish secretion from accessory glands such as the seminal vesicles and prostate, which are crucial for reproductive function. Curcumin, a naturally derived polyphenol renowned for its anti-inflammatory and antioxidative attributes, has demonstrated potential in mitigating tissue damage across various organs in diabetic patients. Despite its established benefits, the specific impact of curcumin on seminal vesicle damage in the context of diabetes remains underexplored. This investigation delves into the therapeutic potential of curcumin in ameliorating seminal vesicle damage in diabetic rats, thereby elucidating its underlying mechanisms. This study focused on twenty male SD rats divided into two distinct groups, a control cohort and a diabetic contingent, and employed a streptozocin (STZ)-induced type 1 diabetic rat model to ascertain seminal vesicle alterations secondary to diabetes. Ultrasonography was used to measure rat seminal vesicle sizes for comparison with postdissection measurements. This study revealed that (1) seminal vesicle volume and seminal fluid secretion were reduced in diabetic rats and (2) ultrasonography can predict seminal vesicle secretory dysfunction in diabetic rats, providing a theoretical basis for selecting animal models of diabetic seminal vesicle dysfunction for subsequent studies. Thirty male SD rats were subsequently divided into three groups: control, diabetic, and curcumin-treated. The curcumin group, which was subjected to a one-month-long intervention after STZ-induced diabetes onset, exhibited significant histological and functional recovery. Haematoxylin‒eosin (HE) staining revealed disordered seminal vesicle tissue structures and decreased epithelial cell height in diabetic rats, which was partially restored after curcumin treatment. Western blot and PCR results demonstrated that the expression levels of androgen receptor (AR) and aquaporin (AQP)8 in the seminal vesicle tissues of diabetic rats were decreased, whereas curcumin treatment led to increases in the expression levels of AR and AQP8. Seminal vesicle cells were cultured in vitro and divided into six groups: control, HG, HG-CUR-5 µM, HG-CUR-10 µM, HG-CUR-20 µM, and HG-CUR-50 µM. After 48 h of intervention, the fructose concentration in the culture medium was measured, and the expression of AR and AQP8 in the control, HG, and HG-CUR-20 µM groups was determined via Western blotting and PCR. The results revealed that the expression of AR and APQ8 in high glucose-treated seminal vesicle cells was decreased and that curcumin treatment upregulated the expression of AR and AQP8. After the addition of bicalutamide (an AR inhibitor), the expression of AQP8 was reduced. These findings suggest that curcumin may alleviate seminal vesicle damage in type 1 diabetic rats by activating the AR-AQP8 pathway.
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Affiliation(s)
- Dawei Ni
- Department of urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China
- Department of andrology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Kun Liu
- Department of urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China
| | - Ning Wu
- Department of andrology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Bin You
- Department of Andrology, Guoyang County Traditional Chinese Medicine Hospital in Bozhou City, Bozhou City, Anhui Province, China
| | - Baibing Yang
- Department of andrology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Wei Wu
- Department of urology, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, China.
| | - Yutian Dai
- Department of andrology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China.
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Özsan M, Saygili Düzova Ü, Dönmez N. Neuroprotective role of curcumin on the hippocampus against the oxidative stress and inflammation of streptozotocin-induced diabetes in rats. Metab Brain Dis 2024; 40:24. [PMID: 39565437 DOI: 10.1007/s11011-024-01438-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 10/21/2024] [Indexed: 11/21/2024]
Abstract
In recent years, it has gained importance to determine the effects of diabetes on central nervous system complications. This study aimed to assess the neuroprotective properties of curcumin against neuronal damage in the rat hippocampus caused by diabetes. In accordance with this purpose, we investigated the effects of curcumin on oxidative/antioxidative parameters and pro-inflammatory cytokines in the hippocampal tissue of diabetic Wistar rats. For this purpose, 32 adults, male and healthy Wistar Albino rats were used. Animals were randomly divided into four separate groups: control (C), curcumin(Cu), diabetes (D) and Diabetes + Curcumin (DCu)-treated groups. 60 mg/kg STZ i.p. A single dose was administered to D and DCu groups. Cu and DCu groups were given 50 mg/kg/day curcumin by gavage. After four weeks of treatment, the animals were decapitated under anesthesia and tissue samples were taken for analyses of the parameters (TNF-α, IL-6, IL-1, IL-10, MDA, SOD, catalase, and GSH activities) in the hippocampal tissue. TNF-α, IL-6, IL-1, and MDA levels were increased significantly (p < 0.05) in rats with diabetes compared to the other three groups. TNF-α, IL-6, IL-1, and MDA levels were lower in DCu group animals compared to the D group. It was determined that IL-10, SOD, Catalase, and GSH levels, which were significantly decreased in the D group, increased in the curcumin-supplemented diabetic group (DCu). The relevant sentence has been changed as follows. In conclusion, our findings from this study prove the protective effect of curcumin against diabetes-induced neuropathy in the hippocampus in rats with STZ-induced diabetes.
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Affiliation(s)
- Mehmet Özsan
- Faculty of Medicine, University of Niğde Ömer Halis Demir, Niğde, Turkey.
| | | | - Nurcan Dönmez
- Faculty of Veterinary, University of Selcuk, Konya, Turkey
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Wang X, Zhang W, Zhou S. Multifaceted physiological and therapeutical impact of curcumin on hormone-related endocrine dysfunctions: A comprehensive review. Phytother Res 2024; 38:3307-3336. [PMID: 38622915 DOI: 10.1002/ptr.8208] [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: 01/09/2024] [Revised: 03/28/2024] [Accepted: 03/28/2024] [Indexed: 04/17/2024]
Abstract
Over the past five decades, Curcumin (Cur), derived from turmeric (Curcuma longa), has gained considerable attention for its potential therapeutic applications. Synthesizing insights from clinical trials conducted over the last 25 years, this review delves into diseases where Cur has demonstrated promise, offering a nuanced understanding of its pharmacokinetics, safety, and effectiveness. Focusing on specific examples, the impact of Cur on various human diseases is explored. Endocrine glands and associated signaling pathways are highlighted, elucidating how Cur influences cellular signaling. The article underscores molecular mechanisms such as hormone level alteration, receptor interaction, cytokine and adipokine expression inhibition, antioxidant enzyme activity, and modulation of transcription factors. Cur showcases diverse protective mechanisms against inflammation and oxidative damage by suppressing antiapoptotic genes and impeding tumor promotion. This comprehensive overview emphasizes the potential of Cur as a natural agent for countering aging and degenerative diseases, calling for further dedicated research in this realm.
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Affiliation(s)
- Xiuying Wang
- College of Chinese Medicine, Jilin Agricultural Science and Technology College, Jilin, China
| | - Wei Zhang
- College of Chinese Medicine, Jilin Agricultural Science and Technology College, Jilin, China
| | - Shengxue Zhou
- College of Chinese Medicine, Jilin Agricultural Science and Technology College, Jilin, China
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7
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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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Guney C, Bal NB, Akar F. The impact of dietary fructose on gut permeability, microbiota, abdominal adiposity, insulin signaling and reproductive function. Heliyon 2023; 9:e18896. [PMID: 37636431 PMCID: PMC10447940 DOI: 10.1016/j.heliyon.2023.e18896] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 07/24/2023] [Accepted: 08/02/2023] [Indexed: 08/29/2023] Open
Abstract
The excessive intake of fructose in the regular human diet could be related to global increases in metabolic disorders. Sugar-sweetened soft drinks, mostly consumed by children, adolescents, and young adults, are the main source of added fructose. Dietary high-fructose can increase intestinal permeability and circulatory endotoxin by changing the gut barrier function and microbial composition. Excess fructose transports to the liver and then triggers inflammation as well as de novo lipogenesis leading to hepatic steatosis. Fructose also induces fat deposition in adipose tissue by stimulating the expression of lipogenic genes, thus causing abdominal adiposity. Activation of the inflammatory pathway by fructose in target tissues is thought to contribute to the suppression of the insulin signaling pathway producing systemic insulin resistance. Moreover, there is some evidence that high intake of fructose negatively affects both male and female reproductive systems and may lead to infertility. This review addresses dietary high-fructose-induced deteriorations that are obvious, especially in gut permeability, microbiota, abdominal fat accumulation, insulin signaling, and reproductive function. The recognition of the detrimental effects of fructose and the development of relevant new public health policies are necessary in order to prevent diet-related metabolic disorders.
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Affiliation(s)
| | | | - Fatma Akar
- Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey
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Balakumar P, Venkatesan K, Abdulla Khan N, Raghavendra NM, Venugopal V, Bharathi DR, Fuloria NK. Mechanistic insights into the beneficial effects of curcumin on insulin resistance: opportunities and challenges. Drug Discov Today 2023:103627. [PMID: 37224995 DOI: 10.1016/j.drudis.2023.103627] [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: 02/15/2023] [Revised: 05/03/2023] [Accepted: 05/17/2023] [Indexed: 05/26/2023]
Abstract
The past couple of decades in particular have seen a rapid increase in the prevalence of type 2 diabetes mellitus (T2DM), a debilitating metabolic disorder characterised by insulin resistance. The insufficient efficacy of current management strategies for insulin resistance calls for additional therapeutic options. The preponderance of evidence suggests potential beneficial effects of curcumin on insulin resistance, while modern science provides a scientific basis for its potential applications against the disease. Curcumin combats insulin resistance by increasing the levels of circulating irisin and adiponectin, activating PPARγ, suppressing Notch1 signalling, and regulating SREBP target genes, among others. In this review, we bring together the diverse areas pertaining to our current understanding of the potential benefits of curcumin on insulin resistance, associated mechanistic insights, and new therapeutic possibilities. Teaser: Current approaches to manage insulin resistance are not highly efficacious, which necessitates additional therapeutic options; curcumin combats insulin resistance by improving the levels of circulating irisin and adiponectin, upregulating and activating PPARγ, and suppressing Notch‑1 signalling.
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Affiliation(s)
- Pitchai Balakumar
- The Office of Research and Development, Periyar Maniammai Institute of Science & Technology, Vallam, Thanjavur 613 403, Tamil Nadu, India.
| | - Kumar Venkatesan
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Al-Qara, Abha 61421, Saudi Arabia
| | - Noohu Abdulla Khan
- Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Al-Qara, Abha 61421, Saudi Arabia
| | - N M Raghavendra
- Department of Pharmaceutical Chemistry, College of Pharmaceutical Sciences, Dayananda Sagar University, Bengaluru 560 111, India
| | - Vijayan Venugopal
- School of Pharmacy, Sri Balaji Vidyapeeth Deemed-to-be University, Puducherry 607 402, India
| | - D R Bharathi
- Department of Pharmacology, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B G Nagara, Nagamangala 571 448, India
| | - Neeraj K Fuloria
- Pharmaceutical Chemistry Unit, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Malaysia
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Metformin alleviates long-term high-fructose diet-induced skeletal muscle insulin resistance in rats by regulating purine nucleotide cycle. Eur J Pharmacol 2022; 933:175234. [PMID: 36058289 DOI: 10.1016/j.ejphar.2022.175234] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 08/17/2022] [Accepted: 08/22/2022] [Indexed: 11/24/2022]
Abstract
Nutrient excess caused by excessive fructose intake can lead to insulin resistance and dyslipidemia, which further causes the development of metabolic syndrome. Metformin is a well-known AMPK activator widely used for the treatment of metabolic syndrome, while the mechanism of AMPK activation remains unclear. The present study aimed to investigate the pharmacological effects of metformin on fructose-induced insulin resistance rat, and the potential mechanism underlying AMPK activation in skeletal muscle tissue. Results indicated that metformin significantly ameliorated features of insulin resistance, including body weight, Lee's index, hyperinsulinemia, dyslipidemia, insulin intolerance and pancreatic damage. Moreover, treatment with metformin attenuated the inflammatory response in serum and enhanced the antioxidant capacity in skeletal muscle tissue. The therapeutic effects of metformin on fructose-induced insulin resistance may be related to the activation of AMPK to regulate Nrf2 pathway and mitochondrial abnormality. Additionally, metformin suppressed the expression of adenosine monophosphate deaminase 1 (AMPD1) and up-regulated the expression of adenylosuccinate synthetase (ADSS) in the purine nucleotide cycle (PNC), which facilitated the increase of AMP level and the ratio of AMP/ATP. Therefore, we proposed a novel mechanism that metformin activated AMPK via increasing AMP by regulating the expression of AMPD1 and ADSS in PNC pathway.
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Khursheed R, Singh SK, Wadhwa S, Gulati M, Jha NK, Gupta G, Devkota HP, Prasher P, Chellappan DK, Dua K. A sojourn into therapeutic and nutraceutical potential of curcumin and its novel drug delivery system: Current achievements and future perspectives. SOUTH AFRICAN JOURNAL OF BOTANY 2022; 149:944-962. [DOI: 10.1016/j.sajb.2022.04.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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El Shahawy M, El Deeb M. Assessment of the possible ameliorative effect of curcumin nanoformulation on the submandibular salivary gland of alloxan-induced diabetes in a rat model (Light microscopic and ultrastructural study). Saudi Dent J 2022; 34:375-384. [PMID: 35814842 PMCID: PMC9263756 DOI: 10.1016/j.sdentj.2022.04.009] [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: 02/19/2022] [Revised: 04/17/2022] [Accepted: 04/22/2022] [Indexed: 11/28/2022] Open
Abstract
Background Nowadays, attention is directed to herbal treatments in an attempt to lessen the adverse effects of diabetes. Nanoformulation of curcumin (NC) was shown to enhance stability and water solubility compared to native curcumin. Objective To examine the effect of different NC concentrations on the histopathological structure of the submandibular salivary gland of diabetic rats. Methods 28 rats were divided equally into 4 groups. Group I: Control group, Group II (diabetic), III (diabetic + nanocurcumin low dose), and IV (diabetic + nanocurcumin high dose): Rats of groups II, III and IV were injected with a single dose of alloxan (140 mg/kg) to induce diabetes. After 7 days, groups III and IV were treated for 6 weeks with NC (100 mg/kg/day) for group III, and (200 mg/kg/day) for group IV. Submandibular salivary glands were assessed histologically, immunohistochemically using α smooth muscle actin (α SMA) and ultrastructurally. Results Diabetic samples showed destruction of parenchymal elements of the gland, with thick fiber bundles encircling the excretory ducts and minimal reaction for α SMA. Amelioration of the gland's architecture was detected in groups III and IV with reduction of collagen deposition and elevation of positive immunoreactivity to α SMA. Conclusion NC profoundly repaired the induced diabetic histopathological and ultrastructural alterations of the gland in a dose dependent manner.
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Key Words
- DM, diabetes mellitus
- Diabetes
- H&E, Hematoxylin and Eosin
- Masson trichrome
- NC, nanocurcumin
- NHD, nanocurcumin high dose
- NLD, nanocurcumin low dose
- Nanocurcumin
- RER, rough endoplasmic reticulum
- ROS, reactive oxygen species
- SD, standard deviation
- Submandibular salivary glands
- TEM, transmission electron microscope
- α SMA
- α SMA, α Smooth Muscle Actin
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Affiliation(s)
- Maha El Shahawy
- Associate Professor, Oral Biology Department, Faculty of Dentistry, Minia University, Egypt
| | - Mona El Deeb
- Professor, Oral Biology Department, Faculty of Oral & Dental Medicine, Future University in Egypt (FUE), Egypt
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Oliveira S, Monteiro-Alfredo T, Henriques R, Ribeiro CF, Seiça R, Cruz T, Cabral C, Fernandes R, Piedade F, Robalo MP, Matafome P, Silva S. Improvement of Glycaemia and Endothelial Function by a New Low-Dose Curcuminoid in an Animal Model of Type 2 Diabetes. Int J Mol Sci 2022; 23:ijms23105652. [PMID: 35628465 PMCID: PMC9144453 DOI: 10.3390/ijms23105652] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/12/2022] [Accepted: 05/16/2022] [Indexed: 11/16/2022] Open
Abstract
Curcumin has been suggested as a promising treatment for metabolic diseases, but the high doses required limit its therapeutic use. In this study, a new curcuminoid is synthesised to increase curcumin anti-inflammatory and antioxidant potential and to achieve hypoglycaemic and protective vascular effects in type 2 diabetic rats in a lower dose. In vitro, the anti-inflammatory effect was determined through the Griess reaction, and the antioxidant activity through ABTS and TBARS assays. In vivo, Goto-Kakizaki rats were treated for 2 weeks with the equimolar dose of curcumin (40 mg/kg/day) or curcuminoid (52.4 mg/kg/day). Fasting glycaemia, insulin tolerance, plasma insulin, insulin signalling, serum FFA, endothelial function and several markers of oxidative stress were evaluated. Both compounds presented a significant anti-inflammatory effect. Moreover, the curcuminoid had a marked hypoglycaemic effect, accompanied by higher GLUT4 levels in adipose tissue. Both compounds increased NO-dependent vasorelaxation, but only the curcuminoid exacerbated the response to ascorbic acid, consistent with a higher decrease in vascular oxidative and nitrosative stress. SOD1 and GLO1 levels were increased in EAT and heart, respectively. Altogether, these data suggest that the curcuminoid developed here has more pronounced effects than curcumin in low doses, improving the oxidative stress, endothelial function and glycaemic profile in type 2 diabetes.
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Affiliation(s)
- Sara Oliveira
- Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine and Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal; (S.O.); (T.M.-A.); (C.C.); (R.F.); (S.S.)
- Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal;
- Clinical-Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal;
| | - Tamaeh Monteiro-Alfredo
- Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine and Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal; (S.O.); (T.M.-A.); (C.C.); (R.F.); (S.S.)
- Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal;
- Clinical-Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal;
- Research Group on Biotechnology and Bioprospecting Applied to Metabolism (GEBBAM), Federal University of Grande Dourados, Dourados 79825-070, MS, Brazil
| | - Rita Henriques
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; (R.H.); (T.C.)
| | - Carlos Fontes Ribeiro
- Clinical-Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal;
- Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Raquel Seiça
- Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal;
- Clinical-Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal;
| | - Teresa Cruz
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; (R.H.); (T.C.)
- CNC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
| | - Célia Cabral
- Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine and Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal; (S.O.); (T.M.-A.); (C.C.); (R.F.); (S.S.)
- Clinical-Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal;
| | - Rosa Fernandes
- Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine and Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal; (S.O.); (T.M.-A.); (C.C.); (R.F.); (S.S.)
- Clinical-Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal;
| | - Fátima Piedade
- CQE, Complexo I, Instituto Superior Técnico, University of Lisbon, 1049-001 Lisbon, Portugal; (F.P.); (M.P.R.)
- Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal
| | - Maria Paula Robalo
- CQE, Complexo I, Instituto Superior Técnico, University of Lisbon, 1049-001 Lisbon, Portugal; (F.P.); (M.P.R.)
- Instituto Superior de Engenharia de Lisboa (ISEL), Instituto Politécnico de Lisboa, 1959-007 Lisbon, Portugal
| | - Paulo Matafome
- Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine and Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal; (S.O.); (T.M.-A.); (C.C.); (R.F.); (S.S.)
- Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal;
- Clinical-Academic Center of Coimbra (CACC), University of Coimbra, 3000-548 Coimbra, Portugal;
- Instituto Politécnico de Coimbra, Coimbra Health School (ESTeSC), 3046-854 Coimbra, Portugal
- Correspondence:
| | - Sónia Silva
- Coimbra Institute of Clinical and Biomedical Research (iCBR), Faculty of Medicine and Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal; (S.O.); (T.M.-A.); (C.C.); (R.F.); (S.S.)
- Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal; (R.H.); (T.C.)
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Hao M, Chu Y, Lei J, Yao Z, Wang P, Chen Z, Wang K, Sang X, Han X, Wang L, Cao G. Pharmacological Mechanisms and Clinical Applications of Curcumin: Update. Aging Dis 2022; 14:716-749. [PMID: 37191432 DOI: 10.14336/ad.2022.1101] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 11/01/2022] [Indexed: 11/19/2022] Open
Abstract
Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in the last ten years due to its multiple pharmacological activities. A growing body of evidence has manifested that curcumin has extensive pharmacological activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity and minor adverse reactions. However, the disadvantages of low bioavailability, short half-life in plasma, low drug concentration in blood, and poor oral absorption severely limited the clinical application of curcumin. Pharmaceutical researchers have carried out plenty of dosage form transformations to improve the druggability of curcumin and have achieved remarkable results. Therefore, the objective of this review summarizes the pharmacological research progress, problems in clinical application and the improvement methods of curcumin's druggability. By reviewing the latest research progress of curcumin, we believe that curcumin has a broad clinical application prospect for its wide range of pharmacological activities with few side effects. The deficiencies of lower bioavailability of curcumin could be improved by dosage form transformation. However, curcumin in the clinical application still requires further study regarding the underlying mechanism and clinical trial verification.
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Smoak P, Burke SJ, Collier JJ. Botanical Interventions to Improve Glucose Control and Options for Diabetes Therapy. SN COMPREHENSIVE CLINICAL MEDICINE 2021; 3:2465-2491. [PMID: 35098034 PMCID: PMC8796700 DOI: 10.1007/s42399-021-01034-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Diabetes mellitus is a major public health problem worldwide. This endocrine disease is clustered into distinct subtypes based on the route of development, with the most common forms associated with either autoimmunity (T1DM) or obesity (T2DM). A shared hallmark of both major forms of diabetes is a reduction in function (insulin secretion) or mass (cell number) of the pancreatic islet beta-cell. Diminutions in both mass and function are often present. A wide assortment of plants have been used historically to reduce the pathological features associated with diabetes. In this review, we provide an organized viewpoint focused around the phytochemicals and herbal extracts investigated using various preclinical and clinical study designs. In some cases, crude extracts were examined directly, and in others, purified compounds were explored for their possible therapeutic efficacy. A subset of these studies compared the botanical product with standard of care prescribed drugs. Finally, we note that botanical formulations are likely suspects for future drug discovery and refinement into class(es) of compounds that have either direct or adjuvant therapeutic benefit.
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Affiliation(s)
- Peter Smoak
- Laboratory of Islet Biology and Inflammation, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA
| | - Susan J. Burke
- Immunogenetics Laboratory, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, LA 70808 Baton Rouge, USA
| | - J. Jason Collier
- Laboratory of Islet Biology and Inflammation, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA
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Dziegielewska-Gesiak S. Metabolic Syndrome in an Aging Society - Role of Oxidant-Antioxidant Imbalance and Inflammation Markers in Disentangling Atherosclerosis. Clin Interv Aging 2021; 16:1057-1070. [PMID: 34135578 PMCID: PMC8200137 DOI: 10.2147/cia.s306982] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 04/23/2021] [Indexed: 12/16/2022] Open
Abstract
INTRODUCTION The prevalence of metabolic syndrome among the elderly population is growing. The elements of metabolic syndrome in an aging society are currently being researched. Atherosclerosis is a slow process in which the first symptoms may be observed after many years. The mechanisms underlying the progression of atherosclerosis are oxidative stress and inflammation. Inflammation and oxidative stress are associated with the increased incidence of metabolic syndrome. Taking the above into consideration, metabolic syndrome is thought to be a clinical equivalent of atherosclerosis. AIM The aim of this paper is to review the impact of the interplay of oxidant-antioxidant and inflammation markers in metabolic syndrome in general as well as its components in the pathophysiology which underlies development of atherosclerosis in elderly individuals. METHODS A systematic scan of online resources designed for elderly (≥65 years) published from 2005 to the end of 2020 were reviewed. This was supplemented with grey literature and then all resources were narratively analyzed. The analysis included the following terms: "atherosclerosis or metabolic syndrome" and "oxidative stress or inflammation" and "elderly" to find reports of atherosclerotic disease from asymptomatic to life-threatening among the elderly population with metabolic syndrome . RESULTS The work summarizes articles that were applicable to this study, including systematic reviews, qualitative studies and opinion pieces. Current knowledge focuses on monitoring the inflammation and oxidant-antioxidant imbalance in disentangling atherosclerosis in patients diagnosed with metabolic syndrome. The population-based studies described inflammation, increased oxidative stress and weak antioxidant defense systems as the mechanisms underlying atherosclerosis development. Moreover, there are discussions that these targets could potentially be a point of intervention to reduce the development of atherosclerosis in the elderly, especially those with altered glucose and lipid metabolism. Specific markers may be used as an approach for the prevention and lifestyle modification of atherosclerotic disease in such population. CONCLUSION Metabolic syndrome and its components are important contributors in the progression of atherosclerotic disease in the elderly population but constant efforts should be made to broaden our knowledge of elderly groups who are the most susceptible for the development of atherosclerosis complications.
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Alidadi M, Sahebkar A, Eslami S, Vakilian F, Jarahi L, Alinezhad-Namaghi M, Arabi SM, Vakili S, Tohidinezhad F, Nikooiyan Y, Norouzy A. The Effect of Curcumin Supplementation on Pulse Wave Velocity in Patients with Metabolic Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1308:1-11. [PMID: 33861432 DOI: 10.1007/978-3-030-64872-5_1] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Cardiovascular disease is a leading cause of death in many societies. Arterial stiffness is an initial sign of structural and functional changes in the arterial wall. Pulse wave velocity (PWV) is the gold standard for non-invasive evaluation of aortic stiffness and a modifiable cardiovascular risk factor. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. Since arterial stiffness is affected by inflammation and oxidative stress, it may be improved by curcumin supplementation. The purpose of this clinical trial was to investigate the potential effects of curcumin on improving arterial stiffness in patients with metabolic syndrome. This placebo-controlled, double-blind, randomized clinical trial was conducted among metabolic syndrome patients. Sixty-six eligible individuals were randomly assigned to active intervention or control groups. The active intervention group received curcumin supplement at a dose of 500 mg daily for 12 weeks, whereas the control group received placebo capsule. Physical activity, daily dietary energy intake, anthropometric body composition, and biochemical hemodynamic and arterial stiffness parameters were evaluated at baseline and at the end of the study. Body weight decreased significantly in the curcumin group compared to placebo. Also, curcumin intervention improved PWV, which remained significant after adjustment for potential confounding factors (p = 0.011). The current clinical trial demonstrated that daily intake of 500 mg of curcumin for 12 weeks can lead to the improvement of arterial stiffness and weight management among subjects with metabolic syndrome.
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Affiliation(s)
- Mona Alidadi
- Department of Nutrition, Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.,Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
| | - Saeid Eslami
- Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
| | - Farveh Vakilian
- Department of Cardiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Lida Jarahi
- Department of Community Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Alinezhad-Namaghi
- Department of Nutrition, Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mostafa Arabi
- Department of Nutrition, Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saba Vakili
- Medical Genetics Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fariba Tohidinezhad
- Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Yasaman Nikooiyan
- Medical Student, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Abdolreza Norouzy
- Department of Nutrition, Faculty of medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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Tabaee S, Sahebkar A, Aghamohammadi T, Pakdel M, Dehabeh M, Sobhani R, Alidadi M, Majeed M, Mirhafez SR. The Effects of Curcumin Plus Piperine Supplementation in Patients with Acute Myocardial Infarction: A Randomized, Double-Blind, and Placebo-Controlled Trial. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1328:199-211. [PMID: 34981479 DOI: 10.1007/978-3-030-73234-9_13] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Acute myocardial infarction (AMI) is a leading cause of death and disability worldwide. Previous investigations have demonstrated that curcumin has a cardioprotective effect and may improve myocardial injury. So this study was performed to assess whether supplementation with curcumin could diminish myocardial injury following AMI. METHODS To conduct this randomized, double-blinded, and placebo-controlled clinical trial, seventy-two patients with acute myocardial infarction, aged 18-75 years, were enrolled and randomly divided into the active intervention and control groups. The active intervention group (n = 38) received curcumin capsules with piperine supplement (500 mg/day, 95% curcuminoids) for 8 weeks, whereas the control group (n = 34) received a placebo capsule. At the baseline and end of the study, ejection fraction was assessed, and blood samples were taken from all patients to measure the levels of cardiac troponin I(cTnI), lipid profile, FBG, HbA1C, liver enzymes, renal function parameters, and electrolytes. RESULTS In this trial, curcumin supplementation significantly reduced the levels of HbA1C (-0.3 ± 2.2 vs. +1.1 ± 1.3, P = 0.002), LDL (-10.3 ± 20.7 vs. +0.2 ± 22.5, P = 0.039), ALT (-10.2 ± 28.5 vs. +7.3 ± 39.2, P = 0.029), and ALP (+6.4 ± 39.5 vs. +38.0 ± 69.0, P = 0.018) compared to the placebo group. Moreover, the serum concentration of HDL significantly improved in comparison with the placebo group (+4.5 ± 8.9 vs. -1.6 ± 7.7, P = 0.002). However, no substantial difference was perceived between the groups regarding the ejection fraction and serum levels of cTnI, FBG, renal function parameters, and electrolytes. CONCLUSION Our results indicated that daily intake of 500 mg of curcumin capsules with piperine supplement for 8 weeks modified lipid profile, liver enzymes, and glycemic status, but did not have any effect on ejection fraction and serum concentration of cardiac troponin I, renal function parameters, and electrolytes in acute myocardial infarction patients.
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Affiliation(s)
- Samaneh Tabaee
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Tayebe Aghamohammadi
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Manizhe Pakdel
- Faculty of Nursing, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Maryam Dehabeh
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Reza Sobhani
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Mona Alidadi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Seyed Reza Mirhafez
- Noncommunicable Diseases Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
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Li P, Ding L, Cao S, Feng X, Zhang Q, Chen Y, Zhang N, Qiu F. Curcumin metabolites contribute to the effect of curcumin on ameliorating insulin sensitivity in high-glucose-induced insulin-resistant HepG2 cells. JOURNAL OF ETHNOPHARMACOLOGY 2020; 259:113015. [PMID: 32464315 DOI: 10.1016/j.jep.2020.113015] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 05/22/2020] [Accepted: 05/22/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL EVIDENCE Curcumin (CUR) is the active ingredient of Traditional Chinese Medicine turmeric (Curcuma longa L.), which has been used for treatment of diabetes in Ayurveda and China. CUR exerts potent anti-insulin-resistant effects in various cell lines. However, previous studies indicated CUR was metabolized extensively in vivo and massively degraded in a medium alkaline buffer solution. The real active component of the anti-insulin-resistant activity of CUR in vitro is not clear. AIM OF THE STUDY Our study identified the functional contribution of the metabolites of CUR and the related molecular mechanism in improving insulin sensitivity. MATERIALS AND METHODS HPLC and UPLC-QQQ-MS analyses were used to investigate the stability and metabolism of CUR in HepG2 cells. The effect of the metabolic products of CUR on insulin sensitivity was evaluated in high glucose (HG)-induced insulin-resistant HepG2 cells. A network pharmacology approach was used to examine the potential targets of the metabolites, and Western blotting was performed to verify changes in the targets. RESULTS CUR was unstable in the cell culture medium, but the prototypes, metabolites and degradation products of CUR coexisted in the HepG2 cell culture experiment. The insulin sensitivity assay demonstrated that CUR and its metabolites enhanced insulin sensitivity in HG-induced insulin-resistant HepG2 cells, but the total degradation products of CUR may not play the major role. Similar to CUR, hexahydrocurcumin (HHC) and octahydrocurcumin (OHC) improved insulin sensitivity by strengthening the PI3K-AKT-GSK3B signal and suppressing the phosphorylation of ERK/JNK in HG-induced insulin-resistant HepG2 cells. CONCLUSIONS Metabolites of CUR played a critical role in counteracting insulin resistance in HG-induced HepG2 cells. CUR exerted anti-insulin resistance effect in HepG2 cells in a multi-component, multi-target, and multi-pathway manner.
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Affiliation(s)
- Pan Li
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Liqin Ding
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Shijie Cao
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Xinchi Feng
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Qiang Zhang
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Yuwei Chen
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Nan Zhang
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
| | - Feng Qiu
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
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Curcumin derivatives for Type 2 Diabetes management and prevention of complications. Arch Pharm Res 2020; 43:567-581. [PMID: 32557163 DOI: 10.1007/s12272-020-01240-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 06/09/2020] [Indexed: 02/08/2023]
Abstract
Type 2 diabetes Mellitus (T2DM) is characterized by chronically increased blood glucose levels, which is associated with impairment of the inflammatory and oxidative state and dyslipidaemia. Although it is considered a world heath concern and one of the most studied diseases, we are still pursuing an effective therapy for both the pathophysiological mechanisms and the complications. Curcumin, a natural compound found in the rhizome of Curcuma longa, is well known for its numerous biological activities, as demonstrated by several studies supporting that curcumin possesses hypoglycaemic, hypolipidemic, anti-inflammatory and antioxidant properties, among others. These effects have been explored to the attenuation of hyperglycaemia and progression of DM complications, being appointed as a potential therapeutic approach. Besides its strong intrinsic activity, the polyphenol has low bioavailability, compromising its therapeutic efficacy. In order to overcome this limitation, several chemical strategies have been applied to curcumin, such as drug delivery systems, chemical manipulation and the use of adjuvant therapies. Given the promising results obtained with curcumin derivative, in this review we discuss not only the therapeutic targets of curcumin, but also its most recently developed analogues and their efficacy in the management of T2DM pathophysiology and complications.
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Zhao Q, Li L, Zhu Y, Hou D, Li Y, Guo X, Wang Y, Olatunji OJ, Wan P, Gong K. Kukoamine B Ameliorate Insulin Resistance, Oxidative Stress, Inflammation and Other Metabolic Abnormalities in High-Fat/High-Fructose-Fed Rats. Diabetes Metab Syndr Obes 2020; 13:1843-1853. [PMID: 32547146 PMCID: PMC7266517 DOI: 10.2147/dmso.s247844] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Obesity is characterized by excessive body fat, insulin resistance and dyslipidemia, which increases the chances of developing chronic diseases like type 2 diabetes, cardiovascular diseases, hypertension, nonalcoholic fatty liver diseases, some types of cancers and neurodegenerative diseases. Kukoamine B (Kuk B) is a spermine alkaloid obtained from Lycium chinense, and it has been shown to possess antidiabetic, antioxidant and anti-inflammatory properties. In this study, we evaluated the therapeutic effect of Kuk B on high-fat diet/high-fructose (HFDFr)-induced insulin resistance and obesity in experimental rats. MATERIALS AND METHODS Rats were fed with either normal rat diet or HFDFr for 10 consecutive weeks. The groups that were fed with HFDFr received Kuk B (25 and 50 mg/kg) from the beginning of the 6th week to the 10th week. After treatment, the effect of Kuk B on body weight, food, water intake, insulin, blood glucose, serum biochemical parameters, hepatic oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and proinflammatory cytokine (interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α)) levels was determined. Histopathological analysis of the liver tissues was also performed. RESULTS HFDFr-fed rats showed a significant increase in body weight, fasting blood glucose, insulin, lipid accumulation and liver function enzymes. In addition, HFDFr diet increased hepatic MDA, TNF-α, IL-1β and IL-6 and decreased hepatic SOD, CAT and GSH-Px activities. On the other hand, Kuk B significantly attenuated body weight, insulin resistance, lipid accumulation, oxidative stress and inflammation. CONCLUSION These results indicated that Kuk B showed protective effect against HFDFr-induced metabolic disorders by downregulating lipid accumulation, oxidative stress and inflammatory factors.
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Affiliation(s)
- Quan Zhao
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Linhai Li
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Yu Zhu
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Dezhi Hou
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Yuejin Li
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Xiaodong Guo
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Yongzhi Wang
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | | | - Ping Wan
- Department of Digestive Internal Medicine, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
- Ping Wan Department of Digestive Internal Medicine, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China Email
| | - Kunmei Gong
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
- Correspondence: Kunmei Gong Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China Email
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Di Meo F, Margarucci S, Galderisi U, Crispi S, Peluso G. Curcumin, Gut Microbiota, and Neuroprotection. Nutrients 2019; 11:2426. [PMID: 31614630 PMCID: PMC6835970 DOI: 10.3390/nu11102426] [Citation(s) in RCA: 138] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Revised: 09/29/2019] [Accepted: 10/04/2019] [Indexed: 12/16/2022] Open
Abstract
Curcumin, a nontoxic, naturally occurring polyphenol, has been recently proposed for the management of neurodegenerative and neurological diseases. However, a discrepancy exists between the well-documented pharmacological activities that curcumin seems to possess in vivo and its poor aqueous solubility, bioavailability, and pharmacokinetic profiles that should limit any therapeutic effect. Thus, it is possible that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of curcumin are present after oral administration. Indeed, a new working hypothesis that could explain the neuroprotective role of curcumin despite its limited availability is that curcumin acts indirectly on the central nervous system by influencing the "microbiota-gut-brain axis", a complex bidirectional system in which the microbiome and its composition represent a factor which preserves and determines brain "health". Interestingly, curcumin and its metabolites might provide benefit by restoring dysbiosis of gut microbiome. Conversely, curcumin is subject to bacterial enzymatic modifications, forming pharmacologically more active metabolites than curcumin. These mutual interactions allow to keep proper individual physiologic functions and play a key role in neuroprotection.
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Affiliation(s)
- Francesco Di Meo
- Institute of Biosciences and BioResources-UOS Naples CNR, Via P. Castellino, 80100 Naples, Italy.
- Department of Biology, University of Naples Federico II, Complesso Universitario Monte Sant'Angelo via Cinthia, 80100 Naples, Italy.
| | - Sabrina Margarucci
- Institute of Research on Terrestrial Ecosystems, 05010 Porano TR, Italy.
| | - Umberto Galderisi
- Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Via Santa Maria di Costantinopoli, 80100 Naples, Italy.
| | - Stefania Crispi
- Institute of Biosciences and BioResources-UOS Naples CNR, Via P. Castellino, 80100 Naples, Italy.
- Department of Biology, University of Naples Federico II, Complesso Universitario Monte Sant'Angelo via Cinthia, 80100 Naples, Italy.
| | - Gianfranco Peluso
- Institute of Research on Terrestrial Ecosystems, 05010 Porano TR, Italy.
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Morris G, Puri BK, Walker AJ, Maes M, Carvalho AF, Bortolasci CC, Walder K, Berk M. Shared pathways for neuroprogression and somatoprogression in neuropsychiatric disorders. Neurosci Biobehav Rev 2019; 107:862-882. [PMID: 31545987 DOI: 10.1016/j.neubiorev.2019.09.025] [Citation(s) in RCA: 80] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 08/13/2019] [Accepted: 09/16/2019] [Indexed: 12/13/2022]
Abstract
Activated immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways and consequent mitochondrial aberrations are involved in the pathophysiology of psychiatric disorders including major depression, bipolar disorder and schizophrenia. They offer independent and shared contributions to pathways underpinning medical comorbidities including insulin resistance, metabolic syndrome, obesity and cardiovascular disease - herein conceptualized as somatoprogression. This narrative review of human studies aims to summarize relationships between IO&NS pathways, neuroprogression and somatoprogression. Activated IO&NS pathways, implicated in the neuroprogression of psychiatric disorders, affect the pathogenesis of comorbidities including insulin resistance, dyslipidaemia, obesity and hypertension, and by inference, metabolic syndrome. These conditions activate IO&NS pathways, exacerbating neuroprogression in psychiatric disorders. The processes whereby proinflammatory cytokines, nitrosative and endoplasmic reticulum stress, NADPH oxidase isoforms, PPARγ inactivation, SIRT1 deficiency and intracellular signalling pathways impact lipid metabolism and storage are considered. Through associations between body mass index, chronic neuroinflammation and FTO expression, activation of IO&NS pathways arising from somatoprogression may contribute to neuroprogression. Early evidence highlights the potential of adjuvants targeting IO&NS pathways for treating somatoprogression and neuroprogression.
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Affiliation(s)
- Gerwyn Morris
- Deakin University, IMPACT Strategic Research Centre, Barwon Health, School of Medicine, Geelong, Victoria, Australia
| | - Basant K Puri
- Department of Medicine, Hammersmith Hospital, Imperial College London, London, UK
| | - Adam J Walker
- Deakin University, IMPACT Strategic Research Centre, Barwon Health, School of Medicine, Geelong, Victoria, Australia
| | - Michael Maes
- Deakin University, IMPACT Strategic Research Centre, Barwon Health, School of Medicine, Geelong, Victoria, Australia
| | - Andre F Carvalho
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Chiara C Bortolasci
- Deakin University, CMMR Strategic Research Centre, School of Medicine, Geelong, Victoria, Australia
| | - Ken Walder
- Deakin University, CMMR Strategic Research Centre, School of Medicine, Geelong, Victoria, Australia
| | - Michael Berk
- Deakin University, IMPACT Strategic Research Centre, Barwon Health, School of Medicine, Geelong, Victoria, Australia; Deakin University, CMMR Strategic Research Centre, School of Medicine, Geelong, Victoria, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, the Department of Psychiatry and the Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
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25
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Saadati S, Sadeghi A, Mansour A, Yari Z, Poustchi H, Hedayati M, Hatami B, Hekmatdoost A. Curcumin and inflammation in non-alcoholic fatty liver disease: a randomized, placebo controlled clinical trial. BMC Gastroenterol 2019; 19:133. [PMID: 31345163 PMCID: PMC6659284 DOI: 10.1186/s12876-019-1055-4] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 07/21/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND The aim of the present study was to evaluate the effects of curcumin supplementation on inflammatory indices, and hepatic features in patients with non-alcoholic fatty liver disease (NAFLD). METHODS Fifty patients with NAFLD were randomized to receive lifestyle modification advice plus either 1500 mg curcumin or the same amount of placebo for 12 weeks. RESULTS Curcumin supplementation was associated with significant decrease in hepatic fibrosis (p < 0.001), and nuclear factor-kappa B activity (p < 0.05) as compared with the baseline. Hepatic steatosis and serum level of liver enzymes, and tumor necrosis-α (TNF-α) significantly reduced in both groups (p < 0.05). None of the changes were significantly different between two groups. CONCLUSION Our results indicated that curcumin supplementation plus lifestyle modification is not superior to lifestyle modification alone in amelioration of inflammation. TRIAL REGISTRATION IRCT20100524004010N24, this trial was retrospectively registered on May 14, 2018.
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Affiliation(s)
- Saeede Saadati
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asieh Mansour
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Yari
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Poustchi
- Liver and pancreatobiliary research group, Digestive Disease Research Institute, Tehran, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Low-Dose Curcumin Nanoparticles Normalise Blood Pressure in Male Wistar Rats with Diet-Induced Metabolic Syndrome. Nutrients 2019; 11:nu11071542. [PMID: 31288419 PMCID: PMC6682951 DOI: 10.3390/nu11071542] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 06/27/2019] [Accepted: 07/05/2019] [Indexed: 12/20/2022] Open
Abstract
Nanoparticle formulations improve bioavailability and so may allow low-dose formulations of food-derived compounds such as curcumin to attenuate chronic systemic disease despite intrinsically low oral bioavailability. The current study induced metabolic syndrome in male Wistar rats aged eight–nine weeks using a high-carbohydrate, high-fat diet (H) with corn starch diet (C) as control. Using a reversal protocol, rats were given curcumin as either nanoparticles encapsulated in poly(lactic–co–glycolic acid) (5 mg/kg/day, HCNP) or as an unformulated low dose or high-dose suspension in water (low-dose, 5 mg/kg/day, HC5; high-dose, 100 mg/kg/day, HC100) or blank nanoparticles (HBNP) for the final eight weeks of the 16 week study. We analysed cardiovascular parameters including systolic blood pressure and left ventricular diastolic stiffness along with histopathology, liver parameters including plasma liver enzymes, histopathology and metabolic parameters, including glucose tolerance, blood lipid profile and body composition, and plasma curcumin concentrations. HC100 and HCNP but not HBNP normalised systolic blood pressure (C = 120 ± 4; H = 143 ± 5; HBNP = 141 ± 3; HC5 = 143 ± 4; HC100 = 126 ± 4; HCNP = 128 ± 4 mmHg), left ventricular diastolic stiffness and liver fat deposition. No other improvements were induced in HC100 or HCNP or other intervention groups (HC5 and HBNP). We conclude that 5 mg/kg/day curcumin nanoparticles in H rats showed similar improvements in cardiovascular function as 100 mg/kg/day unformulated curcumin correlating with similar plasma curcumin concentrations.
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27
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Lee HJ, Kang MG, Cha HY, Kim YM, Lim Y, Yang SJ. Effects of Piceatannol and Resveratrol on Sirtuins and Hepatic Inflammation in High-Fat Diet-Fed Mice. J Med Food 2019; 22:833-840. [PMID: 31268397 DOI: 10.1089/jmf.2018.4261] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Piceatannol (PIC) is a natural hydroxylated analog of resveratrol (RSV) and considered as a potential metabolic regulator. The purpose of this study was to compare the effects of PIC and RSV on parameters affecting inflammation, oxidative stress, and sirtuins (Sirt). Male C57BL/6J mice, 20 weeks old, were assigned to the following groups; (1) lean control, (2) high-fat diet control (HF), (3) HF_PIC, and (4) HF_RSV. Oral administration of PIC and RSV (10 mg/kg/day) for 4 weeks improved glucose control as shown by decreasing levels of area under the curve (AUC) during the oral glucose tolerance test compared with HF group. PIC improved glycemic control by increasing hepatic levels of insulin receptor and AMP-activated protein kinase. PIC increased the levels of Sirt1, Sirt3, and Sirt6 and also increased two downstream targets of Sirt, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and forkhead box O1, in the liver. The inflammatory markers, interleukin (IL)-1 and IL-6, in the liver were downregulated by RSV treatment. Exposure to PIC and RSV significantly lowered hepatic levels of tumor necrosis factor-alpha. However, PIC and RSV treatments showed minimal effects on hepatic markers of oxidative stress. The levels of antioxidant enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), were only increased in livers of RSV-treated mice compared with HF control mice. In conclusion, PIC was superior to an equal concentration of RSV in the regulation of Sirt and its downstream targets as well as insulin signaling-related parameters, while RSV potentially suppressed levels of proinflammatory markers and increased NQO1 protein levels.
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Affiliation(s)
- Hee Jae Lee
- 1Department of Food and Nutrition, Seoul Women's University, Seoul, Republic of Korea
| | - Min-Gyung Kang
- 2Department of Food and Nutrition, Chonnam National University, Gwangju, Republic of Korea
| | - Hee Yun Cha
- 1Department of Food and Nutrition, Seoul Women's University, Seoul, Republic of Korea
| | - Youn Mi Kim
- 3Department of Food and Nutrition, Kyung Hee University, Seoul, Republic of Korea
| | - Yunsook Lim
- 3Department of Food and Nutrition, Kyung Hee University, Seoul, Republic of Korea
| | - Soo Jin Yang
- 1Department of Food and Nutrition, Seoul Women's University, Seoul, Republic of Korea
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Curcumin attenuates insulin resistance and hepatic lipid accumulation in a rat model of intra-uterine growth restriction through insulin signalling pathway and sterol regulatory element binding proteins. Br J Nutr 2019; 122:616-624. [PMID: 31237229 DOI: 10.1017/s0007114519001508] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
The objective of the present study was to investigate the effect of curcumin on insulin resistance (IR) and hepatic lipid accumulation in intra-uterine growth restriction (IUGR). Rats with a normal birth weight (NBW) or IUGR were fed basic diets (NBW and IUGR groups) or basic diets supplemented with curcumin (NBW-C and IUGR-C groups) from 6 to 12 weeks. Rats in the IUGR group showed higher levels of glucose and homeostasis model assessment for insulin resistance index (HOMA-IR) (P < 0·05) than in the NBW group. The livers of IUGR rats exhibited higher (P < 0·05) concentration of TAG and lower (P < 0·05) activities of lipolysis enzymes compared with the normal rats. In response to dietary curcumin supplementation, concentrations of serum insulin, glucose and HOMA-IR, pyruvate, TAG, total cholesterol and NEFA in the liver were decreased (P < 0·05). The concentrations of glycogen and activities of lipolysis enzymes in the liver were increased (P < 0·05) in the IUGR-C group compared with the IUGR group. These results were associated with lower (P < 0·05) phosphorylated insulin receptor substrate 1, protein kinase B or Akt, glycogen synthase kinase 3β and expressions of sterol regulatory element binding protein 1 and fatty acid synthase (FASN); decreased expressions for Cd36, sterol regulatory element binding protein 1c (Srebf1) and Fasn; increased (P < 0·05) expression of PPARα; and expressions for Ppara and hormone-sensitive lipase in the liver of IUGR-C rats than the IUGR rats. Maternal malnutrition caused IR and lipid accumulation in the liver. Curcumin supplementation prevented IR by regulating insulin signalling pathways and attenuated hepatic lipid accumulation.
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Patel SS, Acharya A, Ray RS, Agrawal R, Raghuwanshi R, Jain P. Cellular and molecular mechanisms of curcumin in prevention and treatment of disease. Crit Rev Food Sci Nutr 2019; 60:887-939. [PMID: 30632782 DOI: 10.1080/10408398.2018.1552244] [Citation(s) in RCA: 263] [Impact Index Per Article: 43.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Curcumin is a naturally occurring polyphenolic compound present in rhizome of Curcuma longa belonging to the family zingiberaceae. Growing experimental evidence revealed that curcumin exhibit multitarget biological implications signifying its crucial role in health and disease. The current review highlights the recent progress and mechanisms underlying the wide range of pharmacological effects of curcumin against numerous diseases like neuronal, cardiovascular, metabolic, kidney, endocrine, skin, respiratory, infectious, gastrointestinal diseases and cancer. The ability of curcumin to modulate the functions of multiple signal transductions are linked with attenuation of acute and chronic diseases. Numerous preclinical and clinical studies have revealed that curcumin modulates several molecules in cell signal transduction pathway including PI3K, Akt, mTOR, ERK5, AP-1, TGF-β, Wnt, β-catenin, Shh, PAK1, Rac1, STAT3, PPARγ, EBPα, NLRP3 inflammasome, p38MAPK, Nrf2, Notch-1, AMPK, TLR-4 and MyD-88. Curcumin has a potential to prevent and/or manage various diseases due to its anti-inflammatory, anti-oxidant and anti-apoptotic properties with an excellent safety profile. In contrast, the anti-cancer effects of curcumin are reflected due to induction of growth arrest and apoptosis in various premalignant and malignant cells. This review also carefully emphasized the pharmacokinetics of curcumin and its interaction with other drugs. Clinical studies have shown that curcumin is safe at the doses of 12 g/day but exhibits poor systemic bioavailability. The use of adjuvant like piperine, liposomal curcumin, curcumin nanoparticles and curcumin phospholipid complex has shown enhanced bioavailability and therapeutic potential. Further studies are warranted to prove the potential of curcumin against various ailments.
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Affiliation(s)
- Sita Sharan Patel
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
| | - Ashish Acharya
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
| | - R S Ray
- Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India
| | - Ritesh Agrawal
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
| | - Ramsaneh Raghuwanshi
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
| | - Priyal Jain
- Department of Pharmacy, Sagar Institute of Research and Technology, Bhopal, India
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Hodaei H, Adibian M, Nikpayam O, Hedayati M, Sohrab G. The effect of curcumin supplementation on anthropometric indices, insulin resistance and oxidative stress in patients with type 2 diabetes: a randomized, double-blind clinical trial. Diabetol Metab Syndr 2019; 11:41. [PMID: 31149032 PMCID: PMC6537430 DOI: 10.1186/s13098-019-0437-7] [Citation(s) in RCA: 96] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Accepted: 05/17/2019] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Diabetes mellitus is a common metabolic disorders in human and affect a lot of people around the world. Curcumin is a component of turmeric and in many studies therapeutic effects such as anti-hypertensive, anti-hyperlipidemia, anti-hyperglycemia for this substance are shown. AIM The aim of this study was to investigate the effect of curcumin supplementation on anthropometric indices glycemic control and oxidative stress in overweight patients with type 2 diabetes. MATERIALS AND METHODS In this randomized, double-blind, placebo-controlled trial, 53 participants with type 2 diabetes were divided randomly into the experimental and control groups to receive either 1500 mg curcumin or placebo capsule three times in a day for 10 weeks. RESULT Supplementation with curcumin in type 2 diabetes compare to placebo causes a significant changes in mean weight (- 0.64 ± 0.22 vs. 0.19 ± 0.37 p < 0.05), body mass index (BMI) (0.3 ± 0.03 vs. 0.1 ± 0 p < 0.05), waist circumference (WC) (- 1.2 ± 0.4 vs. - 0.43 ± 0.11 p < 0.05) and fasting blood sugar (FBS) (- 7 ± 2 vs. 3 ± 0.2 p < 0.05) but did not show any difference for hemoglobin A1c (HbA1c), insulin, malondialdehyde (MDA), total antioxidant capacity (TAC), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and pancreatic B cell function (HOMA-B) at end of study. CONCLUSION This study indicated that daily administration of 1500 mg curcumin has positive effects in reducing fasting blood glucose and weight in patients with type 2 diabetes.Trial registration NCT02529982. Registered 19 August 2015, http://www.clinicaltrial.gov.
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Affiliation(s)
- Homa Hodaei
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, 9, Hafezi St., Farahzadi Blvd., Shahrak Qods, P.O. Box: 19395-4741, Tehran, Iran
| | - Mahsa Adibian
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, 9, Hafezi St., Farahzadi Blvd., Shahrak Qods, P.O. Box: 19395-4741, Tehran, Iran
| | - Omid Nikpayam
- Talented Student Center, Student Research Committee, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Hedayati
- Cellular & Molecular Research Center, Research Institute of Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golbon Sohrab
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, 9, Hafezi St., Farahzadi Blvd., Shahrak Qods, P.O. Box: 19395-4741, Tehran, Iran
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Utility of curcumin for the treatment of diabetes mellitus: Evidence from preclinical and clinical studies. JOURNAL OF NUTRITION & INTERMEDIARY METABOLISM 2018. [DOI: 10.1016/j.jnim.2018.05.001] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Lee HJ, Seo HI, Cha HY, Yang YJ, Kwon SH, Yang SJ. Diabetes and Alzheimer's Disease: Mechanisms and Nutritional Aspects. Clin Nutr Res 2018; 7:229-240. [PMID: 30406052 PMCID: PMC6209735 DOI: 10.7762/cnr.2018.7.4.229] [Citation(s) in RCA: 118] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 10/13/2018] [Accepted: 10/14/2018] [Indexed: 12/13/2022] Open
Abstract
Blood glucose homeostasis is well maintained by coordinated control of various hormones including insulin and glucagon as well as cytokines under normal conditions. However, chronic exposure to diabetic environment with high fat/high sugar diets and physical/mental stress can cause hyperglycemia, one of main characteristics of insulin resistance, metabolic syndrome, and diabetes. Hyperglycemia impairs organogenesis and induces organ abnormalities such as cardiac defect in utero. It is a risk factor for the development of metabolic diseases in adults. Resulting glucotoxicity affects peripheral tissues and vessels, causing pathological complications including diabetic neuropathy, nephropathy, vessel damage, and cardiovascular diseases. Moreover, chronic exposure to hyperglycemia can deteriorate cognitive function and other aspects of mental health. Recent reports have demonstrated that hyperglycemia is closely related to the development of cognitive impairment and dementia, suggesting that there may be a cause-effect relationship between hyperglycemia and dementia. With increasing interests in aging-related diseases and mental health, diabetes-related cognitive impairment is attracting great attention. It has been speculated that glucotoxicity can result in structural damage and functional impairment of brain cells and nerves, hemorrhage of cerebral blood vessel, and increased accumulation of amyloid beta. These are potential mechanisms underlying diabetes-related dementia. Nutrients and natural food components have been investigated as preventive and/or intervention strategy. Among candidate components, resveratrol, curcumin, and their analogues might be beneficial for the prevention of diabetes-related cognitive impairment. The purposes of this review are to discuss recent experimental evidence regarding diabetes and cognitive impairment and to suggest potential nutritional intervention strategies for the prevention and/or treatment of diabetes-related dementia.
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Affiliation(s)
- Hee Jae Lee
- Department of Food and Nutrition, Seoul Women's University, Seoul 01797, Korea
| | - Hye In Seo
- Department of Food and Nutrition, Seoul Women's University, Seoul 01797, Korea
| | - Hee Yun Cha
- Department of Food and Nutrition, Seoul Women's University, Seoul 01797, Korea
| | - Yun Jung Yang
- Department of Food and Nutrition, Seoul Women's University, Seoul 01797, Korea
| | - Soo Hyun Kwon
- Department of Food and Nutrition, Seoul Women's University, Seoul 01797, Korea
| | - Soo Jin Yang
- Department of Food and Nutrition, Seoul Women's University, Seoul 01797, Korea
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High Fat/High Glucose Diet Induces Metabolic Syndrome in an Experimental Rat Model. Nutrients 2018; 10:nu10101502. [PMID: 30322196 PMCID: PMC6213024 DOI: 10.3390/nu10101502] [Citation(s) in RCA: 127] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 10/09/2018] [Accepted: 10/12/2018] [Indexed: 02/06/2023] Open
Abstract
Metabolic syndrome (MetS) is defined as a constellation of many metabolic disorders such as hypertension, impaired glucose tolerance, dyslipidemia and obesity, being this last disorder a key factor in the etiology of the syndrome. The widespread of MetS in actual society, mainly in developed countries, is becoming an important health problem and is increasing the need to develop new treatments against this pathology is increasing fast. The main objective of the present study was to evaluate the MetS-associated alterations developed in a new glucose diet-induced-obesity (DIO) rodent model. These alterations were also compared to those alterations developed in a fructose-DIO rodent model. Wistar rats were divided into four groups: Control (C), High-fat (HF), High-fat/high-fructose (HFF) and High-fat/high-glucose (HFG). The animals were fed ad libitum for 20 weeks. At the end of the study, HFG animals showed lower expression of energy expenditure genes when compared to the other DIO groups. Oxidative stress biomarkers such as MDA and mitochondrial RT-qPCR analyses showed an increase of oxidative damage together with mitochondrial dysfunction in HFG group. This group also showed increased insulin and glucose plasma levels, though HFF animals showed the greatest increase on these parameters. All DIO groups showed increased plasma levels of triglycerides. Altogether, our results indicated a better impact of glucose than fructose, when combined with a high-fat diet, to induce most of the alterations associated with MetS in rats. In addition, our research facilitates a new animal model to evaluate future treatments for MetS.
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Kord Varkaneh H, Fatahi S, Tajik S, Rahmani J, Zarezadeh M, Shab-Bidar S. Dietary inflammatory index in relation to obesity and body mass index: a meta-analysis. ACTA ACUST UNITED AC 2018. [DOI: 10.1108/nfs-09-2017-0203] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Purpose
Studies investigating the association between dietary inflammatory index (DII) and body mass index (BMI) have led to inconsistent findings. Therefore, to decisively conclude, this paper aims to clarify the relationship between DII and obesity by performing meta-analysis.
Design/methodology/approach
PubMed, Scopus and Google Scholar were searched up to July 2017 using key words selected from Medical Subject Headings and other related keywords to identify all relevant articles. In total, 22 articles were entered into the meta-analysis; 22 studies compared the mean of BMI among subjects with highest versus the lowest DII and 4 studies had data on the hazard risk (HR) or odds ratio (OR) for obesity.
Findings
A meta-analysis on included studies indicated a significant association on either mean differences (MD) in BMI (MD = 0.811; 95 per cent CI: 0.365-1.256; p: 0.0001) or obesity OR (OR: 1.310; 95 per cent CI: 1.144-1.500; p = 0.000) by comparing the highest and lowest DII categories. Between-study heterogeneity was high (Cochrane Q test, p < 0.001, I2 = 98.1 per cent, df = 21, τ2 = 0.9273), and only dietary assessment methods could explain the source of heterogeneity in which 24-h dietary recalls were homogeny (I2 = 8.4 per cent, df = 2, p = 0.335).
Originality/value
The results of the present meta-analysis suggest that adherence to high DII score increased BMI and obesity. More prospective studies in different populations are needed to better clarify this relation.
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Sadeghi A, Rostamirad A, Seyyedebrahimi S, Meshkani R. Curcumin ameliorates palmitate-induced inflammation in skeletal muscle cells by regulating JNK/NF-kB pathway and ROS production. Inflammopharmacology 2018; 26:1265-1272. [PMID: 29644554 DOI: 10.1007/s10787-018-0466-0] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2017] [Accepted: 03/12/2018] [Indexed: 12/14/2022]
Abstract
Curcumin, a natural polyphenol compound, has the beneficial effects on several diseases such as metabolic syndrome, cancer, and diabetes. The anti-inflammatory property of curcumin has been demonstrated in different cells; however, its role in prevention of palmitate-induced inflammation in skeletal muscle C2C12 cells is not known. In this study, we examined the effect of curcumin on the inflammatory responses stimulated by palmitate in C2C2 cells. The results showed that palmitate upregulated the mRNA expression and protein release of IL-6 and TNF-α cytokines in C2C12 cells, while pretreatment with curcumin was able to attenuate the effect of palmitate on inflammatory cytokines. The anti-inflammatory effect of curcumin was associated with the repression of phosphorylation of IKKα-IKKβ, and JNK. Palmitate also caused an increase in reactive oxygen species (ROS) level that curcumin abrogated it. Collectively, these findings suggest that curcumin may represent a promising therapy for prevention of inflammation in skeletal muscle cells.
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Affiliation(s)
- Asie Sadeghi
- Department of Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Islamic Republic of Iran
| | - Atefeh Rostamirad
- Department of Clinical Biochemistry, Faculty of Medicine Sciences, Tarbiat Modares University, Tehran, Islamic Republic of Iran
| | - Shadisadat Seyyedebrahimi
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Reza Meshkani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. .,Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
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Lembede BW, Joubert J, Nkomozepi P, Erlwanger KH, Chivandi E. Insulinotropic Effect of S-Allyl Cysteine in Rat Pups. Prev Nutr Food Sci 2018; 23:15-21. [PMID: 29662843 PMCID: PMC5894781 DOI: 10.3746/pnf.2018.23.1.15] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2017] [Accepted: 02/08/2018] [Indexed: 12/18/2022] Open
Abstract
S-Allyl cysteine (SAC) is found in garlic and has been reported to exert antidiabetic and antiobesity properties in drug-induced adult experimental models of metabolic dysfunction, but its potential beneficial effects in high-fructose diet neonatal rat models have not been determined. This study investigated the potential prophylactic effects of SAC in high-fructose diet fed suckling rat pups modelling human neonates fed a high-fructose diet. Four-day-old male (n=32) and female (n=32) Wistar rat pups, were randomly assigned to and administered the following treatment regimens daily for 15 days: group I, distilled water; group II, 20% fructose solution (FS); group III, SAC; group IV, SAC+FS. The pups' blood glucose, triglyceride, cholesterol, plasma leptin and insulin concentration, liver lipid content, and liver histology were determined at termination. In female rat pups, orally administered SAC prevented FS-induced hypoinsulinemia but significantly increased (P≤0.05) liver lipid content. Oral administration of SAC significantly increased (P≤0.05) plasma insulin concentration and homeostasis model assessment for insulin resistance in the male pups. The potential sexually dimorphic effects of SAC (insulinotropic effects in male pups and protection of female pups against fructose-induced hypoinsulinemia) suggest that SAC could be potentially exploited as an antidiabetic and insulinotropic agent. Caution should, however, be exercised in the use of SAC during suckling as it could result in excessive liver lipid accumulation and insulin resistance.
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Affiliation(s)
- Busisani W Lembede
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Jeanette Joubert
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Pilani Nkomozepi
- Department of Human Anatomy and Physiology, Faculty of Health Sciences, University of Johannesburg, Johannesburg 2092, South Africa
| | - Kennedy H Erlwanger
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
| | - Eliton Chivandi
- School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa
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Yang F, Yu J, Ke F, Lan M, Li D, Tan K, Ling J, Wang Y, Wu K, Li D. Curcumin Alleviates Diabetic Retinopathy in Experimental Diabetic Rats. Ophthalmic Res 2018; 60:43-54. [PMID: 29597206 DOI: 10.1159/000486574] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 12/30/2017] [Indexed: 11/19/2022]
Abstract
PURPOSE To investigate the potential protective effects of curcumin on the retina in diabetic rats. METHODS An experimental diabetic rat model was induced by a low dose of streptozotocin combined with a high-energy diet. Rats which had blood glucose levels ≥11.6 mmol/L were used as diabetic rats. The diabetic rats were randomly divided into 3 groups: diabetic rats with no treatment (DM), diabetic rats treated with 100 mg/kg curcumin (DM + Cur 100 mg/kg), and diabetic rats treated with 200 mg/kg curcumin (DM + Cur 200 mg/kg). Curcumin was orally administered daily for 16 weeks. After 16 weeks of administration, the rats were euthanized, and eyes were dissected. Retinal histology was examined, and the thickness of the retina was measured. Ultrastructural changes of retinal ganglion cells, inner layer cells, retinal capillary, and membranous disks were observed by electron microscopy. Malondialdehyde, superoxide dismutase, and total antioxidant capacity were measured by ELISA. Expression levels of vascular endothelial growth factor (VEGF) in retina tissues were examined by immunohistochemical staining and ELISA. Expression levels of Bax and Bcl-2 in retina tissues were determined by immunohistochemical staining and Western blotting. RESULTS Curcumin reduced the blood glucose levels of diabetic rats and decreased diabetes-induced body weight loss. Curcumin prevented attenuation of the retina in diabetic rats and ameliorated diabetes-induced ultrastructure changes of the retina, including thinning of the retina, apoptosis of the retinal ganglion cells and inner nuclear layer cells, thickening of retinal capillary basement membrane and disturbance of photoreceptor cell membranous disks. We also found that curcumin has a strong antioxidative ability in the retina of diabetic rats. It was observed that curcumin attenuated the expression of VEGF in the retina of diabetic rats. We also discovered that curcumin had an antiapoptotic effect by upregulating the expression of Bcl-2 and downregulating the expression of Bax in the retina of diabetic rats. CONCLUSIONS Taken together, these results suggest that curcumin may have great therapeutic potential in the treatment of diabetic retinopathy which could be attributed to the hypoglycemic, antioxidant, VEGF-downregulating and neuroprotection properties of curcumin.
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Affiliation(s)
- Fang Yang
- Department of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Jinqiang Yu
- Department of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Feng Ke
- Department of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Mei Lan
- Department of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Dekun Li
- Department of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Ke Tan
- Department of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Jiaojiao Ling
- Department of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Ying Wang
- Department of Ophthalmology, Renmin Hospital, Hubei University of Medicine, Shiyan, China
| | - Kaili Wu
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
| | - Dai Li
- Xianning Aier Eye Hospital, Hubei University of Science and Technology, Xianning, China
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Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:9698258. [PMID: 29743988 PMCID: PMC5884026 DOI: 10.1155/2018/9698258] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 02/12/2018] [Accepted: 02/15/2018] [Indexed: 01/14/2023]
Abstract
The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-known polyphenol derived from the rhizomes of turmeric Curcuma longa, has attracted a great deal of attention as a natural compound with beneficial antidiabetic and anticancer properties, partly due to its antioxidative and anti-inflammatory actions. Although this polyphenolic compound is increasingly being recognized for its growing number of protective health effects, the precise molecular mechanisms through which it reduces diabetes- and cancer-related pathological events have not been fully unraveled. Hence, CUR is the subject of intensive research in the fields Diabetology and Oncology as a potential candidate in the treatment of both T2DM and cancer, particularly since current therapeutic options for their treatment are not satisfactory in clinics. In this review, we summarize the recent progress made on the molecular targets and pathways involved in antidiabetic and anticancer activities of CUR that are responsible for its beneficial health effects.
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High fructose diet-induced metabolic syndrome: Pathophysiological mechanism and treatment by traditional Chinese medicine. Pharmacol Res 2018; 130:438-450. [PMID: 29471102 DOI: 10.1016/j.phrs.2018.02.020] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 02/09/2018] [Accepted: 02/14/2018] [Indexed: 02/08/2023]
Abstract
Fructose is a natural monosaccharide broadly used in modern society. Over the past few decades, epidemiological studies have demonstrated that high fructose intake is an etiological factor of metabolic syndrome (MetS). This review highlights research advances on fructose-induced MetS, especially the underlying pathophysiological mechanism as well as pharmacotherapy by traditional Chinese medicine (TCM), using the PubMed, Web of science, China National Knowledge Infrastructure, China Science and Technology Journal and Wanfang Data. This review focuses on de novo lipogenesis (DNL) and uric acid (UA) production, two unique features of fructolysis different from glucose glycolysis. High level of DNL and UA production can result in insulin resistance, the key pathological event in developing MetS, mostly through oxidative stress and inflammation. Some other pathologies like the disturbance in brain and gut microbiota in the development of fructose-induced MetS in the past years, are also discussed. In management of MetS, TCM is an excellent representative in alternative and complementary medicine with a complete theory system and substantial herbal remedies. TCMs against MetS or MetS components, including Chinese patent medicines, TCM compound formulas, single TCM herbs and active compounds of TCM herbs, are reviewed on their effects and molecular mechanisms. TCMs with hypouricemic activity, which specially target fructose-induced MetS, are highlighted. And new technologies and strategies (such as high-throughput assay and systems biology) in this field are further discussed. In summary, fructose-induced MetS is a multifactorial disorder with the underlying complex mechanisms. Current clinical and pre-clinical evidence supports the potential of TCMs in management of MetS. Additionally, TCMs may show some advantages against complex MetS as their holistic feature through multiple target actions. However, further work is needed to confirm the effectivity and safety of TCMs by high-standard clinical trials, clarify the molecular mechanisms, and develop new anti-MetS drugs by development and application of optimized and feasible strategies and methods.
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Li J, Yu H, Wang S, Wang W, Chen Q, Ma Y, Zhang Y, Wang T. Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism. DRUG DESIGN DEVELOPMENT AND THERAPY 2018; 12:121-135. [PMID: 29391777 PMCID: PMC5768189 DOI: 10.2147/dddt.s151860] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.
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Affiliation(s)
- Jian Li
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin
| | - Haiyang Yu
- Department of Phytochemistry, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Sijian Wang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin
| | - Wei Wang
- Internal Medicine, Houston Methodist Hospital, Houston, TX, USA
| | - Qian Chen
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin
| | - Yanmin Ma
- Department of Phytochemistry, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Yi Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin
| | - Tao Wang
- Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin
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Geng S, Wang S, Zhu W, Xie C, Li X, Wu J, Zhu J, Jiang Y, Yang X, Li Y, Chen Y, Wang X, Meng Y, Zhong C. Curcumin suppresses JNK pathway to attenuate BPA-induced insulin resistance in LO2 cells. Biomed Pharmacother 2018; 97:1538-1543. [PMID: 29793316 DOI: 10.1016/j.biopha.2017.11.069] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 11/09/2017] [Accepted: 11/10/2017] [Indexed: 11/24/2022] Open
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de Matos AM, de Macedo MP, Rauter AP. Bridging Type 2 Diabetes and Alzheimer's Disease: Assembling the Puzzle Pieces in the Quest for the Molecules With Therapeutic and Preventive Potential. Med Res Rev 2017; 38:261-324. [PMID: 28422298 DOI: 10.1002/med.21440] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 01/18/2017] [Accepted: 02/14/2017] [Indexed: 12/19/2022]
Abstract
Type 2 diabetes (T2D) and Alzheimer's disease (AD) are two age-related amyloid diseases that affect millions of people worldwide. Broadly supported by epidemiological data, the higher incidence of AD among type 2 diabetic patients led to the recognition of T2D as a tangible risk factor for the development of AD. Indeed, there is now growing evidence on brain structural and functional abnormalities arising from brain insulin resistance and deficiency, ultimately highlighting the need for new approaches capable of preventing the development of AD in type 2 diabetic patients. This review provides an update on overlapping pathophysiological mechanisms and pathways in T2D and AD, such as amyloidogenic events, oxidative stress, endothelial dysfunction, aberrant enzymatic activity, and even shared genetic background. These events will be presented as puzzle pieces put together, thus establishing potential therapeutic targets for drug discovery and development against T2D and diabetes-induced cognitive decline-a heavyweight contributor to the increasing incidence of dementia in developed countries. Hoping to pave the way in this direction, we will present some of the most promising and well-studied drug leads with potential against both pathologies, including their respective bioactivity reports, mechanisms of action, and structure-activity relationships.
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Affiliation(s)
- Ana Marta de Matos
- Faculdade de Ciências, Universidade de Lisboa, Ed. C8, Campo Grande, 1749-016, Lisbon, Portugal.,CEDOC Chronic Diseases, Nova Medical School, Rua Câmara Pestana n 6, 6-A, Ed. CEDOC II, 1150-082, Lisbon, Portugal
| | - Maria Paula de Macedo
- CEDOC Chronic Diseases, Nova Medical School, Rua Câmara Pestana n 6, 6-A, Ed. CEDOC II, 1150-082, Lisbon, Portugal
| | - Amélia Pilar Rauter
- Faculdade de Ciências, Universidade de Lisboa, Ed. C8, Campo Grande, 1749-016, Lisbon, Portugal
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Geng S, Wang S, Zhu W, Xie C, Li X, Wu J, Zhu J, Jiang Y, Yang X, Li Y, Chen Y, Wang X, Meng Y, Zhu M, Wu R, Huang C, Zhong C. Curcumin attenuates BPA-induced insulin resistance in HepG2 cells through suppression of JNK/p38 pathways. Toxicol Lett 2017; 272:75-83. [DOI: 10.1016/j.toxlet.2017.03.011] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 03/07/2017] [Accepted: 03/10/2017] [Indexed: 12/11/2022]
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Chen Q, Wang T, Li J, Wang S, Qiu F, Yu H, Zhang Y, Wang T. Effects of Natural Products on Fructose-Induced Nonalcoholic Fatty Liver Disease (NAFLD). Nutrients 2017; 9:nu9020096. [PMID: 28146130 PMCID: PMC5331527 DOI: 10.3390/nu9020096] [Citation(s) in RCA: 123] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 01/22/2017] [Indexed: 01/21/2023] Open
Abstract
As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance. Cellular signaling research indicated that partial factors play significant roles in fructose-induced NAFLD, involving liver X receptor (LXR)α, sterol regulatory element binding protein (SREBP)-1/1c, acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD), peroxisome proliferator–activated receptor α (PPARα), leptin nuclear factor-erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), c-Jun amino terminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K) and adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK). Until now, a series of natural products have been reported as regulators of NAFLD in vivo and in vitro. This paper reviews the natural products (e.g., curcumin, resveratrol, and (−)-epicatechin) and their mechanisms of ameliorating fructose-induced NAFLD over the past years. Although, as lead compounds, natural products usually have fewer activities compared with synthesized compounds, it will shed light on studies aiming to discover new drugs for NAFLD.
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Affiliation(s)
- Qian Chen
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan Road, Nankai District, Tianjin 300193, China.
| | - Tingting Wang
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan Road, Nankai District, Tianjin 300193, China.
| | - Jian Li
- Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.
| | - Sijian Wang
- Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.
| | - Feng Qiu
- Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.
| | - Haiyang Yu
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan Road, Nankai District, Tianjin 300193, China.
| | - Yi Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193, China.
| | - Tao Wang
- Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshan Road, Nankai District, Tianjin 300193, China.
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Yanez M, Blanchette J, Jabbarzadeh E. Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds. Curr Pharm Des 2017; 23:6347-6357. [PMID: 28521709 PMCID: PMC5681444 DOI: 10.2174/1381612823666170510124348] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 04/17/2017] [Accepted: 04/28/2017] [Indexed: 02/06/2023]
Abstract
Tissue engineering offers a promising strategy to restore injuries resulting from trauma, infection, tumor resection, or other diseases. In spite of significant progress, the field faces a significant bottleneck; the critical need to understand and exploit the interdependencies of tissue healing, angiogenesis, and inflammation. Inherently, the balance of these interacting processes is affected by a number of injury site conditions that represent a departure from physiological environment, including reduced pH, increased concentration of free radicals, hypoglycemia, and hypoxia. Efforts to harness the potential of immune response as a therapeutic strategy to promote tissue repair have led to identification of natural compounds with significant anti-inflammatory properties. This article provides a concise review of the body's inflammatory response to biomaterials and describes the role of oxygen as a physiological cue in this process. We proceed to highlight the potential of natural compounds to mediate inflammatory response and improve host-graft integration. Herein, we discuss the use of natural compounds to map signaling molecules and checkpoints that regulate the cross-linkage of immune response and skeletal repair.
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Affiliation(s)
- Maria Yanez
- Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA
| | - James Blanchette
- Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208, USA
| | - Ehsan Jabbarzadeh
- Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA
- Biomedical Engineering Program, University of South Carolina, Columbia, SC 29208, USA
- Department of Orthopedic Surgery, University of South Carolina School of Medicine, Columbia SC, 29209, USA
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Zouari R, Hamden K, Feki AE, Chaabouni K, Makni-Ayadi F, Kallel C, Sallemi F, Ellouze-Chaabouni S, Ghribi-Aydi D. Protective and curative effects of Bacillus subtilis SPB1 biosurfactant on high-fat-high-fructose diet induced hyperlipidemia, hypertriglyceridemia and deterioration of liver function in rats. Biomed Pharmacother 2016; 84:323-329. [DOI: 10.1016/j.biopha.2016.09.023] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Revised: 09/06/2016] [Accepted: 09/07/2016] [Indexed: 01/16/2023] Open
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Rattanavichit Y, Chukijrungroat N, Saengsirisuwan V. Sex differences in the metabolic dysfunction and insulin resistance of skeletal muscle glucose transport following high fructose ingestion. Am J Physiol Regul Integr Comp Physiol 2016; 311:R1200-R1212. [PMID: 27834291 DOI: 10.1152/ajpregu.00230.2016] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Revised: 10/20/2016] [Accepted: 11/04/2016] [Indexed: 01/20/2023]
Abstract
The role of high fructose ingestion (HFI) in the development of conditions mimicking human metabolic syndrome has mostly been demonstrated in male animals; however, the extent of HFI-induced metabolic alterations in females remains unclear. The present study investigated whether HFI-induced metabolic perturbations differ between sexes and whether HFI aggravates the metabolic disturbances under ovarian hormone deprivation. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were given either water or liquid fructose (10% wt/vol) for 6 wk. Blood pressure, glucose tolerance, insulin-stimulated glucose transport activity and signaling proteins, including insulin receptor (IR), insulin receptor substrate 1 (IRS-1), Akt, Akt substrate of 160 kDa (AS160), AMPKα, JNK, p38 MAPK, angiotensin-converting enzyme (ACE), ANG II type 1 receptor (AT1R), ACE2, and Mas receptor (MasR) in skeletal muscle, were evaluated. We found that HFI led to glucose intolerance and hypertension in male and OVX rats but not in female rats with intact ovaries. Moreover, HFI did not induce insulin resistance in the skeletal muscle of female and OVX rats but impaired the insulin-stimulated glucose transport activity in the skeletal muscle of male rats, which was accompanied by lower insulin-stimulated IRS-1 Tyr989 (44%), Akt Ser473 (30%), and AS160 Ser588 (43%), and increases in insulin-stimulated IRS-1 Ser307 (78%), JNK Thr183/Tyr185 (69%), and p38 MAPK Thr180/Tyr182 (81%). The results from the present study show sex differences in the development of metabolic syndrome-like conditions and indicate the protective role of female sex hormones against HFI-induced cardiometabolic abnormalities.
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Affiliation(s)
- Yupaporn Rattanavichit
- Exercise Physiology Laboratory, Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Natsasi Chukijrungroat
- Exercise Physiology Laboratory, Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Vitoon Saengsirisuwan
- Exercise Physiology Laboratory, Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand
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Kelany ME, Hakami TM, Omar AH. Curcumin improves the metabolic syndrome in high-fructose-diet-fed rats: role of TNF-α, NF-κB, and oxidative stress. Can J Physiol Pharmacol 2016; 95:140-150. [PMID: 27901349 DOI: 10.1139/cjpp-2016-0152] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
This study aimed to investigate effects of curcumin on high fructose diet (HFD)-induced metabolic syndrome (MetS) in rats and the possible mechanisms involved. MetS was induced in male albino rats (n = 20), over 8 weeks, by 65% HFD. For 8-week experiment period, rats were assigned to 2 equal groups: curcumin-treated rats received curcumin (200 mg/kg, p.o, once daily) along with HFD, and untreated rats were fed with HFD only. We evaluated body mass (BM), systolic blood pressure (SBP), homeostasis model assessment of insulin resistance (HOMA-IR), and serum levels of glucose, insulin, leptin, total cholesterol (TC), triglycerides (TGs), uric acid, malondialdehyde (MDA; lipid peroxidation product), and tumor necrosis factor-α (TNF-α; inflammatory cytokine), and serum catalase (endogenous antioxidant) activity and immunohistochemical expression of nuclear factor κB (NF-κB; inflammation-related transcription factor) in hepatocytes. HFD produced increases in BM, SBP, HOMA-IR, and serum levels of glucose, insulin, leptin, TC, TGs, uric acid, MDA, and TNF-α, a decrease in catalase activity, and strong positive expression of NF-κB in hepatocytes. Curcumin, in presence of HFD, produced significant improvements in all glucose and fat metabolism parameters, and in oxidative stress and inflammation biomarkers. Curcumin may potentially be useful in the treatment of MetS through its ability to modulate oxidation stress status and inflammation cascades.
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Affiliation(s)
| | - Tahir M Hakami
- b Clinical Pharmacology Department, Faculty of Medicine, Jazan University, Saudi Arabia
| | - Adel H Omar
- c Clinical Pharmacology Department, Faculty of Medicine, Menoufeya University, Egypt
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Sah SP, Singh B, Choudhary S, Kumar A. Animal models of insulin resistance: A review. Pharmacol Rep 2016; 68:1165-1177. [PMID: 27639595 DOI: 10.1016/j.pharep.2016.07.010] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Revised: 07/26/2016] [Accepted: 07/28/2016] [Indexed: 12/22/2022]
Abstract
Insulin resistance can be seen as a molecular and genetic mystery, with a role in the pathophysiology of type 2 diabetes mellitus. It is a basis for a number of chronic diseases like hypertension, dyslipidemia, glucose intolerance, coronary heart disease, cerebral vascular disease along with T2DM, thus the key is to cure and prevent insulin resistance. Critical perspicacity into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by various transgenic and non-transgenic models which is not possible in human studies. The following review comprises the pathophysiology involved in insulin resistance, various factors causing insulin resistance, their screening and various genetic and non-genetic animal models highlighting the pathological and metabolic characteristics of each.
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Affiliation(s)
- Sangeeta Pilkhwal Sah
- Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.
| | - Barinder Singh
- Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India
| | - Supriti Choudhary
- Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India
| | - Anil Kumar
- Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India
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Kang MG, Lee HJ, Cho JY, Kim K, Yang SJ, Kim D. Anti-inflammatory effects of sucrose-derived oligosaccharides produced by a constitutive mutant L. mesenteroides B-512FMCM dextransucrase in high fat diet-fed mice. Biochem Biophys Res Commun 2016; 477:350-5. [PMID: 27342664 DOI: 10.1016/j.bbrc.2016.06.102] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 06/20/2016] [Indexed: 01/07/2023]
Abstract
Oligosaccharide (OS) is used as a sugar replacement as well as an ingredient in functional foods because of its beneficial effects, mainly on reducing calorie content and promoting intestinal health. By contrast, the effects of OS on inflammation are less well investigated. The purpose of this study was to investigate the effects of sucrose-derived OS on glucose control and inflammation in high fat (HF) diet-fed mice. Male C57BL6 mice were randomly assigned to six treatment groups (n = 10-14 mice per group): 1) lean control (CON), 2) HF control, 3) HF-low sucrose (LS, 100 mg/kg/day), 4) HF-high sucrose (HS, 1000 mg/kg/day), 5) HF-low OS (LOS, 100 mg/kg/day), and 6) HF-high OS (HOS, 1000 mg/kg/day). PBS (vehicle), sucrose, and OS were administered by stomach gavage. Body weight, food intake, and markers of liver function (activities of aspartate aminotransferase and alanine aminotransferase) were not affected by the treatments. HOS treatment decreased levels of serum glucose, insulin, and homeostasis model assessment-insulin resistance compared with sucrose treatment. However, serum adiponectin levels of the HOS group were higher than those of the sucrose groups. Serum levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and fetuin-A were lower in the HOS group than in the sucrose groups. Hepatic gene expression levels of pro-inflammatory cytokines and related factors (fetuin-A, NF-κB, TLR4, TNF-alpha, and IL-6) were decreased and the levels of insulin signaling-related molecules (sirtuin 1, insulin receptor, and Akt) were increased in HOS-treated mice as compared with sucrose-treated mice. These results demonstrate that OS treatment is effective in improving glucose control and inflammation in high fat diet-fed mice.
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Affiliation(s)
- Min-Gyung Kang
- Division of Food and Nutrition, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Hee Jae Lee
- Department of Food and Nutrition, Seoul Women's University, Seoul, 01797, Republic of Korea
| | - Jae-Young Cho
- Graduate School of International Agricultural Technology and Institute of Food Industrialization, Institutes of Green Bio Science & Technology, Seoul National University, Gangwon-do, 25354, Republic of Korea
| | - Kanghwa Kim
- Division of Food and Nutrition, Chonnam National University, Gwangju, 61186, Republic of Korea
| | - Soo Jin Yang
- Department of Food and Nutrition, Seoul Women's University, Seoul, 01797, Republic of Korea.
| | - Doman Kim
- Graduate School of International Agricultural Technology and Institute of Food Industrialization, Institutes of Green Bio Science & Technology, Seoul National University, Gangwon-do, 25354, Republic of Korea.
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