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Jeon S, Lee H, Kim SY, Lee CH, Lim Y. Effects of Metabolites Derived from Guava ( Psidium guajava L.) Leaf Extract Fermented by Limosilactobacillus fermentum on Hepatic Energy Metabolism via SIRT1-PGC1α Signaling in Diabetic Mice. Nutrients 2024; 17:7. [PMID: 39796441 PMCID: PMC11722574 DOI: 10.3390/nu17010007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/20/2024] [Accepted: 12/22/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND/OBJECTIVES Type 2 diabetes mellitus (T2DM) is considered a serious risk to public health since its prevalence is rapidly increasing worldwide despite numerous therapeutics. Insulin resistance in T2DM contributes to chronic inflammation and other metabolic abnormalities that generate fat accumulation in the liver, eventually leading to the progression of metabolic dysfunction-associated fatty liver disease (MAFLD). Recently, the possibility that microbial-derived metabolites may alleviate MAFLD through enterohepatic circulation has emerged, but the underlying mechanism remains unclear. In this research, we utilized metabolites obtained from the fermentation of guava leaf extract, which is well-known for its antidiabetic activity, to investigate their effects and mechanisms on MAFLD. METHODS Diabetes was induced by a high-fat diet and streptozotocin injection (80 mg/kg body weight) twice in mice. Subsequently, mice whose fasting blood glucose levels were measured higher than 300 mg/dL were administered with metabolites of Limosilactobacillus fermentum (LF) (50 mg/kg/day) or guava leaf extract fermented by L. fermentum (GFL) (50 mg/kg/day) by gavage for 15 weeks. RESULTS GFL supplementation mitigated hyperglycemia and hepatic insulin resistance. Moreover, GFL regulated abnormal hepatic histological changes and lipid profiles in diabetic mice. Furthermore, GFL enhanced energy metabolism by activating the sirtuin1 (SIRT1)/proliferator-activated receptor γ coactivator 1α (PGC1α)/peroxisome proliferator-activated receptor (PPAR)-α pathway in diabetic mice. Meanwhile, GFL supplementation suppressed hepatic inflammation in diabetic mice. CONCLUSIONS Taken together, the current study elucidated that GFL could be a potential therapeutic to ameliorate hyperglycemia and hepatic steatosis by improving SIRT1/PGC-1α/ PPAR-α-related energy metabolism in T2DM.
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Affiliation(s)
- Sohyun Jeon
- Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea; (S.J.); (H.L.)
| | - Heaji Lee
- Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea; (S.J.); (H.L.)
| | - Sun-Yeou Kim
- College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea;
| | - Choong-Hwan Lee
- Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea;
| | - Yunsook Lim
- Department of Food and Nutrition, Kyung Hee University, 26 Kyunghee-Daero, Dongdaemun-Gu, Seoul 02447, Republic of Korea; (S.J.); (H.L.)
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Behairy A, Hashem MMM, Abo-El-Sooud K, El-Metwally AE, Soliman AM, Mouneir SM, Hassan BA, Abd-Elhakim YM. Mitigating effect of gallic acid on zinc oxide nanoparticles and arsenic trioxide-induced spermatogenesis suppression, testicular injury, hormonal imbalance, and immunohistochemical changes in rats. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:9859-9875. [PMID: 38935127 PMCID: PMC11582332 DOI: 10.1007/s00210-024-03228-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 06/06/2024] [Indexed: 06/28/2024]
Abstract
The current study compared the effects of incorporated exposure to arsenic trioxide (As) and zinc oxide nanoparticles (ZnONPs) on male reproductive hormones, oxidative stress, and inflammatory biomarkers in adult rats to each metal alone. A defensive trial with gallic acid (GA) has also been studied. A total of 60 adult male Sprague Dawley rats were categorized into six groups: control, GA (20 mg/kg), ZnONPs (100 mg/kg), As (8 mg/kg), ZnONPs with As, and GA concurrently with ZnONPs and As at the same previous doses. The regimens were applied for 60 days in sequence. Current findings showed significant weight loss in all study groups, with testicular weights significantly decreased in the As and combined groups. Testosterone, follicular stimulating hormone, and luteinizing hormone serum levels were also considerably reduced, while serum levels of estradiol increased. Inducible nitric oxide synthase (iNOS) immunoexpression was significantly upregulated while proliferating cell nuclear antigen (PCNA) was downregulated. Moreover, there was a significant elevation of testicular malondialdehyde, reduction of testicular superoxide dismutase, and glutathione peroxidase with disruptive testes, prostate glands, and seminal vesicle alterations in all experimental groups with marked changes in the combined group. Additionally, the present results revealed the protective effects of GA on ZnONPs and As adverse alterations in rats. GA enhanced sperm picture, oxidant status, and hormonal profile. Also, it modulates iNOS and PCNA immunoexpression and recovers the histoarchitecture of the testes, prostate glands, and seminal vesicles. Ultimately, GA may be a promising safeguarding agent against ZnONPs and As-induced disturbances to reproductive parameters.
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Affiliation(s)
- Amany Behairy
- Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt
| | - Mohamed M M Hashem
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Khaled Abo-El-Sooud
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Abeer E El-Metwally
- Pathology Department, Animal Reproduction Research Institute, Giza, 3514805, Egypt
| | - Ahmed M Soliman
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Samar M Mouneir
- Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Bayan A Hassan
- Pharmacology Department, Faculty of Pharmacy, Future University, Cairo, 11835, Egypt
| | - Yasmina M Abd-Elhakim
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt.
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Gomaa S, Nassef M, Hafez A. Potentials of bone marrow cells-derived from naïve or diabetic mice in autoimmune type 1 diabetes: immunomodulatory, anti-inflammatory, anti hyperglycemic, and antioxidative. Endocrine 2024; 86:959-979. [PMID: 39014283 PMCID: PMC11554735 DOI: 10.1007/s12020-024-03929-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 06/11/2024] [Indexed: 07/18/2024]
Abstract
BACKGROUND The scarcity of transplanted human islet tissue and the requirement for immunosuppressive drugs to prevent the rejection of allogeneic grafts have hindered the treatment of autoimmune type 1 diabetes mellitus (T1DM) through islet transplantation. However, there is hope in adoptively transferred bone marrow cells (BMCs) therapy, which has emerged as a propitious pathway for forthcoming medications. BMCs have the potential to significantly impact both replacement and regenerative therapies for a range of disorders, including diabetes mellitus, and have demonstrated anti-diabetic effects. AIM The main goal of this study is to evaluate the effectiveness of adoptively transferred bone marrow cells derived from either naïve mice (nBMCs) or diabetic mice (dBMCs) in treating a T1DM mice model. METHODS Male Swiss albino mice were starved for 16 h and then injected with streptozotocin (STZ) at a dose of 40 mg/kg body weight for 5 consecutive days to induce T1DM. After 14 days, the diabetic mice were distributed into four groups. The first group served as a diabetic control treated with sodium citrate buffer, while the other three groups were treated for two weeks, respectively, with insulin (subcutaneously at a dose of 8 U/kg/day), nBMCs (intravenously at a dose of 1 × 106 cells/mouse/once), and dBMCs (intravenously at a dose of 1 × 106 cells/mouse/once). RESULTS It is worth noting that administering adoptively transferred nBMCs or adoptively transferred dBMCs to STZ-induced T1DM mice resulted in a significant amelioration in glycemic condition, accompanied by a considerable reduction in the level of blood glucose and glycosylated hemoglobin % (HbA1C %), ultimately restoring serum insulin levels to their initial state in control mice. Administering nBMCs or dBMCs to STZ-induced T1DM mice led to a remarkable decrease in levels of inflammatory cytokine markers in the serum, including interferon-γ (INF-γ), tumor necrosis factor- α (TNF-α), tumor growth factor-β (TGF-β), interleukin-1 β (L-1β), interlekin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10). Additionally, STZ-induced T1DM mice, when treated with nBMCs or dBMCs, experienced a notable rise in total immunoglobulin (Ig) level. Furthermore, there was a significant reduction in the levels of islet cell autoantibodies (ICA) and insulin autoantibodies (IAA). Furthermore, the serum of STZ-induced T1DM mice showed a significant increase in Zinc transporter 8 antigen protein (ZnT8), islet antigen 2 protein (IA-2), and glutamic acid decarboxylase antigen protein (GAD) levels. Interestingly, the administration of nBMCs or dBMCs resulted in a heightened expression of IA-2 protein in STZ-induced T1DM mice treated with nBMCs or dBMCs. Furthermore, the level of malondialdehyde (MDA) was increased, while the levels of catalase (CAT) and superoxide dismutase (SOD) were decreased in non-treated STZ-induced T1DM mice. However, when nBMCs or dBMCs were administered to STZ-induced T1DM mice, it had a significant impact on reducing oxidative stress. This was accomplished by reducing the levels of MDA in the serum and enhancing the activities of enzymatic antioxidants like CAT and SOD. STZ-induced T1DM mice displayed a significant elevation in the levels of liver enzymes ALT and AST, as well as heightened levels of creatinine and urea. Considering the crucial roles of the liver and kidney in metabolism and excretion, this research further examined the effects of administering nBMCs or dBMCs to STZ-induced T1DM mice. Notably, the administration of these cells alleviated the observed effects. CONCLUSION The present study suggests that utilizing adoptively transferred nBMCs or adoptively transferred dBMCs in the treatment of T1DM led to noteworthy decreases in blood glucose levels, possibly attributed to their capacity to enhance insulin secretion and improve the performance of pancreatic islets. Additionally, BMCs may exert their beneficial effects on the pancreatic islets of diabetic mice through their immunomodulatory, antioxidant, anti-inflammatory, and anti-oxidative stress properties.
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Affiliation(s)
- Soha Gomaa
- Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt.
| | - Mohamed Nassef
- Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt
| | - Amira Hafez
- Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt
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Shahidi F, Danielski R. Review on the Role of Polyphenols in Preventing and Treating Type 2 Diabetes: Evidence from In Vitro and In Vivo Studies. Nutrients 2024; 16:3159. [PMID: 39339759 PMCID: PMC11435057 DOI: 10.3390/nu16183159] [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: 08/19/2024] [Revised: 09/08/2024] [Accepted: 09/10/2024] [Indexed: 09/30/2024] Open
Abstract
Type 2 diabetes (T2D) is one of the leading causes of death globally. There was a 70% increase in diabetes-related deaths between 2000 and 2020, particularly among males. This non-communicable disease is characterized by increased insulin resistance, leading to elevated blood sugar levels and, if untreated, resulting in complications such as nerve damage, kidney disease, blindness, and poor wound healing. T2D management includes dietary intervention, physical exercise, and the administration of blood sugar-lowering medication. However, these medications often have side effects related to intestinal discomfort. Therefore, natural alternatives to standard diabetes medications are being sought to improve the quality of life for individuals with this condition. Polyphenols, which are naturally occurring plant metabolites, have emerged as strong candidates for T2D control. Various phenolic acids (e.g., chlorogenic acid), flavonoids (e.g., quercetin), proanthocyanidins (e.g., procyanidin B2), gallotannins (e.g., monogalloyl hexoside), and ellagitannins (e.g., ellagic acid hexoside) can enhance insulin sensitivity in tissues, reduce chronic inflammation, scavenge free radicals, improve insulin secretion, inhibit enzymes involved in carbohydrate digestion, regulate glucose transport across cell membranes, and modulate gut microbiota. This contribution compiles up-to-date evidence from in vitro and in vivo studies on the role of polyphenols in the prevention and management of T2D, emphasizing the mechanisms of action underlying these effects.
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Affiliation(s)
- Fereidoon Shahidi
- Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1C 5S7, Canada
| | - Renan Danielski
- Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL A1C 5S7, Canada
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Hadidi M, Liñán-Atero R, Tarahi M, Christodoulou MC, Aghababaei F. The Potential Health Benefits of Gallic Acid: Therapeutic and Food Applications. Antioxidants (Basel) 2024; 13:1001. [PMID: 39199245 PMCID: PMC11352096 DOI: 10.3390/antiox13081001] [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: 07/17/2024] [Revised: 08/14/2024] [Accepted: 08/15/2024] [Indexed: 09/01/2024] Open
Abstract
Gallic acid (GA), a phenolic acid found in fruits and vegetables, has been consumed by humans for centuries. Its extensive health benefits, such as antimicrobial, antioxidant, anticancer, anti-inflammatory, and antiviral properties, have been well-documented. GA's potent antioxidant capabilities enable it to neutralize free radicals, reduce oxidative stress, and protect cells from damage. Additionally, GA exerts anti-inflammatory effects by inhibiting inflammatory cytokines and enzymes, making it a potential therapeutic agent for inflammatory diseases. It also demonstrates anticancer properties by inhibiting cancer cell growth and promoting apoptosis. Furthermore, GA offers cardiovascular benefits, such as lowering blood pressure, decreasing cholesterol, and enhancing endothelial function, which may aid in the prevention and management of cardiovascular diseases. This review covers the chemical structure, sources, identification and quantification methods, and biological and therapeutic properties of GA, along with its applications in food. As research progresses, the future for GA appears promising, with potential uses in functional foods, pharmaceuticals, and nutraceuticals aimed at improving overall health and preventing disease. However, ongoing research and innovation are necessary to fully understand its functional benefits, address current challenges, and establish GA as a mainstay in therapeutic and nutritional interventions.
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Affiliation(s)
- Milad Hadidi
- Institute of Physiological Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria
| | - Rafael Liñán-Atero
- Department of Organic Chemistry, Faculty of Chemical Sciences and Technologies, University of Castilla-La Mancha, 13071 Ciudad Real, Spain;
| | - Mohammad Tarahi
- Department of Food Science and Technology, School of Agriculture, Shiraz University, Shiraz 7144165186, Iran;
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Khadrawy SM, Altoom NG, Alotaibi AG, Othman SI. Hepatoprotective potential of taxifolin in type 2 diabetic rats: modulation of oxidative stress and Bcl2/Bax/Caspase-3 signaling pathway. Mol Biol Rep 2024; 51:897. [PMID: 39115553 DOI: 10.1007/s11033-024-09805-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 07/01/2024] [Indexed: 02/06/2025]
Abstract
BACKGROUND Diabetes mellitus (DM) is a global metabolic problem. Several factors including hyperglycemia, oxidative stress, and inflammation play significant roles in the development of DM complications. Apoptosis is also an essential event in DM pathophysiology, -with B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) determining apoptotic susceptibility. The present study aimed to elucidate the protective effects of two doses of taxifolin (TXF) on liver damage in diabetic rats and explore the possible mechanisms of action. METHODS AND RESULTS DM was induced in eighteen rats through intraperitoneal injections of 50 mg/kg streptozotocin and 110 mg/kg nicotinamide. Diabetic rats received daily oral intubation of 25 and 50 mg/kg TXF for 3 months. In the untreated diabetic group, there was a significant increase in fasting and postprandial glucose levels, glycosylated hemoglobin A1C (HbA1c), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while insulin and adiponectin levels decreased significantly. Both TXF doses mitigated hyperglycemia, regulated cytokine production, and increased insulin level. Gene expressions and protein levels of Bax, caspase 3, and cytochrome c were significantly increased, while Bcl-2 was significantly decreased in the livers of diabetic rats, effects that were significantly ameliorated after TXF treatment. The results of the TUNEL assay supported the apoptotic pathway. Additionally, TXF significantly decreased lipid peroxidation and enhanced antioxidant enzyme activity in diabetic rats. Liver enzymes and histopathological changes also showed improvement. CONCLUSIONS TXF mitigated diabetes-associated hepatic damage by reducing hyperglycemia, oxidative stress, inflammation, and modulating anti-/pro-apoptotic genes and proteins. A dose of 50 mg/kg TXF was more effective than 25 mg/kg and is recommended for consumption.
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Affiliation(s)
- Sally M Khadrawy
- Genetics and Molecular Biology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, 62514, Egypt.
| | - Naif G Altoom
- Biology Department, King Khalid Military Academy, P.O. Box 22140, Riyadh, 11495, Saudi Arabia
| | | | - Sarah I Othman
- Biology Department, College of Science, Princess Nourah bint Abdulrahman University, P.O. BOX 84428, Riyadh, 11671, Saudi Arabia
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Hafez MH, Ez Elarab SM, Tohamy HG, El-Far AH. Thymoquinone attenuates diabetes-induced hepatic damage in rat via regulation of oxidative/nitrosative stress, apoptosis, and inflammatory cascade with molecular docking approach. Sci Rep 2024; 14:13016. [PMID: 38844763 PMCID: PMC11156670 DOI: 10.1038/s41598-024-62780-y] [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: 01/23/2024] [Accepted: 05/21/2024] [Indexed: 06/09/2024] Open
Abstract
Diabetes mellitus (DM) is a complex metabolic condition that causes organ dysfunction. The current experiment sought to determine the effect of thymoquinone (TQ) on hyperglycemia, hyperlipidemia, oxidative/nitrosative stress, inflammation, and apoptosis in diabetic rats prompted by streptozotocin (STZ) (55 mg/kg body weight i/p). The animals were allocated into control, TQ (50 mg/kg B.W. orally administered for 4 succeeding weeks), Diabetic, and Diabetic + TQ groups. This study confirmed that TQ preserves the levels of insulin, fasting blood glucose, HOMA β-cell indices, HbA1c %, body weight, and lipid profile substantially relative to the DC group. Furthermore, hepatic antioxidant (CAT, GSH, and T-SOD) values were reduced. Conversely, the enzymatic activity of liver functions (AST, ALT, ALP, cytochrome P450, and hepatic glucose-6-phosphatase), lipid peroxidation (MDA), pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), nitric oxide (NO) and inflammatory marker (CRP) enhanced with STZ administration, which is substantially restored after TQ treatment. Relative to the diabetic rats, TQ reestablished the hepatic architectural changes and collagen fibers. Additionally, TQ downregulated the intensity of the immunohistochemical staining of pro-apoptotic marker (caspase-3), p53, and tumor necrosis factor-alpha (TNF-α) proteins in hepatic tissues. Furthermore, TQ displayed abilities to interact and inhibit the binding site of caspase-3, interleukin-6 receptor, interleukin-1 receptor type 1, TNF receptor superfamily member 1A, and TNF receptor superfamily member 1B in rats following the molecular docking modeling. All these data re-establish the liver functions, antioxidant enzymes, anti-inflammatory markers, and anti-apoptotic proteins impacts of TQ in STZ-induced DM rats. Founded on these outcomes, the experiment proposes that TQ is a novel natural supplement with various clinical applications, including managing DM, which in turn is recommended to play a pivotal role in preventing the progression of diabetes mellitus.
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Affiliation(s)
- Mona H Hafez
- Department of Physiology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, 22758, Egypt.
| | - Samar M Ez Elarab
- Department of Histology and Cytology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, 22758, Egypt
| | - Hossam G Tohamy
- Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Alexandria, 22758, Egypt
| | - Ali H El-Far
- Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, Egypt
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Chen F, Zhang X, Wang J, Wang F, Mao J. P-coumaric Acid: Advances in Pharmacological Research Based on Oxidative Stress. Curr Top Med Chem 2024; 24:416-436. [PMID: 38279744 DOI: 10.2174/0115680266276823231230183519] [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: 09/25/2023] [Revised: 11/20/2023] [Accepted: 11/28/2023] [Indexed: 01/28/2024]
Abstract
P-coumaric acid is an important phenolic compound that is mainly found in fruits, vegetables, grains, and fungi and is also abundant in Chinese herbal medicines. In this review, the pharmacological research progress of p-coumaric acid in recent years was reviewed, with emphasis on its role and mechanism in oxidative stress-related diseases, such as inflammation, cardiovascular diseases, diabetes, and nervous system diseases. Studies have shown that p-coumaric acid has a positive effect on the prevention and treatment of these diseases by inhibiting oxidative stress. In addition, p-coumaric acid also has anti-tumor, antibacterial, anti-aging skin and other pharmacological effects. This review will provide reference and inspiration for further research on the pharmacological effects of p-coumaric acid.
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Affiliation(s)
- Feixiang Chen
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xinxin Zhang
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Junxiang Wang
- Experimental Center of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Fukai Wang
- Breast Cancer Center, Shandong Cancer Hospital and Institute, Jinan, China
| | - Jinlong Mao
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China
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Brahma S, Goyal AK, Dhamodhar P, Kumari MR, Jayashree S, Usha T, Middha SK. Can Polyherbal Medicine be used for the Treatment of Diabetes? - A Review of Historical Classics, Research Evidence and Current Prevention Programs. Curr Diabetes Rev 2024; 20:e140323214600. [PMID: 36918778 DOI: 10.2174/1573399819666230314093721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/05/2023] [Accepted: 01/17/2023] [Indexed: 03/16/2023]
Abstract
Diabetes mellitus (DM), a chronic medical condition, has attained a global pandemic status over the last few decades affecting millions of people. Despite a variety of synthetic drugs available in the market, the use of herbal medicines for managing diabetes is gaining importance because of being comparatively safer. This article reviews the result of a substantial literature search on polyherbal formulations (PHFs) developed and evaluated with potential for DM. The accumulated data in the literature allowed us to enlist 76PHFs consisting of different parts of 147 plant species belonging to 58 botanical families. The documented plant species are laden with bioactive components with anti-diabetic properties and thus draw attention. The most favoured ingredient for PHFs was leaves of Gymnema sylvestre and seeds of Trigonella foenum-graecum used in 27 and 22 formulations, respectively. Apart from herbs, shilajit (exudates from high mountain rocks) formed an important component of 9 PHFs, whereas calcined Mytilus margaritiferus and goat pancreas were used in Dolabi, the most commonly used tablet form of PHF in Indian markets. The healing properties of PHFs against diabetes have been examined in both pre-clinical studies and clinical trials. However, the mechanism(s) of action of PHFs are still unclear and considered the pitfalls inherent in understanding the benefits of PHFs. From the information available based on experimental systems, it could be concluded that plant-derived medicines will have a considerable role to play in the control of diabetes provided the challenges related to their bioavailability, bioefficacy, optimal dose, lack of characterization, ambiguous mechanism of action, and clinical efficiency are addressed.
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Affiliation(s)
- Sudem Brahma
- Department of Biotechnology, Bodoland University, Kokrajhar-783370, BTR, Assam, India
| | - Arvind Kumar Goyal
- Department of Biotechnology, Bodoland University, Kokrajhar-783370, BTR, Assam, India
| | - Prakash Dhamodhar
- Department of Biotechnology, M.S. Ramaiah Institute of Technology, Bangaluru-560054, Karnataka, India
| | - Mani Reema Kumari
- Department of Botany, Maharani Lakshmi Ammanni College for Women, Bengaluru-560012, Karnataka, India
| | - S Jayashree
- School of Allied Health Sciences, REVA University, Bengaluru-560064, Karnataka, India
| | - Talambedu Usha
- Department of Biochemistry, Maharani Lakshmi Ammanni College for Women, Bengaluru-560012, Karnataka, India
| | - Sushil Kumar Middha
- Department of Biochemistry, Maharani Lakshmi Ammanni College for Women, Bengaluru-560012, Karnataka, India
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Yuxuan A, Xiaoqin L, Songtao L, Jinmiao T, Xiaxia F, Kaili C, Lichao Z, Zhuoyu L. Polyphenols from whole millet grain (Setaria italica) alleviate glucose and lipid homeostasis in diet-induced obese mice by increasing endogenous GLP-1. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:7785-7797. [PMID: 37548615 DOI: 10.1002/jsfa.12901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Revised: 06/10/2023] [Accepted: 08/07/2023] [Indexed: 08/08/2023]
Abstract
BACKGROUND Foxtail millet (Setaria italica) is a whole millet grain that has been considered for improving the disorder of glucose and lipid metabolism. The purpose of the work is to explore the extraction and enrichment of polyphenols from foxtail millets which can regulate the disorder of glucose and lipid metabolism by increasing endogenous GLP-1 (glucagon-like peptide-1). RESULTS The optimum ultrasound-assisted extraction (UAE) of foxtail millet polyphenols (FMPs) was as follows: 70 °C and 400 W and 70% ethanol concentration, further purification using macroporous resin. In vitro, the FMP eluent of 60% ethanol (FMP-60) has the best effect in promoting GLP-1 secretion from L cells among the different active components of FMP. Millet polyphenols (MPs) were obtained from finishing foxtail millet with the bran removed by the same extraction and purification method. Compared with MP-60, FMP-60 mainly included eight active phenolic constituents and contained more ferulic acid, p-coumaric acid, 2-hydroxycinnamic acid, and coniferaldehyde. After gavage treatment of diet-induced obese (DIO) mice with FMP-60, FMP-60 promoted endogenous GLP-1 secretion in mice and ameliorated disorders of glucolipid metabolism in DIO mice. CONCLUSION FMP-60 could improve glucose homeostasis and ameliorates metabolic disease by promoting the endogenous GLP-1 level and preventing weight gain in DIO mice. © 2023 Society of Chemical Industry.
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Affiliation(s)
- An Yuxuan
- Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education, Shanxi University, Taiyuan, China
| | - La Xiaoqin
- Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China
| | - Li Songtao
- Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education, Shanxi University, Taiyuan, China
| | - Tian Jinmiao
- Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education, Shanxi University, Taiyuan, China
| | - Fan Xiaxia
- Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education, Shanxi University, Taiyuan, China
| | - Cui Kaili
- Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education, Shanxi University, Taiyuan, China
| | - Zhang Lichao
- Institutes of Biomedical Sciences, Shanxi University, Taiyuan, China
| | - Li Zhuoyu
- Institute of Biotechnology, The Key Laboratory of Chemical Biology and Molecular, Engineering of Ministry of Education, Shanxi University, Taiyuan, China
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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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Oyebode OA, Erukainure OL, Mopuri R, Sanni O, Koorbanally NA, Islam MS. Butanol fraction of Alstonia boonei De Wild. leaves ameliorate oxidative stress and modulate key hypoglycaemic processes in diabetic rats. Arch Physiol Biochem 2023; 129:1091-1104. [PMID: 33840309 DOI: 10.1080/13813455.2021.1899240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 02/19/2021] [Accepted: 03/01/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE The effect of Alstonia boonei fractions on glucose homeostasis was investigated via in vitro enzyme inhibition activity, ex vivo glucose uptake assay, and in vivo methods in diabetic rats. METHODOLOGY A. boonei fractions were subjected to in vitro α-glucosidase inhibitory assay and then ex vivo glucose uptake activity. The butanol fraction of the leaves (ABBF) was picked for the in vivo assay since it showed more activity in the initial tests conducted. ABBF was administrated via oral dosing to six-weeks old fructose-fed STZ-induced type 2 diabetic rats over a 5-week experimental period. RESULTS ABBF treatment at a low dose of 150 mg/kg bw, significantly (p < .05) reduced blood glucose level, enhanced oral glucose tolerance ability, restored insulin secretion and hepatic glycogen synthesis as well as promoted islet regeneration than the high dose (300 mg/kg bw). CONCLUSION These results suggest that ABBF could be exploited as a therapeutic potential for treating T2D.
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Affiliation(s)
- Olajumoke A Oyebode
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein, South Africa
| | - Ochuko L Erukainure
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
- Department of Pharmacology, University of the Free State, Bloemfontein, South Africa
| | - Ramgopal Mopuri
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
- Department of Biotechnology, SriKrishnadevara University, Anantapur, India
| | - Olakunle Sanni
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
- Centre of Excellence for Pharmaceutical Sciences (Pharmacen), North-West University (NWU), Potchefstroom, South Africa
| | - Neil A Koorbanally
- School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa
| | - Md Shahidul Islam
- Department of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Durban, South Africa
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Tamel Selvan K, Goon JA, Makpol S, Tan JK. Therapeutic Potentials of Microalgae and Their Bioactive Compounds on Diabetes Mellitus. Mar Drugs 2023; 21:462. [PMID: 37755075 PMCID: PMC10532649 DOI: 10.3390/md21090462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 08/01/2023] [Accepted: 08/07/2023] [Indexed: 09/28/2023] Open
Abstract
Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to impaired insulin secretion, insulin resistance, or both. Oxidative stress and chronic low-grade inflammation play crucial roles in the pathophysiology of diabetes mellitus. There has been a growing interest in applying natural products to improve metabolic derangements without the side effects of anti-diabetic drugs. Microalgae biomass or extract and their bioactive compounds have been applied as nutraceuticals or additives in food products and health supplements. Several studies have demonstrated the therapeutic effects of microalgae and their bioactive compounds in improving insulin sensitivity attributed to their antioxidant, anti-inflammatory, and pancreatic β-cell protective properties. However, a review summarizing the progression in this topic is lacking despite the increasing number of studies reporting their anti-diabetic potential. In this review, we gathered the findings from in vitro, in vivo, and human studies to discuss the effects of microalgae and their bioactive compounds on diabetes mellitus and the mechanisms involved. Additionally, we discuss the limitations and future perspectives of developing microalgae-based compounds as a health supplement for diabetes mellitus. In conclusion, microalgae-based supplementation has the potential to improve diabetes mellitus and be applied in more clinical studies in the future.
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Affiliation(s)
| | | | | | - Jen Kit Tan
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Jalan Ya’acob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
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Benameur T, Porro C, Twfieg ME, Benameur N, Panaro MA, Filannino FM, Hasan A. Emerging Paradigms in Inflammatory Disease Management: Exploring Bioactive Compounds and the Gut Microbiota. Brain Sci 2023; 13:1226. [PMID: 37626582 PMCID: PMC10452544 DOI: 10.3390/brainsci13081226] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/06/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
The human gut microbiota is a complex ecosystem of mutualistic microorganisms that play a critical role in maintaining human health through their individual interactions and with the host. The normal gastrointestinal microbiota plays a specific physiological function in host immunomodulation, nutrient metabolism, vitamin synthesis, xenobiotic and drug metabolism, maintenance of structural and functional integrity of the gut mucosal barrier, and protection against various pathogens. Inflammation is the innate immune response of living tissues to injury and damage caused by infections, physical and chemical trauma, immunological factors, and genetic derangements. Most diseases are associated with an underlying inflammatory process, with inflammation mediated through the contribution of active immune cells. Current strategies to control inflammatory pathways include pharmaceutical drugs, lifestyle, and dietary changes. However, this remains insufficient. Bioactive compounds (BCs) are nutritional constituents found in small quantities in food and plant extracts that provide numerous health benefits beyond their nutritional value. BCs are known for their antioxidant, antimicrobial, anticarcinogenic, anti-metabolic syndrome, and anti-inflammatory properties. Bioactive compounds have been shown to reduce the destructive effect of inflammation on tissues by inhibiting or modulating the effects of inflammatory mediators, offering hope for patients suffering from chronic inflammatory disorders like atherosclerosis, arthritis, inflammatory bowel diseases, and neurodegenerative diseases. The aim of the present review is to summarise the role of natural bioactive compounds in modulating inflammation and protecting human health, for their safety to preserve gut microbiota and improve their physiology and behaviour.
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Affiliation(s)
- Tarek Benameur
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Chiara Porro
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
| | - Mohammed-Elfatih Twfieg
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Nassima Benameur
- Faculty of Exact Sciences and Sciences of Nature and Life, Research Laboratory of Civil Engineering, Hydraulics, Sustainable Development and Environment (LARGHYDE), Mohamed Khider University, Biskra 07000, Algeria
| | - Maria Antonietta Panaro
- Department of Biosciences, Biotechnologies and Environment, University of Bari, 70125 Bari, Italy
| | | | - Abeir Hasan
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
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Ouahabi S, Loukili EH, Daoudi NE, Chebaibi M, Ramdani M, Rahhou I, Bnouham M, Fauconnier ML, Hammouti B, Rhazi L, Ayerdi Gotor A, Dépeint F, Ramdani M. Study of the Phytochemical Composition, Antioxidant Properties, and In Vitro Anti-Diabetic Efficacy of Gracilaria bursa-pastoris Extracts. Mar Drugs 2023; 21:372. [PMID: 37504903 PMCID: PMC10381155 DOI: 10.3390/md21070372] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 06/17/2023] [Accepted: 06/23/2023] [Indexed: 07/29/2023] Open
Abstract
In this study, a comparison was made of the chemical makeup of different extracts obtained from Gracilaria bursa-pastoris, a type of red seaweed that was gathered from the Nador lagoon situated in the northern part of Morocco. Additionally, their anti-diabetic and antioxidant properties were investigated. The application of GC-MS technology to analyze the fatty acid content of the samples revealed that linoleic acid and eicosenoic acid were the most abundant unsaturated fatty acids across all samples, with palmitic acid and oleic acid following in frequency. The HPLC analysis indicated that ascorbic and kojic acids were the most prevalent phenolic compounds, while apigenin was the most common flavonoid molecule. The aqueous extract exhibited significant levels of polyphenols and flavonoids, registering values of 381.31 ± 0.33 mg GAE/g and 201.80 ± 0.21 mg QE/g, respectively. Furthermore, this particular extract demonstrated a remarkable ability to scavenge DPPH radicals, as evidenced by its IC50 value of 0.17 ± 0.67 mg/mL. In addition, the methanolic extract was found to possess antioxidant properties, as evidenced by its ability to prevent β-carotene discoloration, with an IC50 ranging from 0.062 ± 0.02 mg/mL to 0.070 ± 0.06 mg/mL. In vitro study showed that all extracts significantly inhibited the enzymatic activity of α-amylase and α-glucosidase. Finally, molecular docking models were applied to assess the interaction between the primary phytochemicals identified in G. bursa-pastoris extracts and the human pancreatic α-amylase and α-glucosidase enzymes. The findings suggest that these extracts contain bioactive substances capable of reducing enzyme activity more effectively than the commercially available drug acarbose.
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Affiliation(s)
- Safae Ouahabi
- Laboratory of Applied and Environmental Chemistry (LCAE), Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60000, Morocco
| | - El Hassania Loukili
- Laboratory of Applied and Environmental Chemistry (LCAE), Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60000, Morocco
| | - Nour Elhouda Daoudi
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60000, Morocco
| | - Mohamed Chebaibi
- Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy of the Fez, University of Sidi Mohamed Ben Abdellah, Fez 30000, Morocco
| | - Mohamed Ramdani
- Biochemistry and Biotechnology Laboratory, Faculty of Sciences, Mohamed First University, B.P. 717, Oujda 60000, Morocco
| | - Ilyesse Rahhou
- Higher Institute of Nursing Professions and Health Techniques (ISPITSO), Oujda 63303, Morocco
| | - Mohamed Bnouham
- Laboratory of Bioresources, Biotechnology, Ethnopharmacology and Health, Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60000, Morocco
| | - Marie-Laure Fauconnier
- Laboratory of Chemistry of Natural Molecules, University of Liège, Gembloux Agro-Bio Tech. 2, Passage des Déportés, B-5030 Gembloux, Belgium
| | - Belkheir Hammouti
- Laboratory of Applied and Environmental Chemistry (LCAE), Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60000, Morocco
- CREHEIO Centre de Recherche de l'Ecole des Hautes Etudes d'Ingénierie, Oujda 60000, Morocco
- Université Euro-Méditerranéenne de Fès, Fez BP 51, Morocco
| | - Larbi Rhazi
- Institut Polytechnique UniLaSalle, Université d'Artois, ULR 7519, UniLaSalle, 19 Rue Pierre Waguet, BP 30313, 60026 Beauvais, France
| | - Alicia Ayerdi Gotor
- Institut Polytechnique UniLaSalle, AGHYLE, UP 2018.C101, UniLaSalle, 19 Rue Pierre Waguet, BP 30313, 60026 Beauvais, France
| | - Flore Dépeint
- Institut Polytechnique UniLaSalle, Université d'Artois, ULR 7519, UniLaSalle, 19 Rue Pierre Waguet, BP 30313, 60026 Beauvais, France
| | - Mohammed Ramdani
- Laboratory of Applied and Environmental Chemistry (LCAE), Faculty of Sciences, Mohammed First University, B.P. 717, Oujda 60000, Morocco
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16
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Ağagündüz D, Icer MA, Yesildemir O, Koçak T, Kocyigit E, Capasso R. The roles of dietary lipids and lipidomics in gut-brain axis in type 2 diabetes mellitus. J Transl Med 2023; 21:240. [PMID: 37009872 PMCID: PMC10068184 DOI: 10.1186/s12967-023-04088-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 03/25/2023] [Indexed: 04/04/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM), one of the main types of Noncommunicable diseases (NCDs), is a systemic inflammatory disease characterized by dysfunctional pancreatic β-cells and/or peripheral insulin resistance, resulting in impaired glucose and lipid metabolism. Genetic, metabolic, multiple lifestyle, and sociodemographic factors are known as related to high T2DM risk. Dietary lipids and lipid metabolism are significant metabolic modulators in T2DM and T2DM-related complications. Besides, accumulated evidence suggests that altered gut microbiota which plays an important role in the metabolic health of the host contributes significantly to T2DM involving impaired or improved glucose and lipid metabolism. At this point, dietary lipids may affect host physiology and health via interaction with the gut microbiota. Besides, increasing evidence in the literature suggests that lipidomics as novel parameters detected with holistic analytical techniques have important roles in the pathogenesis and progression of T2DM, through various mechanisms of action including gut-brain axis modulation. A better understanding of the roles of some nutrients and lipidomics in T2DM through gut microbiota interactions will help develop new strategies for the prevention and treatment of T2DM. However, this issue has not yet been entirely discussed in the literature. The present review provides up-to-date knowledge on the roles of dietary lipids and lipidomics in gut-brain axis in T2DM and some nutritional strategies in T2DM considering lipids- lipidomics and gut microbiota interactions are given.
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Affiliation(s)
- Duygu Ağagündüz
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, 06490, Ankara, Turkey.
| | - Mehmet Arif Icer
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Amasya University, 05100, Amasya, Turkey
| | - Ozge Yesildemir
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Bursa Uludag University, 16059, Bursa, Turkey
| | - Tevfik Koçak
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Gazi University, 06490, Ankara, Turkey
| | - Emine Kocyigit
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Ordu University, 52200, Ordu, Turkey
| | - Raffaele Capasso
- Department of Agricultural Sciences, University of Naples Federico II, Portici, 80055, Naples, Italy.
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Hashim KN, Chin KY, Ahmad F. The Mechanism of Kelulut Honey in Reversing Metabolic Changes in Rats Fed with High-Carbohydrate High-Fat Diet. Molecules 2023; 28:2790. [PMID: 36985762 PMCID: PMC10056699 DOI: 10.3390/molecules28062790] [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: 02/27/2023] [Revised: 03/13/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
Metabolic syndrome (MetS) is composed of central obesity, hyperglycemia, dyslipidemia and hypertension that increase an individual's tendency to develop type 2 diabetes mellitus and cardiovascular diseases. Kelulut honey (KH) produced by stingless bee species has a rich phenolic profile. Recent studies have demonstrated that KH could suppress components of MetS, but its mechanisms of action are unknown. A total of 18 male Wistar rats were randomly divided into control rats (C group) (n = 6), MetS rats fed with a high carbohydrate high fat (HCHF) diet (HCHF group) (n = 6), and MetS rats fed with HCHF diet and treated with KH (HCHF + KH group) (n = 6). The HCHF + KH group received 1.0 g/kg/day KH via oral gavage from week 9 to 16 after HCHF diet initiation. Compared to the C group, the MetS group experienced a significant increase in body weight, body mass index, systolic (SBP) and diastolic blood pressure (DBP), serum triglyceride (TG) and leptin, as well as the area and perimeter of adipocyte cells at the end of the study. The MetS group also experienced a significant decrease in serum HDL levels versus the C group. KH supplementation reversed the changes in serum TG, HDL, leptin, adiponectin and corticosterone levels, SBP, DBP, as well as adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) level, area and perimeter at the end of the study. In addition, histological observations also showed that KH administration reduced fat deposition within hepatocytes, and prevented deterioration of pancreatic islet and renal glomerulus. In conclusion, KH is effective in preventing MetS by suppressing leptin, corticosterone and 11βHSD1 levels while elevating adiponectin levels.
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Affiliation(s)
- Khairun-Nisa Hashim
- Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia;
| | - Fairus Ahmad
- Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur 56000, Malaysia
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18
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Attenuation of hepatic fibrosis by p-Coumaric acid via modulation of NLRP3 inflammasome activation in C57BL/6 mice. J Nutr Biochem 2023; 112:109204. [PMID: 36400112 DOI: 10.1016/j.jnutbio.2022.109204] [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: 02/21/2022] [Revised: 09/28/2022] [Accepted: 11/02/2022] [Indexed: 11/17/2022]
Abstract
A prolonged high-fat and high-sucrose (HFHS) diet induces hepatic inflammation and mediates hepatic stellate cell (HSC) activation, which result in hepatic fibrosis. Aberrant activation of the innate immune system components, such as the NOD-like receptor protein 3 (NLRP3) inflammasome, has been implicated in HSC activation and hepatic fibrosis. We have previously shown that p-coumaric acid (PCA)-enriched peanut sprout extracts exert anti-inflammatory effects. However, it is unknown whether PCA reduces hepatic fibrosis by modulating innate immunity and HSC activation. To test this hypothesis, C57BL/6 male mice were randomly assigned to three groups and fed low-fat (LF) diet (11% calories from fat), high-fat (HF) diet (60% calories from fat, 0.2% cholesterol) with sucrose drink (20% sucrose, HFHS), or HFHS diet with PCA treatment (HFHS+PCA, 50 mg/kg body weight, intraperitoneally) for 13 weeks. The results showed that PCA treatment (1) partly improved systemic insulin sensitivity without altering adiposity, (2) attenuated hepatic signaling pathways associated with NLRP3 inflammasome activation, including toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB), and endoplasmic reticulum/oxidative stress, and (3) reduced circulating interleukin (IL)-1β levels. More importantly, PCA ameliorated hepatic fibrosis compared to that in the HFHS group, and the anti-fibrogenic effects of PCA were confirmed in vitro in transforming growth factor β (TGFβ) treated-LX-2 HSCs. The role of PCA in decreased NLRP3 activation and caspase-1 cleavage was recapitulated in primary bone marrow‒derived macrophages. These findings indicate that PCA contributes to the prevention of HFHS diet‒mediated liver fibrosis, partly by attenuating the activation of the NLRP3 inflammasome.
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Khodeer DM, Nasr AM, Swidan SA, Shabayek S, Khinkar RM, Aldurdunji MM, Ramadan MA, Badr JM. Characterization, antibacterial, antioxidant, antidiabetic, and anti-inflammatory activities of green synthesized silver nanoparticles using Phragmanthera austroarabica A. G. Mill and J. A. Nyberg extract. Front Microbiol 2023; 13:1078061. [PMID: 36687608 PMCID: PMC9849905 DOI: 10.3389/fmicb.2022.1078061] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/07/2022] [Indexed: 01/07/2023] Open
Abstract
Introduction Diabetes mellitus is a chronic metabolic disorder that exhibited great expansion all over the world. It is becoming an epidemic disease adding a major burden to the health care system, particularly in developing countries. Methods The plant under investigation in the current study Phragmanthera austroarabica A. G. Mill and J. A. Nyberg is traditionally used in Saudi Arabia for the treatment of diabetes mellitus. The methanolic extract (200 mg/kg) of the plant and pure gallic acid (40 mg/kg), a major metabolite of the plant, as well as their silver nanoparticle formulae (AgNPs) were evaluated for their antidiabetic activity. Results and Discussion The results showed a decrease in body fat, obesity, an improvement in lipid profiles, normalization of hyperglycemia, insulin resistance, and hyperinsulinemia, and an improvement in liver tissue structure and function. However, the results obtained from AgNPs for both extract and the pure gallic acid were better in most measured parameters. Additionally, the activity of both the crude extract of the plant and its AgNPs were evaluated against a number of gram-positive, gram-negative bacteria and fungi. Although the activity of the crude extract ranged from moderate to weak or even non-active, the AgNPs of the plant extract clearly enhanced the antimicrobial activity. AgNPs of the extract demonstrated remarkable activity, especially against the Gram-negative pathogens Proteus vulgaris (MIC 2.5 μg/ml) and Pseudomonas aeruginosa (MIC 5 μg/ml). Furthermore, a promising antimicrobial activity was shown against the Gram-positive pathogen Streptococcus mutants (MIC 1.25 μg/ml).
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Affiliation(s)
- Dina M. Khodeer
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt,*Correspondence: Dina M. Khodeer, ✉
| | - Ali M. Nasr
- Department of Pharmaceutics, Faculty of Pharmacy, Port Said University, Port Said, Egypt,Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Galala University, Suez, Egypt
| | - Shady A. Swidan
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt,The Centre for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt
| | - Sarah Shabayek
- Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
| | - Roaa M. Khinkar
- Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohammed M. Aldurdunji
- Department of Clinical Pharmacy, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Maryam A. Ramadan
- Department of Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Jihan M. Badr
- Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt,Jihan M. Badr, ✉
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Dolrahman N, Mukkhaphrom W, Sutirek J, Thong-Asa W. Benefits of p-coumaric acid in mice with rotenone-induced neurodegeneration. Metab Brain Dis 2023; 38:373-382. [PMID: 36308586 DOI: 10.1007/s11011-022-01113-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 10/17/2022] [Indexed: 02/03/2023]
Abstract
The paper examines the use of natural antioxidant and anti-inflammation substances as therapeutic candidates for brain disease. Para-coumaric acid (pCA), a phenolic compound with a variety of medicinal properties, was used against deterioration caused by various diseases. Recently, pCA has gained attention for use against cardiovascular disease but less so for neurodegenerative disease (i.e., Parkinson's disease). Therefore, the present study intended to investigate the effect of pCA against rotenone-induced Parkinson's disease-like pathology in mice. Thirty male institute of cancer research (ICR) mice were randomly divided into three experimental groups: Sham-veh, Rot-veh, and Rot-pCA100. Rotenone (Rot) 2.5 mg/kg was subcutaneously injected every 48 h in the rotenone groups. Alternately, a 100 mg/kg pCA dose was given every 48 h via intragastric gavage to the Rot-pCA100 group for 6 weeks. Motor ability was assessed at the second, fourth, and sixth week before brain collection for biochemical and histological analyses. Results indicated significant motor deficits appeared from the second to sixth week after rotenone injection. Brain analysis detected a significant effect of rotenone in the increase of malondialdehyde and tumor necrosis factor-alpha (TNF-α). This result was observed in accordance with a reduction of tyrosine hydroxylase (TH) and an increase of neuronal degeneration in the substantia nigra par compacta (SNc) and striatum. However, pCA was able to reverse all of the deterioration (i.e., reduced malondialdehyde and TNF-α) rotenone had caused, and it protected against TH and neuronal loss in the SNc and striatum. Therefore, the present study has depicted the neuroprotective effect of pCA against rotenone-induced Parkinson's disease-like pathology in mice. Benefits of pCA include anti-lipid peroxidation and anti-inflammatory effects, inhibition of neurodegeneration, and a nurturing effect on the TH level in the SNc and striatum, leading to mitigation of motor deficits.
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Affiliation(s)
- Nurinee Dolrahman
- Animal Toxicology and Physiology Specialty Research Unit (ATPSRU), Physiology Division, Department of Zoology, Faculty of Science, Kasetsart University, 50 Ngamwongwan Road, Jatuchak, Bangkok, 10900, Thailand
| | - Waritsara Mukkhaphrom
- Animal Toxicology and Physiology Specialty Research Unit (ATPSRU), Physiology Division, Department of Zoology, Faculty of Science, Kasetsart University, 50 Ngamwongwan Road, Jatuchak, Bangkok, 10900, Thailand
| | - Jeanjira Sutirek
- Animal Toxicology and Physiology Specialty Research Unit (ATPSRU), Physiology Division, Department of Zoology, Faculty of Science, Kasetsart University, 50 Ngamwongwan Road, Jatuchak, Bangkok, 10900, Thailand
| | - Wachiryah Thong-Asa
- Animal Toxicology and Physiology Specialty Research Unit (ATPSRU), Physiology Division, Department of Zoology, Faculty of Science, Kasetsart University, 50 Ngamwongwan Road, Jatuchak, Bangkok, 10900, Thailand.
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Magerusan L, Pogacean F, Rada S, Pruneanu S. Sulphur-doped graphene based sensor for rapid and efficient gallic acid detection from food related samples. J Taiwan Inst Chem Eng 2022. [DOI: 10.1016/j.jtice.2022.104539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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22
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Capozzi A, Saucier C, Bisbal C, Lambert K. Grape Polyphenols in the Treatment of Human Skeletal Muscle Damage Due to Inflammation and Oxidative Stress during Obesity and Aging: Early Outcomes and Promises. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27196594. [PMID: 36235130 PMCID: PMC9573747 DOI: 10.3390/molecules27196594] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/23/2022] [Accepted: 09/28/2022] [Indexed: 11/21/2022]
Abstract
Today, inactivity and high-calorie diets contribute to the development of obesity and premature aging. In addition, the population of elderly people is growing due to improvements in healthcare management. Obesity and aging are together key risk factors for non-communicable diseases associated with several co-morbidities and increased mortality, with a major impact on skeletal muscle defect and/or poor muscle mass quality. Skeletal muscles contribute to multiple body functions and play a vital role throughout the day, in all our activities. In our society, limiting skeletal muscle deterioration, frailty and dependence is not only a major public health challenge but also a major socio-economic issue. Specific diet supplementation with natural chemical compounds such as grape polyphenols had shown to play a relevant and direct role in regulating metabolic and molecular pathways involved in the prevention and treatment of obesity and aging and their related muscle comorbidities in cell culture and animal studies. However, clinical studies aiming to restore skeletal muscle mass and function with nutritional grape polyphenols supplementation are still very scarce. There is an urgent need for clinical studies to validate the very encouraging results observed in animal models.
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Affiliation(s)
- Adriana Capozzi
- PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, CEDEX 5, 34295 Montpellier, France
- SPO, INRAE, Institute Agro, University of Montpellier, 34000 Montpellier, France
| | - Cédric Saucier
- SPO, INRAE, Institute Agro, University of Montpellier, 34000 Montpellier, France
| | - Catherine Bisbal
- PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, CEDEX 5, 34295 Montpellier, France
- Correspondence: (C.B.); (K.L.); Tel.: +33-(0)4-1175-9891 (C.B. & K.L.)
| | - Karen Lambert
- PhyMedExp, INSERM U1046, CNRS UMR 9214, University of Montpellier, CEDEX 5, 34295 Montpellier, France
- Correspondence: (C.B.); (K.L.); Tel.: +33-(0)4-1175-9891 (C.B. & K.L.)
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23
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Abdel-Moneim A, Abd El-Twab SM, Yousef AI, Ashour MB, Reheim ESA, Hamed MAA. New insights into the in vitro, in situ and in vivo antihyperglycemic mechanisms of gallic acid and p-coumaric acid. Arch Physiol Biochem 2022; 128:1188-1194. [PMID: 32401050 DOI: 10.1080/13813455.2020.1762659] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Objective: To explore the probable in vitro, in situ and in vivo mechanisms of gallic acid (GA) and p-coumaric acid (PCA) as anti-hyperglycemic agents.Animals and methods: Male albino rats were allocated into four groups, group1 was used as normal control. Group 2 was established as a diabetic control and group3 and 4 were treated with an oral dose of GA and PCA, respectively.Results: GA and PCA revealed a significant decrease in the activity of α-amylase, a noticeable rise in glucose induced-insulin secretion and glucose-uptake in peripheral glucose-uptake in vitro, increase also liver glycogen and serum insulin levels in vivo. Further, GA and PCA exhibited a significant reduction in intestinal glucose absorption in situ compared to blank.Conclusion: The antihyperglycemic activities of GA and PCA can be mediated through delaying intestinal glucose absorption, enhancing β-cell activity and promoting glucose uptake by peripheral tissue via enhancing insulin sensitivity.
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Affiliation(s)
- Adel Abdel-Moneim
- Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
| | - Sanaa M Abd El-Twab
- Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
| | - Ahmed I Yousef
- Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
| | - Mohamed B Ashour
- Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
| | - Eman S Abdel Reheim
- Molecular Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
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24
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Wang S, Du Q, Meng X, Zhang Y. Natural polyphenols: a potential prevention and treatment strategy for metabolic syndrome. Food Funct 2022; 13:9734-9753. [PMID: 36134531 DOI: 10.1039/d2fo01552h] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Metabolic syndrome (MS) is the term for a combination of hypertension, dyslipidemia, insulin resistance, and central obesity as factors leading to cardiovascular and metabolic disease. Epidemiological investigation has shown that polyphenol intake is negatively correlated with the incidence of MS. Natural polyphenols are widely found in cocoa beans, tea, vegetables, fruits, and some Chinese herbal medicines; they are a class of plant compounds containing a variety of phenolic structural units, which are potent antioxidants and anti-inflammatory agents in plants. Polyphenols are composed of flavonoids (such as flavanols, anthocyanidins, anthocyanins, isoflavones, etc.) and non-flavonoids (such as phenolic acids, stilbenes, and lignans). Modern pharmacological studies have proved that polyphenols can reduce blood pressure, improve lipid metabolism, lower blood glucose, and reduce body weight, thereby preventing and improving MS. Due to the unique characteristics and potential development and application value of polyphenols, this review summarizes some natural polyphenols that could treat MS, including their chemical properties, plant sources, and pharmacological action against MS, to provide a basis for the further study of polyphenols in MS.
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Affiliation(s)
- Shaohui Wang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Qinyun Du
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xianli Meng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Yi Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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25
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Ramorobi LM, Matowane GR, Mashele SS, Bonnet SL, Noreljaleel AEM, Swain SS, Makhafola TJ, Chukwuma CI. Bioactive synergism between zinc mineral and p-coumaric acid: A multi-mode glycemic control and antioxidative study. J Food Biochem 2022; 46:e14360. [PMID: 35929608 DOI: 10.1111/jfbc.14360] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 06/24/2022] [Accepted: 07/20/2022] [Indexed: 12/19/2022]
Abstract
Natural supplements are important in diabetes and oxidative stress management. A complexation-mediated antihyperglycemic and antioxidant synergism between zinc(II) and p-coumaric acid was investigated. p-Coumaric acid was complexed with ZnSO4 and characterized by FT-IR, 1 H NMR, and mass spectroscopy. The antioxidant and antihyperglycemic potential of the complex and precursors were evaluated with different experimental models. Molecular docking with target proteins linked to diabetes was performed. A Zn(II)-bicoumarate.2H2 O complex was formed. The in vitro radical scavenging, α-glucosidase inhibitory, antiglycation, and anti-lipid peroxidative activities of the complex were several folds stronger than p-coumaric acid. In Chang liver cells and rat liver tissues, the complex inhibited lipid peroxidation (IC50 = 56.2 and 398 μM) and GSH depletion (IC50 = 33.9 and 38.7 μM), which was significantly stronger (2.3-5.4-folds) than p-coumaric acid and comparable to ascorbic acid. Zn(II) and p-coumaric synergistically modulated (1.7- and 2.8-folds than p-coumaric acid) glucose uptake in L-6 myotubes (EC50 = 10.7 μM) and rat muscle tissue (EC50 = 428 μM), which may be linked to the observed complexation-mediated increase in tissue zinc uptake. Glucose uptake activity was accompanied by increased hexokinase activity, suggesting increased glucose utilization. Docking scores α-glucosidase, GLUT-4, and PKB/Akt showed stronger interaction with the complex (-6.31 to -6.41 kcal/mol) compared to p-coumaric acid (-7.18 to -7.74 kcal/mol), which was influenced by the Zn(II) and bicoumarate moieties of the complex. In vitro, the complex was not hepatotoxic or myotoxic. Zn(II) complexation may be a therapeutic approach for improving the antioxidative and glycemic control potentials of p-coumaric acid. PRACTICAL APPLICATIONS: In functional medicine, natural supplements, plant-derived phenolics, and nutraceuticals are becoming popular in the management of diseases, including diabetes and oxidative stress. This has been largely attributed to their perceived holistic medicinal profile and the absence of notable toxicity concerns. In the past two decades, considerable attention has been drawn toward zinc mineral as a possible therapeutic supplement for diabetes due to its role in insulin secretion and reported insulin mimetic potentials. p-Coumaric acid is a known natural antioxidant with reported diabetes-related pharmacological effects. In this study, we took advantage of these properties and complexed both natural supplements, which resulted in a more potent nutraceutical with improved glycemic control and antioxidant potential. The complexation-mediated synergistic interaction between zinc and p-coumaric acid could be an important therapeutic approach in improving the use of these natural supplements or nutraceuticals in managing diabetes and associated oxidative complications.
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Affiliation(s)
- Limpho M Ramorobi
- Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, South Africa.,Centre for Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, South Africa
| | - Godfrey R Matowane
- Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, South Africa.,Centre for Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, South Africa
| | - Samson S Mashele
- Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, South Africa.,Centre for Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, South Africa
| | - Susanna L Bonnet
- Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, South Africa
| | - Anwar E M Noreljaleel
- Department of Chemistry, Faculty of Natural and Agricultural Sciences, University of the Free State, Bloemfontein, South Africa
| | - Shasank S Swain
- Division of Microbiology & NCDs, ICMR-Regional Medical Research Centre, Bhubaneswar, India
| | - Tshepiso J Makhafola
- Centre for Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, South Africa
| | - Chika I Chukwuma
- Centre for Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, South Africa
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Hu X, Chen Y, Dai J, Yao L, Wang L. Rhodomyrtus tomentosa Fruits in Two Ripening Stages: Chemical Compositions, Antioxidant Capacity and Digestive Enzymes Inhibitory Activity. Antioxidants (Basel) 2022; 11:1390. [PMID: 35883880 PMCID: PMC9311718 DOI: 10.3390/antiox11071390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 11/17/2022] Open
Abstract
Rhodomyrtus tomentosa fruit (RTF) has been known as a food source with multiple health-care components. In this work, nutrition characteristics, free and bound phenolic profiles, antioxidant properties in vitro and digestive enzymes inhibitory activities of un-fully mature RTF (UM-RTF) and fully mature RTF (FM-RTF) were evaluated for the first time. Results verified that high levels of energy, ascorbic acid, organic acids and total phenolics were observed in FM-RTF. Moreover, FM-RTF had significant higher total phenolic content (TPC), but significantly lower total flavonoid content (TFC) than UM-RTF. In addition, twenty phenolic compounds in RTF were identified by high performance liquid chromatography-electrospray ionization-quadrupole time-of-flight tandem mass spectrometry (HPLC-ESI-qTOF-MS/MS) method. Quantitative analysis results indicated that gallic acid, ellagic acid and astragalin were the predominant free phenolics, while gallic acid and syringetin-3-O-glucoside were dominant in bound phenolic fractions. In contrast, higher contents of phenolics were observed in FM-RTF. The results also confirmed that FM-RTF exhibited higher antioxidant activities and digestive enzymes inhibitory activities than UM-RTF. Strong inhibitory ability on α-glucosidase was found in RTF, while bound phenolics showed a stronger α-amylase inhibitory effect than free phenolics. Moreover, the interaction between the main phenolic compounds and α-glucosidase/α-amylase was preliminary explored by molecular docking analysis. The results provided valuable data about the chemical compositions and biological potential of R. tomentosa fruits in both maturation stages studied.
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Affiliation(s)
- Xiaoping Hu
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou 570228, China; (X.H.); (Y.C.); (J.D.); (L.Y.)
- Engineering Research Center of Utilization of Tropical Polysaccharide Resources, Ministry of Education, Hainan University, Haikou 570228, China
| | - Yuting Chen
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou 570228, China; (X.H.); (Y.C.); (J.D.); (L.Y.)
| | - Jincheng Dai
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou 570228, China; (X.H.); (Y.C.); (J.D.); (L.Y.)
| | - Linling Yao
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou 570228, China; (X.H.); (Y.C.); (J.D.); (L.Y.)
| | - Lu Wang
- Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou 570228, China; (X.H.); (Y.C.); (J.D.); (L.Y.)
- Engineering Research Center of Utilization of Tropical Polysaccharide Resources, Ministry of Education, Hainan University, Haikou 570228, China
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27
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Pérez Gutiérrez RM, Soto Contreras JG, Martínez Jerónimo FF, de la Luz Corea Téllez M, Borja-Urby R. Assessing the Ameliorative Effect of Selenium Cinnamomum verum, Origanum majorana, and Origanum vulgare Nanoparticles in Diabetic Zebrafish (Danio rerio). PLANTS 2022; 11:plants11070893. [PMID: 35406873 PMCID: PMC9002390 DOI: 10.3390/plants11070893] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 03/15/2022] [Accepted: 03/16/2022] [Indexed: 12/03/2022]
Abstract
Cinnamomum verum, Origanum majorana, and Origanum vulgare have been used in traditional medicine for a long time to treat diabetes because of their promising therapeutic effects. The combination of these plants (COO) was tested to improve their efficacy using selenium nanoparticles (Se-COO-NPs) and gum Arabic (GA) as stabilizers for sustained release. Phenolic compounds of plants were identified using liquid chromatography–mass spectrometry (LC–MS/MS). GA-Se-COO-NPs were characterized by spectroscopic and microscopic methods and evaluated in diabetic zebrafish. The ultraviolet spectrum was assessed to confirm the formation of plasmon resonance at 267 nm. The obtained particle size of selenium nanospheres was 65.76 nm. They were maintained in a stable form for 5 months at 4 °C. Transmission electron microscopy (TEM) images demonstrated the presence of individual spherical nanoparticles. Fourier transform infrared spectroscopy (FT-IR) showed the interaction between COO extract and selenium, exhibiting good entrapment efficiency (87%). The elemental analysis of COO extract and GA-COO-SeNPs confirmed that NPs were obtained. The zebrafish were exposed to a high glucose concentration for two weeks, and type 2 diabetes and oxidative stress responses were induced. In diabetic zebrafish, treatment with NPs showed antilipidemic and hypoglycemic effects, high survivability, and reduced levels of glucose, reactive oxygen species (ROS), and lipids in the blood. This group this had a higher survivorship rate than the diabetic control. The results demonstrated that GA-Se-COO-NPs have high antidiabetic potential, most likely because of the synergic effects of phenolic compounds and Se nanoparticles.
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Affiliation(s)
- Rosa Martha Pérez Gutiérrez
- Laboratorio de Investigación de Productos Naturales, Escuela Superior de Ingeniería Química e Industrias Extractivas, Instituto Politécnico Nacional (IPN), Mexico City 07708, Mexico;
- Correspondence:
| | - José Guadalupe Soto Contreras
- Laboratorio de Investigación de Productos Naturales, Escuela Superior de Ingeniería Química e Industrias Extractivas, Instituto Politécnico Nacional (IPN), Mexico City 07708, Mexico;
| | - Felipe Fernando Martínez Jerónimo
- Laboratorio de Hidrobiología Experimental, Instituto Politécnico Nacional (IPN), Escuela Nacional de Ciencias Biológicas, Carpio y Plan de Ayala S/N, Casco de Santo Tomás, Mexico City 11340, Mexico;
| | - Mónica de la Luz Corea Téllez
- Laboratorio de Investigación en Polímeros y Nanomateriales, Escuela Superior de Ingeniería Química e Industrias Extractivas, Instituto Politécnico Nacional (IPN), Edificio Z-5 Planta Baja Del Gustavo A. Madero, Mexico City 07730, Mexico;
| | - Raúl Borja-Urby
- Laboratorio de Microscopía Electrónica de Transmisión, Centro de Nanociencias y Micro-Nanotecnologías (CNMN), Instituto Politécnico Nacional (IPN), Mexico City 07758, Mexico;
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28
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Ren SM, Zhang QZ, Jiang M, Chen ML, Xu XJ, Wang DM, Pan YN, Liu XQ. Systematic characterization of the metabolites of defatted walnut powder extract in vivo and screening of the mechanisms against NAFLD by UPLC-Q-Exactive Orbitrap MS combined with network pharmacology. JOURNAL OF ETHNOPHARMACOLOGY 2022; 285:114870. [PMID: 34848359 DOI: 10.1016/j.jep.2021.114870] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 11/19/2021] [Accepted: 11/22/2021] [Indexed: 06/13/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Walnut kernel, a well-known TCM, is often used after being defatted in tradition. And defatted walnut powder extract (DWPE) has the actions of tonifying the liver and kidney, dissipating stagnation and removing blood stasis, which has the effect on non-alcoholic fatty liver disease (NAFLD). However, the effective components of DWPE in vivo were unclear and the multiple mechanisms of DWPE against NAFLD have not been explored. AIM OF THE STUDY The studies were performed to screen the effective substances in vivo by identification of the metabolites of DWPE in rats and to seek the potential mechanisms of DWPE on NAFLD by construction of the network pharmacology based on metabolites and verification of the highly correlated pathway. MATERIALS AND METHODS To explore the effective substances in vivo, the metabolites of DWPE were identified in SD rats' bio-samples through UPLC-Q-Exactive Orbitrap MS. To analyze the mechanisms of DWPE on NAFLD, a Metabolite-Target-Disease network was established and the potential mechanisms were predicted. Then, highly correlated pathway was verified in animal and cells studies. RESULTS A total of 52 metabolites of DWPE were identified in vivo, which were derived from gallic acid, ellagic acid (EA) and glansreginin A (Gla A). The possible metabolic pathways were phase Ⅰ (hydroxylation, hydrolyzation, etc) and phase Ⅱ metabolic reactions (methylation, sulfation and glucuronidation). Furthermore, in the network pharmacology, 54 core targets were enriched into pathways in cancer, nitrogen metabolism and other 9 pathways, which were essential pathways of DWPE against NAFLD. And the mechanism of nitrogen metabolism was verified in both of animal and cells studies. The results showed that DWPE could decline the concentration of ammonia and increase the expressions of carbonic anhydrase 2 (CA2) and carbamoylphosphate synthetase (CPS1) in nitrogen metabolism. CONCLUSION Taken together, the study revealed the absorption components and their metabolic pathways and demonstrated the mechanism of nitrogen metabolism of DWPE on anti-NAFLD.
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Affiliation(s)
- Shu-Meng Ren
- School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
| | - Qing-Zhu Zhang
- School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
| | - Man Jiang
- School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
| | - Meng-Lin Chen
- School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
| | - Xia-Jing Xu
- School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
| | - Dong-Mei Wang
- School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
| | - Ying-Ni Pan
- School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
| | - Xiao-Qiu Liu
- School of Traditional Chinese Medicine, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning, 110016, PR China.
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The Use of Bioactive Compounds in Hyperglycemia- and Amyloid Fibrils-Induced Toxicity in Type 2 Diabetes and Alzheimer’s Disease. Pharmaceutics 2022; 14:pharmaceutics14020235. [PMID: 35213966 PMCID: PMC8879577 DOI: 10.3390/pharmaceutics14020235] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/14/2022] [Accepted: 01/19/2022] [Indexed: 12/29/2022] Open
Abstract
It has become increasingly apparent that defective insulin signaling may increase the risk for developing Alzheimer’s disease (AD), influence neurodegeneration through promotion of amyloid formation or by increasing inflammatory responses to intraneuronal β-amyloid. Recent work has demonstrated that hyperglycemia is linked to cognitive decline, with elevated levels of glucose causing oxidative stress in vulnerable tissues such as the brain. The ability of β-amyloid peptide to form β-sheet-rich aggregates and induce apoptosis has made amyloid fibrils a leading target for the development of novel pharmacotherapies used in managing and treatment of neuropathological conditions such as AD-related cognitive decline. Additionally, deposits of β-sheets folded amylin, a glucose homeostasis regulator, are also present in diabetic patients. Thus, therapeutic compounds capable of reducing intracellular protein aggregation in models of neurodegenerative disorders may prove useful in ameliorating type 2 diabetes mellitus symptoms. Furthermore, both diabetes and neurodegenerative conditions, such as AD, are characterized by chronic inflammatory responses accompanied by the presence of dysregulated inflammatory biomarkers. This review presents current evidence describing the role of various small bioactive molecules known to ameliorate amyloidosis and subsequent effects in prevention and development of diabetes and AD. It also highlights the potential efficacy of peptide–drug conjugates capable of targeting intracellular targets.
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Pérez Gutiérrez RM, Martínez Jerónimo FF, Contreras Soto JG, Muñiz Ramírez A, Estrella Mendoza MF. Optimization of ultrasonic-assisted extraction of polyphenols from the polyherbal formulation of Cinnamomum verum, Origanum majorana, and Origanum vulgare and their anti-diabetic capacity in zebrafish ( Danio rerio). Heliyon 2022; 8:e08682. [PMID: 35036595 PMCID: PMC8749454 DOI: 10.1016/j.heliyon.2021.e08682] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 11/12/2021] [Accepted: 12/23/2021] [Indexed: 11/21/2022] Open
Abstract
The Cinnamomum verum (CV), Origanum majorana (CM), and Origanum vulgare (OV) have been used in traditional medicine in several regions of México for their anti-diabetic properties. In this study investigated the variables of ultrasound-assisted extraction for the polyphenolic compounds from the combination of these plants and explore their potential antidiabetic activities on glucose-induced-diabetic zebrafish. Determined the optimum conditions for ultrasonic-assisted extraction (UAE) to maximum recovery amounts of phenolic compounds from the extract of these plants. Polyphenols were detected in the extracts using HPLC-DAD-analysis. Extracts were evaluated on zebrafish exposed to high glucose concentration (110 mM) for two weeks. Results showed second-order polynomial mathematical models with a high coefficient of determination (R2 > 0.9564). Optimized extraction conditions for UAE from the combination of the 3 plants (COV) were as follows: 66.03%, ethanol, 28.87 min, and 21.51 mL/g for maximal flavonoids extraction. Used the same optimal extraction conditions for CV, CM, and OV. Results from LC-MS/MS indicated 9 polyphenolic compounds in CV, 12 in CM, and 6 in OV, the content of total polyphenols was 310.28, 90.42, and 126.74 mg GAE 100 g-1 dry weight, respectively. However, hyperglycemic fish showed an increase in cholesterol and triglyceride levels whereas extracts completely prevented these metabolic alterations. COV showed higher anti-diabetic ability than CV, CM, and OV, suggesting a synergistic effect between them. Our investigation developed a new herbal formulation of Cinnamomum verum; Origanum majorana; Origanum vulgare that has proven effective in animals with type 2 diabetes will form a new class of supplements to treat diabetic complications.
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Affiliation(s)
- Rosa Martha Pérez Gutiérrez
- Laboratorio de Investigación de Productos Naturales, Escuela Superior de Ingeniería Química e Industrias Extractivas, Instituto Politécnico Nacional (IPN), Unidad Profesional Adolfo López Mateos S/N Av, Instituto Politécnico, Nacional Ciudad de Mexico, cp 07708, Mexico
- Insituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Hidrobiología Experimental, Carpio y Plan de Ayala S/N, Col. Santo Tomás, CDMX 11340, Mexico
| | - Felipe Fernando Martínez Jerónimo
- Laboratorio de Investigación de Productos Naturales, Escuela Superior de Ingeniería Química e Industrias Extractivas, Instituto Politécnico Nacional (IPN), Unidad Profesional Adolfo López Mateos S/N Av, Instituto Politécnico, Nacional Ciudad de Mexico, cp 07708, Mexico
- Insituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Hidrobiología Experimental, Carpio y Plan de Ayala S/N, Col. Santo Tomás, CDMX 11340, Mexico
| | - José Guadalupe Contreras Soto
- Laboratorio de Investigación de Productos Naturales, Escuela Superior de Ingeniería Química e Industrias Extractivas, Instituto Politécnico Nacional (IPN), Unidad Profesional Adolfo López Mateos S/N Av, Instituto Politécnico, Nacional Ciudad de Mexico, cp 07708, Mexico
- Insituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Laboratorio de Hidrobiología Experimental, Carpio y Plan de Ayala S/N, Col. Santo Tomás, CDMX 11340, Mexico
| | - Alethia Muñiz Ramírez
- CONACYT-División de Materiales Avanzados, Instituto Potosino de Investigación Científica y Tecnológica A. C. San Luis Potosí, Mexico
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Mierziak J, Kostyn K, Boba A, Czemplik M, Kulma A, Wojtasik W. Influence of the Bioactive Diet Components on the Gene Expression Regulation. Nutrients 2021; 13:3673. [PMID: 34835928 PMCID: PMC8619229 DOI: 10.3390/nu13113673] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/13/2021] [Accepted: 10/14/2021] [Indexed: 02/07/2023] Open
Abstract
Diet bioactive components, in the concept of nutrigenetics and nutrigenomics, consist of food constituents, which can transfer information from the external environment and influence gene expression in the cell and thus the function of the whole organism. It is crucial to regard food not only as the source of energy and basic nutriments, crucial for living and organism development, but also as the factor influencing health/disease, biochemical mechanisms, and activation of biochemical pathways. Bioactive components of the diet regulate gene expression through changes in the chromatin structure (including DNA methylation and histone modification), non-coding RNA, activation of transcription factors by signalling cascades, or direct ligand binding to the nuclear receptors. Analysis of interactions between diet components and human genome structure and gene activity is a modern approach that will help to better understand these relations and will allow designing dietary guidances, which can help maintain good health.
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Affiliation(s)
- Justyna Mierziak
- Faculty of Biotechnology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland; (A.B.); (M.C.); (A.K.)
| | - Kamil Kostyn
- Department of Genetics, Plant Breeding & Seed Production, Faculty of Life Sciences and Technology, Wroclaw University of Environmental and Life Sciences, pl. Grunwaldzki 24A, 50-363 Wroclaw, Poland;
| | - Aleksandra Boba
- Faculty of Biotechnology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland; (A.B.); (M.C.); (A.K.)
| | - Magdalena Czemplik
- Faculty of Biotechnology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland; (A.B.); (M.C.); (A.K.)
| | - Anna Kulma
- Faculty of Biotechnology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland; (A.B.); (M.C.); (A.K.)
| | - Wioleta Wojtasik
- Faculty of Biotechnology, University of Wrocław, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland; (A.B.); (M.C.); (A.K.)
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Zhang LL, He Y, Sheng F, Hu YF, Song Y, Li W, Chen J, Zhang J, Zou L. Towards a better understanding of Fagopyrum dibotrys: a systematic review. Chin Med 2021; 16:89. [PMID: 34530893 PMCID: PMC8447528 DOI: 10.1186/s13020-021-00498-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 08/30/2021] [Indexed: 01/12/2023] Open
Abstract
Fagopyrum dibotrys (F. dibotrys) (D.Don) H.Hara is a well-known edible herbal medicine in Asian countries. It has been widely used for the treatment of lung diseases, swelling, etc., and is also an important part of many Chinese medicine prescriptions. At present, more than 100 compounds have been isolated and identified from F. dibotrys, and these compounds can be primarily divided into flavonoids, phenols, terpenes, steroids, and fatty acids. Flavonoids and phenolic compounds are considered to be the main active ingredients of F. dibotrys. Previous pharmacological studies have shown that F. dibotrys possesses anti-inflammatory, anti-cancer, anti-oxidant, anti-bacterial, and anti-diabetic activities. Additional studies on functional genes have led to a better understanding of the metabolic pathways and regulatory factors related with the flavonoid active ingredients in F. dibotrys. In this paper, we systemically reviewed the research advances on the phytochemistry and pharmacology of F. dibotrys, as well as the functional genes related to the synthesis of active ingredients, aiming to promote the development and utilization of F. dibotrys.
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Affiliation(s)
- Le-Le Zhang
- School of Basic Medical Sciences, Chengdu University, Chengdu, China
| | - Yan He
- School of Basic Medical Sciences, Chengdu University, Chengdu, China
| | - Feiya Sheng
- School of Basic Medical Sciences, Chengdu University, Chengdu, China.
| | - Ying-Fan Hu
- School of Basic Medical Sciences, Chengdu University, Chengdu, China
| | - Yu Song
- Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu, China
| | - Wei Li
- School of Basic Medical Sciences, Chengdu University, Chengdu, China
| | - Jiarong Chen
- Affiliated Hospital of Chengdu University, Chengdu, China
| | - Jinming Zhang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Liang Zou
- Key Laboratory of Coarse Cereal Processing of Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu, China.
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Moroccan antidiabetic medicinal plants: Ethnobotanical studies, phytochemical bioactive compounds, preclinical investigations, toxicological validations and clinical evidences; challenges, guidance and perspectives for future management of diabetes worldwide. Trends Food Sci Technol 2021. [DOI: 10.1016/j.tifs.2021.03.032] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Plants Secondary Metabolites as Blood Glucose-Lowering Molecules. Molecules 2021; 26:molecules26144333. [PMID: 34299610 PMCID: PMC8307461 DOI: 10.3390/molecules26144333] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 07/06/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Recently, significant advances in modern medicine and therapeutic agents have been achieved. However, the search for effective antidiabetic drugs is continuous and challenging. Over the past decades, there has been an increasing body of literature related to the effects of secondary metabolites from botanical sources on diabetes. Plants-derived metabolites including alkaloids, phenols, anthocyanins, flavonoids, stilbenoids, saponins, tannins, polysaccharides, coumarins, and terpenes can target cellular and molecular mechanisms involved in carbohydrate metabolism. In addition, they can grant protection to pancreatic beta cells from damage, repairing abnormal insulin signaling, minimizing oxidative stress and inflammation, activating AMP-activated protein kinase (AMPK), and inhibiting carbohydrate digestion and absorption. Studies have highlighted many bioactive naturally occurring plants' secondary metabolites as candidates against diabetes. This review summarizes the current knowledge compiled from the latest studies published during the past decade on the mechanism-based action of plants-derived secondary metabolites that can target various metabolic pathways in humans against diabetes. It is worth mentioning that the compiled data in this review will provide a guide for researchers in the field, to develop candidates into environment-friendly effective, yet safe antidiabetics.
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Dahabiyeh LA, Mujammami M, Arafat T, Benabdelkamel H, Alfadda AA, Abdel Rahman AM. A Metabolic Pattern in Healthy Subjects Given a Single Dose of Metformin: A Metabolomics Approach. Front Pharmacol 2021; 12:705932. [PMID: 34335266 PMCID: PMC8319764 DOI: 10.3389/fphar.2021.705932] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 06/28/2021] [Indexed: 01/27/2023] Open
Abstract
Metformin is a widely prescribed medication for the treatment of type 2 diabetes mellitus (T2DM). It possesses effective roles in various disorders, including cancer, dyslipidemia, and obesity. However, the underlying mechanisms of metformin's multiple benefits are not fully understood. Herein, a mass spectrometry-based untargeted metabolomics approach was used to investigate the metabolic changes associated with the administration of a single dose of metformin in the plasma of 26 healthy subjects at five-time points; pre-dose, before the maximum concentration of metformin (Cmax), Cmax, after Cmax, and 36 h post-dose. A total of 111 metabolites involved in various biochemical processes were perturbed, with branched-chain amino acid (BCAA) being the most significantly altered pathway. Additionally, the Pearson similarity test revealed that 63 metabolites showed a change in their levels dependent on metformin level. Out of these 63, the level of 36 metabolites was significantly altered by metformin. Significantly altered metformin-dependent metabolites, including hydroxymethyl uracil, propionic acid, glycerophospholipids, and eicosanoids, pointed to fundamental biochemical processes such as lipid network signaling, energy homeostasis, DNA lesion repair mechanisms, and gut microbiota functions that could be linked to the multiple beneficial roles of metformin. Thus, the distinctive metabolic pattern linked to metformin administration can be used as a metabolic signature to predict the potential effect and mechanism of actions of new chemical entities during drug development.
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Affiliation(s)
- Lina A Dahabiyeh
- Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman, Jordan
| | - Muhammad Mujammami
- Endocrinology and Diabetes Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.,University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia
| | - Tawfiq Arafat
- Jordan Center for Pharmaceutical Research, Amman, Jordan
| | - Hicham Benabdelkamel
- Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Assim A Alfadda
- Endocrinology and Diabetes Unit, Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.,Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Anas M Abdel Rahman
- Metabolomics Section, Department of Clinical Genomics, Center for Genome Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh, Saudi Arabia.,Department of Biochemistry and Molecular Medicine, College of Medicine, Al Faisal University, Riyadh, Saudi Arabia.,Department of Chemistry, Memorial University of Newfoundland, St. John's, NL, Canada
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Pérez Gutiérrez RM, Muñiz-Ramirez A, Garcia-Campoy AH, Mota Flores JM. Evaluation of the Antidiabetic Potential of Extracts of Urtica dioica, Apium graveolens, and Zingiber officinale in Mice, Zebrafish, and Pancreatic β-Cell. PLANTS 2021; 10:plants10071438. [PMID: 34371645 PMCID: PMC8309382 DOI: 10.3390/plants10071438] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Revised: 07/08/2021] [Accepted: 07/10/2021] [Indexed: 01/31/2023]
Abstract
Medicinal plants are commonly used in the treatment of diabetes, particularly as they contain flavonoids and phenolic compounds. The present study aims to investigate the activities of a polyherbal formulation made from Urtica dioica, Apium graveolens, and Zingiber officinale (UAZ) against streptozotocin–nicotinamide ((STZ-NA)-induced type 2 diabetes in CD1 mice, glucose-induced type 2 diabetes (T2DM) in zebrafish, and high glucose-induced damage in RINm5F pancreatic β-cells. In fasting mice, plasma glucose, glycosylated hemoglobin (HbA1C), lipid hydroperoxides (LOOH), thiobarbituric acid reactive substances (TBARS), and lipid profiles were significantly increased, whereas insulin, enzymatic antioxidants, and carbohydrate metabolic enzymes were altered significantly in diabetic mice. Zebrafish had similar glucose levels, liver enzymes, and lipid profiles compared to mice. The study investigated the effects of the extract in enhancing cell viability, insulin secretion, and reducing lipid peroxidation and intracellular reactive oxygen species (ROS) levels in RINm5F cells damaged by high glucose. All the above biochemical parameters were enhanced in both mice and zebrafish treated; the combined extract UAZ normalized all the biochemical parameters. The medicinal plant extracts, used either separately or in combination, ameliorated the adverse effect of glucose on cell viability and functionality of beta-RINm5F cells.
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Affiliation(s)
- Rosa Martha Pérez Gutiérrez
- Laboratorio de Investigación de Productos Naturales, Escuela Superior de Ingeniería Química e Industrias Extractivas, Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional S/N, Unidad Profesional Adolfo López Mateos, Ciudad de México CP 07708, Mexico; (A.H.G.-C.); (J.M.M.F.)
- Correspondence:
| | - Alethia Muñiz-Ramirez
- CONACYT/IPICYT-CIIDZA, Camino a la Presa de San José 2055, Col. Lomas 4 Sección, San Luis Potosí CP 78216, Mexico;
| | - Abraham Heriberto Garcia-Campoy
- Laboratorio de Investigación de Productos Naturales, Escuela Superior de Ingeniería Química e Industrias Extractivas, Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional S/N, Unidad Profesional Adolfo López Mateos, Ciudad de México CP 07708, Mexico; (A.H.G.-C.); (J.M.M.F.)
| | - José María Mota Flores
- Laboratorio de Investigación de Productos Naturales, Escuela Superior de Ingeniería Química e Industrias Extractivas, Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional S/N, Unidad Profesional Adolfo López Mateos, Ciudad de México CP 07708, Mexico; (A.H.G.-C.); (J.M.M.F.)
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Enhanced permeability and photoprotective potential of optimized p-coumaric acid-phospholipid complex loaded gel against UVA mediated oxidative stress. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2021; 221:112246. [PMID: 34243023 DOI: 10.1016/j.jphotobiol.2021.112246] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 06/11/2021] [Accepted: 06/17/2021] [Indexed: 01/14/2023]
Abstract
Photo-oxidative skin damage is mainly caused by the UV-A radiation of the sun. Synthetic sunscreens used to counter this acts mostly on the superficial skin layer and possess serious side effects. P-coumaric acid (PCA) is a UV-A protective plant phenolic having quick diffusion and distribution in superficial skin layers limiting its application as herbal sunscreen. The present study was designed to formulate an optimized phospholipid complex of PCA (PCAPC) through response surface methodology to enhance its skin permeation to deeper skin layers providing protection against photo-oxidative stress. PCAPC was characterized by FT-IR, DTA, PXRD, TEM, zeta potential etc. PCAPC was then incorporated into a gel formulation (PCAPC-GE) to facilitate its transdermal delivery. Physicochemical properties of the gel were assessed by pH, homogeneity, rheology, spreadability etc. In-vitro SPF and UVA-PF of the gel was evaluated and compared with conventional gel (PCA-GE). Ex-vivo skin permeation flux, permeability coefficient, skin deposition and dermatokinetic analysis were carried out to measure the rate and level of skin permeation. This was accompanied by in-vivo evaluation of PCAPC-GE and PCA-GE in the experimental rat model by measuring the various oxidative stress markers such as superoxide dismutase, catalase etc. PCAPC-GE provided high SPF and UVA-PF value compared to PCA-GE. The physicochemical parameters were suitable for transdermal application. PCAPC-GE enhanced the permeation rate of PCA by almost 6 fold compared to PCA-GE. Besides, a significant reduction of UV-A induced oxidative stress biomarkers were observed for PCAPC-GE. Thus, the PCAPC-GE may be an effective alternative of synthetic sunscreens due to its enhanced permeation and protection against UVA-induced oxidative stress.
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Contardi M, Lenzuni M, Fiorentini F, Summa M, Bertorelli R, Suarato G, Athanassiou A. Hydroxycinnamic Acids and Derivatives Formulations for Skin Damages and Disorders: A Review. Pharmaceutics 2021; 13:999. [PMID: 34371691 PMCID: PMC8309026 DOI: 10.3390/pharmaceutics13070999] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 06/25/2021] [Accepted: 06/26/2021] [Indexed: 02/06/2023] Open
Abstract
Alterations of skin homeostasis are widely diffused in our everyday life both due to accidental injuries, such as wounds and burns, and physiological conditions, such as late-stage diabetes, dermatitis, or psoriasis. These events are locally characterized by an intense inflammatory response, a high generation of harmful free radicals, or an impairment in the immune response regulation, which can profoundly change the skin tissue' repair process, vulnerability, and functionality. Moreover, diabetes diffusion, antibiotic resistance, and abuse of aggressive soaps and disinfectants following the COVID-19 emergency could be causes for the future spreading of skin disorders. In the last years, hydroxycinnamic acids and derivatives have been investigated and applied in several research fields for their anti-oxidant, anti-inflammatory, and anti-bacterial activities. First, in this study, we give an overview of these natural molecules' current source and applications. Afterwards, we review their potential role as valid alternatives to the current therapies, supporting the management and rebalancing of skin disorders and diseases at different levels. Also, we will introduce the recent advances in the design of biomaterials loaded with these phenolic compounds, specifically suitable for skin disorders treatments. Lastly, we will suggest future perspectives for introducing hydroxycinnamic acids and derivatives in treating skin disorders.
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Affiliation(s)
- Marco Contardi
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
| | - Martina Lenzuni
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
- DIBRIS, University of Genoa, 16145 Genoa, Italy
| | - Fabrizio Fiorentini
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
- DIBRIS, University of Genoa, 16145 Genoa, Italy
| | - Maria Summa
- Translational Pharmacology, Italian Institute of Technology, 16163 Genoa, Italy; (M.S.); (R.B.)
| | - Rosalia Bertorelli
- Translational Pharmacology, Italian Institute of Technology, 16163 Genoa, Italy; (M.S.); (R.B.)
| | - Giulia Suarato
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
- Translational Pharmacology, Italian Institute of Technology, 16163 Genoa, Italy; (M.S.); (R.B.)
| | - Athanassia Athanassiou
- Smart Materials, Italian Institute of Technology, 16163 Genoa, Italy; (M.L.); (F.F.); (G.S.)
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Zhang S, Xu M, Zhang W, Liu C, Chen S. Natural Polyphenols in Metabolic Syndrome: Protective Mechanisms and Clinical Applications. Int J Mol Sci 2021; 22:ijms22116110. [PMID: 34204038 PMCID: PMC8201163 DOI: 10.3390/ijms22116110] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/29/2021] [Accepted: 06/02/2021] [Indexed: 12/14/2022] Open
Abstract
Metabolic syndrome (MetS) is a chronic disease, including abdominal obesity, dyslipidemia, hyperglycemia, and hypertension. It should be noted that the occurrence of MetS is closely related to oxidative stress-induced mitochondrial dysfunction, ectopic fat accumulation, and the impairment of the antioxidant system, which in turn further aggravates the intracellular oxidative imbalance and inflammatory response. As enriched anti-inflammatory and antioxidant components in plants, natural polyphenols exhibit beneficial effects, including improving liver fat accumulation and dyslipidemia, reducing blood pressure. Hence, they are expected to be useful in the prevention and management of MetS. At present, epidemiological studies indicate a negative correlation between polyphenol intake and MetS incidence. In this review, we summarized and discussed the most promising natural polyphenols (including flavonoid and non-flavonoid drugs) in the precaution and treatment of MetS, including their anti-inflammatory and antioxidant properties, as well as their regulatory functions involved in glycolipid homeostasis.
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Affiliation(s)
| | | | | | | | - Siyu Chen
- Correspondence: ; Tel./Fax: +86-25-86185645
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Evaluation of bioactive compounds, phytochemicals profile and antioxidant potential of the aqueous and ethanolic extracts of some traditional fruit tree leaves used in Brazilian folk medicine. Food Res Int 2021; 143:110282. [PMID: 33992382 DOI: 10.1016/j.foodres.2021.110282] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 02/07/2021] [Accepted: 02/26/2021] [Indexed: 11/20/2022]
Abstract
The aim of this study was to analyze eight selected species of leaves, used in the traditional medicine of the Northeast region of Brazil obtained from several fruit trees (grageru, soursop, jambolanum, passion fruit, insulin, nogueira, pedra ume kaá and stévia), regarding their polyphenols contents and antioxidant activity. Condensed and hydrolysable tannins, phenolics and flavonoids contents were determined and the antioxidant activities measured by ABTS, FRAP and ORAC assays. Organic acids were analyzed by HPLC-DAD system. Phenolic compounds of aqueous and ethanolic extracts were determined by UHPLC-DAD-MS. The results revealed high contents of total phenolics (13.34 ± 0.19 - 127.65 ± 0.21 mg.g-1 of GAE:QE (2:1) of sample) and flavonoids (12.30 ± 0.42 - 71.79 ± 0.00 mg.g-1 QE of sample). The ABTS results exhibited extraordinary activity in the extracts (74.48 ± 6.23 - 1487.33 ± 2.67 µmol Trolox.g-1 of sample). Acids quinic, tartaric, citric, gallic, chlorogenic, p-coumaric, ferulic and vanillic along with naringenin, rutin, vanillin, catechin, epicatechin, kaempferol were the most important compounds. Thus, these leaves extracts may be considered as sources of phenolics compounds having a high potential as natural antioxidants. In addition, the polyphenols present in these leaves have many beneficial effects and can also be used in medicinal and nutraceuticals products with enhanced bioactivities.
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Potentiation of incretin hormones and modulation of metabolic enzymes as possible mechanisms behind the insulin sensitizing effects of cabbage-metformin treatment. Transl Res 2021; 230:44-54. [PMID: 33115637 DOI: 10.1016/j.trsl.2020.10.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 10/19/2020] [Accepted: 10/23/2020] [Indexed: 11/20/2022]
Abstract
In our study, we treated high fructose diet-induced insulin resistance in rats with any of metformin, cabbage (80%w/w) or combined metformin and cabbage (MetCabb), and observed the activities of glycolysis and gluconeogenesis regulatory enzymes, incretin hormones and other hormones affecting glucose homeostasis. Comparisons were made with normoglycemic noninsulin resistance rats (control) and insulin-resistant untreated rats (INres). Baseline analysis showing elevated fasting blood sugar (>250 mg/dl), insulin (>25 µIU/ml) and HOMA-IR (>10) satisfied the criteria for recruitment into the insulin-resistant groups. Treatment lasted for 12 weeks. HOMA-IR values significantly (P < 0.05) decreased from 24.7 to 5.5 and 10.6 respectively with MetCabb treatment. MetCabb normalized HOMA-IR values and mean β-cell responsiveness of the INres. Cabbage and metCabb normalized the leptin levels relative to control. The mean fasting blood sugar, insulin, and c-peptide levels with MetCabb treatment reverted to control levels. We found a strong positive linear correlation between the glucagon levels (r = 0.9145) and increasing HOMA-IR values while both incretin hormones; GLP-1 and GIP negatively regressed (r = -0.8084 and -0.8488). MetCab treatment produced comparable values of GLP-1 and GIP to the control. A strong positive correlation was found between the HOMA-IR values and the PEPCK (r = 0.9065), F-1,6-BPase (r = 0.7951), and G-6-Pase (r = 0.7893). The hexokinase (r = -0.807), PFK (r = -0.9151), and PK (r = -0.7448) levels regressed as HOMA-IR values increased. The glycolytic and gluconeogenic enzymes except PEPCK reverted to control levels with MetCabb treatment. Combination of metformin and cabbage was more effective than individual treatments.
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Savant S, Srinivasan S, Kruthiventi AK. Potential Nutraceuticals for COVID-19. NUTRITION AND DIETARY SUPPLEMENTS 2021. [DOI: 10.2147/nds.s294231] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
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p-Coumaric Acid Enhances Hypothalamic Leptin Signaling and Glucose Homeostasis in Mice via Differential Effects on AMPK Activation. Int J Mol Sci 2021; 22:ijms22031431. [PMID: 33572687 PMCID: PMC7867021 DOI: 10.3390/ijms22031431] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 01/25/2021] [Accepted: 01/28/2021] [Indexed: 12/17/2022] Open
Abstract
AMP-activated protein kinase (AMPK) plays a crucial role in the regulation of energy homeostasis in both peripheral metabolic organs and the central nervous system. Recent studies indicated that p-Coumaric acid (CA), a hydroxycinnamic phenolic acid, potentially activated the peripheral AMPK pathway to exert beneficial effects on glucose metabolism in vitro. However, CA’s actions on central AMPK activity and whole-body glucose homeostasis have not yet been investigated. Here, we reported that CA exhibited different effects on peripheral and central AMPK activation both in vitro and in vivo. Specifically, while CA treatment promoted hepatic AMPK activation, it showed an inhibitory effect on hypothalamic AMPK activity possibly by activating the S6 kinase. Furthermore, CA treatment enhanced hypothalamic leptin sensitivity, resulting in increased proopiomelanocortin (POMC) expression, decreased agouti-related peptide (AgRP) expression, and reduced daily food intake. Overall, CA treatment improved blood glucose control, glucose tolerance, and insulin sensitivity. Together, these results suggested that CA treatment enhanced hypothalamic leptin signaling and whole-body glucose homeostasis, possibly via its differential effects on AMPK activation.
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Adedara IA, Owumi SE, Oyelere AK, Farombi EO. Neuroprotective role of gallic acid in aflatoxin B 1 -induced behavioral abnormalities in rats. J Biochem Mol Toxicol 2020; 35:e22684. [PMID: 33319922 DOI: 10.1002/jbt.22684] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 10/07/2020] [Accepted: 11/26/2020] [Indexed: 12/12/2022]
Abstract
The neurotoxic impact of dietary exposure to aflatoxin B1 (AFB1 ) is documented in experimental and epidemiological studies. Gallic acid (GA) is a triphenolic phytochemical with potent anticancer, anti-inflammatory, and antioxidant activities. There is a knowledge gap on the influence of GA on AFB1 -induced neurotoxicity. This study probed the influence of GA on neurobehavioral and biochemical abnormalities in rats orally treated with AFB1 per se (75 µg/kg body weight) or administered together with GA (20 and 40 mg/kg) for 28 uninterrupted days. Behavioral endpoints obtained with video-tracking software demonstrated significant (p < .05) abatement of AFB1 -induced anxiogenic-like behaviors (increased freezing, urination, and fecal bolus discharge), motor and locomotor inadequacies, namely increased negative geotaxis and diminished grip strength, absolute turn angle, total time mobile, body rotation, maximum speed, and total distance traveled by GA. The improvement of exploratory behavior in animals that received both AFB1 and GA was confirmed by track plots and heat maps appraisal. Abatement of AFB1 -induced decreases in acetylcholinesterase activity, antioxidant status and glutathione level by GA was accompanied by a marked reduction in oxidative stress markers in the cerebellum and cerebrum of rats. Additionally, GA treatment abrogated AFB1 -mediated decrease in interleukin-10 and elevation of inflammatory indices, namely tumor necrosis factor-α, myeloperoxidase activity, interleukin-1β, and nitric oxide. Further, GA treatment curtailed caspase-3 activation and histological injuries in the cerebral and cerebellar tissues. In conclusion, abatement of AFB1 -induced neurobehavioral abnormalities by GA involves anti-inflammatory, antioxidant, and antiapoptotic mechanisms in rats.
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Affiliation(s)
- Isaac A Adedara
- Department of Biochemistry, Drug Metabolism and Toxicology Research Laboratories, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Solomon E Owumi
- Department of Biochemistry, Cancer Research and Molecular Biology Laboratory, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Adegboyega K Oyelere
- School of Biochemistry and Chemistry, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA
| | - Ebenezer O Farombi
- Department of Biochemistry, Drug Metabolism and Toxicology Research Laboratories, College of Medicine, University of Ibadan, Ibadan, Nigeria
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Kutluay VM, Diker NY. Constitution of a comprehensive phytochemical profile and network pharmacology based investigation to decipher molecular mechanisms of Teucrium polium L. in the treatment of type 2 diabetes mellitus. PeerJ 2020; 8:e10111. [PMID: 33150068 PMCID: PMC7585722 DOI: 10.7717/peerj.10111] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 09/16/2020] [Indexed: 12/18/2022] Open
Abstract
Background Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting a huge population worldwide. Teucrium polium L. has been used as a folk medicine for the treatment of T2DM in Anatolia, Turkey. The antihyperglycemic effect of the plant was reported previously. However, there was no detailed study on the underlying molecular mechanisms. In this study, we generated a research plan to clarify the active constituents of the extract and uncover the molecular mechanisms using network pharmacology analysis. Methods For this purpose, we composed a dataset of 126 compounds for the phytochemical profile of the aerial parts of T. polium. Drug-likeness of the compounds was evaluated, and 52 compounds were selected for further investigation. A total of 252 T2DM related targets hit by selected compounds were subjected to DAVID database. Results The KEGG pathway analysis showed enrichment for the TNF signaling pathway, insulin resistance, the HIF-1 signaling pathway, apoptosis, the PI3K-AKT signaling pathway, the FOXO signaling pathway, the insulin signaling pathway, and type 2 diabetes mellitus which are related to T2DM . AKT1, IL6, STAT3, TP53, INS, and VEGFA were found to be key targets in protein-protein interaction. Besides these key targets, with this study the role of GSK3β, GLUT4, and PDX1 were also discussed through literature and considered as important targets in the antidiabetic effect of T. polium. Various compounds of T. polium were shown to interact with the key targets activating PI3K-AKT and insulin signaling pathways. Conclusions According to these findings, mainly phenolic compounds were identified as the active components and IRS1/PI3K/AKT signaling and insulin resistance were identified as the main pathways regulated by T. polium. This study reveals the relationship of the compounds in T. polium with the targets of T2DM in human. Our findings suggested the use of T. polium as an effective herbal drug in the treatment of T2DM and provides new insights for further research on the antidiabetic effect of T. polium.
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Affiliation(s)
- Vahap Murat Kutluay
- Department of Pharmacognosy, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
| | - Neziha Yagmur Diker
- Department of Pharmaceutical Botany, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
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Xue N, He B, Jia Y, Yang C, Wang J, Li M. The mechanism of binding with the α-glucosidase in vitro and the evaluation on hypoglycemic effect in vivo: Cocrystals involving synergism of gallic acid and conformer. Eur J Pharm Biopharm 2020; 156:64-74. [DOI: 10.1016/j.ejpb.2020.08.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 05/27/2020] [Accepted: 08/25/2020] [Indexed: 12/14/2022]
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dos S. Baião D, da Silva DVT, Paschoalin VMF. Beetroot, a Remarkable Vegetable: Its Nitrate and Phytochemical Contents Can be Adjusted in Novel Formulations to Benefit Health and Support Cardiovascular Disease Therapies. Antioxidants (Basel) 2020; 9:E960. [PMID: 33049969 PMCID: PMC7600128 DOI: 10.3390/antiox9100960] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 10/01/2020] [Accepted: 10/02/2020] [Indexed: 02/06/2023] Open
Abstract
The cardioprotective effects of dietary nitrate from beetroot in healthy and hypertensive individuals are undeniable and irrefutable. Nitrate and nitrate-derived nitrite are precursors for nitric oxide synthesis exhibiting an effect on cardiomyocytes and myocardial ischemia/reperfusion, improving endothelial function, reducing arterial stiffness and stimulating smooth muscle relaxation, decreasing systolic and diastolic blood pressures. Beetroot phytochemicals like betanin, saponins, polyphenols, and organic acids can resist simulated gastrointestinal digestion, raising the hypothesis that the cardioprotective effects of beetroots result from the combination of nitrate/nitrite and bioactive compounds that limit the generation of reactive oxygen species and modulate gene expression. Nitrate and phytochemical concentrations can be adjusted in beet formulations to fulfill requirements for acute or long-term supplementations, enhancing patient adherence to beet intervention. Based on in vitro, in vivo, and clinical trials, beet nitrate and its bioactive phytochemicals are promising as a novel supportive therapy to ameliorate cardiovascular diseases.
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Affiliation(s)
| | | | - Vania M. F. Paschoalin
- Instituto de Química, Universidade Federal do Rio de Janeiro, Avenida Athos da Silveira Ramos 149, Rio de Janeiro 21941-909, Brazil; (D.d.S.B.); (D.V.T.d.S.)
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48
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Rice bran phenolic extract supplementation ameliorates impaired lipid metabolism in high-fat-diet fed mice through AMPK activation in liver. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.104131] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Yang K, Zhang L, Liao P, Xiao Z, Zhang F, Sindaye D, Xin Z, Tan C, Deng J, Yin Y, Deng B. Impact of Gallic Acid on Gut Health: Focus on the Gut Microbiome, Immune Response, and Mechanisms of Action. Front Immunol 2020; 11:580208. [PMID: 33042163 PMCID: PMC7525003 DOI: 10.3389/fimmu.2020.580208] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2020] [Accepted: 08/17/2020] [Indexed: 12/11/2022] Open
Abstract
Gallic acid (GA) is a naturally occurring polyphenol compound present in fruits, vegetables, and herbal medicines. According to previous studies, GA has many biological properties, including antioxidant, anticancer, anti-inflammatory, and antimicrobial properties. GA and its derivatives have multiple industrial uses, such as food supplements or additives. Additionally, recent studies have shown that GA and its derivatives not only enhance gut microbiome (GM) activities, but also modulate immune responses. Thus, GA has great potential to facilitate natural defense against microbial infections and modulate the immune response. However, the exact mechanisms of GA acts on the GM and immune system remain unclear. In this review, first the physicochemical properties, bioavailability, absorption, and metabolism of GA are introduced, and then we summarize recent findings concerning its roles in gastrointestinal health. Furthermore, the present review attempts to explain how GA influences the GM and modulates the immune response to maintain intestinal health.
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Affiliation(s)
- Kang Yang
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Limeng Zhang
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Pinfeng Liao
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Zaili Xiao
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Fan Zhang
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Daniel Sindaye
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Zhongquan Xin
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Chengquan Tan
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Jinping Deng
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
| | - Yulong Yin
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China.,National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Baichuan Deng
- Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, China
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Owumi SE, Adedara IA, Akomolafe AP, Farombi EO, Oyelere AK. Gallic acid enhances reproductive function by modulating oxido-inflammatory and apoptosis mediators in rats exposed to aflatoxin-B1. Exp Biol Med (Maywood) 2020; 245:1016-1028. [PMID: 32558593 DOI: 10.1177/1535370220936206] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
IMPACT STATEMENT Infertility resulting from reproductive deficiency can be stressful. Exposure to aflatoxin B1, a dietary mycotoxin prevalent in improperly stored grains, is reported to elicit reproductive insufficiencies and infertility. We, therefore, examined the likely beneficial effect of gallic acid (GA) a phytochemical, recognized to exhibit in vitro and in vivo pharmacological bioactivities against oxidative stress and related inflammatory damages in rats, since AFB1 toxicities are predicated on oxidative epoxide formation, in a bid to proffer new evidence to advance the field of nutriceutical application from plant-derived chemopreventive agents. Our findings will advance the field of chemoprevention by presenting data absent in the literature on GA. Our results demonstrate further evidence for GA conferred protection against AFB1-mediated histological lesions in testes, epididymis, and hypothalamus of treated rats; suppresses oxidative damages, relieved inflammatory and apoptotic responses, restored sperm functional characteristics, and hormonal levels relevant for reproductive integrity and function.
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Affiliation(s)
- Solomon E Owumi
- Cancer Research and Molecular Biology Laboratory, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan 200004, Nigeria
| | - Isaac A Adedara
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan 200004, Nigeria
| | - Ayomide P Akomolafe
- Cancer Research and Molecular Biology Laboratory, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan 200004, Nigeria
| | - Ebenezer O Farombi
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan 200004, Nigeria
| | - Adegboyega K Oyelere
- School of Chemistry & Biochemistry, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA
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