A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice.
AGE rich diet
Diabetes
Exercise
Herbal drug
Nrf2-keep pathway
Stress oxidative
Journal
Nutrition & metabolism
ISSN: 1743-7075
Titre abrégé: Nutr Metab (Lond)
Pays: England
ID NLM: 101231644
Informations de publication
Date de publication:
19 Jan 2021
19 Jan 2021
Historique:
received:
19
06
2020
accepted:
05
01
2021
entrez:
20
1
2021
pubmed:
21
1
2021
medline:
21
1
2021
Statut:
epublish
Résumé
SPTC is a mix of four herbal components (Salvia officinalis, Panax ginseng, Trigonella foenum-graeceum, and Cinnamomum zeylanicum) which might be prevented the development of AGE rich diet-induced diabetic complication and liver injury through activated the nuclear factor erythroid-2-related-factor-2 (Nrf2) pathway. Nrf2, as a master regulator of antioxidant response elements by activating cytoprotective genes expression, is decreased oxidative stress that associated with hyperglycemia and increases insulin sensitivity. the aim of this study was to assess whether the combination therapy of SPTC along with exercise or metformin moderate oxidative stress related liver injurie with more favorable effects in the treatment of AGE rich diet-induced type 2 diabetic mice. We induced diabetes in C57BL/6 mice by AGE using a diet supplementation and limitation of physical activity. After 16 weeks of intervention, AGE fed mice were compared to control mice. Diabetic mice were assigned into seven experimental groups (each group; n = 5): diabetic mice, diabetic mice treated with SPTC (130 mg/kg), diabetic mice treated with Salvia Officinalis (65 mg/kg), diabetic mice treated with metformin (300 mg/kg), diabetic mice with endurance exercise training, diabetic mice treated with SPTC + metformin (130/300 mg/kg), diabetic mice treated with SPTC + exercise training. SPTC + exercise and SPTC + metformin reduced diabetic complications like gain weight, water and calorie intake, blood glucose, insulin, and GLUT4 content more efficiently than each treatment. These combinations improved oxidative stress hemostasis by activating the Nrf2 signaling pathway and attenuating keap1 protein more significantly. Eventually, combined treatment of SPTC with exercise or metformin as a novel approach had more beneficial effects to prevent the development of diabetes and oxidative stress associated with hyperglycemia.
Sections du résumé
BACKGROUND
BACKGROUND
SPTC is a mix of four herbal components (Salvia officinalis, Panax ginseng, Trigonella foenum-graeceum, and Cinnamomum zeylanicum) which might be prevented the development of AGE rich diet-induced diabetic complication and liver injury through activated the nuclear factor erythroid-2-related-factor-2 (Nrf2) pathway. Nrf2, as a master regulator of antioxidant response elements by activating cytoprotective genes expression, is decreased oxidative stress that associated with hyperglycemia and increases insulin sensitivity. the aim of this study was to assess whether the combination therapy of SPTC along with exercise or metformin moderate oxidative stress related liver injurie with more favorable effects in the treatment of AGE rich diet-induced type 2 diabetic mice.
METHODS
METHODS
We induced diabetes in C57BL/6 mice by AGE using a diet supplementation and limitation of physical activity. After 16 weeks of intervention, AGE fed mice were compared to control mice. Diabetic mice were assigned into seven experimental groups (each group; n = 5): diabetic mice, diabetic mice treated with SPTC (130 mg/kg), diabetic mice treated with Salvia Officinalis (65 mg/kg), diabetic mice treated with metformin (300 mg/kg), diabetic mice with endurance exercise training, diabetic mice treated with SPTC + metformin (130/300 mg/kg), diabetic mice treated with SPTC + exercise training.
RESULTS
RESULTS
SPTC + exercise and SPTC + metformin reduced diabetic complications like gain weight, water and calorie intake, blood glucose, insulin, and GLUT4 content more efficiently than each treatment. These combinations improved oxidative stress hemostasis by activating the Nrf2 signaling pathway and attenuating keap1 protein more significantly.
CONCLUSION
CONCLUSIONS
Eventually, combined treatment of SPTC with exercise or metformin as a novel approach had more beneficial effects to prevent the development of diabetes and oxidative stress associated with hyperglycemia.
Identifiants
pubmed: 33468193
doi: 10.1186/s12986-021-00543-6
pii: 10.1186/s12986-021-00543-6
pmc: PMC7816367
doi:
Types de publication
Journal Article
Langues
eng
Pagination
14Commentaires et corrections
Type : ErratumIn
Références
Baxi D, et al. Evaluation on the efficacy of a Poly-herbal supplement along with exercise in alleviating Dyslipidemia, Oxidative stress and hepatic and renal toxicity associated with Type-1 diabetes. 2010;4(2):35–43
Roblin L. Childhood obesity: food, nutrient, and eating-habit trends and influences. Appl Physiol Nutr Metab. 2007;32(4):635–45.
pubmed: 17622277
Anders S, Schroeter C. Diabetes, diet-health behavior, and obesity. Front Endocrinol. 2015;6:33.
Matzinger M, Fischhuber K, Heiss EH. Activation of Nrf2 signaling by natural products-can it alleviate diabetes? Biotechnol Adv. 2018;36(6):1738–67.
pubmed: 29289692
Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39(4):199–218.
Giudice A, Montella M. Activation of the Nrf2–ARE signaling pathway: a promising strategy in cancer prevention. BioEssays. 2006;28(2):169–81.
pubmed: 16435293
Canning P, Sorrell FJ, Bullock AN. Structural basis of Keap1 interactions with Nrf2. Free Radical Biol Med. 2015;88:101–7.
Itoh K, et al. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun. 1997;236(2):313–22.
pubmed: 9240432
pmcid: 9240432
Rushmore TH, Pickett C. Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants. J Biol Chem. 1990;265(24):14648–53.
pubmed: 2387873
Tu W, et al. The anti-inflammatory and anti-oxidant mechanisms of the Keap1/Nrf2/ARE signaling pathway in chronic diseases. Aging Dis. 2019;10(3):637.
pubmed: 31165007
pmcid: 6538222
Tong X-L, et al. Treatment of diabetes using traditional Chinese medicine: past, present and future. Am J Chin Med. 2012;40(05):877–86.
pubmed: 22928822
Colberg SR. Physical activity, insulin action, and diabetes prevention and control. Curr Diabetes Rev. 2007;3(3):176–84.
pubmed: 18220669
Di Meo S, Napolitano G, Venditti P. Mediators of physical activity protection against ROS-linked skeletal muscle damage. Int J Mol Sci. 2019;20(12):3024.
pmcid: 6627449
Done AJ, Traustadóttir T. Nrf2 mediates redox adaptations to exercise. Redox Biol. 2016;10:191–9.
pubmed: 27770706
pmcid: 5078682
Higashida K, et al. Normal adaptations to exercise despite protection against oxidative stress. Am J Physiol Endocrinol Metab. 2011;301(5):E779–84.
pubmed: 21750271
pmcid: 3214004
Paulsen G, et al. Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double-blind, randomised, controlled trial. J Physiol. 2014;592(8):1887–901.
pubmed: 24492839
pmcid: 4001759
Walsh EI, et al. Midlife susceptibility to the effects of poor diet on diabetes risk. Eur J Clin Nutr. 2020;1:1–6 (In press).
Dujic T, et al. Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes. Diabet Med. 2016;33(4):511–4.
pubmed: 26605869
Serra MC, et al. Long-term metformin treatment and risk of peripheral neuropathy in older Veterans. Diabetes Res Clin Pract. 2020;170:108486.
pubmed: 33035597
pmcid: 8015419
Hyogo H, Yamagishi S-I. Advanced glycation end products (AGE) and their involvement in liver disease. Curr Pharm Des. 2008;14(10):969–72.
pubmed: 18473847
Garcia-Compean D, et al. Liver cirrhosis and diabetes: risk factors, pathophysiology, clinical implications and management. World J Gastroenterol WJG. 2009;15(3):280.
pubmed: 19140227
Yamagishi S-I, et al. Role of advanced glycation end products (AGE) and oxidative stress in vascular complications in diabetes. Biochimica et Biophysica Acta (BBA) Gen Subj. 2012;1820(5):663–71.
Wu C-H, Huang S-M, Yen G-C. Silymarin: a novel antioxidant with antiglycation and antiinflammatory properties in vitro and in vivo. Antioxid Redox Signal. 2011;14(3):353–66.
pubmed: 20578796
Wautier M-P, et al. Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. Am J Physiol Endocrinol Metab. 2001;280(5):E685–94.
pubmed: 11287350
Chen XJ, et al. Advanced glycation end-products induce oxidative stress through the Sirt1/Nrf2 axis by interacting with the receptor of AGE under diabetic conditions. J Cell Biochem. 2019;120(2):2159–70.
He X, et al. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. J Mol Cell Cardiol. 2009;46(1):47–58.
pubmed: 19007787
Zhang Y-KJ, et al. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. Toxicol Appl Pharmacol. 2012;264(3):305–14.
pubmed: 23017736
pmcid: 3507999
Panahi M, et al. Cytoprotective effects of antioxidant supplementation on mesenchymal stem cell therapy. J Cell Physio. 2020;235(10):6462–95.
Kang GG, et al. Dietary polyphenols and gene expression in molecular pathways associated with type 2 diabetes mellitus: a review. Int J Mol Sci. 2020;21(1):140.
Hamidpour M, et al. Chemistry, pharmacology, and medicinal property of sage (Salvia) to prevent and cure illnesses such as obesity, diabetes, depression, dementia, lupus, autism, heart disease, and cancer. J Tradit Complement Med. 2014;4(2):82–8.
pubmed: 24860730
pmcid: 4003706
Satoh T, et al. Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1. J Neurochem. 2008;104(4):1116–31.
pubmed: 17995931
Zhang H, et al. Salvianolic acid A protects RPE cells against oxidative stress through activation of Nrf2/HO-1 signaling. Free Radical Biol Med. 2014;69:219–28.
Wu P, et al. Effects of the Nrf2 protein modulator salvianolic acid A alone or combined with metformin on diabetes-associated macrovascular and renal injury. J Biol Chem. 2016;291(42):22288–301.
pubmed: 27417135
pmcid: 5064007
Gao Y, et al. Ginsenoside Rg1 protects mice against streptozotocin-induced type 1 diabetic by modulating the NLRP3 and Keap1/Nrf2/HO-1 pathways. Eur J Pharmacol. 2020;866:172801.
pubmed: 31738935
Buelna-Chontal M, Zazueta C. Redox activation of Nrf2 & NF-κB: a double end sword? Cell Signal. 2013;25(12):2548–57.
pubmed: 23993959
Ramachandran R, Saraswathy M. Up-regulation of nuclear related factor 2 (NRF2) and antioxidant responsive elements by metformin protects hepatocytes against the acetaminophen toxicity. Toxicol Res. 2014;3(5):350–8.
Tian X, et al. Downregulation of Bach1 protects osteoblasts against hydrogen peroxide-induced oxidative damage in vitro by enhancing the activation of Nrf2/ARE signaling. Chem Biol Interact. 2019;309:108706.
pubmed: 31194955
Vargas-Mendoza N, et al. Antioxidant and adaptative response mediated by Nrf2 during physical exercise. Antioxidants. 2019;8(6):196.
pmcid: 6617290
Thirupathi A, De Souza CT. Multi-regulatory network of ROS: the interconnection of ROS, PGC-1 alpha, and AMPK-SIRT1 during exercise. J Physiol Biochem. 2017;73(4):487–94.
pubmed: 28707280