Effect of genipin-1-β-d-gentiobioside on diabetic nephropathy in mice by activating AMP-activated protein kinase/silencing information regulator-related enzyme 1/ nuclear factor-κB pathway
| Autor: | Jing Chen, Lijun Song, Meizi Huang, Fengtao Li, Wenchang Zhao, Li Yongjun, Chen Yu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Pharmaceutical Science Inflammation Pharmacology AMP-Activated Protein Kinases medicine.disease_cause Kidney Diabetes Mellitus Experimental Diabetic nephropathy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine AMP-activated protein kinase Sirtuin 1 NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Diabetic Nephropathies Iridoids Protein kinase A 030304 developmental biology 0303 health sciences biology Plant Extracts Podocytes NF-kappa B AMPK medicine.disease Gardenia Blot Mice Inbred C57BL Oxidative Stress chemistry 030220 oncology & carcinogenesis biology.protein Genipin medicine.symptom Oxidative stress Phytotherapy |
| Zdroj: | The Journal of pharmacy and pharmacology. 73(9) |
| ISSN: | 2042-7158 |
| Popis: | Objectives Genipin-1-β-d-gentiobioside (GG) is a kind of compound extracted from Gardenia jasminoides Ellis. The chemical structure of GG is similar to that of geniposide and has antidiabetic effects. We aimed to investigate the efficacy of GG on diabetic nephropathy (DN) in vivo and in vitro experiments and explore its potential mechanism. Methods For high-fat diet/streptozotocin-induced DN mice used in our study, the general features of mice were analysed after GG treatment. Oxidative stress parameters and inflammatory factors were also measured by commercial kits. Kidney damage was assessed using hematoxylin and eosin (H&E), periodic acid-Schiff (PAS) and Masson staining, respectively. In vitro, podocyte injury was assessed by TUNEL and flow cytometric analyses. AMP-activated protein kinase/silencing information regulator related enzyme 1 (AMPK/SIRT1)/nuclear factor-κB (NF-κB) pathway-related proteins were detected by AMPK-siRNA intervention and western blotting. Key findings Treatment of GG could increase cell survival and attenuated kidney damage. Despite the presence of inflammatory and oxidative stress, when GG retained the expression of AMPK/SIRT1, it could be observed that the downstream NLRP3 inflammatory-related proteins were inhibited. Conclusions Results showed that the protective efficacy of GG on DN works together with hypoglycemia and suppressing oxidative stress and inflammation, which at least partly involved in APMK/SIRT1/NF-κB-dependent pathway. |
| Databáze: | OpenAIRE |
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