Effects of gastrodin against carbon tetrachloride induced kidney inflammation and fibrosis in mice associated with the AMPK/Nrf2/HMGB1 pathway

• Published in: Food & function Vol. 11; no. 5; pp. 4615 - 4624
• Main Authors: Ma, Jie-Qiong, Sun, Yun-Zhi, Ming, Qing-Lei, Tian, Zhi-Kai, Zhang, Yu-Jia, Liu, Chan-Min
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 01.05.2020
• Subjects: Actin; Activation; Adenosine monophosphate; Advanced glycosylation end products; AMP; Animals; Antioxidants; Benzyl Alcohols - administration & dosage; Benzyl Alcohols - therapeutic use; Carbon; Carbon Tetrachloride; CCL4 protein; Collagen; Cytokines; Disease Models, Animal; Fibrosis; Fibrosis - prevention & control; Glucosides - administration & dosage; Glucosides - therapeutic use; Glycosylation; Growth factors; HMGB1 protein; HMGB1 Protein - metabolism; Inflammation; Inflammation - prevention & control; Interleukin 6; Kidney Diseases - prevention & control; Kidneys; Kinases; Male; Mice; Mice, Inbred ICR; Muscles; NF-E2-Related Factor 2 - metabolism; NF-κB protein; Oxidative stress; Phenolic compounds; Phenols; Phytotherapy; Protein kinase; Protein Kinases - metabolism; Receptors; Smooth muscle; Supplements; Toll-like receptors; Transforming growth factor-b; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/d0fo00711k

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibits potential renoprotective properties. Here, we examined the protective effects of GAS on carbon tetrachloride (CCl 4 )-induced kidney inflammation and fibrosis in mice, and explored its underlying mechanisms. Our research findings revealed that GAS improved CCl 4 -induced renal damage in mice. GAS inhibited kidney fibrosis and the deposition of collagen and α-smooth muscle actin (α-SMA). GAS suppressed CCl 4 -induced inflammation in kidney tissue, as indicated by the decreased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The renoprotective effects of GAS were associated with inhibiting oxidative stress by regulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling and increasing adenosine 5′-monophosphate activated protein kinase (AMPK) activation. Furthermore, GAS supplementation inactivated the receptor for advanced glycation end products (RAGE) and the high-mobility group box-1 (HMGB1) pathway. GAS inhibited the activation of Toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB) and transforming growth factor (TGF)-β. Collectively, this study clarified that GAS attenuates CCl 4 -induced kidney inflammation and fibrosis via the AMPK/Nrf2/HMGB1 pathway. Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibits potential renoprotective properties.