Gastrodin inhibits high glucose‑induced inflammation, oxidative stress and apoptosis in podocytes by activating the AMPK/Nrf2 signaling pathway

Abstract

Diabetic nephropathy (DN) is a serious and common complication of type 1 and 2 diabetes. Gastrodin has been reported to suppress high glucose (HG)-induced inflammation and oxidative stress in vivo and in vitro. However, the effect of gastrodin on DN has not been fully elucidated. The present study aimed to investigate the underlying mechanism involved in the effect of gastrodin on podocyte injury caused by DN. Cell viability was evaluated using Cell Counting Kit-8 assay and secretion levels of TNF-α, IL-1β and IL-6 were measured using ELISA. The levels of malondialdehyde, activities of lactate dehydrogenase and superoxide dismutase were quantified using corresponding assay kits. Additionally, cell apoptosis was analyzed by TUNEL assay, whilst protein expressions related to inflammation, apoptosis and the 5'-AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were measured by western blot analysis. The results showed that gastrodin increased the viability of MPC5 cells following HG stimulation. Gastrodin also alleviated HG-induced inflammation, oxidative stress and apoptosis in MPC5 cells. Furthermore, gastrodin promoted activation of the AMPK/Nrf2 pathway in MPC5 cells. Treatment with the AMPK inhibitor, compound C, reversed the inhibitory effects of gastrodin on inflammation, oxidative stress and cell apoptosis. To conclude, treatment of MPC5 cells with gastrodin can attenuate HG-induced inflammation, oxidative stress and cell apoptosis by activating the AMPK/Nrf2 signaling pathway. Results from the current study suggest that gastrodin can be used as an effective therapeutic agent against HG-induced podocyte injury in DN.

Sestrin2 Signaling Pathway Regulates Podocyte Biology and Protects against Diabetic Nephropathy

“…AMPK phosphorylation was also followed by upregulation of ULK1, enhancement of autophagy, and decrease in oxidative stress, podocyte loss, fibrosis, and albuminuria in a mouse model of diabetic nephropathy [125]. Conversely, inhibition of AMPK by compound C abolished the beneficial effects of AMPK in podocyte viability and aggravated high glucosemediated oxidative stress, inflammation, apoptosis, collagen accumulation, and GMB thickening (Figure 2) [126,127]. Decreased function of PGC-1α was shown to impair mitochondrial function and facilitate fibrogenesis in diabetic nephropathy [128].…”

Molecular Mechanistic Pathways Targeted by Natural Compounds in the Prevention and Treatment of Diabetic Kidney Disease

“…Huang et al found that gastrodin increased the activity of antioxidant enzymes and reduced the level of inflammatory factors, thus reducing the inflammation, oxidative stress, and apoptosis of MPC-5 cells induced by HG. The mechanism is related to activating the AMPK/Nrf2 signaling pathway and reducing the formation of NLRP3 inflammasome [ 71 ]. Gastrodin is relatively safe to use.…”

Eriodictyol attenuates doxorubicin-induced nephropathy by activating the AMPK/Nrf2 signalling pathway

“… 8 , 9 , 10 , 11 , 12 AMP-activated protein kinase (AMPK) acts as an energy sensor in the majority of mammalian cells and is stimulated by low ATP levels or a high ratio of AMP/ADP to ATP. 13 , 14 Interestingly, suppression of AMPK was implicated in DOX-induced cardiac, hepatic, and renal damage whereas genetic or pharmacological activation of these molecules improved organs’ structure and function by attenuating oxidative stress, fibrosis, inflammation, and apoptosis. 13 , 15 , 16 In this context, it was shown that AMPK stimulates antioxidant expressions by upregulating and activating Nrf2.…”