6-Gingerol protects cardiocytes H9c2 against hypoxia-induced injury by suppressing BNIP3 expression

Abstract

Background: Cardiomyocytes loss is the predominant pathogenic characteristic in the hypoxia-induced injury. Meanwhile, it has been corroborated that Bcl-2 E1B 19-KDa interacting protein 3 (BNIP3) provokes apoptosis and autophagy. For moderating cardiomyocytes loss, we initially probed the cyto-protection effects of 6-Gingerol (6 G), meanwhile, its potential mechanisms associated with BNIP3 were elucidated in our studies. Methods: We pretreated cardiomyocytes H9c2 cells with 6 G at different concentrations (0-100 lM) before exposure to hypoxia. Thereafter, the cell viability, lactate dehydrogenase (LDH), apoptosis and protein expression were respectively assessed using cell counting kit-8 and methyl thiazolyl tetrazolium (MTT) assay, LDH assay kit, Annexin V-fluorescein isothiocyannate/propidium iodide (Annexin V-FITC/PI) apoptosis detection kit and Western blotting analysis. In addition, we also analyzed BNIP3 level after treatment. Moreover, we enforced the exogenous overexpression of BNIP3 and then evaluated the cell viability, apoptosis, and protein level again. Results: In our present work, we observed that the cell viability was promoted by 6 G in the hypoxiainduced H9c2 cells in a dose-dependent manner. Moreover, hypoxia-induced LDH release, apoptosis and autophagy were inhibited by 6 G pretreatment through promoting phosphorylation of PI3K, AKT and mTOR. Remarkably, accumulation of BNIP3 protein was significantly reduced by 6 G in hypoxia-induced H9c2 cells. Mechanistically, 6 G initiated the phosphorylated expression of PI3K, AKT and mTOR by down-regulating BNIP3 with reducing cardiomyocytes apoptosis and autophagy. Conclusion: Hypoxia-induced cardiomyocytes injury was ameliorated by 6 G through suppressing BNIP3 expression with triggering PI3K/AKT/mTOR signalling pathway.

Salvianolic acid A blocks vasculogenic mimicry formation in human non‐small cell lung cancer via PI3K/Akt/mTOR signalling

“…Flow cytometry analysis was applied by assessing the apoptotic cell death 25 . Apoptosis rates were estimated via Annexin V–FITC/PI apoptosis kit (BD biosciences).…”

Ginger: A complementary approach for management of cardiovascular diseases

“…102 In another study, 6G induced the expression of PI3K/AKT/mTOR, thus reducing cardiomyocyte apoptosis and autophagy. 117,120 Given the anti-inflammatory and antioxidative properties of 6G, further investigations of 6G in CVD, including diabetes and insulin resistance and atherosclerotic and cardiometabolic disease, are warranted. nanomedicines has been implicated as promising drug delivery system methods in a variety of CVD, mainly due to the capacity of the nanomedicines to be mobilized in the vascular system and other organelles for multiple purposes.…”

6-Gingerol Alleviates Neonatal Hypoxic-Ischemic Cerebral and White Matter Injury and Contributes to Functional Recovery

“…Therefore, there is an urgent need to explore new treatments. Recent studies have shown that 6-Gingerol, as a new Chinese herbal medicine in nervous system therapy, has significant therapeutic anti-inflammatory, anti-apoptotic and anti-oxidative stress effects ( Ren et al, 2019 ; Sun et al, 2020 ; Zahoor et al, 2020 ). In present study, we explored the therapeutic effect of 6-Gingerol in HIBI model, defined its benefical effects in acute and long-term injury.…”

“…Previous studies have shown that 6-Gingerol can reduce neuroinflammatory responses in primary peripheral nerve injury in mice and play an anti-inflammatory role in mastitis and myocardial fibrosis ( Borgonetti et al, 2020 ; Han et al, 2020 ; Zahoor et al, 2020 ). In hypoxia-induced cardiomyocyte injury, 6-Gingerol can enhance the vitality of cardiomyocytes, and reduce apoptosis and oxidant stress, thereby protecting cardiomyocytes from hypoxic damage ( Ren et al, 2019 ). The above studies have fully suggested that 6-Gingerol can play a protective role in hypoxia induced cell injury and neuroinflammation response.…”