Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphate‐activated protein kinase/mammalian target of the rapamycin pathway modulation

Abstract

Studies demonstrated that Ginkgo biloba extract (GBE) played a cardioprotective role in diabetic conditions. Impaired autophagy is one of the mechanisms underlying diabetic cardiomyopathy (DCM). The effect of GBE on autophagy has been observed in several diseases; however, whether GBE can ameliorate DCM by regulating autophagy remains unclear. Here, we investigated the effect of GBE on DCM and the potential mechanisms regarding autophagy using a streptozotocin (STZ)-induced diabetic rat model and a high-glucose (HG)-stimulated H9C2 cell model. We demonstrated that GBE attenuated metabolic disturbances, improved cardiac function, and reduced myocardial pathological changes in diabetic rats. Impaired autophagy as well as dysregulation of the adenosine monophosphate-activated protein kinase/ mammalian target of the rapamycin (AMPK/mTOR) signaling pathway were observed in diabetic hearts, as evidenced by the reduced conversion of LC3B-I to LC3B-II along with excessive p62 accumulation, decreased AMPK phosphorylation, and increased mTOR phosphorylation, which could be reversed by GBE treatment. In vitro, GBE reduced the apoptosis induced by HG in H9C2 cells by activating AMPK and inhibiting mTOR to restore autophagy. However, this effect was inhibited by the AMPK inhibitor Compound C. In conclusion, the ameliorative effect of GBE on DCM might be dependent on the restoration of autophagy through modulation of the AMPK/ mTOR pathway.

Exosomal MALAT1 from macrophages treated with high levels of glucose upregulates LC3B expression via miR-204-5p downregulation

“…43 Our study results revealed that hyperglycemia upregulated MALAT1 expression and LC3B , an autophagy marker, in both macrophages and diabetic rats after balloon injury of the carotid artery. However, Yang et al 44 reported that impaired autophagy was observed in high glucose-stimulated H9C2 cells and heart tissue from diabetic patients. Analysis of the effect of MALAT1 on different cell types and disease models may help us understand these seemingly contradictory reports on MALAT-mediated activation and inhibition of autophagy.…”

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy

“…Ginkgo biloba extract has been shown to regulate the AMPK/mTOR pathway, activate autophagy, and improve cardiac function by decreasing myocardial pathological changes ( Yang et al, 2023 ).…”