Molecular mechanism of Ginkgo biloba in treating type 2 diabetes mellitus combined with non‐alcoholic fatty liver disease based on network pharmacology, molecular docking, and experimental evaluations

Abstract

Ginkgo biloba has gained increasing attention owing to its remarkable effects against cardiovascular disease. However, the role of G. biloba in hepatic lipid metabolism disorders in type 2 diabetes mellitus (T2DM) combined with non‐alcoholic fatty liver disease (NAFLD) and its underlying mechanisms have not been elucidated. Here, the effective ingredients and mechanisms of action of G. biloba in T2DM combined with NAFLD were investigated via an integrated strategy of network pharmacology and molecular docking. Thirty‐four core targets for the alleviation of T2DM combined with NAFLD were identified and retrieved from multiple open‐source databases, after validating the ameliorative effect of G. biloba on lipid accumulation in vitro. The targets IL6, IL1B, VEGFA, PTGS2, and CCL2, among others, with high network association values, were screened using Cytoscape. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that 34 compounds derived from G. biloba may exert therapeutic effects via response to molecule of bacterial origin, cellular response to lipid, and response to the hormone. In addition, the AGE‐RAGE and IL‐17 signaling pathways were predicted to be most significantly affected. Meanwhile, the outcomes of the molecular docking experiment showed that the most effective ingredients in G. biloba showed a strong binding affinity to the potential target active sites. Findings from further in vitro experiments confirmed that G. biloba treatment decreased the level of IL6, IL1B, and VEGFA protein. In conclusion, our findings provided novel insights into the mechanisms underlying the therapeutic effect of G. biloba in T2DM combined with NAFLD. Practical applications As a medicinal food plant, G. biloba has been shown to exert benefits in cardiovascular diseases. However, the pharmacological material basis and complex mechanism of action in G. biloba in T2DM combined with NAFLD remain unknown. Here, the mechanism by which G. biloba could ameliorate T2DM combined with NAFLD was investigated, and the potential target and molecular mechanism were explored, through a comprehensive strategy combining network pharmacology and molecular docking. Our findings indicate that G. biloba exerts synergistic effects in treating T2DM combined with NAFLD through multi‐ingredients, multi‐targets, and multi‐pathways; the findings also elucidate the nutritional and therapeutic potential of G. biloba in preventing and treating T2DM combined with NAFLD and provides robust evidence for its clinical application.

Effects and safety of Ginkgo biloba on blood metabolism in type 2 diabetes mellitus: a systematic review and meta-analysis

“…By decreasing the transcription of pro-apoptotic caspase-9 and JNK and increasing the activity of anti-apoptotic Bcl-2 protein, Ginkgo biloba extract EGb761 attenuated proinflammatory and pro-apoptotic processes, thus preventing the initiation of apoptotic signaling cascade and thus protecting the integrity of the mitochondrial membrane (35). Research has demonstrated that the administration of Ginkgo biloba extract can impede adipogenesis and modulate lipid metabolism, resulting in a decrease in body weight and food consumption (8). Diabetic peripheral vasculopathy had a prevalence of about 20% in diabetic patients and was a common vascular complication of T2DM, with the lower limb arteries being the main site of onset (36,37).…”

“…A serious concern for healthcare was diabetes mellitus (DM), which has several features including chronic hyperglycemia and aberrant protein, fat, and carbohydrate metabolism (2,(4)(5)(6). Diabetes is one of the five priority noncommunicable diseases (NCDs) in WHO's NCDs control strategy (7,8). Ongoing complex, expensive efforts are required to prevent and treat chronic problems in patients with diabetes, especially type 2 diabetes mellitus (T2DM).…”

Exploring the mechanism of dendrobine in treating metabolic associated fatty liver disease based on network pharmacology and experimental validation

“…Finally, docking of receptor proteins with dendrobine was performed using AutoDock Vina [ 20 ]. According to references [ 21 – 23 ], a binding energy of ≤ -5 kJ/mol is commonly considered the standard for successful docking. Under this criterion, if the docking binding energy is ≤ -7 kJ/mol, it can be considered that the molecule and its target exhibit a high level of interaction stability, indicating a potentially effective binding between them.…”

Theabrownin from Dark Tea Ameliorates Insulin Resistance via Attenuating Oxidative Stress and Modulating IRS-1/PI3K/Akt Pathway in HepG2 Cells

“…Persistent hyperglycemia is known to elevate oxidative stress and induced IR in target tissues, thereby playing a significant role in the development of T2DM. Furthermore, impaired mitochondrial function caused by IR can lead to reducing insulin sensitivity and elevating blood glucose levels in a vicious cycle [ 4 ].…”