Network pharmacology-based strategy to investigate pharmacological mechanisms of Ginkgo Biloba Extract for Aging

Abstract

Background Aging represents the main risk factor for a number of debilitating diseases and contributes to increase in mortality. Previous studies have shown that ginkgo biloba extract (EGb) can prevent and treat aging-related diseases, but its pharmacological effects need to be further clarified. In this study, we proposed a network pharmacology-based method to identify the therapeutic pathways of EGb for aging.Methods The active components of EGb and targets of sample chemicals were obtained from TCMSP database. Aging-related genes were obtained by retrieving the Human Ageing Genomic Resources database and the JenAge Ageing Factor Database. Then, a network containing the interactions between the putative targets of EGb and known therapeutic targets of aging was built, which was used to investigate pharmacological mechanisms of EGb for Aging.Results 24 active components, 154 targets of active components of EGb and 308 targets of aging were obtained. Network construction and pathway enrichment were carried out after data integration. The research found that flavonoids (quercetin, luteolin, kaempferol) and beta-sitosterol might be the main active component of EGb. The top eight candidate targets, including PTGS2, PPARG, DPP4, GSK3B, CCNA2, AR, MAPK14, ESR1, were chosen as EGb’s main therapeutic targets. The results of pathway enrichment participated in various pathways associated with inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance and regulating cellular biological processes, etc. Molecular docking results showed that PPARG had better binding capacity with beta-sitosterol and PTGS2 had better binding capacity with kaempferol and quercetin.Conclusions The main components of EGb might act on multiple targets, such as PTGS2, PPARG, DPP4, GSK3B, etc., to regulate multiple pathways and played an anti- aging role by inhibiting oxidative stress, inhibiting inflammation, ameliorating insulin resistance.

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“…Docking results demonstrate that all CP compounds, including scopoletin and quercetin, exhibited substantial binding affinity to COX-2 and COX-1, suggesting their potential application in the development of antineuroinflammatory agents. Previous in silico reports on interaction of COX-2 with quercetin and kaempferol also support our data [76].…”

Ginkgo biloba: A Treasure of Functional Phytochemicals with Multimedicinal Applications

“…Total lactones of Ginkgo (TLG) applied to aged mice displayed antiaging effects by attenuating lipid peroxidation, Evidence-Based Complementary and Alternative Medicine NO levels, and cerebral apoptosis [125]. e main components of EGb 716 can regulate numerous pathways and exert antiaging effects by inhibiting inflammation, reducing oxidative stress, and improving insulin resistance, mediated by several targets, such as PPARG, DPP4, and GSK3B [126].…”

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“…Luteolin has antioxidant activity and inhibits the activation of NF-κB and the expression of cyclooxygenase-2, thus reduce the production of inflammatory factors such as IL-6 and IL-12. And it also participates in immune regulation and is able to inhibit Toll-like receptor signaling pathways [24][25] . Kaempferol exerts antibacterial, anti-inflammatory and anticancer effects by inducing apoptosis, reducing cell viability, reduce phosphatidylinositol 3 kinase and protein kinase B [26] .…”