New insight into the mechanisms of Ginkgo biloba leaves in the treatment of cancer

Ginkgo biloba leaves (GBLs), as an herbal dietary supplement and a traditional Chinese medicine, have been used in treating diseases for hundred years. Recently, increasing evidence reveals that the extracts and active ingredients of GBLs have anti-cancer (chemo-preventive) properties. However, the molecular mechanism of GBLs in anti-cancer has not been comprehensively summarized. To systematically summarize the literatures for identifying the molecular mechanism of GBLs in cellular, animal models and clinical trials of cancers, as well as for critically evaluating the current evidence of efficacy and safety of GBLs for cancers. Employing the search terms "Ginkgo biloba" and "cancer" till July 25, 2023, a comprehensive search was carried out in four electronic databases including Scopus, PubMed, Google Scholar and Web of Science. The articles not contained in the databases are performed by manual searches and all the literatures on anti-cancer research and mechanism of action of GBLs was extracted and summarized. The quality of methodology was assessed independently through PRISMA 2020. Among 84 records found in the database, 28 were systematic reviews related to GBLs, while the remaining 56 records were related to the anticancer effects of GBLs, which include studies on the anticancer activities and mechanisms of extracts or its components in GBLs at cellular, animal, and clinical levels. During these studies, the top six cancer types associated with GBLs are lung cancer, hepatocellular carcinoma, gastric cancer, breast cancer, colorectal cancer, and cervical cancer. Further analysis reveals that GBLs primarily exert their anticancer effects by stimulating cancer cell apoptosis, inhibiting cell proliferation, invasion and migration of cancers, exhibiting anti-inflammatory and antioxidant properties, and modulating signaling pathways. Besides, the pharmacology, toxicology, and clinical research on the anti-tumor activity of GBLs have also been discussed. This is the first paper to thoroughly investigate the pharmacology effect, toxicology, and the mechanisms of action of GBLs for anti-cancer properties. All the findings will reinforce the need to explore the new usage of GBLs in cancers and offer comprehensive reference data and recommendations for future research on this herbal medicine.