Alzheimer\'s disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords-GB in AD and dementia-yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

BACKGROUND: One of the most unique plants that have ever grown on the planet is Ginkgo biloba L., a member of the Ginkgoaceae family with no close living relatives. The existence of several differently structured components of G. biloba has increased the chemical variety of herbal therapy. Numerous studies that investigated the biochemical characteristics of G. biloba suggest this plant as a potential treatment for many illnesses.
OBJECTIVE: Review the molecular mechanisms involved in the signaling pathways of G. biloba activity in varied circumstances and its potential as a novel treatment for various illnesses.
METHODS: Studies focusing on the molecular processes and signaling pathways of compounds and extracts of G. biloba were found and summarized using the proper keywords and operators from Google Scholar, PubMed, Web of Science, and Scopus without time restrictions.
RESULTS: G. biloba exerts its effects through its anti-inflammatory, anti-apoptotic, anti-cancer, neuroprotective, cardioprotective, hepatoprotective, antiviral, antibacterial, pulmoprotective, renoprotective, anti-osteoporosis, anti-melanogenic, retinoprotective, otoprotective, adipogenic, and anti-adipogenic properties. The most important mechanisms involved in these actions are altering the elevation of ROS formation, inhibiting NADPH oxidases activation, altering the expression of antioxidant enzymes, downregulating MAPKs (p38 MAPK and ERK, and JNK) and AP-1, increasing cAMP, inactivating Stat5, activating the AMPK signaling pathway, affecting Stat3/JAK2, NF-κB, Nrf-2, mTOR, HGF/c-Met, Wnt/β-catenin and BMP signaling pathways, and changing the mitochondrial transmembrane potential, the Bax/Bcl-2 ratio, the release of Cyc from mitochondria to cytosol, the protein cleavage of caspases 3, 7, 8, 9, and 12, poly (ADP-ribose) polymerase, and MMPs levels.
CONCLUSIONS: G. biloba and its components have gained attention in recent years for their therapeutic benefits, such as their anti-inflammatory, antioxidant, anti-apoptotic, and apoptotic effects. By understanding their molecular mechanisms and signaling pathways, potential novel medicines might be developed in response to the rising public desire for new therapies.