<i>Ginkgo biloba</i> as a Promising Candidate for Traumatic Brain Injury: Insights From Preclinical and Clinical Studies

Traumatic brain injury (TBI) is a leading cause of mortality and long-term neurological disability, while effective pharmacological therapies for its neurobehavioral consequences remain limited. This systematic review evaluates the therapeutic potential of Ginkgo biloba (GB), particularly the standardized extract EGb 761, in TBI management. A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to February 2026. Sixty-five studies met the inclusion criteria, including 42 in vivo experimental studies and 23 clinical trials examining neuroprotective, cognitive, behavioral, or functional outcomes following GB administration. Preclinical evidence consistently demonstrates that Ginkgo biloba (GB) exerts neuroprotective effects through attenuation of oxidative stress, as evidenced by increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, alongside reduced malondialdehyde (MDA) levels. These effects are accompanied by modulation of the Slc7a11-Eif4ebp1 signaling axis, suppression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α, and regulation of key molecular pathways. Specifically, GB inhibits JAK/STAT and TXNIP/NLRP3 signaling while activating PI3K/AKT-associated pathways and autophagy. Clinical studies indicate potential improvements in cognitive and functional outcomes. However, adverse events, particularly bleeding, have been reported, especially when GB is co-administered with anticoagulants or nonsteroidal anti-inflammatory drugs. This underscores the importance of careful patient monitoring. The current evidence supports the promising neuroprotective potential of GB in traumatic brain injury. Nevertheless, clinical data remain insufficient to justify routine therapeutic use. Large-scale, well-designed, randomized controlled trials are necessary to confirm efficacy, optimize dosing regimens, and establish long-term safety profiles.