Ginkgo Biloba's anti-anxiety and mild antidepressant properties stem from the reversible inhibition of two MAOA and MAOB enzymes. Its antioxidant, anti-inflammatory, and neuroprotective effects are primarily due to the flavonoid and terpenoid content in Ginkgo Biloba. The abundant alkaloid ketones, amino acids, cyanogenic glycosides, and phenols found in this plant extract are the active substances responsible for its therapeutic effects. Ginkgo Biloba has positive effects on psychosis, anxiety, schizophrenia, and depression. It stimulates cerebral blood circulation and is beneficial in Alzheimer's disease, addressing issues stemming from impaired blood flow to the brain such as anxiety, stress, poor memory, hearing problems, poor concentration, impaired thinking, social behavior, and dementia. In addition to its free radical scavenging properties, it has also been shown to influence the transcription of several genes associated with oxidative stress regulation. Several recent studies have shown that Ginkgo Biloba protects against Aβ-induced neurotoxicity by inhibiting Aβ-induced events such as glucose uptake, reactive oxygen species (ROS) accumulation, AKT activation, mitochondrial dysfunction, JNK and ERK 1/2 pathways, and apoptosis. Since AβPP processing and amyloidogenesis are hypothesized to be influenced by circulating and intracellular cholesterol levels, Ginkgo Biloba has been reported to inhibit Aβ production in the brain by reducing circulating free cholesterol levels. Ginkgo Biloba may also interfere with Aβ oligomer formation. It is well known that the β-sheet structure of Aβ oligomers is primarily responsible for Aβ neurotoxicity and can also help Aβ evade clearance via proteolytic cleavage. Therefore, inhibiting the formation of the β-sheet structure of Aβ oligomers could be a key strategy in preventing Aβ toxicity. Ginkgo Biloba also possesses iron chelation properties that can inhibit Aβ fibril formation. Ginkgo Biloba can also prevent Aβ fibril formation by increasing transthyretin gene expression. The anti-Aβ effect of Ginkgo Biloba on Aβ aggregation was also observed with the flavonoid compounds ginkgolide J and bilobalide. Furthermore, Ginkgo Biloba has been shown to regulate mitochondrial oxidative phosphorylation (OXPHOS) against Aβ-induced oxidative stress, thus helping to maintain ROS/RNS (reactive oxygen species/reactive nitrogen species) balance in cells. Studies demonstrate that Ginkgo Biloba has beneficial effects on cellular OXPHOS function, thus helping to improve mitochondrial function against Aβ-induced toxicity. The antioxidant activity in Ginkgo Biloba extract is related to flavonoid components such as kaempferol and quercetin, which suppress ROS in the body in both in vitro and in vivo models. The flavonoid fraction is responsible for its antioxidant effect through direct ROS scavenging, chelation of pro-oxidative heavy metal ions, and increased expression of antioxidant proteins such as superoxide dismutase (SOD) and glutathione reductase (GSH).

PUBLICATIONS ON THE SUBJECT:

** CNS Neurosci Ther. 2019 Feb;25(2):288-298. doi: 10.1111/cns.13095.

Treatment of dementia and mild cognitive impairment with or without cerebrovascular disease: Expert consensus on the use of Ginkgo biloba extract, EGb 761®

**Front Pharmacol. 2021 Nov 4;12:775034. doi: 10.3389/fphar.2021.775034. eCollection 2021.

The Use of Ginkgo Biloba L. as a Neuroprotective Agent in the Alzheimer's Disease

** Neurotherapeutics. 2019 Jul;16(3):666-674. doi: 10.1007/s13311-019-00767-8.

Neuroprotective and Antioxidant Effect of Ginkgo biloba Extract Against AD and Other Neurological Disorders

** Pharmaceuticals (Basel). 2021 Apr 1;14(4):305. doi: 10.3390/ph14040305.

Mild Cognitive Impairment and Mild Dementia: The Role of Ginkgo biloba (EGb 761®)

**JAMA. 2008 Nov 19;300(19):2253-62. doi: 10.1001/jama.2008.683.

Ginkgo biloba for prevention of dementia: a randomized controlled trial

**Front Pharmacol. 2021 Aug 3;12:721216. doi: 10.3389/fphar.2021.721216. eCollection 2021.

Ginkgo Biloba Extract Is Comparable With Donepezil in Improving Functional Recovery in Alzheimer's Disease: Results From a Multilevel Characterized Study Based on Clinical Features and Resting-State Functional Magnetic Resonance Imaging

**Front Pharmacol. 2020 Feb 21;10:1688. doi: 10.3389/fphar.2019.01688.

An Updated Review of Randomized Clinical Trials Testing the Improvement of Cognitive Function of Ginkgo biloba Extract in Healthy People and Alzheimer's Patients