Ginkgo biloba has been an effective medicine in addition to traditional herbs and herbal dietary supplements. The latest research has proven that many bioactive components in G. biloba exhibit various pharmacological activities, including anti-inflammatory, anti-tumor, antidepressant, hepatoprotective, antiviral, antifungal, anticancer, and antioxidant effects.

4.1 Anti-oxidant activities

The antioxidant effect is linked to increased amounts of superoxide dismutase, glutathione, cytochrome P-450, and catalase activity. Stefanovits-Bányai et al. (2006). Both male and female Ginkgo biloba leaf extracts exhibit antioxidant activity. The male extract showed greater free radical-scavenging ability, while the female extract contained more beneficial ions (Mg²⁺, Ca²⁺, K⁺, Na⁺, and Zn²⁺) that positively affected degenerative brain diseases. At concentrations of about 10–500 µg/mL, the Ginkgo biloba extract helped protect human lymphocyte DNA and cell membranes from damage caused by free radicals. Its antioxidant activity is similar to that of α-tocopherol. Polyphenols are important antioxidants found in plants. They help protect the plant by neutralizing harmful free radicals, reducing certain substances, or binding to metals. The maximum classes of plant phenolics, flavonoids, and phenolic acids have shown significant antioxidant activity in various studies [19]. Most compounds in GBL significantly decreased during intestinal digestion, except for vanillic acid and bioflavonoids. There were notable reductions in total flavonoid and phenolic content after in vitro digestion. While DPPH and ABTS scavenging capacities dropped post-gastric digestion, they were enhanced during intestinal digestion. The FRAP assay, however, showed a different trend [20]. Polysaccharides derived from Ginkgo biloba are recognized as a highly effective and rising source of antioxidants, making them an excellent choice for those seeking natural ways to enhance their health [21]. Biflavonoids possess a less potent antioxidant capacity when contrasted with the other remarkable compounds found in ginkgo. Notably, the biflavonoids amentoflavone, bilobetin, ginkgetin, and sciadopitysin have been evaluated alongside 25 other ginkgo-derived compounds for their effectiveness in combating oxidative stress in HL-60 (promyeloblast) cells. In addition to amentoflavone, derived from various plants, it demonstrates powerful antioxidant activity [6]. Ginkgo extract is a powerhouse of flavonoids, celebrated for its potential as a natural antioxidant. It works by skillfully scavenging free radicals, superoxide anions, and nitric oxide, while also inhibiting harmful free radical reactions and lipid peroxidation. By harnessing the remarkable protective properties of Ginkgo, we can embrace a vibrant, healthier future [22].

4.2 Anti-tumor Activity

Polysaccharides extracted from G. biloba leaves, in addition to the exocarp, have demonstrated a remarkable ability to block human endometrial cancer cell HEC-1B, in addition to the proliferation of 4T1 breast cancer cells, showing a clear dose-dependent effect [21]. Ginkgolide B, isolated from G. biloba, inhibits the proliferation of tumor cells [23]. GBSP, a highly purified polysaccharide derived from G. biloba seeds, powerfully induces apoptosis in the SMMC-7721 hepatoma cell line and significantly inhibits its cell division [24]. Endophytic fungi, ingeniously extracted from Ginkgo biloba leaves, encompass the remarkable strains J-1, J-2, and J-3, all of which exhibit the fascinating ability to produce podophyllotoxin. These three strains were meticulously identified through advanced molecular biology techniques. The secondary metabolites derived from J-1, J-2, and J-3 display a striking potency, significantly inhibiting the proliferation of HeLa cells, increasing their apoptosis, and effectively halting their migration. Furthermore, these remarkable compounds have been shown to profoundly diminish the growth of HeLa tumors, highlighting their potential as powerful allies in the fight against cancer [10].

4.3 Anti-inflammatory activity

The extracts and their commercial procedure, including ginkgolides (A or B), bilobalide, water-soluble polysaccharides also amentoflavone, and have shown positive anti-inflammatory effects. Studies indicate significant reductions in interferon, nitric oxide, prostaglandin E2, TNF-α, IL-4, IL-6, IL-1β in inflamed tissues and IL-12, IL-1. There were also alternatives in the MAPK and NF-κB signaling routes, linked to decreased translocation of NF-κB, alongside enhanced activation of AMPK protein kinase, as well as heme oxygenase and Natural polysaccharides, such as those from G. biloba leaves (PGBL), have notable anti-inflammatory effects. They reduce monocytes' sensitivity to lipopolysaccharide (LPS) and inhibit inflammatory factor expression in RAW 264.7 cells [25-29]. GBSP3a (a water-soluble polysaccharide from Ginkgo biloba sarcotesta) has significant effects on LPS-induced RAW264.7 macrophages. It effectively reduces the release of key inflammatory intermediaries, including nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). Additionally, GBSP3a inhibits the disclosure of inducible nitric oxide synthase (iNOS) as well as cyclooxygenase-2 (COX-2) in a dose-dependent fashion. Its anti-inflammatory effect primarily stems from the prevention of nuclear factor-κB (NF-κB) and MAPK signaling routes [30]. EGb 761 alleviates inflammation in the hippocampus of mouse brains after 8 minutes of extended ischemia by examining the activation of microglia and astrocytes, key markers of inflammation. Microglia activation results in an "amoeboid" cell shape, with a larger soma and retracted, thicker processes and enhanced expression of the integrin CD11b. Similarly, activated astrocytes have larger soma and increased GFAP expression. The vehicle-treated group had a significantly increased number of GFAP-positive cells and activated microglia in the hippocampus after seven days compared to the sham group's baseline values. EGb 761 pretreatment revealed a decrease in GFAP-positive and activated microglia, indicating the anti-inflammatory function of EGb 761 [31].

4.4 Anti-cancer activity

Ginkgo leaves have been shown to exhibit remarkable anticancer and antiproliferative effects in numerous in vitro studies targeting diverse cell lines [32]. Bilobetin, isoginkgetin, in addition to sciadopitysin, are less studied compounds with a significant role in the anticancer treatments of ginkgo extracts [33]. Amentoflavone contributes to anti-cancer action by regulating key signaling routes like ERK, NF-κB, and PI3K/Akt [34]. Ginkgetin, extracted from Ginkgo biloba, effectively stops cancer progression by blocking the cell cycle and stimulating autophagy and apoptosis. It targets key disrupted signaling pathways, including JAK/STAT and MAPKs, and is a powerful Hsp90 inhibitor. Ginkgetin, isolated from Ginkgo leaves, also increases the anticancer effects of cisplatin by disrupting the Nrf2/HO-1 axis through ferroptosis, which is especially monumental in non-small-cell lung cancer that has an EGFR wild-type. This suggests its potential as a valuable adjunct in cancer treatment [6]. We clearly established that Ginkgo Biloba extract (GBE) exhibits significant anti-cancer effects on human gastric cancer cells (SGC-7901 & MGC-803), effectively inhibiting metastasis in a dose-dependent manner. Furthermore, ginkgolic acid from ginkgo biloba powerfully impedes the growth of pancreatic tumor cells by downregulating essential adipogenesis enzymes, including acetyl-CoA carboxylase, in addition to fatty acid synthesis [35, 36]. We began our investigation into the effects of EGb 761 on cancer cell invasion and migration. As expected, Ginkgo biloba extract 761 significantly reduced the migration of HT29 and HCT116 cells after 48 hours, demonstrating a strong dose-dependent response, particularly between the 500 mg/L and 250 mg/L groups [37]. The Ginkgo biloba extract not only boosts the rate of DNA mending following oxidative stress but also demonstrates a remarkable enhancement of the DNA repair mechanisms. Additionally, it provides robust protection against the damaging effects of oxidative stress on DNA [37].

4.5 Anti-bacterial and anti-fungal activity

The extract of Ginkgo biloba shows activity against various Gram-negative bacteria in addition to Gram-positive bacteria [38]. Biflavonoids are derived from Ginkgo biloba and exhibit antibacterial activity [39]. The biflavonoids of ginkgo are also protected from antifungal agents (Krauze-Baranowska, 2003). Amentoflavone exhibits antimicrobial activity against Pseudomonas aeruginosa, Streptococcus mutans, Escherichia coli O-157, Escherichia coli, Staphylococcus aureus, and Enterococcus faecium. It shows significant antibacterial effects and synergistic interactions with antibiotics against a range of strains, excluding S. mutans. Amentoflavone also demonstrated effectiveness against food-borne pathogens like S. aureus and Escherichia coli in food models, including apple juice and chicken [6, 40, 41][14]. The protein extracted from Ginkgo biloba seeds in this study, named ginkbilobin, is a novel antifungal protein determined based on its N-terminal sequence. A notable feature of ginkbilobin is its strong antifungal activity against various fungal species, including Coprinus comatus, Mycosphaerella arachidicola, Fusarium oxysporum, Rhizoctonia solani, and Botrytis cinerea. It's important to note that specific antifungal proteins are ineffective against bacteria. Both the antimicrobial protein from garlic, Allium cepa (ACE-mp1), and ginkbilobin share antifungal and antibacterial properties [42]. The bioactive compounds are tannins, alkaloids, and saponins obtained from ginkgo biloba leaf extract. These plants are activated against the S. cerevisiae organism, while the organism is inactivated by fluconazole [43]. Ginkgo biloba exhibits the most antibacterial properties, as it not only has 94% antibacterial activity against Bacillus cereus but also prevents 96% of Escherichia coli (E. coli) [44].

4.6 Anti-viral activity

Ginkgetin's antiviral activity was tested against two influenza virus sialidases: A/PR/8/34 (H1N1) with a 50% inhibitory concentration of 55.00 µg/mL, and A/Guizhou/54/89 (H3N2) at 9.78 µg/mL. Amentoflavone can intercept herpes simplex virus 1 (HSV-1), including Acyclovir-resistant strains. Ginkgetin, from ginkgo leaves, exhibits anti-influenza properties and protects against various viruses. Bioflavonoids have shown potential as antiviral agents, demonstrating inhibitory effects against viruses like influenza A, influenza B, and respiratory syncytial virus [6, 45-47].

4.7 Alzheimer’s and dementia

Ginkgo biloba L. is a potent herbal remedy for Alzheimer's disease. The extract EGb 761 has demonstrated referable efficacy in alleviating cognitive dysfunction in gerbil models of vascular dementia, showcasing its promise in the realm of cognitive health [48]. GbE with cholinesterase inhibitors, which act to treat dementia [49]. The study found that when used to treat patients with dementia who also had neuropsychiatric signs, EGb 761, 240 mg once a day, was markedly more effective than a placebo. EGb 761 is highly beneficial in treating patients with cognitive impairment and enhancing cognitive function, according to another study involving 188 middle-aged volunteers [4]. Ginkgo biloba leaf extract has accumulated observations for its remarkable effects on increasing learning and memory, along with its potential anti-aging benefits in humans. A daily oral dose of 240 mg of EGb 761 has demonstrated important promise in alleviating both presenile and senile major degenerative dementia of the Alzheimer type, as well as multi-infarct dementia, as classified by the DSM-III-R [35,50]. Research indicates that EGb 761 positively affects individuals with mild to moderate Alzheimer’s disease. In a study on diabetic rats, Ginkgo biloba Extracts (GBEs) led to a reduction in neuronal populations in the jejunum and the myenteric plexus of the ileum. Conversely, the cell body area increased significantly in the myenteric and submucosal plexuses. Furthermore, GBEs enliven the left temporal and prefrontal cortex, enhancing cognitive performance. Randomized regular trials with a 240 mg daily dosage in patients with mild to moderate dementia showed a notable reduction in behavioral, in addition to neuropsychiatric signs [51].

4.8 Other pharmacological activities.

Ginkgo biloba is a medicinal tree with strong antioxidant characteristics. It has been shown to benefit degenerative conditions, inclusive of neurodegenerative retinal diseases. Antioxidants help address health issues caused of oxidative tension by regulating anxiety levels and reducing redox homeostasis [95]. The extract of Ginkgo biloba contains the biologically active compound Ginkgo biloba extract 761, which offers a defensive effect against impairment to both neurons and blood vessels, and is also used to treat vascular dementia (VaD) [96]. Ginkgo biloba contains polysaccharides that have been shown to exhibit various biological activities. It regulates cardiovascular activity and also reduces liver disease. G. biloba polysaccharide promotes insulin secretion, controls obesity, and regulates blood glucose levels [21]. GBE has demonstrated its remarkable ability to enhance cerebral blood flow. However, it's worth noting that individual lobar regions do not exhibit any significant changes following GBE consumption [4].

Table 1. The pharmacologically active compounds are obtained from Ginkgo biloba extracts.

Table 2. The structure of phytochemical compounds in Ginkgo biloba extract.

Ginkgo biloba, one of the oldest living tree species, has fascinated humans for over a hundred years due to its valuable applications in health food and medicine. The latest phytochemical studies have isolated key bioactive compounds from its leaves, seeds, and sarcotesta, including polysaccharides, biflavonoids, amentoflavone, ginkgetin, and phenolic acids, which are proven active ingredients with significant health benefits. G. biloba has diverse pharmacological activities, including antioxidants, anti-inflammatory, antiviral, immunostimulatory, anticancer, hepato-protective, anti-fungal, and anti-depressant in addition to anti-tumor properties, and can help reduce blood glucose levels, and so on. Ginkgo biloba is widely recognized for its safety, demonstrating a low incidence of adverse reactions. To maximize its therapeutic potential, it is essential to conduct more rigorously controlled clinical studies in the future. These studies will help pinpoint the groups of individuals who stand to gain the most from treatments involving Ginkgo biloba.

The authors confirm contribution to the paper as follows: study conception and design: PRD and DN. Methodology: MSR and DN; data analysis and interpretation of results: BAR, NU, FA, JFS. Supervision: PRD and DN. Draft manuscript preparation: BAR. All authors reviewed and approved the final version of the manuscript. All authors have read and agreed to the published version of the manuscript.

 This research did not receive any specific grant from any funding agency in the public, commercial, or non-profit sectors. 

This article does not contain any studies with human participants or animals performed by any of the authors.

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