Omidkhoda SF, Razavi BM, Hosseinzadeh H. Protective effects of Ginkgo biloba L. against natural toxins, chemical toxicities, and radiation: A comprehensive review. Phytother Res. November 2019;33(11):2821-2840. doi: 10.1002/ptr.6469.
Ginkgo (Ginkgo biloba, Ginkgoaceae) is a medicinal plant with a long history of use in traditional Chinese medicine (TCM) in the treatment of asthma and in Western medicine for tinnitus and cognitive problems. The main bioactive components, including flavonoids, terpene trilactones, and proanthocyanidins, are thought to be responsible for its antioxidant, anti-inflammatory, and neuromodulatory properties. The purpose of this paper was to review the protective effects of ginkgo against toxicities induced by natural toxins, chemical toxic agents, and radiation.
Scopus, PubMed, Web of Science, and Google scholar were searched from inception to February 2019. Search terms included "Ginkgo biloba" or "ginkgolide" in combination with "toxicity," "toxin," "toxic," "venom," "poison," "chemical", "radiation," "metal," or "pesticide." The most relevant titles were selected. Articles were included if they assessed the effect of ginkgo against toxicities in humans and animals. Selected articles (n=126) were categorized into three headings – natural toxins, chemical toxicities, and radiation – and reviewed.
Natural toxins are chemicals naturally produced by living organisms. Ginkgo may have protective effects against damage induced by lipopolysaccharides (LPS), a component of the outer membrane of Gram-negative bacteria known to stimulate the immune system and provoke inflammatory responses. For example, studies in mice demonstrated that ginkgo leaf extracts (GLE) protected against LPS-induced acute lung injury and inhibited the LPS-induced overactivation of cytokines and inflammatory markers of neurons in rat brain. In human coronary artery endothelial cells, GLE ameliorated the LPS-induced release of inflammatory mediators that increase the risk for atherosclerosis. GLE shows promise in alleviating LPS-induced damages in renal tissues of rats, but more research is required to determine efficacy and mechanisms involved. A study in guinea pigs demonstrated that ginkgo supplementation for three days in a concentration of 3 mg/mL ameliorated hearing loss, structural hair cell damages, and decreased cochlear blood flow following the administration of otic drops containing LPS. In vitro data also suggest that GLE has protective effects against aflatoxin B1, lysophosphatidylcholine, and toxins derived from plants, namely lantadenes, cassava cyanogenic glycosides (Manihot esculenta, Euphorbiaceae), and gossypol. Lantadenes are pentacyclic triterpenoids from lantana (Lantana camara, Verbenaceae) leaf, and gossypol are polyphenols from cotton (Gossypium species, Malvaceae) seed.
Chemical toxins are organic or inorganic substances, such as metals, ethanol, pesticides, and cigarette smoke. Studies report that GLE has a protective effect against oxidative stress and neurotoxicity induced by metals. Studies in mice demonstrated that GLE administration ameliorated aluminum trichloride-induced learning and memory deficits by inhibiting the expression of acetylcholinesterase and reducing levels of the amyloid precursor protein. GLE was also shown to inhibit oxidative stress induced by lead acetate, cadmium chloride, and mercury intoxication in rats. Similarly, studies suggest GLE reduces ethanol- and carbon tetrachloride-induced hepatic oxidative stress in vitro. Pesticides are another primary source of chemical toxins and include insecticides (e.g., methamidophos and diazinon), rodenticides (e.g., bromethalin), herbicides (e.g., glyphosate and paraquat), and fungicides (e.g., topsin). GLE ameliorated the toxic effects of pesticides on the animal vascular, respiratory, and nervous systems through its antioxidant properties. The antioxidant and radical scavenging activities of GLE also lowered the toxic effect of cigarette smoke on animals in one study reviewed. Other in vitro studies showed that GLE may have protective effects against monosodium glutamate, naphthalene, fluoride, and chemotherapy medications. Two studies in humans suggested that GLE may enhance the efficacy of chemotherapy with 5-fluorouracil and reduce oxaliplatin-induced neurotoxicity in patients with colorectal cancer.
Radiation is the emission of energy particles, which depending on the energy level, can be categorized as either ionizing or non-ionizing. Lower energy non-ionizing radiation includes radio waves, microwaves, and infrared radiation. Higher energy ionizing radiation includes x-rays and gamma rays. Studies in mice demonstrated that GLE reverses disturbances related to fertility and inhibits oxidative stress induced by radio waves. One study in patients with a thyroid tumor demonstrated that 120 mg/day of EGb 761® [Ginkgo biloba extract EGb 761; Rökan, Tanakan, Tebonin®; Dr. Wilmar Schwabe GmbH; Karlsruhe, Germany] for three days prior inhibited free radicals and reactive oxygen species induced by the treatment of radioactive iodine-131 but did not influence clinical outcomes. Other studies suggest that GLE reduces uranium- and ultraviolet skin radiation-induced oxidative stress.
Based on their review, the authors conclude that GLE has an established link in ameliorating various types of intoxication through its antioxidant and anti-inflammatory effects. According to the International Agency for Research on Cancer, GLE is classified as a possible human carcinogen. Studies evaluating the toxicology of GLE in animals have demonstrated that the potential adverse effects of GLE are dose-, time-, and sex-dependent. Based on this information and limited efficacy and safety data in humans, the authors call for additional clinical studies examining the protective effects and potential toxic effects in humans.
The authors declare no conflicts of interest.
– Gavin Van De Walle, MS, RD