ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
A single amino acid determines the toxicity of Ginkgo biloba extracts.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Review of neuroprotective potential of natural products against hypoxia-induced neuronal injury.Frontiers in pharmacology · 2026Review
- Convergent resistance to GABA receptor neurotoxins through plant-insect coevolution.Nature ecology & evolution · 2023Article
- Review
- Changes in Polar Metabolites Content during Natural and Methyl-Jasmonate-Promoted Senescence ofInternational journal of molecular sciences · 2021Article
- Synthetic, Mechanistic, and Biological Interrogation ofJournal of the American Chemical Society · 2020Article
- Concise asymmetric synthesis of (-)-bilobalide.Nature · 2019Article
- Phytochemicals for Improving Aspects of Cognitive Function and Psychological State Potentially Relevant to Sports Performance.Sports medicine (Auckland, N.Z.) · 2019Review
- Ginkgolic acids induce HepG2 cell death via a combination of apoptosis, autophagy and the mitochondrial pathway.Oncology letters · 2018Article
- Review of Ginkgo biloba-induced toxicity, from experimental studies to human case reports.Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews · 2017Review
- An atypical residue in the pore of Varroa destructor GABA-activated RDL receptors affects picrotoxin block and thymol modulation.Insect biochemistry and molecular biology · 2014Article
- A single channel mutation alters agonist efficacy at 5-HT3A and 5-HT3AB receptors.British journal of pharmacology · 2013Article
- Discriminating between 5-HT₃A and 5-HT₃AB receptors.British journal of pharmacology · 2013Review
- Mixed antagonistic effects of the ginkgolides at recombinant human ρ1 GABAC receptors.Neuropharmacology · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Ginkgo biloba extracts are currently used for a wide range of health-related conditions. Some of the medical benefits of these extracts are controversial, but their lack of toxicity in humans is not in doubt. These extracts are, however, highly toxic to insects. Their active components (ginkgolides and bilobalide) have structures similar to the convulsant picrotoxin, a GABA(A) receptor antagonist, so their lack of toxicity in mammals is puzzling. Here, we show that the different compositions of insect and vertebrate GABA receptor pores are responsible for the differing toxicities. Insect GABA receptors contain Ala at their 2' position in the pore. Substitution with Val, which is the equivalent residue in vertebrate GABA(A) receptor α-subunits, decreases ginkgolide potency by up to 10,000-fold. The reverse mutation in vertebrate GABA(A) α1 subunits increased the sensitivity of α1β2 and α1β2γ2 receptors to ginkgolides. Mutant cycle analysis demonstrates a strong interaction between the ginkgolides and the 2' residue, a result supported by in silico docking of compounds into a model of the pore. We conclude that the insecticidal activity of G. biloba extracts can be attributed to their effects at insect GABA receptors, and the presence of a Val at the 2' position in vertebrate GABA(A) receptors explains why these compounds are not similarly toxic to humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.