ArticleAnesthesia and analgesia2025
Glabridin Hypnosis in Zebrafish Larvae Is Associated With Effects on Multiple Anesthetic Target Receptors.
Article in Anesthesia and analgesia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Effect of glabridin on ion transport across primary human bronchial epithelial cells.American journal of physiology. Cell physiology · 2026Article
- Xiaofeng Granules alleviate intrathecal morphine-induced pruritus via inhibiting the NR2B/PKC/CAMK II signaling pathway.Journal of anesthesia · 2026Article
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Authors and funding
9 authors.
Funding
Abstract
backgroundR -Glabridin is a major flavonoid of licorice ( Glycyrrhiza glabra ) root and known to modulate GABA A receptors, which are targets of many clinical hypnotics. However, R -glabridin hypnotic activity has not been reported in animals.
methodsInverted photomotor responses (IPMRs) were used to assess the hypnotic effects of natural R -glabridin and synthetic R/S -glabridin in wild-type zebrafish larvae and transgenic larvae lacking functional GABA A receptor β3 subunits (β3 0/0 ). Two-electrode voltage-clamp electrophysiology in Xenopus oocytes heterologously expressing ion channels quantified the effects of R -glabridin on wild-type and mutated human α1β3γ2L GABA A receptors, NR1B/NR2A N-methyl-D-aspatate (NMDA) receptors, and α4β2 neuronal nicotinic (nnACh) receptors.
resultsIPMRs in wild-type zebrafish larvae identified R/S -glabridin as an inhibitor (IC50 = 7.5 µM; 95% confidence interval [CI], 5.9-9.3 µM) that was about half as potent as R -glabridin (IC50 = 4.4. µM; 95% CI, 3.6-5.4 µM). In β3 0/0 zebrafish larvae, R -glabridin inhibited IPMRs with IC50 = 7.5 µM (95% CI, 5.6-10.0 µM). Electrophysiologic studies revealed that R -glabridin directly activated and positively modulated α1β3γ2L GABA A receptors. Modulation was significantly reduced by α1L232W and β3N265M mutations in the β+/α- transmembrane intersubunit sites where etomidate binds, but not by 5 other point mutations in 4 other transmembrane modulator binding sites. NMDA and nnACh receptors were inhibited by R -glabridin. DISCUSSION/
conclusionsOur findings in zebrafish larvae indicate that IPMR inhibition by R -glabridin is more potent than S -glabridin and that β3-containing GABA A receptors contribute significantly to this behavioral effect. Molecular studies show that R -glabridin modulates at least 3 known anesthetic-sensitive ion channels, suggesting that it is a multimodal hypnotic.
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