An investigation of the differential effects of ursane triterpenoids from Centella asiatica, and their semisynthetic analogues, on GABAA receptors

Kaiser Hamid, Irene Ng, Vikram J. Tallapragada, Linda Váradi, David E. Hibbs, Jane Hanrahan, Paul W. Groundwater*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

The ursane triterpenoids, asiatic acid 1 and madecassic acid 2, are the major pharmacological constituents of Centella asiatica, commonly known as Gotu Kola, which is used traditionally for the treatment of anxiety and for the improvement of cognition and memory. Using the two-electrode voltage-clamp technique, these triterpenes, and some semisynthetic derivatives, were found to exhibit selective negative modulation of different subtypes of the GABAA receptor expressed in Xenopus laevis oocytes. Despite differing by only one hydroxyl group, asiatic acid 1 was found to be a negative modulator of the GABA-induced current at α1β2γ2L, α2β2γ2L and α5β3γ2L GABAA receptors, while madecassic acid 2 was not. Asiatic acid 1 exhibited the greatest effect at α1β2γ2L (IC50 37.05 μm), followed by α5β3γ2L (IC50 64.05 μm) then α2β2γ2L (IC50 427.2 μm) receptors. Conversion of the carboxylic acid group of asiatic acid 1 to a carboxamide group (2α,3β,23-trihydroxy-urs-12-en-28-amide 5) resulted in enhanced inhibition at both the α1β2γ2L (IC50 14.07 μm) and α2β2γ2L receptor subtypes (IC50 28.41 μm). The results of this study, and the involvement of α5-containing GABAA receptors in cognition and memory, suggest that asiatic acid 1 may be a lead compound for the enhancement of cognition and memory.

Original languageEnglish
Pages (from-to)386-397
Number of pages12
JournalChemical Biology and Drug Design
Volume88
Issue number3
DOIs
Publication statusPublished - 2016
Externally publishedYes

Keywords

  • Centella asiatica
  • GABA receptors
  • Xenopus laevis oocytes
  • asiatic acid
  • cognition
  • madecassic acid
  • memory

Fingerprint

Dive into the research topics of 'An investigation of the differential effects of ursane triterpenoids from Centella asiatica, and their semisynthetic analogues, on GABA<sub>A</sub> receptors'. Together they form a unique fingerprint.

Cite this