Reconstituted mother tinctures of Gelsemium sempervirens L. improve memory and cognitive impairment in mice scopolamine-induced dementia model

J Ethnopharmacol. 2015 Jan 15:159:274-84. doi: 10.1016/j.jep.2014.09.008. Epub 2014 Nov 21.

Abstract

Ethnopharmacological relevance: Gelsemium sempervirens (L.) J.St.-Hil is a herb used for the treatment of various neuroses in both homeopathic and Ayurvedic systems. The present study examines whether Gelsemium reconstituted tincture can protect against scopolamine induced cognitive discrepancies in amnesic mouse model. In order to investigate the protective mechanism of Gelsemium against dementia, in vitro acetyl cholinesterase and β-secretase enzyme inhibition and estimation of glutathione level in mouse brain were carried out.

Materials and methods: The inhibition study on acetyl cholinesterase and β-secretase enzyme was conducted on brain homogenate supernatant spectrophotometrically using specific substrate. Cognitive enhancement activity was assessed by elevated plus maze and passive avoidance study in scopolamine induced dementia mouse model. Glutathione, an anti-oxidant, was measured spectrophotometrically from scopolamine induced amnesic mice brain supernatant using 5,5'-dithiobis 2-nitrobenzoic acid in the presence and absence of Gelsemium tincture.

Results: Significant inhibition was found with Gelsemium on AChE and β-secretase enzyme with an IC50 of 9.25 and 16.25 µg/ml, respectively, followed by increasing glutathione levels in comparison to the untreated dementia group. The effect of Gelsemium of scopolamine-induced cognitive deficits was determined by measuring the behavioral parameters and the antioxidant status of the brain after scopolamine (1mg/kg i.p.) injected amnesic mice. Gelsemium significantly demonstrated in vivo anti-dementia activity (60% protection) and increased exploratory behavior.

Conclusion: Our investigations indicated that alkaloid, iridoids and coumarin enriched reconstituted Gelsemium tincture extract displays promising cognitive enhancement in adult mice after short-term oral treatment. Hence, Gelsemium can be a promising anti-dementia agent, mediating the protection against amnesia, attention disorders and learning dysfunctions through dual inhibition of both acetyl cholinesterases (no false positive effect was shown), β-secretase and antioxidant activity.

Keywords: Acetylcholine-esterase; Anti-dementia activity; Cognitive; Gelsemium sempervirens (Gelsemiaceae); Glutathione; β-secretase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / genetics
  • Acetylcholinesterase / metabolism
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / antagonists & inhibitors
  • Aspartic Acid Endopeptidases / metabolism
  • Avoidance Learning / drug effects
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Cognition Disorders / chemically induced
  • Cognition Disorders / drug therapy*
  • Dementia / chemically induced
  • Dementia / drug therapy*
  • Gelsemium*
  • Glutathione / metabolism
  • Male
  • Memory / drug effects*
  • Mice
  • Phytotherapy*
  • Plant Preparations / pharmacology
  • Plant Preparations / therapeutic use*
  • Plant Preparations / toxicity
  • RNA, Messenger / metabolism
  • Scopolamine
  • Toxicity Tests, Acute

Substances

  • Plant Preparations
  • RNA, Messenger
  • Scopolamine
  • Acetylcholinesterase
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, mouse
  • Glutathione