Cassia obtusifolia seed ameliorates amyloid β-induced synaptic dysfunction through anti-inflammatory and Akt/GSK-3β pathways

J Ethnopharmacol. 2016 Feb 3:178:50-7. doi: 10.1016/j.jep.2015.12.007. Epub 2015 Dec 7.

Abstract

Ethnopharmacological relevance: Tea infused with the seed of Cassia obtusifolia has been traditionally used as an herbal remedy for liver, eye, and acute inflammatory diseases. Recent pharmacological reports have indicated that Cassiae semen has neuroprotective effects, attributable to its anti-inflammatory actions, in ischemic stroke and Parkinson's disease models.

Aim of the study: Previously, the ethanol extract of C. obtusifolia seeds (COE) was reported to have memory enhancing properties. However, the effects of COE in an Alzheimer's disease (AD) model are currently unknown. In this study, we investigated the effect(s) of COE on aberrant synaptic plasticity and memory impairment induced by amyloid β (Aβ), a key toxic component found in the AD brain.

Materials and methods: To determine the effect of COE on Aβ-induced aberrant synaptic plasticity, we used acute mouse hippocampal slices and delivered theta burst stimulation to induce long-term potentiation (LTP). Western blots were used to detect Aβ- and/or COE-induced changes in signaling proteins. The novel object location recognition test was conducted to determine the effect of COE on Aβ-induced recognition memory impairment.

Results: COE was found to ameliorate Aβ-induced LTP impairment in the acute hippocampal slices. Glycogen synthase kinase-3β (GSK-3β), a key molecule in LTP impairment, was activated by Aβ. However, this process was inhibited by COE via Akt signaling. Moreover, COE was found to attenuate Aβ-induced microglia, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX) activation. In the in vivo studies performed, COE ameliorated the Aβ-induced object recognition memory impairment.

Conclusion: These results suggest that COE exhibits neuroprotective activities against Aβ-induced brain disorders.

Keywords: Amyloid beta; Cassia obtusifolia seeds; Long-term potentiation; Recognition memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Cassia / chemistry*
  • Chromosome Pairing / drug effects*
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Long-Term Potentiation / drug effects
  • Male
  • Memory / drug effects
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism
  • Mice
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Seeds / chemistry*
  • Signal Transduction / drug effects

Substances

  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents
  • Neuroprotective Agents
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3