In vitro multimodal-effect of Trichilia catigua A. Juss. (Meliaceae) bark aqueous extract in CNS targets

J Ethnopharmacol. 2018 Jan 30;211:247-255. doi: 10.1016/j.jep.2017.09.039. Epub 2017 Sep 29.

Abstract

Ethnopharmacological relevance: The bark of Trichilia catigua A. Juss. (Meliaceae), popularly known as "big catuaba", is traditionally used in Brazilian folk medicine for its neuroactive potential as memory stimulant, and antinociceptive and antidepressant effects.

Aim of the study: To study the aqueous extract of T. catigua bark as dual inhibitor of monoamine oxidase A (MAO-A) and acetylcholinesterase (AChE). To explore its antioxidant potential through interaction with xanthine/xanthine oxidase (X/XO) pathway, and to attempt a relationship between its phenolic profile and effects displayed.

Materials and methods: Phenolic profiling was achieved by HPLC-DAD-ESI/MSn and UPLC-ESI-QTOF-MS analyses. The capacity to inhibit hMAO-A was assessed in vitro, as was that for AChE, evaluated in rat brain homogenates. The direct inhibition of the X/XO pathway and the scavenging of superoxide anion radical were the selected in vitro models to explore the antioxidant potential. The cytotoxic effects were assayed in the human neuronal SH-SY5Y cells by MTT reduction, after direct exposure (24h).

Results: Twenty-six compounds were identified and quantified (551.02 ± 37.61mg/g of lyophilized extract). The phenylpropanoid substituted flavan-3-ols were the most representative compounds (~81% of quantified mass). The extract inhibited hMAO activity in a concentration-dependent manner (IC50 = 121.06 ± 2.13μg/mL). A mixed model of inhibition of AChE activity was observed, reflected by the pronounced increase of Km values and a more discreet effect over the Vmax parameters, calculated from Michaelis-Menten fitted equations. In addition, it was demonstrated that the extract directly inhibits the X/XO pathway (IC50 = 121.06 ± 2.13μg/mL) and also imbalances the oxidative stress acting as superoxide anion radical scavenger (EC50 = 104.42 ± 10.67μg/mL), an oxidative by-product of this reaction. All these neuroprotective and neurotrophic effects were displayed within the non-toxic range of concentrations (0.063-0.500μg/mL) in SH-SY5Y cells.

Conclusions: Our results validate the traditional use of T. catigua bark for its neuroactive and neuroprotective potential. A novel approach upon its application towards the management of neurodegenerative and related symptomatology was likewise demonstrated.

Keywords: AChE; Antioxidant; HMAO-AhMAO-A; Polyphenols; Trichilia catigua.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Brain / enzymology*
  • Cell Line, Tumor
  • Cholinesterase Inhibitors / pharmacology
  • Humans
  • Male
  • Meliaceae*
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology
  • Neuroprotective Agents / pharmacology
  • Phenols / analysis
  • Phenols / pharmacology
  • Plant Bark
  • Plant Extracts / pharmacology*
  • Rats
  • Rats, Wistar
  • Xanthine Oxidase / antagonists & inhibitors
  • Xanthine Oxidase / metabolism

Substances

  • Cholinesterase Inhibitors
  • Monoamine Oxidase Inhibitors
  • Neuroprotective Agents
  • Phenols
  • Plant Extracts
  • Xanthine Oxidase
  • Monoamine Oxidase
  • Acetylcholinesterase