Moringa oleifera seed ethanol extract and its active component kaempferol potentiate pentobarbital-induced sleeping behaviours in mice via a GABAergic mechanism

Pharm Biol. 2022 Dec;60(1):810-824. doi: 10.1080/13880209.2022.2056207.

Abstract

Context: Moringa oleifera Lam. (Moringaceae) (MO) is an important food plant that has high nutritional and medical value. However, there is limited information on whether its seeds can improve sleep.

Objective: This study investigated the effects of MO seed ethanol extracts (EEMOS) on sleep activity improvement and examined the underlying mechanisms.

Materials and methods: Male ICR mice were placed into six groups (n = 12) and treated as follows: Control (sodium carboxymethyl cellulose, 20 mL/kg), estazolam tablets (2 mg/kg), EEMOS (1, 2 g/kg) and kaempferol (1, 2 mg/kg). These samples were successively given intragastric for 14 d. Locomotor activity assay, pentobarbital-induced sleeping and pentetrazol-induced seizures tests were utilized to examine the sedative-hypnotic effects (SHE) of EEMOS.

Results: Compared with the control group, the results revealed that EEMOS (2 g/kg) and KA (2 mg/kg) possessed good SHE and could significantly elevate the levels of γ-aminobutyric acid and reduce the levels of glutamic acid in the mouse hypothalamus (p < 0.05). Moreover, SHE was blocked by picrotoxin, flumazenil and bicuculline (p < 0.05). EEMOS (2 g/kg) and KA (2 mg/kg) significantly upregulated the protein expression levels of glutamic acid decarboxylase-65 (GAD65) and α1-subunit of GABAA receptors in the hypothalamus of mice (p < 0.05), not affecting glutamic acid decarboxylase-67 (GAD67) and γ2-subunit expression levels (p > 0.05). Additionally, they cause a significant increase in Cl- influx in human cerebellar granule cells at a concentration of 8 µg/mL (p < 0.05).

Discussion and conclusions: These findings demonstrated that EEMOS could improve sleep by regulating GABAA-ergic systems, and encourage further clinical trials to treat insomnia.

Keywords: Cl– influx; GABAA receptors; GABAA-ergic systems; Sedative-hypnotic.

MeSH terms

  • Animals
  • Ethanol / pharmacology
  • Glutamate Decarboxylase / metabolism
  • Hypnotics and Sedatives / pharmacology
  • Kaempferols / pharmacology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Moringa oleifera*
  • Pentobarbital* / pharmacology
  • Plant Extracts / pharmacology
  • Receptors, GABA-A / metabolism
  • Seeds
  • Sleep
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Hypnotics and Sedatives
  • Kaempferols
  • Plant Extracts
  • Receptors, GABA-A
  • Ethanol
  • gamma-Aminobutyric Acid
  • Glutamate Decarboxylase
  • Pentobarbital

Grants and funding

This study was supported by the National Science Foundation of China [Grant No. 31560431]; Yun-Ling Industrial Technology Leading Talent [Grant No. 2014-1782]; National Aerospace Science Foundation of China; School-level project of Qujing Normal University [Grant No. 2107410131X741]; and Doctoral research start-up fee [Grant No. 2107450003X745].