Essential oil from Lippia microphylla Cham. modulates nitric oxide pathway and calcium influx to exert a tocolytic effect in rat uterus

Nat Prod Res. 2021 Mar;35(6):1046-1051. doi: 10.1080/14786419.2019.1614578. Epub 2019 Jun 5.

Abstract

The essential oil of Lippia microphylla (LM-OE) presents several pharmacological activities. This work evaluates the tocolytic effect of LM-OE on rats. LM-OE inhibited phasic contractions and relaxed tonic contractions on rat uterus. Considering that nitric oxide (NO) pathway regulates uterine contraction, LM-OE potency was attenuated in the presence of NO synthase (NOS) inhibitor and this reduction was reversed in the presence of a NOS substrate. Similarly, the relaxant potency of LM-OE was reduced in the presence of soluble guanylyl cyclase (sGC) and protein kinase G (PKG) inhibitors. LM-OE also demonstrates a positive modulation of large and small conductance calcium-activated, voltage-gated and adenosine triphosphate-sensitive potassium channels and inhibited curves to CaCl2 as well as relaxed the uterus pre-contracted by S-(-)-Bay K8644, suggesting voltage-gated calcium channels type-1 (CaV1) blockade. Thus, the tocolytic effect of LM-OE on rat involves positive modulation of NO/NOS/sGC/PKG/K+-channels pathway and Ca2+ influx blockade through CaV1.[Formula: see text].

Keywords: Lippia microphylla Cham; calcium influx; nitric oxide pathway; potassium channels; rat uterus; tocolytic effect.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Female
  • Lippia / chemistry*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Oils, Volatile / pharmacology*
  • Oxytocin / pharmacology
  • Potassium Channels / metabolism
  • Potassium Chloride / pharmacology
  • Rats
  • Signal Transduction* / drug effects
  • Tocolytic Agents / pharmacology*
  • Uterine Contraction / drug effects
  • Uterus / drug effects*
  • Uterus / metabolism

Substances

  • Oils, Volatile
  • Potassium Channels
  • Tocolytic Agents
  • Nitric Oxide
  • Oxytocin
  • Potassium Chloride
  • Nitric Oxide Synthase
  • Calcium
  • NG-Nitroarginine Methyl Ester