Glabridin Alleviates Inflammation and Nociception in Rodents by Activating BK Ca Channels and Reducing NO Levels

Biol Pharm Bull. 2020 May 1;43(5):884-897. doi: 10.1248/bpb.b20-00038. Epub 2020 Mar 6.

Abstract

Inflammation, and the pain that accompanies it, is a natural response of the body. The licorice plant (Glycyrrhiza glabra) have demonstrated anti-inflammatory, anti-edematous, and anti-nociceptive effects of its extracts. The effective ingredient remains unidentified; however, one possibility is the unique isoflavone glabridin. The anti-nociceptive, and anti-inflammatory effects of glabridin and its possible mechanism with focus on the large conductance Ca2+-activated K+ (BKCa) channels and L-arginine-nitric oxide (NO) pathway were examined by using different tests. In order to determine the anti-edematous, anti-nociceptive, and anti-oxidative effects of glabradin, some tests such as the tail flick, hotplate, carrageenan-induced paw edema, air pouch, acetic-acid-induced writhing, formalin, and capsaicin tests, as well as toxicity and open field tests were made. Glabridin was administered to rats (n = 8) or mice (n = 8) for 3 d at 3 doses (10, 20, and 40 mg/kg). Glabridin inhibited cytokine production and showed an anti-nociceptive response via the activating of BKCa channels and downregulating NO level and partially transient receptor potential vanilloid-1 pathways. It also demonstrated anti-inflammatory effects by inhibiting cyclooxygenase (COX) activity, while showing no cytotoxicity. Glabridin, however, showed no anti-nociceptive effect in the neurogenic phase. Glabridin is a promising substance in terms of its anti-nociceptive and anti-inflammatory effects by disrupting peripheral NO production, inhibiting cyclic guanosine monophosphate (cGMP) activation and activating BKCa channels and its lack of acute and subacute toxic effects.

Keywords: Glabridin; N(ω)-nitro-L-arginine methyl ester; inflammation; large conductance Ca++-activated K+; nociception; transient receptor potential cation channel subfamily vanilloid 1.

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use*
  • Analgesics / toxicity
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Anti-Inflammatory Agents / toxicity
  • Cytokines / immunology
  • Edema / drug therapy*
  • Edema / immunology
  • Edema / metabolism
  • Isoflavones / pharmacology
  • Isoflavones / therapeutic use*
  • Isoflavones / toxicity
  • Large-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Lethal Dose 50
  • Leukocytes / drug effects
  • Leukocytes / physiology
  • Male
  • Mice, Inbred BALB C
  • Nitric Oxide / metabolism
  • Pain / drug therapy*
  • Pain / immunology
  • Pain / metabolism
  • Phenols / pharmacology
  • Phenols / therapeutic use*
  • Phenols / toxicity
  • Rats, Wistar

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Cytokines
  • Isoflavones
  • Large-Conductance Calcium-Activated Potassium Channels
  • Phenols
  • Nitric Oxide
  • glabridin