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

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 antinociceptive effects of its extracts. The effective ingredient remains unidentified; however, one possibility is the unique isoflavone glabridin. The anti-nociceptive, and antiinflammatory effects of glabridin and its possible mechanism with focus on the large conductance Ca ++ -activated K + (BK Ca ) channels and L-Arginine-nitric oxide (NO) pathway were examined by using different tests. In order to determine the anti-edematous, antinociceptive, 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 days 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 cGMP activation and activating BKCa channels and its lack of acute and subacute toxic effects. N(ω)-nitro-L-arginine methyl ester; transient receptor potential cation channel subfamily vanilloid 1.Inflammation is a natural response of the body's immune system to various external stimuli, including those triggered by microorganisms, pathogens, trauma, stress, and chemicals. 1) As a response to stimuli such as toxin and infection, inflammation is generally characterized by microvascular leakage, edema, vasodilation, cell migration to the inflamed site, oxidative stress, and the release inflammatory mediators. 2) Among the cells migrating to the injury site are macrophages, which produce several different mediators, including nitric oxide (NO), histamine, serotonin, tumor necrosis factor-α (TNF-α), leukotrienes, interleukins (especially IL-1 and IL-6), and peptides. 3-5) Prostaglandins (PGs) and thromboxanes (TXs) generated by cyclooxygenase (COX) also play a major role in inflammatory reactions. 6) Pain, which is one symptom of inflammation, is a biological response that protects the body from harmful stimuli. Nociceptors, which convey pain stimuli from the sensory nerve endings to the central nervous system, are specialized receptors that enable the detection of a pain stimulus as the primary pain unit and the transformation of the mechanical and chemical response into electrical conduction. 7) Previous studies have revealed a relationship between nociception and pain that involves the interaction of...

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Ameliorative impacts of Glycyrrhiza glabra root extract against nephrotoxicity induced by gentamicin in mice

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