Analysis of the Antinociceptive Effect of the Flavonoid Myricitrin: Evidence for a Role of the l-Arginine-Nitric Oxide and Protein Kinase C Pathways

Abstract

The present study investigated the antinociceptive effects of the flavonoid myricitrin in chemical behavioral models of pain in mice and rats. Myricitrin given by i.p. or p.o. routes produced dose-related antinociception when assessed on acetic acidinduced visceral pain in mice. In addition, the i.p. administration of myricitrin exhibited significant inhibition of the neurogenic pain induced by intraplantar (i.pl.) injection of capsaicin. Likewise, myricitrin given by i.p. route reduced the nociception produced by i.pl. injection of glutamate and phorbol myristate acetate (PMA). Western blot analysis revealed that myricitrin treatment fully prevented the protein kinase C (PKC) ␣ and PKC⑀ activation by PMA in mice hind paws. Myricitrin given i.p. also inhibited the mechanical hyperalgesia induced by bradykinin, without affecting similar responses caused by epinephrine and prostaglandin E 2 . The antinociception caused by myricitrin in the acetic acid test was significantly attenuated by i.p. treatment of mice with the nitric oxide precursor, L-arginine. In contrast, myricitrin antinociception was not affected by naloxone (opioid receptor antagonist) or neonatal pretreatment of mice with capsaicin and myricitrin antinociceptive effects is not related to muscle relaxant or sedative action. Together, these results indicate that myricitrin produces pronounced antinociception against chemical and mechanical models of pain in rodents. The mechanisms involved in their actions are not completely understood but seem to involve an interaction with nitric oxide-L-arginine and protein kinase C pathways.

St. John's Wort reduces neuropathic pain through a hypericin-mediated inhibition of the protein kinase C γ and ɛ activity

“…Recent studies report antidepressive, antineoplastic, antitumor and antiviral activities of hypericin [18]. Flavonoids contribute to the anti-inflammatory effects of the plant [32] and antinociceptive properties have been reported for the flavonoid myricitrin [33]. Enzyme assays performed on rat brains demonstrated that hypericin and pseudohypericin are potent and selective inhibitors of the protein kinase C (PKC) [34,18].…”

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

“…Consistent with previous reports [16], our results showed that myricitrin increased HO-1 and NQO-1 expression, activated Akt phosphorylation and promoted Nrf2 signaling. Recent researches have reported that myricitrin can effectively inhibit protein kinase C pathways, which are mostly focus on antipsychotic effects of the agent [37,38]. It is highly limited to search for the related literature on myricitrin, as a PKC inhibitor to fight against apoptosis.…”

Jian carp ( Cyprinus carpio var. Jian) intestinal immune responses, antioxidant status and tight junction protein mRNA expression are modulated via Nrf2 and PKC in response to dietary arginine deficiency

“…However, information regarding the effect of arginine on PKC signalling in fish is lacking. Work in mice showed that dietary arginine activated PKC in paw tissue [26]. These findings indicated that a likely correlation exists between arginine and PKC signalling molecules involved in TJ mRNA expression in fish intestine, which requires additional exploration.…”