Myricitrin, a nitric oxide and protein kinase C inhibitor, exerts antipsychotic-like effects in animal models

Abstract

Myricitrin is a nitric oxide (NO) and protein kinase C (PKC) inhibitor that has central nervous system activity, including anxiolytic-like action. Nitric oxide inhibitors blocked the behavioral effects of apomorphine, suggesting an antipsychotic-like effect. Furthermore, PKC inhibition reduced psychotic symptoms in acute mania patients and blocked amphetamine-induced hyperlocomotion, suggesting a potential antipsychotic-like effect. The present study evaluated the effects of myricitrin in animal models that assess antipsychotic-like effects (apomorphine-induced stereotypy and climbing and the paw test) and extrapyramidal side effects (catalepsy test and paw test). Olanzapine was used as a positive control. 7-Nitroindazole (7-NI), a NOS inhibitor, and l-arginine, a NO precursor, were used to evaluate nitrergic modulation, and tamoxifen was used to test the effect of PKC inhibition. In mice, myricitrin dose-dependently and olanzapine blocked the stereotypy and climbing induced by apomorphine at doses that did not induce catalepsy. 7-Nitroindazole also blocked apomorphine-induced stereotypy and climbing, which were reversed by l-arginine pretreatment. l-arginine only attenuated the effects of myricitrin on apomorphine's effects. Tamoxifen also blocked apomorphine-induced stereotypy and climbing. In the paw test in rats, myricitrin and olanzapine increased hindlimb retraction time at doses that did not affect forelimb reaction time, whereas haloperidol affected both parameters at the same dose. Myricitrin did not induce catalepsy in the bar test. Tamoxifen did not affect hindlimb retraction time or forelimb retraction time, whereas 7-NI significantly increased hindlimb reaction time. Thus, myricitrin exhibited an antipsychotic-like profile at doses that did not induce catalepsy, and this effect may be related to nitrergic action.

Myricitrin Protects Cardiomyocytes from Hypoxia/Reoxygenation Injury: Involvement of Heat Shock Protein 90

“…These data demonstrated that myricitrin effectively inhibits H/R-induced apoptosis and provides further evidence supporting its anti-apoptotic role (Qin et al, 2015;Zhang et al, 2016). Myricitrin interacts with proteins, such as PI-3 kinase, nitric oxide synthase (NOS), PKCα, and PKCε (Pereira et al, 2011;Schwanke et al, 2013;Qin et al, 2015). In addition, previous studies have demonstrated that myricitrin potently inhibits calcium transport, likely through the interaction of the phenolic groups of this flavonoid with the Ca 2+ transporting protein (Thiyagarajah et al, 1991;Meotti et al, 2007).…”

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.…”

Myricitrin and bioactive extract ofAlbizia amaraleaves: DNA protection and modulation of fertility and antioxidant-related genes expression

“…Consequently, our observations on the protective role of myricitrin and HAE on DNA could be attributed to their potential effect on gene expression and/or its antioxidant activity. Moreover, Pereira et al (2011) reported that myricitrin is a nitric oxide and protein kinase C inhibitor that exerts anti-psychotic and anti-anxiolytic-like effects. Thus, further deep research needs to be conducted to introduce the bioactive myricitrin and A. amara leaves to the market as non-convential source of fertility regulating herbal drug with less deleterious side effects.…”

“…Active constituent and plant material administration Myricitrin (major compound) was administrated orally at a dose of 30 mg/kg bw/d (1/10 of LD 50 300 mg) (Pereira et al 2011). Its chemical purity was > 95%, determined by HPLC.…”