Effect of quercetin and role of nitric oxide pathway in chloroquine-induced scratching

Abstract Nitric oxide (NO) is an abundant mediator which is demonstrated to be involved in pruritus. Assuming that the increased NO also mediates chloroquine-induced pruritus, which is a frequent complication seen in the chronic chloroquine treatment, the current study aimed to investigate the effect of quercetin and the role of NO in chloroquine-induced pruritus in C57BL/6 mice. Model was created with subcutaneous chloroquine (400µg/site) injection to the nape of the mice. Effect of quercetin and role of NO were investigated with administration of quercetin, and co-administration with L-NAME, 7-NI and L-arginine before chloroquine injection. Locomotor activity was assessed by activity cage and number of the scratching bouts after chloroquine injection was recorded for 30 minutes. Our results show that quercetin significantly reduced scratching bouts at the doses of 10, 20, 40 and 80 mg/kg. Locomotor activity was decreased at the 40 and 80 mg/kg doses of quercetin. Additionally, decrease of the number of scratching bouts by quercetin prevented by L-arginine treatment, while L-NAME and 7-NI enhanced the anti-pruritic effect of sub-effective doses of quercetin. Therefore, our study demonstrated that acute injection of quercetin significantly diminished chloroquine-induced scratching behavior, and this effect is partly mediated by inhibition of neuronal nitric oxide synthase enzyme.

Neuroprotective effects of sinapic acid involve the iron regulatory role on the rotenone-induced Parkinson's disease model

Abstract In the last decades, ferroptosis and its relationship with Parkinson's disease have gained significant attention. Compounds that affect ferroptosis and iron-dependent pathways in particular, have possible candidates for study in this context.Sinapic acid is an iron-chelator and high antioxidant bioactive phenolic acid. Its neuroprotective action, due to the antioxidant capacity, has been shown in several experimental models.However, the relationship between iron and antioxidant actions is still misunderstood and therefore, in the current study, we tried to investigate the effects of sinapic acid in rotenone-induced Parkinson's disease with the aspect of ferroptosis and iron-dependent alterations.The Parkinson's disease model was induced by a single dose intrastriatal and intrategmental rotenone (5µg/µl) injection.Sinapic acid (30mg/ kg) was orally administered during a 28-day period after the Parkinson's disease model was validated.Our results demonstrated that sinapic acid treatment attenuated rotenone-induced increase of serum transferrin and iron levels.Furthermore, sinapic acid inhibited rotenone-induced heme oxygenase-1(HO-1) increase and decrease of glutathione peroxidase-4 (GPx-4) levels in brain tissue. Also, sinapic acid treatment decreased motor impairment, likely as a result of the ameliorative effects on the tyrosine hydroxylase immunoreactivity loss after the rotenone insult.Our study suggests that the iron regulatory role of sinapic acid possibly plays a role in the protective effect on rotenone-induced neuronal damage.