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DOI: 10.1055/s-0034-1394755
Protective effect of WIN-1001X, an herbal extract, on Parkinson's disease experimental model via autophagy enhancement
To find out if autophagy can rescue the damages in Parkinson's disease (PD), we examined the autophagy enhancing effect of WIN-1001X, an herbal extract containing Angelica tenuissima Nakai, Polygala tenuifolia and Dimocarpus longan Lour, on cells and on MPTP rodent models of PD. After 24h from WIN-1001X treatment on SH-SY5Y cells, autophagy-related proteins were measured. 3-MA was also used to check the relationship between WIN-1001X and autophagy. For behavioral changes and initial detection of autophagy enhancement in vivo, acute MPTP rodent model was used. MPTP 22 mg/kg were injected i.p. 4 times on first experimental day to induce severe PD-like symptoms in mice, and daily WIN-1001X 100 mg/kg treatment was continued for next 3 days. Subchronic MPTP rodent model was also used for analysis. After 2 days of WIN-1001X (100 and 200 mg/kg) pre-treatment, MPTP 30 mg/kg single i.p. injection was carried out for next 5 consecutive days. After 1 week from last MPTP injection day, mice brains were dissected and analyzed. WIN-1001X exhibited no toxicity in cells. WIN-1001X significantly induced LC3II/I, GATE16, DOR and Beclin-1 protein expressions. In addition, p-AMPK protein expressions were also significantly increased with WIN-1001X treatment. Running behavior was measured by rota-rod test on 1st and 3 rd days after MPTP injection. Significant decrease of running time caused by MPTP injection was rescued by WIN-1001X treatment. LC3II/I, DOR and GATE16 protein expressions were also significantly increased in the midbrains of WIN-1001X treated group. Significant neuronal cell rescue against MPTP toxicity was observed by tyrosine hydroxylase detection in the brains of subchronic MPTP rodent model. Furthermore, LC3II/I, Beclin-1 and p-ULK(S757) protein expressions were increased while mTOR and p62 protein expressions were decreased in WIN-1001X treated groups which, altogether, reflects the beneficial effect of WIN-1001X in enhancing the autophagy.
Keywords: WIN-1001X, Parkinson's disease, Autophagy, Natural medicine, MPTP