Protective effect of WIN-1001X, an herbal extract, on Parkinson's disease experimental model via autophagy enhancement

Protective effect of WIN-1001X, an herbal extract, on Parkinson's disease experimental model via autophagy enhancement
Issue Date
62nd International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research
Background:Parkinson’s disease (PD) is characterized by the loss of pigmented dopaminergic neurons in the substantianigrapars compacta(SNc) of the midbrain. This cell loss results the reduction of dopamine (DA) levels in the striatum (ST), which triggers a cascade of abnormal neural circuits that are manifest as distinct symptoms of PD. To find out if autophagy can rescuethe damages in PD, we examined the autophagy enhancing effect of WIN-1001X, an herbal extract containing Angelica tenuissimaNakai, Polygala tenuifoliaand DimocarpuslonganLour, on cells and especially on 1-methyl-4-phenyl-1,2,3,6-tetrahydrophenylpyridine (MPTP) rodent models of PD. Methods:SH-SY5Y neuroblastomawas used to test the cytotoxicity and autophagy induction by treatment of WIN-1001X in vitro. After 24 h from WIN-1001X treatment, autophagy-related proteins such as LC3II/I, DOR, GATE16, Beclin-1, p-AMPK, p-tuberin/TSC2 and mTORwere measured using western blot method. Also, 3-MA, an autophagy inhibiting agent was 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. For deeper analysis of mice brain tissues with PD-like symptoms, subchronicMPTP rodent model was used. 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 frozen for further analysis. Results:In SH-SY5Y cells, WIN-1001X exhibited no toxicity. Besides, WIN-1001X significantly induced LC3II/I, GATE16, DOR and Beclin-1 protein expressions in dose-dependent manner. In addition, p-AMPK -Thrand -Serprotein expressions were al
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