Mulberry fruit ameliorates Parkinson's-disease-related pathology by reducing α-synuclein and ubiquitin levels in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid model

Mulberry fruit, which has been long used in traditional oriental medicine, was reported to ameliorate motor dysfunction and dopaminergic neuronal degeneration via antioxidant and antiapoptotic effects in an animal model of Parkinson's disease (PD). More than 95% of PD patients exhibit nonmotor problems such as olfactory dysfunction and gastrointestinal constipation, which are generally considered to be early symptoms of PD. However, few studies have actually examined potential drugs to treat early PD symptoms. The present study examined the protective effects of mulberry fruit extract (ME) against neurotoxicity in a 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) model of early PD. MPTP/p model was developed by systemic administration with MPTP (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. The behavioral studies showed that treatment of mice with ME significantly improved PD-related nonmotor symptoms as well as motor impairment, demonstrated by utilizing the olfactory, pole, rotarod and open field tests. In addition, immunohistochemical analysis indicated that ME exhibits the protective effects against dopaminergic neuronal damage induced by MPTP/p in the substantia nigra and striatum. Moreover, by using Western blot analysis, we found that treatment with ME inhibited the up-regulation of α-synuclein and ubiquitin, well known as composition of Lewy bodies in the substantia nigra and striatum of the MPTP/p mice. Taken together, these data suggest that ME may have therapeutic potential for preventing PD.