Neuroprotective Effects of Jitai Tablet, a Traditional Chinese Medicine, on the MPTP‐Induced Acute Model of Parkinson’s Disease: Involvement of the Dopamine System

Abstract

Jitai tablet (JTT) is a traditional Chinese medicine used to treat neuropsychiatric disorders. We previously demonstrated that JTT treatment led to increased level of dopamine transporter (DAT) in the striatum, thus indicating that JTT might have therapeutic potential for Parkinson's disease (PD), which is characterized by dysregulated dopamine (DA) transmission and decreased striatal DAT expression. The aim of this study was to investigate the neuroprotective effect of JTT on MPTP-induced PD mice. Using locomotor activity test and rotarod test, we evaluated the effects of JTT (0.50, 0.15, or 0.05 g/kg) on MPTP-induced behavioral impairments. Tyrosine hydroxylase TH-positive neurons in the substantia nigra and DAT and dopamine D2 receptor (D2R) levels in the striatum were detected by immunohistochemical staining and/or autoradiography. Levels of DA and its metabolites were determined by HPLC. In MPTP-treated mice, behavioral impairments were alleviated by JTT treatment. Moreover, JTT protected against impairment of TH-positive neurons and attenuated the MPTP-induced decreases in DAT and D2R. Finally, high dose of JTT (0.50 g/kg) inhibited the MPTP-induced increase in DA metabolism rate. Taken together, results from our present study provide evidence that JTT offers neuroprotective effects against the neurotoxicity of MPTP and thus might be a potential treatment for PD.

Longitudinal changes of dopamine transporters in heroin users during abstinence

“…After 12 months of treatment with JTT, DAT levels almost recovered to normal levels in the right striatum of heroin users. Prior studies in human and animals have reported that some herbs and components in the JTT formula were effective at regulating DA function (Kin et al 1995;Liu et al 2014;Tsukada et al 2000;Yang et al 2008). For example, scopolamine, a muscarinic cholinergic antagonist, modulates DA turnover in the striatum by simultaneous enhancement on the dynamics of DA synthesis and DAT availability through the inhibition of muscarinic cholinergic neuronal activity (Tsukada et al 2000).…”

Dorsal hypothalamic dopaminergic neurons play an inhibitory role in the hypothalamic‐pituitary‐adrenal axis via activation of D2R in mice

“…Mice were decapitated under deep anaesthesia with isoflurane and the brains were rapidly removed. The coronal brain slices (500 μm) were cut using a cryostat, then the hypothalamic ARC (anterior margin: bregma −1.46 mm, posterior margin: bregma −2.00 mm) and PVN (anterior margin: bregma −0.58 mm, posterior margin: bregma −1.08 mm), and striatum (anterior margin: bregma +1.1 mm, posterior margin: bregma 0.1 mm) were rapidly harvested using a 15‐gauge needle (inner diameter 1.5 mm). The brain tissue samples were placed into cold tissue buffer (0.1 mol L −1 phosphate‐citrate buffer pH 2.5) and sonicated with three consecutive 1 seconds bursts (Heat Systems Ultrasonics, Plainview, NY, USA).…”

Chinese Medicine: A Hope for Neurodegenerative Diseases?

“…In addition, traditional herbal formulations such as "Kaixinsan" which are composed of 4 herbs, Radix Ginseng, Radix Polygalae, Rhizoma Acori Tatarinowii, and Poria, is a famous TCM formula for the treatment of mental disorders, forgetfulness, and depression possibly via the pCREB pathways [35]. Additional herbal formulations such as Danggui-Shaoyao-San, Tianma Gouteng Yin, and Jitai Tablet, are reported to exert their neuroprotective effects via ameliorating cognitive dysfunction in AD model [36], preventing degeneration of dopaminergic neurons in PD model [37], and improving behavioral impairments in PD mice [38], respectively. Ginkgo biloba extract EGb 761 ® , and a modified formulation of SuHeXiang Wan, were found effective in modulating cognitive behavior and neuropsychiatric symptoms of AD [39], A␤-induced memory impairment, and A␤ levels in AD mice model [40], respectively.…”