Botanical Therapeutics for Parkinson's Disease / 中国结合医学杂志

Parkinson's disease (PD) was first formally described by James Parkinson in 1817, but the shaking of limbs was described in the literature of several ancient civilizations, such as ancient Chinese civilization and ancient Indian civilization. Historically, botanical drugs were used as the main source for the treatment of such kind of disorders. In Western countries, plant extracts also occupied an important place in the earlier medications of PD. With the adventure of synthetic drugs, the role of plant-derived drugs in management of PD has been diminished. Nowadays, there is still no cure for PD, dopaminergic (DA) medication is the treatment of choice, which is just designed to ameliorate symptoms of PD, and long-term use of DA medication will result in reduced efficacy and severe adverse reactions. It is necessary to explore new methods for the treatment of PD. Chinese medicine (CM) developed a holistic and unique theoretical system, and botanical drugs are widely used in practice for more than two millennia. Modern pharmacological studies have proved that Chinese herbs have potential therapeutic effects on PD, such as enhancing neurotrophic activity, clearing protein aggregates, regulating neuroinflammation, etc. All the advances provide us with hope for developing CM as a mainstream medication for treating PD.

Preliminary optimization of a Chinese herbal medicine formula based on the neuroprotective effects in a rat model of rotenone-induced Parkinson's disease / 中西医结合学报

<p><b>OBJECTIVE</b>The main objective of this study was to preliminarily determine the optimum formulation of a Chinese herbal formula that may have neuroprotective effects against rotenone-induced Parkinson's disease (PD).</p><p><b>METHODS</b>Seven recipes were made from Dihuang (DH, Rehmannia glutinosa Libosch), Roucongrong (RCR, Cistanche deserticola Y.C.Ma), Niuxi (NX, Achyranthes bidentata Bl.) and Shanzhuyu (SZY, Cornus officinalis Sieb. et Zucc) in different proportions, according to the principles of uniform design (4 factors 7 levels). Tyrosine hydroxylase (TH)-positive neurons in substantia nigra pars compacta (SNpc) were detected by immunohistochemistry and rotenone-exposure days necessary to induce PD symptoms were recorded. To probe one likely mechanism of the formulas, echinacoside (ECH) concentrations of all seven recipes were determined by high-performance liquid chromatography and related to number of TH-positive neurons.</p><p><b>RESULTS</b>The data showed that recipe 4 (DH:RCR:SZY:NX = 1:1:1:1) and recipe 7 (DH:RCR:SZY:NX = 7:5:3:1) partially reversed rotenone-induced death of TH-positive neurons in the SNpc and significantly increased rotenone-exposed days compared with model group. Pharmacologically, there was not a strong correlation between ECH concentration and TH-positive neurons.</p><p><b>CONCLUSION</b>The investigated formulations of Chinese herbs had neuroprotective effects against PD models, and the neuroprotective effects were weakly related to the proportion of key herbs. However the neuroprotective effects of the formula may not result from a single active constituent.</p>

The reliance and significance of stability as a new way to reveal the essence of syndrome in Chinese medicine / 中国中西医结合杂志

Stability is the important feature of the control system. Stability exists extensively in the biological systems such as different cell types during the process of individual development, new biological properties formed under the environment and/or diet factors, drug addition, long-term memory formation, and so on. The underlying mechanisms generally include epigenetically modification, the emergence of certain substance with long half life, the formation of positive feedback loop, and the activation of stem cells. Introduction of stability into researches of Chinese medicine syndrome is essentially to explore the mechanisms of quantitative changes into the qualitative alternation. It is also helpful for us to choose an appropriate time window of animal models for Chinese syndrome and to consider what are the core effects of Chinese materia medica in improving syndrome. The stability not only meets the features of Chinese medicine theories, but also agrees with the progress of modern systems theory and biology. We hope it could promote studies on Chinese medicine syndrome.

Protective effects of Cistanche total glycosides on dopaminergic neuron in substantia nigra of model mice of Parkinson's disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of cistanche total glycosides (CTG) on dopaminergic neuron in substantia nigra (SN) of model mice of Parkinson's disease (PD).</p><p><b>METHODS</b>Experimental mice were randomly divided into 5 groups, the normal control group, the model group, the high (400 mg/kg), moderate (200 mg/kg) and low (100 mg/kg) dose CTG groups. Mouse model of chronic PD was induced by peritoneal injection of MPTP (1-methyl-4-phenyl-1,2,3,6-ttrahydropyridine) 30 mg/kg for 5 successive days. Climbing test was used to estimate the neurobehavior of mice on the 7th and 14th day (D7 and D14) after initiating MPTP injection; meantime, quantitative immunohistochemistry was conducted to detect the number of dopaminergic neuron in SN and expression of tyrosine hydroxylase (TH) in striatum.</p><p><b>RESULTS</b>The average time of climbing in the high dose CTG group on D7 and D14 was significantly shorter than that in the model group (P < 0.01). The mean optic density (OD) of TH in striatum was higher in the three CTG groups than that in the model group on D7 (P < 0.01); but on D14, significance only showed in the high and moderate dose CTG groups (P < 0.01). Moreover, the MPTP induced decrease of TH positive neuron could be antagonized by CTG, but significant difference only showed between the high dose CTG group and the model group at the two time points of observation (P < 0.05).</p><p><b>CONCLUSION</b>CTG could improve the neurobehavior of PD model mice significantly, and inhibit the decrease of nigral dopaminergic neurons and TH expression in striatum.</p>

Triptolide protects against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats: implication for immunosuppressive therapy in Parkinson's disease / 神经科学通报·英文版

<p><b>OBJECTIVE</b>Neuroinflammation with microglial activation has been implicated to have a strong association with the progressive dopaminergic neuronal loss in Parkinson's disease (PD). The present study was undertaken to evaluate the activation profile of microglia in 1-methyl-4-phenyl pyridinium (MPP+)-induced hemiparkinsonian rats. Triptolide, a potent immunosuppressant and microglia inhibitor, was then examined for its efficacy in protecting dopaminergic neurons from injury and ameliorating behavioral disabilities induced by MPP+.</p><p><b>METHODS</b>The rat model of PD was established by intranigral microinjection of MPP+. At baseline and on day 1, 3, 7, 14, 21 following MPP+ injection, the degree of microglial activation was examined by detecting the immunodensity of OX-42 (microglia marker) in the substantia nigra (SN). The number of viable dopaminergic neurons was determined by measuring tyrosine hydroxylase (TH) positive neurons in the SN. Behavioral performances were evaluated by counting the number of rotations induced by apomorphine, calculating scores of forelimb akinesia and vibrissae-elicited forelimb placing asymmetry.</p><p><b>RESULTS</b>Intranigral injection of MPP+ resulted in robust activation of microglia, progressive depletion of dopaminergic neurons, and ongoing aggravation of behavioral disabilities in rats. Triptolide significantly inhibited microglial activation, partially prevented dopaminergic cells from death and improved behavioral performances.</p><p><b>CONCLUSION</b>These data demonstrated for the first time a neuroprotective effect of triptolide on dopaminergic neurons in MPP+-induced hemiparkinsonian rats. The protective effect of triptolide may, at least partially, be related to the inhibition of MPP+-induced microglial activation. Our results lend strong support to the use of immunosuppressive agents in the management of PD.</p>

Clinical trial on treatment of Parkinson's disease of Gan-Shen yin deficiency type by recipe for nourishing Gan-Shen / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the curative effect of the recipe for nourishing Gan-Shen on Parkinson's disease (PD) of Gan-Shen yin deficiency type.</p><p><b>METHODS</b>One hundred and twenty-one PD patients were ran-domly assigned by blocking design to the control group and the treated group in the ratio of 1:1. All were treated according to the international medication guiding principle for PD treatment, but the treated group was ad-ministered with the recipe for nourishing Gan-Shen additionally. The treatment course lasted for 12 consecutive months, and the end point was the end of the 12th month. The unified Parkinson's disease rating scale (UP-DRS) score, TCM primary and secondary symptom scores were evaluated before treatment, every 3 months of treatment and at the end point. The average daily levodopa dose and the Hoehn & Yahr grading were assessed before treatment and at the end point.</p><p><b>RESULTS</b>After treatment, UPDRS score in both groups showed an ascending trend at a slower rate in the treated groups than in the control group. At the 9th and 12th month of medication, a significant difference was found in UPDRS score between the two groups (P < 0.05), and the TCM symptom score was obviously lower in the treated group than in the control group (P < 0.05). At the end point of the trial, the average daily levodopa dose used was lower in the treated group than in the control group (P < 0.05) and there was no significant difference in the Hoehn & Yahr score between the two groups (P > 0.05).</p><p><b>CONCLUSION</b>The recipe for norishing Gan-Shen can slow the ascending trend of UPDRS score in the PD patients, improve the symptoms of Gan-Shen yin deficiency, and decrease the daily levodopa dose used, showing a curative effect on PD of Gan-Shen yin deficiency type.</p>