L-stepholidine reduced L-DOPA-induced dyskinesia in 6-OHDA-lesioned rat model of Parkinson's disease.

L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) remains a challenge in Parkinson's disease (PD) drug therapy. In the present study, we examined the effect of L-stepholidine (L-SPD), a known dual dopamine receptor agent, on LID in 6-hydroxydopamine (6-OHDA)-lesioned PD rat model. Daily administration of L-DOPA to PD rats for 22 days induced steady expression of LID, co-administration of L-SPD with L-DOPA significantly ameliorated LID without compromising the therapeutic potency of L-DOPA, indicating that L-SPD attenuated LID development. L-SPD alone elicited stable contralateral rotational behavior without inducing significant dyskinesia. Acute administration of L-SPD to rats with established LID produced significant relief of dyskinesia; this effect was mimicked by D(2) receptor antagonist haloperidol, but blunted by 5-HT(1A) receptor antagonist WAY100635. Furthermore, the mRNA level of 5-HT(1A) decreased significantly on 6-OHDA-lesioned striata, whereas chronic L-SPD treatment restored 5-HT(1A) receptor mRNA level on the lesioned striata. The present data demonstrated that L-SPD elicited antidyskinesia effects via both dopamine (D(2) receptor antagonistic activity) and nondopamine (5-HT(1A) agonistic activity) mechanisms.

Medication of l-tetrahydropalmatine significantly ameliorates opiate craving and increases the abstinence rate in heroin users: a pilot study.

AIM: Drug addiction is a chronic brain disease with constant relapse requiring long-term treatment. New pharmacological strategies focus on the development of an effective antirelapse drug. This study examines the effects of levotetrahydropalmatine (l-THP) on reducing heroin craving and increasing the abstinence rate among heroin-dependent patients. METHODS: In total, 120 heroin-dependent patients participated in the randomized, double-blinded, and placebocontrolled study using l-THP treatment. The participants remained in a ward during a 4-week period of l-THP treatment, followed by 4 weeks of observation after treatment. The patients were followed for 3 months after discharge. Outcome measures are the measured severity of the protracted abstinence withdrawal syndrome (PAWS) and the abstinence rate. RESULTS: Four weeks of l-THP treatment significantly ameliorated the severity of PAWS, specifically, somatic syndrome, mood states, insomnia, and drug craving, in comparison to the placebo group. Based on the 3 month follow-up observation, participants who survived the initial 2 weeks of l-THP medication and remained in the trial program had a significantly higher abstinence rate of 47.8% (95% confidence interval [CI]: 33%- 67%) than the 15.2% in the placebo group (95% CI: 7%-25%), according to a log- rank test (P<0.0005). CONCLUSION: l-THP significantly ameliorated PAWS, especially reducing drug craving. Furthermore, it increased the abstinence rate among heroin users. These results support the potential use of l-THP for the treatment of heroin addiction.

Effects of (-)stepholidine in animal models for schizophrenia.

AIM: (-)Stepholidine (SPD) is an active ingredient of the Chinese herb Stephania intermedia, which binds to the dopamine D(1) and D(2) like receptors. Biochemical, electrophysiological and behavioural experiments have provided strong evidence that SPD is both a D(1) and a D(2) antagonist, which could make SPD a unique antipsychotic drug. The present study aimed to investigate the antipsychotic properties of SPD in two animal models for schizophrenia. METHODS: The effects of SPD, clozapine and haloperidol in increasing forelimb and hindlimb retraction time in the paw test and in reversing the apomorphine and MK801-induced disruption of prepulse inhibition was investigated. RESULTS: In the paw test, clozapine and SPD increased the hindlimb retraction time, with only a marginal effect on the forelimb retraction time, whereas haloperidol potently increased both. In the prepulse inhibition paradigm, all three drugs reverse the apomorphine-induced disruption in prepulse inhibition, while none of the drugs could reverse the MK801-induced disruption. SPD even slightly, but significantly, potentiated the effects of MK801. CONCLUSION: The data show that SPD showed antipsychotic-like effects in both the prepulse inhibition paradigm and in the paw test. Moreover, the results of the paw test suggest that SPD has an atypical character with a relatively small potency to induce extrapyramidal side effects.

A novel therapeutic approach to 6-OHDA-induced Parkinson's disease in rats via supplementation of PTD-conjugated tyrosine hydroxylase.

The present study aimed to evaluate whether the protein transduction domain (PTD)-conjugated human tyrosine hydroxylase (TH) fusion protein was effective on the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) model rats. An expression vector pET-PTD-TH harbouring the PTD-TH gene was constructed and transformed to the Escherichia coli BL21 cells for expression. The expressed recombinant PTD-TH with a molecular weight of 61 kD was successfully transduced (1 microM) into the dopaminergic SH-sy5y human neuroblastoma cells in vitro and visualized by immunohistochemical assay. An in vivo experiment in rats showed that the iv administered PTD-TH protein (8 mg/kg) permeated across the blood-brain barrier, penetrated into the striatum and midbrain, and peaked at 5-8 h after the injection. The behavioral effects of PTD-TH on the apomorphine-induced rotations in the PD model rats 8 weeks after the 6-OHDA lesion showed that a single bolus of PTD-TH (8 mg/kg) iv injection caused a decrement of 60% of the contralateral turns on day 1 and 40% on days 5-17. The results imply that iv delivery of PTD-TH is therapeutically effective on the 6-OHDA-induced PD in rats, the PTD-mediated human TH treatment opening a promising therapeutic direction in treatment of PD.

Effect of astraglus injection on serum apoptosis relevant factors in patients with chronic heart failure / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of Astragalus injection (AGI) on serum apoptosis related factors such as soluble Fas (sFas), soluble Fas ligand (sFasL) and tumor necrosis factor alpha (TNF-alpha) in patients with chronic heart failure (CHF).</p><p><b>METHODS</b>Eighty-four patients with CHF of NYHA II-IV grade were randomly divided into two groups, the treated group (42 patients) treated with AGI and the control group (42 patients) treated with routine treatment. The level of serum sFas, sFasL, and TNF-alpha were measured with ELISA before and after treatment. At the same time, patients' heart function were graded according to the NYHA classification and their indices of left ventricular function were determined.</p><p><b>RESULTS</b>Patients' NYHA grade was improved in both groups after treatment (P < 0.05 or P < 0.01), and it was better in the treated group than that in the control group (P < 0.05). Moreover, in the treated group, the left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) decreased, the left ventricular ejection fraction (LVEF) increased, which was significantly different than that before treatment (P < 0.05) respectively; level of serum apoptosis related factors sFas, sFas L and TNF-alpha were significantly decreased after treatment, showing significant difference as compared with those before treatment or with those in the control group after treatment (P < 0.05 or P < 0.01). While all indices had no obvious change in the control group.</p><p><b>CONCLUSION</b>AGI may be regarded as an effective remedy for treatment of CHF owing to its effects in decreasing the level of serum apoptosis related factors in patients with CHF.</p>

Effect of Astragalus injection on plasma levels of apoptosis-related factors in aged patients with chronic heart failure / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Astragalus injection (AI) on plasma levels of apoptosis-related factors in aged patients with chronic heart failure (CHF).</p><p><b>METHODS</b>Seventy-two CHF patients were randomly divided into the AI group (36 cases) treated with AI and the control group (36 cases) treated with conventional treatment. Plasma levels of soluble Fas (sFas), soluble Fas ligand (sFasL), tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays (ELISA) with monoclonal anti-human antibodies. Besides, New York Heart Association (NYHA) grading was assessed according to improved symptoms and left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were assessed by echocardiogram after 4 weeks of treatment.</p><p><b>RESULTS</b>After 4 weeks of treatment, NYHA grading was markedly improved in the two groups, but it was significantly better in AI group than that in the control group (P < 0.05). As compared with the control group, sFas, sFasL, TNF-alpha and IL-6 in the AI group were obviously lower, the difference between the two groups and between before and after treatment were significant (P < 0.05 or P < 0.01). Moreover, in AI group, LVESV and LVEDV decreased, LVEF increased, which was significantly different than that before treatment (P < 0.05), respectively.</p><p><b>CONCLUSION</b>AI could lower plasma levels of apoptosis-related factors, and is one of the effective drugs in improving cardiac function in the aged patients with CHF.</p>

Clinical study on effect of Astragalus injection on left ventricular remodeling and left ventricular function in patients with acute myocardial infarction / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Astragalus injection (AI) on left ventricular remodeling and left ventricular function in patients with acute myocardial infarction (AMI).</p><p><b>METHODS</b>AMI patients were randomly divided into the AI group (54 cases) treated with AI and the control group (54 cases) treated with conventional treatment. Left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), anterior endocardial segmental length (ASL), posterior endocardial segmental length (PSL) were assessed by echocardiogram at the 1st and the 4th week of treatment; and the cardiac systolic and diastolic functions were detected by nuclide gating cardiac blood pool imaging on the 4th week. Besides, the plasmic levels of lipid peroxide (MDA), count of endothelial cell (CEC) and superoxide dismutase (SOD) were determined before and after treatment.</p><p><b>RESULTS</b>At the 4th week, changes of LVEDVI, LVESVI and ASL in the AI group were not obvious, but increased significantly in the control group, the significant difference in comparison between the two groups was shown (P < 0.05). As compared with the control group, in the AI group, the left ventricular ejection fraction, left ventricular peak ejecting rate and left ventricular peak filling rate were higher, and the left ventricular time for peak filling rate was shorter, moreover, MDA and CEC were lower and SOD was higher. The difference between groups and between before and after treatment were significant (P < 0.01 or P < 0.05).</p><p><b>CONCLUSION</b>AI is one of the effective drugs in reversal of left ventricular remodeling and improving left ventricular function in patients with AMI.</p>