Herbal Medicine Formulas for Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Double-Blind Placebo-Controlled Clinical Trials.

Background: Parkinson's disease (PD) is a debitlitating, chronic, progressive neurodegenerative disorder without modifying therapy. Here, we aimed to evaluate the available evidence of herbal medicine (HM) formulas for patients with PD according to randomized double-blind placebo-controlled clinical trials. Methods: HM formulas for PD were searched in eight main databases from their inception to February 2018. The methodological quality was assessed using Cochrane Collaboration risk of bias tool. Meta-analysis was performed using RevMan 5.3 software. Results: Fourteen trials with Seventeen comparisons comprising 1,311 patients were identified. Compared with placebo groups, HM paratherapy (n = 16 comparisons) showed significant better effects in the assessments of total Unified Parkinson's Disease Rating Scale (UPDRS) (WMD: -5.43, 95% CI:-8.01 to -2.86; P < 0.0001), UPDRS I (WMD: -0.30, 95% CI: -0.54 to -0.06; P = 0.02), UPDRS II (WMD: -2.21, 95% CI: -3.19 to -1.22; P < 0.0001), UPDRS III (WMD: -3.26, 95% CI:-4.36 to -2.16; P < 0.00001), Parkinson's Disease Quality of Life Questionnaire (p < 0.01) and Parkinson's Disease Questionnaire-39 (WMD: -7.65, 95% CI: -11.46 to -3.83; p < 0.0001), Non-motor Symptoms Questionnaire (p < 0.01) and Non-Motor Symptoms Scale (WMD: -9.19, 95% CI: -13.11 to -5.28; P < 0.00001), Parkinson's Disease Sleep Scale (WMD: 10.69, 95% CI: 8.86 to 12.53; P < 0.00001), and Hamilton depression rating scale (WMD: -5.87, 95% CI: -7.06 to -4.68; P < 0.00001). The efficiency of HM monotherapy (n = 1 comparison) was not superior to the placebo according to UPDRS II, UPDRS III and total UPDRS score in PD patients who never received levodopa treatment, all P > 0.05. HM formulas paratherapy were generally safe and well tolerated for PD patients (RR: 0.41, 95% CI: 0.21 to 0.80; P = 0.009). Conclusion: The findings of present study supported the complementary use of HM paratherapy for PD patients, whereas the question on the efficacy of HM monotherapy in alleviating PD symptoms is still open.

Chinese herbal medicine adjunct therapy in patients with acute relapse of multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Many patients with multiple sclerosis (MS) resort to complementary and alternative medicine, which is used in 33%-80% of MS patients in the developed country. The purpose of this study is to assess the efficacy and safety of Chinese herbal medicine (CHM) as an adjunct therapy of patients with acute relapse of MS. METHODS: Six databases were searched for randomized-controlled trial of CHM for acute relapse of MS. The risk of bias was assessed by using the twelve criteria recommended by the Cochrane Back Review Group. The primary outcome measures of interest are the Expanded Disability Status Score, annual relapse frequency, annual relapse rate, and annual relapse interval. The secondary outcome measures are the clinical efficacy rate and adverse events. The selection criteria of high-frequency herbs for MS are those with cumulative frequency over 50%. We analyzed the data using Review Manager (version 5.3). RESULTS: A total of 1100 participants were included in the 20 studies from 2004 to 2015. The number of risk of bias which met the criteria varied from 5/12 to 7/12. The top 5 most frequently used herbs are ordinally Radix Angelicae Sinensis, Radix Glycyrrhizae, Radix Paeoniae Rubra, Radix Rehmanniae Preparata, and Bombyx Batryticatus. The meta-analysis showed a significant effect of CHM for improving Expanded Disability Status Score (P<0.01), annual relapse frequency (P<0.01) and the total clinical efficacy rate (P<0.01) compared with western conventional treatment. In analysis of annual relapse rate and annual relapse interval, there was a significant difference between CHMs and western conventional treatment (P<0.01). Adverse effects were monitored in 6 studies, and were well tolerated in all MS patients. CONCLUSIONS: The available evidence from present study supported but limited to recommend the routine use of CHM adjuvant therapy for MS because of the poor methodological quality and clinical heterogeneity. However, we identified an area that is worthy of further study. Furthermore, we selected high frequent use of CHMs as a promising candidate for further clinical application and MS trials. Further rigorous randomized-controlled trials are needed.

Efficacy and safety of suanzaoren decoction for chronic insomnia disorder in adults: study protocol for randomised, double-blind, double-dummy, placebo-controlled trial.

BACKGROUND: Insomnia disorder is defined as a combination of dissatisfaction with sleep quantity or quality and a significant negative impact on daytime functioning. Chronic insomnia disorder refers to clinical symptoms of persistent insomnia at least three nights a week for at least 3 months. Prevalence estimates of insomnia disorder range from 12% to 20% in the adult population, with approximately 50% having a chronic course. The potential side effects of hypnotic medications hinder their clinical application. Thus, traditional Chinese medicine is considered as an alternative option for treating insomnia. OBJECTIVE: To evaluate the efficacy and safety of suanzaoren decoction (SZRD), a classic Chinese herbal prescription, for adult chronic insomnia disorder. METHODS/ANALYSIS: This is a randomised, double-blind, double-dummy, placebo-controlled clinical trial. A total of 150 patients with chronic insomnia disorder are randomised, allocated in a ratio of 1:1:1 to three groups: intervention group, control group and placebo group. The intervention group receives SZRD granule plus zolpidem tartrate (ZT) placebo; the control group receives ZT tablet plus SZRD granule placebo; and the placebo group receives ZT placebo and SZRD granule placebo. The patients receive medicine or placebo for 5 weeks and are followed up at 20 weeks. The primary outcome measures are polysomnography and Pittsburgh Sleep Quality Index. Secondary outcome measures are the Insomnia Severity Index, sleep diary and safety assessment. Outcomes will be assessed at baseline and after treatment. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16009198. pre-results.

Active Compounds of Rhubarb Root and Rhizome in Animal Model Experiments of Focal Cerebral Ischemia.

Rhubarb root and rhizome (RRR) has been clinically used for stroke at least 2000 years and is still used in modern times in both China and elsewhere worldwide. The objective of present study was to evaluate the efficacy of active compounds of RRR (ACRRR) for experimental ischemic stroke. Studies of ACRRR in animal models of ischemic stroke were identified from 5 databases until April 2014. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measures were neurological deficit score and infarct size. All the data were analyzed using RevMan 5.1 software. As a result, 20 studies were identified describing procedures involving 577 animals. The quality score of studies ranges from 2 to 6, and the median was 3.4. Six studies showed significant effects of ACRRR for improving infarct size compared with model group (P < 0.01). Six studies indicated significant effects of ACRRR for improving the neurological deficit scores according to Zea longa criterion or eight-point criterion (P < 0.01). In conclusion, these findings demonstrated a possible efficacy of ACRRR that have potential neuroprotective effect for experimental ischemic stroke. However, these apparently positive findings should be interpreted with caution because of the methodological flaws.

Electro-acupuncture improves the social interaction behavior of rats.

Oxytocin (OXT) and arginine-vasopressin (AVP) are two closely related neuropeptides and implicated in the regulation of mammalian social behaviors. A prior clinical study in our laboratory suggested that electro-acupuncture (EA) alleviated social impairment in autistic children accompanied by changes of peripheral levels of OXT and AVP. However, it remains unclear whether EA stimulation had an impact on central OXT and AVP levels. In the present study, rats were subjected to a single session of EA (sEA) or repeated sessions of EA (rEA). Following the stimulation, mRNA levels and peptide levels of OXT/AVP systems were determined. The results showed that sEA led to region-specific up-regulation of OXT and AVP mRNA levels in the hypothalamus where the peptides were produced, without affecting the content of OXT and AVP in the hypothalamus and peripheral blood. The rEA of 5 sessions in 9 days was given to the low socially interacting (LSI) rats. LSI rats that underwent rEA showed significant improvement of social behavior characterized by spending more time investigating the strange rats in the three-chamber sociability test. The improved sociability was accompanied by an up-regulation of mRNA and the peptide levels of OXT or AVP in SON of the hypothalamus as well as a significant increase of the serum level of AVP. It is concluded that activation of OXT/AVP systems may be associated with the pro-social effect caused by EA stimulation.

[Study on clinical efficacy of zhennaoning capsules in treatment of cerebral arteriosclerosis and analysis on its economic benefits].

To study clinical efficacy of Zhennaoning capsules in treating cases with cerebral arteriosclerosis, and analyze its economic benefits. Totally 254 cases with cerebral arteriosclerosis were randomly divided into two groups according to their doctor-consulting sequence: the test group (n = 128) that was administered with Zhennaoning capsules, and the control group (n = 126) that was administered with Yangxueqingnao granules. A double-blind parallel-controlled study was conducted for four weeks, in order to observe the clinical efficacy and adverse effects of the two groups, and evaluate their pharmacoeconomics. Additionally, the clinical efficacy and safety of Zhennaoning capsules in treating cerebral arteriosclerosis, as well as its pharmacoeconomics were also discussed. This study showed that Zhennaoning capsules had a better efficacy than its control drug Yangxueqingnao granules in relieving traditional Chinese medicinal syndromes (according to traditional Chinese medicinal syndrome coring, efficacy and cure rate), suggesting a statistical significance (P < 0.01). Despite statistical significance showed from the differences in the remaining indexes and the occurrence rate of adverse effects, the test group displayed a lower cost effectives than the control group (P < 0.01). Zhennaoning capsules have a better clinical efficacy in treating cases with cerebral arteriosclerosis than Yangxueqingnao granules, demonstrating safe clinical application and better economic advantages.

Remediation of soil co-contaminated with petroleum and heavy metals by the integration of electrokinetics and biostimulation.

Successful remediation of soil co-contaminated with high levels of organics and heavy metals is a challenging task, because that metal pollutants in soil can partially or completely suppress normal heterotrophic microbial activity and thus hamper biodegradation of organics. In this study, the benefits of integrating electrokinetic (EK) remediation with biodegradation for decontaminating soil co-contaminated with crude oil and Pb were evaluated in laboratory-scale experiments lasting for 30 days. The treated soil contained 12,500 mg/kg of total petroleum hydrocarbons (TPH) and 450 mg/kg Pb. The amendments of EDTA and Tween 80, together with a regular refreshing of electrolyte showed the best performance to remediate this contaminated soil. An important function of EDTA-enhanced EK treatment was to eliminate heavy metal toxicity from the soil, thus activating microbial degradation of oil. Although Tween 80 reduced current, it could serve as a second substrate for enhancing microbial growth and biodegradation. It was found that oil biodegradation degree and microbial numbers increased toward the anode and cathode. Microbial metabolism was found to be beneficial to metal release from the soil matrix. Under the optimum conditions, the soil Pb and TPH removal percentages after 30 days of running reached 81.7% and 88.3%, respectively. After treatment, both the residual soil Pb and TPH concentrations met the requirement of the Chinese soil environmental quality standards.

[Advance of studies on interaction between active components of natural medicines and lysozymes].

Lysozyme (LYSO), as an alkalescent protein micromolecule in living organisms, exhibits important pharmacological actions such as antibiosis, anti-inflammatory, antivirus and enhancing immunity. LYSO can combine with many exogenous and endogenous substances and carry many drugs. This essay summarizes interaction between different kinds of active components of natural medicines and lysozymes, which is significant to comprehensively understand pharmacological mechanism of natural drugs and their transfer and metabolic process in organisms, optimize molecule structures of drugs and increase bioavailability and biological effects of natural drugs.

[Clinical study of total glucosides of paeony in patients with systemic lupus erythematosus].

OBJECTIVE: To study the therapeutic efficacy and adverse reaction of total glucosides of paeony (TGP, extracted from Paeonia lactiflora Pall.) in patients with systemic lupus erythematosus (SLE). METHODS: Clinical data of patients with SLE were analyzed. Those who orally took TGP continuously for five years or more were taken as TGP1 group (29 cases). Those who orally took TGP continuously or intermittently for more than one year but less than five years were taken as TGP2 group (47 cases). Twenty patients matched with the TGP1 group and the TGP2 group in age, affected duration, urine protein, and SLE disease activity index (SLEDAI) were selected as the control group. The average daily dose of prednisone, total cyclophosphamide (CTX) dose, urine protein, SLEDAI score, recurrent case, and episodes of infection were compared among the three groups after five-year treatment. RESULTS: The average daily dose of prednisone, total CTX dose, and SLEDAI score were obviously lower in the TGP1 group than in the control group (P<0.01). The average daily dose of prednisone, total CTX dose, and SLEDAI score were obviously lower in the TGP1 group than in the TGP2 group, Significant difference was shown (P <0. 05). The average daily dose of prednisone and total CTX dose were lower in the TGP2 group than in the control group (P<0.05, P<0.01). There was no statistical difference in the urine protein among the three groups. As for the recurrence, one case occurred in the TGP1 group, nine in the TGP2 group, and seven in the control group. As for episodes of infection, there were three cases in the TGP1 group, seventeen in the TGP2 group, and eighteen in the control group during the five years. No adverse reaction correlated to TGP was found in the three groups. CONCLUSIONS: TGP had definite therapeutic efficacy in treatment of patients with SLE. It could reduce the average daily dose of prednisone and the total CTX dose, lower the recurrent cases and episodes of infection, especially for the medication of more than five years.

Antiproliferative and apoptotic sesquiterpene lactones from Carpesium faberi.

Four new (1-4) and 13 known (5-17) sesquiterpene lactones along with two known diterpenes (18, 19) were isolated from the whole plant of Carpesium faberi. The new structures were elucidated by means of spectroscopic techniques and some chemical transformations to be pseudoguaian-1α(H)-8α,12-olide-4ß-O-ß-d-glucopyranoside (1), 4ß,10α-dihydroxy-5α(H)-1,11(13)-guaidien-8α,12-olide (2), 4ß,10ß-dihydroxy-5α(H)-1, 11(13)-guaidien-8ß,12-olide (3), and (4S)-acetyloxyl-11(13)-carabren-8ß,12-olide (4). All isolates were tested against MCF-7 human breast cancer cells using the MTT assay. Among them, the sesquiterpene lactones (except tomentosin 17) possessing an α-methylene-γ-lactone moiety were found to have in vitro antiproliferative activities, with IC(50) values of 3.0-38.8µg/mL. The effects of four selected sesquiterpene lactones (guaianolide 2, carabranolide 4, pseudoguaianolide 9, eudesmanolide 13) on the cell cycle were examined using flow cytometry (FCM).

Antiproliferative and apoptotic activities of linear furocoumarins from Notopterygium incisum on cancer cell lines.

Bioassay-guided fractionation of the antiproliferative chloroform extract of the traditional Chinese medicine Qiang-Huo (Notopterygium incisum) led to the isolation of nine linear furocoumarins (1- 9). All the isolates were tested against two human cancer cell lines (HepG-2 and MCF-7) and a rat cancer cell line (C6) using the MTT assay method. Among them, notopol (1), notopterol (2), 5-[(2 E,5 Z)-7-hydroxy-3,7-dimethyl-2,5-octadienoxy]psoralene (3), and 5-[(2,5)-epoxy-3-hydroxy-3,7-dimethyl-6-octenoxy]psoralene (4) showed significant antiproliferative activity against the HepG-2 and C6 cancer cell lines, with IC(50) values of 7.7-24.8 microg/mL (5-FU: ca. 5 microg/mL). Compounds 1- 3 also showed moderate cytotoxicity against the MCF-7 cancer cell line, with IC(50) values of 39.4-61.3 microg/mL (5-FU: 17.3 microg/mL). The cell cycle-specific inhibition and apoptosis induced by compounds 1 and 2 were determined using flow cytometry. The structure-activity relationship (SAR) is briefly discussed herein. It was found that the presence of a free hydroxy at the lipophilic side chain linked to C-5 of the linear furocoumarins was essential for their in vitro antiproliferative activity.

[Clinical observation of Shuxuetong Injection in treating patients with active rheumatoid arthritis].

OBJECTIVE: To observe the efficacy and adverse reaction of Shuxuetong Injection (SXTI, the extracted liquor from Pheretima and Hirudo) in treating patients with active rheumatoid arthritis (RA). METHODS: Ninety-seven patients with active RA assigned in the SXTI group were treated with high or low dose SXTI (6 mL/d or 8 mL/d) combined with conventional therapy and the 30 in the control group treated with conventional therapy alone. Thompson index, Ritchie index, time of morning stiffness (TMS), erythrocyte sedimentation rate (ESR) and plasma fibrinogen (Fib) in patients were determined before treatment (T0), by the end of the 1st (T1), second (T2) and 4th (T3) week of treatment, respectively, as well as the SXTI associated adverse reaction monitored. RESULTS: Marked improvement of all indexes, including Thompson index, Ritche index, TMS, ESR and Fib, was shown in the SXTI groups at T1 (P < 0.01), but in the control group, it only appeared at T3 (P < 0.01). Compared with the control group, TMS, ESR and Fib at T1, Thompson index and Ritche index at T2 in the SXTI groups were significantly improved (P < 0.01), especially significant in the high dose group (P < 0.01). However, hands edema appeared in 2 patients, foot edema in 1 and fullness sensation of head in 1 in the high dose SXTI group. The dose was forced to redue to 6 mL/d, and then all the symptoms were improved. CONCLUSION: SXTI shows good efficacy with less adverse reaction in treating patients with active RA, and better efficacy was obtained at the dose of 8 mL/d.

[Clinical observation on effect of total glucosides of paeony in treating patients with non-systemic involved Sjögren syndrome].

OBJECTIVE: To investigate the efficacy and adverse reaction of total glucosides of paeony (TGP) in treating patients with non-systemic involved Sjögren syndrom (NSI-SS). METHODS: Retrospective study was conducted on 27 patients with NSI-SS who received TGP treatment for over two years as the TGP group, and 20 patients received hydroxychloroquine sulfate (HCQs) for over two years in the HCQs group for positive control. Salivary flow, Schirmer's test and serum gamma-globulin at different time points, i.e. before treatment, and at the end of 1st, 3rd, 6th, 12th and 24th month respectively, were compared between groups, and adverse reactions associated with TGP and HCQ were also observed. RESULTS: In the TGP group, saliva secretion was significantly increased and serum gamma-globulin decreased significantly from the 6th month (P <0.01), Schirmer's test improved significantly after 12 months (P< 0.01). While in the HCQs group serum gamma-globulin was significantly decreased from the 3rd month (P <0.01), saliva secretion and Schirmer's test improved significantly after six months (P<0.01). However, the 3 indexes determined at the end of the 3rd month were insignificantly different from those before treatment. Mild diarrhea occurred in 4 cases in the TGP group, they were improved two weeks later, but one case with severe diarrhea was dropped. While in the HCQs group, 2 patients were dropped, one for the raising of alanine aminotransferase at the 6th month and the other for decreased vision at the 9th month. CONCLUSION: Efficacy of TGP is equivalent to that of HCQs in treating NSI-SS, but with higher safety and the effect initiating time being about 6 - 12 months.

[Cloning, expression, purification of protein kinase Cdelta and its preliminary application in drug lead compounds screening].

Protein kinase Cdelta (PKCdelta) is a member of protein kinase C family, which possess phospholipid-dependent serine and threonine kinase activity. PKCdelta is a potential drug target of diabetes and some cancers. The abnormal activation of PKCdelta can arouse diabetes and some cancers. Therefore the specific inhibitors of PKCdelta can be applied in the research and development of the drug candidate of these diseases. The present aim is to obtain active recombinant PKCdelta from COS1 cells. For cloning of mouse PKCdelta a pair of specific primers were designed based on the published sequence of this gene. The cDNA of full coding region was obtained by RT-PCR. The amplified cDNA was subsequently cloned into FLAG-tagged pcDNA3.0 and its sequence was confirmed by DNA sequencing analysis. FLAG-tagged pcDNA3.0-PKCdelta was transfected into COS1 cells. A cell strain which can stably express PKCdelta was obtained by G418 screening. FLAG-tagged PKCdelta in the supernant of COS1 cells extracts was absorbed by anti-FLAG resin and eluted by FLAG peptide. The purified protein appeared as a single band on both SDS-PAGE and western blotting, indicating that it was chemical and antigenic pure. By kinase assay, the recombinant PKCdelta was active. Positive inhibitor, staurosporine, was used to prove the enzyme could be greatly inhibited. Several compounds have been found to inhibit the enzyme, which indicates the preliminary application in drug lead compounds screening.

[Development and application of ultrasound technology for hyperthermia].

It has been a long time since ultrasound hyperthermia began to be used in the clinical management of cancers and benign diseases. Numerous biological and clinical investigations have demonstrated that: hyperthermia in the range of 41-45 degrees C can significantly enhance clinical response to radiation therapy and chemotherapy, and high-temperature hyperthermia (greater than 65 degrees C) alone is now being used as an alternative to conventional invasive surgery for selective tissue destruction, causing tumor coagulation and necrosis. As a promising noninvasive and effective local therapy, HIFU has attracted great attention. China is advanced in the clinical applications of HIFU. This article gives an introduction of the development and applications of ultrasound hyperthermia technology, and also provides a general review of a selection of ultrasound hyperthermia systems both in clinical use and under development.