In vitro study on the antiviral activity of 9 extracts of traditional Chinese herbal medicine against the human respiratory syncytial virus

Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea officinalis and Elaeagnus gonyanthes,the alcohol extracts of Nauclea officinalis,Elaeagnus gonyanthes and Zanthoxylumarmatum)on human respiratory syncytial virus(HRSV).Methods:The cytotoxic effect of the extracts on cells was evaluated by a cell viability assay using the CCK-8 method,a concentration of the extracts with cell viability greater than 50%was selected for the follow-up anti-HRSV effect assay,the 50%effective concentration(EC50)was assessed by an in vitro cell infection model.Results:The EC50s of the water extract from Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes were 0.05 mg/mL,0.03 mg/mL and 0.05 mg/mL,and the therapeutic index(TI)of them were 18.60,21.67 and 56.80 respectively.Conclusion:The water extracts of Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes possess the activity of anti-HRSV virus.

Traditional Chinese herbal medicine plus triple therapy in treating Helicobacter pylori-induced chronic atrophic gastritis: a meta-analysis and cumulative meta-analysis

Objectives:To evaluate the benefits of traditional Chinese herbal medicine(TCHM)plus triple therapy(TT)in the management of Helicobacter pylori(H.pylori)-induced chronic atrophic gastritis(CAG).Methods:A comprehensive access and electronic database search were carried out from inception to June 2020.Prospective randomized trials(TCHM plus TT vs.TT)were selected to assess the eradication rate of H.pylori(ER of H.pylori),clinical symptom relief rate(SRR),treatment-related adverse reactions(TRAR)and 95%confidence intervals(CI)in the meta-analysis and cumulative meta-analysis(CMA).Meta-regression analysis was used to analyze heterogeneity between studies and publication bias.Results:33 studies contained 3,226 participants were included.Compared with the TT group,TCHM plus TT group showed a significantly higher ER of H.pylori(OR=4.14,95%CI:3.21-5.35;P=0.000)and SRR(OR=4.50,95%CI:3.59-5.64).Meanwhile,the TRAR of TCHM plus TT remedy was significantly lower than TT monopoly(RR=0.43,95%CI:0.29-0.64;P=0.000).The results of the CMA,sorted by publication year,duration of treatment,and sample size,confirmed that combined treatment remedy was superior to TT monopoly in respect of ER of H.pylori and SRR.Conclusions:The present study obtained reliable and convincing evidence suggesting that TCHM plus TT remedy was efficacious and safe in treating H.pylori-induced CAG.

Traditional Chinese Herbal Medicine for Perimenopausal Depression of Chinese Women:A Meta-analysis

Objective: The objective of this study is to evaluate the effectiveness and safety of traditional Chinese herbal medicine(TCHM) in treatment of perimenopausal depression(PD) in China. Methods: To identify randomized controlled trials, an electronic search has been conducted through databases as follows: PubMed, the Cochrane Central Register of Controlled Trials, Web of Science, Chinese Biological Medicine Database, China National Knowledge Infrastructure Database, Chinese Scientific Journal Database, and WanFang Digital Periodicals Database.Methodological quality was evaluated by Cochrane Collaboration's tool which is able to assess the risk of bias in Review Manager Software.What's more, meta-analysis was performed by using Cochrane Collaboration's RevMan 5.2 software,(Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, and Denmark). Dichotomous data were analyzed by using relative risk(RR) and 95% confidence interval(CI).Continuous variables were analyzed using weighted mean differences(WMDs) and 95% CI. Subgroup analysis was performed by the type of medicine which was used in the experimental group. Results: This meta-analysis includes 11 randomized control trials with 818 patients.Compared to the control group(RR: 1.14, 95% CI: [1.03, 1.26], P = 0.009 and WMD:-2.09, 95% CI: [-3.58,-0.18]), the experimental group had a significant higher clinical efficacy rate and relatively lower Hamilton Depression Rating Scale(HAM-D) score. For clinical efficacy rate, the results varied depending on the detail treatment measures of the experimental group. In the experimental group with TCHM,no significant difference was observed(RR: 1.14, 95% CI: [0.97, 1.33]), while in the experimental group combined with western medicine,a significant difference in the clinical efficacy rate between the experimental group and control group showed up(RR: 1.15, 95% CI: [1.01,1.32], P = 0.04). For the HAM-D score, subgroup analyses revealed that the pure TCHM therapy was not associated with significant HAM-D score reduction compared to the control group(WMD:-2.48, 95% CI: [-6.00,1.03], P = 0.17). However, in the experimental group where western medicine was added to, the HAM-D score decreased statistically compared to the control group(WMD:-1.88, 95% CI: [-3.58,-0.18], P = 0.03). There is no serious adverse event in both groups. Conclusions: Combination therapy of TCHM and western medicine is more effective in treating PD in terms of clinical efficacy rate. However, the results should be interpreted with caution due to the mediocre methodological quality of the included trials.

Traditional Chinese Medicine Induced Liver Injury

Traditional Chinese Medicine (TCM) is popular around the world and encompasses many different practices with parti-cular emphasis on herbal TCM. Using the PubMed database, a literature search was undertaken to assess the extent herbal TCM products exert rare hepatotoxicity. Analysis of reported cases revealed numerous specified herbal TCM products with potential hepatotoxicity. Among these were An Shu Ling, Bai Fang, Bai Xian Pi, Ban Tu Wan, Bo He, Bo Ye Qing Niu Dan, Bofu Tsu Sho San, Boh Gol Zhee, Cang Er Zi, Chai Hu, Chaso, Chi R Yun, Chuan Lian Zi, Ci Wu Jia, Da Chai Hu Tang, Da Huang, Du Huo, Gan Cao, Ge Gen, Ho Shou Wu, Hu Bohe You, Hu Zhang, Huang Qin, Huang Yao Zi, Hwang Geun Cho, Ji Gu Cao, Ji Ji, Ji Xue Cao, Jiguja, Jin Bu Huan, Jue Ming Zi, Kamishoyosan, Kudzu, Lei Gong Teng, Long Dan Xie Gan Tang, Lu Cha, Ma Huang, Mao Guo Tian Jie Cai, Onshido, Polygonum multiflorum, Qian Li Guang, Ren Shen, Sairei To, Shan Chi, Shen Min, Shi Can, Shi Liu Pi, Shou Wu Pian, Tian Hua Fen, White flood, Wu Bei Zi, Xi Shu, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, Zhen Chu Cao, and various unclassified Chinese herbal mixtures. Causality was firmly established for a number of herbal TCM products by a positive reexposure test result, the liver specific scale of CIOMS (Council for International Organizations of Medical Sciences), or both. Otherwise, the quality of case data was mixed, especially regarding analysis of the herb ingredients because of adulteration with synthetic drugs, contamination with heavy metals, and misidentification. In addition, non-herbal TCM elements derived from Agaricus blazei, Agkistrodon, Antelope, Bombyx, Carp, Fish gallbladder, Phellinus, Scolopendra, Scorpio, and Zaocys are also known or potential hepatotoxins. For some patients, the clinical course was severe, with risks for acute liver failure, liver transplantation requirement, and lethality. In conclusion, the use of few herbal TCM products may rarely be associated with hepatotoxicity in some susceptible individuals, necessitating a stringent pretreatment evaluation of the risk/benefit ratio, based on results of multicenter, randomized, double-blind, placebo-controlled clinical trials.

Challenges in Research and Development of Traditional Chinese Medicines

This review is briefly to recall the history of research and development (R&D) of Chinese materia medica (CMM) and to discuss the challenges of Chinese traditional and herbal medicines (CTHM) facing the modern science and technology. The R&D of CTHM is thought to be an important pathway for new drug discovery. Since1949, about 140 approved new drugs have been developed, among which about 80 originated directly or indirectly from medicinal plants. CTHM has gained interest from the international medical, biomedical, and pharmaceutical institutions as a valuable source of potential medicines. For the modernization of CMM and innovative research of CTHM, there are following challenges to be faced: (1) to evaluate the efficacy, pharmacological properties, action mechanism, and active chemical constituents; (2) to develop new methodologies for the quality and safety of CTHM; (3) to apply new '-omics' techniques to accelerate drug discoveries developed from CTHM; and (4) to apply international practices including good agricultural practice, good manufacturing practice, good laboratory practice, and good clinical practice in the R&D of CTHM.

Exploring Traditional Chinese Medicine by A Novel Therapeutic Concept of Network Target

Traditional Chinese medicine（TCM） holds a holistic theory, and specializes in balancing disordered human body using numerous natural products, particularly Chinese herbal formulae. TCM has certain treatment advantages for patients suffering from various complex diseases. However, due to the complex nature of TCM, it remains difficult to unveil such holistic medicine by the current reductionism research strategies, which treat both herbal ingredients and targets in isolation. Recently, an emerging network pharmacology approach has been introduced to tackle this bottleneck problem. A TCM-derived novel therapeutic concept, ＂network target＂, which is different from the Western medicine＇s ＂onetarget＂ concept, has been proposed from China. The network target strategy is able to illustrate the complex interactions among the biological systems, drugs, and complex diseases from a network perspective, and thus provides an innovative approach to access ancient remedies in a precision manner and at a systematic level, which also highlights TCM＇s potential in current medical systems.

Buyang Huanwu Decoction fraction protects against cerebral ischemia/reperfusion injury by attenuating the inflammatory response and cellular apoptosis

Buyang Huanwu Decoction fraction extracted from Buyang Huanwu Decoction contains saponins of Astragalus, total paeony glycoside and safflower flavones. The aim of this study was to demonstrate the neuroprotective effect and mechanism of Buyang Huanwu Decoction fraction on ischemic injury both in vivo and in vitro. In vivo experiments showed that 50-200 mg/kg Buyang Huanwu Decoction fraction reduced infarct volume and pathological injury in ischemia/reperfusion rats, markedly inhibited expression of nuclear factor-KB and tumor necrosis factor-a and promoted nestin protein expression in brain tissue. Buyang Huanwu Decoction fraction （200 mg/kg） exhibited significant effects, which were similar to those of 100 mg/kg Ginkgo biloba extract. In vitro experimental results demonstrated that 10-100 mg/L Buyang Huanwu Decoction fraction significantly improved cell viability, decreased the release of lactate dehydrogenase and malondialdehyde levels, and inhibited the rate of apoptosis in HT22 cells following oxygen-glucose deprivation. Buyang Huanwu Decoction fraction （100 mg/L） exhibited significant effects, which were similar to those of 100 mg/L Ginkgo biloba extract. These findings suggest that Buyang Huanwu Decoction fraction may represent a novel, protective strategy against cerebral ischemia/reperfusion injury in rats and oxygen-glucose deprivation-induced damage in HT22 cells in vitro by attenuating the inflammatory response and cellular apoptosis.

Effects of ephedrine on expression of Nogo-A and synaptophysin in neonatal rats following hypoxic-ischemic brain damage

BACKGROUND： Central nervous system axons regenerate poorly following neonatal hypoxic-ischemic brain damage （HIBD）, partly due to inhibitors, such as Nogo-A. Very few studies have addressed the regulation of Nogo-A in neonatal rats following HIBD. However, numerous studies have shown that ephedrine accelerates neuronal remodeling and promotes recovery of neural function in neonatal rats following HIBD. OBJECTIVE： To investigate the effects of ephedrine on expression of Nogo-A and synaptophysin in brain tissues of neonatal rats following HIBD. DESIGN, TIME AND SETTING： A completely randomized, controlled study was performed at the Immunohistochemistry Laboratory of the Research Institute of Pediatrics, Children＇s Hospital of Chongqing Medical University from August 2008 to March 2009. MATERIALS： Ephedrine hydrochloride （Chifeng Pharmaceutical Group, China）, rabbit anti-Nogo-A polyclonal antibody （Abcam, UK）, and rabbit anti-synaptophysin polyclonal antibody （Lab Vision, USA） were used in this study. METHODS： A total of 96 healthy, neonatal, Sprague Dawley rats were randomly assigned to three groups （n = 32）： sham operation, HIBD, and ephedrine. The HIBD model was established by permanent occlusion of the left common carotid artery, followed by 2 hours of hypoxia （8% oxygen and 92% nitrogen）. In the sham operation group, the left common carotid artery was exposed, but was not ligated or subjected to hypoxia. Rats in the ephedrine group were intraperitoneally injected with ephedrine immediately following HIBD, with 1.5 mg/kg each time. Rats in the sham operation and HIBD groups were injected with an equal volume of saline. All neonatal rats were treated once daily for 7 days. MAIN OUTCOME MEASURES： Histopathological damage to the cortex and hippocampus was determined by hematoxylin-eosin staining. Expression of Nogo-A and synaptophysin was detected using immunohistochemical staining. RESULTS： Neuronal degeneration and edema were observed in the hypoxJc-Jschemic cortex and hippocampus by hematoxylin-eosin staining. Compared with the sham operation group, the levels of Nogo-A significantly increased in the HIBD group at various time points （P 〈 0.01）. Nogo-A expression was significantly reduced in the ephedrine group compared with the HIBD group （P 〈 0.01）. Synaptophysin expression was significantly decreased in the hypoxic-ischemJc cortex, compared with the sham operation group （P 〈 0.01）. Synaptophysin levels were significantly increased in the ephedrine group, compared with the HIBD group （P 〈 0.01）. CONCLUSION： Altered Nogo-A expression was associated with inversely altered synaptophysin expression. The use of ephedrine normalized expression levels of Nogo-A and synaptophysin following HIBD.

Review of the Regulations for Clinical Research in Herbal Medicines in USA

In 2012,USA Food and Drug Administration（FDA） approved 39 new drugs,however,there are only two botanical drugs（one topical and one oral）approved by FDA since the publication of the FDA＇s industry guidelines for the botanical drug product in June 2004.The approval shows the Western guideline can be used for herbal medicines,authors investigate current regulation on herbal medicine clinical research,identify challenges conducting clinical trials,and seek to produce some guidance for potential investigators and sponsors considering a clinical trial in this area.Key words were formulated for searching on Medline and FDA website to locate relevant regulations for clinical research in herbal medicines to understand current environment for herbal medicine usage and examine the barriers affecting herbal medicine in clinical trials.Authors critically explore case study of the 1st FDA approved botanical drugs,Veregen（sinecatechins）,green tea leaves extract,a topical cream for perianal and genital condyloma.In consideration of current regulation environment in USA,based on the findings and analysis through the literature review and Veregen case study,authors produce and propose a Checklist for New Drug Application of Herbal Medicines for potential investigators and sponsors considerina in a herbal medicine clinical trial.

Phytochemistry,Metabolism, and Metabolomics of Ginseng

Ginseng, as a medicinal plant, has been used for thousands of years in China, Korea, and Japan, and the study on ginseng is a hotspot in the research field as evidenced by about 7000 scientific papers in PUBMED. In recent decades, many ginseng studies focused on the metabolism and metabolomics of ginseng or its active ingredients using modern bioanalytical technologies. To date, more than 200 ginsenosides and non-saponin constituents have been isolated and identified. In the past decades, rapid development of analytical technologies has facilitated the advancement of ginseng research in many ways. In this review, we focus on the advances of ginseng research in chemistry, pharmacology, and metabolomics. We also provide the comments on the significance as well as challenges of metabolomics-based ginseng studies.