PROGRESS OF RESEARCH IN THE PREPARATION OF CHINESE TRADITIONAL AND HERBAL DRUGS WITH ANTICANCER ACTIVITY

Research into anticancer substances madefrom Chinese herbal drugs and their clinicalapplication is gaining international attention bythe medical profession of the more than 20analogues of camptothecine isolated from Camp-totheca tree in China, most exhibited anticanceractivity. Among them, 10-hydroxycamptothe-cine has a wide anticancer spectrum and is lesstoxic. In suspension, it exhibits some therapeu-tic effects on primary hepatic cancer, gastriccarcinoma, cancer of the urinary bladder andleukemia.

Effects of Chinese herbal medicine Yiqi Huaju Formula on hypertensive patients with metabolic syndrome:a randomized,placebo-controlled trial

BACKGROUND： Patients with hypertension coupled with metabolic syndrome （MetS） are among the high risk population in cardiovascular and cerebrovascular diseases. To reduce the prevalence of cardiovascular and cerebrovascular diseases, it is essential to appropriately control b^ood pressure together with other cardiovascular risk factors. OBJECTIVE： The current study was designed to investigate the therapeutic effects on blood pressure, blood pressure variability and other cardiovascular risk factors by giving Yiqi Huaju Formula, a compound traditional Chinese herbal medicine, in addition to routine treatment to hypertensive patients coupled with MetS. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： A total of 43 patients with hypertension coupled with MetS were recruited into this study. The enrolled patients were randomly divided into the Chinese herbal formula group （anti-hypertensive drugs plus Yiqi Huaju Formula, CHF） and the control group （anti-hypertensive drugs plus placebo）. The CHF group enrolled 22 patients while the control group received 21 cases. Treatments were given for 12 weeks in both groups. MAIN OUTCOME MEASURES： Parameters examined include 24-hour ambulatory blood pressure monitoring, body mass index, waist circumference, waist-to-hip ratio, homeostatic model assessment for insulin resistance （HOMA-IR）, fasting glycosylated hemoglobin （HbAlc）, fasting plasma glucose, 2-hour postprandial plasma glucose （PPG）, fasting plasma insulin, serum lipid, etc. RESULTS： Compared with the control group, the CHF group had significant improvement （P〈0.01） in anthropometric parameters, FPG, HOMA-IR, blood pressure amplitude, blood pressure variability and blood pressure load. CONCLUSION： This study showed that integrated traditional Chinese and Western medicine treatment can achieve better results in controlling blood pressure as well as other cardiovascular risk factors. The mechanism of controlling of blood pressure may be associated with the improvement of insulin sensitivity due to the Yiqi Huaju intervention. TRIAL REGISTRATION IDENTIFIER： ChiCTR-TRC-11001633.

Evaluation on the efficacy and safety of Chinese herbal medication Xifeng Dingchan Pill in treating Parkinson's disease: study protocol of a multicenter, open-label, randomized active-controlled trial

BACKGROUND： Parkinson＇s disease （PD） is a complicated disease, commonly diagnosed among the elderly, which leads to degeneration of the central nervous system. It presently lacks an effective therapy for its complex pathogenesis. Adverse effects from Western drug-based medical intervention prevent long-term adherence to these therapies in many patients. Traditional Chinese medicine （TCM） has long been used to improve the treatment of PD by alleviating the toxic and adverse effects of Western drug-based intervention. Therefore, the aim of this study is to evaluate the efficacy and safety of Xifeng Dingchan Pill （XFDCP）, a compound traditional Chinese herbal medicine, taken in conjunction with Western medicine in the treatment of PD patients at different stages in the progression of the disease. METHODS AND DESIGN： This is a multicenter, randomized controlled trial. In total, 320 patients with early- （n = 160） and middle-stage PD （n = 160） will be enrolled and divided evenly into control and trial groups. Of the 160 patients with early-stage PD, the trial group （n = 80） will be given XFDCP, and the control group （n = 80） will be given Madopar. Of the 160 patients with middle-stage PD, the trial group （n = 80） will be given XFDCP combined with Madopar and Piribedil, and the control group （n = 80） will be given Madopar and Piribedil. The Unified Parkinson＇s Disease Rating Scale scores, TCM symptoms scores, quality of life, change of Madopar＇s dosage and the toxic and adverse effects of Madopar will be observed during a 3-month treatment period and through a further 6-month follow-up period. DISCUSSION： It is hypothesized that XFDCP, combined with Madopar and Piribedil, will have beneficial effects on patients with PD. The results of this study will provide evidence for developing a comprehensive therapy regimen, which can delay the progress of the disease and improve the quality of life for PD patients in different stages. TRIAL REGISTRATION： This trial has been registered in the Chinese Clinical Trial Registry with the identifer ChiCTR-TRC-12002150.

Antidiarrheal properties of different extracts of Chinese herbal medicine formula Bao-Xie-Ning

OBJECTIVE： Bao-Xie-Ning （BXN）, a traditional Chinese herbal medicine （CHM） formula composed of Fructus Evodiae, Flos Caryophylli and Cortex Cinnamomi, and used for the treatment of infant diarrheal illness, was subject to systematic assessment for its putative multiple pharmacodynamic effects and pharmacological antidiarrheal mechanisms. METHODS： High-performance liquid chromatography-diode array detector-electrospray ionization- mass spectrometric/mass spectrometry was developed and validated for identification and quantification of the main constituents in different extracts of BXN. Male Kunming mice weighing 20 to 25 g were used for detecting the antidiarrheal activity of the extracts. Ethanolic extract （EE）, volatile oil extract （VOE）, and aqueous extract （AE） of BXN were respectively subjected to pharmacodynamic and pharmacological comparison in assessing antidiarrheal effects with senna-induced diarrhea, castor oil-induced diarrhea, acetic acid-induced writhing assay, and isolated duodenum test. RESULTS： The highest yields of three detected components of BXN, rutaecarpine, eugenol and cinnamaldehyde were observed in EE. EE showed the most remarkable antidiarrheal activity in dose-dependent and time-dependent manners in both senna- and castor oil-induced diarrhea models, and presented dose-dependent analgesic activity in acetic acid-induced algesthesia model. In addition, EE extract of BXN also exhibited strong antimobility action on the intestine and strongest depression on spontaneous contraction of isolated duodenum. CONCLUSION： Ethanol extraction is an efficient method to extract the active constituents of BXN. BXN extract demonstrated multiple pharmacological activities affecting the main mechanisms of diarrhea, which validated BXN＇s usage in the comprehensive clinical treatment of diarrhea.

Protective effects of components of the Chinese herb grassleaf sweetflag rhizome on PC12 cells incubated with amyloid-beta42

The major ingredients of grassleaf sweetflag rhizome are β-asarone and eugenol, which can cross the blood-brain barrier and protect neurons. This study aimed to observe the neuroprotective effects and mechanisms of β-asarone and eugenol, components of the Chinese herb grassleaf sweetflag rhizome, on PC12 cells. First, PC12 cells were cultured with different concentrations（between 1 × 10–10 M and 1 × 10–5 M） of β-asarone and eugenol. Survival rates of PC12 cells were not significantly affected. Second, PC12 cells incubated with amyloid-beta42, which reduced cell survival, were cultured under the same conditions（1 × 10–6 M β-asarone and eugenol）. The survival rates of PC12 cells significantly increased, while expression levels of the m RNAs for the pro-apoptotic protein Bax decreased, and those for the anti-apoptotic protein Bcl m RNA increased. In addition, the combination of β-asarone with eugenol achieved better results than either component alone. Our experimental findings indicate that both β-asarone and eugenol protect PC12 cells through inhibiting apoptosis, and that the combination of the two is better than either alone.

Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes

BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/reperfusion injury(MI/RI).Shuxin decoction(SXT)is a proven recipe modification from the classic herbal formula"Wu-tou-chi-shi-zhi-wan"according to the traditional Chinese medicine theory.It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting.However,the underlying mechanism is still unclear.AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.METHODS This paper presents an ensemble model combining network pharmacology and biology.The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT.In parallel,therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus,DisGeNet,Genecards,Drugbank,OMIM,and PharmGKB.The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation,Visualization and Integrated Discovery.The major results of bioinformatics analysis were subsequently validated by animal experiments.RESULTS According to the hypothesis derived from bioinformatics analysis,SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein(LDL)and inhibiting the advanced glycation end products(AGE)-receptor for AGE(RAGE)signaling pathway.Subsequent animal experiments confirmed the hypothesis.The treatment with a dose of SXT(2.8 g/kg/d)resulted in a reduction in oxidized LDL,AGEs,and RAGE,and regulated the level of blood lipids.Besides,the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated,whereas Bcl-2 expression was up-regulated.The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes.Moreover,animal experiments verified that SXT could regulate the level of blood lipids,alleviate cardiomyocyte apoptosis,and improve cardiac function through the AGE-RAGE signaling pathway.

Highlight of Publications on Chinese Traditional and Herbal Drugs in 2008

Chinese Traditional and Herbal Drugs (CTHD),also known as Zhongcaoyao,was founded in January 1970. There are 40 volumes,near 500 issues including supplemental to 2009 have been published. In 1992 it was awarded national core publication published in Chinese and kept the title to date via four times reevaluations at 1996,2000, 2004,and 2008. As one of

New Progress in Modern Research on Chinese Herbal Medicines Published in Chinese Traditional and Herbal Drugs in 2010:Annual Highlights and Comments

As a series of and continuous publication,the papers published on Chinese Traditional and Herbal Drugs in 2010 were selectively and briefly highlighted to reflect the new progress on modern research of Chinese herbal medicines.Within 617 articles,chemical constituents(127),pharmaceutics and technology(149),pharmacological studies and clinical observation,and medicinal materials are still major categories.Some comments have also been personally provided.

Introduction of Chinese Traditional and Herbal Drugs

The journal published monthly since January 1970 is an academic and technical journal sponsored by Chinese Pharmaceutical Association and Tianjin Institute of Pharmaceutical Research (TIPR). The journal which has a long history of 40-years offers the columns of research papers brief reports, reviews, dissertation, and special treatises to report the recent achievements of our basic study, production quality control, and clinic application on traditional Chinese medicine and Chinese materia medica.

Introduction of Chinese Traditional and Herbal Drugs

The journal, published monthly since January 1970, is an academic and technical journal sponsored by Chinese Pharmaceutical Association and Tianjin

Study on Effect of Chinese Herbal Medicine for Enhancing Therapeutic Efficacy on Refractory Drug Resistant Leukemia

The so-called multidrug resistance （MDR） of leukemic cells means the cross resistance of leukemic cells against multiple anti-tumor agents with different constitution and acting mechanism, which takes place simultaneous after resistance to a single contacted drug has been produced. Tumor cells with MDR would now show a low sensitivity to anti-tumor agents, making chemotherapy ineffective or of little effect. Moreover, MDR is one of the pathogenetic factors for inducing refractory leukemia.

Experimental study on the effect of Kang-Lai-Te induced apoptosis of human hepatoma carcinoma cell HepG2

BACKGROUND: Kang-Lai-Te (KLT) is extracted from the traditional Chinese herbal medicine Semen Coicis, which has been used in China as an effective clinical drug for over a thousand years. It contains numerous ingredients with anti-tumor effects. In our previous studies on transplanted hepatomas in rats, KLT could stop the cells in the G2+M stage of cell cycle and then reduce the number of cells entering the stage G0 and G1, but the mechanism of the anti-proliferative effect was unknown. In this experiment, we examined whether KLT inhibits HepG2 cell growth, if so, tried to explore its mechanism. METHODS: KLT at different concentrations was used for the treatment of hepatocellular carcinoma cells in vitro, respectively. The proliferation inhibitory rate was evaluated by MTT assay, induction of cell apoptosis rate and the protein levels of Fas and Fas ligand (FasL) were determined by flow cytometry (FCM), and the expression of Fas and FasL mRNA was detected by real-time fluorescent quantitative RT-PCR. RESULTS: KLT produced an obvious time and dose-dependent inhibitory effect on HepG2 cells, and marked apoptosis was detected by FCM The protein of Fas increased by 11.01%, 18.71%, 28.71% and 37.15%; the protein of FasL increased by 1.49%, 1.91%, 3.27% and 3.38% in comparison with the control (P<0.05). Real-time fluorescent quantitative RT-PCR showed that treating HepG2 cells with KLT caused the upregulation of Fas and FasL mRNA. CONCLUSION: KLT inhibits HepG2 growth by inducing apoptosis, which may be mediated through activation of the Fas/FasL pathway. (Hepatobiliary Pancreat Dis Int 2009; 8: 267-272)

Comparative efficacy and safety of Chinese herbal injections combined with transcatheter hepatic arterial chemoembolization in treatment of liver cancer: a bayesian network Meta-analysis

OBJECTIVE: To address the optimal Chinese herbal injections(CHIs) against liver cancer, the present network Meta-analysis is designed to investigate the comparative efficacy and safety of different CHIs.METHODS: Several electronic databases were searched up to June 1 st, 2017. The quality assessment was conducted and network Meta-analysis was performed to compare the efficacy and safety of different CHIs plus transcatheter hepatic arterial chemoembolization(TACE). Primary outcomes were 1-year and 2-year survival rate, the secondary outcomes includes the clinical effective rate, performance status and the adverse reactions(ADRs). Data analysis was applied Stata 13.0 and Win BUGS 1.4 software.RESULTS: A total of 105 randomized controlled trials(RCTs) were identified for inclusion in this analysis, with data for 7683 patients and 13 CHIs. The results suggested that Javanica oil emulsion,Huachansu injection plus TACE were more favorable for 1-year and 2-year survival rate than other CHIs. Kanglaite, Astragalus polysaccharide injection plus TACE showed superiority in the clinical effective rate and performance status over other CHIs.And Shenmai injection plus TACE was superior to reducing ADRs than other CHIs for patients with liver cancer.CONCLUSION: Our findings indicated that receiving CHIs combined with TACE may have therapeutic benefits for patients with liver cancer in improving survival rate, clinical effective rate, the performance status and alleviating the ADRs.

Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-β1 signaling pathway

OBJECTIVE： To investigate the tumor inhibition effect of Yangfei Kongliu Formula （YKF）, a compound Chinese herbal medicine, combined with cisplatin （DDP） and its action mechanisms. METHODS： C57BL/6 mice with Lewis lung carcinoma were divided into six groups： control group （C）, DDP group （2 mg/kg, DDP）, low-dose YKF group （2.43 g/kg, L）, high-dose YKF group （24.3 g/kg, H）, low- dose YKF combined with DDP group （L ＋ DDP） and high-dose YKF combined with DDP group （H ＋ DDP）. Transforming growth factor-β1 （TGF-β1）, mothers against decapentaplegic homolog 3 （Smad3） and Smad7 levels were measured with quantitative real-time polymerase chain reaction （qPCR）, Western blotting and immunohistochemistry. An enzyme-linked immunosorbent assay was used to analyze the expressions of interleukin-2 （IL-2） and tumor necrosis factor-α （TNF-α）. RESULTS： YKF combined with DDP significantly inhibited the growth and metastasis of tumors relative to the control group, and YKF groups （P 〈 0.05）. There was no significant difference between high-dose YKF group and low-dose YKF group （P 〉 0.05）. We also found that the expression levels of TGF-β1 and Smad3 were both significantly decreased by YKF relative to the control group （P 〈 0.05）. Furthermore, after treatment with YKF combined with DDP, the expression levels of TGF-β1 and Smad3 were decreased but the expression level of Smad7 was increased relative to the DDP group （P 〈 0.05）. Compared to the DDP group, the combination of YKF and DDP enhanced the effect of tumor inhibition （P 〈 0.05）, showing obvious synergy between YKF and DDP. Treatment with DDP or YKF decreased serum levels of IL-2 and TNF-α relative to the control group （P 〈 0.05）. Furthermore, the expression levels of IL-2 and TNF-α were significantly decreased when treated with YKF in combination with DDP. Co-treatment with YKF and DDP significantly inhibited tumor growth, decreased the expressions of TGF-β1, Smad3, IL-2 and TNF-α and increased the expression of Smad7; these differences were significant relative to both YKF groups and the control group （P 〈 0.05）. CONCLUSION： YKF can inhibit tumor growth synergistically with DDP, mainly through the TGF-β1 signaling pathway.

Efficacy of Rebixiao Chinese herbal tablets and Chinese formula granules in acute gout arthritis patients:a randomized,multicenter,double-blind,controlled trial

OBJECTIVE:To evaluate the clinical efficacy and safety of Rebixiao(RBX)Chinese herbal tablets(CHT)and Chinese formula granules(CFG)in the treatment of acute gout arthritis(AGA).METHODS:This randomized,multicenter,double-blind,controlled trial included 165 AGA patients with the damp-heat symptom pattern who were randomly divided into an RBX CHT group and an RBX CFG group and treated for 7 d at three centers.The total effective rates of the joint symptom score,Traditional Chinese Medicine(TCM)symptoms score,erythrocyte sedimentation rate(ESR),and C-reactive protein(CRP)were used to evaluate the clinical efficacy.Safety assessments were also performed.RESULTS:Of the 165 enrolled patients,147 completed the clinical observation.There was no difference in baseline between the two groups.The total effective rates of the joint symptom score were 94.36%and 97.36%,and the total effective rates of the TCM symptoms score were 95.77%and 97.36%in the CFG group and CHT group,respectively.No statistical difference was found between the two groups(P>0.05).Additionally,ESR and CRP were similar in both groups(P>0.05).Furthermore,treatment efficacy regarding TCM and joint symptoms,the ESR,and CRP were consistent within each center and among the different centers(P>0.05).In addition,the incidence of adverse events was 4.22%and 2.63%in the CFG group and CHT group,respectively,and no difference was observed between the two groups(P>0.05).CONCLUSION:RBX CFG and CHT have significant and similar efficacy in the treatment of AGA,and CFG did not increase adverse side effects.

Enhancing the treatment of metabolic syndrome with integrative medicine

Metabolic syndrome, with the main clinical manifestations of obesity, dyslipidemia, elevated blood pressure, and elevated blood glucose levels, has become an increasingly prevalant global public health concern. Metabolic syndrome is a convergence of multiple risk factors related to cardiovascular disease. When the concept of metabolic syndrome was initially proposed, some researchers thought the concept was unnecessary, since there were already measures in place to describe the separate cardiovascular risk factors such as dyslipidemia, hypertension and diabetes. However, a large number of epidemiological investigations confirmed that even if blood glucose or blood pressure did not reach the cutoff point of the diseases,

Hepatic veno-occlusive disease induced by Gymura segetum: report of two cases

BACKGROUND: Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome is associated with a high mortality because of its severity. Gymura segetum, a Chinese herbal medicine, is always used to cure injury and bleeding in rural areas in China. This study was undertaken to better understand VOD and its relations to the effect of Gymura segetum. METHODS: Between 2000 and 2002,two patients were admitted to our department because of VOD. Before admission, both of them had been injured and taken oral decoction of patent drug Gymura segetum. We analyzed the clinical manifestations, diagnosis and therapy of the two patients. RESULTS: Pyrrolizidine in Panax notginseng was proved to induce VOD. The diagnosis of VOD depended on hepatic biopsy. CONCLUSION: Gymura segetum can induce VOD. More attention should be paid to its unsuscepted side effects.

Traditional Chinese medicine for treatment of liver diseases: progress, challenges and opportunities

Traditional Chinese medicine （TCM） is commonly used in treating liver diseases worldwide, especially in China. The advantages of using TCM for treatment of liver diseases include： protecting hepatocytes, inhibiting hepatic inflammation and antifibrosis in the liver. In this article, we introduce TCM herbal preparations from the Chinese materia medica （such as Fuzheng Huayu） that are typically used for the treatment of liver diseases. Literature surrounding the mechanisms of TCM therapy for treatment of liver diseases is presented and discussed. We propose that side effects of herbal compounds are often under-appreciated, and that more care should be taken in the prescription of potentially hepatotoxic medicines. Further, to deepen the understanding of TCM mechanisms, new techniques and methodologies must be developed. Future studies will lead to the enhancement of clinical outcomes of TCM. As complementary and alternative therapies, TCMs will play an expanding role in the future of liver disease treatment.

Autophagy in cerebral ischemia and the effects of traditional Chinese medicine

Autophagy is a lysosome-mediated degradation process for non-essential or damaged cellular constituents, playing an important homeostatic role in cell survival, differentiation and development to maintain homeostasis. Autophagy is involved in tumors as well as neurodegenerative, cardiovascular and cerebrovascular diseases. Recently, active compounds from traditional Chinese medicine （TCM） have been found to modulate the levels of autophagy in tumor cells, nerve cells, myocardial cells and endothelial cells. Ischemic stroke is a major cause of neurological disability and places a heavy burden on family and society. Regaining function can significantly reduce dependence and improve the quality of life of stroke survivors. In healthy cells, autophagy plays a key role in adapting to nutritional deprivation and eliminating aggregated proteins, however inappropriate activation of autophagy may lead to cell death in cerebral ischemia. This paper reviews the process and the molecular basis of autophagy, as well as its roles in cerebral ischemia and the roles of TCM in modulating its activity.

Interventional mechanisms of herbs or herbal extracts on renal interstitial fibrosis

Renal interstitial fibrosis（RIF） is a common development in chronic renal diseases that can lead to uremia and be life-threatening. The RIF pathology has complicated extracellular and intercellular mechanisms, involving many cells and cytokines, resulting in an incomplete mechanistic understanding of the disease. Finding effective herbs or herbal extracts for prevention and treatment of RIF is crucial because current medical approaches do not reliably slow or reverse RIF. In recent years, many experts have worked to identify herbs or herbal extracts to combat RIF both in vivo and in vitro, with some success. This review attempts to summarize the possible interventional mechanisms of herbs or herbal extracts involved in protecting and reversing RIF. The authors found some herbs and their extracts that may ameliorate renal impairments through anti-inflammation, anti-fibrogenesis and stabilization of extra cellular matrix. Among them, tetramethylpyrazine/ligustrazine, curcumin and polyglucoside of Tripterygium have experimentally shown good potential for improving RIF. However, conclusive evidence is still needed, especially in randomized controlled clinical trials. We expect that herbs or herbal extracts will play an important role in RIF treatment and reversal in the future.