Meaning， Efficacy and Mechanism of Huoxin Pills in Treating Coronary Heart Disease with Qi Deficiency and Blood Stasis Syndrome / 中国实验方剂学杂志

Cardiovascular diseases， with high incidence and high mortality， belong to the category of "chest impediment and heart pain" in traditional Chinese medicine （TCM）. Chinese medicines have unique effect on the prevention and treatment of cardiovascular diseases with little side effects. Huoxin pills， one of the National Essential Drugs， is formulated based on the basic pathogenesis of weak pulse at Yang and wiry pulse at Yin and the pathological basis of myocardial ischemia and hypoxia and used for treating angina pectoris of coronary heart disease （Qi deficiency and blood stasis syndrome）. This medicine is derived from the classic famous prescription and is composed of ten precious Chinese medicinal herbs. It can replenish Qi， activate blood， and warm collaterals to diffuse impediment by enhancing myocardial contractility and cardiac output to improve micro-circulation and increase coronary blood flow， regulating immune functions， alleviating inflammation， detoxifying， and tranquilizing mind. Clinically， it is suitable for patients with angina pectoris caused by the lack of heart Yang， chest tightness， shortness of breath， palpitation， fear of cold for limbs and so on， especially for the elderly with Yang deficiency or the patients with a history of myocardial infarction. On the basis of the available research reports， this paper explains the formula meaning of Huoxin pills from the perspective of the basic pathogenesis of coronary heart disease and predicts its action targets， location and links. Furthermore， we expound the mechanism of action of Huoxin pills based on basic research and clinical evidence-based research， aiming to provide data support and evidence for the clinical application of this medicine.

Systematic Review and Sequential Analysis on Efficacy of Modified Buyang Huanwu Tang in Treatment of Chronic Heart Failure / 中国实验方剂学杂志

Objective:To systematically evaluate the efficacy and safety of modified Buyang Huanwu Tang in the treatment of chronic heart failure. Method:CNKI database，Wanfang database，VIP database，Pubmed，MEDLINE，EMBASE and Cochrane database were retrieved systematically. The literature retrieval period is from no limit to December 2019，with "Buyang Huanwu Tang" and "chronic heart failure" "heart failure" as the key words for full-text retrieval of Chinese and English databases. Literatures of randomized controlled trials（RCTs） for chronic heart failure were included， and the data were extracted. Cochrane system evaluation method was used to score the quality of literature. Stata 14.0 was applied in Meta-analysis on the retrieval results. TSA0.9 was applied in test sequential analysis. Sensitivity analysis was made to explain heterogeneity，and funnel chart was used to evaluate publication bias. Result:A total of 2 037 patients were included in 21 RCT studies. The article quality risk assessment was generally unclear risk of bias. The results of meta-analysis showed that the left ventricular ejection fraction （LVEF） in the experimental group was significantly higher than that in the control group，with statistically significant differences ［MD=0.901，95% CI （0.772，1.029），P<0.01］，the left ventricular end diastolic diameter （LVEDd） in the experimental group was significantly lower than that in the control group，with statistically significant differences ［OR=-0.650，95% CI=（-0.854，-0.446），P<0.01］，BNP in the experimental group was significantly lower than that in the control group，with statistically significant differences ［MD=-1.212，95% CI=（-1.359，-1.066），P<0.01］，6-minute walk test （6MWT） in the experimental group was significantly higher than that in the control group，with statistically significant differences ［MD=0.797， 95% CI=（0.447，1.146），P<0.01］，and the effective rate in the experimental group was significantly improved，with statistically significant differences ［OR=1.840，95% CI=（1.680，2.016），P<0.01］. Conclusion:Modified Buyang Huanwu Tang combined with conventional western medicine treatment of chronic heart failure is more effective than single administration of western medicine treatment，and can improve clinical efficacy， effectively improve the LVEF of patients with chronic heart failure，reduce the LVEDd reduces plasma BNP levels，prolong the 6-minute walking distance，and reduce the incidence of adverse reactions.

Effect of Triptonide on Proliferation and Apoptosis of SHI-1 Cells / 中国实验方剂学杂志

Objective:This study aims to investigate the effect of triptonide （TN） on proliferation， cell cycle， apoptosis and expressions of apoptosis-related proteins of human acute monocytic leukemia（AML） cell line SHI-1， and to explore its possible mechanism of action. Method:The thiazolyl blue （MTT） colorimetric assay was applied to detect the inhibitory effect of 20，40，80，160，320 nmol·L^-1 triptonide on the proliferation of SHI-1 cells for 48， 72 h. Changes in SHI-1 cell cycle before and after triptonide treatment were detected by flow cytometry propidium iodide （PI） simple staining， and changes in SHI-1 cell apoptosis before and after triptonide treatment were detected by flow cytometry with AnnexinV/PI double staining. Western blot was applied to detect the protein expression of cysteine protease （Caspase）-3， Caspase-8 and nuclear transcription factor kappaB（NF-<italic>κ</italic>B） in SHI-1 cells before and after treatment with 80， 160 nmol·L^-1triptonide. Result:Compared with the blank group， 40，80，160，320 nmol·L^-1 triptonide significantly inhibited the proliferation of SHI-1 cells（<italic>P</italic><0.01） in a dose-dependent manner for 48， 72 h， while 160， 320 nmol·L^-1 triptonide induced apoptosis of SHI-1 cells（<italic>P</italic><0.01） for 48， 72 h， and 160 nmol·L^-1 triptonide could decrease the S phase ratio of SHI-1 cells（<italic>P</italic><0.01）. In addition， compared with the blank group， 80，160 nmol·L^-1 triptonide induced the downregulation of NF-<italic>κ</italic>B significantly（<italic>P</italic><0.01）， 160 nmol·L^-1 triptonide induced the downregulation of Caspase-3， Caspase-8 significantly（<italic>P</italic><0.01）. Conclusion:Triptonide can inhibit the proliferation and induce apoptosis <italic>in vitro</italic> of SHI-1 cells， which may be related to the reduction of the cells in S phase proportion by triptonide， and the downregulation of the expression levels of Caspase-3， Caspase-8 and NF-<italic>κ</italic>B proteins.

Research Progress on Pharmacological Activities and Mechanism of Triptonide / 中国实验方剂学杂志

The root of Tripterygium wilfordii has the effect in dispelling wind and eliminating dampness. Now it is mostly used in the treatment of systemic lupus erythematosus and other diseases. Triptonide is a diterpene small molecule compound extracted from T. wilfordii. In the early years， it was studied as a potential drug with anti-inflammatory and anti-reproductive effects. Recently， researchers found that its anti-tumor effect was particularly prominent because triptonide could inhibit the growth of a variety of tumors with different mechanisms at the nanomole dose， with a potential to be used as a broad-spectrum anti-cancer drug. In addition， due to the low yield from T. wilfordii， low bioavailability due to poor water solubility and anti-reproductive side effect as an antitumor drug， it will become study hotspots to exploring its synthesis and preparation and modifying its structure to reduce cost， improve bioavailability and reduce side effect， while maintaining its pharmacological activity. The authors reviewed domestic and foreign studies and patents on triptonide， and summarized its pharmacological activity and mechanism. It is found that although current studies on triptonide are still in the preliminary stage， there have been increasingly more studies on its anti-tumor mechanism year by year since 2014. This paper mainly introduces the antitumor pharmacological activity and mechanism of triptonide. In addition， it reviews anti-inflammatory， immunosuppression and anti-reproductive pharmacological effect of triptonide， as well as the existing studies on its toxicity， synthesis and structural modification. The authors put forward some personal ideas on its future study direction， in the hope to provide thinking and inspirations for other researchers and provide references for further development and research.

Research Progress on Pharmacological Effect and Mechanism of Imperatorin / 中国实验方剂学杂志

Imperatorin, which is extracted from umbelliferous plants such as Radix Angelicae Dahuricae, Radix Saposhnikoviae and Fructus Cnidii, belongs to furanocoumarins and is especially rich in Radix Angelicae Dahuricae. Research has shown that imperatorin possesses functions of anti-inflammatory, analgesic, antibactrial, antiviral, antiallergic, anti-tumor, reverse drug resistance in tumor cells, interaction with drug metabolizing enzymes, affecting cardiovascular and nervous system effect. It is also one of the standard components in quality control of various analgesics. In recent years, research findings related to imperatorin is increasing fast. A number of patent applications have been approved for the application of imperatorin in the treatment of anti-tumor and cardiovascular diseases. In addition, since the water insolubility of imperatorin affects its bioavailability, most researchers have gradually attached importance to this aspect of research, such as modifying its structure or synthesizing its derivatives. The literatures on the pharmacological effects and mechanisms of imperatorin at home and abroad in recent years were consulted and summarized in this paper. Imperatorin was found not only to display other pharmacological effects like furanocoumarins but also could cure osteoporosis, skin diseases and show photosensitization. Moreover, the mechanism of its action has the effect of multi-pathway and multi-target, but most of the studies have not identified its targets, which still needs further study. Extensive and significant pharmacological effect make imperatorin show a great potential for development of new drugs. This paper reviews the basic properties, the progress on pharmacological effects and mechanisms of imperatorin, proposes the research status and direction of future reseach. Hopes to provide ideas for researchers and beneficial references for the future development and utilization of imperatorin.

Effect of Arsenic Trioxide Combined with Dihydroartemisinin on THP-1 Cells Proliferation and Apoptosis / 中国实验方剂学杂志

Objective:To investigate the effects of arsenic trioxide combined with dihydroartemisinin on proliferation, cell cycle, and apoptosis of THP-1 cells, and explore the mechanism. Method:The thiazolyl blue （MTT） method was applied to detect the effect of different concentrations of arsenic trioxide, dihydroartemisinin and arsenic trioxide combined with dihydroartemisinin on the proliferation of THP-1 cells. Annexin V/propidium iodide（PI）assay was used to detect the change of THP-1 cell cycle and apoptosis．Western blot was performed to assess the expression of cysteine protease-3（Caspase-3）, cleaved Caspase-3, B-lymphocytoma-2（Bcl-2） and Bcl-2 associated X protein （Bax）. The changes of cell morphology were observed under high intension microscope. Result:Compared with blank group, arsenic trioxide and dihydroartemisinin both exhibited obvious antiproliferative effect on the human acute monocytic leukemia cell line THP-1 in time-dose dependence （P<0.01）. After 48 h, compared with the same dose of arsenic trioxide or that of dihydroartemisinin alone, the inhibition effect of 1 µmol·L-1 arsenic trioxide combined with 2 µmol·L-1 dihydroartemisinin on proliferation of THP-1 cells was significantly stronger （P<0.01）. Compared with the control group, arsenic trioxide combined with dihydroartemisinin significantly arrested the cells in G1 phase （P<0.01）, induced the downregulation of Caspase-3 and Bcl-2 （P<0.01） and upregulation of cleaved Caspase-3 significantly（P<0.05）. Conclusion:Arsenic trioxide combined with dihydroartemisinin can significantly inhibit the proliferation and induce apoptosis of THP-1 cells. The possible mechanism may be related to arrest the cells in G1 phase, reduce the expression of Caspase-3 and Bcl-2, increase the expression of cleaved Caspase-3.

Clinical Research Progress of Traditional Chinese Medicine in Treating High-normal Blood Pressure / 中国实验方剂学杂志

The incidence of high-normal blood pressure gradually increased. With the popularization of basic medical knowledge， the detection rate has increased. Without intervention， high-normal blood pressure is very likely converted into hypertension， and the risk of cardiovascular and cerebrovascular diseases will continue to rise. Studies have shown that the blood lipids for detection of people with high-normal blood pressure， cytokines and other laboratory indicators have been changed， causing certain damage to target organs. Normal-high blood pressure people and high-blood pressure people also need to be given attention. Traditional Chinese medicine （TCM） believes that high-normal blood pressure has intermingled deficiency and excess， which is closely correlated to the liver， spleen and kidney. The syndrome is constantly changing and developing in the course of disease， which is affected by physical fitness， environment， age and other factors. With respect to treatment， conventional western medicine for lowering blood pressure has not yet been incorporated into the guidelines， and exercise， diet， and health education still play a major role. Studies have shown that the intervention methods with TCM characteristics are applied in addition to the improvement of lifestyle， so as to intervene in people with high-normal blood pressure， such as TCM， acupuncture， herbal tea， Baduanjin， with a significant clinical effect. These therapies can effectively reduce blood pressure， improve symptoms， regulate physique， and protect target organ damage， with a good compliance. With the advantages in preventing the disease， TCM is of far-reaching significance to prevent disease in advance， and transform high-normal blood pressure into ideal blood pressure. Based on the study on the intervention of high-normal blood pressure with TCM therapy， it was found that the sample size was small and the preciseness needed to be improved. Further research is needed due to the complicated mechanism of TCM and acupuncture. There is a lack of insufficient evidence to support the long-term efficacy and safety of TCM therapy because of the limitations in clinical study intervention and follow-up time. This article reviews the clinical research of the effect of TCM on high-normal blood pressure， in order to provide guidance and reference for clinical and subsequent research.

Effect and Mechanism of Dihydroartemisinin on Rheumatoid Arthritis Animal Models / 中国实验方剂学杂志

Objective:To study the protective effect of dihydroartemisinin (DHA) on adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) in rats, in order to explore its possible mechanism. Method:Wistar rats were randomly divided into eight groups, namely AIA control group, AIA model group, AIA DHA group and AIA methotrexate group, CIA control group, CIA model group, CIA DHA group and CIA methotrexate group. To establish adjuvant-induced arthritis (AIA) model, rheumatoid arthritis rats were induced through intradermal injection with 0.1 mL Freund's complete adjuvant (FCA) into right postpedes except for the control group. To establish the model of collagen-induced arthritis (CIA), except for control group, the caudal root of rats was immunized subcutaneously with 0.2 mL of emulsion containing 1 g·L-1 of Collagen type Ⅱ (CⅡ). One week later, CⅡ emulsion was injected for the second time. After the rheumatoid arthritis model was successfully established and the administration with DHA (30 mg·kg-1·d-1), the anti-inflammatory effect of DHA on AIA/CIA rats was observed, including the arthritis index (AI), paw swelling degree and effect of DHA on immune organ index of AIA/CIA rats. Interleukin (IL)-6 levels in serum was detected by enzyme-linked immunosorbent assay (ELISA) and pathological sections of ankle joints of AIA/CIA rats. RAW264.7 macrophage cells were cultured in vitro and treated with DHA at various doses (0.5, 1, 2, 4, 8, 16 μmol·L-1) for 24 h, and the cell viability was detected by methyl thiazolyl tetrazolium(MTT) assay. Lipopolysaccharides (LPS) group, LPS+DHA groups (0.5, 1, 2 μmol·L-1) and control group were established. The level of IL-6 was detected by enzyme-linked immunosorbent assay(ELISA). The protein expression levels of nuclear transcription factor-κB p65 (NF-κB p65) was tested by Western blot. Result:Compared with control group, the paw swelling, AI, spleen index and IL-6 levels of model group were significantly increased (PPPPPPPP-1) groups had a remarkable effect on the cell viability (PP-1. The level of IL-6 and the protein expression of NF-κB p65 in LPS group were higher than those of control group. Compared with LPS group, DHA (0.5 μmol·L-1) groups could significantly reduce the secretion of IL-6 (PκB p65. Conclusion:DHA can alleviate the ankle joint lesion on rheumatoid arthritis rats. Its mechanism may be related to NF-κB signal pathway.

Preliminary study on antibacterial activity of artemisinin and its derivatives / 中国中药杂志

In this study,in order to detect the antimicrobial activity of artemisinin and its derivatives artesunate and dihydroartemisinin,two methods including broth dilution and plate punching method were used to detect the antibacterial activity against gram-negative bacteria(Escherichia coli)and gram-positive bacteria(Staphylococcus aureus)of artemisinin,dihydroartemisinin and artesunate at various concentrations within 5 mmol·L~(-1)and at four time points(8,16,24,32 h).Two antibacterial positive drugs,streptomycin against E.coli and penicillin against S.aureus,were used as positive controls.Plate punching method showed that,unlike the results of 5 mmol·L~(-1)dihydroartemisinin or artesunate,no inhibition zone was detected at the same concentration of artemisinin after 24 h-treatment against E.coli.Broth dilution method showed that,the antibacterial activity of dihydroartemisinin against E.coli.was stronger than those of both artesunate and artemisinin;IC_(50)at24 h-treatment was 155.9μmol·L~(-1)for dihydroartemisinin,370.0μmol·L~(-1)for artesunate and none for artemisinin.Interestingly,dihydroartemisinin and artesunate showed the strongest antibacterial activity between 16-24 h,while artemisinin showed relatively stronger antibacterial activity between 8-16 h.Dihydroartermisinin showed no antibacterial activity against S.aureus.Above all,the antibacterial activity of artemisinins against E.coli is dihydroartemisinin>artesunate>artemisinin.Artemisinin and its derivatives have showed different antibacterial kinetics,and no antibacterial activity against S.aureus.has been detected with dihydroartemisinin.

Mechanism of anti-endotoxemia based on LPS-TLR4 signaling pathway:research advances / 国际药学研究杂志

Toll-like receptors 4(TLR4),an important member of the TLR family,is considered as gene encoding LPS recep?tors,and major receptors for identifying lipopolysaccharide(LPS).LPS-induced TLR4 signaling pathway plays a key role in endotox?emia.After TLR4 activated by LPS,the mitogen-activated protein kinase(MAPK)signaling pathway and nuclear transcription factor κB(NF-κB)are activated and large amounts of inflammatory factors are released,triggering inflammatory cascade reaction.This arti?cle reviews the mechanisms of endotoxemia in treatment based on TLR4 signal pathway in three perspectives:the effects of LPS-TLR4 signaling pathway on the upstream target proteins,LPS-induced TLR4 signal transduction,and the downstream target proteins regulat?ed by LPS-TLR4 signaling pathway.