Research Progress and Research Ideas on Anti-hepatic Fibrosis and Promoting Blood Circulation and Removing Blood Stasis of the National Drug Plumbapin Based on TLR4 Signal Pathway

Hepatic fibrosis is a reversible pathological phenomenon in the early and middle stages,but but no satisfactory intervention drugs have been available so far.Recent studies have suggested that microcirculation disturbance of liver is one of the important pathogenesis of chronic liver disease,the improvement of microcirculation is beneficial to the recovery of liver function and the delay of liver fibrosis.Hepatic stellate cells are the core cells of hepatic fibrosis,and also the most critical cells that affect the microcirculation of the liver.While TLR4/MyD88/NF-κB and TLR4/MyD88/MAPKs which are based on the action of hepatic stellate cells are two pathways that have very important influence on the inflammatory response of liver,the proliferation and apoptosis of hepatic stellate cells,and the secretion of fibrogenic cytokines.It was found that Plumbapin,the active ingredient of Guangxi specialty ethnic medicine,has the definite effect of promoting blood circulation and removing blood stasis and anti-hepatic fibrosis,but its mechanism is not clear.In this study,the research progress of the above problems was reviewed,and further research ideas were derived as follows:the pharmacological effect of Plumbapin on anti-hepatic fibrosis,promoting blood circulation and removing stasis was based on the influence of TLR4/MyD88/NF-κB and MAPKs signal pathway.

Revealing the material basis of MMP9-mediated activating blood and removing blood stasis drugs on Danshen-Ligusticum chuanxiong anti- vascular effect

Objective:Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners.Methods:The effective components of Danshen and chuanxiong were searched in the TCM System Pharmacology Database(TCMSP),and the drug targets were searched in the Swiss Target Prediction database;in the Disease-Gene Database(DisGeNET))Search for angiogenesis-promoting and inhibiting angiogenesis targets;use the protein interaction database(STRING)database and Cytoscape software to analyze the network core targets;use the DAVID database to enrich the drug-disease target intersection for GO and KEGG;RT-qPCR experiments verified the effect of luteolin on MMP9 gene expression;in vitro tube formation experiments analyzed the effect of luteolin on endothelial cell neovascularization.Results:After analysis,it is concluded that Danshen has 10 active ingredients and 50 angiogenesis targets;Chuanxiong has 2 active ingredients and 4 angiogenesis targets.The intersection of drug-taking targets yielded 9 targets,including AR,PARP1,MMP9,MMP2,MMP12,AKR1B10,ABCC1,CDK6,and STAT3.After analyzing the active ingredient-target network graph of Danshen/Chuanxiong,it was concluded that luteolin is the key chemical ingredient.After protein interaction(PPI)analysis,the results showed that MMP9 is the core target.The KEGG pathway is mainly enriched in 5 signaling pathways,the most important pathway is cancer-related pathways.There are 22 main biological processes of GO,which mainly involve collagen catabolism,protein extracellular matrix,metal endopeptidase activity,etc.The preliminary analysis of tubule formation experiment shows that luteolin inhibits angiogenesis and down-regulates the expression of MMP9 gene.Conclusion:Luteolin,the key chemical component of the Danshen-Ligusticum chuanxiong drug pair,inhibits angiogenesis by regulating the MMP9 target,and develops the reverse regulation of angiogenesis for the traditional Chinese medicine for promoting blood circulation and removing blood stasis on the basis of the known treatment of ischemic diseases.Provide a new perspective and theoretical basis for the use of Danshen and Chuanxiong medicine in clinical cancer patients.Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners.

Efficacy and safety of activating blood circulation and removing blood stasis of Traditional Chinese Medicine for managing renal fibrosis in patients with chronic kidney disease:a systematic review and Meta-analysis

OBJECTIVE:To evaluate the efficacy and safety of activating blood circulation and removing blood stasis in terms of Traditional Chinese Medicine(TCM) for managing renal fibrosis(RF) in patients with chronic kidney disease(CKD).METHODS:We searched randomized controlled trials(RCTs) from eight databases.RESULTS:Sixteen eligible studies with 1,356 participants were included in this study.Compared to treatment with Western Medicine(WM) alone,the combined treatment with activating blood circulation and removing blood stasis in terms of TCM(ARTCM) and WM to manage RF in patients with CKD significantly ameliorated type Ⅳ collagen(C-Ⅳ)(SMD:-2.17,95% CI:3.01 to-1.34),type Ⅲ procollagen(PC-Ⅲ)(SMD:-1.08,95% CI:-1.64 to-0.53),laminin(LN)(SMD:-1.28,95% CI:-1.65 to-0.90),transforming growth factor β 1(TGF-β1)(SMD:-0.65,95% CI:-1.18 to-0.12),serum creatinine(Scr)(SMD:-1.36,95% CI:-1.85 to-0.87),blood urea nitrogen(BUN)(MD:-1.51,95% CI:-2.59 to-0.43),and 24 h urine protein(24h Upro)(SMD:-1.23;95% CI:-1.96 to-0.50).The level of hyaluronic acid(HA) was similar in both types of treatment(SMD:-0.74,95% CI:-1.91 to 0.44).The subgroup analysis showed that the duration of 8 weeks might affect the concentration of C-Ⅳ,PC-Ⅲ,and LN(P < 0.05).The effectiveness of the longer duration to C-Ⅳ,PC-Ⅲ,and LN was not certain.However,the result should be interpreted in care.The safety of the treatment using ARTCM and WM could not be evaluated because a few studies had reported adverse effects.The results of the Meta-analysis were not stable enough.There was publication bias for the reports on Scr(P = 0.001),C-Ⅳ(P = 0.001),PC-Ⅲ(P = 0.026),and LN(P = 0.030) and no publication bias for the reports on BUN(P = 0.293).The quality of evidence varied from low to very low.CONCLUSIONS:The combined treatment using ARTCM and WM to manage RF in patients with CKD has some advantages over treatment with WM alone.High-quality RCTs need to be conducted for the strong support.

Research Progress in Chinese Medicine Preparations for Promoting Blood Circulation and Removing Blood Stasis for Cirrhotic Patients with Portal Vein Thrombosis Following Splenectomy

This article presented an overview of the therapeutic effects of Chinese medicine(CM)preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis(PVT)after splenectomy.Based on published clinical researches of CM preparations for PVT after splenectomy in patients with cirrhotic portal hypertension(CPH),this paper evaluated the incidence of PVT,and explored potential active components and mechanisms of CM preparations.Safflower Yellow Injection,Danshen Injection,Danhong Injection,and Compound Danshen Dropping Pill achieved good curative effect alone or combined with anticoagulant therapy.In addition,Compound Biejia Ruangan Tablet and Anluo Huaxian Pill can also significantly improve the hemodynamic disorders of portal vein system in patients with cirrhosis.Considering the role of CM preparations in ameliorating the incidence of PVT after splenectomy in patients with CPH,we suggested that future research should provide more attention to CM alone or CM combined with anticoagulant for cirrhosis with PVT.

A PROSPECTIVE STUDY TO EVALUATE THE SAFETY AND EFFICACY USING REMOVING BLOOD STASIS HERBALS FOR PATIENTS WITH INTRACRANIAL HEMORRHAGE OF HYPERACUTE STAGE AND RELATIVE FACTORS OF HEMATOMA ENLARGEMENT(A MULTICENTER PROSPECTIVE RANDOMIZED DOUBLE-BLIND PLACEBO

The aim was to investigate whether using a removing blood stasis method in hyperacute intracranial hemorrhage stage can lead to hematoma enlargement and its clinical efficacy.A multicenter retrospective randomized double-blind placebo-controlled clinical study.We recruited patients aged 18 years or older and presenting at less than 6 h from symptom onset in 8 research centers.All the patients

Clinical Observation on Patients with Endometriosis Treated by Tonifying Kidney and Removing Blood Stasis

Objective: To explore the mechanism of treating endometriosis by tonifying Kidney and removing blood stasis with Neiyixiao recipe, ( , NYXR).Methods: One hundred and three patients of endometriosis were divided randomly into the NYXR group (58 cases, treated with NYXR) and the control group (45 cases, treaed with danazol) and were reviewed for the improvement of clinical symptoms, serum level of FSH, LH, PRL, E2, P and T, humoral and cellular immunity (C3, C4, CD3, CD4, CD8), and plasma prostaglandin after treatment.Results: There was no significant difference in effect between the NYXR group and the control group in relief of dysmenorrhea and degradation of elevated plasma prostaglandin (x2 = 0.71,P >0.05). But there was significant difference between the two groups in curing infertility (x2 = 14.77, P<0. 01), and the effect of NYXR in regulating endocrine and immunity was significantly better than that of danazol.Conclusion: By tonifying Kidney and removing blood stasis, NYXR is multi-effective and being one of effective methods in clinical practice for treatment of endometriosis.

Clinical Observation on Influence of Chinese Medicines for Promoting Blood Circulation to Remove Blood Stasis on FIB and DD in Plasma of Patients with Cerebral Thrombosis

Objective: to study the influence of Chinese medicines for promoting blood circulation to remove blood stasis on fibrinogen (FIB) and D-dimer (DD) in plasma of patients with cerebral thrombosis. Method: 73 inpatients with acute cerebral thrombosis were randomly divided into a control group of 34 cases and a treatment group of 39 cases. The content of FIB and DD in plasma was detected before treatment and on the 7th and 14th days after treatment. Result: FIB content in plasma after treatment was lower than that before treatment in the control group (P<0.01) and more remarkable in the treatment group (P<0.001). There was an obvious difference in DD content before and after treatment in both groups. DD content on the 7th and 14th days after treatment in the treatment group was obviously higher than that in the control group (P<0.01 and P<0.05 respectively). Conclusion: Chinese medicines for promoting blood circulation to remove blood stasis can reduce the FIB content in plasma of patients with cerebral thrombosis, raise the DD content in plasma, cause the peak of DD content appear earlier and obviously improve hypercoagulability of blood in patients with cerebral thrombosis.

Treatment of Hypertensive Cerebral Hemorrhage by Activating Blood Circulation to Remove Stasis

The treatment of hy-pertensive cerebral hemorrhage(HCH)by activatingblood circulation to removestasis(ABCRS)is a newtherapeutic approach,which is initiated by clinical specialists of TCM andintegrative Chinese andwestern medicine.Al-though it is not a flawless

Clinical Experience in the Treatment of Vitiligo by the Method of Invigorating Qi,Promoting Blood Circulation and Detoxification

Studies have shown that traditional Chinese medicines have clear curative effects in the treatment of vitiligo with few side effects.Through literature research and clinical observation,the study summarized the etiology and pathogenesis of vitiligo in traditional Chinese medicine as"deficiency,toxin,and stasis",formulated the method of invigorating qi,promoting blood circulation and detoxification,and prescribed Fuse Hexue Jiawei Decoction for the treatment of vitiligo.

Medication Rules of Traditional Chinese Medicine for Treating Threatened Abortion in the Early Stage of Pregnancy with Subchorionic Haematoma Based on Data Mining

Objective:Using data mining technology to explore the rules of traditional Chinese medicine(TCM)in the treatment of threatened abortion in the early stage of pregnancy with sub-chorionic haematoma(SCH).Methods:Literature of TCM in the treatment of threatened abortion in the early stage of pregnancy with SCH were retrieved from CNKI,VIP,WANFANG and Pubmed,EMBASE.The literature information database was established to be used for descriptive analysis,association rule analysis and cluster analysis of relevant data.Results:A total of 100 literatures were included,involving 114 Chinese herbs.The efficacy of Chinese herbs were mainly tonic drugs,hemostatic drugs,heat-clearing drugs,dissolving blood stasis and hemostatic drugs.The medicinal properties were mostly mild and warm,and the taste of the drug was mainly sweet,bitter and pungent.The liver meridian,spleen meridian and kidney meridian were frequently used.The commonly used drug pair combination was"Xu duan(Radix dipsaci,续断)-Tusizi(Semen Cuscutae,菟丝子)",and the core combination was"Tusizi-Xu duan-Ejiao(Donkeyhide gelatin,阿胶)-Baizhu(Atractylodes macrocephala,白术)-Dangshen(Codonopsis pilosula,党参)".Commonly used drugs for removing blood stasis and hemostasis were with Sanqi(Panax notoginseng,三七),Puhuang(cattail pollen,蒲黄),and Qiancao(Radix Rubiae,茜草).Conclusion:Data mining traditional Chinese medicine for the treatment of threatened abortion in the early stage of pregnancy with SCH clinically commonly used drug efficacy,taste,meridian,commonly used drug pairs,core combination and commonly used blood stasis hemostatic drugs,has important reference significance for the treatment of threatened abortion in the early stage of pregnancy combined with SCH.

Exploration of the Effect and Mechanism of Activating Blood Circulation and Stasis-Removing Therapy on Tumor Metastasis

Metastasis is one of the specificities of late stage tumor and also a lethal factor often encountered. The study of tumor metastasis has important meaning for prolonging patients＇ survival and elevating their quality of life, but no really ideal prevention and treatment method has been found so far. Recent researches showed that tumor metastasis is correlated with platelet aggregation and blood hyperviscosity manner. Therefore, the early application of surgery, radiotherapy, chemotherapy and biological therapies, in combination with Chinese medicine therapy for activating blood circulation and removing stasis （ABCRS） may be, after all, an effective approach. ABCRS therapy is an important therapy of Chinese medicine, which, composed of several methods like smoothening blood flow in vessels, promoting blood circulation and dispersing stagnant blood, could influence tumor metastasis to different extents, and could coordinate with some other Chinese medicine therapeutic methods like supplementing qi, promoting qi, clearing heat, removing toxic substances, warming meridian, dispelling wind, eliminating dampness, nourishing yin, dissolving sputum, relieving stagnancy, emptying viscerals, etc. The effect and acting mechanism of ABCRS on tumor metastasis is summarized in this paper and its bi-directional regulatory effects discussed as well.

Activating Blood Circulation to Remove Stasis Treatment of Hypertensive Intracerebral Hemorrhage:A Multi-Center Prospective Randomized Open-Label Blinded-Endpoint Trial

Objective： To investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation （TRABC） in treatment of hypertensive intracerebral hemorrhage （HICH）. Methods： This was a multi-center prospective randomized open-label blinded-endpoint （PROBE） trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale （mRS）. Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale （NIHSS） scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded. Results： After 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups （P〈0.01）. Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group （P=0.038）. Average Barthel scores in the treatment group after treatment was 89.11 ＋ 19.93, and in the control group 82.18 ＋ 24.02 （P=0.003）. NIHSS scores of the two groups after treatment decreased significantly compared with before treatment （P=0.001）. Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment （P〈0.05）. There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group. Conclusion： The integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding.

Effect on platelet aggregation activity: extracts from 31 Traditional Chinese Medicines with the property of activating blood and resolving stasis

OBJECTIVE: To evaluate the anti-platelet aggregation effects of extracts from 31 Traditional Chinese Medicines(TCM) with the property of activating blood and resolving stasis in terms of TCM theory.METHODS: The 31 TCMs extracts were prepared using water, 90% ethanol and ethyl acetate., and the effects on anti-platelet aggregation were tested on a platelet aggregation analyzer in vitro with adenosine 5'-diphosphate, bovine thrombin and arachi-donic acid(AA) as aggregation inducers, respectively. Aspirin was the positive control.RESULTS: Lots of the tested TCMs had inhibitory effects with concentration-dependent manner on platelet aggregations induced by various agonists.Especially, some of the TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae) showed good anti-platelet aggregation effect similar or higher than that in positive control group.CONCLUSION: The study provided scientific references that several TCMs such as Chuanxiong(Rhizoma Chuanxiong), Yanhusuo(Rhizoma Corydalis Yanhusuo) and Danshen(Radix Salviae Miltiorrhizae),possess the property of anti-platelet aggregation.

Study on the Therapeutic Mechanism of the Active Principle of the Chinese Drug Paeoniae Radix 801 through Affinity Biosensors IAsys Plus Quartz Crystal Microbalance

Objective: To study the targeted point and mechanism of the function of the blood-activating and stasis-removing Chinese drugs, Paeoniae Radix 801(PR801) in its cardiovascular protective effects and its specific binding with endothelin 1(ET-1) as well as the dynamics of the two's interactive function by means of using affinity biosensors: IAsys Plus and quartz crystal microbalance (IAQCM). Methods: ET-1 was immobilized on the surfaces of IAQCM by using the new surface modification methods. The PR801 in the solution was detected by modified substrates and the specific binding between PR801 and ET-1 was studied. Results: The curves went up or down after adding PR801.There is specific binding between PR801 and ET-1. The bound mass were 0.458 ng/mm 2 and 133.54 ng/cm 2, respectively. There exists relatively good stability with these two methods. Conclusion: The affinity biosensors: IAQCM can be used to study the interaction mechanism between PR801 and ET-1, providing a new way to study the interaction mechanism of TCM. PR801 can bind ET-1 specifically in the experiments. Therefore, ET-1 is another target that PR801 can bind specifically besides thromboxane A 2.

The Resrch on the PreventiOn and Treetment of Bronchial Asthma by Chuanxiong Antiasthma Mixture

Chuanxiong Antiasthma Mixture is a prescription for bronchial asthma which we have adoptedin the clinic for many years. The results of the animal experiment showed that it lias the function of relaxing ,the isolated bronchial smooth muscle spasm of the animal, lowering the experimented animal's asthma inci-dence and mortality. On the basis ot these results, we have expanded our clinical observation samples set-ting up the Chuanxiong antiasthma group : 100 cases and the control group : 50 cases. The results showed thatthe mixtore can apparently increase the ratio of 1 second forcoful expiration volume/ forceful vital capacity(FEV1%) and redce the value of thromboxane B2. The total effective rate is 92 % which is obviously superi-or than the control group (P<0. 05) . It suggests that the mixture has the antagonistic effect toward the syn-thesis and release of thromboxane B2. Also it has the fonction of relaxing the smcoth muscle and improve thepulmonary fonction.

原发性开角型青光眼案

In this case,the acupuncture treatment for open-angle glaucoma patient achieved a significant result.The acupoints Jingming(睛明BL1),Qiuhou(球后Extra),Fengchi(风池GB20),and Taichong(太冲LR3)were used as the main ones plus some symptomatic acupoints.After one course of treatment,the left eye pressure decreased by 12 mmHg compared with that before treatment,the left eye vision improved,and the fundus oozing was significantly reduced.After two courses of treatment,the left eye pressure was below 20 mmHg,left eye vision obviously improved,and the fundus oozing completely disappeared.