Novel technologies and models for studying pharmacological activities of traditional Chinese medicine for promoting blood circulation and removing blood stasis

OBJECTIVE Our previous studies demonstrated that various ingredients from the traditional Chinese medicine(TCM)for promoting blood circulation and removing blood stasis,as exemplified by cryptotanshinone and salvianolic acid B,exerted striking effects on modulating angiogenesis and vascular permeability,which suggests that they may be effective in treating vascular leak-driven diseases(e.g.tumor,cerebral cavernous malformation and diabetic retinopathy).However,the lack of reliable and advanced technologies and models sets up difficult hurdles for better understanding the role of TCM for promoting blood circulation and removing blood stasis.To this end,this study is to outline numerous cutting-edge platforms that can be utilized for exploring the function of TCM for promoting blood circulation and removing blood stasis in vascular leak-driven diseases.METHODS Two-photon laser scanning fluorescence microscopy was used to observe the interactions between neutrophils and blood vessels in a real-time manner.Dynamic flow system was employed to mimic the in vivo behaviors of neutrophils.RIP1-Tag5 spontaneous pancreatic cancer model was used to study the function of tumor blood vessels.CCM2ECKO(deletion of CCM2 in endothelial cells)mice were employed to establish the cerebral cavernous malformation(CCM)animal model.Micro-computed tomography(micro-CT)was utilized to assess the CCM lesion.Müller cell-knockout mouse model was used to study the progression of diabetic retinopathy.Vascular permeability in this model was assessed by fluorescein angiography.RESULTS The interactions between neutrophils and endothelial cells involve a series of complicated processes,including rolling,adhesion,intraluminal crawling and transmigration,which were all monitored in vivo by two-photon laser scanning fluorescence microscopy in a real-time manner.Dynamic flow system was capable of recapitulating the biological behaviors of neutrophils in vitro.Tumor vascular function in particular vascular perfusion could be assessed in the RIP1-Tag5 spontaneous pancreatic cancer model.In terms of CCM studies,specific deletion of CCM2 in endothelial cells resulted in the initiation of CCM lesion.The size and number of CCM lesions could be visualized and quantified by micro-CT.Furthermore,the Müller cell-knockout mouse model was able to precisely reflect the clinical symptoms of diabetic retinopathy.Vascular leak could be monitored at different time points using fluorescein angiography.CONCLUSION An array of high technologies and animal models can be used in investigating the occurrence and progression of multiple vascular leak-driven diseases.The pre-clinical and clinical studies of TCM for promoting blood circulation and removing blood stasis provide fundamental support for the application of the above-mentioned platforms,with the purpose of uncovering the scientific basis of TCM for promoting blood circulation and removing blood stasis.

Traditional Chinese medicine for activating blood circulation and detoxifying in unstable angina pectoris:A systematic review and meta-analysis

Objective:The purpose of this review was to evaluate the effectiveness of traditional Chinese medicine for activating blood circulation and detoxifying(ABCD)in patients with unstable angina pectoris.Methods:We performed an electronic literature search of six medical databases for relevant articles published up to December 2014.Randomized controlled trials that compared ABCD Chinese medicine(alone or alongside conventional drugs)with conventional drugs or other Chinese medicines alone were included.A meta-analysis was performed for the following outcome measures:reduction of angina symptoms,electrocardiogram improvement,blood lipid levels,inflammatory factor levels,and plasma fibrinogen levels.Results:In total,11 moderate-to low-quality studies involving 686 patients were included.The evidence indicated that ABCD Chinese medicine exhibited superior effectiveness in relieving angina symptoms compared with conventional drugs[relative risk,1.23;95%confidence interval,1.05e1.44];however,electrocardiogram improvement was not very significant(relative risk,1.21;95%confidence interval,0.91e1.62).Moreover,ABCD Chinese medicine exhibited superior anti-inflammatory,anticoagulant,and lipid-lowering effects compared with other medicines.Conclusions:Within the methodological limitations of the included studies,our results suggest that ABCD Chinese medicine is beneficial for the treatment of unstable angina pectoris.

Analysis on the rules of prescriptions for ischemic stroke based on the traditional Chinese medicine inheritance auxiliary system

In China,traditional Chinese medicine is widely used in the treatment of ischemic stroke,but its prescription rules needs to be further studied.This paper uses the traditional Chinese medicine inheritance auxiliary system(a software)to analyze the composition rules of a large number of prescriptions for the treatment of ischemic stroke,and discusses the clinical rationality of the new prescriptions.We found that the prescriptions for the treatment of ischemic stroke are mainly composed by herbs for promoting blood circulation and removing blood stasis,dredging collaterals and tonifying deficiency,and some of the new prescriptions are also in line with this characteristic.This paper can provide reference for clinical prescription in the treatment of ischemic stroke and the development of related new drugs.

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.

Therapeutic effect of traditional Chinese medicine on coagulation disorder and accompanying intractable jaundice in hepatitis B virus-related liver cirrhosis patients

AIM： TO observe the therapeutic effects of new traditional Chinese medicine （TClVl） therapy on coagulation disorder and accompanying intractable jaundice in HBV-related liver cirrhosis patients. METHODS： Using stratified random sampling according to fibrinogen （Fib） levels, 145 liver cirrhosis patients due to hepatitis B complicated by coagulation disorder were treated. Of them, 70 in research group were treated with TCM by ＂nourishing yin, cooling blood and invigorating blood circulation＂ and Western medicine, 75 in control group were treated with conventional Western medicine. The indexes of liver function, coagulation function and bleeding events were observed and compared. RESULTS： The prothrombin time （PT） was shorter and the fibrinogen （Fib） level was higher in the research group than in the control group （Fib = 1.6-2.0 g/L, 1.1-1.5 g/L, and ≤ 1.0 g/L）. The total bilirubin （TBIL） level was significantly lower in the research group than in the control group, except for the subgroup of FIB ≤ 1.0 g/L. CONCLUSION： TCM therapy can improve coagulation fuction and decrease TBIL.

A summary of research on benefiting Qi and activating blood to regulate mitophagy to prevent and treat ischemic heart disease

Ischemic heart disease has the characteristics of high morbidity and high mortality, which seriously endangers people's health. Mitophagy can selectively remove damaged organelles, and has a role in maintaining the homeostasis of myocardial cells and protecting ischemic myocardium. Significance. More and more studies have found that traditional Chinese medicine can improve ischemic damage of cardiomyocytes by regulating mitochondrial function and autophagy. Using mitochondria as the target of traditional Chinese medicine in cardiomyocytes to explore the treatment of ischemic Effective measures for heart disease have become a hotspot for related Chinese medicine workers. Based on the above background, this article outlines the main regulatory pathways of mitochondrial autophagy, and reviews related researches on traditional Chinese medicine of benefiting qi and activating blood and mitophagy in this field.

Clinical Study on Effect of Chinese Herbal Medicine for Supplementing Kidney and Qi and Activating Blood Circulation in Treating Intrauterine Growth Retardation of Fetus

Objective: To explore the therapeutic effect and the possible working mechanism in using Chinese herbal medicine (CHM) for supplementing Kidney and Qi, and activating blood circulation in treating intrauterine growth retardation of fetus (IUGR). Methods: Fifty-five cases of IUGR were divided into two groups, 30 cases in the CHM group treated with CHM and the 25 in the control group treated with amino acids. The effect of CHM treatment was observed and compared with that of the control group, normal pregnancy group and non-treated IUGR group. Results: Body weight of the newborns in the CHM was markedly higher than that in the control group. Not only the maternal fundal height (FH) and the abdominal circumference (AC), but also the fetal growth parameters, including biparietal diameter, head circumference (HC), and femur length (FL) in the CHM group increased much faster than those in the control group. After CHM treatment, the maternal serum levels of estriol (E3) and human placental lactogen (hPL) approached to those in the normal pregnancy group, but the control group,in comparison with the normal pregnancy group, was significantly different. The umbilical venous plasma concentration of essential amino acids in both treated groups improved, but the improvement in the CHM group was more significant than that in the control group. No apparent adverse effect of CHM was observed in either mother or fetus.Conclusion: CHM for supplementing Kidney and Qi and activating blood circulation was more effective in improving placental function and enhancing amino acid transportation than amino acid

Platelet proteomics and its advanced application for research of blood stasis syndrome and activated blood circulation herbs of Chinese medicine

The development of novel and efficient antiplatelet agents that have few adverse effects and methods that improve antiplatelet resistance has long been the focus of international research on the prevention and treatment of cardiovascular and cerebrovascular diseases.Recent advances in platelet proteomics have provided a technology platform for high-quality research of platelet pathophysiology and the development of new antiplatelet drugs.The study of blood stasis syndrome(BSS)and activated blood circulation of traditional Chinese medicine(TCM)is one of the most active fields where the integration of TCM and western medicine in China has been successful.Activated blood circulation herbs(ABC herbs)of Chinese medicine are often used in the treatment of BSS.Most ABC herbs have antiplatelet and anti-atherosclerosis activity,but knowledge about their targets is lacking.Coronary heart disease(CHD),BSS,and platelet activation are closely related.By screening and identifying activated platelet proteins that are differentially expressed in BSS of CHD,platelet proteomics has helped researchers interpret the antiplatelet mechanism of action of ABC herbs and provided many potential biomarkers for BSS that could be used to evaluate the clinical curative effect of new antiplatelet drugs.In this article the progress of platelet proteomics and its advanced application for research of BSS and ABC herbs of Chinese medicine are reviewed.

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.

Mechanism of Erhuang capsule for treatment of multiple sclerosis

Erhuang capsule, a typical formula based on traditional Chinese medicine theory, is widely used to ameliorate multiple sclerosis, inflammation and side effects of glucocortJcoid treatment. Oligodendrocyte precursor cells are neural stem cells that are important for myelin repair and regeneration. In the present study, Erhuang capsule effectively improved clinical symptoms and neurological function scores, reduced mortality and promoted recovery of neurological functions of mice with experimental autoimmune encephalomyelitis. The mechanism of action involved significant increases in oligodendrocyte precursor cell proliferation in specific regions of the brain and spinal cord, increased oligodendrocyte lineage gene 2 expression and enhanced oligodendrocyte precursor cell differentiation.

活血化瘀治疗冠脉微循环障碍的研究进展

冠状动脉微循环障碍广泛存在于多种心血管疾病中,与左室重构、心血管事件密切相关。本病病机演变以血瘀为核心,活血化瘀法可改善患者冠状动脉血流储备及微循环阻力指数,对于冠状动脉微循环障碍具有良好的治疗效果。机制方面,活血化瘀诸法可调节冠状动脉微血管功能障碍的诸多关键病理生理环节:如,活血化瘀可有效抑制炎症、氧化应激及血栓形成;活血化痰可保护血管内皮;益气活血能改善能量代谢;补肾活血促进血管新生、建立冠脉侧支循环。应用现代科学深入挖掘活血化瘀诸法治疗本病的机制,或为解决本病治疗提供新的思路。

基于调控免疫炎症微血管损伤的补气活血法治疗肺炎“瘥后防复”思路的提出

肺炎恢复期后遗症严重影响患者身心健康,存在二次感染的风险,且与基础病相互影响导致恶性循环。做好肺炎恢复期康复工作,减少后遗症并预防反复发作是疾病防治的首选。研究显示肺炎长期后遗症和反复发作的机制可能与持续的机体免疫抑制和全身微炎症状态及微血管损伤有关。团队根据传统中医理论,结合长期临床与基础研究,提出“气虚血瘀”是肺炎恢复期的核心病机。因此,团队提出补气活血法治疗肺炎“瘥后防复”的机制与调控免疫炎症微血管损伤有关,调控T淋巴细胞紊乱提高免疫、抑制炎症因子改善机体微炎症状态和抗氧化保护内皮细胞调控微血管损伤,阐明其内在机制将为中医药治疗呼吸系统重大感染性疾病提供理论依据,传承精华、守正创新。

益气活血方药治疗原发性肝癌的免疫学机制概述

归纳总结具有益气和/或活血功效的中药单体、单味中药以及中药复方治疗原发性肝癌的免疫学机制,包括对T淋巴细胞亚群、巨噬细胞、髓源性抑制细胞(myeloid-derived suppressor cell,MDSC)、肿瘤细胞表面受体、细胞因子以及红细胞免疫在数量和功能上的调节,阐述其抗肿瘤作用,为进一步的基础研究和临床应用提供思路。

郑惠芳教授采用补肾活血法提高薄型子宫内膜容受性的经验总结

郑惠芳教授系全国首批名老中医,临证经验丰富,擅用温补,尤其重用补肾。近几年子宫内膜容受性已经成为生殖医学领域研究的焦点问题,而补肾提高子宫内膜容受性在临床中得到普遍的应用,并且取得可喜的成果,其中中医药发挥了自己独特的优势。郑惠芳教授认为薄型内膜所致不孕的主要病机为肾精亏虚,精血不足,并提出补肾填精、活血养血为主要治疗原则,结合患者的具体情况,辨证论治,取得了显著的疗效,并提供了明确的辨证思路及治疗的方法。

活血类膏药外敷治疗膝关节炎及中医药对其认识的进展

膝关节炎具有发病率高、治疗相对困难、易复发等特点,且与多种因素密切相关,严重威胁中老年的生活质量与身体健康。对于膝关节炎患者,目前可采用止痛治疗、激素治疗、物理治疗、手术治疗、中医药治疗等。近年来,中医药对膝关节炎认识越来越深入,这对于提高中老年膝关节炎的关注度,提升膝关节炎的治疗效果,促进中老年膝关节炎患者疾病的恢复与生活健康有重要的参考意义。本文从膝关节炎的特点、中医药治疗膝关节炎相关研究方面进行综述,重点叙述活血类膏药外敷治疗及相关疗法的作用。

活血化瘀涂搽药治疗冠脉介入穿刺并发症临床观察

目的观察活血化瘀涂搽药剂外敷治疗冠脉介入穿刺并发症的疗效。方法选取2021年1月1日—2022年12月31日在江西中医药大学附属医院行冠脉介入治疗后伴桡动脉穿刺点并发症的患者100例,随机分为试验组和对照组,各50例。对照组采用50%硫酸镁湿敷,试验组采用活血化瘀涂搽药剂湿敷,均连续治疗7 d,比较2组穿刺部位淤青面积变化、穿刺部位肿胀程度、穿刺部位疼痛程度及临床有效率。结果2组患者淤青面积、肿胀程度及疼痛评分均较治疗前降低(P<0.05),且试验组均低于对照组(P<0.05),试验组总有效率高于对照组(P<0.05)。结论活血化瘀涂搽药剂外敷相对于硫酸镁外敷更能有效减少冠脉介入穿刺并发症患者的淤青面积、肿胀程度及疼痛评分,提高临床有效率,疗效好,值得临床推广应用。

张勉之教授基于补肾活血法论治尿酸性肾病

尿酸升高是肾功能异常的独立危险因素,肾脏损伤也会导致患者尿酸排泄异常。尿酸性肾病的病因病机以禀赋素薄,脾肾亏虚为病理基础,饮食不节,湿瘀侵袭为发病机制。张勉之教授在以国医大师张大宁教授创立的补肾活血法为根本治疗大法的前提下,依据潜伏期、发作期、缓解期体现出的不同证型辨证施治,疗效满意。

骨质疏松症“亏瘀致痿”的理论构建及临床应用

骨质疏松症(OP)是一种以增龄性骨量降低,骨微结构破坏,骨脆性增加且易骨折的代谢性骨病。该病好发于绝经后女性和中老年男性,起病隐匿,多数患者在骨折后才被确诊,造成了大量的医疗资源消耗。浙江中医药大学附属第三医院姚新苗教授研究团队基于“肾主骨”“肾气虚损”等基础理论,创新性提出了OP“亏瘀致痿”的致病理论,认为OP的病机是亏虚瘀互结、夹杂致痿。在该理论指导下,认为应采用“补肾健脾活血法”对OP患者进行辨证论治。补肾健脾活血法主要包括虚瘀同治;补肾为本、健脾为要;筋骨并重3个方面。该研究团队开展了一系列临床与基础研究,从不同角度阐释“亏瘀致痿”理论指导下OP康复策略的科学内涵。

Effect of Yang-activating and stasis-eliminating decoction from Traditional Chinese Medicine on intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium

OBJECTIVE: To evaluate the effect of decoction prepared with Yang-activating and stasis-eliminating medicinals from Traditional Chinese Medicine(TCM) on the intestinal mucosal permeability in rats with ulcerative colitis induced by dextran sulfate sodium(DSS).METHODS: Totally 55 male Wistar rats(body weight of 170-190 g) were randomly divided into the blank group(n = 10) and the model duplication group(n = 45). The blank group was not intervened, while the other was modeled with 5% dextran sulfate sodium by gavaging in a dosage of4 m L per day to induce ulcerative colitis, a total of7 days. Then, the model rats were divided into model blank group, mesalazine group and TCM group,and each group was consisted of 15 rats. They were given retention enema 10 min with normal saline,mesalazine enema(0.036 g/m L), and Yang-activating and stasis-eliminating decoction [0.54 g/m L of a decoction boiled by Puhuang(Pollen Typhae), Xiebai(Bulbus Allii Macrostemonis) and Wulingzhi(Faeces Trogopteri)] for 10 days respectively. Afterwards,all of the rats were evaluated by disease activity index(DAI), histological changes of distal colon, expression of occludin protein and ultrastructure of intestinal epithelial cells. Furthermore, ratio of lactulose to mannitol(L/M) discharged in urine was evaluated.RESULTS: Comparing the results between TCM and model control groups, scores of DAI and histological lesions decreased significantly(P = 0.000 <0.01), ultrastructures of intestinal epithelial cells and tight junctions were more complete. The expression of occludin protein(P = 0.001 < 0.01) increased while the L/M value decreased significantly(P = 0.000 < 0.01) in TCM group. There was no statistical difference between the TCM and mesalazine groups in results of each item(P > 0.05).CONCLUSION: The decoction prepared with Yang-activating and stasis-eliminating TCM medicianls can restore intestinal mucosal epithelial cells and tight junctions the model rats with ulcerative colitis; it can reduce histological lesions and protect the permeability of intestinal mucosa barrier in the rats as well.

独活寄生汤内服联合中药外洗治疗类风湿关节炎肝肾亏虚证的疗效观察

目的 探讨独活寄生汤内服联合中药外洗治疗类风湿关节炎肝肾亏虚证的临床疗效。方法 选取2019年12月—2022年12月南京中医药大学徐州附属医院收治的86例类风湿关节炎肝肾亏虚证患者,依照随机数表法分为观察组和对照组各43例。观察组予甲氨蝶呤+硫酸羟氯喹,并配合独活寄生汤+中药外洗治疗,对照组予甲氨蝶呤+硫酸羟氯喹治疗。比较两组患者临床疗效、简化疾病活动指数(SDAI)、临床疾病活动指数(CDAI)、红细胞沉降率(ESR)、C反应蛋白(CRP)及白细胞介素-6(IL-6)等指标。结果 观察组总有效率高于对照组(P<0.05)。治疗后,两组CDAI评分和SDAI评分均较本组治疗前下降(P<0.05),且观察组下降水平高于对照组(P<0.05)。治疗后,两组ESR、CRP、IL-6水平均较本组治疗前降低(P<0.05),且观察组低于对照组(P<0.05)。结论 独活寄生汤内服联合中药外洗治疗类风湿关节炎肝肾亏虚证,改善患者临床症状,疗效确切,并且能够减少炎症因子释放,安全可靠。