Research advances in antiplatelet activation of water soluble compounds in Salvia miltiorrhiza

Platelets are fragments of cytoplasm that are released from the mature megakaryocyte of the bone marrow.The main function of platelets is coagulation and hemostasis.Platelets play a central role in formation of pathological thrombosis.Many ischemic diseases are caused by excessive activa.tion of platelets,which can lead to thrombosis and death.Salvia miltiorrhiza Bunge,the dry roots and rhizomes of the Salvia miltiorrhiza plants,includes some water-soluble compounds,which play positive effects on diverse diseases such as neurodegenerative diseases,diabetic complications or cardiovas.cular diseases.In this paper,the components of the water-soluble in Salvia miltiorrhiza,as well as the applications in thrombotic diseases are summarized.The results show that water-soluble compounds include salvianolic acid A,salvianolic acid B,protocatechuic aldehyde,Danshensu,etc.The water-soluble compounds are applied to ischemic stroke,myocardial infarction and other diseases caused by thrombus.We also discussed the mechanisms of water-soluble compounds on the platelets based on our research results and the data obtained from references.The results indicate that water soluble compounds in Salvia miltiorrhiza play the antiplatelet and antithrombotic effects via different mechanisms,for example,salvianolic acid A inhibits platelet aggregation without promoting bleeding by increasing cAMP,inhibiting phosphoinositide 3-kinase(PI3K) and affecting GPCRs(G protein-coupled receptors) signaling path.ways;salvianolic acid B inhibit platelets as a P2Y12 antagonist and PDE inhibitor;Danshensu inhibits platelet activity may be related to inhibition of calcium influx.In conclusion,thrombotic diseases seriously affect human life and health.The existing antiplatelet drugs have some disadvantages.For example,aspirin may cause intracranial hemorrhage,and clopidogrel may play a slower role.Salvia miltiorrhiza as a traditional Chinese medicine has positive pharmacological activity and exerts antiplatelet aggrega.tion through different mechanisms.In the future,we will develop the new drugs which prevent and treat thrombotic diseases with the further study of the pharmacological effects and mechanisms of Salvia miltiorrhiza.

Microwave digestion polarography for determining seven trace elements in Salvia Miltiorrhiza Root and compound Salvia Miltiorrhiza Root injection simultaneously

The sensitive second derivative waves of Cu(Ⅱ),Pb(Ⅱ),Cd(Ⅱ),Ni(Ⅱ),Zn(Ⅱ),Fe(Ⅱ)and Mn(Ⅱ),forming in the substrate solution(pH=9.26)consisting of ammonia,ammonium chlorid,gelatin and ascorbic acid were researched.The peak potentials of the polarographic waves of the seven ions are at about 0.48,0.63,0.79,1.04,1.28,1.44 and 1.60 V respectively.Combining with microwave technique,a new method for the simultaneous determination of the seven trace elements in Chinese traditional medicine was developed.The method is easy to operate,rapid,simple and convenient.When the signal-to-noise rate equals 3,the detection limits of Cu,Pb,Cd,Ni,Zn,Fe and Mn are 4.2×10 3,5.3×10 3,2.1×10 3,5.8×10 4,3.0×10 3,7.7×10 4 and 1.1×10 3 μg/mL respectively.Well linear relationships exist between the concentrations and the peak currents when Cu,Pb,Cd,Ni,Zn,Fe and Mn concentrations are within 8.5×10 3 10,9.7×10 3 10,4.5×10 3 10,1.2×10 3 10,6.4×10 3 10,1.5×10 3 10 and 2.8×10 3 10 μg/mL,respectively.The method has been used to the simultaneous determination of the seven trace elements in Salvia Miltiorrhiza Root and compound Salvia Miltiorrhiza Root injection,the relative standard deviations(RSDs)of the Cu,Pb,Cd,Ni,Zn,Fe and Mn in the two medicines are 3.9% and 5.8%,4.0% and 4.1%,4.3% and 5.7%,4.9% and 5.3%,4.4% and 4.7%,3.5% and 4.0%,0.51% and 2.8%,respectively;the comparisons of the determination results with the values obtained by the standard method indicate that the presented method has very well veracity.

Compound Astragalus and Salvia miltiorrhiza extract exerts anti-tumor activity by intervening the interaction of microRNA-145/microRNA-21 and Smad3C/3L phos-phorylation in hepatocellular carcinoma

OBJECTIVBE To investigate the intervention of compound Astragalus and Salvia miltiorrhiza extract(CASE) consisted of astragalosides,astragalus polysaccharides and salvianolic acids on the interaction of microRNA-145/microRNA-21(miR-145/miR-21) and Smad3 C/3 L phosphorylation(pSmad3 C/pSmad3 L) down-stream of transforming growth factor-β(TGF-β)/mitogen activated protein kinase(MAPK) signaling in hepatocellular carcinoma(HCC) progression by in vitro and in vivo experi.ments.METHODS In HepG2 cells and xenografts of nude mice,antagomir/agomir and plasmids of Smad3 C/3 L phosphorylation site mutation(Smad3 3 S-A/Smad3 EPSM) were used to intervene miR-145/miR-21 and pSmad3 C/pSmad3 L expression respectively,then incorporative CASE treatment.Cell proliferation,migration,apoptosis,tumor growth and histopathologic characteristics of xenografts,relevant proteins of TGF-β/Smad pathway and miR-145/miR-21 were evaluated.RESULTS CASE up-regulated miR-145 while down-regulated miR-21,inhibited cell proliferation,migration and tumor growth,accelerated cell apoptosis in HepG2 cells respectively transfected with Smad3 WT,Smad3 EPSM,Smad3 3 S-A plasmids in cultured dishes and xenografts of nude mice,the above effects were more evident in HepG2 cells with increased pSmad3 C.In TGF-β1-stimulated HepG2 cells and xenografts of nude mice,CASE antagonized the facilitating effects of miR-145 antagomir/miR-21 agomir on cell migration,proliferation,tumor growth and inhibiting effects of miR-145 antagomir/miR-21 agomir on cell apoptosis;CASE increased miR-145 down-regulated by miR-145 antagomir and decreased miR-21 up-regulated by miR-21 agomir,reduced protein level of pSmad3 L and their proteins including TβRⅡ,pERK1/2,pJNK1/2 and pp38 while elevated pSmad3 C expression.CONCLUSION These results suggest that pSmad3 C/pSmad3 L maybe interact with miR-145/miR-21 in HCC progression,which may be one of important molecular mechanisms of CASE's anti-HCC effects.

TREATMENT OF 40 CASES OF CHRONIC ECZEMA WITH POINT-INJECTION OF COMPOUND RADIX SALVIAE MILTIORRHIZAE INJECTION

The authors have used point-injection of compound Radix Salviae Miltiorrhizae Injection to treat 40 cases of chronic eczema and achieved a satisfactory therapeutic effect. The total effective rate was 95%.

Study on Optimization of Ethanol Reflux Extraction of Phenolic Acids from Salvia miltiorrhiza

The extraction technology of phenolic acid compounds from Salvia miltiorrhiza by ethanol reflux was studied. In this experiment, salvianolic acid B standard was used to make the standard curve. Single factor experiment and orthogonal experiment were used to study the extraction of different ethanol concentrations, reflux times and material-to-liquid ratios. The OD value of salvianolic acid compounds was measured with a spectrophotometer. The extraction rate of phenolic acid compounds under different extraction conditions was calculated through a regression equation, so as to obtain the optimal conditions for the ethanol reflux extraction process of Salvia miltiorrhiza. The experimental data can provide a reference for the ethanol reflux extraction process of salvianolic acids in the industry. According to the experiment, the extraction rate of phenolic acids in Salvia miltiorrhiza was the highest when the ethanol concentration was 60%, the reflux time was 1.5 hours, and the ratio of material-to-liquid was 1:10.

复方丹参滴丸联合丁苯酞治疗急性脑梗死的疗效及对患者血清炎性因子的影响

目的基于核转录因子(NF-κB)信号通路探究复方丹参滴丸联合丁苯酞对急性脑梗死(ACI)患者炎性反应的影响。方法选取2020年7月至2022年5月平顶山市第一人民医院收治的ACI患者118例,按随机数表法分为观察组和对照组各59例。对照组患者予以丁苯酞注射液治疗,观察组患者在对照组治疗的基础上联合复方丹参滴丸治疗,均连续治疗两周。治疗两周后,比较两组患者的疗效,以及治疗前、治疗一周后、两周后的美国国立研究院卒中量表(NIHSS)、简易智能状态量表(MMSE)、Barthel指数(BI)评分、脑神经因子[神经生长因子(NGF)及神经营养因子(NTF)]、NF-κB信号通路相关蛋白、mRNA和NF-κB信号通路相关因子[白细胞介素(IL)-1β、IL-6、IL-8、肿瘤坏死因子(TNF)-α]水平,同时比较两组患者治疗期间的不良反应发生情况。结果观察组患者的临床治疗总有效率为94.92%,明显高于对照组的81.36%,差异有统计学意义(P<0.05);治疗一周和两周后,两组患者的NIHSS评分均呈下降趋势,且观察组明显低于对照组,MMSE及BI评分呈升高趋势,且观察组明显高于对照组,差异均有统计学意义(P<0.05);治疗一周和两周后,两组患者的NGF、NTF均呈升高趋势,且观察组明显高于对照组,差异均有统计学意义(P<0.05);治疗一周后、两周后,两组患者的NF-κB p50蛋白、NF-κB p50 mRNA、NF-κB p65蛋白、NF-κB p65 mRNA均呈下降趋势,且观察组明显低于对照组,差异均有统计学意义(P<0.05);治疗一周后、两周后,两组患者的NF-κB信号通路相关因子IL-1β、IL-6、IL-8、TNF-α均呈下降趋势,且观察组明显低于对照组,差异均有统计学意义(P<0.05);治疗期间,观察组患者不良反应总发生率为11.86%,略高于对照组的8.47%,但差异无统计学意义(P>0.05)。结论复方丹参滴丸联合丁苯酞可通过调控NF-κB信号通路,抑制炎性反应,加速神经功能缺损恢复,临床应用效果显著且安全性较高。

利用MINITAB多元统计法分析不同企业复方丹参片质量

基于单因素方差分析、相关性分析、主成分分析和聚类分析等多元统计分析,评价不同企业多批次复方丹参片的质量。用高效液相色谱法测定不同企业复方丹参片中指标成分丹参酮ⅡA和丹酚酸B、人参皂苷Rg_1及人参皂苷Rb_1、三七皂苷R1及人参皂苷Re的含量,通过统计分析、聚类分析,对不同企业复方丹参片质量进行评价。11家企业20个批次复方丹参片中各指标成分均符合《中华人民共和国药典》2020年版规定,但存在较大差异。以样品编号为12的主成分综合评价得分最高(2.32),质量评价最优。主成分分析和聚类分析结果可为复方丹参片的质量控制、优劣评价提供科学依据。

Effects of Compound Salviae Miltiorrhizae Injection on Metabolism of Phosphoinosititides in Myocardial Ischemia

Using the model of acute myocardial ischemia in rats formed by ligation of the descending an-terior branch of the left coronary artery, this study showed some effects of compound Salviae miltiorrhizae in-jection ( CSMI) on metabolism of phosphoinositide in myocardial ischemia. The results of the experimentshowed that after 10 minutes of acute ischemia, the function of myocardial messangers ot phosphoinositide in-creased, and the levels of phosphatidylinositol-4, 5-biphosphate ( PIP2 ) and inositol-1, 4, 5-trisphosphate(IP3 ) were obviously higher than those of the non-ischemia control groups ( P < 0. 01 , n = 7) . CSMI (2 glkgbody weight) could markediy inhibit myocardial PIP2 and IP3, whose levels became lower than those of theischemia control groups ( P < 0 . 01 , n = 7 ) .

Therapeutic Effects of Pefusing Compound Salvia Miltiorrhiza Injection Through the Hepatic Artery in the Late Stage of Hepatocarcinoma

In the treatment of 20 patients with advanced hepatocarcinoma, whose conditions wors-ened affer chemotherapy, with hepatic artery intubation, by injection of Compound Salvia Miltiorrhizathrough the hepatic artery, it can be seen that their signs were relaxed and tumor masses were diminishedand biochemical indices were improved. The test group had a 65% rate of general efficiency, while thecontrol group had only 25%. There is a significant difference (P<0. 01) between the two groups. There-fore the method of treatment for such patients is thought to be worthy of being further studied.

Clinical Study of Compound Radix Salvia Miltiorrhizae for Severe Pancreatitis

Compound Radix Salvia Miltiorrhizae injection was administered after operation for 28 casesof severe pancreatitis, and 13 cases were taken as a control group. The results showed that : (1) The differ-ence was not obvious in the morbidity of complications between the two groups, but the mortality (3.6% ) ofthe trial group was significantly lower tlian that ( 30. 8% ) of the control group ( P < 0. 05 ) ; ( 2 ) Hematocritwas clearly decreased from 46. 1 5. 2% to 33. 2 3. 9% in the trial one ( P < 0. 05) , but platelet andhemoglobin showed no statistical signiticance. It is concluded that compound Salvia miltiorrhizae inlectionmight improve hemorheologic abnormalities of the disease, promote the recovery of the pancreatic tissue,and correct the serious complications such as adult respiratory distress syndrome etc.

中药专利复方治疗糖尿病周围神经病变的用药规律分析

【目的】采用数据挖掘方法分析国家专利中药复方治疗糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)的用药规律,为临床用药提供参考。【方法】在国家知识产权局网站检索中药复方治疗DPN的专利,使用Excel 2021进行频数统计,运用RAW Graphs 2.0制作高频中药功效的桑基图,运用SPSS Statistics 25.0软件进行药物的系统聚类分析,基于Cytoscape 3.9.1挖掘核心处方。【结果】共纳入101首中药专利复方,涉及243味中药。出现频次居前3位的中药为丹参、黄芪、白芍。治疗DPN的专利复方药物的药性以温、平为主,药味以甘、苦、辛为主,归经以归肝、心、脾经居多。药物按功效主要可分为补虚药、活血化瘀药、解表药、平肝熄风药、清热药、止血药、安神药、利水渗湿药。关联规则分析中支持度最高的药物组合为黄芪-当归;系统聚类分析将出现频次居前31位的中药分成7组,挖掘得到的核心处方包含黄芪、川芎、鸡血藤、丹参、牛膝、桂枝、当归共7味药。【结论】专利中药复方治疗DPN以补虚、活血化瘀为主,兼以温通经络,重视后天之本,健脾更不忘疏肝;临证时可选用黄芪-当归及白芍-丹参药对;核心方(黄芪、川芎、鸡血藤、丹参、牛膝、桂枝、当归)可加减用于DPN的全病程治疗。

复方丹参注射液对心内直视手术心肌缺血再灌注后血清内皮素及前列环素/血栓素A_2比值的影响

目的 :观察复方丹参注射液对心内直视手术心肌缺血再灌注后血清内皮素 (ET) ,前列环素(PGI2 ) ,血栓素A2 (TXA2 )及PGI2 /TXA2 比值的影响。方法 :2 0例先天性室间隔缺损或房间隔缺损患者随机分为治疗组 ( 10例 )及对照组 ( 10例 )。治疗组于手术开始前及复温后心脏复跳前分别静脉注射复方丹参注射液 2 0 0mg/kg ,对照组给予等容量平衡盐溶液。经中心静脉取血测定ET、PGI2 及TXA2 含量 ,并计算PGI2 /TXA2 比值。结果 :在体外循环开始 (T1)后两组血清ET显著降低 (P <0 0 5) ,PGI2 及TXA2 显著增加 (P <0 0 5)。心肌缺血再灌注后对照组ET进行性增加 ,从再灌注后 30min(T3)～ 2 4h(T5)均显著高于治疗组 (P <0 0 5)。再灌注期间治疗组PGI2 及TXA2 降低速度比对照组快 ,但治疗组PGI2 /TXA2 比值高于对照组。T5时治疗组PGI2 及TXA2 含量显著低于对照组 (P <0 0 5) ,但PGI2 /TXA2 比值高于对照组 (P <0 0 5)。血清ET含量与PGI2 /TXA2 比值呈显著负相关 (r =- 0 82 2 ,P <0 0 5)。治疗组患者术后心功能的恢复优于对照组。结论 :复方丹参注射液能升高再灌注期PGI2 /TXA2 比值 ,有效抑制再灌注期内皮素的产生 ,促进缺血再灌注心脏功能的恢复。

丹参制剂中丹参酮Ⅱ_A的稳定性影响因素考察

目的 :考察空气 (氧气 )、水、p H及复方成分等对丹参酮 A降解速度的影响。方法 :在 70℃下 ,对丹参及复方丹参片的乙醇提取试样进行恒温加速试验 ,用薄层扫描法测定丹参酮 A的含量变化及降解速度常数 ,比较各因素的影响程度。结果 :在大气中丹参酮 A降解迅速 ,但在较高真空度时明显较慢 ;随着乙醇溶液中水分含量的增加 ,降解速度略有增大 ;不同 p H丹参试样以及复方丹参片试样的降解速度常数之间没有明显差别。结论 :空气 (氧气 )对丹参酮 A的降解有较大影响 ,其次为水分 ,p

复方丹参注射液治疗重症胰腺炎的临床研究

手术治疗重症胰腺炎后，应用复方丹参注射液治疗２８例，对照组１３例。结果表明：（１）两组并发症的发生率无明显差异，治疗组病死率３．６％，对照组病死率３０．８％，其差异显著（Ｐ＜０．０５）。（２）治疗组的红细胞压积从术前的４６．１±５．２％降低到３３．２±３．９％，其差异显著（Ｐ＜０．０５），而血小板和血红蛋白的变化无统计学意义。认为：复方丹参注射液能够改善重症胰腺炎的血液流变学异常，有助于胰腺组织的康复和成人呼吸窘迫综合征等严重并发症的纠正。

金刚烷胺单用及与复方丹参或丙炔苯丙胺合用治疗早期帕金森病的临床观察

目的评定单用金刚烷胺、金刚烷胺与复方丹参或丙炔苯丙胺合用对早期帕金森病 (PD)患者治疗的效果和安全性。方法采用多中心、开放式分组 ,单用金刚烷胺组 (金刚烷胺组 ) 3 5例 ,金刚烷胺 +复方丹参组 (复方丹参组 ) 3 4例 ,金刚烷胺 +丙炔苯丙胺 (丙炔苯丙胺 )组 2 9例。临床疗效采用改良Webster量表和帕金森病运动功能 (MDRSPD)量表 ,在治疗前及以后每 2个月进行 1次评定 ,期限为 1年 ,观察药物的临床疗效及副作用。同时在治疗前后取血查肝肾功能、血糖及血常规、尿常规。结果Webster量表和MDRSPD量表的临床有效率 ,单用金刚烷胺组分别为 42 9%和 3 7 1% ,复方丹参组分别为 3 4 2 %和 2 6 5 % ,丙炔苯丙胺组分别为 5 1 1%和 48 3 % ,经t检验差异无显著性。MDRSPD量表的临床显效率 ,金刚烷胺组为 2 8% ,复方丹参组为 11 8% ,丙炔苯丙胺组为 2 7 6%。复方丹参组与金刚烷胺组相比 ,差异无显著性 ;丙炔苯丙胺组与金刚烷胺组相比 ,差异有显著性。不良反应的发生率在以上 3组分别为 2 7 8%、8 8%和 3 1% ,但均较轻微 ,持续时间短 ,不影响治疗。结论 3组方案对早期PD患者均有一定的疗效 。

复方丹参CO_2超临界萃取液抗大鼠血栓形成的实验研究

目的探讨复方丹参萃取液对大鼠实验性血栓形成的影响。方法采用大鼠颈总动脉-颈外静脉血流旁路法,进行复方丹参萃取液抗血栓形成实验,并检测其相关指标。结果复方丹参萃取液有明显抑制血栓形成,并有降低血小板聚集性的作用。结论复方丹参萃取液具有抗血栓形成的作用。

HPLC-DAD-ESI/MS^n-DPPH在线筛选与鉴别丹参和康定鼠尾草中抗氧化活性成分

本研究建立了在线高效液相色谱-质谱-二苯基三硝基苯肼(HPLC-DAD-ESI/MSn-DPPH)快速筛选和鉴别丹参和康定鼠尾草中抗氧化活性成分和含量的方法。经液相色谱、质谱和文献报道综合分析鉴定出丹参和康定鼠尾草中的3种抗氧化活性化合物,分别为咖啡酸、异迷迭香酸苷和迷迭香酸。比较了热回流、超声辅助提取和快速溶剂萃取的提取效果,并对色谱条件进行优化。在优化条件下,这3种化合物均可有效分离,并在1.7~35.3μg/m L范围内线性关系良好,相关系数为0.999 5~0.999 8,检出限为0.05~1.85μg/m L,定量下限为0.18~6.16μg/m L,平均回收率为96.6%~97.2%,相对标准偏差为1.1%~1.3%。运用该方法测定丹参和鼠尾草样品中这3个化合物的含量分别为:咖啡酸0.303,0.254 mg/g;异迷迭香酸苷1.019,1.401 mg/g;迷迭香酸17.279,8.104 mg/g。本方法简便、快速、准确、重现性好,适用于从复杂天然产物中快速筛选与鉴别抗氧化活性成分。

生长抑素联合复方丹参注射液治疗急性胰腺炎临床研究

目的:观察生长抑素联合复方丹参注射液治疗急性胰腺炎(AP)的临床疗效。方法:采用随机对照分组的临床研究方法,将2002年6月—2006年12月收治的62例AP患者分为对照组和观察组,每组31例。对照组在常规禁食、胃肠减压等治疗的基础上,先静脉注射生长抑素250μg,然后改用3 000μg加生理盐水500 ml以250μg/h的速度持续静脉滴注(静滴),连续7～14 d;观察组在对照组治疗基础上,予复方丹参注射液20 ml溶于生理盐水250 ml中静滴,每日1次,连续7～14 d。观察并比较两组患者的症状,腹部体征消失时间,血、尿淀粉酶,肝功能恢复正常时间,血钙浓度变化和多器官功能障碍综合征(MODS)发生率、病死率。结果:观察组治疗后血淀粉酶显著低于对照组,而血钙水平显著高于对照组,尤以治疗后3 d和5 d更为明显(P均<0.01)。观察组痊愈率(38.7%)和总有效率(90.4%)均明显高于对照组(16.2%和77.4%,P<0.01和P<0.05),而MODS的发生率(19.3%)和病死率(6.5%)均显著低于对照组(45.1%和16.2%,P均<0.05)。结论:生长抑素联合复方丹参注射液治疗AP疗效好于单纯生长抑素治疗。

丹参品质与主导气候因子的灰色关联度分析

气候因子对丹参(Salvia miltiorrhiza Bunge)生长及有效成分含量有重要影响,为科学选择人工种植基地,需要明确影响丹参品质的主导气候因子。研究了丹参在商洛6个不同地区的生长量及有效成分含量差异,并应用灰色关联度分析了其与气候因子的关系,结果表明:6地区丹参有效成分含量均达到药典要求,但品质存在显著差异。年日照和年均降水量是影响丹参根系生长量的主导因子;无霜期与年极高温度是影响丹参素含量的主导因子;7月份均温、年均温度、年极高温度是影响丹参酮IIA含量的主导因子;年日照、无霜期是影响丹酚酸B含量的主导因子。以上几个指标可以作为选择丹参适生基地的参考指标,为科学合理的选择丹参规范化种植基地,保证中成药生产原料质量提供参考。

复方丹参注射液抗脂多糖诱导的兔弥漫性血管内凝血

目的:研究复方丹参注射液对脂多糖(LPS)诱导的兔弥漫性血管内凝血(DIC)的作用。方法:用LPS诱导兔DIC模型。凝固法测定纤维蛋白原含量,全自动凝血分析仪检测活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)和纤维蛋白原含量;全自动血细胞分析仪进行血小板计数;全自动血浆分析仪测定谷丙转氨酶(ALT)以及血尿素氮(BUN);发色底物法测定蛋白C及抗凝血酶Ⅲ的活性。观察复方丹参注射液对LPS诱导的兔DIC的拮抗作用。结果:兔耳缘静脉持续滴注LPS,观察到:APTT和PT显著延长;血小板计数和纤维蛋白原含量明显减少;ALT和BUN显著升高;蛋白C和抗凝血酶Ⅲ的活性明显降低。给予复方丹参注射液后,APTT和PT的延长明显缩短;血小板计数和纤维蛋白原的含量均明显恢复;ALT和BUN显著下降;蛋白C及抗凝血酶Ⅲ的活性显著改善。结论:复方丹参注射液对LPS诱导的兔DIC有良好的拮抗作用。