Protective effect of ultrashortwave versus radix salviae miltiorrhizae on brains of rats with cerebral ischemia-reperfusion injury

BACKGROUND： HOW to control the effect of oxygen-derived free radicals on development of cerebral injury and cerebral edema is a key factor for treating cerebral ischemia-reperfusion injury. OBJECTIVE： To observe and compare the protective effects, synergistic action and mechanisms of ultrashortwave （USW） and radix salviae miltiorrhizae （RSM） on the focal cerebral ischemia-reperfusion injuries in rats. DESIGN： Randomized controlled animal study SEI-FING： Department of Rehabilitation Medicine, First Hospital affiliated to China Medical University MATERIALS： A total of 160 healthy Wistar rats of both genders and aged 18-20 weeks weighing 250-300 g of clean grade were selected in this study. 5 mL/ampoule RSM injection fluid was produced by the First Pharmaceutical Corporation of Shanghai （batch number： 011019, 0.01 mug）. The USW therapeutic device was produced by Shanghai Electronic Device Factory with the frequency of 40.68 MHz and the maximal export power of 40 W. The first channel of power after modulation was 11 W. METHODS： The experiment was carried out in the Rehabilitation Medicine Department of the First Hospital affiliated to China Medical University from May 2002 to January 2003. Focal ischemia-reperfusion model was established in rats by reversible right middle cerebral artery occlusion with filament. Right cerebral ischemia was for 2 hours and then with 24 hours reperfusion. The scores of neurological deficits were evaluated by 0 to 4 scales. After surgery, 64 successful rats models were divided into four groups according to digital table： control group, USW group, RSM group and RSM ＋ USW group with 16 cases in each group. Rats in control group were intraperitoneally injected with the same volume of saline （0.1 mL/g）; rats in USW group were given small dosage of USW on head for 10 minutes at 6 hours after reperfusion; rats in RSM group were intraperitoneally injected with 0.01 mL/g RSM solution at 30 minutes before reperfusion; rats in RSM ＋ USW group were intraperitoneally injected with 0.01 mL/g RSM parenteral solution at 30 minutes before reperfusion and given small dosage of USW on head for 10 minutes once at 6 hours after reperfusion; sixteen rats in sham operation group did not receive any treatment. All 80 rats were taken brains at 24 hours after reperfusion to measure wet and dry weights to calculate water content： Cerebral water content （%） = （1-dry/wet weight） × 100%. Superoxide dismutase （SOD） activity was measured by hydroxylamine method and malondialdehyde （MDA） content was measured by TBA photometric method. MAIN OUTCOME MEASURES ： Cerebral water content, SOD activity and MDA content RESULTS： All 160 rats except 80 failing in modeling were involved in the final analysis. （① The cerebral water content of left hemisphere made no significant difference （P 〉 0.05）. The cerebral water content of right hemisphere in the control group and the three treatment groups was obviously higher than that of the sham operation group [（81.26±0.77）%, （79.74±0.68）%, （79.76±0.81）%, （79.61±0.79）%, （77.43±0.61）%, P 〈 0.05]. The cerebral water content of right hemisphere in the three treatment groups was obviously lower than that of the control group （P〈 0.05）. There was no significant difference among the three treatment groups （P 〉 0.05）. ② Compared with the control group, SOD activity （right） of the control group decreased obviously （P 〈 0.05）, while MDA content increased obviously （P 〈 0.05）. SOD activity in the three therapeutic groups increased obviously, while MDA content decreased obviously （P 〈 0.05）; there was no significant difference among the three treatment groups （P 〉 0.05）. CONCLUSION： ① USW and RSM therapy have neuroprotective effects against focal cerebral ischemia-reperfusion injuries by means of decreasing cerebral water content and MDA and increasing the activity of SOD. ② Synergistic action was not observed between these two therapeutic methods.

Chemical constituents and pharmacological activities of Salvia miltiorrhiza

Salvia miltiorrhiza Bunge(S.miltiorrhiza),a perennial plant of the genus Salvia,is widely used in traditional folklore medicine.Previous chemical research on this plant contains diterpenoid quinones,phenolic acids,polysaccharides and other compounds.The pharmacological investigation of S.miltiorrhiza has shown that it has various pharmacological activities,such as cardiovascular system protection,anti-inflammatory,anti-oxidant,anti-tumor,liver protection,and neuroprotection activities.This research tends to give an overview of the main chemical constituents and pharmacological effects of S.miltiorrhiza,aiming to reveal its potential value and provide reference for its further development.

Biomechanical Experimental Study on Effective Fraction of Radix Salviae Miltiorrhizae on Healing of Bone Fracture

Objective: To assess the effect of Danshen 9403 (DS 9403), an effective fraction of Radix Salviae miltiorrhizae (RSM) on healing of bone fracture. Methods: Standardized radial fracture was performed in 120 Wistar rats. The model rats were randomized into four groups: Group A was fed with DS 9403, group B injected with Staphylococcus aureus , group C with normal saline administration, and group D with RSM injection. The treatment began at the first day of fracture. The rats were sacrificed on the day 25, 39 and 50 separately in batches and their intact radii were removed by dissection for detecting load and stress of three point bending test with autograph universal material testing machine (Shimazu, Japan). Results: The parameters of load in DS 9403 treated group on the 39th day and that of stress at 25th, 39th and 50th day were (6.20±1.32)N, (5.71±3.58)N/mm 2, (8.27±2.42)N/mm 2 and (66.25±26.21)N/mm 2 respectively, which were significantly higher than those in other groups, P <0.05. Conclusion: DS 9403 has the action of increasing the strength of fracture broken end.

EFFECTS OF HYPOXIC ENDOTHELIAL CELL CONDITIONED MEDIUM ON PROLIFERATION AND COLLAGEN SYNTHESIS OF SMOOTH MUSCLE CELLS AND INHIBITORY EFFECTS OF RADIX SALVIAE MILTIORRHIZAE

The effects of hypoxic endothelial cell conditioned medium (HECCM) on proliferation and collagen synthesis of cultured porcine pulmonary arterial smooth muscle cells (PASMCs) were studied by 3H-thymidine (3H-TdR) and 3H-proline incorporations, image analysis for determination of DNA content and colorimetric assay using MTT, and the inhibitory effects of radix salviae miltiorrhizae (RSM) on them were also investigated. The results showed that HECCM could induce enhancement of the enzymatic activity of mitochondria, increase of the nucleic DNA content and increases of the 3H-TdR and 3H-proline incorporations in PASMCs. The 3H-proline incorporation in PASMCs cultured in HECCM was 1.83 times as much as that cultured in normoxic endothelial cell conditioned medium (NECCM). Compared with the control, Chinese herb medicine RSM could inhibit the proliferation of PASMCs cultured in HECCM and decrease the 3H-prolinc incorporation in PASMCs cultured in both HECCM and NECCM (P< 0.001). However, RSM had no ef fects on the nucleic DNA content and 3H-TdR incorporation into DNA of PASMCs cultured in NECCM. It suggests that hypoxia may stimulate the endothelia to synthesize and secrete some cytokines which can stimulate the proliferation and the synthesis of collagen of PASMCs and RSM can inhibit this process.

Effects of Tetramethylpyrazine and Radix Salviae Miltiorrhizae on Collagen Synthesis and Proliferation of Cardiac Fibroblasts

Objective: To explore the effects of Tetramethylpyrazine (TMP) and Radix Salviae Miltiorrhizae (RSM) on collagen synthesis and proliferation of cardiac fibroblasts. Methods: Using collagenase and pancreatin digested rat cardiac tissue assay to isolate cardiac fibroblasts (FB). Different dosage of TMP, RSM and norepinephrine were used to study their effects on the collagen synthesis and proliferation of cultured cardiac FB. Results: Compared with the control group, moderate or high dosage TMP and RSM could significantly inhibit the collagen synthesis and the proliferation of cultured cardiac FB. Moreover, low-dose TMP (50 mg/L) and low-dose RSM (3 g/L) could antagonize the collagen synthesis and the proliferation of cultured cardiac FB stimulated by NE (500μg/L). Conclusion: Both TMP and RSM can inhibit the collagen synthesis and proliferation of cultured cardiac FB processes.The mechanisms of these effects might be correlated to their Ca++ antagonistic action. Original article on CJIM(Chin) 1998; 18(7): 423

Effects of Radix Salviae Miltiorrhizae on Proliferation,Apoptosis and c-myc Protein Expression of Fibroblast in Culture of Kindney with Lupus Nephritis

Objectiv:To observe the effects ofRadix Salviae Miltiorrhizae (SM) on humanfibroblast in culture of kidney with lupus nephritis (LN ). Methods: Fibroblasts wereisolated from culture of kidney biopsy of LN patients, and effect of SM on 3H-TdR incorporated rate of fibroblasts was observed. Theapoptosis and c-myc expression were detectedin the same time by flow cytometry.Results:SM could inhibit the proliferation of fibrolast,and promote the programmed cell deaththrough upregulate c-myc protein expression inhuman renal fibroblasts. Conclusions: Longterm administration of SM in large dosagecould be effective on interstial fibrosis of LN,so that to prevent or reduce the scar tissue for-mation and teatrd the occurrence of uremia.

Study on Preventive and Therapeutic Effect of Radix Salviae Miltiorrhizae on Recurrence and Metastasis of Liver Cancer

Objective: To study the inhibitory effect of Radix Salviae Miltiorrhizae (RSM) on adhesive and invasive ability of SMMC 7721 liver cancer cells, and on the metastasis and recurrence on post hepatectomy liver cancer in nude mice. Methods: Effect of RSM on SMMC 7721 cell membrane intercellular adhesive molecule 1 (ICAM 1) expression was observed by immunofluorescence flow cytometry; effect on invasive ability and of SMMC 7721 cell and the detachment of which attached to fibronectin (FN) by cell migration experiment; effect on adhesion of SMMC 7721 cell with FN by MTT method and effect on adhesion between 7721 7721, 7721 lymphocyte and 7721 endothelial cell by cell adhesion experiment. LCI D20 human liver cancer metastasis model, after hepatectomy, was used to observe the effect of RSM on recurrence and metastasis of liver carcinoma in nude mice. Results: ICAM 1 expression in SMMC 7721 cells incubated with RSM was significantly lower than that in cells did not treated with RSM. RSM could inhibit the invasive ability of SMMC 7721 cell and made the cells already attached to FN exfoliated. It could also inhibit the adhesion of 7721 7721, 7721 lymphocyte and 7721 endothelial cell. And RSM showed preventive and therapeutic effect on intrahepatic and remote metastasis/recurrence of early and late human post hepatectomy liver cancer in nude mice. Conclusion: RSM could inhibit the invasion and adhesion of SMMC 7721 cell and could also prevent and inhibit metastasis and recurrence of human liver cancer after hepatectomy in nude mice.

丹参-当归治疗缺血性脑卒中作用机制网络药理学研究

目的探讨丹参-当归治疗缺血性脑卒中(CIS)的潜在作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、Swiss TargetPrediction数据库获取丹参和当归的活性成分及作用靶点,并通过检索PubMed、中国知网相关文献进行补充;通过GeneCards、人类孟德尔遗传数据库(OMIM)、DisGeNET数据库获取CIS的潜在靶点;将丹参-当归治疗CIS的共有靶点导入String 11.0平台,构建活性成分与疾病靶点蛋白的蛋白相互作用(PPI)网络,利用Cytoscape 3.8.2软件构建疾病-药物-活性成分-靶点可视化网络;将共有靶点导入DAVID数据库进行基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,并利用Cytoscape 3.8.2软件构建活性成分-核心靶点-通路网络;利用AutoDock软件对疾病-药物-活性成分-靶点网络中度值排名前6的核心靶点和活性成分进行分子对接验证。结果共检索到82种活性成分,其中丹参65个、当归17个,潜在作用靶点787个,疾病靶点671个,共有靶点76个。度值排名前6的活性成分为丹参醇B、丹参新醌D、木犀草素、阿魏酸、藁本内酯、丹参酮ⅡA,核心靶点为MAPK14,MAPK1,AKT1,PTGS2,EGFR,JAK2。共获得GO功能条目2545个,其中生物学过程2244个,细胞组成128个,分子功能173个,分别涉及对脂多糖的反应、膜筏、内肽酶活性等;KEGG信号通路152条,主要涉及PI3K-Akt信号通路、脂质和动脉粥样硬化、钙信号通路等。分子对接结果证明了6种活性成分与其相应核心靶点均有较好的结合活性。结论丹参-当归治疗CIS具有多成分-多靶点-多通路的调控特点,其作用机制可能与抗炎、抗氧化应激、抗神经细胞凋亡、调节自噬功能等有关。

丹参及其制剂治疗冠心病的药理及机制研究新进展

传统中药丹参及其制剂在临床应用范围广泛,对于冠心病(coronary heart disease,CHD)有良好疗效,其脂溶性成分丹参酮ⅡA具有抗动脉粥样硬化、抗心肌缺血、抗心肌纤维化和抑制心肌肥厚等作用,通过作用于Toll样受体/核转录因子-κB(toll like receptor 4/nuclear transcription factor-κB,TLR/NF-κB)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)/NF-κB、磷脂酰肌醇3-激酶/蛋白激酶B(phosphoinositide 3-kinase/protein kinase B,PI3 K/AKT)、雷帕霉素靶蛋白/内皮型一氧化氮合酶(mammalian target of rapamycin/endothelial nitric oxide synthase,mTOR/eNOS)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)/Smad2/3、应激激活蛋白激酶(stressac-tivated pro-tein kinase,SAPK)/MAPK、胞外信号调节蛋白激酶(extracellular regulated protein kinases,ERK)/核转录因子红细胞系2相关因子2(nuclear factor erythroid-2-related factor 2,Nrf2)、胱抑素C/Wnt(cystatin C/Wnt,Cys-C/Wnt)等信号转导通路发挥效应;隐丹参酮通过抑制炎性介质预防早期冠脉粥样硬化。水溶性成分丹酚酸A通过调节PI3 K/Akt、丝氨酸/苏氨酸激酶(serine/threonine kinase,GSK-3β)、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)和ERK1/2等通路抑制心肌细胞凋亡,降低炎症水平,改善心肌梗死;丹酚酸B通过抑制TLR4和核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)炎性体表达减轻心肌损伤;丹参素通过抑制Janus酪氨酸蛋白激酶(janus tyrosine protein kinase,JAK)/信号转导及转录激活因子(signal transduction and transcriptional activator,STAT)信号通路改善微循环、抗炎抗氧化、抗内皮损伤和抗血小板聚集。丹参水溶性成分制剂的主要靶点有前列腺素-内过氧化物合酶(prostaglandin-endoperoxidase synthase 2,PTGS2)、半胱氨酸天冬氨酸蛋白酶(Caspase-3)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、基质金属蛋白酶9(matrix metalloproteinase-9,MMP9)、MAPKs、TLR4、JUN、STAT3、TLR/NF-κB、PI3 K/Akt、JAK2/STAT3和Nrf2/血红素加氧酶-1(heme oxygenase-1,HO-1)等,具有抗炎、改善血液流变性、保护血管内皮、抗血小板聚集等药理作用;复方丹参滴丸具有扩张冠脉、减少心肌耗氧、增加冠脉流量、增强心肌收缩等作用,还具备用量小、不良反应少,对胃肠刺激小等优点;冠心宁片治疗CHD的靶点包括核受体共激活因子2(nuclear receptor coactivator 2,NCOA2)、一氧化氮合酶2(nitric oxide synthase 2,NOS2)等,主要调控PI3 K/Akt、白细胞介素-17(interleukin-17,IL-17)、低氧诱导因子-1(hypoxic inducible factor-1,HIF-1)等通路;新加丹参饮具有扩张冠脉、增加血流量、改善微循环等作用;冠心丹参方的主要药理活性在于增加冠脉血流量,降低心肌耗氧,从而改善心肌缺血,提高心功能。

丹参及其有效成分对心血管系统的药理机制研究进展

中国传统药材丹参因极佳的活血祛瘀、通经止痛、清心除烦等功效历来被广泛用于医疗实践中,尤以在心血管系统中的应用突出。现代研究发现,丹参及其活性成分具有抗凝、降脂、抗血栓形成、抗炎抗氧化应激、降压、保护心肌细胞、减少心肌细胞凋亡率、保护血管和促进血管扩张、改善线粒体功能障碍和微循环、防治心室肥大等作用,使得其对心血管系统疾病有着良好的防治效果。综述丹参及其有效活性成分从抗动脉粥样硬化、保护心肌细胞、保护血管、改善心肌缺血和缺血再灌注损伤、防治高血压和心室肥大等内容,力求为丹参在心血管系统疾病的应用和研究提供参考。

丹参有效成分及药理作用研究进展

丹参是一种多年生植物,属于唇形科、丹参属,是一种遮荫草本植物。唇形科植物丹参的干燥根和根茎在中国通常被称为丹参,作为广泛使用的传统中药有着近2000年悠久历史,具有活血化瘀、通经止痛、清心除烦、凉血消痈之功效。丹参的有效成分复杂,并且具有多种药理作用。丹参的化学成分主要为水溶性的酚酸类以及脂溶性的丹参酮类化合物,该植物及其提取物具有抗炎、抗氧化、抗动脉粥样硬化、抗肿瘤、抗纤维化、糖尿病肾病保护等药理作用。文章参阅近些年文献以及相关研究深入阐述丹参有效成分以及药理作用,以期为丹参临床应用研究提供理论依据。目前关于丹参的药理作用研究虽取得了一定的成果,但对其化学成分及药理机制的研究尚不完善,后续可从细胞、组织、分子生物学、代谢学等多学科、多方面进行深入研究,以期为明确丹参的有效成分及开展丹参有效成分机制和临床应用研究提供理论依据。

丹参活性成分防治心力衰竭药理作用研究进展

丹参活性成分通过抑制磷脂酰肌醇3-激酶/蛋白激酶B信号通路激活,阻止转化生长因子β(transforming growth factor β,TGF-β)/Smad信号通路激活,抑制细胞外调节蛋白激酶(extracellular regulatory protein kinase, ERK)1/2-GATA结合蛋白4信号通路,抑制基质金属蛋白酶的激活,下调半乳糖凝集素-3的表达,抑制血管紧张素/转化生长因子/骨膜蛋白信号通路,调控激活素A/卵泡抑素系统,抑制Ras信号通路,减轻心肌纤维化,延缓心脏重构。丹参活性成分通过抑制Toll受体/髓样分化因子/肿瘤坏死因子受体相关因子/核因子κB信号通路激活,减轻心肌炎症反应。丹参活性成分通过恢复氧化和抗氧化的平衡,调节核因子E_(2)相关因子2/丝裂原活化蛋白激酶信号通路,减轻氧化应激反应,降低心肌氧化损伤。丹参活性成分通过阻断NOD样受体家族蛋白3炎症小体形成,激活沉默信息调节器1信号通路,激活死亡域相关蛋白/丝裂原激活蛋白激酶/细胞外调节蛋白激酶1/2通路,调节凋亡相关蛋白的分泌,促进c-Jun氨基末端激酶/ERK信号通路,抑制TGF-β1信号通路,降低心肌细胞凋亡,发挥心脏保护作用。丹参活性成分通过调节腺苷酸活化蛋白激酶/哺乳动物雷帕霉素靶蛋白通路,增强细胞自噬,以促进心脏修复。丹参活性成分通过降低心房颤动,发挥抗心衰作用。

丹参及其药对的药理研究进展

丹参为我国传统中药,常用大宗药材品种之一,用药历史久远,为活血祛瘀、通经止痛的良药,具有抗肿瘤、保护心脑血管、调节女性生殖、抗氧化等药理作用。在临床应用中,丹参常与川芎、红花、葛根、黄芪、大黄、当归等组成药对使用,可增强或扩大疗效。重点对丹参的药理作用及常用丹参药对的药理作用、临床应用进行综述,并对丹参药对使用规律、配伍理论进行探讨,以期为丹参及其药对进一步的开发利用提供参考。

天麻-丹参药对治疗高血压作用机制的网络药理学分析及实验验证

目的基于网络药理学方法及动物实验验证探讨天麻-丹参药对治疗高血压的作用机制。方法(1)通过TCMSP、BATMAN及TCMIP数据库筛选天麻-丹参药对活性成分及其作用靶点;通过Drugbank、Genecard、TTD、Disgenet数据库检索获得高血压疾病相关靶点;对药对的活性成分作用靶点与高血压疾病相关靶点取交集(共同靶点),所得交集靶点即为天麻-丹参药对治疗高血压的潜在作用靶点。将天麻-丹参药对活性成分及其作用靶点导入Cytoscape 3.9.1软件,构建“中药-活性成分-靶点”网络,筛选关键活性成分;构建潜在作用靶点的蛋白互作(PPI)网络,筛选潜在核心靶点;使用Metascape平台对潜在作用靶点进行GO功能及KEGG通路富集分析。选择关键活性成分与潜在核心靶点进行分子对接验证。(2)将30只雄性自发性高血压大鼠(SHR)随机分为模型组、西药组(坎地沙坦酯,0.72 mg·kg^(-1))及天麻-丹参药对低、中、高剂量组(2.25、4.50、9.00 g·kg^(-1)),另选雄性WKY大鼠为空白组,每组6只,每日1次,连续灌胃给药8周。分别在给药前及药物干预2、4、6、8周后检测大鼠尾动脉收缩压;采用HE染色法观察胸主动脉组织病理变化;Western Blot法检测腹主动脉中GRP78、CHOP、Caspase-12蛋白表达水平。结果(1)共得到天麻-丹参药对活性成分83个,筛选出天麻-丹参药对治疗高血压的潜在作用靶点(交集靶点)158个;5个关键活性成分:对羟基苯甲酸、4-羟基苄胺、丹参酮Ⅰ、丹参酮、γ-谷甾醇;6个潜在核心靶点:IL6、TNF、CASP3、JUN、PTGS2、IL1B;GO功能富集分析得到1826条生物学过程条目、89条细胞组分条目、199条分子功能条目;KEGG通路富集分析获得186条通路,主要涉及神经活性配体-受体相互作用、钙信号通路、炎症应答(如TNF和MAPK信号通路)、血管保护(如HIF-1和cAMP信号通路)、氧化应激(如PI3K-Akt信号通路)等信号通路;丹参酮Ⅰ、丹参酮对6个潜在核心靶点均有较强的结合力,γ-谷甾醇对IL6、CASP3、JUN、PTGS2、IL1B具有较强的结合力。(2)与空白组比较,模型组大鼠的收缩压显著升高(P<0.01);胸主动脉内皮损伤明显,内皮细胞形态异常,可见肿胀、脱落细胞,组织内膜排序紊乱,内膜结构不完整,出现内膜增厚;腹主动脉中GRP78、CHOP、Caspase-12蛋白表达量显著升高(P<0.01)。与模型组比较,给药组大鼠的收缩压均显著下降(P<0.01);胸主动脉损伤减轻,内皮细胞形态、内膜结构及厚度等均得到不同程度改善;腹主动脉中GRP78、CHOP、Caspase-12蛋白表达量显著降低(P<0.01)。结论天麻-丹参药对可能是通过对羟基苯甲酸、丹参酮、γ-谷甾醇等关键活性成分,作用于IL6、TNF、CASP3、JUN、PTGS2、IL1B等核心靶点,调控TNF信号通路、MAPK信号通路、PI3K-Akt信号通路、PERK信号通路等关键信号通路,发挥改善血管内皮功能障碍、抑制内质网应激及降血压的作用。

基于网络药理学与分子对接探讨当归丹参药对治疗急性肝损伤的作用机制

基于网络药理学与分子对接技术及试验验证探讨当归丹参药对(ASM)治疗急性肝损伤(ALI)的作用机制。本研究采用网络药理学方法筛选ASM治疗ALI的核心作用靶点,构建核心靶点进行蛋白互作网络和分子对接分析,通过构建大鼠ALI模型检测相关血清生化指标和肝脏蛋白的表达模式并验证分子对接结果。结果显示,从ASM中获得了67个活性成分,其中75个靶点与ALI相互作用。蛋白质–蛋白质相互作用(PPI)网络分析显示,TP53、CASP3、JUN、STAT3、AKT1、VEGFA、TNF、IL-6、MMP9和PTGS2可能是ASM治疗ALI的关键作用靶点。基因本体(GO)分析和京都基因和基因组百科全书(KEGG)信号通路分析表明,靶点主要富集于乙肝信号通路、脂质与动脉粥样硬化、糖基化终产物受体(RAGE)和细胞凋亡等信号通路。分子对接结果显示,核心靶点(TP53和CASP3)与β-谷甾醇、黄芩苷和隐丹参酮有良好的结合位点。体内试验结果表明,ASM能够有效改善四氯化碳(CCl4)诱导的大鼠肝损伤,降低大鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)及丙二醛(MDA)的表达水平,提高肝脏超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性及谷胱甘肽(GSH)水平,上调肝脏组织中BCL2蛋白的表达水平,下调BAX、CASP3和TP53蛋白的表达水平。本研究表明,ASM改善ALI的机制可能是通过β-谷甾醇、黄芩苷和隐丹参酮等主要化学成分作用于TP53和CASP3等关键靶点,通过抑制氧化应激及调控细胞凋亡等信号通路来实现。本研究为临床上ASM治疗ALI提供理论与试验依据,为进一步研究和发展传统中医药提供新的思路和方法。

川芎-丹参配伍治疗脊髓损伤的网络药理学研究与验证

目的:基于网络药理学,预测川芎-丹参配伍治疗脊髓损伤的作用机制。方法:利用网络药理学工具,获得川芎-丹参治疗脊髓损伤的有效成分、核心靶点及信号通路。采用改良Allen重物打击法构建脊髓损伤模型,采用酶联免疫吸附试验(ELISA)测定各组大鼠活性氧(ROS)、丙二醛(MDA)水平;采用蛋白质印迹法检测各组大鼠脊髓组织中磷脂酰肌醇3激酶(PI3K)、p-PI3K、蛋白激酶B(AKT)、p-AKT蛋白表达。结果:化合物-靶点网络包含154个化合物和484个相应靶点;基因本体(GO)功能富集分析得447个条目;京都基因和基因组百科全书(KEGG)通路富集分析得到126条信号通路。动物实验结果表明,与假手术组比较,模型组ROS、MDA水平显著增高(P<0.01);p-PI3K、p-AKT蛋白表达显著下降(P<0.01);与模型组比较,中药高剂量组ROS、MDA水平显著下降(P<0.01);p-PI3K、p-AKT蛋白表达显著增高(P<0.01)。结论:川芎-丹参联合治疗脊髓损伤具有多成分、多靶点、多通路的优势,其作用机制可能与调控PI3K/AKT信号通路有关。

丹参活性成分治疗心血管疾病的药理作用、临床应用及不良反应研究进展

心血管疾病是目前我国死亡率最高的疾病,随着心血管疾病的危险因素日益增加,其患病率持续升高,防治心血管疾病成为当前临床研究的重中之重。丹参是中国常见的中药材之一,具有活血化瘀、凉血消痈的功效,常被用于心脑血管科、妇科的常见病症的治疗。本文主要从丹参的药理作用、临床应用及不良反应等方面系统地总结其在心血管疾病的研究成果。

基于本草考证的丹参功效研究

丹参用药历史悠久,《神农本草经》中即有相关记载。2020版《中华人民共和国药典》载丹参功效为活血祛瘀、通经止痛、清心除烦、凉血消痈。但历代医家对丹参的功效理解认识不一,甚至有相悖的现象。本研究分别从汉晋南北朝时期、唐宋金元时期、明清时期和近代时期,通过本草考证对历代本草进行深入挖掘与梳理。经过系统考证,梳理了历代主流本草中丹参功效认识的沿革。发现历代本草中所记录的正品丹参即为历版《中华人民共和国药典》所载的丹参品种,主要功效为活血化瘀。

基于网络药理学与分子对接探究黄芪-葛根-丹参治疗糖尿病视网膜病变的作用机制

本文运用网络药理学研究方法探究黄芪-葛根-丹参中有效成分治疗糖尿病视网膜病(DR)的潜在机制。采用TCMSP平台筛选黄芪-葛根-丹参的活性成分及靶点,通过GeneCards、OMIM、TTD、DisGeNET和DrugBank数据库筛选DR相关靶点,以及在UniProt数据库查询成分和疾病靶点对应的基因名。利用STRING数据库结合Cytoscape软件进行拓扑分析,筛选出核心靶标并绘制网络互作图,再利用Metascape平台对药物-疾病共同靶点进行GO和KEGG通路富集分析并建立成分-靶点-通路网络模型,最后使用Discovery Studio和AutoDock Vina软件对其重要化合物与DR关键靶点进行分子对接验证。通过上述方法共筛选得到中药有效成分89个及靶点基因247个,DR相关基因共4231个,其中药物-疾病共同靶点145个,涉及有效成分76个;GO富集分析涉及生物过程1864条(P<0.05);KEGG富集分析通路共205条(P<0.05),主要有AGE-RAGE、P13K-Akt、TNF和HIF-1信号通路等;关键成分槲皮素、木犀草素、山柰酚、异鼠李素、刺芒柄花素和丹参酮IIA等能与相应靶点蛋白AKT1、TNF、VEGFA、TP53和IL-6形成有效的分子结合。黄芪-葛根-丹参治疗DR的机制可能与抑制炎症因子分泌、降低氧化应激、抑制新生血管形成和抑制细胞凋亡等作用有关,可为后期临床应用和试验提供理论依据。

基于网络药理学探讨丹参-檀香治疗冠心病的作用机制

目的:应用网络药理学相应原理探讨丹参-檀香药对治疗冠心病(CHD)的作用机制。方法:在网络药理学的相应原理基础上,首先分别用“丹参”和“檀香”为关键词,在中药系统药理学数据库与分析平台(TCMSP)中获取其活性成分和相应的靶点蛋白,在数据库检索“冠心病”,筛选出潜在的、可治疗CHD的“丹参-檀香”药对的靶点,然后在DAVID数据库和Matescape数据库中进行GO分析、KEGG的富集分析。结果:通过使用TCMSP进行检索,可得到檀香的有效成分有3个,丹参的有效成分有65个。在韦恩图中,筛选出的CHD与药对共有靶点27个。KEGG和GO富集分析表明丹参-檀香药对改善CHD可能与脂质与动脉粥样硬化途径、流体切应力和动脉粥样硬化途径有关。分子对接结果表明丹参-檀香能够与CHD相关靶点紧密结合。分析表明,丹参-檀香配伍后可能存在针对CHD的协同作用。结论:丹参-檀香药对治疗CHD的过程涉及多种有效成分、靶点和通路,该结果可进一步为研究丹参-檀香药对治疗CHD的作用机制提供相应参考。