Study on multi-target mechanism of Radix et Rhizoma Rhei (Dahuang) and Semen Persicae (Taoren) on adhesion intestinal obstruction based on network pharmacology

Objective: To explore the mechanism of action of Radix et Rhizoma Rhei (Dahuang)(RERR) and Semen Persicae (Taoren)(SP) on adhesive intestinal obstruction (AIO). Methods: The main targets of the active ingredients of RERR and SP were filtered based on the traditional Chinese medicine system pharmacology analysis platform. Cytoscape 3.2.1 was applied to build the ingredient-target network of RERR and SP for AIO. Results: Fifteen active components were predicted from the RERR and SP herb pair, such as aloe-emodin, catechin, rhein, gibberellin (GA) 119, GA120 and GA121. These components were applied to 59 targets mainly involved in many biological processes such as signal transduction, anti-apoptosis, and inflammatory response involved in activating the immune effect. Conclusion: This study proposes the system pharmacology method and identifies the potent combination therapeutic mechanism of RERR and SP for AIO. This strategy will provide a new insight to the study of herb combinations.

Identification of Mucilage Cavity as a Significant Microscopic Characteristic Existing in Phloem Instead of Pith of Radix et Rhizoma Rhei

The morphologic and microscopic features of Radix et Rhizoma Rhei were studied. The study verified that the mucilage cavities did exist in phloem of rhizomes and roots or abnormal vascular bundles. Also, they were in similar distribution in three species of Radix et Rhizoma Rhei. The diagnostic characteristic for microscopic identification was found to be the similar distribution of abnormal vascular bundles in pith of rhizomes in all three species. And the appearance of the crude drug varied more depending on the plants＇ geographical origin and different preliminary treatment on the spot of collection than on the species differences. Our findings, having not been delineated clearly so far in the previous reports, are helpful for clarifying current descriptions in different literatures or standards and make a full understanding on microscopic and macroscopic identification of Radix et Rhizoma Rhei.

Study on the mechanism and active components of Radix et Rhizoma Rhei in the treatment of Alzheimer's disease based on molecular docking

Objective:To explore the mechanism and active components of Radix et Rhizoma Rhei in the treatment of Alzheimer's disease(AD)based on molecular docking.Methods:22 major components of Radix et Rhizoma Rhei were screened from TCMSP and related literatures,which docked with the key targets of NLRP3/Caspase-1/GSDMD signaling pathway.NLRP3,Caspase-1,GSDMD inhibitors MCC950,ML132 and LDC7559 were used as positive control to analyze the docking results.Results:The docking results showed that the main components of Radix et Rhizoma Rhei had different degrees of binding with NLRP3,Caspase-1 and GSDMD targets,and the potential active components were mutanochrome and physciondiglucoside.Conclusion:Molecular docking predicts that the main components of Radix et Rhizoma Rhei may act on NLRP3/Caspase-1/GSDMD signaling pathway,and the active components may be mutanochrome and physciondiglucoside,which provides theoretical basis for revealing the anti-inflammatory mechanism and active components of Radix et Rhizoma Rhei in the treatment of AD.

Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics

Objective:Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry(HPLC-MS/MS)and hydrogen nuclear magnetic resonance spectroscopy(^(1)H NMR),the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma(RhRR,Dahuang in Chinese),Eupolyphaga Steleophaga(EuS,Tubiechong in Chinese)combined with RhRR acting on acute liver injury were explored.Methods:Models of acute liver injury were established,and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS.The liver tissues of different groups of mice were analyzed by ^(1)H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.Results:Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups,and the absorption of free anthraquinone in RhRR increased after compatibility with EuS.In addition,the pathological state of acute liver injury in rats can selectively promote the absorption of emodin,chrysophanol,physcion and aloe emodin.Through 15 differential metabolites in the liver tissue of acute liver injury mice,it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid,alanine,aspartic acid and glutamic acid,and phosphoinositide.However,the regulation of RhRR was weaker than that of RhRR-EuS.Conclusion:For the first time,we studied the pharmacokinetics and metabolomics differences of RhRREuS and RhRR in rats and mice with acute liver injury,in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae) herb pair

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.

国医大师张志远先生大黄方药解析

运用中医各家学说名医研究方法,以国医大师张志远先生大黄药性研究为例,收集张志远先生大黄药性相关论述,从药物溯源、功用考辨、疑难病证治疗方面,从大黄化食辨、上焦病忌大黄辨、破血止血辨中进一步研究大黄功用,论述大黄在虚劳、郁证、狂证治疗中的独特价值,从中医文献中考证解析大黄作用机理,从中医各家学说学科角度重新认识理解张志远先生理论渊源与学术创新,为继承发扬国医大师学术思想服务。

枳实消痞方联合大黄神阙穴贴敷治疗阿片类药物相关性便秘临床观察

目的探讨枳实消痞方联合大黄神阙穴贴敷治疗阿片类药物相关性便秘(OIC)的临床疗效。方法选取医院中西医结合科2021年1月至2022年1月收治的口服盐酸羟考酮缓释片治疗癌性疼痛的OIC患者70例,按随机数字表法分为观察组和对照组,各35例。观察组患者予枳实消痞方联合大黄粉神阙穴贴敷治疗,对照组患者予乳果糖口服溶液治疗,均连续用药2周。结果观察组患者的便秘治疗总有效率为85.71%,显著高于对照组的57.14%(P<0.05)。观察组患者治疗后的慢性便秘严重程度评分量表及便秘患者生活质量量表各项评分和总分均显著低于对照组(P<0.05);观察组患者的卡氏体力状况量表(KPS)评分有效率为82.86%,显著高于对照组的60.00%(P<0.05)。结论枳实消痞方联合大黄神阙穴贴敷能缓解OIC症状,改善患者的生活质量,增强其体力。

A Quantitative Method for Simultaneous Determination of Four Anthraquinones with One Marker in Rhei Radix et Rhizoma

Objective To develop a quantitative method for simultaneously determining multi-components in Rhei Radix et Rhizoma using one chemical reference substance.Methods The contents of multi-components were calculated by the UV relative correction factors(RCFs)of chrysophanol,physcion,and rhein to emodin.Results The values of RCFs at 274 nm for rhein,chrysophanol,and physcion to emodin were 0.712,0.674,and 1.051.The calibration curves were linear over the ranges of 0.02-4.08,0.02-4.12,0.07-12.92,and 0.02-3.68μg/mL for rhein,emodin, chrysophanol,and physcion,respectively.The contents of emodin in 18 samples were determined by the external standard method,and the contents of the other three anthraquinone aglycones were calculated according to their RCFs. Conclusion No significant difference is found in comparison with the classical method,indicating that the RCFs have high reliability within their linear ranges and could be used in quality control of Rhei Radix et Rhizoma.The quantitative analysis of multi-component with a single marker is especially suitable for herbal medicines containing unstable or hard to be purified components as quality control markers.

大黄的主要化学成分及药理作用研究进展

大黄是我国大宗中药材之一,其药用历史悠久且临床应用广泛。大黄具有泻下攻积、清热泻火、凉血解毒、逐瘀通经和利湿退黄等功效,其主要化学成分包括蒽醌类、蒽酮类、二苯乙烯类、苯丁酮类、多糖类、鞣质类和挥发油等,药理作用主要包括泻下、抗炎、抗肿瘤、调节血脂、肾保护、肝保护及抗血管生成等。本文对大黄的主要化学成分及现代药理作用进行概括总结,旨在为大黄的临床使用及药理作用研究提供参考依据。

肠道菌群与慢性肾脏病的关系及中医药干预作用

慢性肾脏病作为一种严重危害身心健康的进行性疾病,发病机制复杂,疾病缠绵难愈,病情预后不佳。近年来,随着对肠道菌群的研究不断深入,发现胃肠道微生物群在维持机体内环境的稳定及身心健康上具有重要的作用。研究发现肠道、肾脏可通过肠道菌群相互影响,双向调控,形成肠-肾轴平衡,维持机体健康,肠-肾轴失衡与慢性肾脏病的发生发展存在一定的关联。中医药具有多靶点、多通路、多途径的特点,临床补虚泻实、扶正祛邪,对慢性肾脏病的防治具有一定的效果,其中以大黄、黄芪颇为显著。故该文基于肠-肾轴探讨中医药防治慢性肾脏病的可能作用机制,发现大黄、黄芪可调节肠道菌群结构,降低致病菌的表达,促进益生菌的生成,维持菌群平衡,延缓肠源性内毒素的移位,修复肠道黏膜的损伤,维持肠道屏障的完整。此外还能减轻局部及周身氧化应激及炎症反应,减轻肾脏损伤,恢复肾功能。但临证之时还需谨守病机,三因制宜,辨证论治,灵活配伍,斟酌剂量。肠道菌群可能是防治慢性肾脏病的关键靶点,但慢性肾脏病病机复杂,与多个系统相关联,所以基于肠道菌群加强慢性肾脏病与多学科中医药研究将是未来科学研究的发展方向。

基于电子感官系统和GC-IMS技术的大黄饮片基原辨识研究

目的探寻不同基原大黄饮片滋味、气味和挥发性有机物的差异,对大黄饮片进行基原辨识。方法采用电子舌、电子鼻和气相-离子迁移谱(GC-IMS)技术,对不同基原大黄饮片间的滋味、气味和挥发性有机物进行对比分析,运用主成分分析(PCA)、偏最小二乘法判别分析(PLS-DA)、正交偏最小二乘法判别分析(OPLS-DA)、Fisher判别等方法对大黄饮片基原进行辨识研究并建立基原判别标准。结果3种基原大黄饮片的滋味差异主要表现在苦味、涩味以及苦和涩的回味,气味的差异主要表现在无机硫化物、芳香成分有机硫化物、甲烷等短链烷烃、醇醚醛酮类化合物以及氮氧化合物,差异性挥发性有机物主要为醇醛酮酸类成分,并且8批样品均能很好地聚集为3类。根据差异性挥发物质之间的峰强度比值可有效辨识3种大黄饮片,如当2-乙酰基呋喃峰强度是异丁酸[二聚体]峰强度的3~19倍时为药用大黄。结论本研究建立的判别模型以及特征挥发性物质峰强度判别标准可用于大黄饮片基原的鉴别。

三七皂苷成分及临床药理作用研究进展

三七作为传统中草药现已受到医药界的共同认可和关注,现代植物化学研究表明三七皂苷是三七的主要化学成分。现代药理研究及临床应用发现,其具有抗癌、抗氧化及治疗心血管疾病等作用。综述三七主要化学成分和药理作用的研究进展,以期为三七的临床应用及后期研究提供帮助。

黄连大黄药对调控ROS/NF-κB/GSDMD信号通路对2型糖尿病大鼠胰岛β细胞焦亡的影响

目的基于活性氧(reactive oxygen species,ROS)/核转录因子κB(nuclear transcription factor-κB,NF-κB)/消皮素D(gasdermin D,GSDMD)焦亡信号通路探讨黄连大黄药对发挥2型糖尿病(type 2 diabetes mellitus,T2DM)胰岛β细胞保护作用的分子机制。方法选取自发性T2DM大鼠—Goto-Kakizaki(GK)大鼠构建动物模型,24只符合成模标准的GK大鼠随机分为模型组、二甲双胍组(0.1 g·kg^(-1)·d^(-1))、黄连大黄高剂量组(4.72 g·kg^(-1)·d^(-1))及低剂量组(2.36 g·kg^(-1)·d^(-1)),并随机选取6只正常Wistar大鼠设为正常组,连续灌胃干预8周后采用免疫荧光法检测大鼠胰腺组织胰岛素(insulin,INS)阳性表达,RT-PCR法检测细胞增殖相关细胞周期蛋白D1(cyclin D1,CCND1)、髓细胞瘤病毒癌基因(cellular-myelocytomatosis viral oncogene,c-Myc)mRNA表达,TUNEL染色检测胰岛细胞死亡,流式细胞术检测ROS水平,Western blot法检测NF-κB p65、GSDMD及消皮素D N端片段(gasdermin D-N,GSDMD-N)蛋白的表达,ELISA法检测白介素1β(interleukin 1β,IL^(-1)β)水平。结果与正常组比较,模型组大鼠胰腺组织INS平均光密度值显著降低,CCND1、c-Myc mRNA表达显著下调,TUNEL阳性率、ROS水平和NF-κB p65、GSDMD-N蛋白表达以及IL-1β水平均显著升高(P均<0.01);与模型组比较,黄连大黄低剂量组INS平均光密度值有效升高,CCND1、c-Myc mRNA表达有效上调,TUNEL阳性率、ROS水平以及NF-κB p65、GSDMD-N蛋白表达、IL-1β水平均明显降低(P<0.01,P<0.05),黄连大黄高剂量组仅c-Myc mRNA表达有效上调,NF-κB p65蛋白表达明显降低(P均<0.05)。结论黄连大黄药对可能通过ROS/NF-κB/GSDMD信号通路抑制细胞焦亡,促进增殖进而起到保护T2DM大鼠胰岛β细胞的作用。

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。

中药内服方治疗毒蛇咬伤的用药规律的数据挖掘

【目的】采用数据挖掘方法分析国内主要文献数据库及《中华医方》外科卷中有关治疗毒蛇咬伤的中药内服方,以探讨其潜在的组方用药规律,为基层治疗毒蛇咬伤提供参考。【方法】通过检索中国知网、维普、万方数据库中有关治疗毒蛇咬伤的中药内服方,并查阅《中华医方》外科卷,筛选其中治疗毒蛇咬伤的古方。运用Excel软件提取方药的相关信息,采用R语言对中药的使用频率、性味归经、关联规则、聚类情况等进行分析。【结果】共得到治疗毒蛇咬伤内服方187首,涉及中药284味;使用频次居前15位的中药依次为半边莲、大黄、白芷、甘草、重楼、地黄、黄连、黄芩、金银花、赤芍、牡丹皮、白花蛇舌草、白茅根、车前草、半枝莲;治疗毒蛇咬伤方药的药味偏苦、辛、甘,药性偏寒,归经以归肝、肺经为主;关联规则分析及聚类分析得到以大黄、半边莲、重楼为基础的核心组方。【结论】中药治疗毒蛇咬伤以清热解毒为主,常在大黄、半边莲、重楼的基础上配以清热凉血、熄风止痉、清热利尿等药物。

酒大黄(唐古特大黄)配方颗粒超高效液相色谱指纹图谱及化学模式识别研究

目的为酒大黄(唐古特大黄)配方颗粒的质量评价提供参考。方法采用超高效液相色谱(UPLC)法,色谱柱为CORTECS UPLC T3柱(100 mm×2.1 mm,1.6μm),流动相为甲醇-0.05%磷酸水溶液(梯度洗脱),流速为0.25 mL/min,检测波长为265 nm,柱温为35℃,进样量为1μL。采用中药色谱指纹图谱相似度评价系统(2012版)建立21批样品的UPLC指纹图谱,并进行相似度评价。采用聚类分析(CA)法、主成分分析(PCA)法、正交偏最小二乘-判别分析(OPLS-DA)法评价样品质量,并筛查标志性成分。结果共标定并指认出18个共有峰。21批样品的指纹图谱相似度均大于0.950,3种分析方法均将样品分为3类,OPLS-DA法分析显示,异莲花掌苷、白藜芦醇-4'-O-β-D-(6''-O-没食子酰)葡萄糖苷、儿茶素、大黄酚、没食子酸、番泻苷A、莲花掌苷和大黄酚-1-O-β-D-葡萄糖苷为制剂的标志性成分。结论该方法简单可行,可为酒大黄(唐古特大黄)配方颗粒的质量评价提供参考。

基于网络药理学研究“黄芪-大黄-积雪草”角药治疗慢性肾功能衰竭的作用机制

目的通过网络药理学方法研究“黄芪-大黄-积雪草”治疗慢性肾功能衰竭(chronic renal failure,CRF)的核心成分、作用靶点、信息通路及作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)获取并筛选“黄芪-大黄-积雪草”角药的活性成分及作用靶点,CRF相关靶基因通过GeneCards、人类孟德尔遗传数据库和疾病关联数据库(GAD)数据库检索,对CRF的相关靶点及“黄芪-大黄-积雪草”角药的作用靶点取交集,其中蛋白信息转换成基因信息通过Uniprot数据库完成,绘制Venny图。将靶点导入STRING数据库制作蛋白质相互作用(PPI)网络图,通过Cytoscap3.9.1软件对PPI网络进一步分析,得到关键蛋白靶点。借助京都基因与基因组百科全书(KEGG)与注释、可视化和集成发现数据库(DAVID)数据库进行基因本体(GO)功能及KEGG信号通路富集分析。应用Cytoscape 3.9.1软件构建“黄芪-大黄-积雪草”角药治疗CRF的疾病-通路-靶点-成分-药物网络图。结果获得“黄芪-大黄-积雪草”共39种活性成分、226个靶点,其中黄芪-大黄-积雪草角药治疗CRF关键靶点82个。PPI网络图显示78个节点,互作关系269条,平均度值为6.9。GO分析共得到富集结果614个,KEGG分析得到142条信号通路,涉及晚期糖基化终未产物(AGE-RAGE)信号通路、癌症通路、肿瘤坏死因子(TNF)信号通路、白细胞介素(IL)-17信号通路、Toll样受体信号通路等。结论“黄芪-大黄-积雪草”角药可通过多种成分、多个靶点、多条信号通路治疗CRF。

生大黄灌肠、芒硝外敷联合泮托拉唑治疗重症急性胰腺炎临床研究

目的:观察生大黄灌肠、芒硝外敷联合泮托拉唑治疗重症急性胰腺炎(SAP)的临床疗效及对血清淀粉酶(AMY)、脂肪酶(LPS)的影响。方法:选取86例SAP患者为研究对象,随机分为对照组及观察组各43例。对照组在营养支持治疗、解痉止痛、抗感染及胃肠减压等基础上加用泮托拉唑治疗,观察组在对照组基础上联合生大黄灌肠、芒硝外敷治疗。比较2组临床疗效、中医证候评分、胃肠功能恢复时间、并发症发生率,以及治疗前后白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)、AMY、LPS水平。结果:观察组总有效率为90.70%,对照组为69.77%,2组比较,差异有统计学意义(P<0.05)。治疗后,2组腹痛腹胀、痞满燥实等证候评分均较治疗前降低(P<0.05),且观察组上述2项中医证候评分均低于对照组(P<0.05)。治疗后,2组血清IL-6、TNF-α水平均较治疗前降低(P<0.05),且观察组IL-6、TNF-α水平均低于对照组(P<0.05)。治疗后,2组AMY、LPS水平均较治疗前降低(P<0.05),且观察组AMY、LPS水平均低于对照组(P<0.05)。治疗后,观察组腹痛缓解、腹部压痛缓解、排便恢复、肠鸣音恢复时间均短于对照组,差异有统计学意义(P<0.05)。治疗期间,观察组并发症发生率为4.65%,对照组为16.28%,2组比较,差异无统计学意义(P>0.05)。结论:生大黄灌肠、芒硝外敷联合泮托拉唑治疗SAP患者能够减轻机体的炎症反应,改善中医证候,加快胃肠功能恢复,有效提高临床疗效。

不同配伍比例大黄-丹参有效成分溶出率及抗模型大鼠肾纤维化作用比较

目的比较大黄-丹参药对在不同配伍比例时两药7个有效成分(芦荟大黄素、大黄酸、大黄素、大黄酚、大黄素甲醚、丹酚酸B、丹参酮ⅡA)溶出率和抗模型大鼠肾纤维化作用的差异。方法采用高效液相色谱(HPLC)法测定大黄单提液、丹参单提液及6种配伍比例(1∶1、1∶1.25、1∶1.75、1∶2、1∶3、1∶4)大黄-丹参混提液中7个有效成分的含量及溶出率。采用单侧输尿管梗阻复制肾纤维化大鼠模型,比较大黄、丹参及1∶1.25、1∶1.75、1∶2配伍比例大黄-丹参混提液对模型大鼠肾组织病理形态及血尿素氮(BUN)、血清肌酐(SCr)、24 h尿蛋白(24 h-UTP)水平的影响。结果不同配伍比例大黄-丹参混提液中7个有效成分含量均小于单提液,大黄-丹参(1∶2)混提液中有效成分整体溶出率优于其他配伍比例。与模型组比较,大黄单提液、丹参单提液及1∶1.25、1∶1.75、1∶2配伍比例大黄-丹参混提液作用下,大鼠肾纤维化程度显著减轻,BUN、SCr、24 h-UTP水平均显著降低,其中以大黄单提液作用最强。结论所建立的含量测定方法可用于大黄-丹参药对中7个有效成分的含量测定;大黄-丹参不同比例配伍后有效成分溶出率均小于单提液;大黄-丹参配伍后在抗模型大鼠肾纤维化作用方面未产生协同作用,大黄单提液抗肾纤维化作用最佳。

Research Overview of Zhuang Medicine Fumigation Lotions

At present,there is little research on the application of Zhuang medicine fumigation lotions in skin diseases,and there is no research on related preparation processes and quality standards.In this paper,the characteristics of its formulation and the research progress in skin diseases are reviewed,in order to deepen the understanding of Zhuang medicine fumigation lotions and provide a more detailed theoretical basis for its clinical research,development and application.