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.

Identification of potential anti-pneumonia pharmacological components of Glycyrrhizae Radix et Rhizoma after the treatment with Gan An He Ji oral liquid

Glycyrrhizae Radix et Rhizoma,a traditional Chinese medicine also known as Gan Cao(GC),is frequently included in clinical prescriptions for the treatment of pneumonia.However,the pharmacological components of GC for pneumonia treatment are rarely explored.Gan An He Ji oral liquid(GAHJ)has a simple composition and contains GC liquid extracts and paregoric,and has been used clinically for many years.Therefore,GAHJ was selected as a compound preparation for the study of GC in the treatment of pneumonia.We conducted an in vivo study of patients with pneumonia undergoing GAHJ treatments for three days.Using the intelligent mass spectrometry data-processing technologies to analyze the metabolism of GC in vivo,we obtained 168 related components of GC in humans,consisting of 24 prototype components and 144 metabolites,with 135 compounds screened in plasma and 82 in urine.After analysis of the metabolic transformation relationship and relative exposure,six components(liquiritin,liquiritigenin,glycyrrhizin,glycyrrhetinic acid,daidzin,and formononetin)were selected as potential effective components.The experimental results based on two animal pneumonia models and the inflammatory cell model showed that the mixture of these six components was effective in the treatment of pneumonia and lung injury and could effectively downregulate the level of inducible nitric oxide synthase(iNOS).Interestingly,glycyrrhetinic acid exhibited the strongest inhibition on iNOS and the highest exposure in vivo.The following molecular dynamic simulations indicated a strong bond between glycyrrhetinic acid and iNOS.Thus,the current study provides a pharmaceutical basis for GC and reveals the possible corresponding mechanisms in pneumonia treatment.

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.

Mechanism of Inhibitory Effect of Essential Oil from Valerianae Jatamansi Rhizoma et Radix on Activation of Microglia

[Objectives]To investigate the inhibitory effect and possible mechanism of essential oil from Valerianae Jatamansi Rhizoma et Radix on microglia activation induced by lipopolysaccharide(LPS).[Methods]The LPS-induced microglia activation model was established and treated with different doses of essential oil from Valerianae Jatamansi Rhizoma et Radix.MTT assay was used to detect cell viability,ELISA to detect IL-6 secretion,RT-PCR to detect mRNA expression levels of IL-6,IL-1β,NF-κB,and IκBα,Western blotting to detect the protein expression of IL-6,IL-1β,NF-κB,IκBα,and their phosphorylated products.[Results]Compared with the normal control group,the model group showed increased IL-6 content(P<0.01),upregulated mRNA and protein levels of IL-6,IL-1β,and NF-κB(P<0.01),and elevated ratio of P-IκBα/IκBα(P<0.05).Compared with the model group,4 and 2μg/L essential oil from Valerianae Jatamansi Rhizoma et Radix reduced the content of IL-6(P<0.05),while 4,2,and 1μg/L essential oil from Valerianae Jatamansi Rhizoma et Radix down-regulated the mRNA and protein levels of IL-6,IL-1β,and NF-κB to varying degrees(P<0.05 or P<0.01),up-regulate the mRNA expression of IκBα(P<0.05 or P<0.01),and decreased the ratio of P-IκBα/IκBα(P<0.05 or P<0.01).[Conclusions]Essential oil from Valerianae Jatamansi Rhizoma et Radix can inhibit LPS-induced microglia activation,and its mechanism may be related to the inhibition of the NF-κB/IκBαsignaling pathway.

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.

Isolation of exogenous fungi from Notoginseng Radix et Rhizoma and preliminary analysis of toxigenic fungi

Notoginseng Radix et Rhizoma(Sanqi in Chinese)is a precious traditional Chinese herbal medicine.It has the effect of dispersing blood stasis and stopping bleeding,reducing swelling and fixing pain.However,it tends to contaminate with harmful fungi during storage,which may make it much less effective.In order to understand the fungal contamination of Notoginseng Radix et Rhizoma and master its composition of the exogenous fungi.The surface fungi of Notoginseng Radix et Rhizoma samples collected from six Chinese provinces and districts were investigated by using dilution plate method.Detection of aflatoxins by UPLC-MS/MS.The results showed that Penicillium citrinum was dominantly isolated from Notoginseng Radix et Rhizoma samples from No.1 to No.4.Aspergillus flavus,which produces aflatoxin,was dominantly isolated from Notoginseng Radix et Rhizoma samples from No.5 and No.6.In addition,kinds of mycotoxin were assayed which were produced by three of those identified A.flavus.All three fungi strains produced aflatoxin B1(AFB1)and one strain HBSQ1-5 additionally produced other three kinds of mycotoxin,AFB2,AFG1 and AFG2.It is the results implied that it will be very important to take serious cautions when using Notoginseng Radix et Rhizoma.As well as,understanding the composition of the exogenous fungi of Notoginseng Radix et Rhizoma and the strains of toxin-producing fungi,which can play an important role in guiding the storage of Notoginseng Radix et Rhizoma.

三七药对的研究进展

三七作为临床常用中药,在临床应用中有多种药对形式。围绕近年来基于网络药理学的三七药对、传统三七药对及三七药对配伍前后化学成分变化的实验研究进行归纳和总结,系统阐释三七药对在临床应用的作用机制和科学内涵,为进一步研究三七药对使用规律、配伍理论、临床应用等方面提供新的思路。

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。

7576张含丹参-当归药对的门诊中药饮片处方回顾性分析

目的:了解江苏省中西医结合医院南部院区/南京市溧水区中医院(以下简称“该院”)含丹参-当归药对的门诊中药饮片处方情况,探究该药对的临床配伍应用规律,为该药对的合理使用提供参考。方法:采用回顾性分析方法,统计2020—2022年该院使用丹参-当归药对的7576张门诊中药饮片处方,对患者的性别、年龄、处方药味数、金额、疗程、涉及科室及病症、使用剂量、常用的配伍比例及配伍饮片等相关内容进行统计分析。结果:7576张含丹参-当归药对的门诊中药饮片处方中,女性患者处方数约为男性患者处方数的3.21倍(5776张vs.1800张),>30~40岁患者居多。单张处方的中药饮片味数多集中在16~20味,开具的疗程均<30 d。丹参的使用剂量为《中华人民共和国药典》规定的10~15 g的处方有6490张,占85.67%;当归的使用剂量为《中华人民共和国药典》规定的6~12 g的处方有6608张,占87.22%。处方数排序居前3位的科室依次为国医堂、妇科及脑病科,治疗的病证以冲任失调、心脾两虚及气滞血瘀证为主。单张处方中丹参用量大于等于当归用量,丹参与当归的配伍比例以1∶1为多,高频配伍饮片为茯苓、川芎、炒白芍。结论:基于处方用药分析,该院含丹参-当归药对的门诊中药饮片处方基本合理,为丹参-当归药对的使用剂量范围及配伍规律研究提供了数据支持,有利于促进临床合理用药。

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。

甘草抗炎活性物质基础及其作用机制研究进展

炎症是机体对于刺激所产生的一种防御反应,随着炎症的发展可能导致组织的变异和增生,进一步加剧疾病的进程。甘草作为“众药之王”“国之药老”,早在《神农本草经》中就记载其清热作用较强,能“主五脏六腑寒热邪气”。现代研究表明,甘草提取物对肾小球肾炎、结肠炎症状改善明显,甘草及其制剂在治疗肝炎、胃炎、支气管炎、心肌炎、强直性脊柱炎等炎症性疾病方面亦具有一定的独特优势和发展潜力。该文旨在通过对近期国内外甘草抗炎活性物质基础及其作用机制方面的相关文献进行收集和整理,探索甘草发挥抗炎作用的主要活性成分及靶点通路,以期为甘草抗炎作用的进一步研究及抗炎药物的研发提供思路和参考。

解郁清心颗粒的定性鉴别和含量限度的制定

摸索解郁清心颗粒的定性鉴别和指标成分含量限度制定方法。采用TLC法对制剂中炒白芍、甘草进行定性鉴别;采用HPLC法对制剂中芍药苷的含量进行测定并制定含量限度。TLC用于方中药味鉴别分离度良好,供试品与对照品对应处有相同颜色的斑点,阴性无干扰。采用HPLC法测定的指标成分芍药苷的含量限度建议为≥0.8 mg/g。本实验得到的定性鉴别方法和指标成分的含量限度制定方法均具较强的专属性、准确性和可靠性,可为该制剂质控标准提供参考依据。

高光谱结合人工神经网络鉴别不同来源的丹参饮片

提出了高光谱结合人工神经网络法(ANN)鉴别不同来源丹参饮片的方法。采集了9种不同来源丹参饮片的高光谱;分别采用最大最小归一化、均值中心化、标准正态变量变换、Savitzky-Golay平滑滤波、多元散射校正等5种光谱预处理方法,结合ANN建立了鉴别这些样品来源的分类模型。测试集验证结果表明,当隐含层节点数设置为17时,对光谱进行均值中心化预处理可建立最佳的ANN模型,分类准确率为98.77%。7种丹参样品判别结果的真正率、命中率和特异度均达到100.00%;其余2种丹参样品的真正率、命中率和特异度也不小于90.00%。

刺五加及其复方防治帕金森病研究进展

帕金森病是中老年人常见的中枢神经系统慢性进展性疾病,发病机制复杂,致残率高,西医临床主要采用左旋多巴与卡比多巴复合使用,但长期用药会引起多种不良反应,患者无法被完全治愈。中医认为肝肾不足是引起帕金森病(parkinson’s disease,PD)的主要病机所在,刺五加作为传统中药,具有补肝肾、坚筋骨、强志意的作用,近年来,越来越多研究发现中药刺五加在帕金森病的治疗方面具有显著的临床价值。刺五加中所含的皂苷类、香豆素类、黄酮类等成分可通过保护多巴胺能神经元、抗氧化应激、保护线粒体、抗炎症反应、抑制神经元免疫、抑制富亮氨酸重复激酶2(leucine-rich repeat kinase 2,LRRK2)蛋白表达等多通路、多途径来防治帕金森病。该文通过检索国内外相关文献,对刺五加及其复方防治帕金森病的药理作用及作用机制进行归纳梳理,旨在为刺五加治疗帕金森病的进一步开发利用提供参考。

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。

冠心生脉丸质量标准提升

目的提升冠心生脉丸质量标准。方法TLC法定性鉴别人参和三七,分析采用硅胶G薄层板,以三氯甲烷-甲醇-水(13∶7∶2)10℃以下放置的下层溶液为展开剂,10%硫酸乙醇溶液为显色剂。HPLC法测定人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1、人参皂苷Rd的含量,分析采用Thermo Accucore-C18色谱柱(4.6 mm×150 mm,2.6μm);流动相乙腈-水,梯度洗脱;体积流量0.8 mL/min;柱温20℃;检测波长203 nm。结果TLC斑点清晰,阴性无干扰。4种成分在各自范围内线性关系良好(R^(2)≥0.9999),平均加样回收率91.21%~106.86%,RSD 0.68%~1.43%。结论该方法专属性、重复性良好,可为冠心生脉丸质量控制提供参考。

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。

三七治疗动脉粥样硬化药理机制研究进展

动脉粥样硬化(atherosclerosis,AS)是引发心脑血管系统疾病的主要原因之一,是动脉内膜异常沉积日久所致的慢性炎症性疾病,病机复杂、治疗周期长久,是临床需要重点解决的重点疾病之一。其病理机制涉及血管平滑肌细胞增殖、内皮损伤、血管内血栓形成、炎症反应、脂质代谢异常、氧化应激加剧、自噬稳态失衡等,而当前对中药三七有效成分是近年来研究的热点和重点,其富含多种皂苷类和非皂苷类有效化学成分,能够综合调理多方面的通路、分子机制,达到减轻炎症反应和内皮损伤,恢复正常脂质代谢、重新调整自噬稳态等的平衡,抑制血管内血栓形成、血管平滑肌细胞增殖,并最终达到预防和治疗AS的目的。鉴于三七在抗AS中的重要作用,该文就三七及其有效成分对AS保护作用的体内外等研究进行综述,为中医药新产品研究开发及临床应用辨证治疗用药提供参考和依据。

基于整合药理学探讨“茯苓-甘草”协同配伍对肺腺癌的作用机制及验证研究

目的:基于网络药理学和生物信息学探讨“茯苓-甘草”协同配伍对肺腺癌的作用机制及靶点,并通过实验验证“茯苓-甘草”主要成分槲皮素对肺腺癌的抑制作用。方法:对肺腺癌相关基因进行差异分析,从TCMSP数据库下载“茯苓-甘草”有效成分及靶标,获取药物-疾病共同靶标,进行网络构建、富集分析、生存分析等。通过对“茯苓-甘草”主要成分与肺腺癌关键靶点进行分子对接,选出构效关系良好的有效成分进行后续实验验证。通过细胞增殖、划痕及侵袭实验检测药物对肺腺癌细胞的干预作用,实时荧光定量法检测药物对关键靶点的作用。结果:肺腺癌8 109个差异表达基因和102个药物靶基因取交集共获得32个共同基因,富集分析显示靶基因主要参与p53信号通路、细胞衰老等癌症相关通路,分子对接结果显示槲皮素具有良好的构效关系,因此选择槲皮素进行后续实验验证。有效成分槲皮素可以抑制肺腺癌A549及H1299细胞的增殖、迁移及侵袭能力,并且可以显著下调关键靶点含杆状病毒IAP重复序列蛋白5(BIRC5)、细胞周期蛋白B1(CCNB1)、检查点蛋白激酶1(CHEK1)的表达。结论“:茯苓-甘草”有效成分槲皮素可以有效抑制肺腺癌恶性表型,其机制可能与靶向调节关键基因BIRC5、CCNB1、CHEK1的表达有关。