Recent advances in network pharmacology applications in Chinese herbal medicine

Network pharmacology is a new discipline based on the theory of systems biology and network analysis of biological systems to design the drugs.It comprehensively observes the intervention and influence of drugs on the disease network,and reveals the mystery of multi-molecular drugs synergistically acting on disease.These concepts reflect the ideas of multi-component,multi-target and system regulation,and have many similarities with the research ideas of traditional Chinese medicine,which focuses on syndrome differentiation and treatment,emphasizes the overall understanding of the etiology and pathogenesis.Network pharmacology can be used to predict and identify the target and active component of traditional herbal medicine,to clarify the mechanism of action,to scientifically explain the rules of the prescription,to explore the rules of real-world prescription,to discover new indications and new active compounds,and to study drug relocation,etc.The applications of network pharmacology in traditional herbal medicine were systematically summarized to demonstrate the significant value in these areas.

Understanding Interactions Between Chinese Medicines and Pharmaceutical Drugs in Integrative Healthcare

In the 21st century, the public are more informed, mainly via the Internet, about health and medical products and have become more knowledgeable about matters relating to their health conditions and well-being in curing and preventing illnesses. They often self-medicate themselves with various health products and over-the-counter （OTC） medicines apart from prescribed pharmaceutical drugs （PD）. Some of those non-prescribed products may have doubtful quality control and contain harmful additives or unchecked ingredients; thus their usefulness is in doubt. The increasing popularity world-wide of using Chinese medicines （CM） and related OTC functional products has raised concerns over their concomitant use with PD and the consequential adverse effects. In most cases the alleged causes of adverse effects are linked with herbal sources, although the authorised information on the interactions between CM-PD is not plentiful in the literature. There is an urgent need for such a data base. The future professionals in health and medical care should be knowledgeable or aware of what their patients have been taking or given. In actual practice the patients may receive both treatments intentionally or unintentionally, with or without the awareness of the practitioner. In these situations a reliable database for interactions between CM-PD will be extremely useful for consultation when treatment problems appear or during emergency situations. Their combining of medications may be involved with possible outcomes of adverse reactions or beneficial effects. Such a database will be welcomed by both practitioners of herbal medicines and orthodox medicine practitioners in the emerging trend of integrative medicine. The author has been involved in various research projects of basic and clinical aspects in mainly CM among other herbal and PD. Examples will be given largely on those related to these disciplines as illustrations in this overview.

Research Progress of Traditional Chinese Medicine in Treating Irritable Bowel Syndrome Based on Network Pharmacology and Molecular Docking Technology

In recent years,using network pharmacology and molecular docking technology to reveal the therapeutic targets of irritable bowel syndrome(IBS)has become a research hotspot.This paper summarizes 31 studies of traditional Chinese medicine for IBS by domestic and foreign scholars,and expounds the action mechanism of single drug,drug pair and compound prescription in the treatment of IBS from the aspects of drug activity,action target,biological process and pathway analysis.It also discusses the shortcomings and prospects of network pharmacology and molecular docking technology in the field of traditional Chinese medicine research,and provides reference for expanding the research ideas of traditional Chinese medicine in treating IBS.

Analysis of Traditional Chinese Medicine Syndromes and Treatment Laws of Diabetic Kidney Disease and the Action Mechanism of High-Frequency Chinese Herbs in the Treatment of Diabetic Kidney Disease Based on Real-World Study

Objective Our objective was to analyze the traditional Chinese medicine(TCM)syndrome and treatment laws of diabetic kidney disease(DKD)and the action mechanism of high-frequency Chinese herbs in the treatment of DKD based on realworldstudy.MethodsThe data of patients with DKD who had been treated in the First Hospital Affiliated to Henan Universityof ChineseMedicine from January1,2014to December 31,2021 were retrospectively analyzed through the hospital information management system.The contents of the cases were statistically analyzed using IBM SPsS Statistics 25 software,and the laws of DKDtreatment were summarized.Network pharmacology and molecular docking were used to analyze the action mechanism of high-frequency Chinese herbs in the treatment of DKD.ResultsThe data of a total of 1,201 patients with DKD were included,involving 72 kinds of TCM syndromes.Nine disease nature elements and six disease location elements were extracted,involving 405 Chinese herbs.The top five high-frequency Chinese herbs were Baizhu(Atractylodis Macrocephalae Rhizoma),Fuling(Poria),Huangqi(Astragali Radix),Chuanxiong(Chuanxiong Rhizoma),and Danshen(Salviae Miltiorrhizae Radix et Rhizoma).Thirty kinds of Chinese herbs with the frequency of≥100 were mainly deficiency-tonifying herbs and blood-activating and stasis-eliminating herbs.The medicinal properties were mainly warm and mild,and the medicinal flavors were sweet and bitter mostly.For the meridian tropism,the main meridian tropism of these herbs is spleen meridian and lung meridian.The clustering method.

Chinese herb pollen derived micromotors as active oral drug delivery system for gastric ulcer treatment

Considerable efforts have been devoted to treating gastric ulcers.Attempts in this field tend to develop drug delivery systems with prolonged gastric retention time.Herein,we develop novel Chinese herb pollen-derived micromotors as active oral drug delivery system for treating gastric ulcer.Such Chinese herb pollen-derived micromotors are simply produced by asymmetrically sputtering Mg layer onto one side of pollen grains.When exposed to gastric juice,the Mg layer can react with the hydrogen ions,resulting in intensive generation of hydrogen bubbles to propel the micromotors.Benefiting from the autonomous motion and unique spiny structure,our micromotors can move actively in the stomach and adhere to the surrounding tissues.Besides,their special architecture endows the micromotors with salient capacity of drug loading and releasing.Based on these features,we have demonstrated that our Chinese herb pollen-derived micromotors could effective deliver berberine hydrochloride and show desirable curative effect on the gastric ulcer model of mice.Therefore,these Chinese herb pollen-derived micromotors are anticipated to serve as promising oral drug delivery carriers for clinical applications.

Network pharmacology approaches for research of Traditional Chinese Medicines

Pharmacodynamics material basis and effective mechanisms are the two main issues to decipher the mechnisms of action of Traditional Chinese medicines(TCMs)for the treatment of diseases.TCMs,in“multi-component,multi-target,multi-pathway”paradigm,show satisfactory clinical results in complex diseases.New ideas and methods are urgently needed to explain the complex interactions between TCMs and diseases.Network pharmacology(NP)provides a novel paradigm to uncover and visualize the underlying interaction networks of TCMs against multifactorial diseases.The development and application of NP has promoted the safety,efficacy,and mechanism investigations of TCMs,which then reinforces the credibility and popularity of TCMs.The current organcentricity of medicine and the“one disease-one target-one drug”dogma obstruct the understanding of complex diseases and the development of effective drugs.Therefore,more attentions should be paid to shift from“phenotype and symptom”to“endotype and cause”in understanding and redefining current diseases.In the past two decades,with the advent of advanced and intelligent technologies(such as metabolomics,proteomics,transcriptomics,single-cell omics,and artificial intelligence),NP has been improved and deeply implemented,and presented its great value and potential as the next drug-discovery paradigm.NP is developed to cure causal mechanisms instead of treating symptoms.This review briefly summarizes the recent research progress on NP application in TCMs for efficacy research,mechanism elucidation,target prediction,safety evaluation,drug repurposing,and drug design.

Brain organoids are new tool for drug screening of neurological diseases

At the level of in vitro drug screening,the development of a phenotypic analysis system with highcontent screening at the core provides a strong platform to support high-throughput drug screening.There are few systematic reports on brain organoids,as a new three-dimensional in vitro model,in terms of model stability,key phenotypic fingerprint,and drug screening schemes,and particula rly rega rding the development of screening strategies for massive numbers of traditional Chinese medicine monomers.This paper reviews the development of brain organoids and the advantages of brain organoids over induced neurons or cells in simulated diseases.The paper also highlights the prospects from model stability,induction criteria of brain organoids,and the screening schemes of brain organoids based on the characteristics of brain organoids and the application and development of a high-content screening system.

Network Pharmacology-based Analysis on Determining the Mechanisms of Yishen Qutong Granules(益肾祛痛颗粒)in Alleviating Cancer-related Fatigue

Cancer-related fatigue(CRF)is associated with cancer-related anemia(CRA).As the common comorbidities of cancer,both of them can seriously affect the quality of patient life.Yishen Qutong Granules(益肾祛痛颗粒,YSQTG)have achieved good curative effects in the treatment of CRA.However,the mechanism of whether it can alleviate CRF needs further confirmation.We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription.Through the analysis and research in this paper,we obtained 76 effective compounds and 76 drug-disease intersection targets to construct a network,indicating that quercetin,luteolin,baicalein,β-sitosterol and stigmasterol were possibly the most important compounds in YSQTG.The key targets of YSQTG for CRF were mainly enriched in IL-17 and TNF pathways.816 GO entries and 113 pathways were obtained by GO and KEGG enrichment,respectively,which proved that YSQTG might have a comprehensive therapeutic effect on CRF mainly through regulating IL-17,TNF,MAPK,NF-κB and chemokines,as well as cholinergic synapse and 5-HT synapse pathways.The results of molecular docking showed thatβ-sitosterol and stigmasterol could form PI-Alkyl or Alkyl hydrophobic interactions with CXCL8 and ESR1 at residues LEU25,ARG26,PHE65,ALA69 and LEU346,ALA350,LEU391,PHE404,LEU525,VAL533,respectively.In conclusion,the therapeutic effect of YSQTG on CRF is based on the comprehensive pharmacological effect of multicomponent,multitarget,and multichannel pathways.This study provides a theoretical basis for further experimental research.

Efficacy of integrating short-course chemotherapy with Chinese herbs to treat multi-drug resistant pulmonary tuberculosis in China: a study protocol

Background:Tuberculosis(TB)causedMycobacterium tuberculosis(M.tb)is one of infectious disease that lead a large number of morbidity and mortality all over the world.Although no reliable evidence has been found,it is considered that combining chemotherapeutic drugs with Chinese herbs can significantly improves the cure rate and the clinical therapeutic effect.Methods:Multi-drug resistant pulmonary tuberculosis(MDR-PTB,n=258)patients with Qi-yin deficiency syndrome will be randomly assigned into a treatment group(n=172)or control/placebo group(n=86).The treatment group will receive the chemotherapeutic drugs combined with Chinese herbs granules(1+3 granules),while the control group will receive the chemotherapeutic drugs combined with Chinese herbs placebo(1+3 placebo granules).In addition,MDR-PTB(n=312)patients with Yin deficiency lung heat syndrome will be randomly assigned to a treatment(n=208)or control/placebo(n=104)group.The treatment group will receive the chemotherapeutic regimen combined with Chinese herbs granules(2+4 granules),while the control group will receive the chemotherapeutic drugs and Chinese herbs placebo(2+4 placebo granules).The primary outcome is cure rate,the secondary outcomes included time to sputum culture conversion,lesion absorption rate and cavity closure rate.BACTEC^(TM)MGIT^(TM)automated mycobacterial detection system will be used to evaluate theM.tb infection and drug resistance.Chi-square test and Cox regression will be conducted with SAS 9.4 Statistical software to analyze the data.Discussion:The treatment cycle for MDR-PTB using standardized modern medicine could cause lengthy substantial side effects.Chinese herbs have been used for many years to treat MDR-PTB,but are without high-quality evidence.Hence,it is unknown whether Chinese herbs enhances the clinical therapeutic effect of synthetic drugs for treating MDR-PTB.Therefore,this study will be conducted to evaluate the clinical therapeutic effect of combining Chinese herbs and chemotherapeutic drugs to treat MDR-PTB cases.It will assist in screening new therapeutic drugs and establishing treatment plan that aims to improve the clinical therapeutic effect for MDR-PTB patients.Trial registration This trial was registered at ClinicalTrials.gov(ChiCTR1900027720)on 24 November 2019(prospective registered).

基于网络药理学及分子对接技术探讨金匮肾气丸“异病同治”多囊卵巢综合征和甲状腺功能减退的作用机制

目的 以中医“异病同治”理论为依据,采用网络药理学与分子对接方法探究金匮肾气丸对多囊卵巢综合征和甲状腺功能减退的作用机制。方法 自2022年3—10月通过中药系统药理学数据库与分析平台(TCMSP)检索获取金匮肾气丸活性成分及潜在靶点,利用DrugBank、GeneCards数据库获取疾病靶点,将两者取交集获取共有靶点,通过STRING11.5数据库构建蛋白质-蛋白质相互作用(PPI)网络,使用Cytoscape 3.7.1构建金匮肾气丸“药物-疾病-靶点”网络,利用R语言对共有靶点进行富集分析,运用SYBYL-X 2.0软件进行分子对接。结果 筛选得到疾病与药物共有靶点65个,核心靶点主要涉及血管内皮生长因子A(VEGFA)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、胱天蛋白酶-3(CASP-3)、细胞肿瘤抗原p53(TP53)、基质金属蛋白酶-9(MMP-9)等,潜在靶点主要富集在AGE-RAGE信号通路、癌症的途径、PI3K-Akt信号通路、胰岛素抵抗、JAK-STAT信号通路等多条信号通路中。结论 金匮肾气丸中多种活性成分通过多靶点、多途径发挥抑制炎症反应及细胞凋亡、促进组织血管生成等作用,初步揭示了金匮肾气丸“异病同治”多囊卵巢综合征与甲状腺功能减退的潜在靶点与现代生物学机制,为深入研究开展实验及临床应用提供参考。

子痫前期的中药临床应用与现代药理学进展

子痫前期是一种妊娠特异性疾病,临床以妊娠20周后出现高血压、蛋白尿等症状为主要特征,子痫前期严重危害母婴生命健康,是导致孕产妇和围产儿死亡率增高的重要因素之一。近年来,采用中药汤剂、活血化瘀类中药注射液等治疗子痫前期的研究增多,取得了良好的临床疗效。现代药理学研究发现,葛根素、天麻素、钩藤碱、人参皂苷、白术内酯、丹参素、川芎嗪、黄芪甲苷等成分能够促进滋养细胞增殖和侵袭,改善实验动物妊娠过程,对子痫前期的治疗起到积极作用。梳理相关文献,通过结合临床疗效与机制研究,分析中药临床用药合理性,为中药防治子痫前期的临床应用与开发提供参考。

中药活性成分调控糖代谢抗胆管癌的分子机制

胆管癌是一种高度异质性的肿瘤,其发病隐匿、病情凶险、恶性程度高、预后极差。葡萄糖是胆管癌增殖和转移的主要能量来源,胆管癌细胞在快速增殖过程中其糖代谢途径会被重新编辑,产生大量能量以满足自身需求。中医药在胆管癌治疗中具有独特优势,中药活性成分已被证明可以通过调控糖代谢抑制胆管癌的发生和发展。本文对胆管癌中的糖代谢特点和中药活性成分调控糖代谢抗胆管癌进行综述,为胆管癌的治疗提供新思路。

基于问卷调研的中药材质量监测机制优化探索

目的:为进一步优化完善中药材质量监测机制,探索建立国家与省级中药材质量监测统筹模式提供参考。方法:基于国家药品抽检协作网络,在国家药品抽检信息系统内,采用在线问卷调研的方式,面向国家药品抽检承检机构以及省级药品监督管理部门征集意见建议。结果:共有46家承检机构与32家药品监督管理部门作答问卷,汇总分析显示,中药材质量监测逐步建立相互衔接、各有侧重的国家与省级协作体系,适当扩大监测品种范围,对药材市场与种植基地、饮片和中成药生产企业重点监测,建立风险分级管理制度,并与国家药品抽检协同发布监测结果。结论:中药材质量监测应当基于国家药品抽检协作网络,进一步优化品种遴选流程与范围,围绕药品生产企业、药材市场与种植基地,完善风险处置机制。

基于数据挖掘探讨中医药在辅助生殖技术中的分期应用

目的:基于数据挖掘技术整合分析名医名家临证应用中医药配合辅助生殖技术(assisted reproductive technology,ART)的各期方药分布规律。方法:计算机系统检索中国知网、维普中文科技期刊数据库、万方数据库和中国生物医学文献数据库中名医名家临证应用中医药配合ART的相关文献,建立文献分析数据库进行整合归纳,获得其中药物分布规律。结果:本研究纳入合格文献共112篇,涉及名家36人。降调期药物共获得总类别13种,相关药物77味,累计出现频次224次,频率较高者为“补虚药”(55.94%)、“活血化瘀药”(10.89%)、“清热药”(6.44%)、“收涩药”(5.45%)、“利水渗湿药”(5.45%)等;促排期药物共获得总类别13种,相关药物92味,累计出现频次398次,频率较高者为“补虚药”(61.34%)、“活血化瘀药”(8.68%)、“收涩药”(8.40%)、“清热药”(5.88%)、“利水渗湿药”(5.32%)等;移植期药物共获得总类别14种,相关药物70味,累计出现频次372次,频率较高者为“补虚药”(68.78%)、“祛风湿药”(5.80%)、“活血化瘀药”(5.52%)等;确认妊娠后用药物共获得总类别11种,相关药物47味,累计出现频次182次,频率较高者为“补虚药”(59.88%)、“祛风湿药”(9.30%)、“清热药”(7.56%)、“收涩药”(5.23%)等。四期用药关联分析显示降调期分析得18组药物组合,促排期分析得14组药物组合,移植期分析得41组药物组合,确认妊娠后分析得22组药物组合。四期用药聚类分析结果显示降调期得到核心药物组:党参-甘草-白术-黄芪-酸枣仁、菟丝子-枸杞子-熟地黄-当归-香附、熟地黄-白芍-阿胶-菟丝子-生地黄;促排期得到核心药物组:菟丝子-熟地黄-山药-枸杞子-桑椹、菟丝子-熟地黄-当归-枸杞子-丹参、熟地黄-山茱萸-山药-菟丝子-生地黄;移植期得到核心药物组:白术-续断-桑寄生-党参-菟丝子、桑寄生-菟丝子-续断-黄芩-阿胶、当归-菟丝子-甘草-山药-巴戟天;确认妊娠后得到核心药物组:白术-黄芪-甘草-党参-续断、菟丝子-续断-白术-桑寄生-阿胶、白术-续断-甘草-苎麻根-杜仲。结论:“补虚药”是四期主要应用的药物种类,药物主要归肝肾脾经,“以补为主,攻补兼施,性以温平,味以甘苦”是四期用药的共同特点,临床应根据四期不同特点进行相应的遣方用药以提高疗效,降调期以防气血躁动为主;促排期应以补肾精为主,同时应加用少量温阳药物,在补肾的同时应涩促结合,防止肾精过耗;移植期与胚胎着床后中药的功效主要在于“稳固胎元”,应注重补养母体气血。

银杏及其制剂药用发展及毒性评价研究述评

基于我国古代银杏药用历史和近现代国内外银杏产业发展史对银杏药用发展概况进行述评,并针对银杏制剂毒副作用及不良反应方面所关注的成分组成、药理活性及检测方法等进行归纳总结,借古论今,以期正确看待联合用药、合理用药及银杏制剂毒性评价研究,为后续进一步开发银杏药用价值提供参考依据。

芪银三两三验方治疗靶向药相关性皮疹的分子机制研究

目的探寻芪银三两三验方核心用药组成的分子作用机制,通过网络药理学分析,构建“芪银三两三-药物有效成分-关键性作用靶点-靶向药相关性皮疹对应靶点”的可视化网络关系。方法基于中药系统药理学数据库和分析平台(TCMSP)、中药作用机制在线分析系统(BATMAN-TCM),对芪银三两三验方核心用药的作用成分和有效靶点进行筛选,通过核心复方靶点垂钓,提取复方中的生物学活性成分及有效靶点。通过药物不良反应靶点分类系统(ADReCS-Target)得到靶向药相关性皮疹对应靶点。通过STRING数据库构建蛋白质相互作用可视化网络图(PPI),并应用Cytoscape3.8.2软件进行网络拓扑分析,筛选关键性作用靶点。采用DAVID v6.8数据库对关键性靶点进行通路富集,预测芪银三两三验方中核心用药组成可能的分子生物学机制。结果经检索得到核心处方中有效生物学活性成分118种,潜在预测靶点328个,靶向药相关性皮疹对应靶点214个,将二者相互匹配得到核心处方有效成分-靶向药相关性皮疹共同作用靶点86个,其中包括8个关键性靶点;复方对210个生物学过程及81条信号通路能产生重要影响。结论芪银三两三验方治疗靶向药相关性皮疹的潜在作用机制,可能是通过PI3K-Akt信号通路及细胞因子-细胞因子受体相互作用等信号转导,调节角质层细胞增殖与分化,修复EGFR-TKI引起的皮肤损伤,这为今后的药物研发及相关临床研究提供了参考方向。

基于中医传承辅助平台与网络药理学探析治疗湿疹方药的用药规律及作用机制

目的通过挖掘治疗湿疹的中医方剂,并且借助网络药理学揭示核心药物群或最佳药对的有效成分,同时明晰这些成分与治疗湿疹相关靶点之间的相互作用,为治疗中医湿疹疾病提供科学依据。方法首先检索《中医方剂大辞典》中有关湿疹治疗的中医方剂,将方剂信息录入中医传承辅助平台系统(V2.5)中进行关联规则分析和高频组合分析,通过分析揭示在治疗湿疹过程中药物之间的互补关系和高频使用的药物组合。利用诸如TCMSP等数据库对高频药物中的药物进行成分分析,确定其中的有效活性成分,并解析其作用靶点。通过OMIM、GeneCards等数据库收集与湿疹相关的基因靶点信息,构建相关靶点数据库,然后用药物靶点和疾病靶点进行映射,使用Cytoscape 3.9.0软件创建“疾病-方药-靶标”网络图。进而运用STRING数据库对关键靶点进行PPI网络分析,揭示靶点之间的相互作用关系。最后,通过GO功能富集分析,了解湿疹相关靶点的功能分类,进一步揭示其在疾病发生和发展中的作用,再利用KEGG数据库进行信号通路富集分析,以确定湿疹相关靶点参与的生物通路,从而深入了解治疗机制。结果本研究收集了104首方剂,涵盖了181种中药。出现频次达到或超过10次的药物有20种,高频中药作用靶点361个,疾病作用靶点744个,两者共有作用靶点46个。PPI分析揭示,STAT1、MAPK1、AKT1等蛋白可能在治疗湿疹中发挥重要作用,这些蛋白质涉及20个细胞生物过程、12个细胞组分以及15个分子功能。通路富集分析揭示了11条富集的信号通路中包括AGE-RAGE信号通路、TNF信号通路、化学致癌-受体激活信号通路、B细胞受体信号通路、NF-κB信号通路、Fcγ受体介导的吞噬信号通路、趋化因子信号通路等。结论治疗湿疹的方剂以清热类药为主,尤其以清热燥湿药为主,辅以凉血药和利水渗湿药。治疗湿疹的药物具有多靶点、多途径、多作用的特点,可能通过影响血管生成、炎症因子、免疫调节等途径发挥治疗作用。

香囊的药理研究和临床应用进展

香囊是一种广泛应用于临床的辅助治疗方式,且有丰富的历史文化背景。香囊中芳香中药的挥发性成分具有抗炎、镇痛、抗抑郁等药理作用。中药香囊在防治传染性疾病、抗抑郁以及缓解焦虑等方面有显著的临床疗效;还有帮助睡眠、提高免疫力和清新空气等作用。中药香囊的有效性已有大量药理研究和临床应用实例,有巨大的应用和开发潜力,但是有待更深入的药理和临床研究。

4种单一中草药及其配伍用药对动物肠道益生菌乳杆菌的促进作用

试验旨在探究4种单一中草药五味子、山楂、木香、白术及其配伍用药对益生菌乳杆菌的激活增殖作用。试验测定添加不同单一和联合配伍中草药前后乳杆菌培养液OD值、菌落数变化情况,探究其激活益生菌乳杆菌增殖的最佳剂量浓度。建立阿莫西林型肠道菌群失衡模型,考察单一中草药及联合配伍中草药对小鼠肠道内乳杆菌的影响。结果显示,五味子、山楂和白术对乳杆菌的最佳激活增殖浓度均为0.250 g/mL,木香最佳激活增殖浓度为0.500 g/mL;五味子+山楂、五味子+白术、五味子+木香的最佳激活增殖浓度均为0.125 g/mL;白术+山楂、木香+山楂的最佳激活增殖浓度均为0.250 g/mL;白术+木香的最佳激活增殖浓度为0.450 g/mL。研究表明,在畜牧生产中,建议添加五味子与山楂水提液的最佳浓度为0.250 g/mL,五味子+山楂、五味子+白术、五味子+木香的最佳添加浓度均为0.125 g/mL,能够最大限度地发挥中草药对动物肠道乳杆菌的促进作用。