A Clinical and Animal Experiment Integrated Platform for Small-Molecule Screening Reveals Potential Targets of Bioactive Compounds from a Herbal Prescription Based on the Therapeutic Efficacy of Yinchenhao Tang for Jaundice Syndrome

A herbal prescription in traditional Chinese medicine(TCM)has great complexity,with multiple components and multiple targets,making it extremely challenging to determine its bioactive compounds.Yinchenhao Tang(YCHT)has been extensively used for the treatment of jaundice disease.Although many studies have examined the efficacy and active ingredients of YCHT,there is still a lack of an in-depth systematic analysis of its effective components,mechanisms,and potential targets—especially one based on clinical patients.This study established an innovative strategy for discovering the potential targets and active compounds of YCHT based on an integrated clinical and animal experiment platform.The serum metabolic profiles and constituents of YCHT in vivo were determined by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry(UPLC-Q-ToF-MS)-based metabolomics combined with a serum pharmacochemistry method.Moreover,a compound–target–pathway network was constructed and analyzed by network pharmacology and ingenuity pathway analysis(IPA).We found that eight active components could modulate five key targets.These key targets were further verified by enzyme-linked immunosorbent assay(ELISA),which indicated that YCHT exerts therapeutic effects by targeting cholesterol 7a-hydroxylase(CYP7A1),multidrug-resistance-associated protein 2(ABCC2),multidrug-resistance-associated protein 3(ABCC3),uridine diphosphate glucuronosyl transferase 1A1(UGT1A1),and farnesoid X receptor(FXR),and by regulating metabolic pathways including primary bile acid biosynthesis,porphyrin and chlorophyll metabolism,and biliary secretion.Eight main effective compounds were discovered and correlated with the key targets and pathways.In this way,we demonstrate that this integrated strategy can be successfully applied for the effective discovery of the active compounds and therapeutic targets of an herbal prescription.

Anti-inflammatory and analgesic properties of Moroccan medicinal plants:Phytochemistry,in vitro and in vivo investigations,mechanism insights,clinical evidences and perspectives

Moroccan medicinal plants exhibit several pharmacological properties such as antimicrobial,anticancer,antidiabetic,analgesic,and anti-inflammatory effects,which are related to the presence of numerous bioactive compounds,including phenolic acids,flavonoids,and terpenoids.In the present review,we systematically evaluate previously published reports on the anti-inflammatory and analgesic effects of Moroccan medicinal plants.The in vitro investigations revealed that Moroccan medicinal plants inhibit several enzymes related to inflammatory processes,whereas in vivo studies noted significant anti-inflammatory and analgesic effects as demonstrated using different experimental models.Various bioactive compounds exhibiting in vitro and in vivo anti-inflammatory and analgesic effects,with diverse mechanisms of action,have been identified.Some plants and their bioactive compounds reveal specific secondary metabolites that possess important anti-inflammatory effects in clinical investigations.Our review proposes the potential applications of Moroccan medicinal plants as sources of anti-inflammatory and analgesic agents.

The Application of Medicinal Plants in Traditional and Modern Medicine: A Review of <i>Thymus vulgaris</i>

Medicinal plants have played an essential role in the development of human culture. Medicinal plants are resources of traditional medicines and many of the modern medicines are produced indirectly from plants. This study illustrates the importance of traditional and modern medicines in the treatment and management of human diseases and ailments. It has been confirmed by WHO that herbal medicines serve the health needs of about 80 percent of the world’s population;especially for millions of people in the vast rural areas of developing countries. Meanwhile, consumers in developed countries are becoming disillusioned with modern health care and are seeking alternatives. Thymus vulgaris is a species of flowering plant in the mint family Lamiacea. Thymus is a widely used medicinal plant in food and pharmaceutical industries. Among different species of Thymus, Thymus vulgaris is used more than other species in therapeutic dosage forms. In Traditional medicine T. vulgaris is cultivated in many countries by most people especially in rural areas depending on herbal medicines to treat many diseases including inflammation-related ailments such as rheumatism, muscle swelling, insect bites, pains, etc. Also the modern medicine in essential oil of thyme has demonstrated that the compounds have shown anti-inflammatory, antioxidant, antibacterial and antifungal properties. In this review the objective is to consider the past and present value of medicinal plants such as Thymus vulgar is used in traditional and modern medical practices as bioactive natural compounds.

中药复方的现代基础研究进展述评

中药复方的现代基础研究是中药现代化发展的必经之路。本文从中药复杂作用模式解析研究策略与方法、中药直接靶点发现技术与应用、系统生物学驱动的中药复杂作用解析三个方面,对中药复方的现代基础研究进行综述,并对其未来发展进行展望。

固定化药靶蛋白中药活性成分定向筛选研究进展

中药活性成分筛选及作用评价一直是破解药物发现周期长和成功率低等瓶颈问题的核心突破口和重要技术支撑。作者团队创新亲和色谱原理,将药靶蛋白定向固定于色谱担体表面,制备了系列高活性功能化色谱固定相,并提出了固定化药靶蛋白定向筛选中药功效成分的新观点。主要综述了作者团队近五年在固定化药靶蛋白色谱固定相制备技术、中药活性成分定向筛选技术以及活性成分早期成药性评价色谱技术等方面的工作,并对固定化药靶蛋白在中药活性成分定向筛选方面的研究进行了展望。

Network Pharmacology-based Approaches Capture Essence of Chinese Herbal Medicines

Traditional Chinese Medicine（TCM）, a crucial component of the current medical system, has been extensively used in clinical practice due to its valuable therapeutic efficacy, and its potentials as an important source of new pharmacophores. TCM is characterized by holistic theory, which emphasizes maintaining the balance of the patient＇s whole body using herbal formulae（fangji in Chinese） composed of mixtures of herbs with multiple bioactive ingredients. Because of the complex nature of these formulae, it is necessary to develop systematic methods to identify their bioactive ingredients and to clarify their mechanisms of action. With the rapid progress in bioinformatics, systems biology, and polypharmacology, ＂network pharmacology＂, which shifts the ＂one target, one drug＂ paradigm to the ＂network target, multi-component＂ strategy, has attracted the attention because it can not only reveal the underlying complex interactions between a herbal formula and cellular proteins but detect the influence of their interactions on the function and behavior of the system. Growing evidence shows that the network pharmacology strategy can be a powerful approach to modern research on TCM. The present paper focuses on the basis of network pharmacology and the recent progress in its methodology, illustrates its utility in screening bioactive ingredients and elucidating the mechanisms of action of TCM herbal formulae, analyzes its limitations and problems, and discusses its development direction and application prospects.

以人血清白蛋白为固定相的分子生物色谱分析几种中药活性成分的研究

提出用人血清白蛋白分子生物色谱分析中药活性成分的方法 ,分别比较了当归等 4种单味中药的分离结果 ,考察了提取当归的 3种溶剂及提取时间对活性物质提取量的影响 ,同时建立了当归中阿魏酸与藁本内酯的定量分析方法 .

菊科植物资源及其开发利用研究

分析了菊科植物资源的种类、分布及化学成分,综述了近年来菊科植物在医疗、保健、农药及其他方面的研究现状,并针对此项研究所面临的问题,提出了菊科植物资源及其进一步开发利用的几点建议。

代谢组学在中药复方研究中的应用

代谢组学是20世纪90年代中期发展起来的对某一生物或细胞所有低相对分子质量代谢产物进行定性、定量分析的一门新学科。在中药复方研究中,代谢组学方法和技术的应用具有广阔的发展前景,尤其是在中药复方多靶点作用机制、中药复方配伍规律及安全性研究等方面具有重要理论意义和应用价值。代谢组学为中药复方的现代研究提供了强力的技术支撑,将有助于系统、深刻地揭示中药复方的科学内涵,指导中药复方新药研发,更好地传承和发展中医药理论。

以非编码RNA为靶点的中药活性成分研究现状

非编码RNA(ncRNA)不仅参与疾病的发生发展过程,同时也是药物干预的潜在靶点。越来越多的研究发现中药活性成分可以通过调节miRNA、lncRNA和circRNA,调控相应基因及蛋白的表达水平,参与多种信号通路,调节细胞增殖、周期和凋亡等,进而发挥抗肿瘤、抗炎、抗动脉粥样硬化、抗感染及抑制结构重构等作用。作为中药活性成分作用的新靶点,这些ncRNA的出现有助于从表观遗传学层面揭示中药的作用机理,解决其多靶点多层次治疗疾病的本质,促进“中药成分—靶点—分子机制—疾病”的精准医疗模式的实现。有鉴于此,本文对目前以ncRNA为靶点的中药活性成分研究进行综述,以梳理发展现状并阐述尚存在的问题。

中药活性成分发现关键技术研究进展

中药是当今新药研发的重要来源之一。现代科学技术的迅猛发展为中药研究带来了新的机遇,同时也促进了中药理论的不断创新。建立既符合中药特点又适应现代药物研发的理论和技术是中药药效物质研究迫切需要解决的问题。本文结合笔者课题组近5年的研究实例,介绍了中药活性成分发现的关键技术,包括化合物库制备-活性评价-结构鉴定一体化技术、生物垂钓和化学垂钓技术、基于配体和受体的虚拟筛选技术、中药谱效关联发现技术、等效成分群发现技术等,以期为中药药效物质研究提供一定的参考,进而加快中药现代化进程。

计算机辅助药物设计在中药现代化中的应用

计算机辅助药物设计(CADD)是多学科交叉的边缘学科,在药物研发过程中起着枢纽作用,特别在先导化合物的发现和优化中发挥重要作用。中药现代化是当前我国中药产业发展之路,也是新药研发的有效途径。借助现代高新技术,特别是CADD技术,结合传统中医药理论进行中药研发,似可为中医药发展开辟一条适合我国国情的创新道路。本文主要探讨CADD在药物作用靶点的发现与验证以及中药现代化中的应用及其前景。

正交设计优化中药类植物提取物组方

为制备可替代饲用抗生素的中药类复合植物提取物,首先以抑菌率、抗炎率和抗氧化IC_(50)值为评价指标,从19种中药类植物中遴选出石榴皮、桂枝、厚朴、青蒿和鸡血藤5种原料作为复合提取物组分;然后采用L_(16)(4^(5))正交试验设计优化组分不同配比,对试验结果进行极差分析,获得分别具有最佳抑菌(F_(ab))、抗炎(F_(ai))和抗氧化(F_(ao))功能的3个组方,其组分中厚朴、鸡血藤、青蒿、桂枝和石榴皮的比例依次为7∶13∶6∶9∶1、7∶13∶4∶1∶1和3∶13∶4∶1∶7。验证试验结果显示:F_(ab)最小抑菌浓度为125 mg·mL^(-1),F_(ai)抗炎IC_(50)值为0.144 mg·mL^(-1),F_(ao)抗氧化IC_(50)值为0.222 mg·mL^(-1)。通过以上研究,获得兼具抑菌、抗炎和抗氧化功能的复合植物提取物最优组方3个。

中药复方抗胃癌基础研究现状与展望

目的:通过梳理部分中药复方抗胃癌效应与机制研究,明确中药复方目前抗胃癌多靶点效应机制研究现状,探讨进一步开展中药复方抗胃癌基础研究的方法与方向。方法:依据胃癌临床辨证分型中的主要证型,整理中药复方体内外研究文献,从多方面梳理各复方抗胃癌效应及机制。结果:中药复方多源于经典医籍或团队临床实践,是在临床疗效上开展的基础研究,从抑制增殖、诱导调亡、调节信号传导、抑制端粒酶活性、逆转多药耐药、抗肿瘤新生血管形成、抑制转移等多方面揭示了中医药治疗胃癌的机制,论证了其临床疗效的机制基础。结论:基于这些研究,提示今后中药现代化研究尚需进一步深入,临床方面应基于真实世界大数据挖掘胃癌主体中医证型及其物质基础,基础研究建议追踪现代医学基因突变、免疫检查点等机制及新靶点、新方法、新技术,并开展组分、组分协同及核心抗肿瘤有效成分研究,籍以推动中西医结合治疗胃癌的新方向、新探索。

以络论治慢性复杂性疾病中药复方的作用靶点探索

阐述以络论治慢性复杂性疾病的理论基础,提出"络虚邪瘀"是以络论治慢性复杂性疾病的共同病机。结合近5年文献报道,从细胞因子与基因角度,总结以络论治慢性复杂性疾病的中药复方作用靶点,提出转生长因子-β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、血管内皮生长因子(VEGFs)、基质金属蛋白酶/基质金属蛋白酶组织抑制剂(MMPs/TIMPs)为其共性作用靶点,旨在为今后以络论治慢性复杂性疾病实验设计和新药研制提供依据。

多目标优化技术在中药复方药物筛选及组方优化中的应用

介绍多目标优化技术在中药复方药物筛选及组方优化中的应用,阐述了多目标优化技术在中药复方研究应用的思路与方法。其方案是以均匀设计法安排实验,综合主要目标法、虚拟目标法和约束条件法等多目标优化方法,以网格法作为优化算法实现复方药物筛选及优化,使多项药效指标都达到较好的平衡,从而取得最佳复方配伍组合。本研究探索建立的基于均匀设计的多目标优化技术在药物复方研究中的应用,有助于解决中药复方药物配伍研究方法的关键技术问题,有助于释放出中药复方中潜在的巨大经济效益。

计算机辅助药物靶标搜寻在探索中草药有效成分机制方面的应用

应用INVDOCK软件进行计算机搜寻药物靶标。研究结果显示该软件具有实际应用潜力及在普及型计算机上可进行运算的可行性。此方法除用于研究药物或先导化合物的未知医疗靶标及毒副作用靶标外 ,亦可用来研究中草药的作用机理。本研究应用INVDOCK寻找数个中草药有效成分的医疗作用靶标并同已知实验结果进行比较。结果表明INVDOCK可作为探索中草药机理的有效辅助工具。

展望从天然产物创新药物研究

展望从天然产物创新药物的研究。创新药物研究关键切入点和前提是发现活性先导物,从天然产物中发现生物活性先导物必须更新观念,用创新思维改革传统天然产物研究模式,采用高效快速分离和高通量活性筛选的组合天然产物化学研究路线。我国丰富的天然资源蕴涵无穷尽的结构多样性,因而是发现特异生物活性先导物,进而创制新药的最佳来源。对具已知结构和生物活性的天然化合物进行结构修饰或类似物合成是创新药物研究的另一重要途径。研究代表性常用中药及其复方的药效物质和作用机理对实现中药现代化是至关重要的。

杏与药复合种植模式对杏幼树生长的影响

为了提高仁用杏果园的经济效益,将仁用杏与四种中药材进行复合种植,然后对仁用杏幼树的生长和生育指标进行了观测与分析。结果表明:同一中药材品种对仁用杏品种"超仁"、"龙王帽"的生长胁迫效应弱,对"超仁"、"一窝蜂"生育指标的降低幅度影响较小;而对仁用杏品种"一窝蜂"、"优一"的生长胁迫效应较强,对"龙王帽"、"优一"生长指标的降低幅度影响较大。仁用杏与中药材的复合种植组合应选择生长势较强的仁用杏品种和植株矮小的中药材品种进行配置,才能保证仁用杏植株的生长发育和优质高产。

乌梅丸治疗结直肠癌可行性探讨

目的:对乌梅丸用于治疗结直肠癌的可行性进行探讨,以期能为结直肠癌的临床治疗提供参考依据,为更加深入的实验研究提供思路。方法:以临床实践观察所得为引,提出乌梅丸可用于结直肠癌治疗的观点,结合中医学对结直肠癌的认识,基于中医症状、病机、治则和现代中药药理学分析乌梅丸治疗结直肠癌的可行性,并运用现代生物信息技术对乌梅丸可能作用的靶点进行预测。结果:从中医理论以及现代药理学综合分析来看,乌梅丸具有良好的抗结直肠癌作用基础,网络药理学的结果也支持乌梅丸可能通过多成分、多靶点、多通路实现治疗结直肠癌的作用。结论:乌梅丸治疗结直肠癌有效,这为进一步的实验研究及临床运用提供了思路和理论依据。