中药提取物调控铁死亡改善阿尔茨海默病的研究新进展

阿尔茨海默病(AD)是一种老年人群中常见的神经退行性疾病,其典型临床表现是进行性记忆障碍。铁死亡是近些年新兴起的潜在的生物学机制研究方向,是一种铁依赖性程序性细胞死亡方式,大量证据表明AD与大脑中的铁死亡密切相关,然而其参与AD的确切机制尚不清楚,其可能由铁代谢紊乱、脂质过氧化和氨基酸代谢诱导,从而影响大脑中铁离子的沉积。迄今为止,部分中药有效化学成分已被深入研究,例如红景天、远志、银杏、茯苓等,这些中药在靶向铁死亡治疗AD的过程中展现出了显著的效果。在此背景下,本综述系统阐述了大脑中铁的代谢、铁死亡的特点,并重点关注铁死亡代谢调控机制。同时,本文还讨论了铁死亡和AD的联系,并同时列举了中药的有效成分通过抑制铁死亡改善AD的药物,以期为今后铁死亡抑制剂的开发研究提供参考信息。

Naturally derived anti-hepatitis B virus agents and their mechanism of action

Despite that some approved drugs and genetically engineered vaccines against hepatitis B virus(HBV)are available for HBV patients,HBV infection is still a severe public health problem in the world.All the approved therapeutic drugs(including interferonalpha and nucleoside analogues)have their limitations.No drugs or therapeutic methods can cure hepatitis B so far.Therefore,it is urgently needed to discover and develop new anti-HBV drugs,especially nonnucleoside agents.Naturally originated compounds with enormous molecular complexity and diversity offer a great opportunity to find novel anti-HBV lead compounds with specific antiviral mechanisms.In this review,the natural products against HBV are discussed according to their chemical classes such as terpenes,lignans,phenolic acids,polyphenols,lactones,alkaloids and flavonoids.Furthermore,novel mode of action or new targets of some representative anti-HBV natural products are also discussed.The aim of this review is to report new discoveries and updates pertaining to anti-HBV natural products in the last 20years,especially novel skeletons and mode of action.Although many natural products with various skeletons have been reported to exhibit potent anti-HBV effects to date,scarcely any of them are found in the list of conventional anti-HBV drugs worldwide.Additionly,in anti-HBV mechanism of action,only a few references reported new targets or novel mode of action of antiHBV natural products.

Natural products as a crucial source of anti-inflammatory drugs: recent trends and advancements

Natural active molecules are key sources of modern innovative drugs. Particularly, a great amount of natural active molecules have been reported to possess promising therapeutic effects on inflammatory diseases, including asthma, rheumatoid arthritis, hepatitis, enteritis, metabolic disorders and neurodegenerative diseases. However, these natural active molecules with various molecular structures usually exert anti-inflammatory effects through diversiform pharmacological mechanisms, which is necessary to be summarized systematically. In this review, we introduced the current major anti-inflammatory natural active molecules based on their chemical structures, and discussed their pharmacological mechanisms including anti-inflammatory molecular signaling pathways and potential target proteins, which providing a referential significance on the development of novel anti-inflammatory drugs, and also revealing new therapeutic strategies for inflammatory diseases.

The First Approved “Deuterated” Drug: A Short Review of the Concept

The first “deuterated” drug has recently been approved by the U.S. FDA (Food & Drug Administration). A “deuterated” drug is a drug in which the hydrogen atom in one or more of the carbon-hydrogen bonds in its chemical structure is replaced by deuterium (“heavy hydrogen”, a hydrogen isotope that has a neutron, i.e., one neutron instead of the usual no neutrons). A carbon-deuterium (C-D) bond is more stable in the body than a carbon-hydrogen (C-H) bond. If the deuterium is strategically located in a drug’s chemical structure, the extra stability of the bond will be more resistant to metabolic breakdown, and the duration of drug action will be prolonged. We review the general concept of deuterated drugs, historical examples of the classes of application, and the new approval.

Repositioning of clinically approved drug Bazi Bushen capsule for treatment of Alzheimer′s disease using network pharma⁃cology approach and in vitro experimental validation

OBJECTIVE To explore the new indications and key mechanism of Bazi Bushen capsule(BZBS)by network pharmacology and in vitro experiment.METHODS The potential tar⁃get profiles of the components of BZBS were pre⁃dicted.Subsequently,new indications for BZBS were predicted by disease ontology(DO)enrich⁃ment analysis and initially validated by GO and KEGG pathway enrichment analysis.Further⁃more,the therapeutic target of BZBS acting on AD signaling pathway were identified by intersec⁃tion analysis.Two Alzheimer′s disease(AD)cell models,BV-2 and SH-SY5Y,were used to pre⁃liminarily verify the anti-AD efficacy and mecha⁃nism of BZBS in vitro.RESULTS In total,1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula,and 1320 BZBS targets with high confidence were predicted.Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treat⁃ment of AD.In vitro experiments showed that BZ⁃BS could significantly reduce the release of TNF-αand IL-6 and the expression of COX-2 and PSEN1 in Aβ25-35-induced BV-2 cells.BZBS reduced the apoptosis rate of Aβ25-35 induced SH-SY5Y cells,significantly increased mitochon⁃drial membrane potential,reduced the expres⁃sion of Caspase3 active fragment and PSEN1,and increased the expression of IDE.CONCLU⁃SIONS BZBS formula has a potential use in the treatment of AD,which is achieved through regu⁃lation of ERK1/2,NF-κB signaling pathways,and GSK-3β/β-catenin signaling pathway.Further⁃more,the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action.The study lays a foun⁃dation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.

Network pharmacology study of drug pair Tubeimu-Zhebeimu in the treatment of breast cancer

Objective:Breast cancer is a malignant tumor endangering women’s safety and health.Clinical medication experience and related studies show that the drug pairs Tubeimu-Zhebeimu has an excellent therapeutic effect on patients with breast cancer,but its treatment mechanism is unclear.In this study,network pharmacology and molecular docking were used to analyze and explore the mechanism of“Tubeimu-Zhebeimu”in treating breast cancer.Methods:Traditional Chinese Medicine Database and Analysis Platform were used to retrieve the chemical constituents of Tubeimu and Zhebeimu,and the relevant targets were predicted through the Swiss Target Prediction Database.Searching the Gene cards,Therapeutic Target Database and Disgenet Database with the keywords“breast cancer”,“mammary cancer”and“mammary adenocarcinoma”obtain disease-related targets.We intersect the disease target with the drug target to obtain the potential drug therapy target.Then the data was imported into Cytoscape 3.9.1 software to construct a compound network of“Disease-Target-Component-Drug”,and the network.Subsequently,using the String Database a“protein-protein interaction network”was constructed and imported into Cytoscape 3.9.1 software for structural optimization and network topology analysis.DAVID was used for Gene Ontolog function enrichment and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analyses,and the results were visualized.The core targets were molecularly docked through AutoDockTools-1.5.6 software and Auto Dock Vina 1.1.2 software.Results:The results showed that the 20 active ingredients in the“Tubeimu-Zhebeimu”includingβ-sitosterol,Chaksine,saponins,and peimuocinine,can treat breast cancer through 139 potential targets including AKT1,AR,TP53,ESR1.Conclusion:The specific mechanism of the drug pairs Tubeimu-Zhebeimu treating breast cancer may be controlling human hormone levels,inducing cell apoptosis,and participating in the P53 protein signaling pathway and PI3K/Akt/mTOR signaling pathway.

槐耳颗粒联合分子靶向药物治疗脾虚型原发性肝癌的临床疗效

目的 探讨槐耳颗粒联合分子靶向药物治疗脾虚型原发性肝癌(PHC)的临床疗效及对肝功能、免疫功能的影响。方法 回顾性分析2020年1月—2021年12月本院收治的PHC患者70例,按就诊先后顺序分为A组和B组各35例。两组患者均实施常规支持治疗。A组在常规治疗上使用分子靶向药物治疗,B组在A组的基础上联合槐耳颗粒治疗,两组患者皆进行4周的治疗。对两组治疗前后中医证候积分、生活质量、肝功能及免疫功能指标的变化实施观察,并评价两组临床疗效与安全性。结果 B组总有效率(97.14%)显著高于A组(80.00%)(P<0.05)。治疗前,两组中医症候积分比较,差异无统计学意义(P>0.05);两组中医症候积分在治疗后均降低,且B组积分低于A组(P<0.05);治疗前,两组患者的CD8^(+)、CD4^(+)和CD4^(+)/CD8^(+)比较,差异无统计学意义(P>0.05);治疗后,两组患者的CD8^(+)、CD4^(+)水平较治疗前显著降低;B组CD4^(+)/CD8^(+)水平较治疗前提高,A组CD4^(+)/CD8^(+)水平较治疗前降低,且B组的CD8^(+)水平低于A组,CD4^(+)与CD4^(+)/CD8^(+)水平高于A组(P<0.05)。治疗前,两组的AST、ALT和TBIL水平比较,差异无统计学意义(P>0.05);治疗后两组AST、ALT和TBIL水平显著减少(P<0.05),且B组明显低于A组(P<0.05)。B组不良反应发生率(11.42%)高于A组(8.57%),但两组高血压、手足综合征、皮疹、恶心呕吐及腹泻等不良反应比较,差异无统计学意义(P>0.05)。治疗后两组生活质量均上升,且B组生活质量优于A组(P<0.05)。结论 槐耳颗粒联合分子靶向药物治疗PHC患者疗效确切,可减轻患者临床症状,改善患者的肝功能以及免疫功能指标,安全性较高,可在临床推广。

苍术健脾、燥湿的作用机制及研究进展

综述苍术健脾、燥湿的作用机制及研究进展。古代医家常用苍术治疗多种疾病的脾胃湿证。苍术有效成分能改善胃排空及小肠推进率;可增加胃泌素、胃动素等,促进胃酸分泌,增加胃肠动力;可降低血管活性肠肽水平,抑制肠蠕动亢进。苍术能双向调节胃肠功能紊乱,且还能改善胃黏膜的异常形态,减轻胃组织损伤,改善肠组织异常结构。苍术燥湿的主要有效成分为挥发油,可导致体液丢失,血黏度增加,影响唾液腺分泌,引起口干,降低肾脏水通道蛋白2的表达量。苍术及其提取物能降低大鼠胃、大肠、尿液中水通道蛋白含量,通过多脏器调节体内水液代谢。故苍术能从影响脏器形态、胃肠道激素水平、水通道蛋白表达等多方面达到健脾、燥湿的功效。

中药治疗糖尿病作用机制研究进展

糖尿病(Diabetes mellitus,DM)是以长期高血糖为主要特征的内分泌代谢性疾病,严重威胁着人类的健康与生活质量,随着我国生活质量的提高以及不健康的生活方式,DM发病率持续升高并趋于年轻化,深入开展降血糖治疗的研究刻不容缓。DM以胰岛素的绝对或相对不足为病理基础,目前尚无根治手段,西医多采用注射胰岛素或口服降糖药物对症治疗,虽然效果显著,但长期使用易产生毒副作用。中药治疗DM具有多途径、多靶点的优势,通过促进胰岛素分泌、改善胰岛素抵抗、调节糖脂代谢、抗氧化应激等发挥降血糖作用,其疗效显著且毒副反应少。近年来,有关中药及复方对DM动物模型的作用机制研究较多,笔者通过回顾近年来相关文献,对单味中药、中药复方、中药有效成分降血糖作用机制及其相关实验设计等进行系统梳理,从促进胰岛素分泌、抑制糖异生、促进糖原合成、改善胰岛素抵抗、抑制糖苷酶活性、缓解氧化应激损伤、抑制炎症反应和调节肠道菌群等方面对中药降血糖的作用机制研究及实验设计进行归纳总结,以期为中药降血糖更广泛的临床应用及其深入的药效学机制研究提供参考。

TREATMENT OF ATROPHIC CHOLECYSTITIS BY REGULATING THE FUNCTION OF THE SPLEEN -A Report of 50 Cases

Fifty cases of atrophic cholecystitis were treated mainly by regulation of the function of the spleen. Of them, 21 cases were cured, 18 markedly effective, and 7 effective. The total effective rate was 92.0%. By comparison of results of ultrasonography B performed before and after treatment, it was shown that both the longitudinal and transverse inner diameters of gallbladder cross section increased evidently, and the condition of atrophy was improved remarkably after treatment.

基于网络药理学和药理学实验探讨参苓白术散治疗脾气虚作用机制

目的基于网络药理学研究参苓白术散治疗脾气虚的作用机制,并结合动物实验验证。方法基于PubMed、中国知网等数据库分析脾气虚的现代科学含义,并采用GeneCards、BATMAN-TCM等挖掘参苓白术散治疗脾气虚的相关靶点;再结合动物实验,对网络药理学分析结果进行验证。结果共检索出脾气虚相关疾病靶点440个,去重后共得到126个,筛选出核心靶点16个,如C反应蛋白(CRP)、白细胞介素-6(IL-6)、前列腺素内过氧化物合酶2(PTGS2)等;通过京都基因和基因组百科全书(KEGG)通路处理分析,发现71个交集靶点主要富集在20条相关信号通路上。ELISA试剂检测显示,大鼠血清靶蛋白CRP、IL-6、PTGS2浓度均显著下降。结论参苓白术散通过各种途径、靶点和信号通路,调节细胞增殖、分化和凋亡以及免疫系统等过程,达到治疗脾气虚疾病的效果。

中医非药物疗法治疗糖尿病前期的应用进展

糖尿病前期是指在正常血糖与糖尿病之间的中间高血糖状态,其中包括空腹血糖受损、糖耐量减低及两者混合状态人群。糖尿病前期是一个可逆的过程,积极干预糖尿病前期人群是预防糖尿病发生和发展的关键。中医非药物疗法在治疗糖尿病前期方面效果显著,不良反应较少。

北苍术与朝鲜苍术健脾作用及机制研究

目的 分析北苍术与朝鲜苍术干预后,脾虚大鼠血浆生物标志物及代谢通路的差异,从非靶向代谢组学的角度讨论两者的健脾机制。方法 将SD大鼠采用饮食不节、疲劳过度加苦寒泻下的复合因素法,造成脾虚症模型。测定胃肠道和免疫学指标的水平;采用超高效液相色谱串联Q Exactive质谱仪(UHPLC-QE-MS)技术,联合主成分分析(PCA)与正交偏最小二乘法判别分析(OPLS-DA)方法,寻找脾虚大鼠血浆中生物标志物;利用Pathway数据库归纳代谢通路。结果 经北苍术与朝鲜苍术给药后,脾虚大鼠血浆中各指标均有不同程度回调。代谢组学分析表明,北苍术与朝鲜苍术分别回调了70个和82个血浆差异代谢物,北苍术主要调节“甘氨酸、丝氨酸和苏氨酸代谢”与“硫胺素代谢”2个代谢通路,朝鲜苍术主要调节“甘氨酸、丝氨酸和苏氨酸代谢”、“硫胺素代谢”、“嘧啶代谢”、“丁酸代谢”与“核黄素代谢”5个代谢通路。结论 北苍术与朝鲜苍术对脾虚大鼠均具有一定的调节作用,其作用机制可能与调节“甘氨酸、丝氨酸和苏氨酸代谢”、“硫胺素代谢”等代谢通路有关。

靶向合成改善病情抗风湿药在类风湿关节炎中的应用评价

近年来,新型抗类风湿关节炎药不断涌现,包括生物类改善病情抗风湿药(bDMARDs)和靶向合成改善病情抗风湿药(tsDMARDs)。其中,tsDMARDs因其良好的临床疗效、口服制剂的便利性及可控的不良反应而在临床广泛应用。本文就tsDMARDs的作用机制、临床研究、不良反应、上市情况等进行综述,以期为临床应用提供参考。

中药调节肠道菌群缓解药物性肝损伤的研究进展

药物性肝损伤是由化学药物、膳食补充剂和草药产品等引起的肝脏损伤疾病,其极易发展为肝衰竭,且在其发生发展的同时常伴随肠道菌群的变化。中药多成分、多靶点的治疗特点可以通过调节肠道菌群、改善肠道屏障、降低炎症因子水平等减轻药物性肝损伤。对中药干预肠道菌群缓解药物性肝损伤的作用进行总结,以期对中药治疗药物性肝损伤的机制研究提供参考。

培土生金法治疗慢性阻塞性肺疾病的研究进展

慢性阻塞性肺疾病(COPD),简称慢阻肺,其发病机制复杂,病理表现繁多。中医学认为该病与肺脾关系最为密切,肺虚及脾,脾虚累肺,相互影响,致使病情迁延,反复发作。治疗时应重视培土生金,不限于肺,不忘于脾,多方兼顾。培土生金法历史悠久,随着朝代更迭,治法被不断丰富与发展,体现出“培土”不仅为补脾益气,更是调和脾胃、濡润中焦、扶正固本、补益宗气,从而达到治理肺脏的效果。在现代医学领域中,培土生金法治疗慢阻肺的科学内涵逐渐清晰,对不同病情都有着卓越的疗效,充分体现出治法的重要性及优越性,以期能为中医药对该病的防治提供参考。

四逆散药理作用及治疗内科疾病的临床应用研究

四逆散为《伤寒论》中记载的经典名方,至今约有1800年的历史,适用于少阴病症,临床多以手足不温、泄利下重、腹痛、脉弦等为辨证要点,具有透邪解郁、疏肝理脾之功效。中医认为该方剂治疗病症与阳衰阴盛有本质的区别,该证属外邪传经入里,气机为之郁遏,失于疏泄,阳气内郁不能达于四末所致,为阴中涵阳、惟气不宣通而致四肢逆冷。四逆散的应用十分广泛,几乎各系统疾病均可以该方剂为基础方进行辨证施治,尤其是现临床对四逆散的研究更加深入,其药理作用和应用领域也进一步被拓展,可广泛用于治疗胃肠肝胆疾病、精神类疾病、肿瘤疾病等。文章通过分析近年来四逆散的应用文献,总结其药理和治疗作用,为临床对四逆散有更加深入地了解,推动该方剂在临床的进一步开发应用。

从补中益气汤管窥李东垣脾胃观之阴火论

“阴火”即内伤之火,其实质为脾胃亏虚,元气虚损所生之内热。“阴火”理论是李东垣提出并应用于临床阐明病机、诊治疾病、遣方用药的重要学说。其产生机制复杂,涵盖内容广泛,自古存在诸多争议,至今未有定论,临床价值尚未完全体现。补中益气汤既是东垣脾胃内伤学说的核心方,也是理解其内伤发热之“阴火”理论的关键。文章将通过探讨李东垣脾胃内伤理论体系中最重要的方剂“补中益气汤”的药物配伍特点及其理论基础,阐述李东垣脾胃观之“阴火”论的学术思想,以及“益气升阳”“甘温除热”的制方思想,浅析“阴火”理论的学术渊源,总结后世医家基于“阴火”理论的临床诊疗应用思路,以期为日后临床工作者应用“阴火”理论临床辨证论治、组方加减提供理论依据。

李东垣内伤病辨治思路探析及思辨

《内外伤辨惑论》为金元四大家李东垣著作之一,其卷中部分主要论述了内伤病的病机证治等内容。李东垣所论内伤病是由脾胃受损所导致的一种不足之病,生理基础主要与脾胃的生成和布散精微功能有关,核心病机为脾胃受损所导致的精气不足及阴火上冲,时令主气也会改变内伤病的主要矛盾。针对不断变化的病机,李东垣立甘温除热、补气升阳等法,又有补中益气汤、参术调中汤等方随于后,形成了完整的内伤病辨治体系。李东垣理法十分精妙,多脱胎于先贤经典,笔者在文献梳理的基础上,选甘温除热、按而收之、风药升阳三点,思辨推敲其本义,以便灵活运用于临床。

基于生物信息学和体外实验验证的肾康注射液治疗肾纤维化作用机制研究

目的 利用生物信息学及体外实验探讨肾康注射液(Shenkang injection, SKI)治疗肾纤维化(renal fibrosis, RF)的作用机制与物质基础。方法 利用GEO数据库筛选RF差异表达基因,借助CMAP数据库,基于基因表达谱相似性原理,重定位出具有调控RF作用的药物,然后通过分子指纹相似性分析筛选出SKI潜在治疗RF的成分;同时基于网络药理学预测SKI调控RF的核心靶点及通路;最后,通过分子对接和细胞实验进行验证。结果 基于GEO数据库筛选到2个RF相关的数据集,CMAP重定位到3个共同的RF治疗药物(saracatinib、dasatinib、PP-2),分子指纹相似性分析发现,RF治疗药物与salvianolic acid B、hydroxysafflor yellow A等5个SKI成分的结构相似性较高。分子对接结果发现,salvianolic acid B、hydroxysafflor yellow A等成分与SKI调控的潜在治疗RF的核心靶标MMP1、MMP13等均有良好的结合能力。网络药理学分析提示,SKI核心靶点主要富集在Relaxin和AGE-RAGE等信号通路。细胞实验表明,SKI可显著降低RF模型细胞AGE-RAGE信号通路中AGER、NFKB1、COL1A1、SERPINE1、VEGFC和Relaxin信号通路中MMP1、MMP13的mRNA表达水平,显著升高RXFP1的mRNA表达水平。结论 SKI可通过调控Relaxin和AGE-RAGE信号通路来发挥治疗RF的作用,其物质基础可能为salvianolic acid B、hydroxysafflor yellow A等成分。