Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase

Radix Bupleuri(RB)is commonly used to treat depression,but it can also lead to hepatotoxicity after longterm use.In many anti-depression prescriptions,RB is often used in combination with Radix Paeoniae Alba(RPA)as an herb pair.However,whether RPA can alleviate RB-induced hepatotoxicity remain unclear.In this work,the results confirmed that RB had a dose-dependent antidepressant effect,but the optimal antidepressant dose caused hepatotoxicity.Notably,RPA effectively reversed RB-induced hepatotoxicity.Afterward,the mechanism of RB-induced hepatotoxicity was confirmed.The results showed that saikosaponin A and saikosaponin D could inhibit GSH synthase(GSS)activity in the liver,and further cause liver injury through oxidative stress and nuclear factor kappa B(NF-kB)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)pathway.Furthermore,the mechanisms by which RPA attenuates RBinduced hepatotoxicity were investigated.The results demonstrated that RPA increased the abundance of intestinal bacteria with glycosidase activity,thereby promoting the conversion of saikosaponins to saikogenins in vivo.Different from saikosaponin A and saikosaponin D,which are directly combined with GSS as an inhibitor,their deglycosylation conversion products saikogenin F and saikogenin G exhibited no GSS binding activity.Based on this,RPA can alleviate the inhibitory effect of saikosaponins on GSS activity to reshape the liver redox balance and further reverse the RB-induced liver inflammatory response by the NFkB/NLRP3 pathway.In conclusion,the present study suggests that promoting the conversion of saikosaponins by modulating gut microbiota to attenuate the inhibition of GSS is the potential mechanism by which RPA prevents RB-induced hepatotoxicity.

Research Progress in Toxicity and Toxicity-reducing and Efficacy-enhancing Compatibility of Radix Aconiti Lateralis Praeparata

Radix Aconiti Lateralis Praeparata contains alkaloids,flavonoids,polysaccharides,organic acids and organic alkalis,among which diester alkaloids are important effective ingredients,which can be used for treating heart failure,rheumatic heart disease,coronary heart disease,hypotension,shock and other diseases.However,it also contains the main ingredients that produce toxic effects and are highly toxic to the cardiovascular system,nervous system,digestive system,reproductive system,embryos,and livers and kidneys.In this study,we analyzed the toxicity-reducing and efficacy-enhancing effects of the compatibility of Radix Aconiti Lateralis Praeparata with with single herbs Glycyrrhiza uralensis Fisch.,Panax ginseng C.A.Meyer,Zingiber ojjicinale Rosc.and Rheum palmatum L.,aiming to provide references for further exploring the appropriate compatibility conditions of traditional Chinese medicine in the future and improving the safety of the clinical application of Radix Aconiti Lateralis Praeparata.

Review of Modern Research on Toxicity of Traditional Chinese Medicine Aconm Lateralis Radix Praeparaia

The traditional Chinese medicine Aconm Lateralis Radix Praeparaia(Fuzi)is pungent and sweet in taste,hot in nature,and has high toxicity.It governs the meridians of the heart,kidney and spleen.It has the functions of restoring yang to save from collapse,dispersing cold and removing dampness,and warming the middle to relieve pain.It is often used for the treatment of yang collapse,cold limbs,weak pulse,heart yang deficiency,heart pain due to chest impediment,abdominal cold-pain,kidney yang deficiency,impotence and cold in womb,and syndrome of exogenous disease due to yang deficiency,etc.Its great yang qi and strong medicinal properties often bring about toxic and adverse effects.However,after processing or combination with other medicinal materials,the effects of Aconm Lateralis Radix Praeparaia are quite different.Not only the toxicity is greatly reduced,but also the curative effects are strengthened.Through searching related literature,this paper reviewed the researches about the toxicity reduction and curative effect improvement of Aconm Lateralis Radix Praeparaia,in order to provide a certain theoretic reference for future further research of Aconm Lateralis Radix Praeparaia.

Network pharmacology-based analysis of the mechanism of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity

Objective:Objective:To analyze and explore the key targets and molecular mechanisms of action of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity and the relationship between corresponding compounds based on network pharmacology.Methods:Using network pharmacology,a"traditional Chinese medicine-chemical composition-key target-pathway"analysis was conducted on Radix Paeoniae Alba for the treatment of Toosendan Fructus-induced hepatotoxicity.The possible mechanism of action was analyzed in terms of function.Results:The core targets,such as interleukin(IL)-6,tumor necrosis factor(TNF),heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator-activated receptor gamma(PPARG),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),Jun proto-oncogene(JUN),caspase-3,estrogen receptor 1(ESR1),and aryl hydrocarbon receptor(AHR)were screened from the targets of Radix Paeoniae Alba against Toosendan Fructus-induced hepatotoxicity.Biological process(BP)of toxic targets(BP terms)involved"response to drug;activation of cysteine-type endopeptidase activity involved in apoptotic process,”positive regulation of transcription.Cellular components(CC terms)mainly involved cytosol and membrane rafts.Molecular function(MF)terms included"protein homodimerization activity,"RNA polymerase II transcription factor activity and enzyme binding,etc."The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway included the TNF signaling pathway,cancer pathways,and apoptosis.Conclusion:Radix Paeoniae Alba might alleviate Toosendan Fructus-induced hepatotoxicity through IL6,TNF,HSP90AA1,PPARG,PTGS2,HMOX1,and other targets,possibly via the activation of cysteine-type endopeptidase activity involved in these pathways.

Active components of Bupleuri Radix in the treatment of schizophrenia analyzed by network pharmacology and clinical verification

Background:Bupleuri Radix is a common Chinese medicinal material in traditional Chinese medicine.Currently,the therapeutic effect of treating schizophrenia is relatively well understood.However,there are fewer studies examining the underlying mechanisms of its treatment.The objective of the study was to investigate the primary mechanisms of Bupleuri Radix in treating schizophrenia through network pharmacology and clinical validation.Method:Network pharmacology revealed possible molecular mechanisms,followed by clinical verification.Sixty-seven schizophrenia patients undergoing treatment at the Hunan Brain Hospital between October and November 2022 were recruited and randomly divided into the olanzapine group and the olanzapine+Bupleuri Radix group.Additionally,32 healthy people undergoing physical examinations during the same period were included as the control group.The patient’s positive and negative symptom scale scores were compared.qPCR was used to detect the mRNA expression levels of ESR1,mTOR,EIF4E,and SMAD4 in peripheral blood.Results:Through network pharmacological analysis,it was concluded in this study that Bupleuri Radix might regulate the mTOR,PI3K-Akt,and HIF-1 signaling pathways.Clinical experiments indicated that compared with before treatment,the positive and negative symptom scale scores and total scores of the two treatment groups were significantly decreased after treatment(P<0.01).In addition,the positive and negative symptom scale scores and total scores in the olanzapine+Bupleuri Radix group were significantly decreased(P<0.01)compared to the olanzapine group after treatment.Before treatment,ESR1 mRNA expression levels in peripheral blood were significantly higher in the two treatment groups than in the control group,whereas the mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly lower(P<0.01).The mRNA expression levels of mTOR,EIF4E,and SMAD4 in peripheral blood were significantly higher after therapy than before treatment,whereas the mRNA expression levels of ESR1 in peripheral blood were significantly lower(P<0.01).After therapy,the olanzapine+Bupleuri Radix group’s mRNA expression levels of mTOR,EIF4E,and SMAD4 were significantly higher than those of the olanzapine group,whereas the mRNA expression levels of ESR1 were significantly lower(P<0.01).Conclusion:The mechanism of Bupleuri Radix’s therapeutic efficacy in schizophrenia may involve the up-regulation of mTOR,EIF4E,and SMAD4 mRNA expression and the down-regulation of ESR1 mRNA expression in peripheral blood.

Network Pharmacology study on Mechanism of Radix Bupleuri Multi-component Synergistic Therapy for Breast Cancer

Objective: To explore the mechanism of Radix Bupleuri Treatment of Breast Cancer through network pharmacology. Methods: TCMSP Database was used and related literature was collected to screen out the active constituents of Radix Bupleuri. Multiple databases were used to search the targets of the constituents and the disease. Next, a visual map of the compound-target-path network were constructed. The protein-protein interaction network was visually analyzed. Finally, the enrichment analysis of GO biological process and pathway enrichment analysis were carried out. Results: Active compounds of Radix Bupleuri related to disease targets have been obtained,and they play therapeutic roles for breast cancer through mainly regulating target proteins such as PTGS2, NOS2, AR and ESR. Meanwhile, the active compounds of Radix Bupleuri have an impact on biological processes such as steroid receptor activity and endocrine resistance, platinum resistance, breast cancer-related signaling pathways. Hence, it plays a role in the treatment of breast cancer. Conclusion: The results of this study preliminarily validate the target and mode of Radix Bupleuri in the treatment of Breast Cancer, and lay a foundation for further revealing its mechanism of action.

Advances in toxicological studies of Radix Phytolaccae

Radix Phytolaccae is the dried root of Phytolacca acinosa Roxb or P.ameri-cana L,which is commonly used as a traditional Chinese medicine to treat diseases like cirrhotic ascites,hepatitis B,nephrotic syndrome,psoriasis,etc.However,there is no exact basis for its clinical application safety.In this paper,the toxic effects and mechanism of Saponin A(EsA),the main component of Radix Phytolaccae,were summarized by searching the results and reports of toxicology related to the plant from 1991 to 2023 on CNKI and pubmed,aiming to provide reference for the toxicological research and future research direction of Radix Phytolaccae,so that Radix Phytolaccae can be safely and effectively used in clinical practice.

Exploring the effect of Radix Bupleuri(Bupleurum chinense DC)on nonalcoholic fatty liver disease based on network pharmacology

Objective:To investigate the main effects of Radix Bupleuri(Chinese name called Chai Hu)in the prevention and improvement of nonalcoholic fatty liver disease using network pharmacology techniques.Methods:We used theTraditional Chinese Medicine Systematic Pharmacologydatabase to query the main active ingredients of Radix Bupleuri;used theDisGenet database,Treatment Target Database,and DrugBank Database to screen the targets of nonalcoholic fatty liver disease;used the matchingtraditional Chinese medicine-disease targets to build the traditional Chinese medicine-component-target network system using Cytoscape software;used STRING software to build the protein protein interactionsystem and visualized the data;DAVID database was used forgene ontologyfunctional enrichment study andKyoto Encyclopedia of Genes and Genomespathway study.Results:Twelve major functional components and 175 targets have been obtained for the prevention and alleviation of nonalcoholic fatty liver disease in Radix Bupleuri;network pharmacology also confirmed the maximum degree value of kaempferol,the main active component of Radix Bupleuri;geneontologyfunctional enrichment analysis obtained the top 10 entries ofbiological process,cellular component,molecular functionand Kyoto Encyclopedia of Genes and Genomespathway analysis obtained the top 30 entries of the signalling pathway.Conclusion:Radix Bupleuri may use Fluid shear stress and atherosclerosis,Cancer,Advanced glycation end-(receptor of advanced glycation,interleukin 17,Hepatitis B,Toxoplasmosis,Relaxin,andtumor necrosis factorsignalling pathway to regulate the inflammatory response of interleukin6,tumor necrosis factor,and prostaglandin endoperoxide synthase2targets and reduce extracellular matrix deposition to improve the therapeutic effect of Nonalcoholic fatty liver disease.And the active ingredient of traditional Chinese medicine Radix Bupleuri,kaempferol,may also play a significant role in this.

醋柴胡多糖的分离纯化及协同抗肝癌活性的研究

对醋柴胡多糖(polysaccharide from vinegar-baked Bupleuri Radix,VBRBP)进行分离纯化,初步分析其结构特征并探究其联合化疗药的协同抗肝癌活性。通过水提醇沉、膜分离及纤维素层析从醋柴胡中分离纯化得到醋柴胡均一多糖,采用高效凝胶渗透色谱法、PMP柱前衍生化法、傅里叶变换红外光谱、气质联用和核磁共振波谱等方法对醋柴胡均一多糖进行结构鉴定,并测定其联合不同化疗药物对HepG2和Huh7两种肝癌细胞株的增殖抑制作用。结果表明,经过分离纯化得到的醋柴胡均一多糖5-1(polysaccharide 5-1 from vinegar-baked Bupleuri Radix,VBRBP5-1)是一种中性多糖,相对分子量为30.78 kDa,由甘露糖、半乳糖醛酸、葡萄糖、半乳糖和阿拉伯糖组成,摩尔比为1.96∶2.38∶58.48∶22.85∶14.32;主链是由1-α-D-葡萄糖、1,6-α-D-葡萄糖、1,4,6-α-D-葡萄糖、1,4-α-D-葡萄糖、1,3,6-β-D-半乳糖残基构成,支链主要含有1-β-D-半乳糖、1,4-β-D-半乳糖和1-α-L-阿拉伯糖、1,3,5-α-L-阿拉伯糖、1,5-α-L-阿拉伯糖残基片段。VBRBP5-1能增强10-羟基喜树碱、甲氨蝶呤和顺铂对肝癌细胞的抑制率,显示出协同增效作用,其中对顺铂的协同增效作用在两种肝癌细胞中均优于其他抗肿瘤药物。本研究解析了VBRBP5-1的结构并探索了其协同抗肝癌活性,为醋柴胡多糖的构效关系阐释及后续深入开发和利用提供参考。

陕产附子炮制前后急性毒性及强心作用研究

目的:考察陕产附子炮制前后的急性毒性和强心作用。方法:通过对生附子LD_(50)的测定和自制黑顺片最大耐受量实验比较生附子和自制黑顺片的急性毒性;通过复制慢性心衰大鼠模型,检测大鼠体质量、心脏指数、血流动力学指标,检测血清BNP及cTnI含量以及组织病理学检查比较其强心作用。结果:生附子的半数致死量(LD_(50))为9.45 g/kg,黑顺片的最大耐受量为27.39 g/kg,经炮制后毒性降低。与模型组相比,自制黑顺片组大鼠症状及体征均有改善,能够降低心脏指数、左心室指数降低和左心室舒张压(LVEDP),升高左心室收缩压(LVSP)、收缩期左心室内压上升最大变化速率(+dp/dt_(max))和舒张期左心室内压下降最大变化速率(-dp/dt_(max))(P<0.05,P<0.01);降低血清中脑钠肽(BNP)、心肌肌钙蛋白I(cTnI)含量(P<0.05);心肌纤维排列相对紧密,胞核清晰可见,但有一定断裂,其中有少量空泡存在,未发现炎性细胞浸润,各指标有明显差异。生附子组各指标有一定程度的改善,但差异无统计学意义(P>0.05)。结论:生附子经炮制后,毒性降低,起到减毒的作用;自制黑顺片较生附子强心作用有显著增强。

基于UPLC-MS法研究5种柴胡皂苷在大鼠体内的药代动力学及组织分布

目的应用超高效液相色谱(ultra performance liquid chromatography,UPLC)-高分辨率质谱联用仪(mass spectrometry,MS)探究5种柴胡皂苷在大鼠体内的药代动力学及组织分布,在找出有效部位中的化学成分及其共性的同时研究其主要有效成分的药代动力学。方法应用UPLC法对指标成分柴胡皂苷a(saikosaponin a,SSa)、柴胡皂苷c(saikosaponin c,SSc)、柴胡皂苷b1(saikosaponin b1,SSb1)、柴胡皂苷d(saikosaponin d,SSd)、柴胡皂苷b2(saikosaponin b2,SSb2)进行含量测定,应用于组织分布研究。选择柴胡醇提物灌胃SD大鼠,给药后0.25、0.5、0.75、3、5 h处死,取心、肝、脾、肺、肾组织,样品经预处理后,采用上述方法测定组织中各皂苷类成分的含量,进行组织分布研究。结果UPLC-MS法提示血清中的内源性物质对内标和待测物质均无干扰,柴胡皂苷类成分的线性良好,高、中、低浓度的日内和日间精密度SD值均低于10%,经冻融循环及长短期稳定性的考察,柴胡皂苷类无明显降解,稳定性良好,符合生物样本分析方法的指导原则。待测成分无明显的基质效应。该研究测定的5种柴胡皂苷类成分组织分布存在一定相似性。在肝、肺组织中的含量高于其他组织,其特点为肝、肺>心、肾>脾,并且在肝脏组织中0.5 h最高,在肺组织中0.75 h较高;SSa与SSd具有相似结构,在组织分布中提现出了相似的特点:肺>肝、肾>心、脾,肺组织中的含量高于其他组织,在0.75 h有最大值,而相对含量较高的肝组织中也是在0.5 h有最大值。结论该研究通过UPLC-MS分析柴胡中SSa、SSc、SSb1、SSd、SSb2等5种皂苷类成分,对其予以定量分析。提示UPLC-MS方法灵敏、快速、可靠,并成功地用于柴胡药代动力学及组织分布研究,获得了柴胡皂昔类成分的药动学参数,提示各成分在不同组织中分布特点。体外柴胡醇提物成分容易吸收,在临床应用时可依据药理作用选择。

京大戟醋制前后对正常大鼠毒性的研究

目的比较京大戟醋制前后对正常大鼠肝、胃、肠、肾毒性的差异。方法采用雄性SD大鼠56只,随机分为7组:空白组、京大戟低、中、高剂量组和醋京大戟低、中、高剂量组。给药组大鼠分别灌胃0.253 g/kg、0.506 g/kg、1.012 g/kg京大戟、醋京大戟粉末,空白组灌胃等量的0.5%羧甲基纤维素钠,连续7天。考察给药后各组大鼠各脏器的组织病理形态学变化,测定血清中的肝肾功能指标及血清和组织中的氧化损伤指标。结果与空白组比较,各给药组大鼠肝、胃、肠病理切片可见不同程度的组织损伤,京大戟各剂量组的大鼠血清中谷丙转氨酶(alanine aminotransferase,ALT)与谷草转氨酶(aspartate transaminase,AST)活性显著升高(P<0.01,P<0.05),肌酐(creatinine,CRE)与尿素氮(blood urea nitrogen,BUN)活性略有升高;血清和肝、胃、肠组织中的超氧化歧化酶(superoxide dismutase,SOD)和谷胱甘肽(glutathione,GSH)含量明显降低,丙二醛(malondialdehyde,MDA)含量显著升高(P<0.01,P<0.05)。与京大戟组比较,醋京大戟组的大鼠肝、胃、肠组织损伤较轻,血清中AST、ALT活性显著降低;血清和肝、胃、肠组织中的MDA含量明显降低,SOD和GSH含量明显升高(P>0.05),但两组间无显著性差异。结论京大戟对正常大鼠肝、胃、肠毒性明显,对肾无明显损伤,醋制后毒性均下降,其毒性作用与氧化损伤相关。

中药远志的炮制研究进展

远志是我国传统中药,具有安神益智、交通心肾、祛痰、消肿等作用,虽然其炮制方法多样,但炮制目的均在于减毒增效。本文对古法炮制中的净制、切制、加辅料炒与不加辅料炒等方法进行了文献概述,并在此基础上,对现代炮制前后化学成分变化及减毒增效机制等方面进行文献分析。现代研究表明,远志的减毒增效机制为远志皂苷的毒性与糖基含量有关,远志皂苷B水解为细叶远志皂苷后胃肠毒性显著降低。现代远志的炮制工艺主要有甘草炙远志、蜜制远志、厚朴汁炙远志、炆远志等,但厚朴汁炙远志、炆远志现代沿用不多,炮制工艺缺乏规范化研究。笔者认为,应加强古法炮制研究,在确定炮制工艺的同时,结合化学成分、药效等方面,开展炮制机制等方面的研究,为远志炮制的合理性提供科学依据,确保临床用药安全。

饲料中添加柴胡及其提取物对锦鲤幼鱼生长、生理生化、肝脏抗氧化及抗菌能力的影响

试验旨在研究饲料中添加柴胡及其提取物对锦鲤幼鱼生长、生理生化、肝脏抗氧化及抗菌能力的影响。选取初始体重(21.0±0.5)g的锦鲤幼鱼360尾,随机分为3组,每组3个重复,每个重复40尾锦鲤幼鱼。K组、C组和T组锦鲤幼鱼分别饲喂基础饲料、基础饲料+5‰柴胡生粉和基础饲料+5‰柴胡提取物。试验期14 d。结果显示,锦鲤幼鱼血清中,14 d时,C组的溶菌酶(LZM)和C组、T组的碱性磷酸酶(AKP)活性显著高于0 d,并显著高于K组(P<0.05)。锦鲤幼鱼肝脏中,14 d时C组的LZM、酸性磷酸酶(ACP)和T组的AKP活性显著高于0 d(P<0.05)。14 d时,C组的超氧化物歧化酶(SOD)活性及总抗氧化能力(T-AOC)显著高于0 d(P<0.05),丙二醛(MDA)含量低于0、7 d。攻毒试验中,24 h内K组锦鲤幼鱼的死亡率为41.7%;C组死亡率为18.3%,保护率为56%;T组死亡率为21.7%,保护率为48%。C组锦鲤幼鱼血清中48 h的白细胞介素-13(IL-13)含量显著高于24、96 h(P<0.05);C组、T组48 h的免疫球蛋白M(IgM)含量显著高于24 h(P<0.05)。肝脏中,C组锦鲤幼鱼48 h的白细胞介素-4(IL-4)、IL-13和IgM含量显著高于24 h,IL-13含量显著高于K组(P<0.05)。研究表明,饲料中添加柴胡及其提取物投喂14 d可以有效提高锦鲤幼鱼的生理生化指标和抗维氏气单胞菌能力,但两者的作用时间和作用效果具有差异性,柴胡的作用效果更为突出。

何首乌化学成分、药理作用及肝毒性的研究进展

从化学成分、药理作用及肝毒性3个方面综述何首乌的研究进展。何首乌含有二苯乙烯苷类、蒽醌类、磷脂类、黄酮类等多种化学成分,具有延缓衰老、抗癌、抗疲劳、抗炎镇痛、保护心血管等药理作用。目前,何首乌引起肝毒性的化学成分探讨主要集中于3类,即蒽醌类、二苯乙烯苷类及鞣质类。加大何首乌肝毒性成分、肝毒性机制研究的力度,加强中药安全用药知识宣教,规范其炮制及使用,可以在一定程度上降低何首乌肝毒性。

基于高通量测序技术的玄参对大鼠有效性和安全性研究

目的研究玄参干预对大鼠基因表达谱的影响,探讨玄参干预对大鼠的潜在保护和毒性作用及其机制。方法将20只雄性SD(Sprague-Dawley)大鼠随机分为玄参组和空白组,每组10只。玄参组大鼠给予玄参提取物1350 mg·kg-1灌胃,空白组灌胃给予等容积0.9%氯化钠溶液,均为1次/d,连续15 d。分别于灌胃15 d后,检测肝脏组织的基因表达谱,通过时间序列趋势分析软件(Short Time-Series Expression Miner,STEM)筛选具有趋势表达的差异表达基因(differentially expressed genes,DEGs),并对其进行基因本体论(Gene Ontology,GO)功能注释和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析。结果玄参组筛选76个DEGs,其中28个上调,48个下调,与对照组相比,差异均具有统计学意义(P<0.05)。KEGG通路分析结果显示,丝裂原活化蛋白激酶(MAPK)、无翅型小鼠乳腺肿瘤病毒整合位点(Wingless-Type MMTV Integration Site Family,Wnt)、转化生长因子-β(Transforming growth factor-β,TGF-β)、非受体酪氨酸激酶家族-信号转导子和转录激活子(Janus Kinase-Signal Transducer and Ac-tivator of Transcription,Jak-STAT)、核因子激活的B细胞的κ-轻链增强(nuclear factor kappa-B,NF-κB)、Toll样受体(Toll-like receptor)、过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor,PPAR)、催产素(Oxyto-cin)、神经生长因子受体(TNFRSF16)相关蛋白1[nerve growth factor receptor(TNFRSF16)associatedprotein 1,Ngfrap1]和神经营养因子受体相关死亡结构域(neurotrophin receptor associated death domain,Neurotrophin)这9条信号通路,包含Mecom、Amhr2、Pias2、Ticam2、Cyp7a1、Ngfrap1和Nfatc4这7个靶基因。经查阅文献,Mecom可能为表征玄参对大鼠潜在保护作用的靶基因,而另外6种则可能为表征玄参对大鼠潜在毒性作用的靶基因。结论玄参作用的两重性,既可对机体产生预防和治疗作用,也会产生潜在的不良反应。

柴胡-白芍配伍抗抑郁药理作用机制研究进展

抑郁症是一种常见的精神障碍,严重影响患者生存质量。目前临床西药治疗抑郁症效果不理想,需寻求新的抗抑郁药物及靶点。柴胡-白芍作为抗抑郁复方的核心和重要组成部分,两者配伍使用具有减毒增效抗抑郁作用,其机制可能与抑制炎症与氧化应激、调节单胺类神经递质、脑源性神经营养因子水平,影响下丘脑-垂体-肾上腺轴、多种氨基酸代谢和能量代谢等有关。本文通过综述柴胡-白芍配伍的协同效应以及抗抑郁药理作用,以期为阐明柴胡-白芍的配伍优势以及抗抑郁的作用机制提供参考。

柴胡治疗卒中后抑郁药理研究机制进展

卒中后抑郁症是脑卒中最常见和最重要的并发症,该病发病机制繁杂,临床治疗有一定挑战性。中医学认为患者卒中后脏腑气血逆乱,风、痰、瘀等病理产物胶搏,使肝气郁滞、魂无所安而病,中医药治疗卒中后抑郁效果显著,柴胡作为肝经引经药,是治疗郁证、中风常用药,也是治疗卒中后抑郁的常用药,在临床上广泛使用,具有极大发展前景。现代药理研究发现柴胡有效成分如柴胡皂苷、山柰酚、异鼠李素、槲皮素、黄芩苷等均能发挥抗抑郁效果。文章通过对已发表的论文及实验进行梳理,结合卒中后抑郁发病机制以及柴胡药理作用为契点,对柴胡治疗卒中后抑郁药理机制进行综述。结果发现柴胡可缓解HPA轴功能障碍、减少炎症因子表达、上调脑源性神经营养因子、提高脑内5-羟色胺含量、提高细胞免疫、抑制氧化应激、减少细胞自噬、减少细胞凋亡、减轻脑缺血再灌注损害等多方面发挥治疗卒中后抑郁的作用。

Chronic toxicity of both raw and processed Polygoni Multiflori Radix on rats

Recently, adverse effects of Polygoni Multiflori Radix（PMR） and Polygoni Multiflori Radix Praeparata（PMRP） have attracted intensive attention worldwide. These adverse effects most occurred in cases with high dose of prolonged medication course. Liver is usually the target organ of these adverse effects. In the present research, we performed in vivo chronic toxicity study and aimed to evaluate relationships between major constituents of water extractions and total anthraquinone of PMR and PMRP and chronic toxicity. SD rats of both sexes were given water extractions as well as total anthraquinone of PMR and PMRP for 12 weeks. We evaluated basic biochemical indexes, conducted microscopic observations of main organs and assessed early indicators of liver and renal fibrosis. Simvastatin, with hypertriglyceridemia and hypercholesterolemia as its main therapeutic areas, was investigated in our study. Component-toxicity relationships were also discussed. Five male rats died in our study, while all female rats survived, suggesting that some gender differences might be involved. Body weight was significantly changed, and basic biochemical indexes were sporadically occurred during the research. Pathological examinations on liver and kidney showed slight alternations after 12 weeks without dose-dependent relationship. Increase in serum laminin（LN） was observed in almost all male rats, indicating that the risks of liver or kidney fibrosis still existed, especially for males, although no fibrosis was found in the pathological examination of liver and kidney. No major and severe adverse effects were observed after 12 weeks of administration of PMR and PMRP. Regular safety monitoring is still necessary during medication in order to prevent possible risks.

甘草对雷公藤治疗类风湿关节炎减毒增效的研究进展

雷公藤是中医治疗风湿性疾病常用的中草药,对以类风湿关节炎(rheumatoid arthritis,RA)为主的风湿性疾病起到良好的治疗作用,但由于其存在的不良反应使得该药的使用受到限制。甘草是中医传统的解毒药物,以甘草对雷公藤治疗RA为例,通过对近些年的文献进行综述,发现甘草可以通过影响机体的应答以及影响药物在体内的代谢过程对雷公藤治疗RA起到减毒增效的作用。既往尚未有综述对这方面的内容进行讨论,希望通过综述,能为安全使用雷公藤及其相关制剂提供技术参考,为RA的发病机制研究提供理论依据,以及对复方的研究和新药的研发提供思路。