Study on Rhizoma Chuanxiong based on capillary electrophoresis with amperometric detection

A high-performance capillary electrophoresis with amperometric detection(CE-AD) method has been developed for the analysis of seven bioactive ingredients,namely ferulic acid(FA),vanillin,vanillic acid,p-hydroxybenzoic acid,caffeic acid,gallic acid and protocatechuic acid,in Rhizoma Chuanxiong.The effects of several factors such as the acidity and concentration of running buffer,the separation voltage,the applied potential to working electrode and the injection time were investigated.Under the optimum condit...

Rhizoma Chuanxiong regulates vascular endothelial growth factor production in hypoxic human umbilical vein endothelial cells in vitro and in peri-infarct rat brain tissue

BACKGROUND： Vascular endothelial growth factor （VEGF） acts as ＂molecular bridge＂ following ischemic stroke to improve and restore blood supply and reduce infarction volume. Clinical studies have demonstrated the efficacy of Rhizoma Chuanxiong （Chuanxiong） in the treatment of ischemic cerebrovascular diseases. However, whether it promotes endogenous VEGF expression in ischemic stroke remains unknown. OBJECTIVE： To investigate the influence of Rhizoma Chuanxiong on VEGF production in vitro cultured human umbilical vein endothelial cells and on VEGF expression in ischemic cerebral tissues to explore its role in angiogenesis. DESIGN, TIME AND SETTING： In vitro basic comparison of traditional Chinese drug-containing serum pharmacology; in vivo randomized, controlled, animal experiment. This study was performed at the Medical Laboratory of West China Hospital, Sichuan University between December 2002 and April 2004. MATERIALS： Two Chinese rabbits were selected. One was intragastrically perfused with 5.8 g/kg Rhizoma Chuanxiong extract twice per day for three consecutive days to prepare Rhizoma Chuanxiong extract-containing serum. The remaining rabbit was intragastrically perfused with the same volume of normal saline twice per day for three consecutive days. Rhizoma Chuanxiong extract was provided by Beijing Traditional Chinese Medicine Research Institute, predominantly composed of ligustrazine, ligustilide, and ferulic acid. ChemiKineTM human VEGF Kit was purchased from Chemicon, USA; mouse anti-VEGF monoclonal antibody and biotin-goat anti-mouse IgG were purchased from Santa Cruz Biotechnology. Inc., USA. METHODS： （1） In vitro experiment： in vitro cultured human umbilical vein endothelial cells were separately incubated in rabbit serum with 10% Rhizoma Chuanxiong extract, normal medium without rabbit serum, and rabbit serum without Rhizoma Chuanxiong extract （blank control）. In addition, cells from the three groups were incubated under normoxia （5% CO2, 95% air） and hypoxia （1% 02, 5% CO2, 94% N2）, respectively, for 24 hours. （2） In vivo experiment： a total of 4/44 Sprague Dawley rats were selected for the sham-operated group （no occlusion）, and the remaining rats were used to establish a cerebral ischemiaJreperfusion model by suture occlusion. 32 animals with ischemia/reperfusion injury were randomly divided into treatment and model groups, with 16 rats in each group. Both groups were intraperitoneally infused with 0.58 g/kg Rhizoma Chuanxiong extract and normal saline two hours following reperfusion. The sham-operated group was administrated normal saline. Animals were treated with saline or Chuanxiong extracts （0.58 g/kg） twice per day for three consecutive days. MAIN OUTCOME MEASURES： In vitro experiment： VEGF concentration was detected in each group by enzyme-linked immunosorbent assay. In vivo experiment： behavioral alterations of rats were evaluated by neurological function scale; infarct volume was assessed by hematoxylin-eosin staining; VEGF protein expression in the infarct regions was determined by immunohistochemistry. RESULTS： （1） VEGF levels were similar between the three groups under normexic condition （P 〉 0.05）; while hypoxia induced VEGF production （P 〈 0.01 ）. VEGF levels in the drug-containing serum group were particularly higher compared with the other groups （P 〈 0.01）. （2） Compared with normal saline treatment, Rhizoma Chuanxiong extract significantly improved the neurological scale and reduced cerebral infarct volumes （P〈 0.05）. The percent of VEGF-positive cells was significantly greater than the model group （P 〈 0.05）. The sham-operated group exhibited normal neurological function, with no infarct focus. CONCLUSION： Rhizoma Chuanxiong extract-containing rabbit serum effectively promoted cultured VEGF production under hypoxia. Rhizoma Chuanxiong extract upregulated VEGF expression in the infarct region, improved neurological function, and reduced infarct size.

The impact of^(60)Co-γirradiation on the chemical constituents of Chuanxiong Rhizoma

Background:In order to clarify the inmpat ofγirradiation on the chemical composition of traditional Chinese medicine,this paper carefully choosed Chuanxiong Rhizoma to carry on a demonstration study.Methods:Through a meticulous assessment,a comprehensive comparison was made between the irradiated and unirradiated Chuanxiong Rhizoma samples.The property characteristics were investigated by colorimeter and electronic nose.The changes in chemical structures and contents was analyzed by fourier infrared spectroscopy,high performance liquid chromatography and fingerprinting.In a quest to uncover the presence of any new radiolysis products,cutting-edge techniques like ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry and gas chromatography-mass spectrometry were employed.Moreover,the difference of antioxidant activity were investigated.Results:The irradiation doses within 12 kGy had no significant effects on the content of the main chemical components,characteristics and in vitro antioxidant activity of Chuanxiong Rhizoma,while changes in some functional groups and degradation of some volatile oil components containing olefins need further study.Conclusion:This study indicates that^(60)Co-γirradiation is a stable method for sterilization of Chuanxiong Rhizoma.It’s also provide a reference for the establishment of irradiation standards for Chuanxiong Rhizoma and other aromatic medicinal plants.

Exploring the mechanism of Saposhnikoviae Radix and Chuanxiong Rhizoma treating Parkinson's disease based on network pharmacology and molecular docking

Backgroud:Parkinson’s disease(PD)is a neurodegenerative disorder with an increasing global prevalence.However,the development of drugs for PD treatment has not kept pace with the continuously growing number of patients.Currently,the search for new effective substances from natural drugs is a major research direction.Two Chinese medicinal materials,Saposhnikoviae Radix(Fangfeng)and Chuanxiong Rhizoma(Chuanxiong),are commonly used in the treatment of PD in China.However,the mechanism of their combination is not clear,and further research is needed.Methods:Data were collected from publicly available databases:TCMSP,UnitProt,GeneCards OMIM,PharmGKB,Therapeutic Target Database and DrugBank.Network pharmacology and molecular docking methods was used to analyze the data to discover the possible pharmacological effects of the two drugs in the treatment of PD.Results:Beta-sitosterol,Mandenol and Wallichilide were the active components of Saposhnikoviae Radix and Chuanxiong Rhizoma(FC),and they stably bonded with PD targets,including PTGS2,CASP3,AKT1 and JUN.The target genes of FC were significantly enriched in PD-associated pathways,including calcium signaling and apoptosis pathways.Moreover,the study revealed that the active components of FC may affect cellular structures,such as membrane rafts,membrane microdomains,membrane regions,and postsynaptic membranes,which,in turn,affect a variety of molecular functions and biological processes.Conclusion:The results of this study indicate the direction for clarifying the pharmacodynamic substances of FC,the extraction method of pharmacodynamic substances,as well as the mechanism and efficacy of pharmacodynamic substances.Importantly,this study provides a strategy for developing new therapeutic drugs for PD.

The mechanism of Chuanxiong Rhizoma on glaucomatous optic nerve injury based on network pharmacology and molecular docking

Based on network pharmacology,this study predicted the potential molecular mechanism and related pathways of the protective effect of traditional Chuanxiong Rhizoma,a traditional Chinese herb,on glaucomatous optic nerve injury,and conducted in vitro experimental verification of the predicted results of network analysis.We analyzed the molecular mechanism of Chuanxiong Rhizoma in the potential treatment of glaucoma by revealing its main active ingredients and predicting its targets,so as to provide reference for subsequent basic research.Network pharmacological research results showed that the potential hub targets and key signaling pathways of Chuanxiong Rhizoma in the treatment of glaucoma were closely related to biological processes such as apoptosis,autophagy,inflammation,oxidative stress and angiogenesis.Molecular docking showed that many active ingredients,such as chrysophanol(CHR),myricanone and retinol,could combine well with their target proteins by intermolecular forces,especially CHR had strong binding ability with each target.We speculated that the main active component of Chuanxiong Rhizoma might be involved in the regulation of PI3K-Akt,Nod-like receptor,IL-4 and IL-13,MAPK,AGE-RAGE and neurotrophin signaling pathway by regulating of PI3K,Akt,TLR4,RAGE,NTRK2 and other key targets.Furthermore,it may achieve multi-directional intervention on apoptosis/autophagy,inflammation/immunity,oxidative stress and nutrient metabolism of axoplasma flow,and then delay the degeneration of optic nerve injury.In vitro experiments showed that the active component CHR of Chuanxiong Rhizoma could reverse the M1-type polarization and autophagy/apoptosis of mouse microglia(BV2)induced by lipopolysaccharide(LPS)at the transcriptional level.Meanwhile,the expression of inflammatory mediators IL-1βand TNF-αwas inhibited,and the mRNA level of anti-inflammatory factor IL-10 was significantly increased.In addition,CHR down-regulates activation of the RAGE-NOX4 pathway mediated by LPS in reducing oxidative stress.In this study,network pharmacology and molecular docking technology were integrated for the first time to explore the potential molecular mechanism of traditional Chinese herb“Chuanxiong Rhizoma”in the treatment on glaucoma,and CHR was innovatively proposed as an important ingredient in Chuanxiong Rhizoma that plays a protective role in the damage of optic nerve.Preliminary verification was conducted through in vitro experiments.The results suggest that Chuanxiong Rhizoma may interfere with autophagy and apoptosis,inhibit immune inflammation,as well as reduce oxidative stress in the treatment of glaucoma through the active components represented by CHR,so as to resist progressive optic nerve injury.Our study provides theoretical basis for the clinical use of Chinese herbal medicine or its extract in glaucoma,and also lays a solid foundation for the research of Chinese medicine in the field of optic nerve protection.

Effects of extracts from Renshen(Radix Ginseng), Sanqi(Radix Notoginseng), and Chuanxiong(Rhizoma Chuanxiong) on F-actin in senescent microvascular endothelial cells

OBJECTIVE: To investigate the effects of extracts from Renshen(Radix Ginseng), Sanqi(Radix Notoginseng), and Chuanxiong(Rhizoma Chuanxiong) on the endothelial actin cytoskeleton in senescent human cardiac microvascular endothelial cells(HCMECs), and to propose the possible mechanism underlying the actions.METHODS: Lentiviral mediated RNA interference was applied to a replicative senescent HCMEC model by knocking down heat shock protein 27(HSP27)gene. Cells were treated with extracts from Renshen(Radix Ginseng), Sanqi(Radix Notoginseng), and Chuanxiong(Rhizoma Chuanxiong) at final concentrations of 50, 100, and 200 mg/L, respectively and with 10 μM resveratrol for 48 h. Untreated cells were used as controls. Senescence was detected by senescence β-galactosidase staining and cell proliferation was analyzed by cell counting kit-8 assays.Secreted nitric oxide levels were detected by nitrate reductase. Morphological changes of F-actin and G-actin were observed by laser scanning confocal microscopy. Protein and gene expression of Factin and HSP27 was detected by western blotting.RESULTS: Compared with the control group, the proportion of senescent HSP27 shRNA cells treated with the extracts was decreased and their proliferation was increased. In the extract intervention group, F-actin around the cell periphery became irregular and jagged fractures formed gradually and then dissipated. Moreover, some dynamic actin stress fiber filaments appeared. The G-actin stretched to the cell periphery and punctate staining was scattered in the cytoplasm. In addition, the mean optical density value of F/G-actin was decreased significantly and the protein expression of F-actin was downregulated.CONCLUSION: The extracts delayed microvascular endothelial cell senescence by downregulating the expression of F-actin through HSP27.

Study on pharmacological effect of Chuanxiong Rhizoma on vascular neuropathic headache

Chuanxiong Rhizoma is the dry rhizome of Ligusticum chuanxiong in the umbelliferae family.Chuanxiong Rhizoma pungent,warm,go to liver,gallbladder and pericardium.Effective in promoting blood circulation,promoting Qi,dispelling wind and relieving pain,it could treat chest pain,tingling pain in chest and flank,lump,irregular menstruation,amenorrhea,symptomatic abdominal pain,headache and rheumatic pain.Neurovascular headache is a primary disease caused by dysregulation of intracranial vascular movement and nerve function.It has the characteristics of long course,intermittent recurrent attacks,lingering and difficult to heal.Attacks are often accompanied by many plant nervous system symptoms,such as rapid breathing,accelerated heart rate,vomiting,and gastrointestinal dysfunction.Vascular nerve headache is a common clinical disease,frequently bidity.Studies have shown that Chuanxiong Rhizoma has good pharmacological effects in the treatment of vascular neuropathic headache.①The action of Qi and blood circulation:vascular and neurovascular headache is caused by the evil of external wind and cold and damp heat,which leads to the disconnection of the veins,the disorder of Qi and blood,the obstruction of Qi and blood channels,the loss of brain collateral,and finally causes migraine.Modern Chinese medicine points out that"wind,blood stasis,deficiency,phlegm"are the key factors of the disease.Chuanxiong Rhizoma is the medicine of Qi in the blood.It is pungent and warm.It is good at activating blood and promoting Qi,dispelling wind,relieving pain and dispelling cold,so as to achieve the effect of treating vascular headaches.②Improve brain circulation:angioneurotic headache is caused by dysfunction of the central nervous system related to the regulation of vascular movement,which causes vasospasm or extreme vasodilation,and the decrease of intracranial blood flow causes cerebral ischemia and hypoxia.Sodium ferulate is a chemical component in Chuanxiong Rhizoma.It has a relatively good inhibitory effect on platelet aggregation and the release of 5-HT from platelets.It can ensure the normal contraction of intracranial and extracranial blood vessels,improve the patient′s brain circulation and nerve function,so as to achieve the effect of treating angioneurotic headaches.③Sedative and analgesic effect:the volatile oil and water decoction of Chuanxiong Rhizoma have sedative and analgesic effects,and the water decoction can counteract the excitatory effect of caffeine.Studies have shown that the ATP activation current of rat dorsal root ganglion neurons can be inhibited by ligustrazine in a non-competitive way,which also indicates that Chuanxiong Rhizoma has a good analgesic effect.In this study,the effects of Chuanxiong Rhizoma on angoneeurotic headache were reviewed,and the pharmacological effects of Chuanxiong Rhizoma were further elucidated,providing basis for clinical application and new drug development of Chuanxiong Rhizoma in the treatment of angoneeurotic headache.

Network pharmacology research of Chuanxiong Rhizoma-Acori Tatarinowii Rhizoma in the treatment of vascular dementia

Objective:Using network pharmacology to explore the target and mechanism of Chuanxiong Rhizoma and Acori Tatarinowii Rhizoma in the treatment of vascular dementia(VaD),so as to provide a reference for treating VaD through them.Methods:Traditional Chinese medicine systems pharmacology database and analysis platform were used to screen the main active ingredients and targets of Chuanxiong Rhizoma and Acori Tatarinowii Rhizoma.By means of Gene Cards and Online Mendelian Inheritance in Man(OMIM),targets of VaD were collected.The intersecting targets were obtained by using the Venn map.The String online database was used to build a protein-protein interactions Network and the Metascape database was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis.A“drug-ingredient-target-pathway”network was constructed by Cytoscape software.Autodock vina software was used to conduct molecular docking between targets.Results:A total of 7 active ingredients in Chuanxiong Rhizoma and 4 active ingredients in Acori Tatarinowii Rhizoma were screened.There were 42 active targets of Chuanxiong Rhizoma and 70 active targets of Acori Tatarinowii Rhizoma and 1152 disease targets.After deleting the repeat value,51 drugs targets were obtained.After the intersection,with a total of 25 targets.According to GO and KEGG enrichment analysis,the main biological processes involved include cellular response to lipid,negative regulation of apoptotic signaling pathway,blood circulation,response to a steroid hormone,etc.The main pathways include pathways in cancer,PI3K-Akt signaling pathway,and AGE-RAGE signaling pathway in diabetic complications,etc.Molecular docking showed that the most active docking combinations were AKT1 and Perlolyrine,RELA and FA,MAPK14 and FA,respectively.Conclusion:Chuanxiong Rhizoma and Acori Tatarinowii Rhizoma play an important role in the treatment of VaD mainly by anti-inflammatory and anti-apoptosis.

川芎对肺癌干细胞原发性肿瘤相关黏附分子影响的实验研究

目的:探究川芎对肺癌干细胞样细胞荷瘤小鼠原发肿瘤的黏附作用机制。方法:通过无血清培养技术,培养肺癌细胞中的干细胞样细胞,并将其种植在小鼠脚垫。按照处理药物分为空白对照组(Con组)、川芎组(RC组)、顺铂组(DDP组)、川芎+顺铂组(RC+DDP组)并干预,3周后,在无菌环境中手术剥取肿瘤组织。通过Western blot实验技术和免疫组化技术,检测分析小鼠肿瘤细胞中相关黏附蛋白CD44v6、β1整合素的表达。结果:CD44v6在RC+DDP中的表达较DDP组、RC组及Con组减少,且差异具有统计学意义(均P<0.05)。β1整合素原发瘤组织在RC+DDP组中的表达低于Con组、RC组及RC+DDP组(均P<0.05)。结论:川芎和顺铂的联合应用,在一定程度上可减少肺癌干细胞样细胞原发肿瘤中黏附分子CD44v6、β1整合素的表达,从而抑制其黏附能力。

川芎挥发油化学成分、制剂及药理作用研究进展

川芎是我国常用传统中药,其中挥发油是主要药效成分,一直是川芎研究工作的重点。早期对川芎挥发性成分的研究主要集中在其中化学成分的定性鉴定及定量分析。近年来研究者对川芎挥发油的研究逐渐深入,开展了川芎不同部位挥发油的差异分析,比较了加工制备方法对挥发油成分的影响;研究人员除了对川芎挥发油镇痛镇静、保护神经细胞、改善血管功能等药理作用及其机制进行深入研究外,新的研究发现川芎挥发油还具有骨保护、抗肿瘤、抗抑郁等药理活性。该文对近年来围绕川芎挥发油性成分的最新研究进展进行汇总,总结不同部位、不同产地、不同加工提取方法挥发油成分种类和含量差异,并综述了川芎挥发油制剂及药理活性研究进展,以期为更好地开发利用川芎挥发油自然资源提供参考。

川芎的化学成分和药理作用研究进展

川芎来源于伞形科植物川芎的干燥根茎,具有活血行气、祛风止痛的功效。川芎中主要含有苯酞、生物碱、酚酸、多糖等化学成分。药理研究表明,川芎对心脑血管系统、神经系统、呼吸系统等均具有一定的药理活性,主要表现为抗脑缺血、抗血栓、镇痛、抗炎、抗氧化、抗哮喘等药理作用。本文对川芎的化学成分及药理作用进行系统整理和归纳,以期为临床应用和资源开发提供参考。

Chuanxiong Rhizoma extracts prevent liver fibrosis via targeting CTCF-c-MYC-H19 pathway

Objective:Hepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases.Chuanxiong Rhizoma(Chuanxiong in Chinese,CX)is a traditional Chinese herbal product to prevent cerebrovascular,gynecologic and hepatic diseases.Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells(HSCs).Here,this study aimed to compare the protection of different CX extracts on bile duct ligation(BDL)-induced liver fibrosis and investigate plausible underlying mechanisms.Methods:The active compounds of CX extracts were identified by high performance liquid chromatography(HPLC).Network pharmacology was used to determine potential targets of CX against hepatic fibrosis.Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation.The expression of targets of interest was determined by quantitative real-time PCR(qPCR)and Western blot.Results:Different CX extracts were identified by tetramethylpyrazine,ferulic acid and senkyunolide A.Based on the network pharmacological analysis,42 overlap targets were obtained via merging the candidates targets of CX and liver fibrosis.Different aqueous,alkaloid and phthalide extracts of CX(CX_(AE),CX_(AL) and CXP_(HL))significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor(CTCF)-c-MYC-long non-coding RNA H19(H19)pathway in the BDL-induced mouse model.Meanwhile,CX extracts,especially CX_(AL) and CX_(PHL) also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with taurocholate acid(TCA),lithocholic acid(LCA)and transforming growth factor beta(TGF-β),as illustrated by decreased bile duct proliferation markers.Conclusion:Our data supported that different CX extracts,especially CX_(AL) and CX_(PHL) significantly alleviated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway,providing novel insights into the anti-fibrotic mechanism of CX.

王济华运用角药治疗类风湿关节炎经验

王济华教授认为,类风湿关节炎早期多因外感风、寒、湿三邪,三者之间相互促进、互相转化,风寒表邪入里日久或郁而化热;病程日久多虚实夹杂,肝肾亏虚、气血不足,同时兼有寒湿痹阻、痰瘀互结。故王教授治疗痹证早期以祛邪散寒为主,兼顾清热利湿、化痰散结,中晚期则偏于滋养气血、补益肝肾。王济华教授运用角药治疗痹证颇有心得,组方精妙、配伍严谨,常用角药川芎-延胡索-白芍行气活血、柔筋止痛;忍冬藤-络石藤-青风藤清热通络、祛风除湿;半夏-陈皮-竹茹燥湿化痰、理气和中;白术-薏苡仁-茯苓益气健脾、利湿消肿;桑寄生-续断-杜仲滋补肝肾、强筋壮骨;酸枣仁-合欢皮-首乌藤宁心安神、解郁除烦。王教授临证时,追求阴阳调和平衡、气机升降有度,临床用药有药简力专、增效减负之功。

Fabrication of nano Rhizama Chuanxiong particles and determination of tetramethylpyrazine

Rhizama Chuanxiong is a kind of traditional medicinal herb used to promote blood circulation and eliminate wind to relieve pain. In this work, nano Rhizoma Chuanxiong particles were successfully prepared by high speed centrifugal sheering (HSCS) pulverizer. The influence of processing parameters on the size of Rhizama Chuanxiong particles and the different properties between nano Rhizoma Chuanxiong particles and original fine powder were systematically studied by ZetaPALS light scattering granulometric analyzer and optical microscope. The content of effective ingredient tetramethylpyrazine (TMP) was determined by high-performance liquid chromatography (HPLC). The results illustrate that general Rhizama Chuanxiong powder can be ultrafinely ground to nanometer within 50 min, and the cellular tissues of Rhizoma Chuanxiong are broken into pieces and dispersed stably and homogeneously after being ultrafinely ground. In addition, the active ingredients can dissolve out directly and fully, and the extraction ratio of TMP is increased 32.2% by HSCS processing.

基于网络药理及分子对接技术探讨贯叶金丝桃-川芎治疗焦虑症的作用机制

目的应用网络药理学及分子对接方法探讨贯叶金丝桃-川芎药对治疗焦虑症作用机制,为临床应用贯叶金丝桃-川芎药对提供依据。方法利用TCMSP数据库进行化合物成分检索,Swiss Target Prediction数据库预测药物靶点,在Uniprot数据库进行标准化处理。使用OMIM数据库、Disgenet数据库、Genecards数据库获焦虑症相关靶点数据。利用Venny 2.1在线软件绘制韦恩图,Cytoscape 3.7.2软件构建“药物-成分-靶点-疾病”可视化网络图。使用Network Analyzer软件对网络图进行拓扑分析,利用DAVID 6.8数据库,基于R3.6.1软件使用Bioconductor生物信息软件包,进行关键靶基因GO与KEGG功能富集分析。对接程序由AutoDock-Vina 1.1.2执行,应用PyMOL 2.3.0和BIOVIA Discovery Studio 2016软件对结果可视化。结果共筛选出贯叶金丝桃-川芎药对12个活性成分,潜在靶点413个,焦虑症相关靶点1871个,活性成分-疾病共同靶点119个,进行拓扑分析得到9个核心成分。对其PPI网络进行MCODE聚类分析共得到4个基因簇和3个核心基因。GO和KEGG分析显示,贯叶金丝桃-川芎药对治疗焦虑症主要涉及化学突触传递调节、神经活性配体-受体相互作用、含5-HT的神经突触、多巴胺(Dopamine,DA)能神经突触等信号通路相关。筛选出4种成分与关键靶点结合强度较强,且具有保护神经细胞、调节神经递质、抗氧化等作用的核心活性成分。结论贯叶金丝桃-川芎药对可能与5-HT、GABA、DA神经递质信号通路调节关系密切,并通过减轻氧化应激、抑制自噬、保护及促进神经细胞再生等机制治疗焦虑症。

川芎-丹参配伍治疗脊髓损伤的网络药理学研究与验证

目的:基于网络药理学,预测川芎-丹参配伍治疗脊髓损伤的作用机制。方法:利用网络药理学工具,获得川芎-丹参治疗脊髓损伤的有效成分、核心靶点及信号通路。采用改良Allen重物打击法构建脊髓损伤模型,采用酶联免疫吸附试验(ELISA)测定各组大鼠活性氧(ROS)、丙二醛(MDA)水平;采用蛋白质印迹法检测各组大鼠脊髓组织中磷脂酰肌醇3激酶(PI3K)、p-PI3K、蛋白激酶B(AKT)、p-AKT蛋白表达。结果:化合物-靶点网络包含154个化合物和484个相应靶点;基因本体(GO)功能富集分析得447个条目;京都基因和基因组百科全书(KEGG)通路富集分析得到126条信号通路。动物实验结果表明,与假手术组比较,模型组ROS、MDA水平显著增高(P<0.01);p-PI3K、p-AKT蛋白表达显著下降(P<0.01);与模型组比较,中药高剂量组ROS、MDA水平显著下降(P<0.01);p-PI3K、p-AKT蛋白表达显著增高(P<0.01)。结论:川芎-丹参联合治疗脊髓损伤具有多成分、多靶点、多通路的优势,其作用机制可能与调控PI3K/AKT信号通路有关。

川芎治疗偏头痛药理机制研究进展

偏头痛在中国是一种常见的搏动性、原发性的头痛病,多一侧起病,重者可致残,对患者的生活质量产生重大影响,是目前治疗的一大难点。中医治疗偏头痛既可以改善疾病的症状,还可以祛除疾病的根源,具有多目标、多途径的特点。通过对治疗偏头痛的古今医案数据进行分析,发现中医治疗主要采取祛瘀、平肝阳、补虚三种治疗策略。其中化瘀方中大多含有川芎,发现川芎可以活血化瘀,改善血液流变学性质,镇静,镇痛,清除氧自由基,同时也发现含有川芎的药对居于偏头痛治疗使用药对之首。川芎是临床上治疗头痛、血管性头痛、偏头痛用药频率最高的单味中药之一。该文对川芎治疗偏头痛的药理作用机制进行综述,为川芎临床治疗和预防偏头痛提供理论科学依据。并对川芎的有效成分现代研究进行归纳梳理。结果发现川芎治疗偏头痛的药理机制包括抑制氧自由基活性,减轻炎症反应;抗神经元凋亡,保护脑神经;调节神经递质,降低痛阈值;抗血小板聚集;调肠道菌群等。

川芎治疗偏头痛药理机制研究进展

偏头痛是临床上常见的原发性神经血管性头痛,与心理社会因素密切相关,对人们日常生活造成极大影响。其发病机制多种多样,目前较为成熟的机制有血管学说、神经元学说、炎症介质学说、神经递质学说、神经营养因子、中枢敏感化及丘脑边缘系统的激活、多巴胺能系统相关基因学说等。中医认为六淫之邪外袭,上犯巅顶,邪气滞留,阻滞清阳,或内伤诸疾,导致气血逆乱,瘀阻经络,脑失所养,均可发生头痛。而川芎作为临床常用中药,具有活血行气、祛风止痛之功用。基于宋金元时期治疗偏头痛用药规律,发现川芎在治疗头痛、头风、首风、偏头痛中应用频率极高。此外,现代药理学研究发现,川芎中主要成分有四甲基吡嗪(川芎嗪)、阿魏酸、挥发油、藁本内酯、洋川芎内酯和丁烯苯肽等烷基苯肽类化合物,并且,川芎具有镇痛、抗炎、抗氧化、抗肿瘤、抗凝血、抗抑郁、抗衰老、抗动脉粥样硬化、细胞保护、改善心功能等作用。综上所述,川芎在治疗偏头痛方面有着极大的研究前景。文章主要对川芎在治疗偏头痛方面的作用加以分类总结,为川芎治疗偏头痛的应用提供科学依据。

基于甲基化捕获联合转录组测序探讨栀子-川芎药对抗动脉粥样硬化的作用机制

目的:观察栀子-川芎药对对氧化型低密度脂蛋白(ox-LDL)诱导的RAW264.7泡沫细胞DNA甲基化和转录组表达的作用。方法:细胞毒性试验(CCK-8)法检测不同浓度栀子-川芎冻干粉对RAW 264.7细胞的增殖抑制情况;以ox-LDL处理RAW 264.7细胞48 h形成泡沫细胞,将细胞分为栀子-川芎冻干粉组(80 mg/L ox-LDL、0.3 g/L栀子-川芎冻干粉干预)、模型组(80 mg/L ox-LDL处理)和空白对照组(未处理);气相、色谱质谱法(GC-MS)和酶联免疫吸附法(ELISA)分别检测各组总胆固醇(TC)、游离胆固醇(FC)以及炎性因子[肿瘤坏死因子α(TNF-α)、白介素6(IL-6)和细胞间黏附分子1(ICAM-1)]的表达;采用DNA甲基化捕获测序(MC-seq)和转录组测序(RNA-seq)方法检测各组细胞全基因组DNA甲基化和转录组基因表达水平,使用DSS工具分析各组样本间的差异甲基化位点(DMS)和差异表达基因(DEGs),并利用生物信息学方法对差异基因进行京都基因与基因组百科全书(KEGG)和基因本体(GO)富集分析。结果:CCK-8检测发现,栀子-川芎冻干粉对RAW264.7细胞具有一定的细胞毒效应;与空白对照组相比,模型组TC、FC水平以及炎性因子TNF-α、IL-6和ICAM-1的表达明显升高(P<0.01);与模型组相比,栀子-川芎冻干粉组TC、FC水平以及TNF-α、IL-6、ICAM-1的表达明显降低(P<0.01)。MC-Seq检测发现,在启动子区域,模型组与空白对照组相比,共有8421个DMSs,分别对应5061个低甲基化和3405个高甲基化基因位点。栀子-川芎冻干粉组与模型组比较,共有8395个DMSs,分别有4257个高甲基化基因位点和4138个低甲基化基因位点。RNA-seq检测方面,经两两比较取交集(栀子-川芎冻干粉组与模型组比较,模型组与空白对照组比较)显示栀子-川芎冻干粉共逆转了119个DEGs,其中下调39个,上调80个。对MC-Seq与RNA-seq数据进行联合分析发现,与模型组相比,栀子-川芎冻干粉组有29个低甲基化高表达基因,包括YAM1、硫酯酶超家族成员4(THEM4)、神经型一氧化氮合酶(NOS1)等;33个高甲化低表达基因,包括血小板源性生长因子受体α多肽(PDGFRα)、纤维连接蛋白1(FN1)及Ⅰ型胶原蛋白α2(COL1A2)等。KEGG富集分析显示上述基因涉及Focal adhesion、PI3K-Akt和AGE-RAGE等信号通路;GO富集分析显示涉及白细胞介素-1产生的调节和上皮细胞增殖的正向调节等生物学过程。结论:体外实验表明,栀子-川芎冻干粉具有明显的抗动脉粥样硬化效应,其机制可能与调控心血管相关基因的甲基化水平进而影响下游基因的表达有关。

川金解郁汤干预轻中度抑郁患者的疗效分析及代谢组学研究

目的分析川金解郁汤(Chuanjin Jieyu Decoction,CJJYD)对轻中度抑郁(mild to moderate depression,MTMD)患者干预前后的代谢物差异性及相关代谢物变化规律,为CJJYD治疗MTMD提供科学依据。方法纳入湖南省脑科医院2020年1月至12月期间23名MTMD患者作为病例组(Dep组)、健康人21名作为对照组(CT组),Dep组予以CJJYD干预6周,早晚各服1剂,每次100 mL。采用汉密尔顿抑郁量表(Hamilton depression scale,HAMD)和抑郁自评量表(self-rating depression scale,SDS)评定疗效;超高效液相色谱-高分辨质谱联用技术分析干预前后血浆代谢物变化;采用多维度统计分析,筛选差异代谢物并进行分析。结果MTMD患者经CJJYD干预后,HAMD和SDS评分明显降低(P<0.01)。与CT组相比,Dep组患者血浆中检测145个差异代谢物,涉及亚油酸代谢等38条代谢通路;Dep组经CJJYD干预后,患者血浆中检测46个差异代谢物,涉及烟酸和烟酰胺代谢等11条代谢通路。结论MTMD患者经CJJYD干预后,抑郁症状得到改善,代谢组学有差异性代谢物,涉及亚油酸代谢、烟酸和烟酰胺代谢、精氨酸和脯氨酸代谢等代谢通路,可能为其抗抑郁的机制之一。