Integrated network pharmacology analysis and in vitro cell experiments to reveal the mechanisms of Ligusticum chuanxiong Hort.in the treatment of non-alcoholic fatty liver disease

Background:Non-alcoholic fatty liver disease(NAFLD)is a liver disease of unknown etiology.A traditional Chinese medicine Ligusticum chuanxiong Hort.(CX),it has been used about 2,000 years.Until now,the mechanism of action of CX on NAFLD remains unclear.Method:We first tested the toxicity of CX to AML12 cells with CCK-8.In vitro cell models of NAFLD were made using free fatty acid,and used Oil Red O staining tested lipid droplets.Then the active compounds of CX were collected from TCMSP and literatures,and SwissTargetPrediction,Search Tool for Interacting Chemicals,Encyclopedia of Traditional Chinese Medicin,Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine database were used to predict the targets of the compounds.DRUGBANK,Online Mendelian Inheritance in Man,Therapeutic Target Database,DisGeNET and GeneCards database were used to predict the targets of NAFLD.Use Venn diagram to obtained the intersection targets by,and analyzed the protein-protein intersection network.Use Kyoto Encyclopedia of Genes and Genomes and Gene Ontology to forecast the function of intersection genes.Molecular docking was used to evaluate the interaction between hub gene and active ingredients.Finally,use western blotting to determine the effects of CX on PPARA,PPARG,IL1B and TNF proteins.Result:CX can reduce the production of AML12 cell lipid droplets.A total of 15 chemical components were identified from CX.Folic acid,chrysophanol and sitosterol were the main components of CX against NAFLD.ALB,TNF,PPARG and PPARA proteins were the main targets of CX in the treatment of NAFLD.PPAR signaling pathway and fatty acid degradation were closely related to anti-NAFLD.Molecular docking results shows that folic acid was the main active ingredient of CX for NAFLD treatment,and TNF is the main potential target.The cellular NAFLD model showed that CX up-regulated the expression of PPARA and PPARG protein and down-regulated inflammatory factor IL-1B and TNF expression.Conclusion:Our study suggests that CX has a therapeutic effect on NAFLDA,which may be related to the PPAR pathway and the reduction of inflammatory cytokines.

Pathogen Identification of the Anthracnose of Ligusticum chuanxiong Hort. and Inhibitory Effect of Four Fungicides on the Pathogen

[Objective] The research aimed to isolate and identify the pathogen of anthracnose of Ligusticum chuanxiong Hort,and make the antifungal test on four kinds of fungicides for selecting the optimum fungicides.[Method] The pathogenic fungi was separated according to Koch＇s rule and the shape characteristics were identified. The antifungal test of fungicides was made by using plate mycelium growth inhibition method.[Result] The pathogenic fungi was separated from leaves of Ligusticum chuanxiong Hort. and morphological characters were consistent with that of Colletotrichum gloeosporioides. In addition to chloroisobromine cyanuric acid,the other three fungicides could inhibit the mycelium growth. The growth inhibition rates of 1 000 times Metalaxyl＋mancozeb,zineb,Thiophanate-methyl for the mycelium were 26.8%,22.1%,59.8% respectively after 7 days.[Conclusion] The anthracnose was caused by Colletotrichum gloeosporioides. Ligusticum chuanxiong Hort. was a new record host plant of Colletotrichum gloeosporioides and the best inhibiting fungicide was Thiophanate methyl.

Optimization of ISSR-PCR Reaction Conditions for Genomic DNA of Ligusticum chuanxiong hort.

[Objective] To investigate the impacts of ISSR-PCR amplification factors, for the establishment and optimization of ISSR-PCR reaction system for Ligusticum chuanxiong hort. [Method] Using genomic DNA of Chuanxiong leaf extracted via an improved CTAB method as template, single factor analysis was performed to investigate the impacts of DNA template concentration, Mg2＋ concentration, dNTPs concentration, primer concentration, Taq DNA polymerase concentration on ISSR-PCR amplification and to optimize this system for Ligusticum chuanxiong hort. [Result] The ISSR-PCR amplification（25 μl） suitable for Ligusticum chuanxiong hort. was determined to be composed of 2.5 μl of 10×reaction buffer, 2.1 mmol/L MgCl2, 300 μmol/L dNTPs, 0.4 μmol/L primer, 1.0 U Taq DNA polymerase and 20-40 ng genomic DNA. [Conclusion] Our study laid basis for analyzing the genetic diversity of Ligusticum chuanxiong hort. resources distributed in 17 different areas of China.

Study on the mechanism of “Ligusticum chuanxiong Hort.-Salvia miltiorrhiza” couplet medicine for coronary heart disease based on network pharmacology

Objective:To study the active components and gene targets of“Ligusticum chuanxiong Hort.-Salvia miltiorrhiza”couplet medicine for the treatment of coronary heart disease(CHD)based on network pharmacology,and to explore its mechanism.Methods:Based on oral bioavailability(OB)>30%and drug-like(DL)>0.18,the active components of“Ligusticum chuanxiong Hort.-Salvia miltiorrhiza”for CHD were screened and the targets of treating CHD were predicted by using TCMSP and GeneCards database.The active component-CHD target network was established by Cytoscape 3.7.2 software.The protein-protein interaction(PPI)network was constructed by utilizing String database.Finally,GO enrichment analysis and KEGG pathway enrichment analysis were performed by using Bioconductor and R language.Results:The study predicted 72 active components in total,including 7 Ligusticum chuanxiong Hort.and 65 Salvia miltiorrhiza,such asβ-sitosterol,tanshinone.Totally 96 target genen of active components were obtained,including PTGS1,NCOA2,NOS2,etc.Results of GO enrichment analysis showed 142 biological processes,related to adrenergic receptor activity,G protein-coupled amine receptor activity,etc.KEGG pathway enrichment analysis showed 131 pathways,including PI3K-Akt signaling pathway,IL-17 signaling pathway,HIF-1 signaling pathway,etc.Conclusion:“Ligusticum chuanxiong Hort.-Salvia miltiorrhiza”couplet medicine exerts therapeutic effects on CHD from multiple targets as PTGS1,PTGS2 and adrenergic receptor activity and PI3K-Akt signaling pathway.The study can provide reference for further researches on its mechanism and the pharmacological effects of Shenzhi Tongxin Capsule.

川芎(Ligusticum chuanxiong Hort)种植地的土壤动物群落特征

采用大型手捡、Tullgren干漏斗和Baermann湿漏斗法对川芎种植基地土壤动物群落进行调查.结果显示,试验所采集土壤动物平均密度为3.13×104只/m2,其中,川芎样地土壤动物平均密度为1.35×104只/m2,11个类群;菜地土壤动物平均密度为4.91×104只/m2,15个类群.同功能种团分析表明,菜地的杂食性和腐食性土壤动物密度显著高于川芎地(P<0.05),植食性和捕食性显著低于川芎样地(P<0.05).菜地的DG和C指数高于川芎样地,而J和H'指数低于川芎样地.表明川芎种植对土壤动物群落分布与多样性特征产生一定影响.

Law of Occurrence and the Damage of Main Diseases and Pests in Ligusticum chuanxiong Hort Field

[Objective]The aim was to provide scientific basis for the prevention and treatment of the main diseases and pests. [Method]The systematic investigation was carried out in the process of seedling and field cultivation of Ligusticum chuanxiong. [Result]The main diseases were root rot,Powdery mildew and Spot blight,while the main pests were Epinotia leucantha Meyrick,Prodenia litura Fabr.,Scarabaeoidea,Tetranychus cinnabarinus Boisduval and Delia platura Meigen. [Conclusion]The law of occurrence of main diseases and pests were confirmed.

A rapid HPLC method for determination of coniferyl ferulate in Angelica sinensis and Ligusticum chuanxiong

Aim A reliable and rapid HPLC method was developed for quantitative determination of coniferyl femlate, an ester of ferulic acid, with multiple pharmacological activities in Angelica sinensis and Ligusticum chuanxiong, two commonly used Chinese medicines. Methods The determination was achieved by using a Zorbax ODS C18 analytical column （250 mm×4.6 mm ID, 5 μm） at isocratic elution of 1% aqueous acetic acid and acetonitrile （1：1） with diode-array detection （318 nm）. The calibration curve of coniferyl femlate showed good linearity （r^2 = 0.9995） within the test range. Results The developed method showed good precision with intra- and inter-day variations of 0.22% - 1.16% and 0.86% - 2.62% between the levels of 0.380 - 0.038 mg·mL^-1, respectively. The repeatability represented as RSD of coniferyl femlate was less than 2.7% for three levels （0.2 - 1.0 g of Angelica sinensis）, and the recovery was 105.3% with RSD of 3.2%. Conclusion The validated method was successfully applied to quantify coniferyl femlate in 12 samples of Danggui and Chuanxiong.

Measurement and Correlation of the Solubility of Ligusticum Chuanxiong oil in Supercritical CO_2

Extraction of the Ligusticum Chuanxiong oil with supercritical CO2 （SC-CO2） was investigated at the temperatures ranging from 55℃ to 70℃ and pressure from 25 MPa to 35 MPa. The mass of Ligusticum Chuanxiong oil extracted increased with pressure at constant temperature. The initial slope of the extraction was considered as the solubility of oil in SC-CO2. Chrastil equation was used to correlate the solubility data of Ligusticum Chuanxiong oil. An improved Chrastil equation was also presented and was employed to correlate the solubility data, The correlation results show that the values of the average absolute relative deviation are 5.94% and 3.33% respectively, indicating the improved version has better correlation accuracy than that of Chrastil equation.

Effect of Ligusticum Chuanxiong on Hypoxic Pulmonary Hypertension in Rats and Its Mechanism

Objective: To explore the mechanism of Chuanxiong in alleviating hypoxic pulmonary hypertension in rats by inhibiting pulmonary vascular remodeling. Methods: Thirty healthy and clean male SD rats weighing (180 - 220) g were randomly divided into three groups (n = 10): normoxia group (n), hypoxia group (H) and Chuanxiong group (L). Group N was fed in normoxic environment, and the other two groups were fed in hypoxic (9% 11% O2) environment for 4 weeks, 8 h/D, 6 days a week. Rats in group L were gavaged with Ligusticum chuanxiong solution diluted with normal saline at the concentration of 300 mg/kg, and rats in group H were gavaged with equal volume of normal saline. After 4 weeks, the mean pulmonary artery pressure was measured. After pulmonary perfusion, the right ventricular free wall and left ventricle plus ventricular septum were taken to measure the right ventricular hypertrophy index. The changes of pulmonary morphology and ultrastructure were observed under light microscope. Results: Compared with group n, the average pulmonary artery pressure and right ventricular hypertrophy index in the other two groups increased, and the thickening of pulmonary vascular wall was obvious under microscope (P Conclusion: Ligusticum chuanxiong can relieve pulmonary artery pressure in rats by inhibiting pulmonary vascular remodeling.

基于多元统计学分析^(60)Co-γ射线辐照对川芎挥发性成分的影响

川芎挥发性成分是其主要活性成分之一,也是评价川芎药用品质的重要指标。为探究^(60)Co-γ射线辐照对川芎挥发性成分的影响,本研究以不同吸收剂量处理川芎样品,采用电子鼻结合顶空固相微萃取-气相色谱-质谱技术(HS-SPME-GC-MS),通过主成分分析、线性判别分析、正交偏最小二乘法和聚类分析的多元统计学方法分析数据,以期了解川芎辐照前后挥发性成分的变化。电子鼻与GC-MS结果都表明:川芎气味主要由烷烃类、醇类、醛类、酮类贡献,10 kGy剂量以下的辐照处理对川芎挥发性气味成分影响不大;川芎经0 kGy(对照组)、3 kGy、7 kGy、10 kGy剂量辐照处理后,共鉴定出60种化合物,其中烃类23种,醇类12种,脂类10种,醛酮类4种,其他类11种;筛选到21种辐照前后的差异特征性指标物,它们在川芎挥发性成分中只占约12.92%,不是川芎的主要挥发性成分。经10 kGy剂量以下的辐照处理后,川芎中没有新生成的物质被鉴定出来。研究结果提示经10 kGy以下剂量处理川芎不会影响其主要挥发性成分。

外源Cd对川芎苓种萌发及幼苗生长的影响

本研究旨在探究不同浓度镉(Cd)对川芎苓种萌发和幼苗生长的影响。采用以石英砂为基质的水培试验,施加不同浓度CdCl 2·2.5 H 2O(0、0.1、0.25、0.5、1、2 mmol/L)溶液处理川芎苓种,研究Cd胁迫对川芎苓种萌发、幼苗生长、生理代谢及Cd含量的影响。结果显示,随着Cd浓度的增加,株高抑制率、根长抑制率上升;根、叶及节盘Cd含量显著升高;株高、根长、叶鲜重、根鲜重下降;抗氧化酶(过氧化氢酶、过氧化物酶、超氧化物歧化酶)活性、非酶系统物质(可溶性蛋白、谷胱甘肽、脯氨酸)含量以及丙二醛含量先升高后降低。研究表明,0.1~2.0 mmol/L Cd对川芎苓种萌发和早期幼苗生长均有明显的毒害作用,随着Cd胁迫浓度的升高毒害作用增强,其中川芎幼苗根对Cd胁迫最敏感。Cd胁迫下川芎幼苗生理生化指标整体上呈现低促高抑的Hormesis效应。川芎幼苗通过提高抗氧化酶活性和非酶系统物质积累,减少膜系统损伤、活性氧蓄积,缓解Cd毒害作用,提高耐受性。

基于全谱非靶向代谢组学技术的川芎不同部位代谢物深度解析

为了深度解析川芎中不同部位代谢物特征,本研究采用高效液相色谱法(HPLC)对川芎的根茎、茎、叶中的活性成分进行含量测定,并整合超高效液相色谱-质谱联用仪(UPLC-MS)和气相色谱-质谱联用仪(GC-MS)的全谱非靶向代谢组学技术,对川芎的根茎、茎和叶的挥发性成分、非挥发性成分进行全面的定性和定量分析。结果表明,川芎根茎中活性成分含量高于茎、叶。川芎的全谱非靶向代谢组学共检出2891个代谢物,总丰度为茎>叶>根茎,各部位化学成分种类相同、含量差异较大,包括氨基酸及其衍生物、萜类、酚酸类等32类化合物。其中LC-MS检出1726个代谢物,GC-MS检出1216个代谢物,两个平台共同检出51个代谢物。对川芎不同部位的差异代谢物进行分析,根茎与茎、根茎与叶、茎与叶中筛选到差异代谢物1683、2054和1844个,差异代谢物总丰度为根茎≈茎>叶。根茎中显著富集含氮化合物、酚类、其他类(糖类、内酯类),茎中的醇、胺类、醚类高度富集,叶中的萜类、酮类、黄酮类高度富集。川芎中大多数活性成分如川芎嗪、阿魏酸、藁本内酯等,呈现根茎>茎>叶的趋势,但茎和叶中也含有含量较高的阿魏酸、欧当归内酯A等重要活性成分,具有较高利用价值。通过KEGG富集分析结果推测差异代谢物可能与次生代谢产物的生物合成等途径相关。本研究深度解析了川芎不同部位的成分积累规律,为川芎资源的合理利用提供了科学依据。

基于网络药理学与分子对接预测川芎-赤芍药对治疗动脉粥样硬化的作用机制

心血管疾病是全球范围内死亡率最高的一种疾病,其主要病理基础是动脉粥样硬化。为了探讨川芎-赤芍药对治疗动脉粥样硬化的潜在作用机制,利用网络药理学平台,挖掘了川芎-赤芍的有效成分及靶点并筛选核心成分;查找了动脉粥样硬化的靶点,然后与药物靶点取交集筛选候选靶点;构建候选靶点的蛋白互作网络得到核心靶点;对候选靶点进行GO功能富集分析与KEGG信号通路富集分析。最后将核心成分和核心靶点进行分子对接。结果从川芎-赤芍药对中筛选到包括核心成分β-谷甾醇、黄芩素、豆甾醇和杨梅酮在内的35个活性成分,获得川芎-赤芍药对治疗动脉粥样硬化的包括核心靶点AKT1、TNF、VEGFA、TP53在内的候选靶点58个,核心成分和核心靶点间均具有较好的结合能力,候选靶点主要参与了对氧水平下降的反应、对细菌来源分子的反应、对激素的反应等生物学过程,富集在癌症信号通路、脂质和动脉粥样硬化信号通路、化学致癌-受体激活通路、流体剪切力与动脉粥样硬化通路等相关通路上,以协同的形式通过调节细胞生长发育、降低血脂水平和控制促炎介质的分泌等对动脉粥样硬化发挥治疗作用,为川芎-赤芍药对的临床应用提供理论基础。

不同浓度川芎复方提取物对“夏黑”葡萄贮藏品质的影响

以“夏黑”葡萄为试材,采用不同浓度川芎复方提取物(质量比为川芎∶藁本∶丁香=4∶4∶6,浓度比为B1∶B2∶B3∶B4∶B5=1∶2∶3∶4∶5)浸泡处理“夏黑”葡萄,每隔7 d对“夏黑”葡萄的腐烂率、失重率、可溶性固形物含量、可滴定酸含量、维生素C含量、丙二醛含量、多酚氧化酶活性和果实硬度进行测定,研究了不同浓度川芎复方提取物对采后“夏黑”贮藏品质的影响,以期为开发植物源葡萄保鲜剂提供参考依据。结果表明:与对照相比,5种不同浓度的川芎复方提取物浸泡处理“夏黑”葡萄,均可有效降低采后葡萄果实的腐烂率及失重率,有效延缓采后葡萄果实维生素C含量的降低,并在一定贮藏时间内有效延缓采后葡萄果实的可滴定酸以及可溶性固形物含量的降低,也延缓了采后葡萄果实硬度的下降,同时也有效抑制了采后葡萄果实丙二醛含量的升高以及多酚氧化酶活性的上升。其中,B4组的川芎复方提取物处理的效果最佳,较好的保持了采后“夏黑”葡萄的贮藏品质。

基于正交设计优化新鲜川芎中挥发油提取工艺

为优化川芎挥发油提取工艺,建立以新鲜川芎为原料提取制备挥发油的新方法,采用正交试验设计对乙醇回流提取工艺条件进行优化,并进一步考察优选回收浓缩、油水分离等关键工艺参数。以藁本内酯和洋川芎内酯A作为指标成分,应用HPLC一测多评法进行含量测定。以提取量、油收率、油含量为评价指标,最终确定川芎挥发油提取制备新方法为:鲜川芎切片,加8倍量70%乙醇回流提取2次(以干药材计,第一次需测定鲜川芎水分,调节乙醇浓度为70%),每次1.5 h,滤液回收浓缩至2.0~3.0 g生药/mL,静置过夜,弃去水层,上层乳化层加热至60℃离心,分取油层,余下乳化层再加氯化钠至饱和并加热至60℃离心,合并油层,即得川芎挥发油。新方法所得川芎挥发油收率约为3%,藁本内酯和洋川芎内酯A含量达70%。该研究所建立的新方法生产设备要求低、操作简便易行,可实现川芎挥发油的高效制备,且含量高、品质优,为川芎挥发油的工业化生产提供了新思路和新方法。

基于转录组和代谢组解析川芎对镉胁迫的响应机制

为了解不同水平镉(Cd)胁迫下川芎基因表达和代谢产物的变化规律,探究川芎对Cd胁迫的响应机制,利用盆栽试验,以不添加Cd溶液的清洁土壤为对照,设置1、3、6、10 mg·kg-1共4个Cd胁迫处理水平,采用转录组学测序(RNA sequencing,RNA-seq)和超高效液相色谱质谱联用(ultra performance liquid chromatography tandem mass spectrometry,UPLC-MS/MS)技术,筛选川芎抗Cd胁迫的关键基因与代谢通路。结果表明,共筛选到8569个差异表达基因,包括上调基因6859个,下调基因1710个。与对照相比,4个Cd处理组的共有差异基因仅1个,为CML19,可能是川芎抗Cd胁迫的关键基因。代谢组共标注和定量了1238种差异代谢物,在KEGG数据库中注释得到76条代谢通路,其中包括氨基酸代谢、氨酰基-tRNA的生物合成和脂肪酸的生物合成等。联合分析表明,当受到不同水平Cd胁迫时,川芎通过调节不同种类氨基酸来维持自身代谢平衡,在川芎抗Cd胁迫中发挥重要作用。研究结果为川芎抗Cd胁迫提供科学支撑与理论依据,为针对川芎资源的栽培育种及缓解Cd胁迫等相关研究提供基础。

复方川芎美白淡斑乳膏的制备工艺研究及质量评价

目的制备复方川芎美白淡斑乳膏并进行质量评价。方法按川芎-益母草-白芷-当归质量比4∶3∶2∶1制备中药提取液,以酪氨酸酶的抑制率及1,1-二苯基-2-三硝基苯肼(DPPH)自由基的清除率为评价指标确定中药提取液的最佳质量浓度。采用机械法制备复方川芎美白淡斑乳膏;采用目测法观察外观;采用生物显微镜观察粒度;采用pH计测定pH;采用高效液相色谱法测定阿魏酸的含量,色谱柱为Elite-ODS柱(200 mm×4.6 mm,5µm),流动相为甲醇-1%冰醋酸(30∶70,V/V),流速为1.0 mL/min,柱温为30℃,检测波长为321 nm,进样量为10µL;对制备样品的微生物限度及初步稳定性进行考察。结果中药提取液的质量浓度在1~50 mg/mL和1~10 mg/mL范围内分别与酪氨酸酶的抑制率及DPPH自由基的清除率呈显著正相关(P<0.01)。制备的复方川芎美白淡斑乳膏质地均匀、细腻、有光泽、硬度适中,易于挑起、涂抹;粒径小于2µm,且分布均匀;pH为6.8。阿魏酸的质量浓度在1.53~30.69µg/mL范围内与峰面积线性关系良好(r=0.9994,n=5);精密度、稳定性、重复性试验结果的RSD均小于2.0%;阿魏酸低、中、高质量浓度(88,132,176µg/mL)平均回收率分别为(99.51±0.97)%,(100.08±0.51)%,(100.97±0.73)%,RSD分别为0.97%,0.51%,0.73%(n=3);3批样品中阿魏酸的含量分别为179.63,185.38,179.30µg/g。微生物限度检测结果显示,样品中需氧菌总数为20 cfu/g,未检出霉菌和酵母菌。耐寒试验及耐热试验后,复方川芎美白淡斑乳膏的外观仍均匀、细腻,无油水分层现象,涂抹在皮肤上无粗颗粒;离心试验后,外观、性状无明显改变,且无油水分层现象。结论所建立的制备工艺操作简便,制备样品的质量稳定,可用于复方川芎美白淡斑乳膏的制备和质量控制。

川芎苓种内生燕麦镰刀菌拮抗川芎根腐病的研究

根腐病是川芎栽培的首要病害,严重影响川芎药材生产。生物防治技术是防控药用植物病害的重要手段。本研究以川芎苓种自身携带的内生潜在生防菌燕麦镰刀菌Fusarium avenaceum对抗川芎根腐病主要致病菌茄腐镰刀菌Fusarium solani,并回接至川芎无菌组培苗进行菌植互作实验和防效验证。结果显示,F.avenaceum对F.solani菌丝生长平均抑制率达48.22%;二者均能在川芎植株体内成功定植;单独接种F.solani浸染率为46.93%,病情指数为66.70%,接种F.avenaceum可显著降低病情指数;组培苗先感染F.avenaceum比先感染F.solani发病率低,当两菌复合回接且F.avenaceum优先接种时促进川芎根茎显著增大。由此说明,川芎苓种内生菌F.avenaceum可以作为F.solani所致川芎根腐病的生防菌,且“防病”效应优于“治疗”效应。

川芎挥发油对雷公藤甲素体外透皮性能及细胞毒性的影响

目的探究川芎挥发油对雷公藤甲素体外透皮性能和细胞毒性的影响。方法采用气相色谱-质谱联用法对川芎挥发油的化学成分进行分析。分离KM小鼠下腹皮肤,分为雷公藤甲素、雷公藤甲素配伍川芎挥发油1∶10、1∶50、1∶100组(以下简称“配伍1∶10“”配伍1∶50”“配伍1∶100”组),将各组小鼠皮肤与相应乳膏各0.2 g充分接触24 h后,采用高效液相色谱法测定各组接收液中雷公藤甲素的累计透皮量(Q_(n)),并计算透皮吸收速率(J_(ss));再以人永生化角质形成细胞(HaCat)为模型,采用CCK-8法检测不同浓度川芎挥发油和雷公藤甲素配伍前后的细胞存活率。结果共鉴定出62个川芎挥发油化学成分,包括Z-藁本内酯、洋川芎内酯、β-瑟林烯等。与雷公藤甲素组比较,配伍1∶10组和配伍1∶50组24 h内雷公藤甲素的Q_(n)(P<0.01)和J_(ss)有所升高,而配伍1∶100组的Q_(n)(P<0.05)和J_(ss)有所下降。与雷公藤甲素组比较,雷公藤甲素浓度在36、72、144 ng/mL时,配伍1∶10组和配伍1∶50组可以显著提高HaCat细胞的存活率(P<0.05或P<0.01),而配伍1∶100组细胞的存活率反而降低,但差异无统计学意义(P>0.05)。结论雷公藤甲素与川芎挥发油在配伍比例为1∶10和1∶50时可以促进雷公藤甲素的透皮吸收,且可降低雷公藤甲素对HaCat细胞的毒性。

历史地理学视域下川芎“苓子”栽培法本草考证

四川道地产区“山区育苓,坝上栽种”的川芎“苓子”栽培法历史悠久,已成为其道地品质的形成要素之一。而现实生产中,药农自发随意、标准不一。拟通过系统分析为优化栽培方法提供参考。从历史地理学角度出发,梳理历代本草文献中川芎栽培方法的源流,分析特定的地理环境和历史背景对其演变的影响,并结合田野调查,总结规律。①自宋代起,青城山-都江堰的历史地理环境与人类活动促进了苓子栽培的成型与衍化,而现代山区自然环境的变迁、地理资源的限制又催生了“坝苓子”栽培法;②成都平原的“粮药争地”矛盾影响了苓子种植与川芎采收时期,为平衡川芎与水稻轮作,逐渐衍变为立秋与处暑之间种植苓子,次年小满与芒种之间采集川芎;③通过实地调查发现,新改良的冷库坝苓子栽培法继承了古法的优点,符合规律,同时守正创新,便捷高效,已有大量实践经验。四川产区特定的历史地理环境与人类活动促进了苓子栽培的成型与衍化,同时新时期地理环境的变迁与限制依然在推动苓子栽培的继续改进。冷库坝苓子栽培法值得深入研究,以平衡药材品质与种植成本,扩大产区,增加药源。