Exploring the mechanism of action of herb pair Pinellia Ternata-Magnolia Officinalis in the treatment of liver cancer based on network pharmacology and molecular docking

Background:Explore the anti-tumor mechanism of herb pair Pinellia ternate-Magnolia officinalis(BX-HP)in liver cancer through network pharmacology using molecular docking methods.Method:The active ingredients and corresponding targets of the herb pair Pinellia ternate-Magnolia officinalis were obtained from the HERB database.The relevant targets for liver cancer were obtained from GeneCards,DisGeNET,TTD,and Drugbank databases.Obtain common targets between herb pair Pinellia ternate-Magnolia officinalis and liver cancer through the Bioinformatics platform,establish a PPI network diagram using STRING software,and perform GO functional enrichment and KEGG pathway enrichment analysis on the DAVID platform.AutoDockTools 1.5.7 software and molecular dynamics simulation analysis are used to evaluate the binding of components to target proteins.HERB database,SwissTargetPrediction database,SwissADME database,UniProt database,GeneCards database,TTD database,DRUGBANK database,DisGeNET database,String,DAVID.Bioinformatics platform,PDB database,PubChem and TCMSP database.Result:A total of 22 active ingredients with a Probability>0.1 targets in Magnolia officinalis were screened,26 active ingredients with a Probability>0.1 targets in Pinellia ternata,ten vital active ingredients,corresponding to 979 and 803 targets with a Probability>0.1 targets,2536 liver cancer-related targets,and 279 targets in the herb pair Pinellia ternata-Magnolia officinalis.The GO functional enrichment analysis resulted in 1297 entries,namely 971 biological process entries,118 cell localization entries,and 208 molecular function entries.Three signaling pathways were annotated through the KEGG pathway.Based on molecular docking,ten vital active ingredients and five target proteins were validated to exhibit an excellent binding affinity.The above data indicates that combining the herb pair Pinellia ternata-Magnolia officinalis may treat liver cancer through specific targets and signaling pathways.Conclusion:Herb pair Pinellia ternata-Magnolia officinalis has a synergistic effect on treating liver cancer through multicomponent,multitarget,and multi-pathway approaches.This study provides a sufficient theoretical basis for subsequent research.

Quality evaluation of Pinelliae Rhizoma using network pharmacology and multi-component quantitative analysis

Background:Pinelliae Rhizoma(Banxia)is a valuable traditional Chinese medicine,and its quality issues are related to the safety and effectiveness of the medicine.Several pharmacological experiments have shown that Pinelliae Rhizoma has anti-inflammatory activity,but the specific chemical components remain unclear.Methods:In the present study,network pharmacology was used to analyze the potential active ingredients and molecular mechanisms of Pinelliae Rhizoma’s anti-inflammatory activity.A new approach to simultaneously determine eight components using high performance liquid chromatography-photo-diode array was developed to evaluate the quality of Pinelliae Rhizoma and different processed Pinelliae Rhizoma products.Results:Twelve active ingredients were identified from Pinelliae Rhizoma,andβ-sitosterol may have a greater effect than the other active ingredients.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the main pathways associated with Pinelliae Rhizoma’s mechanism for treating inflammation.Additionally,theβ-sitosterol content in different processed Pinelliae Rhizoma products decreased significantly,and the level of five nucleosides in Pinelliae Rhizoma was significantly higher than that of the processed Pinelliae Rhizoma products.The 6-gingerol content was detected in eight Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine batches with different origins,and liquiritin and liquiritigenin levels were detected in eight batches of Pinelliae Rhizoma Praeparatum with different origins.Conclusion:Pinelliae Rhizoma quality was affected by different regions and different processing methods,and this research provides a reference for Pinelliae Rhizoma quality evaluation.

Mechanism of Pinelliae Rhizoma in Treatment of Insomnia Based on Network Pharmacology

[Objectives]To explore the mechanism of Pinelliae Rhizoma in the treatment of insomnia.[Methods]Using the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database,the effective components of Pinelliae Rhizoma were explored,to predict its targets,and screen out the targets of insomnia through GeneCards,OMIM and other databases.With the aid of Cytoscape software,a"component-target-pathway-disease"network for the treatment of insomnia by Pinelliae Rhizoma was built.Then,a target protein-related interaction network was created through the String database,and biological function annotation and pathway analysis of key targets were performed.[Results]The 13 active components of Pinelliae Rhizoma take action in the treatment of insomnia by intervening 33 targets,59 GO biological processes,and 10 main biological pathways.[Conclusions]The active components of Pinelliae Rhizoma may treat insomnia by such pharmacological effect as regulating G protein-coupled amine receptor activity,adrenergic receptor activity,catecholamine binding,and neurotransmitter receptor activity.

Mechanism of "Pinelliae rhizoma-Arisaematis rhizoma" in treatment of lung cancer based on network pharmacology

Objective:The study was designed to explore the mechanism of“Pinelliae RhizomaArisaematis Rhizoma”(PR-AP)in treatment of lung cancer based on network pharmacology.Methods:The active components and their targets of“Pinelliae Rhizoma-Arisaematis Rhizoma”were screened out from TCMSP database.The cytoscape3.7.0 software was used to construct the drug-active component-targets network.Searched the DisGeNet database to obtain lung cancer related targets.Bisogenet was used to construct"PPI network of active component target"and"PPI network of lung cancer target",and the intersection of the two networks was taken and the target was screened.AutoDockTools software was used to dock the key active ingredients with the key targets.David database was used to perform Go biological process enrichment analysis and KEGG pathway enrichment analysis.Results:A total of 15 active components were collected,including beta-sitosterol,baicalein,Stigmasterol,Cavidine,coniferin,etc.These active components mainly act on 95 key targets such as ESR1 and CDK2,which enriched in multiple lung cancer related signaling pathways,such as PI3KAkt、MAPK、HIF-1、FoxO、TGF-β、Hippo、TNF、Notch、VEGF、cAMP,etc.The results of molecular docking showed that the active components could regulate the core targets(ESR1 and CDK2).Conclusion:The effect of“Pinelliae Rhizoma-Arisaematis Rhizoma”in the treatment of lung cancer embodies the characteristics of multi-component,multi-target and multi-pathway of traditional Chinese medicine.Its mechanism of action may be to play a role in the treatment of lung cancer by regulating cell cycle,angiogenesis,tumor stem cells,etc.This research can provide ideas and references for further research.

金水六君煎物质基准中半夏和陈皮的薄层鉴别研究

目的:建立经典名方金水六君煎物质基准中半夏和陈皮的薄层鉴别方法。方法:以半夏对照药材为对照,对金水六君煎中半夏进行薄层鉴别研究,以橙皮苷和陈皮对照药材为对照,对金水六君煎中陈皮进行薄层鉴别研究,并对其进行方法学验证。结果:建立的薄层色谱法能鉴别出半夏和陈皮,斑点对应较好,阴性无干扰,方法学考察结果显示,方法适应性良好。结论:本法简单可行、结果可靠、重复性好,可作为金水六君煎物质基准的质量控制方法。

姜制半夏传统制作工艺考证

姜半夏传统制作工艺:完整半夏姜制法多在前期生半夏汤洗的基础上进行,亦有直接用姜汤洗的记载。半夏片为汤洗后切片,再用姜汁浸、炒、煮、蒸等,以炒法为优。半夏粉为半夏汤洗切片研细粉,再用姜汤浸澄,多用于制作糊丸或包衣。半夏饼为汤洗后半夏研粉与生姜汁或去皮生姜混合制成的饼状物,再经炙、煨、炒等法而成。半夏曲始于宋代,当时半夏曲有制饼与发酵两种,均以生姜为辅料。制饼者并没有发酵的过程,实为半夏饼。半夏曲的配方众多,生姜必不可少。地方炮制经验中将生半夏水浸泡,生姜煮取汁,再共同煮制为主流。地方炮制规范中多为生半夏水浸透,姜汤矾水共煮。现代学者的研究方向主要集中在炮制工艺优选与炮制原理两方面。建议恢复姜半夏的传统汤洗姜制工艺。

从“湿”论半夏治疫的古今探析

湿疫是感受湿性疫疠邪气的一类急性传染病,湿性黏滞,缠绵难愈,且最易侵犯太阴,故其病位主要在肺、脾。半夏味辛性温,入肺、脾、胃经,具有燥湿化痰,降逆止呕,消痞散结的功效,在防治湿疫中发挥着重要的作用。本文从湿立论,通过分析古今文献中半夏在疫病防治中发挥的作用,为医者诊治疾病提供参考依据。

半夏曲传统制作工艺沿革探讨

该文对半夏曲传统制作工艺的沿革进行了探讨。宋代半夏曲的制作方法包括半夏姜汁制饼与制饼后发酵两种,以半夏姜汁制饼为主流。金元时沿袭宋代工艺,半夏曲的应用具有一定的局限性。明代医家对半夏曲的炮制机理进行了阐发,认为“片则刀峻,曲则力柔。”明代李时珍对半夏饼与半夏曲的混淆问题进行了澄清,韩懋的《韩氏医通》收载了5首半夏曲方,对半夏曲配方的扩充具有划时代的意义。清代医家在继承《韩氏医通》半夏曲方的基础上,总结为韩飞霞制曲十法;当时的半夏曲与神曲的制作工艺相互影响。建国后,半夏曲的地方炮制经验深受清代影响,地方炮制规范逐渐趋同。该文同时对半夏曲炮制工艺中的“半夏”与“曲”孰重孰轻、半夏的前期处理、半夏饼与半夏曲的概念区分、面粉用量与添加时机、神曲粉的加入、白矾在半夏曲中的作用等问题进行了思考。

基于主成分分析法优选半夏散剂粒度范围

目的:探究天南星科植物半夏生品及炮制品的中药散剂粒度对药材质量的影响,并优选出最佳粒度工艺。方法:首先对不同粒度的半夏生品及炮制品散剂中多个活性成分(尿嘧啶、次黄嘌呤、黄嘌呤、尿苷、鸟苷)含量进行检测,再利用主成分分析法对检测数据进行处理,计算不同散剂的综合评价指标值,并构建回归模型,通过模型函数优选出不同散剂的最佳粒度。结果:通过分析最终得到的最优散剂粒度为:生半夏散过6号药典筛、市售炮制品过7号药典筛、自制炮制品过9号药典筛。结论:本实验方法可靠,以粒度作为因素,结合成分含量数据基于主成分分析法可作为中药散剂的质量评价标准。

息半夏总生物碱的提取工艺优化及其生物活性分析

以息半夏的块茎为原料,乙醇为超声波辅助提取溶剂,考察乙醇体积分数、超声时间、料液比、超声温度等单因素对总生物碱提取率的影响,设计正交试验优化提取工艺,并测试总生物碱的体外抗氧化和降血糖活性。结果表明,最佳提取条件为乙醇体积分数65%、提取时间60 min、料液比1∶45、超声温度65℃,总生物碱的提取率达0.502%;总生物碱对DPPH、ABTS自由基的清除率分别达89.90%和43.60%,对α-葡萄糖苷酶的抑制率达86.40%。该工艺简单可行,总生物碱表现出良好的体外抗氧化和降血糖生物活性。

橘皮半夏汤联合通窍活血汤加减治疗脑小血管病的疗效观察

目的:明确橘皮半夏汤联合通窍活血汤加减治疗脑小血管病(CSVD)的临床疗效,初步探讨其作用机制。方法:将100例脑小血管病患者按照随机数字表法分为对照组(50例)和实验组(50例);对照组给予常规治疗,实验组在常规治疗基础上加服橘皮半夏汤联合通窍活血汤治疗,共治疗3个月;以日常生活能力量表(ADL)评分、C反应蛋白(CRP)、D-二聚体、纤维蛋白原(FIB)水平为评价指标,对两组患者的治疗效果进行比较。结果:治疗后两组患者ADL评分均显著高于治疗前,且实验组高于同期对照组(P<0.05);两组患者血清CRP、D-二聚体、FIB显著低于治疗前,实验组低于对照组(P<0.05)。结论:橘皮半夏汤联合通窍活血汤加减治疗CSVD疗效显著,能显著改善患者日常生活能力,减轻CSVD患者炎性反应、减少微栓子形成,且安全性较高。

中蒙药对幽门螺杆菌的体外抑菌作用研究

目的筛选对幽门螺杆菌(H.pylori)具有抑菌作用的中蒙单药,构建新型抑菌方剂,探索中蒙药对H.pylori的治疗价值。方法取H.pylori标准菌株,常规体外培养;临床分离并培养H.pylori现症感染患者的H.pylori菌株,采用生化反应、H.pylori特异性基因检测进行鉴定。选取黄连、黄芩、大黄、丁香、鱼腥草、黄芪、茯苓、三七、生姜、苦参、诃子、蒲公英分别对H.pylori标准和临床菌株进行药敏试验,采用十字测量法测量抑菌圈直径,直径15~20 mm为高敏、直径10~14 mm为中敏。根据上述药敏试验,选取敏感药物构建新型组方,然后采用药敏试验、浓度梯度试验、尿素酶浓度测定试验评估新型组方的抑菌作用。选取阿莫西林、克拉霉素、甲硝唑、左氧氟沙星、利福平、四环素、庆大霉素、呋喃唑酮对H.pylori临床菌株进行药敏试验,分析耐药情况及耐药患者H.pylori菌株对新型组方的敏感性。结果H.pylori标准菌株对蒲公英、诃子高敏,对丁香、大黄中敏;H.pylori临床菌株对蒲公英高敏,对鱼腥草、三七、苦参、黄芩、黄连、黄芪、诃子、丁香、大黄、生姜中敏。其中蒲公英、诃子、丁香、大黄对H.pylori标准和临床菌株均具有较好抑菌作用,且蒲公英作用最强。构建的新型组方命名为半夏益胃颗粒,包括清半夏15 g、黄连6 g、黄芩10 g、干姜10 g、党参10 g、炙甘草6 g、大枣15 g、诃子10 g、丁香6 g、三七粉6 g、蒲公英30 g、百合30 g、乌药10 g、鱼腥草10 g、海螵蛸15 g。有6例H.pylori临床菌株对半夏益胃颗粒高敏,3例H.pylori临床菌株及标准菌株对半夏益胃颗粒中敏。半夏益胃颗粒最小抑菌浓度为0.5 g/mL,此浓度半夏益胃颗粒应用后,H.pylori标准和临床菌株分泌的尿素酶浓度较应用前明显降低(P均<0.05)。H.pylori临床菌株抗生素耐药情况:甲硝唑7例、左氧氟沙星4例、克拉霉素3例、呋喃唑酮1例、阿莫西林1例;半夏益胃颗粒对甲硝唑、左氧氟沙星耐药H.pylori临床菌株的药敏试验均为高敏。结论蒲公英、诃子、丁香、大黄对H.pylori标准和临床菌株均具有较好抑制作用;新组方半夏益胃颗粒对H.pylori标准和临床菌株抑制作用明显,对有些抗生素耐药的H.pylori临床菌株也有抑制作用,有望成为根除H.pylori的辅助药物。

半夏及其炮制品对SD大鼠的毒性作用

为研究半夏及其炮制品对大鼠心、肝、肾的毒性作用,将SD大鼠随机分为正常组、生半夏组(3 g/(kg·d))、法半夏组(3 g/(kg·d))、清半夏组(3 g/(kg·d))和姜半夏组(3 g/(kg·d)),连续灌胃21 d后,检测各组血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、尿素氨(BUN)、肌酐(Cr)、肌酸激酶(CK)和乳氨酸脱氢酶(LDH)的变化。用HE染色观察心肌组织病理变化,蛋白免疫印迹(Western blot)法测定心肌组织中TGF-β1/Smads/mTOR信号通路相关蛋白的表达。结果发现生半夏经炮制加工后的法半夏、姜半夏和清半夏炮制品的毒性较生半夏的毒性减弱,即对心、肝、肾均无毒性影响。可见合理炮制对半夏的心毒性的减毒作用有显著的改善,有助于临床半夏合理用药。

半夏提取物对淡色库蚊幼虫的杀虫活性

通过不同萃取相(石油醚、氯仿、乙酸乙酯、正丁醇和水)提取半夏(Pinellia ternata)的活性物质,采用浸液法测定半夏提取物对淡色库蚊(Culex pipiens pallens)幼虫的杀虫活性。结果表明,半夏甲醇提取物对淡色库蚊幼虫具有显著的毒杀活性;在0.5 mg·mL^(-1)浓度处理下,石油醚、氯仿萃取相对淡色库蚊幼虫具有显著的杀虫活性,致死率在50%以上。对石油醚、氯仿萃取相进行室内毒力测定,LC50分别为0.21和0.31 mg·mL^(-1)。研究结果可为新型植物源农药综合利用提供参考。

Synergistic effect of pinellia total alkaloids and uncaria total alkaloids on anticonvulsant action in mice and rats

Aim To investigate the synergistic effect of the combination of pinellia total alkaloid （PTA） and uncaria total alkaloid （UTA）, and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1：4, 1 ：1, 4：1, were evaluated in maximal electroshock （MES）-induced seizures and acute toxicity test in mice. Respective ED50 and LD50 were calculated with Bliss＇s method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices （BI） for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high performance liquid chromatography （HPLC）. Results Combinations of PTA and UTA at the ratio of 4：1 were synergistic in MES test and antagonistic in acute toxicity test, showing the best profile for combinations of PTA with UTA. In contrast, the ratios of 1 ：4 and 1 ： 1, despite synergistic in MES test, were additive in acute toxicity test. The 4：1 combination and two drugs alone significantly decreased Glu level and increased GABA level in the hippocampus, but the GABA level in the 4：1 combination group was higher than that in the two drugs alone groups. They did not have significant influence on the levels of ASp and Gly. Conclusion Combinations of PTA and UTA at 4：1 ratio demonstrated synergistic effect in anticonvulsant action and antagonistic effect in toxicity. The anticonvulsant mechanism might be related to decreasing the excitability of Glutamatergic neurons and increasing the inhibition of GABAergic neurons.

半夏白术天麻汤加减联合康复训练治疗风痰瘀阻型急性脑梗死合并H型高血压临床研究

目的:观察半夏白术天麻汤加减联合康复训练对风痰瘀阻型急性脑梗死合并H型高血压患者神经功能及生活质量的影响。方法:将182例风痰瘀血型急性脑梗死合并H型高血压患者按照随机数字表法分为对照组和观察组,每组各91例。两组均接受西医基础治疗,对照组给予康复训练治疗,观察组在对照组治疗的基础上联合半夏白术天麻汤加减。比较两组患者的临床疗效及治疗前后中医证候积分、美国国立卫生研究院卒中量表(national institutes of health stroke scale,NIHSS)评分、世界卫生组织生活质量评定简表(world health organization quality of life-bref,WHOQOL-BREF)评分、收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、同型半胱氨酸(homocysteine,Hcy)水平变化情况。结果:观察组有效率为94.51%,明显高于对照组的75.82%,差异具有统计学意义(P<0.05)。两组患者治疗后中医证候积分、NIHSS评分低于本组治疗前,WHOQOL-BREF评分高于本组治疗前,且治疗后组间比较,差异具有统计学意义(P<0.05)。两组患者治疗后HCY、SBP、DBP水平低于本组治疗前,且观察组治疗后低于对照组(P<0.05)。结论:半夏白术天麻汤加减结合康复训练治疗风痰瘀阻型急性脑梗死合并H型高血压,临床疗效确切,可促进患者神经功能的恢复,提高患者的生活质量。

‘唐半夏’无菌繁殖体系建立

以‘唐半夏’块茎为试材,采用组织培养的方法,研究了不同种类及浓度的植物生长调节剂对不定芽诱导、增殖、生根的影响以及电流刺激对不定芽增殖的影响,以期为‘唐半夏’无性快速繁殖体系的建立提供参考依据。结果表明:最适不定芽诱导培养基为MS+1.5 mg·^(L-1)6-BA+0.1 mg·L^(-1)NAA,平均每个外植体诱导的不定芽数最多(9.38个)且诱导率为93.75%;采用电流刺激不仅提高不定芽的增殖倍数,且对‘唐半夏’植株的生长产生明显的促进作用。特别是20 mA、5 min处理下,不定芽增殖倍数最大(13.31倍),组培苗生长健壮且出现生根的现象。最适生根诱导培养基为1/2 MS+0.2 mg·L^(-1)NAA,生根率为100%,生根数为23.75条。

Optimization of Inducing Conditions for Loose Callus of Pinellia ternata

[Objective] The research aimed to establish the cell suspension culture system of Pinellia ternate.[Method] The petiole of Pinellia ternate was as the explant.The orthogonal test was used to study the influences of four plant growth substances（2,4-D,NAA,picloram and KT）and their mixture ratios on the formation of loose callus.[Result] The induction effect of 2,4-D and picloram on the petiole callus of Pinellia ternate was the most significant.Then,the second ones were KT and NAA.The optimal medium which induced Pinellia ternate petiole to form the loose callus was MS＋0.5 mg/L of 2,4-D＋1.0 mg/L of NAA＋1.0 mg/L of picloram＋1.5 mg/L of KT.[Conclusion] The research laid the foundation for extracting the active ingredient from the cell suspension of Pinellia ternate and producing the artificial seed.

基于电子鼻技术结合网络药理学分析半夏不同炮制品的气味差异标志物

目的借助HeraclesⅡ超快速气相电子鼻获取半夏不同炮制品的气味指纹图谱信息,并结合网络药理学分析半夏不同炮制品之间的气味差异标志物。方法使用HeraclesⅡ超快速气相电子鼻获取半夏不同炮制品的气相色谱图,利用多元分析方法,得到半夏不同炮制品的气味差异标志物,结合网络药理学分析,得到差异成分的靶点和通路,从而预测半夏不同炮制品潜在的气味差异标志物。结果半夏不同炮制品共鉴定出21个与气味相关的化学成分,其中甲基丁香酚、二乙基酮等5个成分是半夏不同炮制品的气味差异标志物,经网络药理学分析,这些成分具有止咳、抗炎等作用。结论所建立的半夏及其炮制品气味指纹图谱专属性强,筛选出5种可作为半夏不同炮制品的潜在气味差异标志物的化学成分,可为中药炮制机制及工艺研究提供新思路和适用方法。

无机元素与计量学模型结合的半夏产地溯源研究

为建立不同产地半夏无机元素的分析方法和溯源体系,为半夏药材的质量控制和道地性评价提供技术支持。采用电感耦合等离子体质谱法(ICP-MS)和电感耦合等离子体原子发射光谱法(ICP-AES)对我国6个主产区72份半夏样品中K、Ca、Na、Mg、Al等37种无机元素的含量进行测定,并采用方差分析、主成分分析、因子分析等计量学方法进行统计与评价。通过对比BP-神经网络算法、K-最近邻算法、最小二乘支持向量机等多种模式识别方法,探索适合半夏产地溯源的最佳模型。结果表明:不同产地半夏中无机元素的构成各具特征,各无机元素含量在产地间差异显著(P<0.05),其中La、Pb、As、Na、Bi、Hg、Sn、Cd、Ag 9种元素在不同产区间的差异最为明显;3D-plots图显示不同产地半夏样品分布相对集中,具备产地分类的可行性;KNN分类模型(曼哈顿距离)是半夏产地溯源的最佳方法,测试集的正确率达到100%。无机元素分析技术结合适当的计量学模型可以实现半夏的产地溯源。