Determination of Benzoylaconitine Compounds in the Decoctions of Aconiti Lateralis Radix Praeparata(Heishun Pieces),Trichosanthis Fructus and Their Combination

[Objectives]This study was conducted to determine the contents of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the decoctions of Heishun pieces,Trichosanthis Fructus and their combination.[Methods]Heishun pieces,Trichosanthis Fructus and their combination were extracted for different time periods,and then grouped.HPLC was performed using an Agilent ZORBAX SB-C 18 chromatographic column(4.6 mm×250 mm,5μm)and acetonitrile-0.02 mol/L sodium dihydrogen phosphate as the mobile phase at a flow rate of 1 mL/min and a column temperature of 30℃,and the sample volume was 20μL.The detection wavelength was 230 nm.[Results]The total amounts of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the single decoction group of Heishun pieces were all significantly different from those in the combined decoction group at corresponding time.[Conclusions]The total content of the benzoylaconitine type increased significantly after the combined decoction of Heishun pieces and Fructus Trichosanthis,which proves the scientificity of"eighteen incompatible medicaments,19 counteraction"in traditional Chinese medicine to some extent.

Advances in Research of Anti-tumor Effect of Aconiti Radix

In this paper,the anti-tumor effects of Aconiti Radix were reviewed and summarized,and the clinical feasibility of Aconiti Radix as a potential anti-tumor drug was analyzed,in order to provide a useful reference for the future research and development of new anti-cancer drugs of Aconiti Radix.

Study on Processing Technology for Aconiti Kusnezoffii Radix by Bean Curd

[Objectives] The aim was to explore the best parameters for processing Aconiti Kusnezoffii Radix by bean curd. [Methods] Orthogonal test( L_(16)(4~3)) was designed to investigate the optimal soaking time,decocting time and bean curd proportion for processing Aconiti Kusnezoffii Radix by bean curd. The contents of monoester alkaloids and diester-alkaloids were measured as the evaluation indexes. [Results]The contents of monoester alkaloids were 0. 11%,0. 07%,0. 062% and 0. 048% respectively under the four levels of soaking time,were0. 081%,0. 066%,0. 074% and 0. 067% respectively under the four levels of decocting time,and were 0. 070%,0. 072%,0. 080% and0. 073% respectively under the four levels of bean curd proportion. The content of diester-alkaloids was all below 0. 034%. The influence intensity of the three factors on the content of monoester alkaloids ranked as soaking time > decocting time > bean curd proportion. Under any of the above conditions,the content of diester-alkaloids was below the limit of Chinese Pharmacopoeia. The content of diester-alkaloids was reduced obviously with the increased use of bean curd. [Conclusions] The optimum processing conditions for Aconiti Kusnezoffii Radix were A_3B_3C_2,i. e.,soaking time of 6 d,decocting time of 5 h and bean curd proportion of 25%.

Research progress on synergetic effects of Fuzi(Radix Aconiti Lateralis Preparata)and Tubeimu(Rhizoma Bolbostemmatis)/Gualou(Trichosanthes kirilowii Maxim)

The compatibility of Chinese herbs is the focus and the difficulty in traditional Chinese medicine research,and it has an important guiding role for clinical medicine.Some scholars believe that the Fuzi(Radix Aconiti Lateralis Preparata,FZ)compatibility with Tubeimu(Rhizoma Bolbostemmatis,TBM)/Gualou(Trichosanthes kirilowii Maxim,GL)does not meet the Chinese medicine theory of“eighteen incompatibilities”.However,this combination has been used many times in many clinical medications.This study reviewed the research progress of pharmacological effects of FZ,and FZ compatibility with TBM/GL,in order to correctly understand and apply the“eighteen incompatibilities”drugs,and provide a reference for further exploration of the combined application in clinical treatment.

Optimization of the Ethanol Extraction Method of Monoester Alkaloids from Radix Aconiti Preparata Based on HPLC-MS and Orthogonal Test

[Objectives] This study was conducted to optimize the ethanol extraction technology of monoester alkaloids from Radix Aconiti Preparata. [Methods]On the basis of defined extraction times,ethanol concentration,ethanol times and extraction time were investigated by HPLC-MS combined with orthogonal test to optimize extraction process using the content of monoester alkaloids( the sum of benzoyl neoaconitine,benzoyl hypoaconitine and benzoyl aconitine) as an index.[Results]The optimum ethanol extraction technology was as follows: 75% ethanol,ethanol amount 25 times of the medicinal material,and each extraction for 1. 5 h.[Conclusions] The optimal extraction technology is simple,feasible,stable and reliable. It can provide reference for the industrial production and quality control of monoester alkaloids from Radix Aconiti Preparata.

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.

Energy pharmacology of aconite(Radix aconiti lateralis reparata)

Objective:To study the energy pharmacology of aconite(Radix aconiti lateralis reparata).Methods:Literature induction method was applied to study the energy properties,energy pharmacological connotation,and energy pharmacological effects of aconite(Radix aconiti lateralis reparata).Results:The warm and hot properties of aconite(Radix aconiti lateralis reparata)are exactly its energy properties.The energy pharmacology of aconite(Radix aconiti lateralis reparata)is based on its energy properties,which is different from the modern aconite(Radix aconiti lateralis reparata)pharmacology that is based on the chemical composition of aconite(Radix aconiti lateralis reparata).In addition,the energy pharmacology of aconite(Radix aconiti lateralis reparata)includes not only the traditional energy pharmacology but also the modern energy pharmacology of aconite(Radix aconiti lateralis reparata).The traditional energy pharmacology of aconite(Radix aconiti lateralis reparata)is mainly manifested as the energy effect of aconite(Radix aconiti lateralis reparata)at the whole-body level,warm yang and dissipate cold,whereas the modern energy pharmacology of aconite(Radix aconiti lateralis reparata)is manifested as the physiological and pathological energy effect of warm and thermal energy properties of aconite(Radix aconiti lateralis reparata)at the tissue,cellular,and molecular levels of the body,mainly strengthening the heart,protecting cardiac muscles,dilating blood vessels,and having anti-arrhythmia,anti-shock,anti-inflammatory,analgesic,and antineoplastic effects.The traditional energy pharmacology and modern energy pharmacology of aconite(Radix aconiti lateralis reparata)constitute the basic connotation of aconite(Radix aconiti lateralis reparata)energy pharmacology.For the aconite(Radix aconiti lateralis reparata)energy pharmacology,there is a substantial foundation,its chemical components such as alkaloids.In addition,the toxicity of aconite(Radix aconiti lateralis reparata)is a manifestation of its energy pharmacology.Conclusion:aconite(Radix aconiti lateralis reparata)has energy properties that have substantial foundation.The energy pharmacology of aconite(Radix aconiti lateralis reparata)is based on its high energy and hot properties and includes the traditional energy pharmacology and modern energy pharmacology of aconite(Radix aconiti lateralis reparata).

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。

扶阳学派运用附子之经验

基于“阳主阴从”观,扶阳学派集百年之经验,将大剂量附子灵活应用于各类急危重症和疑难杂症,取得了显著的临床疗效。文章通过阐述四川江油道地药材附子的辨证运用要点、配伍方法、剂量把握等方面的内容,并结合临床医案,对扶阳学派运用附子的用药经验进行了回顾性总结,旨在为其临床推广和应用提供可借鉴的依据。

关白附炮制前后对缺血性中风沙鼠药效学和代谢组学的影响

目的研究关白附生品及其炮制品对沙鼠缺血性脑中风的保护作用及对尿液代谢物的影响。方法将36只沙鼠随机分成空白组(CG)、模型组(MG)、阳性药组(PG)、生关白附组(RA)、蒸关白附组(SA)和姜矾制关白附组(GA),每组6只,除空白组沙鼠外,其余各组采用右侧单侧结扎沙鼠颈动脉造成中风模型。造模成功后,关白附给药组分别灌胃对应的饮片全粉混悬液(0.586 mg/g),阳性药组灌胃脑络通颗粒混悬液(0.390 mg/g),空白组灌胃生理盐水,共给药14 d。分别采用Longa评分法、氯化三苯基四氮唑(TTC)染色法、酶联免疫法检测关白附生品及其炮制品对神经功能学评分、脑组织梗死面积、氧化应激水平、炎症因子表达;采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱法(UHPLC-Q-Orbitrap-MS)分析空白组、模型组、阳性药组、生关白附组、蒸关白附组和姜矾制关白附组沙鼠尿液样品;采用多元统计方法对数据进行处理,筛选差异代谢物;采用京都基因与基因组百科全书(KEGG)数据库结合MetaboAnalyst 5.0软件对筛选出的差异代谢物进行代谢通路分析。结果关白附及其炮制品可显著改善脑组织梗死面积;明显降低脑组织和血清中丙二醛(MDA),白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)活性(P<0.05),明显升高超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、一氧化氮(NO)活性(P<0.05);代谢组学研究发现L-脯氨酸(L-Proline)、核黄素(Riboflavin)、白三烯D4(Leukotriene D4)、7-甲基黄嘌呤(7-Methylxanthine)等112种差异代谢物可作为缺血性脑中风潜在生物标志物,涉及核黄素代谢、嘧啶代谢、嘌呤代谢等14条代谢通路。生关白附回调了其中的核黄素代谢、嘧啶代谢等4条代谢通路;蒸关白附回调了其中的核黄素代谢、嘧啶代谢、精氨酸和脯氨酸代谢等5条代谢通路;姜矾制关白附回调了其中的咖啡因代谢和乙醛和二羧酸代谢2条代谢通路。结论通过比较药效学实验结果发现蒸制关白附效果较好,并明确了生品和炮制品对缺血性脑中风潜在生物标志物调节作用的异同。

草乌炮制研究概况

乌头类中药草乌是我国广泛使用的毒性药材,性热有大毒,归心、肝、脾、肾经,具有祛风散寒、温经止痛等功效。草乌毒性主要表现为可引发心律失常的心肌毒性,伴有心脏血管系统异常等问题,中毒严重时可导致死亡。因其毒性剧烈,乌头类药材生品不入药使用,需经炮制后入药。草乌炮制方法并无统一标准,差异表现在药材前期处理、蒸煮工艺、辅料选择等方面。本文对草乌毒性研究进展及炮制方法沿革进行归纳,为今后草乌的炮制方法等研究提供参考。

草乌致大鼠肝肾亚急性毒性的代谢组学研究

目的基于代谢组学技术分析和探讨草乌致大鼠肝肾亚急性毒性的生物标志物和可能的作用机制。方法以草乌为示例药物,以大鼠为研究对象,除正常组外,给药组灌胃相应溶液,连续给予28 d。通过代谢组学技术对采集的大鼠血清、肝、肾样本进行检测,用主成分分析结合偏最小二乘判别分析筛选肝肾亚急性毒性敏感标志物及代谢通路。结果代谢组学分析显示,与正常组比较,草乌组血清、肝、肾样本中分别鉴定得到34、23和30个差异代谢物,主要富集于ABC转运蛋白、精氨酸和脯氨酸代谢、癌症的中心碳代谢、烟酸和烟酰胺代谢等通路。结论初步认为草乌通过影响ABC转运蛋白、精氨酸和脯氨酸代谢、癌症的中心碳代谢等对肝肾造成损伤,亚精胺、羟脯氨酸、葡萄糖、L-亮氨酸和尿素可作为潜在的肝肾毒性敏感生物标志物。

王世强运用小青龙汤加附子或石膏经验介绍

介绍王世强教授化裁运用小青龙汤加附子或石膏的临床经验。王世强教授认为小青龙汤证之根结在于“水气”,即水液代谢失常。治疗小青龙汤证,就是“治水”,即“青龙治水”,让“水气”从体内排出。方法无外乎使寒化之水气温热蒸腾,因汗而出,即小青龙汤加附子;热化之水气遇寒,凝结成有形之水从小便排出,即小青龙汤加石膏;三焦阳气不足,气化无力,体内水气又出现热化之象,需在用附子温肾阳助小青龙汤温通三焦之时,再使热化之水气遇寒凝结成有形之水从小便而出,即小青龙汤加附子、石膏。

附子水提物及附子多糖通过抑制TGF-β1/Smads信号通路发挥抗肾脏纤维化作用机制研究

目的:基于TGF-β1/Smads通路探讨附子水提物及附子多糖对肾脏纤维化的影响及可能作用机制。方法:体外培养肾小球内皮细胞(HRGECs),采用TGF-β1刺激诱导HRGECs纤维化样模型。造模成功后将细胞分为正常组、TGF-β1模型组(30 ng/mL)、附子水提物组(10 mg/mL)、附子多糖组(5 mg/mL)。光学显微镜、扫描电镜观察细胞形态的变化;细胞划痕实验、Transwell实验观察细胞迁移和侵袭能力;RT-qPCR法检测α-SMA、FSP-1、ZO-1、CD31 mRNA表达水平;Western-blot法检测α-SMA、FSP-1、ZO-1、CD31、p-Smad3、Smad7蛋白表达水平。结果:与正常组比较,TGF-β1刺激72 h后HRGECs形态出现纤维化样变,迁移和侵袭能力增强(P<0.01),α-SMA、FSP-1蛋白及mRNA表达升高,ZO-1、CD31蛋白及mRNA表达下调(P<0.05,P<0.01)。与TGF-β1模型组比较,附子水提物组、附子多糖组细胞形态改善,迁移和侵袭能力降低(P<0.01),α-SMA、FSP-1、p-Smad3蛋白及mRNA表达下降;ZO-1、CD31、Smad7蛋白及mRNA表达升高(P<0.05,P<0.01)。结论:TGF-β1可明显诱导肾小球内皮细胞发生纤维化改变。附子水提物及附子多糖对TGF-β1诱导的HRGECs纤维化改变有明显的改善作用,其机制可能与调节TGF-β1/Smads信号通路有关。

不同程度制草乌生物碱含量对大鼠迷走神经动作电位和心电图的影响

目的比较不同炮制程度的制草乌生物碱含量及对SD大鼠心电图、颈部迷走神经动作电位的影响,建立生草乌及其炮制品的毒性评价方法。方法采用HPLC测定生草乌及泡煮30 min、不泡煮4 h、泡煮4 h、泡煮8 h的制草乌中苯甲酰新乌头原碱、苯甲酰乌头原碱、苯甲酰次乌头原碱、新乌头碱、次乌头碱、乌头碱6个生物碱成分的含量;SD大鼠舌下引流分别给予草乌生品及4种炮制品,记录给药前后大鼠迷走神经动作电位及心电图,对生物碱含量与迷走神经放电面积和心率进行相关性分析。结果4种制草乌双酯型生物碱含量为:泡煮30 min>不泡煮4 h>泡煮4 h>泡煮8 h;单酯型生物碱含量为:不泡煮4 h>泡煮30 min>泡煮4 h>泡煮8 h。与给药前比较,大鼠舌下给予不同炮制品后迷走神经放电幅度增加,心率升高,心律失常程度增加,且随炮制程度而变化;相关性分析显示,迷走神经放电面积与双酯型生物碱和总生物碱含量有明显相关性。结论大鼠舌下引流给药后迷走神经动作电位和心电图可反映草乌麻舌程度,可为草乌“麻舌感”的研究提供参考。

诃子在藏药炮制中的应用

通过查阅近年来国内外文献,归纳、分析了诃子在藏药炮制中的应用以及诃子炮制一些矿物药和有毒植物药过程的研究进展,根据诃子化学成分推测诃子炮制铁粉、草乌的原理及减毒机制,为进一步深入探讨藏药诃子炮制矿物药、有毒植物药的机制提供参考。

附子及其药对治疗慢性心力衰竭研究进展

慢性心力衰竭(CHF)是多种心血管疾病的终末阶段。中医认为CHF多属本虚标实,病机关键是心肾阳虚。心气虚日久累及心阳,心阳虚贯穿整个病理过程;辨证可分为阳虚血瘀证、阳虚水泛证、心肾阳虚证、阳气虚脱证;治则重在益气温阳。附子为温阳要药,药性刚燥,走而不守,上助心阳以通脉,故在使用温阳法治疗CHF时,多取附子,回阳救逆,常配伍人参、黄芪、干姜、桂枝、甘草等增强补阳功效。本文查阅近年相关文献,重点综述附子及其常用药对治疗CHF的临床应用及机制研究进展,并分析现代医家治疗CHF的临证经验,以期为中医临床治疗CHF提供指导和帮助。

UPLC-QTOF/MS结合网络药理学探讨诃子与草乌配伍“异病同治”类风湿性关节炎和痛风性关节炎作用机制

目的:探讨诃子与草乌配伍“异病同治”类风湿性关节炎(RA)和痛风性关节炎(GA)的作用机制。方法:采用数据挖掘技术找出治疗“图赖”病的核心药物组合(诃子-草乌),并使用超高效液相色谱-四极杆飞行时间质谱法(UPLC-QTOF/MS)检测大鼠灌胃诃子与草乌配伍药物后的入血成分;运用PubChem、Swiss Target Prediction、GeneCards、OMIM、DisGeNET、Metascape等多个数据库检索诃子与草乌化学成分对应靶点、RA和GA的疾病靶点,以及代谢通路等信息,利用Cytoscape3.8.2软件构建成分-靶点-通路-疾病网络,并利用分子对接方法证实诃子与草乌的主要成分与关键靶点之间的高亲合力。结果:诃子与草乌入血成分相应靶点与RA靶点交集后得到323个交集靶点、与GA靶点交集后得到24个交集靶点,两者共有靶点24个,主要有肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53)、基质金属蛋白酶-9(MMP-9)、前列腺素内过氧化物合酶2(PTGS2)和信号转导和转录激活因子3(STAT3),与十八碳四烯酸、绢酸、5-(3-羟基-4-乙酰氧基-1-丁基)-2,2'-联噻吩、灵芝酸H等有紧密联系,涉及通路有TNF信号通路、破骨细胞分化通路、癌症通路等。分子对接结果显示灵芝酸H和TNF、5-(3-羟基-4-乙酰氧基-1-丁基)-2,2'-联噻吩和MMP-9有强烈对接活性。结论:蒙古族药诃子与草乌配伍治疗RA和GA具有多靶点效应,可能通过炎症反应的调节、细胞对生物刺激的反应、对细菌源分子的反应、磷酸盐代谢的正调控和对激素的反应等通路发挥“异病同治”作用。

液相色谱-质谱技术结合网络药理学研究附子-葶苈子药对的抗心力衰竭作用机制

采用超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-Q TOF MS^(E))技术,结合UNIFI软件对附子-葶苈子药对水煎液中的化学成分进行分析鉴定。首先,在UPLC-Q TOF MS^(E)正、负离子模式下采集质谱数据,使用UNIFI软件对化合物精确相对分子质量和串联质谱数据进行辅助解析,结合对照品的质谱信息及相关参考文献,从附子-葶苈子共煎液中共鉴定出142个化合物。以这些成分为候选化合物,采用网络药理学方法,构建了“药物-成分-靶点”关键网络,筛选出附子-葶苈子药对治疗心力衰竭的10个关键靶点,分别为BCL2、IL6、STAT3、CASP3、PPARG、ESR1、EGFR、AKT1、MMP9、PTGS2,它们主要参与调控糖尿病并发症中的AGE-RAGE信号通路、表皮生长因子受体信号通路以及缺氧诱导因子信号通路等;活性成分包括水黄皮素、山柰酚、异鼠李素等黄酮类和惰碱、德尔妥因等生物碱类以及穿心莲内酯类化合物。该研究揭示了附子-葶苈子配伍抗心力衰竭的潜在作用机制,为该药对的临床应用提供了科学依据。

基于网络药理学探究山茱萸-附子治疗心力衰竭的分子机制

目的基于网络药理学探究山茱萸-附子治疗心力衰竭的分子机制。方法2021年4月至2022年5月,运用中药系统药理学数据库和分析平台(TCMSP)数据库对山茱萸-附子有效成分进行筛选,利用SwissTargetPrediction数据库进行靶点预测。通过DisGeNet、DrugBank、OMIM疾病数据库收集心力衰竭的治疗靶点,取疾病与药物之间的靶点交集,将靶点交集导入STRING11.5数据库构建山茱萸-附子蛋白质-蛋白质相互作用(proteinprotein interaction,PPI)网络图。利用DAVID数据库对关键靶点进行基于京都基因和基因组数据库(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,使用AutoDuckTool 1.5.6软件对关键靶点进行分子对接。结果筛选出山茱萸-附子有效化学成分33种、靶点208个,心力衰竭疾病靶点2046个,山茱萸-附子治疗心力衰竭的靶点85个。在DAVID数据库中进行基因本体论(GO)分析得出与疾病最相关的前20个条目,KEGG分析显示81条通路。山茱萸-附子治疗心力衰竭的关键靶点有过氧化物酶体增殖物激活受体γ(PPARG)、表皮生长因子受体(EGFR)、雌激素受体1(ESR1)、前列腺素内过氧化物合酶2(PTGS2),KEGG通路主要有环磷酸鸟苷-蛋白激酶G信号通路(cGMP-PKG)、缺氧诱导因子1信号通路(HIF-1)、过氧化物酶体增殖物激活受体信号通路(PPAR)等;分子对接结果显示活性成分β-谷甾醇与关键靶点ESR1、EGFR的对接亲和力较好。结论山茱萸-附子通过多靶点、多成分、多通路的作用机制治疗心力衰竭。