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.

Effects of Radix Aconiti Lateralis Preparata and Rhizoma Zingiberis on Energy Metabolism and Expression of the Genes Related to Metabolism in Rats

Objective： To study the influence of Radix aconiti lateralis preparata and Rhizoma zingiberis, two species of Chinese medicinal herbs with hot property, on energy metabolism and gene expression spectrum, and to analyze the possible mechanism of their effects. Methods： Forty-eight specific pathogen free Wistar rats were randomly divided into a Radix aconiti lateralis preparata group, a Rhizoma zingiberis group, and a control group. They were intragastrically treated with concentrated decoction of Radix aconiti lateralis preparata, Rhizoma zingiberis and normal saline respectively for 20 days. Toe temperature （TT）, energy intake （El）, digestible energy （DE）, and metabolizable energy （ME） were measured. The content of adenosine triphosphate （ATP） and energy charge （EC） in hepatic tissue were measured with high performance liquid chromatography （HPLC）. The activity of ATPase and succinate dehydrogenase （SDH） in the liver were detected with chemical colorimetry. The gene expression in the liver was detected with Illumina＇s rat Ref-12 gene array. The differential expression genes were selected, annotated and classified based on Gene Ontology （GO）. Real-time quantitative reverse-transcriptase PCR （Q-RT-PCR） was used to test the accuracy of results. Results： Compared with the control group, the -I-r on the 10^th day after the beginning of administration and ATP in the Radix aconiti lateralis preparata and Rhizoma zingiberis groups increased significantly （P〈0.05）. El/body mass （BM）, DE/BM, ME/BM, the hepatic EC and the activity of Na^＋-K^＋-ATPase, Ca^2＋-Mg^2＋-ATPase and SDH of liver increased significantly only in the Radix aconiti lateralis preparata group （P〈0.05）. There were 592 differential expression genes in the Radix aconiti/ateralis preparata group and 1 159 in the Rhizoma zingiberis group compared with the control group. Among the differential expression genes, genes related to metabolic processes were the most significant based on GO analysis. There were 337 strips of gene differential expression in common in both Radix aconiti lateralis preparata and Rhizoma zingiberis groups compared with the control group. Conclusions： Herbs with hot property such as Radix aconiti lateralis preparata and Rhizoma zingiberis could improve the energy metabolism in rats, through influencing the metabolic process of sugar, lipid, and amino acid. It could also promote the production, storage, and utilization of energy by regulating the gene expression related to metabolism, which may be the main molecular mechanism of warming yang and dispelling cold for the treatment of the cold syndrome according to Chinese medicine theory.

Study on Hot Property of Aconiti Lateralis Radix Praeparata and Its Compatibility with Zingiberis Rhizoma Based on Animal Temperature Tropism

Objective To establish an objective method for evaluating the intrinsic characteristics between hot and cold properties of herbal drugs and to study the hot property of Aconiti Lateralis Radix Praeparata(ALRP) and its compatibility with Zingiberis Rhizoma(ZR) on animal temperature tropism.Methods The equipment with cold/hot pads was used to investigate the variety of temperature tropism among mice treated by ALRP and its compatibility with ZR.Meanwhile,the activities of adenosine triphosphatase(ATPase),total anti-oxidant capability(T-AOC),and total superoxide dismutase(T-SOD) were measured.Results Compared with the homologous ALRP group,the compatibility between ALRP and ZR(AZ) had a stronger action against the decreasing of remaining rate on hot pad(P < 0.05),suggesting an enhancement of cold tropism.Meanwhile,the internal indexes of Na+-K+-ATPase activity,Ca2+-Mg2+-ATPase activity,and oxygen consuming volume increased significantly(P < 0.05),suggesting an enhancement of energy metabolism.The changes of T-AOC and T-SOD activity suggested that AZ reinforced the anti-oxidative capability of mice.In addition,it could be inferred from cluster analysis that the activity of AZ was concretely stronger than that of homologous ALRP.Conclusion ALRP and ZR are both herbs with hot property,but AZ has an enhanced trend of hot property.This external behavior of cold tropism and the internal activity of energy metabolism and anti-oxidant might reflect the internal hot property in an intuitive and objective way.The changes of ATPase activity of liver tissue might be the mechanism of drug action.

Hot Property of Aconiti Lateralis Radix Praeparata and its Compatibility with Zingiberis Rhizoma Based on Animal Temperature Tropism

Abstract: Objective To establish an objective method for evaluating the intrinsic characteristics between hot and cold properties of herbal drugs and to study the hot property of Aconiti Lateralis Radix Praeparata (ALRP) and its compatibility with Zingiberis Rhizoma (ZR) on animal temperature tropism. Methods The equipment with cold/hot pads was used to investigate the variety of temperature tropism among mice treated by ALRP and its compatibility with ZR. Meanwhile, the activities of adenosine triphosphatase (ATPase), total anti-oxidant capability (T-AOC), and total superoxide dismutase (T-SOD) were measured. Results Compared with the homologous ALRP group, the compatibility between ALRP and ZR (AZ) had a stronger action against the decreasing of remaining rate on hot pad (P 【 0.05), suggesting an enhancement of cold tropism. Meanwhile, the internal indexes of Na+-K+-ATPase activity, Ca2+-Mg2+-ATPase activity, and oxygen consuming volume increased significantly (P 【 0.05), suggesting an enhancement of energy metabolism. The changes of T-AOC and T-SOD activity suggested that AZ reinforced the anti-oxidative capability of mice. In addition, it could be inferred from cluster analysis that the activity of AZ was concretely stronger than that of homologous ALRP. Conclusion ALRP and ZR are both herbs with hot property, but AZ has an enhanced trend of hot property. This external behavior of cold tropism and the internal activity of energy metabolism and anti-oxidant might reflect the internal hot property in an intuitive and objective way. The changes of ATPase activity of liver tissue might be the mechanism of drug action.

基于网络药理学和体外实验探讨附子-干姜抗心肌缺血再灌注损伤的作用机制

运用网络药理学方法探讨附子-干姜(Aconiti Lateralis Radix Preparata-Zingiberis Rhizoma,AZ)抗心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MI/RI)的潜在机制。通过中药系统药理数据库TCMSP筛选AZ的活性成分;Disgenet数据库获得MI/RI靶点;STITCH数据库获得蛋白互作;用DAVID数据库获得GO功能富集与KEGG信号通路并利用Cytoscape 3.8.0进行绘图;细胞实验验证网络药理学预测的结果。结果共获得AZ活性成分16个、治疗靶点171个;作图分析发现AKT1、IL6、TNF为潜在靶点;GO富集分析发现AZ可能通过凋亡、炎症、血管舒张发挥治疗作用;KEGG分析发现AZ可能通过PI3K-AKT信号通路、TNF信号通路、HIF信号通路发挥治疗作用;体外研究发AZ可使缺氧复氧损伤的大鼠血管内皮细胞存活率提高、降低凋亡率、氧化损伤;提高HIF-α、VEGF、eNOS蛋白的表达。附子-干姜激活HIF/VEGF/eNOS信号通路,降低血管内皮细胞氧化损伤、凋亡率发挥抗心肌缺血再灌注损伤的作用。

附子干姜配伍温阳通脉作用的实验研究

目的观察附子、干姜配伍的温阳通脉作用。方法采用腹腔注射氢化可地松复制大鼠阳虚模型,观察附子、干姜配伍对阳虚大鼠体重和体温的影响;采用活体微循环观测技术,观察附子、干姜配伍对正常小鼠耳廓微循环及局部滴加肾上腺素(Adr)所致微循环障碍的影响。结果附子、干姜配伍能提高阳虚大鼠体重、体温,明显扩张小鼠耳廓微血管,增加血流速度,对抗Adr所致微循环障碍。结论附子、干姜配伍具有温阳通脉的作用。

附子与不同药味药材配伍后乌头碱类生物碱的电喷雾质谱研究

目的通过研究不同药味药材与附子的配伍机制,揭示酸、甘、辛、苦味中药对附子化学成分的影响规律。方法利用电喷雾质谱和内标法,分别对生附子,生附子加五味子、黄芪、独活、黄连共煎液和药渣中乌头碱类生物碱进行考察。结果附子与五味子合用,双酯型和脂型生物碱的量增加,附子与黄芪、独活配伍双酯型生物碱的量下降,附子与黄连配伍脂型生物碱和生物碱的总量均降低,但双酯型生物碱变化无规律。结论附子与五味子合用毒性增加,附子与黄芪、独活毒性降低。

附子、半夏现代药学研究进展及配伍变化

目的对附子和半夏的化学成分研究、药理学研究进行综述。方法查阅文献,并利用传统中医理论和现代药学研究结果分析附子、半夏的配伍合理性。结果与结论附子、半夏化学成分复杂,配伍后变化机理尚未明确,十八反理论有待验证。

基于蛋白质组学的附子、干姜和花椒的性味研究

目的:探讨温热中药(附子、干姜、花椒)对正常大鼠能量代谢及相关蛋白表达的影响,探索温热中药在性味—功效—药理作用上的共性和差异性,为阐明温热中药性味的科学内涵提供依据。方法:选择Sprague Dawley(SD)雌雄大鼠,给药21 d后,大鼠通过腹腔内注射1%戊巴比妥钠麻醉(每100 g体重0.15 m L),差速离心法提取蛋白,BCA蛋白定量和SDS-PAGE检测蛋白完整性,应用同位素标记相对和绝对定量(i TRAQ)技术结合2D LC-MS/MS筛选肝脏中的差异蛋白。结果:与空白对照组相比,温热中药(附子、干姜、花椒)共筛选出50个共有差异蛋白,其中11个差异蛋白在肝脏中低表达,39个差异蛋白在肝脏中高表达,50个共有差异蛋白主要分布在18个通路中,其中绝大多数与能量代谢相关。结论:附子、干姜、花椒等热性中药在蛋白质组学方面存在共性和差异性,这种共性不仅体现在物质代谢和能量代谢上,也体现在其他药理作用上,其中,主要是通过增加体内热量生成和提高对能量的利用两个方面影响机体的能量代谢。研究结果为以"中药同时具有性(气)与味,性(气)与味是中药(包括方剂、单味中药、有效部位或组分、单体化合物)同时兼具的两种特性。药味与药物的具体功效相关。药性(气)是药物通过不同途径以主要影响机体的能量代谢、物质代谢为特征的,可影响药物疗效发挥或与副作用发生有关的一类生物学效应。"的中药性味理论新假说的客观性提供了科学依据,同时为评价中药寒热药性提供了新的方法。

乌附经方预处理对大鼠缺血再灌注心肌细胞凋亡的影响

目的观察含乌头、附子、半夏、栝楼的乌附经方对大鼠心肌缺血再灌注损伤的作用,探讨含有十八反药物的方剂用于特定病理状态的可行性。方法雄性Wistar大鼠50只随机分为5组,即:假手术对照组(SH组)、心肌缺血再灌注模型对照组(I/R组)、乌附经方低剂量组(I/R+JFL组)、乌附经方中剂量组(I/R+JFM组)及乌附经方高剂量组(I/R+JFH组),每组10只。乌附经方低、中、高剂量组分别以0.75、1.50、3.00mL/100g体质量的剂量灌胃14天,浓度500g/L;除SH组外,其他各组结扎冠状动脉左前降支,使心肌缺血30min,再灌注120min。透射电镜观察心肌线粒体的超微结构改变;一步法脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(terminal-deoxynucleotidyl transferase mediated nick end labeling,TUNEL)检测各组缺血心肌细胞凋亡;RT-PCR法测B细胞白血病/淋巴瘤-2基因(B-cell leukemia/lymphoma2,Bcl-2)、与Bcl-2相关的x蛋白(Bcl-2 associated x protein,Bax)的mRNA表达;ELISA检测血清乳酸脱氢酶(lactic dehydrogenase,LDH)、肌酸激酶(creatine kinase,CK)活性,并测定心肌梗死面积的大小。结果与I/R组比较,乌附经方各组均能降低血清中LDH、CK的释放量(且随着剂量的增加LDH、CK的释放量递减),减小心肌梗死面积、降低凋亡指数(P<0.05);经方组凋亡基因Bcl-2表达水平上升,Bax表达水平下降,Bcl-2/Bax比值升高。结论乌附经方预处理可能通过减少细胞凋亡,对心肌缺血再灌注损伤产生保护作用。说明"十八反"不是绝对的,而是相对的,含有相反中药的复方制剂可用于缺血性心肌病等特定的病理状态。

附子配伍半夏对大鼠影响的实验研究

目的研究附子配伍半夏对大鼠心、肝、肾功能和形态学的影响。方法取健康大鼠随机分为正常组(A组)、附子组(B组)、半夏组(C组)及附子配半夏组(D组),A、B、C组每日分别用灌胃法给予200g/L附子、半夏及附子与半夏混合煎液(0.25g/100g)。第14天停药,称重,采集心脏、肝脏及肾脏标本,计算体质量增长率及心、肝、肾脏指数,并观察其形态学改变;心脏取血,测定各组血清的LDH、AST、CK、ALT含量。结果体质量增长率、肝脏指数各组间均无显著差异;D组心脏指数、肾脏指数与B、C组有显著差异;AST、ALT的变化各组间无显著性差异,D组LDH、CK与B、C组有显著性差异。结论附子、半夏配伍用药后,对心脏有明显的毒性反应,对肾脏和肝脏形态学有影响,生化指标方面的影响有待于进一步探讨。

附子配伍干姜对附子总生物碱含量的影响

目的:研究生附子、白附片及黑顺片与干姜不同比例配伍前后水煎液中总生物碱煎出量的变化,探讨两药配伍使用的增效作用机理,体现中药药性中"热热配伍"的理论。方法:采用紫外分光光度法进行水煎液中总生物碱煎出量的测定。结果:水煎液中,不同附子炮制品与干姜不同比例配伍前后总生物碱的煎出量各不相同,但配伍干姜后各组总生物碱煎出量均有所增加。结论:附子、干姜配伍前后总生物碱煎出量的变化为两药配伍提供了科学的依据。

复方加味牵正合剂的鉴别方法

目的 :研究控制复方加味牵正合剂质量的鉴别方法 ,为制定质量标准提供依据。方法 :采用薄层色谱法。结果 :该合剂中黄芪、川芎、当归、防风、白附子、僵蚕的薄层色谱均无干扰 ,6味药的综合鉴别具有很强的专属性。结论 :可作为该合剂的质控方法。

附子大黄配伍的毒副作用研究

目的探讨附子大黄配伍的毒副作用。方法应用甲状腺素片及丙基硫氧嘧啶对大鼠进行造模,并分别以附子及附子大黄配伍对其进行治疗,通过肝肾功能及一般情况的观察了解大黄附子配伍的毒副作用。结果附子组肝肾功能可有损伤,与大黄配伍后肝肾功能损伤更明显。结论附子与大黄配伍可损害大鼠肝肾功能,对肝肾有一定毒性。

附子与干姜配伍对心阳虚衰大鼠血浆肾上腺素、血管紧张素Ⅱ、醛固酮及ANP、NT的影响

目的:研究附子与干姜配伍对心阳虚衰大鼠血浆肾上腺素(E)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)及心钠素(ANP)、内皮素(ET)的影响,揭示二者配伍增强回阳救逆作用的机理。方法:采用盐酸普罗帕酮注射液静脉注射建立大鼠心阳虚衰证心力衰竭动物模型,用放射免疫分析法测定以上指标血浆的含量。结果:附子与干姜配伍对大鼠血浆肾上腺素、血管紧张素、醛固酮、心钠素及内皮素均有一定的调控作用。

鱼腥草、炮姜、附子抗大鼠压力超负荷心室重构作用的比较研究

目的:比较寒性药鱼腥草和热性药炮姜、附子对压力超负荷所致大鼠心室重构及神经内分泌因子的影响。方法:采用大鼠腹主动脉缩窄法制备压力超负荷心室重构模型。一周后模型动物随机分为模型组、阳性对照卡托普利组、鱼腥草组、炮姜组和附子组。另设假手术对照组。灌胃给药干预3周,测量血压,称体重,测定左心室/体重及全心/体重作心室肥大的指标;放射免疫法测定心肌组织血管紧张素Ⅱ、血管内皮素含量以及血浆醛固酮水平;病理切片观察心肌组织胶原容积分数和血管周围胶原面积;测定心肌间质Ⅰ、Ⅲ胶原含量;免疫组织化学方法测定蛋白激酶C表达。结果:寒性药鱼腥草能显著降低血压、心肌质量指数,降低心肌AngⅡ、血管内皮素、血浆醛固酮水平;明显减少心肌组织胶原容积分数和血管周围胶原面积,减少心肌间质Ⅰ、Ⅲ胶原含量,抑制心肌蛋白激酶C表达。热性药炮姜无上述作用。附子除有一定降低心肌血管紧张素Ⅱ含量外,也无上述作用。结论:寒性药鱼腥草能抑制神经内分泌系统过度激活,防治心室重构;热性药炮姜、附子无明显抗心室重构及抑制神经内分泌因子分泌激活的作用。

大黄附子配伍药理与临床的研究现状

大黄与附子配伍是中药反佐配伍中增效减毒的重要方式。从现代药理研究和临床应用两方面综述了这一配伍的研究现状,为进一步研究提供基础。

大黄附子配伍对蒽醌类成分影响的研究

目的通过对附子大黄药材配伍前后大黄蒽醌类组分的研究,探讨附子大黄配伍在临床使用中大黄成分的变化。方法采用醋酸镁染色紫外分光光度法测定附子大黄不同比例配伍样品中蒽醌类成分的含量。结果大黄与附子配伍后总蒽醌和游离蒽醌均有所降低,从而降低其苦寒之性。结合蒽醌是大黄起泻下作用的关键成分,在配伍后略有增加,故配伍较好保持了其泻下作用。结论附子大黄配伍符合传统配伍理论,既有利于抑制寒性,又能保持大黄的泻下作用。

脾阳虚证用药规律浅析

目的:通过对近现代临床应用于脾阳虚证的方剂进行统计分析,探讨脾阳虚证用药规律。方法:运用SPSS 19.0统计软件,对脾阳虚证方剂中的中药进行频次分析,并对所用中药的性味、功效进行统计分析。结果:共收集方剂83首,涉及药物86味。药物使用频次显示甘草、干姜、人参、白术、陈皮、附子、木香、肉桂、茯苓、丁香等为常用药物,以补气药、温里药、理气药为主。性味分布情况显示治疗脾阳虚证以温、热、平性及辛、甘、苦味药为主,以辛热、辛温、甘平、辛苦温药居多。结论:脾阳虚证的遣方用药规律为药性上以温药、热药为主,药味上以辛、甘味为主,药物选择以补气药(甘草、人参、白术)和温里药(干姜、附子)为主,为临床脾阳虚证的治疗提供了理论依据。

传统寒热药对附子大黄配伍研究

目的:以附子大黄为对象研究寒热药对配伍前后影响药性的关键组分的变化情况。方法:分别采用药材/组分配伍层次进行研究,并且结合指纹图谱来研究附子、大黄配伍前后附子总碱和大黄蒽醌类成分的变化。结果:附子总碱配伍后略有增加,保持了附子的温煦作用;大黄总蒽醌配伍后均有所下降。结论:抑制了大黄的寒性,结合蒽醌变化较小,保持了大黄的泻下作用。本研究为附子、大黄传统配伍变寒下为温下提供了理论依据,可为药性配伍研究提供借鉴。