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.

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.

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.

Inhibitory effect of Sumu(Lignum Sappan) plus Fuzi(Radix Aconiti Lateralis Praeparata) on a lung carcinoma model

OBJECTIVE: To investigate the inhibitory effect of Sumu(Lignum Sappan) plus Fuzi(Radix Aconiti Lateralis Praeparata)(SF) on the growth and metastasis of Lewis lung carcinoma.METHODS: A lung carcinoma model was established by subcutaneously inoculating Lewis lung carcinoma cells into C57 BL/6 mice. The mice were randomly divided into four groups of 13 mice(control, low-dose, moderate-dose, and high-dose), and gavaged once-daily for 21 consecutive days. The rates of tumor inhibition, metastasis, and metastasis inhibition were observed. The differential expressions of s P-selectin and vascular endothelial growth factor C(VEGFC) were compared between the treatment groups and the control group.RESULTS: The tumor weights differed significantly between the treatment groups and the control group(P < 0.05). Administration of SF in the moderate-dosage and low-dose groups significantly inhibited the expression of s P-selectin and VEGFC(both P < 0.05), suggesting anti-tumor activity.CONCLUSION: SF can inhibit the growth and metastasis of Lewis lung carcinoma.

A feasible,economical,and accurate analytical method for simultaneous determination of six alkaloid markers in Aconiti Lateralis Radix Praeparata from different manufacturing sources and processing ways

Aconiti Lateralis Radix Praeparata(Fuzi) is a commonly used traditional Chinese medicine in clinic for its potency in restoring yang and rescuing from collapse. Aconiti alkaloids, mainly including monoester-diterpenoidaconitines(MDAs) and diester-diterpenoidaconitines(DDAs), are considered to act as both bioactive and toxic constituents. In the present study, a feasible, economical, and accurate HPLC method for simultaneous determination of six alkaloid markers using the Single Standard for Determination of Multi-Components(SSDMC) method was developed and fully validated. Benzoylmesaconine was used as the unique reference standard. This method was proven as accurate(recovery varying between 97.5%-101.8%, RSD < 3%), precise(RSD 0.63%-2.05%), and linear(R > 0.999 9) over the concentration ranges, and subsequently applied to quantitative evaluation of 62 batches of samples, among which 45 batches were from good manufacturing practice(GMP) facilities and 17 batches from the drug market. The contents were then analyzed by principal component analysis(PCA) and homogeneity test. The present study provided valuable information for improving the quality standard of Aconiti Lateralis Radix Praeparata. The developed method also has the potential in analysis of other Aconitum species, such as Aconitum carmichaelii(prepared parent root) and Aconitum kusnezoffii(prepared root).

Efficacy of Renshen(Radix Ginseng) plus Fuzi(Radix Aconiti Lateralis Preparata) on myocardial infarction by enhancing autophagy in rats

OBJECTIVE:To elucidate the protective effects of Renshen(Radix Ginseng)and Fuzi(Radix Aconiti Lateralis Preparata)on myocardial infarction(MI)through regulating myocardial autophagy.METHODS:Thirty-one male Sprague-Dawley rats were randomized into five groups(n=6 or 7 for each).After treatment for 3 weeks,electrocardiogram(ECG)and cardiac function were recorded.Hematoxylin and eosin(HE)staining was used to detect pathological changes in the heart.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum B-type brain natriuretic peptide(BNP),cardiac troponin T(c Tn T),tumor necrosis factor-α(TNF-α),and serum inflammatory cytokines.Metabolomic analysis was used to identify differential biomarkers of MI in rats.Immunohistochemistry and western blotting were used to detect BNP,cTnT,TNF-α,LC3B,Beclin-1,p62,and adenosine monophosphate activated protein kinase(AMPK)expression in cardiac tissue.RESULTS:Fuzi(Radix Aconiti Lateralis Preparata)alone or Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)markedly ameliorated cardiac dysfunction and abnormal ECGs,demonstrated by decreases in the heart weight/body weight ratio,BNP,and c Tn T.Pro-inflammation cytokine interleukin(IL)-1αsignificantly decreased and anti-inflammatory cytokine IL-10 significantly increased in Renshen(Radix Ginseng)single or Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)groups compared with the control group.HE results suggested that co-treatment produced a greater reduction in cardiomyocyte cross-sectional area than Renshen(Radix Ginseng)or Fuzi(Radix Aconiti Lateralis Preparata)alone.Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)reversed these changes to different degrees in MI rats.Furthermore,Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)down-regulated LC3 B,Beclin-1,and AMPK expression in cardiac tissue and upregulated p62 expression.CONCLUSIONS:Renshen(Radix Ginseng)plus Fuzi(Radix Aconiti Lateralis Preparata)may have a greater effect on heart injury induced by MI in rats than Fuzi(Radix Aconiti Lateralis Preparata)treatment alone,and the underlying mechanism may be associated with the regulation of myocardial autophagy and anti-inflammation effects.These results provide fresh insight into the mechanism of co-treatment with Renshen(Radix Ginseng)and Fuzi(Radix Aconiti Lateralis Preparata)for MI.

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.

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。

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。

张锡纯附子用药解析

张锡纯是清末民初的代表性医家,研究其使用附子的习惯与规律对于指导临证有现实意义。在张锡纯著作《医学衷中参西录》中,含附子方剂共计30首,其中29首为复方汤剂,21首方剂指明使用经过炮制的附子(原文称“乌附子”),无使用生附子的实际案例,均未对煎煮法作特殊要求,其用量为0.6~24 g,总体使用剂量较小。人参、甘草、干姜、山药、白术是常与附子配伍的药味,旨在发挥益火扶阳(温里寒)、温阳通痹、回阳固脱、引火归元等功效。张锡纯使用附子的用法较为谨慎保守,其用药经验可以为现代中医临床提供思路与启示。

淡附片标准汤剂质量标准研究

目的制备淡附片标准汤剂,进行含量测定及指纹图谱分析。方法制备15批淡附片标准汤剂,通过检测单酯型生物碱的含量计算其转移率;采用HPLC建立淡附片标准汤剂指纹图谱,计算指纹图谱相似度。结果15批淡附片标准汤剂的单酯型生物碱转移率为56.93%~94.06%,平均转移率为78.03%。经HPLC指纹图谱分析,发现共有峰9个,确认其中3个;15批淡附片标准汤剂的指纹图谱与对照指纹图谱相似度均大于0.95。结论本研究建立了淡附片标准汤剂HPLC含量测定和指纹图谱分析方法,可为淡附片中药配方颗粒的质量控制提供参考。

人参再造丸中6种乌头类生物碱的含量测定方法研究

建立人参再造丸(浓缩丸)中6种乌头类生物碱含量的检测方法。采用超高效液相色谱-质谱联用法(UPLC-MS)对人参再造丸(浓缩丸)中双酯型生物和单酯型生物碱的含量进行测定,梯度洗脱模式下,以0.1%甲酸溶液-乙腈为流动相,电喷雾离子源(正离子模式),监测模式为多反应监测。结果表明,6种生物碱均有良好的线性关系,精密度试验、稳定性试验、重复性试验中RSD均低于5%,平均回收率和RSD分别为97.27%~108.29%和1.99%~4.01%。所建立的方法能同时准确、快速地测定人参再造丸(浓缩丸)中6种乌头类生物碱成分的含量,专属性强、灵敏度高、重复性好,能为全面有效管控人参再造丸(浓缩丸)质量提供参考。

响应面法优化活性炭对附子多糖的脱色工艺及抗氧化性研究

采用响应面分析法优化活性炭对附子多糖的脱色工艺,并测定了脱色后的附子多糖的抗氧化性。根据前期的单因素实验结果,以活性炭的用量、脱色的温度和脱色的时间为自变量,脱色率为响应值,利用Box-Benhnken中心组合实验并结合响应面分析法,优化附子多糖的脱色工艺,并通过测定DPPH自由基和羟基自由基的清除率,来评价脱色后的附子多糖的抗氧化性。结果表明,附子多糖的最佳脱色工艺条件为:活性炭用量为1.4%(m/m),脱色温度60℃,脱色时间52min,在此条件下,附子多糖的平均脱色率为84.99%,与预测值(85.22%)接近;附子多糖的质量浓度为0.018~0.090 mg·mL^(-1)时,对DPPH·和·OH的清除率,最大分别为85.54%和72.64%。

唐宋时期运用附子治疗肢体痹的文献研究

目的通过对唐宋时期记载治疗肢体痹方剂中附子的应用研究,梳理附子使用剂量、炮制及配伍方法,以期指导现代临床应用。方法整理唐宋医籍中治疗肢体痹方剂,筛选其中含附子的方剂,经古今剂量换算等,分析附子的使用范围、剂量、炮制及配伍情况。结果唐宋时期肢体痹方中,附子应用范围广,不仅用于寒邪所致之痹,通过药物配伍,也运用到热痹的治疗中;痛痹、行痹、着痹三痹之中,以痛痹使用附子为多。唐宋时期肢体痹治疗方药中,汤、丸、散剂的附子常用剂量相仿,以汤剂剂量跨度最甚,最大使用量为160g。宋代煮散剂中附子的每服剂量远远低于唐代剂量。肢体痹方中附子无特殊煎煮法;附子-防风是常见的减毒配伍药对。结论疼痛是应用附子治痹之契机,根据是否兼热酌情佐以清热;中小剂量、常规煎煮或许更能发挥附子抗炎镇痛之效,且无中毒之虞;防风与附子相配治痹,既能增效又可减毒。唐宋时期附子治痹经验对当今风湿病中医临床有重要参考价值。

附子中内源性组分新乌头碱的毒性作用

探究了附子中内源性组分新乌头碱的急性毒性,为附子的安全使用提供一定的科学依据。将50只SPF级SD大鼠(雌雄各半),按体重随机分成10组,每组5只,即1个雄性对照组、4个雄性给药组(1.00、2.15、4.64和10.0 mg·kg^(-1));1个雌性对照组、4个雌性给药组(0.464、1.00、2.15和4.64 mg·kg^(-1))。给药组一次性灌胃各剂量新乌头碱,对照组一次性灌胃等体积食用级玉米油。连续观察14 d,并对大鼠的脏器指数、病理组织切片以及氧化应激能力进行分析。结果表明,新乌头碱对雄性大鼠和雌性大鼠的经口LD 50分别为3.16和1.26 mg·kg^(-1)。病理组织学分析结果表明,一定剂量的新乌头碱会对大鼠肝脏造成一定的损伤。氧化应激能力指标结果显示,雌性1.00 mg·kg^(-1)组、雄性1.00 mg·kg^(-1)组和雄性2.15 mg·kg^(-1)组大鼠的肝脏iNOS指标与对照组相比显著升高(0.01<P<0.05或P<0.01),进一步证实了一定剂量的新乌头碱会对大鼠肝脏造成损伤。

基于全程质量控制理念的附子饮片标准化体系研究与构建

以实施国家中药标准化项目为契机,结合中药产业自身特点和发展现状,通过基于全程质量控制理念的附子饮片标准化建设研究,制定并验证了从种子种苗、种根繁育到药材生产、饮片生产、追溯系统等覆盖全产业链关键环节的附子技术规程和标准,实现附子饮片“从田地到医院”的全产业链无缝对接。构建了高标准的附子饮片全产业链质量管理体系,实现毒性中药附子产量和质量的稳定,为附子规范化生产起到良好的示范作用,从而推动中药产业发展的规范化、标准化,引导行业的良性健康发展。

基于网络药理学分析黄芪-附子治疗慢性心力衰竭的作用机制

目的 运用网络药理学方法分析黄芪-附子治疗慢性心力衰竭的作用靶点和机制。方法 使用TCMSP数据库获取黄芪-附子活性成分和对应靶点,通过PharmGKB、TTD、GeneCards、OMIM数据库获取慢性心力衰竭疾病靶点,将药物靶点与疾病靶点取交集,利用STRING数据库构建蛋白相互作用(PPI)网络,对关键靶点进行GO和KEGG富集分析。结果 获得黄芪-附子活性成分22个,对应靶点191个,主要活性成分有槲皮素、山柰酚、芒柄花素、β-谷甾醇、异鼠李素、脱氧乌头碱等。获取药物-疾病交集靶点183个,PPI核心网络包含靶点14个,包括AKT1、MAPK14、IL6等。GO分析得到生物过程2 324个、细胞组分88个、分子功能213个;KEGG通路富集分析得到173条通路。结论 黄芪-附子可通过多成分、多靶点、多通路治疗慢性心力衰竭,本研究为中药治疗慢性心力衰竭提供思路借鉴。

破格救心汤在心血管疾病中的应用与研究进展

通过文献阅读与整理,对破格救心汤在心血管疾病中的应用与研究进行了总结。破格救心汤具有扶正固脱、回阳救逆之效,在正确的煎煮和合理的配伍下是安全的。破格救心汤能通过改善心功能、心肌代谢和微循环障碍来减缓急慢性心脏衰竭、肺源性心脏病、心源性休克、心脏骤停和脓毒症心肌病等急危重症的病情,提高临床疗效和治愈率,也为心血管急危重症疾病的救治提供新的思路与依据。

15882张含附子的中药处方用药分析

目的:了解该院附子的使用情况,分析该院附子的常用剂量及与《中华人民共和国药典:一部》(以下简称“药典”)相比超剂量使用的比例。方法:采用回顾性分析方法,统计2020-2021年该院使用附子的所有中药处方。对患者的性别、年龄,每张中药处方使用的中药味数、方法、所用附子的剂量、与附子常用的配伍,以及常用的证型等相关资料进行统计分析。结果:共纳入15882张含附子的中药处方;大多为女性患者;附子使用剂量为药典规定的3~15 g的处方有15016张,占94.55%;单张处方的中药味数多集中于7~15味,有11724张(占73.82%);单张处方开具的剂数为1~7剂的处方有9308张(占58.61%),单张处方开具的剂数在30剂以内的处方共15638张(占98.46%);与附子联合使用频率最高的中药为当归。结论:该院中药处方中附子的使用剂量整体符合药典规定,无生附子的使用记录,附子常与其他药材配伍使用。