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On Cardiovascular System Are Re- Periments on the Heart of Toads, Frogs, Guinea Pigs and Rabbits in Vitro, and Showed a Cardiotonic Effect of Aco- Viewed Online Submissions:http://www.journaltcm.com J Tradit Chin Med 2012 September 15; 32(3): 1-2 [email protected] ISSN 0255-2922 © 2012 JTCM. All rights reserved. REVIEW Pharmacological effects of Chinese herb aconite (Fuzi) on cardiovas- cular system Dandan Zhao, Jie Wang, Yanjing Cui, Xinfang Wu aa Dandan Zhao, Jie Wang, Yanjing Cui, Xinfang Wu, (Ranunculaceae). Fuzi tastes spicy and sweet, has a hot Guang'anmen Hospital, China Academy of Chinese Medical nature and toxicity, acts on the heart, kidney and Sciences, Beijing 100053, China spleen meridians and plays a role in saving yang for the Dandan Zhao, Beijing University of Traditional Chinese treatment of collapse, supplementing kidney yang, and Medicine, Beijing 100029, China eliminating cold to stop pain. Fuzi (aconite) consists of Supported by the Capital Medical Science and Technology a variety of alkaloids, such as the diester-diterpene alka- Development Program (No. SF-2007-I-04) loids, aconitine, hypaconitine, mesaconitine, and hige- Correspondence to: Prof. Jie Wang, Guang'anmen Hospi- namine. Aconite also is composed of some lipids, such tal, China Academy of Chinese Medical Sciences, Beijing as fatty acids, phosphatidate calcium, and steroids. It is 100053, China. [email protected] mainly clinically used for treatment of heart failure, Telephone: +86-10-88001381 shock and hypotension subsequent to acute myocardial Accepted: , March 1, 2012 infarction, coronary heart disease and rheumatic heart disease. Along with the repeated application of aconite in clinical practice and studies on pharmacology, its use in the cardiovascular system has been the focus of in- Abstract creasing research. In this article, aconite's pharmacolog- ical effects on the cardiovascular system are summa- Fuzi (aconite, Radix Aconiti praeparata), a widely rized. used Chinese herb, plays a significant role in the cardiovascular system. This is mainly reflected by Fuzi's cardiotonic effect, its protective effect on CARDIOTONIC EFFECT OF ACONITE myocardial cells, and its effect on heart rate and rhythm, blood pressure, and hemodynamics. In this Domestic and international research has shown that ac- article, the pharmacological effects and the corre- onite enhances cardiac contractility and also accelerates sponding mechanisms of Fuzi (aconite) and its ac- myocardial contraction frequency. Rao performed ex- tive components on cardiovascular system are re- periments on the heart of toads, frogs, guinea pigs and rabbits in vitro, and showed a cardiotonic effect of aco- viewed. nite decoction, while experiments on the heart of frogs, cats, and dogs in vivo also suggested a mildly cardioton- © 2012 JTCM. All rights reserved. ic effect of aconite. The mechanism of this action of ac- onite was shown to be related to calcium based on fur- Key words: Radix aconiti lateralis praeparata; Car- ther research.1 diovascular system; Pharmacologic actions Zuo et al. confirmed a "faint pulse verging on expiry" in a pathological cat model where intravenous adminis- tration of aconite water extract could gradually en- INTRODUCTION hance the heart beat. They observed that the heart in this cat model contracted more vigorously with much Fuzi (aconite, Radix Aconiti praeparata) is the pro- greater amplitude than that before drug administra- cessed tuberous root of Aconitum carmichaeli Debx tion, and repeated administration of the drug resulted JTCM | www. journaltcm. com 308 September 15, 2012 | volume 32 | Issue 3 | Zhao DD et al. Pharmacological effects of Fuzi on cardiovascular system in a stronger effect. However, this effect was different Huang et al studied a rat model of heart failure in- according to the different states in the model. For ex- duced by adriamycin, and found that aconite decoc- ample, when the heart beat was weak and the extremi- tion could reduce Brain natriuretic peptide and Inter- ties were cold, aconite had a positive effect, but it did leukin-6 levels in serum, protect blood vessels and not show any cardiotonic function when the heart beat myocardial cells, and improve heart function. They al- was normal. Further experiments indicated that the so showed that the degree of myocardial cell injury was mechanism of effect of aconite may be related to 1 re- significantly less in the aconite decoction group than ceptor and receptor activation in the heart.2 β that in the heart failure model group which was not Xu et al.3 reportedα that aconite decoction can antago- given any drug after the heart failure model is success- nize the inhibition of phenobarbital, chloral hydrate fully made.9 Fang, et al reported that hypaconitine at and other drugs on the heart of the toad, and it an appropriate concentration of 250 ng/mL reduces showed a significant cardiotonic effect on the heart of apoptosis of myocardial cells induced by H2O2. They the reserpinized cat model in vivo or in vitro. They con- speculated that its mechanism may be related to a de- cluded that the cardiotonic effect of drugs of this type crease in expression of the apoptosis proteins, caspases is not caused by catecholamine release, but by a direct 3 and 9, and an increase in cell proliferation activity.10 contribution on the heart. Lee et al showed that higenamine protects myocardial Therefore, based on previous findings, aconite has obvi- cells from ischemia reperfusion injury, and therefore, it ous cardiotonic effects on the heart in vitro and in vi- significantly reduces myocardial infarct size. They vo, as well as in the normal and exhausted heart. The found that administration of higenamine 1 hour prior effective components of aconite include higenamine, to ischemic-reperfusion (I/R)-injury greatly decreased salsoline, methyl chloride dopamine, and aconite glyco- the release of cytochrome C, caspase-3 activity, and sides,3~6 and it is likely that there are other undiscov- Bax expression, but it up-regulated the expression of ered components. Bcl-2 and HO-1, as well as HO enzyme activity in the With regard to the mechanism of the cardiotonic effect left ventricle. These changes could be inhibited by of aconite, different explanations have been provided. ZnPP IX, an enzyme inhibitor of HO-1. As a result, Aconite achieve this effect through some substances they considered that HO-1 plays an important role in contained in it functions as receptor and receptor the protective action of higenamine in I/R-induced α β agonists, and increases intracellular calcium concentra- myocardial injury.11 + tions by activating sodium channels and increasing Na It has also been suggested that the mechanism of the + 2+ 1,2,7 influx, thereby stimulating reverse Na /Ca exchange. above function may be due to blocking sodium chan- A slight decrease in serumTumor Necrosis Factor – nels,12 or protecting the mitochondria of the cells.13 A α (TNF- ) and Nitric oxide (NO) levels of adriamy- previous study investigated the effect of aconite on the α cin-induced heart failure in rats by aconite decoction vascular extracellular matrix of the aorta in a cardiac hy- has been shown, suggesting another mechanism of car- pertrophy rat model induced by thyroxine, and found 8 diotonic function. that the mechanism whereby aconite prevented cardio- Aconite is widely used in the treatment of heart failure vascular hypertrophy could be attributed to inhibition and shock subsequent to acute myocardial infarction, of collagen synthesis.14 especially for symptoms, such as yang debilitation, a Combined administration with ginger in a heart failure cold body and extremities, and a faint pulse verging on model in the rat, aconite causes a decrease in the epi- expiry, which also suggest that aconite has cardiotonic nephrine, atrial natriuretic peptide, and endothelin lev- and anti-shock effects. Although the purified chemical els in plasma. Furthermore, on the one hand, a de- composition from Fuzi has strong cardiotonic and an- crease in epinephrine levels can prevent or reduce the ti-shock effects, the herb, Fuzi, itself hasn't been used toxicity of catecholamines on the heart, reduce myocar- as a cardiotonic drug in research and in the clinical set- dial energy demand and curb excessive adrenergic de- ting. This may be because of the effect of one the compensation during heart failure, and on the other herb's ingredients, aconitine, which can cause rapid ar- hand, a decrease in epinephrine levels can also inhibit rhythmia and ventricular fibrillation. renin release.15 In addition, the active ingredients of aconite have an- ti-inflammatory and antioxidant effects, which both PROTECTIVE EFFECT OF ACONITE play important roles in a variety of cardiovascular dis- ON MYOCARDIAL CELLS eases. For example, an increased expression of adhesion It has previously been shown that aconite and its ex- molecules and inflammatory-induced cytokines was tract can conserve myocardial cells of animal models found in the myocardial tissues of patients with cardio- and clinical patients with heart failure, myocardial in- vascular disease, indicating that local inflammation of farction, cardiac hypertrophy and other cardiovascular microvascular and myocardial cells is important in the diseases. The explanation of the mechanism of action pathological changes of cardiovascular diseases.16~18 This varies because of different viewpoints. also provides a theoretical basis for the protective effect JTCM | www. journaltcm. com 309 September 15, 2012 | volume 32 | Issue 3 | Zhao DD et al. Pharmacological effects of Fuzi on cardiovascular system of aconite on myocardial cells. showing neither synergy
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