Abstract
Aconite Lateralis Radix Praeparata (Fuzi) and Pinelliae Rhizoma (Banxia) are a combination often used to treat cardiovascular diseases in ancient and modern clinical practice. However, eighteen antagonisms based on traditional Chinese medicine (TCM) theory often abided against such combination therapy. Therefore, exploring whether coadministration of the two herbs can be used in adriamycin- (ADR-) induced cardiomyopathy and clarifying the potential mechanism could help to guide its clinical application. Echocardiography experiments revealed that either Fuzi, Banxia, or their combination had effect on ADR-induced heart dysfunction, while high dose Fuzi exerted positive inotropic effect associated with restored PKA levels. Moreover, low dose Fuzi significantly reduced QT/QTc prolongation, inhibited cardiac apoptosis, and upregulated protein expression of PKA. However, combination of Fuzi and Banxia greatly aggravated QT/QTc prolongation and cardiomyocyte apoptosis in ADR rats compared with each drug alone, which was accompanied by a marked decrease in PKA, pSer346 levels. Similarly, Banxia alone treatment promoted cardiac apoptosis and downregulated protein levels of PKA and pSer346. Additionally, high dose Fuzi treatment also produced proapoptotic effect. Taken together, our study has provided the first direct evidence that combination of Fuzi, a positive inotropic agent, with Banxia promoted cardiac apoptosis in an ADR induced rat model of cardiomyopathy, which may be associated with suppression of PKA/β2AR-Gs signaling. This study also provides scientific language for better understanding of the risks and limitations of combination of Fuzi and Banxia in clinical applications.
Highlights
Duality of toxic and efficacious performance is a nature of drugs, and there could be some undesirable effects in the process of curing disease; traditional Chinese medicine (TCM) is no exception [1]
Our study has provided the first direct evidence that combination of Fuzi, a positive inotropic agent, with Banxia promoted cardiac apoptosis in an ADR induced rat model of cardiomyopathy, which may be associated with suppression of protein kinase A (PKA)/β2AR-Gs signaling
As to LVEF, LV mass, cardiac output (CO), and stroke volume (SV), no significant difference was observed in ADR-induced rats following treatment with either Fuzi, Banxia, or combination as compared to ADR model group
Summary
Duality of toxic and efficacious performance is a nature of drugs, and there could be some undesirable effects in the process of curing disease; traditional Chinese medicine (TCM) is no exception [1]. Drug compatibility is highly advocated in TCM for thousands of years; it refers to combination of two or more herbs in order to enhance efficacy and simultaneously reduce toxicity [2, 3]. Aconite Lateralis Radix Praeparata (Fuzi) and Pinelliae Rhizoma (Banxia) are representative of incompatible pairs recorded in “the eighteen antagonisms”, a special rule for TCM incompatibility in formulas, which suggests strictly compatibility prohibition in clinical prescriptions because mutual antagonism results in an undesirable consequence [3, 5]. Coadministration of the two herbs has been used in many clinical formulas for several centuries.
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