Fuzi and Banxia Combination, Eighteen Antagonisms in Chinese Medicine, Aggravates Adriamycin‐Induced Cardiomyopathy Associated with PKA/β2AR‐Gs Signaling

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.

The synergistic compatibility mechanisms of fuzi against chronic heart failure in animals: A systematic review and meta-analysis

“…Then, 49 full-text articles were assessed for eligibility, and 25 of them were excluded based on selection criteria. Eventually, 24 studies ( Yang et al, 2013 ; Zhai et al, 2013 ; Chen S. et al, 2014 ; Liang et al, 2014 ; Jin et al, 2015 ; Miao et al, 2015 ; Xu, 2015 ; Miao et al, 2016 ; Wang et al, 2016 ; Xu et al, 2016 ; Wan et al, 2017 ; Fu et al, 2018 ; Peng, 2018 ; Sun et al, 2018 ; Wu, 2018 ; Jia et al, 2019 ; Sun et al, 2019 ; Wen et al, 2019 ; Yang, 2019 ; Wen et al, 2020a ; Wen et al, 2020b ; Yan et al, 2020 ; Xie et al, 2021 ; Ni et al, 2022 )were included in the qualitative synthesis, and 20 of them were included in the quantitative synthesis (meta-analysis).…”

Network Pharmacology Prediction and Molecular Docking-Based Strategy to Explore the Potential Mechanism of Gualou Xiebai Banxia Decoction against Myocardial Infarction

“…For centuries, Gualou and Xiebai have been used for the clinical treatment of cardiovascular diseases (CVDs), including MI, heart failure and arrhythmia [10,11]. Extracts of Gualou (Trichosanthes kirilowii Maxim) and Xiebai (Allium macrostemon Bge) have been found to improve cardiac function and hemodynamics and have been shown to be effective in treating ischemia/reperfusion injuries and MI [12][13][14]. Banxia (Pinellia pinellia), likewise, has significant therapeutic actions in CVD [14].…”

“…Extracts of Gualou (Trichosanthes kirilowii Maxim) and Xiebai (Allium macrostemon Bge) have been found to improve cardiac function and hemodynamics and have been shown to be effective in treating ischemia/reperfusion injuries and MI [12][13][14]. Banxia (Pinellia pinellia), likewise, has significant therapeutic actions in CVD [14]. The Gualou Xiebai Banxia decoction is a commonly prescribed TCM for the treatment of CVD, including MI [15].…”

Efficacy analysis and research progress of complementary and alternative medicines in the adjuvant treatment of COVID-19

“…For instance, the four compounds in aconite (talatizamine, 14-acetyl-latizamin, hetisine, and 14-benzoylnovine) can counteract doxyrubicin-induced heart failure [ 125 ], while aconitine in aconite can induce apoptosis in H9c2 cardiomyocytes [ 126 ]. Aconite also produces antagonistic chemical components that play a role in antiarrhythmic effects, such as N-aconitine, N-deacetylaconitrile, raconitine, aconitine, 14-acetyl taladiamine, and aconitine [ 127 ]. Thus, different active ingredient composition ratios of aconite and Pinellia may induce different or antagonistic effects from those originally intended.…”