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Plumula nelumbinis has great medicinal potential as a herbal tea and traditional drug in China. This study was aimed to evaluate the anticardiac fibrosis of the total alkaloids of P. nelumbinis (TAP). TAP at 50 mg/kg/day significantly ameliorated isoproterenol‐induced cardiac fibrosis in mice (p <.05). The circulating lipidomics study revealed that TAP improved the lipid metabolism dysfunction in cardiac fibrosis. Meanwhile, TAP suppressed the lipid accumulation, decreased MDA level (p <.01) in heart, and increased FFA level (p <.01). Furthermore, integrating lipidomics, chemical profiles and pharmacology network analysis found that AMPK and PI3K/Akt signaling pathways were the potential targeted pathway by TAP to regulate lipid metabolism dysfunction including glycerophospholipid metabolism. Above all, TAP provided a potential anticardiac fibrosis effect partly through regulation of lipid profiles. Practical applications: The total alkaloids of Plumula nelumbinis (TAP) suppressed ISO‐induced cardiac fibrosis in mice.Network pharmacology analysis and experiments revealed that TAP‐regulated AMPK and PI3K/Akt signaling pathway to improve lipid metabolism disorder in cardiac fibrosis.This study provides evidence to the therapeutic potential of TAP in the treatment of ISO‐induced cardiac fibrosis and could be a drug candidate for prevention and treatment of cardiac fibrosis. [ABSTRACT FROM AUTHOR]

• HXP improves cardiac function in myocardial infarction (MI) mice. • HXP treatment ameliorates cardiac apoptosis partly via suppression of the p53 signaling pathway. • HXP treatment alleviates cardiac fibrosis by inhibiting the activation of TGF-β1/Smad2/3 pathway. Huoxin Pill (HXP), a Traditional Chinese Medicine, is used widely to treat patients with coronary heart disease and angina pectoris in China. However, the underlying protective mechanism of HXP on cardiac apoptosis and fibrosis has never been evaluated. Therefore, the aim of this study was to investigate the role of HXP in a myocardial infarction (MI) mouse model. The mice were randomly divided into 3 groups and subjected to surgical ligation of the left anterior descending (LAD) coronary artery or sham surgery (n = 6 for each group) and treated with HXP (50 mg/kg/day) or saline by gavage for 2 weeks. At 2 weeks post MI, we found that HXP significantly enhanced myocardial function and attenuated the increase of heart weight index (HWI) and pathological changes in MI mice. RNA-sequencing and KEGG pathway analyses identified 660 differentially expressed genes and multiple enriched signaling pathways including p53 and TGF-β. In support of these findings, HXP attenuated cardiac apoptosis and decreased p53 and Bax protein expression, while increasing Bcl-2 protein expression in cardiac tissues of MI mice. Furthermore, HXP treatment inhibited cardiac fibrosis and significantly down-regulated TGF-β1 protein expression and Smad2/3 phosphorylation in cardiac tissues. In summary, HXP can improve cardiac function in mice after MI by attenuating cardiac apoptosis and fibrosis partly via supression of the p53/Bax/Bcl-2 and TGF-β1/Smad2/3 pathways. [ABSTRACT FROM AUTHOR]

SMYAD attenuated cardiac fibrosis via decreasing collagen synthesis by suppressing TGF-β1 pathway and increasing collagen degradation by interfering with MMP-TIMPs expression. • SMYAD reduced fibrosis level and improved TAC-induced heart failure in mice. • SMYAD attenuated cardiac fibrosis via decreasing collagen synthesis by suppressing TGFβ1/Smad pathway and increasing collagen degradation by interfering with MMP-TIMPs expression. • Our study suggests the potential of SMYAD for the treatment of heart failure. Myocardial fibrosis is an important pathological feature of pressure overload cardiac remodeling. Si-Miao-Yong-An decoction (SMYAD), a traditional Chinese formula, is now clinically used in the treatment of cardiovascular diseases in China. However, its mechanisms in the prevention of heart failure are not fully revealed. To determine whether treatment with SMYAD for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a mice model of heart failure. Mice were subjected to transverse aorta constriction to generate pressure overload induced cardiac remodeling and then were administered SMYAD (14.85 g/kg/day) or captopril (16.5 mg/kg/day) intragastrically for 4 weeks after surgery. Echocardiography and immunohistochemical examination were used to evaluate the effects of SMYAD. The mRNA of collagen metabolism biomarkers were detected. Protein expression of TGF-β1/Smad and TGF-β1/TAK1/p38 pathway were assessed by Western blot. SMYAD significantly improved cardiac function, increased left ventricle ejection fraction, and decreased fibrosis area and αSMA expression. Moreover, SMYAD reduced proteins expression related to collagen metabolism, including Col1, Col3, TIMP2 and CTGF. The increased levels of TGF-β1, Smad2, and Smad3 phosphorylation were attenuated in SMYAD group. In addition, SMYAD reduced the levels of TGF-β1, p-TAK1 and p-p38 compared with TAC group. SMYAD improved cardiac fibrosis and heart failure by inhibition of TGF-β1/Smad and TGF-β1/TAK1/p38 pathway. SMYAD protected against cardiac fibrosis and maintained collagen metabolism balance by regulating MMP-TIMP expression. Taken together, these results indicate that SMYAD might be a promising therapeutic agent against cardiac fibrosis. [ABSTRACT FROM AUTHOR]