Putative Prevention of XML Injection Against Myocardial Ischemia Is Mediated by PKC and PLA2 Proteins

Abstract

Background: Xinmailong (XML) injection is a CFDA-approved traditional Chinese medicine with clinical value for heart failure treatment. The present investigation was aimed to evaluate the potential protective roles of this injection on myocardial ischemia and the underlying molecular mechanism.Methods: In our study, we selected two models of myocardial ischemia rats. Rats were randomly divided into six groups, with saline or XML administrated 4 days before ischemia model establishment. ECG of different time intervals and biochemical parameters of end point were measured. The potential mechanisms of the protective role of XML were explored using system pharmacology and molecular biology approaches.Results: Myocardial ischemia rats demonstrated abnormal ECG and serum levels of cTnT. Pretreatment with XML significantly attenuated these damages, especially the medium doses. GO and KEGG analysis revealed that the 90 putative target genes were associated with pathways of fatty acid absorption/metabolism, inflammation, RAAS, and vascular smooth muscle. Further network pharmacology method identified five main chemical ingredients and potential targets of XML injection for myocardial ischemia. Mechanically, the beneficial effect of XML injection was mediated by the reactive oxygen species (ROS) inhibition and inflammation attenuation via regulating the expression levels of targets of PKC and PLA2.Conclusion: These findings indicate that XML exerts protective effects against myocardial injury, with attenuated ROS production, apoptosis, and inflammation. Therefore, we speculate that XML may be an alternative supplementary therapeutic agent for myocardial ischemia prevention.

Effect and mechanism of Tangzhiqing in improving cardiac function in mice with hyperlipidaemia complicated with myocardial ischaemia

“…Caspase-9 is a promoter and participates in the apoptosis process after activation [ 67 ]. Xinmailong exerts protective effects against myocardial injury by increasing the expression of Bcl-2 and decreasing the expression of Bax [ 68 ]. Trimetazidine can increase myocardial function by decreasing the expression of apoptotic proteins, such as Bax and caspase-3, and reducing myocardial infarct size [ 69 ].…”

New approach to heart failure: Integrated traditional Chinese with Western medicine

“…Several studies involving HFpEF patients have demonstrated that Xinmailong injection can alleviate inflammation by reducing BNP, high‐sensitivity C‐reactive protein, and procalcitonin levels [74, 75]. In animal experiments, Xinmailong injection has been shown to protect against myocardial damage by reducing ROS production, apoptosis, and inflammation [87].…”

Xinmailong injection on left ventricular remodeling and inflammatory mediators in patients with CHF: a systematic review and meta-analysis

“…Xinmailong injection (XMLI) is a composite peptide injection extracted from Periplaneta americana L, containing adenosine, inosine, protocatechuic acid, and pyroglutamyl dipeptide as its main active ingredients ( Qi et al, 2017 ). Modern pharmacological studies have elucidated the cardioprotective properties of XMLI, notably in inhibiting oxidative stress ( Jiang et al, 2021 ) and inflammatory response ( Jin et al, 2022 ), regulating cell autophagy ( Li et al, 2016 ), and modulating cytokine expression ( Liu et al, 2017 ). Jiang et al ( Jiang et al, 2021 ) observed that XMLI modulates HO-1 mediated lysosomal function and autophagy in H9C2 cells, reduces oxidative stress and mitigates DOX-induced cardiac toxicity.…”

“…Jiang et al ( Jiang et al, 2021 ) observed that XMLI modulates HO-1 mediated lysosomal function and autophagy in H9C2 cells, reduces oxidative stress and mitigates DOX-induced cardiac toxicity. Jin et al ( Jin et al, 2022 ) revealed that XMLI can reduce ROS production, minimize inflammatory response, and decrease cell apoptosis by improving PKC and PLA2 protein-mediated myocardial ischemia. Li et al ( Li et al, 2016 ) demonstrated that XMLI targets autophagy by activating the PI3K/Akt pathway and inhibiting Erk1/2 and P38 MAPK pathways, effectively alleviating epirubicin-induced cardiomyopathy.…”