The Protective Effects of Shengmai Formula Against Myocardial Injury Induced by Ultrafine Particulate Matter Exposure and Myocardial Ischemia are Mediated by the PI3K/AKT/p38 MAPK/Nrf2 Pathway

Abstract

Background and Purpose: Ultrafine particulate matter (UFPM) induces oxidative stress (OS) and is considered to be a risk factor of myocardial ischemia (MI). Shengmai formula (SMF) is a traditional Chinese medicine with antioxidant properties and has been used to treat cardiovascular diseases for a long time. The aim of this study was to explore the protective role of SMF and the mechanism by which it prevents myocardial injury in UFPM-exposed rats with MI.Methods: An MI rat model was established. Animals were randomly divided into five groups: sham, UFPM + MI, SMF (1.08 mg/kg⋅d) + UFPM + MI, SMF (2.16 mg/kg⋅d) + UFPM + MI, and SMF (4.32 mg/kg⋅d) + UFPM + MI. SMF or saline was administrated 7 days before UFPM instillation (100 μg/kg), followed by 24 h of ischemia. Physiological and biochemical parameters were measured, and histopathological examinations were conducted to evaluate myocardial damage. We also explored the potential mechanism of the protective role of SMF using a system pharmacology approach and an in vitro myoblast cell model with small molecule inhibitors.Results: UFPM produced myocardial injuries on myocardial infarct size; serum levels of LDH, CK-MB, and cardiac troponin; and OS responses in the rats with MI. Pretreatment with SMF significantly attenuated these damages via reversing the biomarkers. SMF also improved histopathology induced by UFPM and significantly altered the PI3K/AKT/MAPK and OS signaling pathways. The expression patterns of Cat, Gstk1, and Cyba in the UFPM model group were reversed in the SMF-treated group. In in vitro studies, SMF attenuated UFPM-induced reactive oxygen species production, mitochondrial damage, and OS responses. The PI3K/AKT/p38 MAPK/Nrf2 pathway was significantly changed in the SMF group compared with that in the UFPM group, whereas opposite results were obtained for pathway inhibition.Conclusion: These findings indicate that SMF prevents OS responses and exerts beneficial effects against myocardial injury induced by UFPM + MI in rats. Furthermore, the PI3K/AKT/p38 MAPK/Nrf2 signaling pathway might be involved in the protective effects of SMF.

Pretreatment with rosavin attenuates PM2.5‐induced lung injury in rats through antiferroptosis via PI3K/Akt/Nrf2 signaling pathway

“…It is reported that Nrf2 activation protects the cells against PM2.5‐caused cytotoxicity (Wang et al, 2019). It was confirmed that the activation of phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) signaling pathway exerts beneficial effects in the PM2.5‐triggered lung injury model by modulating Nrf2 (Chen et al, 2021; Wang Xu et al, 2017). In addition, rosavin increased pulmonary ventilation and improved endurance exercise capacity (Huang et al, 2009).…”

Nrf2 Regulates Oxidative Stress and Its Role in Cerebral Ischemic Stroke

“…Shengmai formula (SMF) is a traditional Chinese medicine with antioxidant properties. Pretreatment of a myocardial ischemia model with SMF significantly relieved heart injury, which was related to the regulation of the PI3K/AKT/p38 MAPK/Nrf2 signal pathway [ 126 ]. Studies have shown that during ischemic stroke, p38 MAPK is transferred from cytoplasm to nucleus, thus promoting apoptosis [ 127 ].…”

Inhibition of Myocardial Cell Apoptosis Is Important Mechanism for Ginsenoside in the Limitation of Myocardial Ischemia/Reperfusion Injury

“…p38 participates in the promotion of apoptosis via its substrates, such as MAPKAP-2, MSK-1, and GADD153 ( Zhang et al, 2019a ; Ashraf et al, 2014 ; Das et al, 2006 ). Inhibition of the p38 MAPK pathway up-regulates the levels of Nrf2 and HO-1 to increase antioxidative proteins and improve apoptosis ( Chen et al, 2021 ). Evidence indicated that ginsenosides Rb1, Rb3, Rg2, Rg3, Rh1, Rh2, and Rk3 had a function of down-regulating JNK, and ginsenosides Rb1 and Rk3 decreased the level of p38 ( Supplementary Table S1 ).…”