Sheng-Mai-Yin inhibits doxorubicin-induced ferroptosis and cardiotoxicity through regulation of Hmox1

Abstract

Doxorubicin (DOX) is a potent chemotherapeutic drug used for treating various cancers. However, its clinical use is limited due to its severe cardiotoxicity, which often results in high mortality rates. Sheng-Mai-Yin (SMY), a Traditional Chinese medicine (TCM) prescription, has been reported to exert a cardioprotective effect in various cardiovascular diseases, including DOX-induced cardiotoxicity (DIC). This study aimed to provide novel insights into the underlying cardioprotective mechanism of SMY. SMY, composed of Codonopsis pilosula (Franch.), Ophiopogon japonicus (Thunb.), and Schisandra chinensis (Turcz.) at a ratio of 3:2:1, was intragastrically administered to male C57BL/6 mice for five days prior to the intraperitoneal injection of mitoTEMPO. One day later, DOX was intraperitoneally injected. Hematoxylin-eosin staining and Sirius red staining were carried out to estimate the pharmacological effect of SMY on cardiotoxicity. Mitochondrial function and ferroptosis biomarkers were also examined. AAV was utilized to overexpress Hmox1 to confirm whether Hmox1-mediated ferroptosis is associated with the cardioprotective effect of SMY on DOX-induced cardiotoxicity. The findings revealed that SMY therapy reduced the number of damaged cardiomyocytes. SMY therapy also reversed the inductions of cardiac MDA, serum MDA, LDH, and CK-MB contents, which dramatically decreased nonheme iron levels. In the meantime, SMY corrected the changes to ferroptosis indices brought on by DOX stimulation. Additionally, Hmox1 overexpression prevented SMY's ability to reverse cardiotoxicity. Our results showed that SMY effectively restrained lipid oxidation, reduced iron overload, and inhibited DOX-induced ferroptosis and cardiotoxicity, possibly via the mediation of Hmox1.

Guideline-directed medical therapy in chemotherapy-induced cardiotoxicity and heart failure: current perspectives and practices

“…Dexrazoxane reduces cardiotoxicity by chelating free radical iron, but resveratrol significantly reduces free radicals and doxorubicin cardiotoxicity compared with dexrazoxane [61] . In addition, various plant-based medicines, for example, Qiliqiangxin [62] , Costus pictus extract [63] , and Sheng-Mai Yin [64] , have been shown to decrease myocardial remodeling and/or free radicals induced by anthracycline-related toxicity.…”

A systematic review of the mechanism of action and potential medicinal value of codonopsis pilosula in diseases

“…Secondly, CP has a protective effect on the cardiovascular system. CP can regulate the function of the cardiovascular system ( Meng P. et al, 2023 ), including lowering blood pressure ( Lee et al, 2019 ; Shin et al, 2019 ), regulating blood lipids, and controlling heart rhythm ( Wang et al, 2021 ), thus helping to prevent and treat cardiovascular diseases. These effects may be related to the antioxidant, anti-inflammatory, and vasodilatory effects of CP and its active ingredients, which protect the health of the heart and blood vessels by improving the functional state of the cardiovascular system and mitigating the onset and progression of cardiovascular diseases.…”

TCM targets ferroptosis: potential treatments for cancer

“…Sheng Mai Yin has previously been reported to have therapeutic effects on acute lymphoblastic leukemia (Guo et al, 2023), cardiac hypertrophy (Ming et al, 2022), heart failure (Kan et al, 2022), type 2 diabetes mellitus (T2DM) (Li et al, 2019). In addition, Sheng Mai Yin has been shown to inhibit the toxic side effects of doxorubicin and induced ferroptosis by modulating HMOX1, assisting cancer treatment and reducing patient complications (Meng et al, 2023).…”