Cardioprotective activity of ethyl acetate extract of Cinnamomi Ramulus against myocardial ischemia/reperfusion injury in rats via inhibiting NLRP3 inflammasome activation and pyroptosis |
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| Affiliation: | 1. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China;2. School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China;1. School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;2. Network and Educational Technology Center, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;3. Department of Gynecology, Affiliated Hospital of Jiangxi University of traditional Chinese Medicine, Nanchang 330004, China;4. State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi 330047, China;5. High School, Jiangxi University of Technology, Nanchang, Jiangxi 330029, China;1. Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, PR China;2. CSSD, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, PR China;3. Department of Pathophysiology, North Sichuan Medical College, Nanchong 637000, PR China;1. School of Life and Environment Sciences, Harbin University of Commerce, Harbin 150076, China.;2. Institute of Medicinal Plant Development, Chinese Academy of Medical Science, Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100094, China.;3. Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 151, Malianwa North Road, Haidian District, Beijing 100094, China.;4. Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100094, China. |
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| Abstract: | BackgroundNLRP3 inflammasome activation and pyroptosis play an important role in myocardial ischemia/reperfusion injury (MI/RI). Cinnamomi ramulus (CR), is an important folk medicinal plant in China, which derived from the dried twig of Cinnamomum cassia (L.) Presl, has function of “warming and tonifying heart yang”, and traditionally utilized to treat the cold, blood-cold amenorrhea, phlegm, edema, arthralgia, and palpitations as well as improve blood circulation. The aqueous extract of C. ramulus was reported to show significant therapeutic potential for treating MI/RI. Whereas, there are no previous investigations in China or abroad has reported the cardioprotective effects and underlying mechanism of the ethyl acetate extract of C. ramulus (CREAE) and its bioactive substance cinnamic acid (CA) in triggering NLRP3 inflammasome activation and subsequent pyroptosis.PurposeThe present study aimed to assess the cardioprotective function of CREAE and CA against the MI/RI in rats and involved the underlying mechanisms.MethodsThe MI/RI model was established in male SD rats by occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min, respectively. The rats were intragastrically administered with CREAE (74 and 37 mg/kg) and CA (45 mg/kg) for 7 successive days before vascular ligation. The cardioprotective effects of CREAE and CA against myocardial injury of rats were detected by HE staining, TTC staining, echocardiograms, and myocardial enzymes detections. Serum levels of inflammatory factors, such as IL-6, IL-1β, and TNF-α, were analyzed by ELISA kits to evaluate the effects of CREAE and CA. The protein and gene expression levels of NLRP3 and the pyroptosis-related factors in heart tissue were conducted by western blot and RT-qPCR.ResultsOur results showed that CREAE and CA decrease myocardial infarct size and improve cardiac function, mitigate myocardial damage, and repress inflammatory response in rats after I/R. Mechanistically, our results revealed that CREAE and CA can dramatically suppress the activation of NLRP3 inflammasome and subsequent cardiomyocyte pyroptosis in myocardial tissues that as evidenced by downregulating the protein and gene expressions of NLRP3, ASC, IL-1β, caspase-1, gasdermin D, and N-terminal GSDMD.ConclusionsOur data indicated that CREAE and CA may attenuate MI/RI through suppression of NLRP3 inflammasome and subsequent pyroptosis-related signaling pathways. |
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