Recently, the team of Deli Dong/Zhijie Sun from School of Pharmacy published their latest research paper online in Acta Pharmaceutica Sinica B (IF: 14.8), a leading journal in the medical discipline, that Nitazoxanide protects against heart failure with preserved ejection and metabolic syndrome induced by high-fat diet (HFD) plus L-NAME “two-hit” in mice. Jiahui Chen, a PhD student of the class of 2021 in the School of Pharmacy, was the first author of the paper, and Prof. Deli Dong and Prof. Zhijie Sun of the School of Pharmacy were the first authors of the paper. and Prof. Zhijie Sun of the School of Pharmacy are the co-corresponding authors of this paper, and China Pharmaceutical University is the sole correspondent of this paper.
Heart failure with preserved ejection fraction (HFpEF) is a group of clinical syndromes in which the ejection fraction of the heart is greater than 50% and still has the clinical manifestations and signs of heart failure. Epidemiology shows that patients with HFpEF account for about 50% of the total heart failure patients, but there are fewer clinical drugs for the treatment of HFpEF, and the only drugs currently approved for the treatment of HFpEF are sacubitril valsartan and sodium-glucose cotransporter protein 2 inhibitors, such as dagliflozin and empagliflozin.HFpEF is a complex factor-related disease, which is associated with the occurrence of aging, obesity, hypertension, glycolipid Its occurrence is related to aging, obesity, hypertension, abnormal glucose-lipid metabolism, and chronic inflammation, etc. Therefore, the ideal therapeutic agents for HFpEF should be those with multi-organ and multi-mechanism effects based on the above pathogenic factors.
Nitazoxanide is a clinical antiprotozoal drug with a good safety profile, which is rapidly metabolized to Tizoxanide after absorption in the body to exert pharmacological effects. The team of Deli Dong/Zhijie Sun in the School of Pharmacy has been focusing on the pharmacological effects of mitochondrial uncoupling agents, and the previous studies have found that nitazoxanide and its active metabolite tizoxanide have mitochondrial uncoupling effects. Nitazoxanide can inhibit experimental hyperlipidemia, hepatic steatosis, atherosclerosis, and improve the fibrosis of the organs; Nitazoxanide and tizoxanide can prolong the lifespan of Cryptosporidium hidradenii nematode, and inhibit the process of senescence; Nitazoxanide and tizoxanide can inhibit inflammasome activation.
Based on the above findings, the team used a high-fat diet combined with L-NAME to establish a mouse HFpEF model to study the effect of nitazoxanide on HFpEF. It was found that oral administration of nitazoxanide could significantly inhibit myocardial hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, cardiac lipid accumulation, elevated blood pressure, impaired exercise tolerance, hepatic steatosis, renal fibrosis, and aortic hypoconstriction induced by high-fat diet combined with L-NAME in HFpEF mice; therapeutic administration of nitazoxanide in established HFpEF mouse model also could In an established HFpEF mouse model, therapeutic administration of nitazoxanide also improved myocardial hypertrophy, cardiac fibrosis, cardiac diastolic dysfunction, and hepatic steatosis induced by high-fat diet combined with L-NAME in mice. This study suggests that nitazoxanide is expected to be a potential drug for the treatment of HFpEF and related metabolic syndrome.
The team of Deli Dong/Zhijie Sun focuses on the role of mitochondrial uncoupling mechanism in cardiovascular and metabolic diseases and the discovery of new drugs based on mitochondrial uncoupling mechanism, and has obtained a series of research results in this field. The above work was supported by the National Natural Science Foundation of China under Grant No. 82373864; No. 82170472.
Original link: https://www.sciencedirect.com/science/article/pii/S2211383525000012
