Celastrol ameliorates energy metabolism dysfunction of hypertensive rats by dilating vessels to improve hemodynamics

• Published in: Journal of natural medicines 2024, Vol.78 (1), p.191-207
• Main Authors: Zou, Gang, Yu, Ruihong, Zhao, Dezhang, Duan, Zhaohui, Guo, Shimin, Wang, Tingting, Ma, Limei, Yuan, Zhiyi, Yu, Chao
• Format: Article
• Language: English
• Subjects: Animals; Bioactive compounds; Biomedical and Life Sciences; Biomedicine; Blood flow; Blood vessels; Calcium channels; Calorimetry; Complementary & Alternative Medicine; Energy Metabolism; Hemodynamics; Hypertension; Hypertension - drug therapy; Medicinal Chemistry; Metabolism; Original Paper; Pharmacology/Toxicology; Pharmacy; Plant Sciences; Rats; Smooth muscle; Structure-function relationships; Triterpenes - chemistry; Triterpenes - pharmacology; Triterpenes - therapeutic use; Vasodilation
• ISSN: 1340-3443; 1861-0293
• DOI: 10.1007/s11418-023-01759-x

The impact of hypertension on tissue and organ damage is mediated through its influence on the structure and function of blood vessels. This study aimed to examine the potential of celastrol, a bioactive compound derived from Tripterygium wilfordii Hook F , in mitigating hypertension-induced energy metabolism disorder and enhancing blood perfusion and vasodilation. In order to investigate this phenomenon, we conducted in vivo experiments on renovascular hypertensive rats, employing indirect calorimetry to measure energy metabolism and laser speckle contrast imaging to evaluate hemodynamics. In vitro, we assessed the vasodilatory effects of celastrol on the basilar artery and superior mesenteric artery of rats using the Multi Wires Myograph System. Furthermore, we conducted preliminary investigations to elucidate the underlying mechanism . Moreover, administration of celastrol at doses of 1 and 2 mg/kg yielded a notable enhancement in blood flow ranging from 6 to 31% across different cerebral and mesenteric vessels in hypertensive rats. Furthermore, celastrol demonstrated a concentration-dependent (1 × 10 –7 to 1 × 10 –5  M) arterial dilation, independent of endothelial function. This vasodilatory effect could potentially be attributed to the inhibition of Ca 2+ channels on vascular smooth muscle cells induced by celastrol. These findings imply that celastrol has the potential to ameliorate hemodynamics through vasodilation, thereby alleviating energy metabolism dysfunctions in hypertensive rats. Consequently, celastrol may hold promise as a novel therapeutic agent for the treatment of hypertension. Graphical abstract