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

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 Ca2+ 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.

[The value of Roferon-A combined with hepatic artery chemoembolization and portal vein chemotherapy after radical resection in hepatocellular carcinoma for preventing recurrence].

OBJECTIVE: To explore the change of T cell subsets in patients suffered from hepatocellular carcinoma (HCC) before and after hepatectomy, and study the value of Roferon-A (interferon alpha-2a) combined with hepatic artery chemoembolization (HACE) and portal vein chemotherapy (PVC) after radical resection of HCC for preventing recurrence. METHODS: On 75 HCC patients, PVC and HACE were respectively given at 2 weeks and 4 weeks after radical tumor resection. In 2nd week after surgery, 33 cases of them accepted Roferon-A treatment for 1 week. Seventy-two patients were followed up over 3 years. Effect of Roferon-A combined with HACE and PVC on postoperative recurrence rate was compared with that of HACE and PVC. Changes of T cell subsets in peripheral blood were examined with labeled monoclonal antibodies before and after hepatectomy or using interferon. Forty cholecystolithiasis patients received cholecystectomy were used as the controls. RESULTS: CD(3)(+) and CD(4)(+) cells in peripheral blood were reduced in patients with HCC. After hepatectomy, they declined further with decrease in CD(4)(+)/CD(8)(+) ratio. The results returned to pre-operative level at the end of 4th week after surgery. The CD(3)(+), CD(4)(+) cells and the CD(4)(+)/CD(8)(+) ratio increased remarkably following the use of Roferon-A. The 1-, 2- and 3-year recurrence rates of patients treated with HACE, PVC and Roferon-A in combination were 0%, 6.2% and 15.6%, respectively, while those treated with HACE and PVC were 5.0%, 12.5% and 27.5%, respectively. CONCLUSION: Patients with HCC suffer from marked immuno-suppression which became ever more severe after hepatectomy, combined use of HACE, PVC and Roferon-A is superior to only HACE and PVC by decreasing the recurrence rate.