Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.
Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, Uttar Pradesh, India.
Eur J Pharmacol. 2022 Aug 15;929:175132. doi: 10.1016/j.ejphar.2022.175132. Epub 2022 Jul 2.
Chronic inflammation and oxidative stress play important role in development of hypertension. Recently, we have reported novel fluorophenyl benzimidazole (FPD) for vasorelaxation and antihypertensive activity in SHRs. The present study envisaged the anti-inflammatory, anti-oxidant and cardio-protective properties of FPD in L-NAME model of hypertension with special emphasis on reversal of vascular remodeling, gene expression and restoration of hemodynamic.
Antihypertensive activity of FPD was evaluated in L-NAME treated Wistar rats, and the parameters studied were anti-inflammatory activity, histomorphological changes, gene expression profile and anti-oxidant properties.
FPD at 50 and 100 mg kg once daily for 15 days significantly reduced SBP, DBP and MAP in L-NAME treated rats and the values were well comparable to vehicle control group. Further, FPD treatment showed a significant increase in hepatic GSH content, SOD, catalase activity, decreased MDA level and restoration of pro and anti-inflammatory cytokine levels. The mRNA expression profile of genes associated with regulation of vascular tone, remodeling and inflammation showed a significant level of alteration by chronic L-NAME treatment and was dose-dependently restored upon treatment with FPD. Further, FPD treatment restored serum lipid profile, CK, CK-MB and LDH level and also reversed the histomorphological changes like intimal wall thickening, hyperplasia of cardiomyocytes and ventricular wall thickening.
Taken together, FPD produced potent antihypertensive activity in L-NAME model through vasorelaxation, anti-oxidative and anti-inflammatory properties leading to restoration of serum lipid profile, cardiac biomarker, expression profile of target genes and reversal of histomorphological changes.
慢性炎症和氧化应激在高血压的发展中起着重要作用。最近，我们报道了一种新型的氟苯基苯并咪唑（FPD），它具有舒张血管和降血压活性，可用于治疗 SHR。本研究旨在探讨 FPD 在 L-NAME 高血压模型中的抗炎、抗氧化和心脏保护作用，特别强调了对血管重构、基因表达和血流动力学的逆转作用。
在 L-NAME 处理的 Wistar 大鼠中评价 FPD 的抗高血压活性，研究的参数包括抗炎活性、组织形态学变化、基因表达谱和抗氧化特性。
FPD 以 50 和 100mg/kg 每天一次连续 15 天给药，可显著降低 L-NAME 处理大鼠的 SBP、DBP 和 MAP，其效果与载体对照组相当。此外，FPD 治疗可显著增加肝 GSH 含量、SOD、过氧化氢酶活性，降低 MDA 水平，并恢复促炎和抗炎细胞因子水平。与血管张力调节、重构和炎症相关的基因表达谱的 mRNA 表达谱显示，慢性 L-NAME 处理后发生了显著改变，并可随 FPD 治疗呈剂量依赖性恢复。此外，FPD 治疗还可恢复血清脂质谱、CK、CK-MB 和 LDH 水平，并逆转内膜壁增厚、心肌细胞增生和心室壁增厚等组织形态学变化。
综上所述，FPD 通过血管舒张、抗氧化和抗炎作用产生了有效的降压活性，从而恢复了血清脂质谱、心脏生物标志物、靶基因的表达谱和组织形态学变化。
