The present study describes the synthesis, characterization, and evaluation of tetrahydropiperine (THP), piperic acid (PA), and tetrahydropiperic acid (THPA) as anti-inflammatory agents. THPA demonstrated potent anti-inflammatory activity among all the compounds. The anti-inflammatory potential was investigated in both and experimental models. Our findings demonstrated that THPA effectively suppressed the production of pro-inflammatory mediators, including nitric oxide and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in both and . Additionally, THPA attenuated the expression of i-NOS and COX-2 in RAW 264.7 macrophages. The oral administration of THPA significantly reduced carrageenan induced paw edema thickness and alleviated liver, lung, and kidney injury induced by LPS. THPA also reduced the infiltration of inflammatory cells, prevented the occurrence of significant lesions, and mitigated tissue damage. Moreover, THPA significantly improved the survival rate of mice challenged with LPS. Our western blot studies also found that LPS induced NF-κB activation was downregulated by treatment with THPA in an system. These results collectively illustrated the potential of THPA as a therapeutic agent for treating inflammatory diseases.

中文翻译：

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四氢胡椒碱、胡椒酸和四氢胡椒酸通过下调 NF-κB 通路的合成、表征和抗炎活性

本研究描述了四氢胡椒碱 (THP)、胡椒酸 (PA) 和四氢胡椒酸 (THPA) 作为抗炎剂的合成、表征和评估。在所有化合物中，THPA 均表现出有效的抗炎活性。在实验模型中研究了抗炎潜力。我们的研究结果表明，THPA 可以有效抑制促炎介质的产生，包括一氧化氮和促炎细胞因子（TNF-α、IL-6 和 IL-1β）。此外，THPA 减弱了 RAW 264.7 巨噬细胞中 i-NOS 和 COX-2 的表达。口服THPA可显着减轻角叉菜胶引起的足水肿厚度并减轻LPS引起的肝、肺和肾损伤。 THPA 还可以减少炎症细胞的浸润，防止重大病变的发生，并减轻组织损伤。此外，THPA 显着提高了 LPS 攻击小鼠的存活率。我们的蛋白质印迹研究还发现，在系统中用 THPA 处理可下调 LPS 诱导的 NF-κB 激活。这些结果共同说明了 THPA 作为治疗炎症性疾病的治疗剂的潜力。