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重楼皂苷 VII 通过下调 MAPK 和 NF-κB 通路的体外和体内抗炎作用。

In Vitro and In Vivo Anti-Inflammatory Effects of Polyphyllin VII through Downregulating MAPK and NF-κB Pathways.

机构信息

School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.

出版信息

Molecules. 2019 Mar 1;24(5):875. doi: 10.3390/molecules24050875.

Abstract

: Polyphyllin VII (PP7), a steroidal saponin from , has been found to exert strong anticancer activity. Little is known about the anti-inflammatory property of PP7. In this study, the anti-inflammatory activity and its underlying mechanisms of PP7 were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in multiple animal models. : The content of nitric oxide (NO) was determined by spectrophotometry. The levels of prostaglandin E2 (PGE₂) and cytokines were measured by enzyme-linked immunosorbent assay (ELISA) assay. The mRNA expression of pro-inflammatory genes was determined by qPCR. The total and phosphorylated protein levels were examined by Western blotting. The in vivo anti-inflammatory activities were evaluated by using mouse and zebrafish models. : PP7 reduced the production of NO and PGE₂ and the protein and mRNA expressions of pro-inflammatory cytokines (, , and ) and enzymes (inducible NO synthase [], cyclooxygenase-2 [], and Matrix metalloproteinase-9 []) in LPS-induced RAW264.7 cells by suppressing the NF-κB and MAPKs pathways. Notably, PP7 markedly inhibited xylene-induced ear edema and cotton pellet-induced granuloma formation in mice and suppressed LPS and CuSO₄-induced inflammation and toxicity in zebrafish embryos. : This study demonstrates that PP7 exerts strong anti-inflammatory activities in multiple in vitro and in vivo models and suggests that PP7 is a potential novel therapeutic agent for inflammatory diseases.

摘要

: 重楼七叶皂苷(PP7)是从重楼中提取的一种甾体皂苷,具有很强的抗癌活性。然而,关于 PP7 的抗炎特性知之甚少。本研究旨在评估 PP7 在脂多糖(LPS)刺激的 RAW264.7 细胞和多种动物模型中的抗炎活性及其潜在机制。 : 通过分光光度法测定一氧化氮(NO)的含量。通过酶联免疫吸附试验(ELISA)测定前列腺素 E2(PGE₂)和细胞因子的水平。通过 qPCR 测定促炎基因的 mRNA 表达。通过 Western blot 检测总蛋白和磷酸化蛋白水平。通过小鼠和斑马鱼模型评估体内抗炎活性。 : PP7 通过抑制 NF-κB 和 MAPKs 通路,降低 LPS 诱导的 RAW264.7 细胞中 NO 和 PGE₂的产生,以及促炎细胞因子(、、和)和酶(诱导型一氧化氮合酶[]、环氧化酶-2[]和基质金属蛋白酶-9[])的蛋白和 mRNA 表达。值得注意的是,PP7 显著抑制二甲苯诱导的小鼠耳肿胀和棉花球诱导的肉芽肿形成,并抑制 LPS 和 CuSO₄诱导的斑马鱼胚胎炎症和毒性。 : 本研究表明,PP7 在多种体外和体内模型中具有很强的抗炎活性,提示 PP7 可能是一种治疗炎症性疾病的新型潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce6/6429153/78bc049fd6a8/molecules-24-00875-g001.jpg

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