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从 Vasconcellea cundinamarcensis 乳胶中提取的蛋白水解部分在急性 TNBS 诱导的结肠炎小鼠模型中显示出抗炎作用。

The Proteolytic Fraction From Vasconcellea cundinamarcensis Latex Displays Anti-Inflammatory Effect in A Mouse Model of Acute TNBS-Induced Colitis.

机构信息

Pharmacology Department, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Mucuri Medicine School, Federal University of Jequitinhonha and Mucuri Valleys, Teófilo Otoni, Minas Gerais, Brazil.

出版信息

Sci Rep. 2020 Feb 20;10(1):3074. doi: 10.1038/s41598-020-59895-3.

Abstract

The proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis, displays gastric protective and healing activities in different skin lesions in mice and human. In an excisional model, this fraction accelerates resolution of lesions and modulates inflammatory mediators. Based on these data, we assessed its anti-inflammatory activity in murine colitis model, induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) adopted by its physiopathological similarity with human colitis. Twenty four hours after colitis induction followed by three days of treatment, P1G10 at 0.3 and 3.0 mg/Kg induced 30% increase in body weight (p < 0.0001) and ~80% reduction in colon macroscopic damage score (p < 0.05) compared to the untreated TNBS-induced colitis group. Histological analyses showed that 0.3 mg/Kg P1G10 reduced the inflammatory profile and tissue damage (47%, p < 0.05) when it was proteolytically active. Compared to TNBS group, 0.3 mg/Kg P1G10 reduced MPO activity (80%, p < 0.01), MCP-1 (47%, p < 0.05) and TNF-α (50%, no significant) and increased IL-10 (330%, p < 0.001) levels in the supernatant of colonic tissue homogenate. P1G10 treatment also reduced COX-2 expression (60%, p < 0.05) and metalloprotease-2 activity (39%, p < 0.05) while increased globet cell density (140%, p < 0.01), that contributes to mucus layer protection in colonic tissue. Taken together, these findings suggest that low doses of active P1G10 promotes lesion resolution, at least in part by its anti-inflammatory activity, in TNBS-colitis model.

摘要

从 Vasconcellea cundinamarcensis 中提取的蛋白水解部分 (P1G10),在不同的皮肤损伤小鼠和人类中显示出胃保护和愈合作用。在切除模型中,该部分加速病变的解决并调节炎症介质。基于这些数据,我们评估了其在由 2,4,6-三硝基苯磺酸 (TNBS) 诱导的小鼠结肠炎模型中的抗炎活性,采用其与人类结肠炎的生理病理学相似性。在结肠炎诱导后 24 小时并在三天的治疗后,与未治疗的 TNBS 诱导的结肠炎组相比,P1G10 在 0.3 和 3.0 mg/Kg 时体重增加了 30%(p < 0.0001),结肠宏观损伤评分降低了~80%(p < 0.05)。组织学分析表明,当 0.3 mg/Kg P1G10 具有蛋白水解活性时,其减少了炎症谱和组织损伤(47%,p < 0.05)。与 TNBS 组相比,0.3 mg/Kg P1G10 降低了 MPO 活性(80%,p < 0.01)、MCP-1(47%,p < 0.05)和 TNF-α(50%,无显著性)并增加了结肠组织匀浆上清液中的 IL-10(330%,p < 0.001)水平。P1G10 处理还降低了 COX-2 表达(60%,p < 0.05)和金属蛋白酶-2 活性(39%,p < 0.05),同时增加了球细胞密度(140%,p < 0.01),这有助于保护结肠组织中的粘液层。总之,这些发现表明,低剂量的活性 P1G10 通过其抗炎活性促进病变的解决,至少在一定程度上在 TNBS-结肠炎模型中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c6c/7033115/38352194487e/41598_2020_59895_Fig1_HTML.jpg

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