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三萜类化合物白桦脂醇通过调节卵清蛋白诱导的哮喘小鼠模型中的抗氧化剂、炎症细胞因子和组织转谷氨酰胺酶来减轻过敏气道炎症。

Triterpenoid compound betulin attenuates allergic airway inflammation by modulating antioxidants, inflammatory cytokines and tissue transglutaminase in ovalbumin-induced asthma mice model.

机构信息

Department of Microbiology, Faculty of Science, Annamalai University, Annamalainagar, Chidambaram, Tamil Nadu, India.

Division of Plant Pathology, UPASI Tea Research Foundation, Valparai, Coimbatore, Tamil Nadu, India.

出版信息

J Pharm Pharmacol. 2021 Jun 8;73(7):968-978. doi: 10.1093/jpp/rgab015.

Abstract

OBJECTIVES

This study hypothesized that to analyse the anti-inflammatory effect of triterpenoid compound betulin in ovalbumin (OVA)-induced asthmatic mice.

METHODS

In this study, betulin was intraperitoneally administered in OVA-challenged and sensitized mice. The effect of betulin on inflammatory cells, lung function, reactive oxygen species (ROS) production, antioxidants status, oxidative stress markers, serum IgE level and inflammatory cytokines status in BALF was examined by enzyme-linked immunosorbent assay. The expression of tTG, TGF-β1, MMP-9 and TIMP-1 in lung tissue was scrutinized by RT-qPCR analysis, and the expression of TREM-1, p-IκB-α and NF-κBp65 proteins in lung tissue was examined by western blot analysis.

KEY FINDINGS

We found that the betulin treatment has effectively attenuated the proliferation of inflammatory cells, reduced the ROS generation, elevated the antioxidant enzymes and attenuated the level of oxidative markers in asthma induced mice. Moreover, reduced the level of serum IgE and pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IFN-γ. Betulin treatment down-regulated the expression of MMP-9, tTG and TGF-β1 genes; moreover, betulin treatment effectively down-regulated the TREM-1, p-IκB-α and NF-κBp65 proteins level in lung.

CONCLUSION

Betulin exhibited effective anti-asthmatic activity by attenuating the accumulation of inflammatory cells, expression of tTG, TGF-β1 and MMP-9 genes in lung tissue.

摘要

目的

本研究假设分析桦木醇三萜化合物在卵清蛋白(OVA)诱导的哮喘小鼠中的抗炎作用。

方法

在本研究中,桦木醇通过腹腔内给药于OVA challenged 和致敏的小鼠。通过酶联免疫吸附试验(ELISA)检测桦木醇对炎症细胞、肺功能、活性氧(ROS)产生、抗氧化剂状态、氧化应激标志物、血清 IgE 水平和 BALF 中炎症细胞因子状态的影响。通过 RT-qPCR 分析检测肺组织中 tTG、TGF-β1、MMP-9 和 TIMP-1 的表达,并通过 Western blot 分析检测肺组织中 TREM-1、p-IκB-α 和 NF-κBp65 蛋白的表达。

主要发现

我们发现桦木醇治疗有效地减弱了炎症细胞的增殖,减少了 ROS 的产生,增加了抗氧化酶并减轻了哮喘诱导小鼠中氧化标志物的水平。此外,降低了血清 IgE 和促炎细胞因子的水平,并增加了抗炎细胞因子 IFN-γ。桦木醇治疗下调了 MMP-9、tTG 和 TGF-β1 基因的表达;此外,桦木醇治疗有效地下调了肺中 TREM-1、p-IκB-α 和 NF-κBp65 蛋白的水平。

结论

桦木醇通过减弱肺组织中炎症细胞的积累、tTG、TGF-β1 和 MMP-9 基因的表达,表现出有效的抗哮喘活性。

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