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罗汉果甜苷V与罗汉果果实提取物相比在变应性肺炎小鼠中的肝脏代谢特征

The liver metabolic features of Mogroside V compared to Siraitia grosvenorii fruit extract in allergic pneumonia mice.

作者信息

Liu Yisa, Wang Juan, Dou Tong, Zhou Luwei, Guan Xiao, Liu Guoxiang, Li Xiaojuan, Han Mengjie, Chen Xu

机构信息

Department of Pharmacy, Guilin Medical University, Guilin 541199, PR China.

Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, the Affiliated Hospital of Guilin Medical University, Guilin 541001, PR China; Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, the Affiliated Hospital of Guilin Medical University, Guilin 541001, PR China.

出版信息

Mol Immunol. 2022 May;145:80-87. doi: 10.1016/j.molimm.2022.03.008. Epub 2022 Mar 17.

Abstract

BACKGROUND

For a long time, Siraitia grosvenorii fruit extract (SGFE) and its dominant compounds, mogroside V(MV) were both reported to have therapeutic effects on allergic pneumonia, while previous studies only stay on phenotype and mechanism of the two active ingredients, hardly have any studies compared the two ingredients on the effect of liver metabolic, and revealed the relationship between mechanism and liver metabolism.

OBJECTIVE

Here we elucidated and compared the curative mechanisms of SGFE and MV on allergic pneumonia through liver metabolomics.

METHODS

We established allergic pneumonia mice using ovalbumin, then treated the mice with SGFE, MV and positive drug of Suhuang Zhike Jiaonang. The effects of the drugs were evaluated by detecting inflammatory cytokines, pathological examination and liver oxidative stress biomarkers. We explored the metabolic features between SGFE and MV through liver metabolomics consequently.

RESULTS

At phenotype, we confirmed that MV and SGFE both inhibited the expression of inflammatory cytokines including interleukins-5 (IL-5), IL-13, IL-17 and OVA-induced immunoglobulin E, which can also relieve inflammatory cells infiltration and mesenchymal thickening in lung tissue compared with positive drug. In addition, both of them can alleviate oxidative stress damage in liver, while MV showed a superior effect than SGFE. In metabolomic analysis, the two ingredients were found to ameliorate inflammatory and oxidative reaction mainly in controlling pathways of Riboflavin metabolism and Glutathione metabolism. While SGFE were found to control other metabolic pathways such as Phenylalanine metabolism, Sphingolipid metabolism, Glycerollipid metabolism, Glycine, serine and threonine metabolism and Arginine and proline metabolism.

CONCLUSION

From the results we can infer that the minor ingredients except MV in SGFE contribute poor function to the treatment of allergic pneumonia and MV may be the main functional constituent that relieve allergic pneumonia in SGFE. This study will be beneficial to figuring out a systematic theory of Siraitia grosvenorii active ingredients and proposing a guidance for pharmacology development.

摘要

背景

长期以来,罗汉果果实提取物(SGFE)及其主要成分罗汉果甜苷V(MV)均被报道对过敏性肺炎具有治疗作用,而以往研究仅停留在两种活性成分的表型和作用机制上,几乎没有研究比较二者对肝脏代谢的影响,也未揭示其机制与肝脏代谢之间的关系。

目的

通过肝脏代谢组学阐明并比较SGFE和MV对过敏性肺炎的治疗机制。

方法

用卵清蛋白建立过敏性肺炎小鼠模型,然后用SGFE、MV及阳性药物苏黄止咳胶囊对小鼠进行治疗。通过检测炎性细胞因子、病理检查及肝脏氧化应激生物标志物评估药物疗效。随后通过肝脏代谢组学探索SGFE和MV之间的代谢特征。

结果

在表型方面,我们证实MV和SGFE均能抑制炎性细胞因子白细胞介素-5(IL-5)、IL-13、IL-17及卵清蛋白诱导的免疫球蛋白E的表达,与阳性药物相比,二者还可减轻肺组织中炎性细胞浸润和间质增厚。此外,二者均可减轻肝脏氧化应激损伤,而MV的效果优于SGFE。在代谢组学分析中,发现这两种成分主要通过控制核黄素代谢和谷胱甘肽代谢途径改善炎症和氧化反应。而SGFE还可控制其他代谢途径,如苯丙氨酸代谢、鞘脂代谢、甘油酯代谢、甘氨酸、丝氨酸和苏氨酸代谢以及精氨酸和脯氨酸代谢。

结论

从结果可以推断,SGFE中除MV外的其他次要成分对过敏性肺炎的治疗作用较差,MV可能是SGFE中缓解过敏性肺炎的主要功能成分。本研究将有助于阐明罗汉果活性成分的系统理论,并为药理学发展提供指导。

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