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通过代谢组学和网络药理学阐明杞菊地黄丸治疗年龄相关性干眼的作用机制。

Mechanistic elucidation of QiJu-DiHuang Wan in management of age-related dry eye through metabolomics and network pharmacology.

机构信息

The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China; Hunan University of Chinese Medicine, Changsha 410208, China; The Key Laboratory of Chinese Medicine for the Prevention and Treatment of Eye, Ear, Nose and Throat Diseases in Hunan Provincial, Changsha 410208, China.

The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.

出版信息

Phytomedicine. 2024 Sep;132:155884. doi: 10.1016/j.phymed.2024.155884. Epub 2024 Jul 18.

DOI:10.1016/j.phymed.2024.155884
PMID:39053245
Abstract

BACKGROUND

QiJu-DiHuang Wan (QJDHW), a frequently employed Chinese herbal formula, is used to treat blurred vision. Even so, it is unclear how it works in treating age-related dry eyes.

OBJECTIVE

The aim of this research is to explore the potential mechanisms of QJDHW in treating dry eye using UHPLC-QE-MS, metabolomics, and network pharmacology.

METHODS

Six male SD rats were segregated into control and QJDHW groups. Following intervention, The primary active ingredients in QJDHW-containing serum were identified using UHPLC-QE-MS. Metabolomics and network pharmacology were utilized to investigate potential targets and pathways involved following QJDHW use. Primary lacrimal epithelial cells were used for validation.

RESULTS

A total of 425 active ingredients of QJDHW were identified, along with 210 active ingredients in QJDHW-containing serum. A comparison of QJDHW-containing serum and control serum samples revealed 40 metabolic differentiators. A total of 24 metabolites were found in QJDHW and QJDHW-containing serum. Network pharmacology identified 3,144 targets for dry eye disease, and 102 metabolite action targets were found for QJDHW-entering components. KEGG Enrichment Analysis revealed significance of HIF-1, apoptosis, cell cycle and PI3K-Akt, among others. HIF-1 and PI3K-Akt were chosen for verification in the oxidative damage model of lacrimal epithelial cells.

CONCLUSION

The main active ingredients of QJDHW and its containing serum were elucidated by UHPLC-QE-MS demonstrating that QJDHW treats age-associated dry eye by inhibiting HIF1α/NF-κB through ROS inhibition and PI3K/p-AKT activation.

摘要

背景

杞菊地黄丸(QJDHW)是一种常用的中草药配方,用于治疗视力模糊。然而,其治疗年龄相关性干眼症的作用机制尚不清楚。

目的

本研究旨在通过 UHPLC-QE-MS、代谢组学和网络药理学探讨 QJDHW 治疗干眼症的潜在机制。

方法

将 6 只雄性 SD 大鼠分为对照组和 QJDHW 组。干预后,采用 UHPLC-QE-MS 鉴定 QJDHW 含药血清中的主要活性成分。利用代谢组学和网络药理学探讨 QJDHW 使用后涉及的潜在靶点和通路。并采用原代泪腺上皮细胞进行验证。

结果

共鉴定出 425 种 QJDHW 的活性成分,其中 QJDHW 含药血清中鉴定出 210 种活性成分。与对照组血清相比,QJDHW 含药血清样本中发现 40 种代谢差异物。QJDHW 和 QJDHW 含药血清中共发现 24 种代谢产物。网络药理学共鉴定出 3144 个干眼症靶点,发现 102 个 QJDHW 进入成分的代谢产物作用靶点。KEGG 富集分析显示 HIF-1、细胞凋亡、细胞周期和 PI3K-Akt 等通路具有显著性。选择 HIF-1 和 PI3K-Akt 进行原代泪腺上皮细胞氧化损伤模型验证。

结论

通过 UHPLC-QE-MS 阐明了 QJDHW 及其含药血清的主要活性成分,表明 QJDHW 通过抑制 ROS 激活和 PI3K/p-AKT 来抑制 HIF1α/NF-κB 治疗年龄相关性干眼症。

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