基于血清药物化学和网络药理学的荜茇抗胃溃疡药效物质基础分析

doi:10.5246/jcps.2024.02.013

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (2): 156-168.DOI: 10.5246/jcps.2024.02.013

基于血清药物化学和网络药理学的荜茇抗胃溃疡药效物质基础分析

张弘¹^,², 张莎莎¹, 王焕芸¹, 梁越³, 武世奎¹, 孙丽君¹, 夏慧敏¹, 白云霞⁴, 张慧文¹^,^*()

^1. 内蒙古医科大学药学院, 内蒙古呼和浩特 010110
^2. 鄂尔多斯市中心医院中心实验室, 内蒙古鄂尔多斯 017000
^3. 内蒙古自治区人民医院, 内蒙古呼和浩特 010017
^4. 包头医学院, 内蒙古包头 014040

收稿日期:2023-08-18 修回日期:2023-09-26 接受日期:2023-10-23 出版日期:2024-03-03 发布日期:2024-03-03
通讯作者: 张慧文

Integrated serum pharmacochemistry and network pharmacology analyses reveal the bioactive metabolites and potential functional mechanism of Piper longum L. in the treatment of gastric ulcer in rats

Hong Zhang¹^,², Shasha Zhang¹, Huanyun Wang¹, Yue Liang³, Shikui Wu¹, Lijun Sun¹, Huimin Xia¹, Yunxia Bai⁴, Huiwen Zhang¹^,^*()

¹ College of Pharmacy, Inner Mongolia Medical University, Hohhot 010110, Inner Mongolia, China
² General Clinical Research Center, Ordos Central Hospital, Ordos 017000, Inner Mongolia, China
³ People's Inner Mongolia Hospital, Hohhot 010017, Inner Mongolia, China
⁴ Baotou Medical College, Baotou 014040, Inner Mongolia, China

Received:2023-08-18 Revised:2023-09-26 Accepted:2023-10-23 Online:2024-03-03 Published:2024-03-03
Contact: Huiwen Zhang
Supported by:
Natural Science Foundation of Inner Mongolia (Grant No. 2022MS08023), Mongolian Medicine Synergy Innovation Center Scientific Research Foundation of Inner Mongolia (Grant No. MYYXTYB202108), Key Technology Project Foundation of Inner Mongolia (Grant No. 2021GG0176), Ph. D. Fund Project of Inner Mongolia Medical University (Grant No. YKD2020BSJJ014).

摘要/Abstract

摘要：

荜茇(PL)是具有药食两用性的常用中药, 中医临床多生用, 具有温中散寒、行气止痛的功效, 用于胃脘冷痛、胃寒呕吐等, 同时也是蒙医、藏医和印度传统常用药物。在本研究中, 首先建立大鼠胃溃疡动物模型, 考察荜茇对胃粘膜的保护作用, 进而将血清药物化学与网络药理学相结合, 挖掘荜茇药效物质基础, 从荜茇中筛选药效物质和潜在作用靶点。研究结果表明, 荜茇对乙醇诱导的胃溃疡具有显著的保护作用; 网络药理学预测了潜在的药物-疾病共同靶点后, GO富集分析预测荜茇可能影响多种生物过程, 如脂质代谢和炎症反应。KEGG富集分析提示TNF和AGE-RAGE信号通路可能参与其中, 分子对接预测芝麻素与胡椒碱等可能是荜茇抗炎和抗菌作用的主要成分。此外, 荜茇的血清药物化学揭示了入血成分中有23种原型成分和17种代谢物。本研究整合了血清药物化学和网络药理学, 为荜茇在胃溃疡治疗中的药效物质研究提供了实验依据。

关键词: 血清药物化学, 网络药理学, 代谢物, 荜茇, 胃溃疡

Abstract:

The fruit of Piper longum L. (PL) is widely utilized in China for medicinal and dietary purposes, and it is also used in Ayurvedic medicine in India to treat gastric disorders and other ailments. In the present study, a strategy combining serum pharmacochemistry with network pharmacology was proposed to screen the bioactive metabolites derived from PL and explore their potential functional mechanisms. The strategy primarily involved investigating the anti-gastric ulcer activities, network pharmacology analysis, and metabolite identification. The results demonstrated the efficacy of PL in protecting against ethanol-induced gastric ulcers. Through network pharmacology approaches, potential drug-disease common targets were identified. GO enrichment analysis predicted that PL might influence multiple biological processes, such as lipid metabolism and inflammatory response. KEGG enrichment analysis suggested the involvement of the TNF and AGE-RAGE signaling pathways. Molecular docking further indicated that the synergistic effect of sesamin, piperine, and other ingredients could be the main contributors to PL’s anti-inflammatory and antibacterial activities. Additionally, the serum pharmacochemistry of PL was established, enabling the screening of absorbed components and metabolites for their anti-gastric ulcer activity. A total of 23 prototypes and 17 metabolites were found to significantly contribute to the anti-gastric ulcer activity, suggesting that these bioactive compounds could serve as potential active components of PL. Overall, this investigation provided an experimental foundation to support the clinical application of PL in gastric ulcer therapy.

Key words: Serum pharmacochemistry, Network pharmacology, Metabolite, Piper longum L., Gastric ulcer

Supporting:

张弘, 张莎莎, 王焕芸, 梁越, 武世奎, 孙丽君, 夏慧敏, 白云霞, 张慧文. 基于血清药物化学和网络药理学的荜茇抗胃溃疡药效物质基础分析[J]. 中国药学(英文版), 2024, 33(2): 156-168.

Hong Zhang, Shasha Zhang, Huanyun Wang, Yue Liang, Shikui Wu, Lijun Sun, Huimin Xia, Yunxia Bai, Huiwen Zhang. Integrated serum pharmacochemistry and network pharmacology analyses reveal the bioactive metabolites and potential functional mechanism of Piper longum L. in the treatment of gastric ulcer in rats[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(2): 156-168.

图/表 8

Figure 1. Protective effects of PL on the stomach and the haematoxylin and eosin-stained gastric tissue micrographs: normal control group (A, E, I), ulcer control group (B, F, J), ranitidine group (C, G, K), and PL group (D, H, L).

Figure 2. Analysis of target genes and potential pathways of PL in GU treatment based on network pharmacology and molecular docking. (A) Venn diagram of target genes of active components and genes associated with GU; (B) GO-enriched bubble map of PL target genes associated with GU; (C) KEGG bubble enrichment of PL target genes associated with GU; (D) Network diagram of active components of PL-GU; (E) A Degree distribution map of the PL target protein interaction network associated with GU; (F) Molecular docking of sesamin (1) and piperine (2).

Figure 3. The typical total-ion chromatograms (TICs) of blank and drug-containing serum samples. (A) drug-containing serum samples "+"; (B) drug-containing serum samples "–"; (C) blank serum "+"; (D) blank serum "–".

Table 1. Mass spectra properties of the absorbed components and their tentative identification results.

Figure 4. Structures of the absorbed components in rat serum after oral administration of PL products.

Table 2. Mass spectra properties of the metabolized components and their tentative identification results.

Figure 5. The extract ion chromatograms of metabolites in the plasma of rats (The upper and lower extract peaks were represented to dosed plasma and blank plasma).

Figure 6. The way that the compounds are metabolized in rat serum after oral administration of PL products.

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基于血清药物化学和网络药理学的荜茇抗胃溃疡药效物质基础分析

Integrated serum pharmacochemistry and network pharmacology analyses reveal the bioactive metabolites and potential functional mechanism of Piper longum L. in the treatment of gastric ulcer in rats

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