基于网络药理学与分子对接的蛋珍油防治放射性食管炎多靶点机制研究

Multi-targeted mechanisms of Danzhen oil against radiation esophagitis based on network pharmacology and molecular docking

摘要

目的 基于网络药理学与分子对接技术, 系统探究蛋珍油治疗放射性食管炎 (RE) 的多靶点作用机制。 方法 通过检索中国知网获取蛋珍油的活性成分, 基于 OB≥30%、DL≥0.01 标准进行成分筛选, 构建“药物成分靶点疾病” 相互作用网络。 利用 STRING 数据库构建蛋白质蛋白质相互作用网络, 筛选核心靶点, 并进行 GO 功能与 KEGG 通路富集分析。 进一步通过分子对接验证核心成分与关键靶点的结合活性。 结果 共筛选出邻苯二甲酸二丁酯 (Degree = 52) 等 7 个关键活性成分。 蛋白质蛋白质相互作用网络分析获得 109 个节点, 经两次筛选确定 GSK3B、 EGFR、 PTGS2 等 12 个核心靶点。GO / KEGG 富集分析显示, 这些靶点显著富集于 IL-17 信号通路、TNF 信号通路 (P<0.01) 及细胞凋亡调控等 23 条生物学过程。 分子对接验证表明, 核心成分与靶点的结合能为-30.1 ~ -20.1 kJ / mol, 其中 Proline 与 ACE 的结合能最低 ( -30.1 kJ/ mol); 邻苯二甲酸二丁酯与 PTGS2 的结合能为-26.8 kJ/ mol, 同样表现出强结合活性。 结论 本研究首次揭示蛋珍油通过 “多成分多靶点多通路” 协同作用调控炎症反应的分子机制, 为蛋珍油临床应用提供了理论依据。 后续仍需开展体内外实验进一步验证其药理作用。

Abstract

Objective To systematically investigate the multi-targeted mechanisms of Danzhen oil in treating radiation esophagitis based on network pharmacology and molecular docking. Methods Active components of Danzhen oil were retrieved from the China National Knowledge Infrastructure. Component screening was performed based on the criteria of OB≥30% and DL≥0.01, and a “drug component target disease” interaction network was constructed. The STRING database was used to build a protein-protein interaction (PPI) network, from which core targets were screened, followed by GO functional annotation and KEGG pathway enrichment analysis. Molecular docking was further performed to validate the binding affinity between core components and key targets. Results A total of 7 key active components, including dibutyl phthalate (Degree= 52), were identified. PPI network analysis yielded 109 nodes, and 12 core targets including GSK3B, EGFR, and PTGS2 were determined through two rounds of screening. GO/ KEGG enrichment analysis showed that these targets were significantly enriched in 23 biological processes, including the IL-17 signaling pathway, TNF signaling pathway (P<0.01), and regulation of apoptosis. Molecular docking verification indicated that the binding energies between core components and targets ranged from -30.1 to -20.1 kJ/ mol, with Proline exhibiting the lowest binding energy with ACE (-30.1 kJ/ mol) and dibutyl phthalate binding to PTGS2 with a binding energy of -26.8 kJ/ mol. Conclusion This study reveals for the first time the molecular mechanism by which Danzhen oil regulates inflammatory responses through synergistic “multi-component, multi-target, multi-pathway” actions, providing a theoretical basis for its clinical application. Further in vitro and in vivo experiments are required to validate its pharmacological effects.

关键词

蛋珍油 / 食管炎 / 分子对接模拟 / 蛋白质相互作用图谱 / 肿瘤坏死因子 / 白细胞介素 17 / 网络药理学 / 药物作用机制

Key words

Danzhen oil / esophagitis / molecular docking simulation / protein interaction maps / tumor necrosis factor / interleukin-17 / network pharmacology / drug mechanisms

参考文献

[1] 郭金, 史恒军. 蛋珍油治疗放射性食管炎 60 例临床观察[J]. 现代肿瘤医学, 2016, 24(13): 2085-2087. DOI: 10.3969/j.issn.1672-4992.2016.13.021.

[2] YU Y L, ZHENG H Y, LIU L Y, et al. Predicting severe radiation esophagitis in patients with locally advanced esophageal squamous cell carcinoma receiving definitive chemoradiotherapy: construction and validation of a model based in the clinical and dosimetric parameters as well as inflammatory indexes[J]. Front Oncol, 2021, 11: 687035. DOI: 10.3389/fonc.2021.687035.

[3] TIAN Y D, GUO Y, KE Y, et al. Determining the efficacy of vitamin B₁₂ mixed oral liquid in the treatment of radiation-induced esophagitis [J]. Oncol Transl Med, 2019, 5(5): 223-228. DOI: 10.1007/s10330-019-0367-7.

[4] WANG Z Y, SHEN L, WANG J, et al. Immunostimulatory effect of a composition isolated from white peony root oral liquid in the treatment of radiation-induced esophagitis[J]. Exp Ther Med, 2013, 6(4): 1010-1014. DOI: 10.3892/etm.2013.1227.

[5] SUGIYAMA K, HIRAI K, SUYAMA Y, et al. Impact of once-daily versus multiple-daily dosing of gentamicin on the incidence of acute kidney injury in patients treated with synergistic combinations of antibiotics[J]. J Pharm Health Care Sci, 2024, 10(1): 40. DOI: 10.1186/s40780-024-00360-y.

[6] 张洁洁. 利多卡因致过敏反应 2 例报道[J]. 重庆医学, 2007, 36(2): 98. DOI: 10.3969/j.issn.1671-8348.2007.02.053.

[7] 陈少泽, 雷雨晨, 黄思琦, 等. 蛋黄油中脂肪酸成分分析及抗氧化作用研究[J]. 化工技术与开发, 2022, 51(1): 30-33. DOI: 10.3969/j.issn.1671-9905.2022.01.008.

[8] 周晓阳, 王丽萍, 李珊, 等. 改良蛋珍油治疗急性放射性食管炎的临床效果[J]. 临床医学研究与实践, 2024, 9(17): 129-132. DOI: 10.19347/j.cnki.2096-1413.202417032.

[9] PEI J Y, WANG Y, ZOU X G, et al. Extraction, purification, bioactivities and application of matrix proteins from pearl powder and nacre powder: a review[J]. Front Bioeng Biotechnol, 2021, 9: 649665. DOI: 10.3389/fbioe.2021.649665.

[10] SONG Y L, CHEN W Y, FU K, et al. The application of pearls in traditional medicine of China and their chemical constituents, pharmacology, toxicology, and clinical research[J]. Front Pharmacol, 2022, 13: 893229. DOI: 10.3389/fphar.2022.893229.

[11] LIU S Y, HU L L, WANG S J, et al. Administration of modified Gegen Qinlian decoction for hemorrhagic chronic radiation proctitis: a case report and review of literature[J]. World J Clin Cases, 2023, 11(5): 1129-1136. DOI: 10.12998/wjcc.v11.i5.1129.

[12] HUNG Y C, HSIEH S C, HOU S R, et al. In vivo evaluation of PVP-gelatin-chitosan composite blended with egg-yolk oil for radiodermatitis[J]. Appl Sci, 2021, 11(21): 10290. DOI: 10.3390/app112110290.

[13] CHEN X, PENG L H, CHEE S S, et al. Nanoscaled pearl powder accelerates wound repair and regeneration in vitro and in vivo[J]. Drug Dev Ind Pharm, 2019, 45(6): 1009-1016. DOI: 10.1080/03639045.2019.1593436.

[14] 杨建刚, 史恒军, 任秦有, 等. 蛋珍油保留灌肠治疗放射性肠炎 60 例[J]. 现代肿瘤医学, 2013, 21(7): 1621-1623. DOI: 10.3969/j.issn.1672-4992.2013.07.62.

[15] 赵参军, 马力天, 王昕洁, 等. 院方制剂新法蛋珍油中所含成分的液质联用解析鉴定[J]. 现代肿瘤医学, 2020, 28(11): 1815-1820. DOI: 10.3969/j.issn.1672-4992.2020.11.002.

[16] 杨乾龙, 王静, 南韦肖, 等. 半胱氨酸的合成代谢及其生物学作用研究进展[J]. 饲料工业, 2022, 43(7): 19-22. DOI: 10.13302/j.cnki.fi.2022.07.003.

[17] HSIN K Y, GHOSH S, KITANO H. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology[J]. PLoS One, 2013, 8(12): e83922. DOI: 10.1371/journal.pone.0083922.

[18] 张莉, 单保恩, 沈莉, 等. 中医药治疗放射性食管炎之现状[J]. 上海中医药杂志, 2007, 41(5): 37-39. DOI: 10.16305/j.1007-1334.2007.05.016.

[19] 朱惠平, 张全安, 苏沐. 姜黄素对人前列腺癌细胞放疗增敏作用的实验研究[J]. 中国现代医学杂志, 2014, 24(18): 27-30.

[20] 王松, 王婷, 蒋刚. 中药调控 Nrf2 通路发挥肿瘤放射治疗增敏作用的研究进展[J]. 中国药业, 2020, 29(15): 1-5. DOI: 10.3969/j.issn.1006-4931.2020.15.001.

[21] 赵志力, 付小兵, 李旭升, 等. 防疤烧伤膏对烫伤创面的促愈合效应[J]. 中国临床康复, 2003, 7(11): 1642-1643. DOI: 10.3321/j.issn:1673-8225.2003.11.009.

[22] 王青, 吴显文, 何健, 等. 基于数据挖掘的中医药外治放射性皮炎的用药规律研究[J]. 中国医药导报, 2020, 17(15): 163-167. DOI: 10.20047/j.issn1673-7210.2020.15.042.

[23] 蒋新云. 复方蛋黄油在放射治疗中皮肤损伤的应用[J]. 医学信息, 2008, 21(4): 554-555. DOI: 10.3969/j.issn.1006-1959.2008.04.061.

[24] 曹继娟. 珍珠粉与维生素B₁₂ 在宫颈癌患者放疗性皮炎中的护理体会及对色素沉着影响 [J]. 中国医疗美容, 2016, 6(6): 77-79. DOI: 10.19593/j.issn.2095-0721.2016.06.038.

[25] DRISHYA S, DHANISHA S S, RAGHUKUMAR P, et al. Amomum subulatum fruits protect against radiation-induced esophagitis by regulating antioxidant status and inflammatory responses[J]. Food Res Int, 2023, 174(Pt 1): 113582. DOI: 10.1016/j.foodres.2023.113582.

[26] 史翱宇. 改良蛋珍油对大鼠急性放射性食管炎黏膜损伤防治作用的实验研究[D]. 咸阳: 陕西中医药大学, 2018.

[27] 杨婧兴, 赵妍, 陈陆泉, 等. 基于网络药理学探究黄芩治疗慢性鼻窦炎的潜在作用机制[J]. 首都医科大学学报, 2024, 45(2): 252-261. DOI: 10.3969/j.issn.1006-7795.2024.02.013.

[28] 畅佳丽, 邱菊. 生物节律对 ILC3 / Th17 介导的肠道免疫应答的调控[J]. 四川大学学报(医学版), 2022, 53(1): 15-19. DOI: 10.12182/20220160502.

[29] 贺毅, 王海霞, 刘敏, 等. 基于分子对接和表面等离子体共振技术筛选 IL-15Rα 小分子抑制剂[J]. 生理学报, 2023, 75(5): 623-628. DOI: 10.13294/j.aps.2023.0064.

[30] 朱云, 郭景华, 史恒军, 等. 蛋珍油对家兔食管急性放射损伤中氧化损伤以及炎性因子表达的影响[J]. 现代肿瘤医学, 2008, 16(8): 1278-1280.

[31] SCHMIDT T, LUEBBE J, PAUST H J, et al. Mechanisms and functions of IL-17 signaling in renal autoimmune diseases[J]. Mol Immunol, 2018, 104: 90-99. DOI: 10.1016/j.molimm.2018.09.005.

[32] 永胜, 郭玉静, 陈晓晨, 等. IL-17 信号通路在高原低氧诱导小鼠脾脏炎症反应的作用机制[J]. 四川大学学报(医学版), 2024, 55(1): 118-124. DOI: 10.12182/20240160208.

[33] WANG K, ZHANG J, ZHOU X Y, et al. Immune cell involvement in ulcer repair in radiation esophagitis and its role in the TGF-β1 / p38MAPK/ FN axis (Review)[J]. Mol Clin Oncol, 2025, 23(6): 109. DOI: 10.3892/mco.2025.2904.

基金资助

陕西省重点研发计划项目(2024SF-YBXM-459)

陕西省中医药管理局项目(SZY-KJCYC-2025-LC-003)

陕西省自然科学基础研究计划项目(2025JC-YBMS-868)

中医药科技创新计划项目(2025-CXRC-09)