黄杜鹃根化学成分及镇痛网络药理学研究

doi:10.16088/j.issn.1001-6600.2023062003

摘要/Abstract

摘要： 研究黄杜鹃根的化学成分及镇痛的作用机制,为揭示黄杜鹃根镇痛药效物质基础提供理论依据。本文运用大孔树脂、硅胶柱色谱和制备色谱对黄杜鹃根进行化学成分分离,利用¹H NMR、¹³C NMR、MS等波谱数据鉴定化合物的结构;综合成分结果联合网络药理学分析黄杜鹃根镇痛作用的主要靶点和关键通路。结果表明,共分离鉴定得到9个化合物:3个二氢查尔酮类化合物,分别是4’-O-甲基根皮苷(1)、根皮素4’-O-葡萄糖苷(2)、根皮素(3);3个三萜类化合物,分别是齐墩果酸(4)、白桦酸(5)、熊果酸(6);3个脂肪酸类化合物,分别是棕榈酸(7)、硬脂酸(8)、山嵛酸(9);网络药理学结果表明,分离得到的9个化合物主要作用在MAPK1、MAPK3、MAPK8、IL-6、CASP3等靶点,通过调控花生四烯酸代谢、炎症介质对色氨酸通道等信号通路发挥抗炎镇痛作用。该研究初步阐明黄杜鹃根的化学成分及潜在的作用机制,为筛选黄杜鹃根镇痛的药效成分及深入阐明作用机制提供了理论依据。

关键词: 黄杜鹃根, 化学成分, 分离鉴定, 网络药理学, 镇痛

Abstract: In order to provide theoretical basis for the material basis of analgesic effect, the chemical constituents and analgesic mechanism of Rhododendron molle G. Don root were studied. Component separation was carried out using macroporous resin, silica gel column chromatography and preparative chromatography, and the compound structures were identified by ¹H NMR, ¹³C NMR and UPLC-QTOF-MS/MS. And the main targets and key pathways of components were analyzed by network pharmacology method. Nine compounds, including three dihydrochalcones, three triterpenoids and three fatty acids, were isolated and identified. The results of network pharmacology showed that 9 compounds mainly acted on MAPK1, MAPK3, MAPK8, IL-6 and CASP3 targets, regulated arachidonic acid metabolism and inflammatory mediators in tryptophan channels, and exerted anti-inflammatory and analgesic effects. In this study, the chemical constituents and potential mechanism were clarified, which provided a scientific theoretical basis for screening of analgesic substance of the root of Rhododendron molle G. Don.

Key words: Rhododendron molle G. Don root, chemical constituents, isolation and identification, network pharmacology, analgesic

中图分类号: R917

吴慧婕, 黄晓梅, 梁芬兰, 黄欣, 雷梦颖, 周艳林, 刘雪梅, 王刚. 黄杜鹃根化学成分及镇痛网络药理学研究[J]. 广西师范大学学报（自然科学版）, 2024, 42(1): 147-155.

WU Huijie, HUANG Xiaomei, LIANG Fenlan, HUANG Xin, LEI Mengying, ZHOU Yanlin, LIU Xuemei, WANG Gang. Identification of Chemical Consituents and Network Pharmacology Research of Rhododendron molle G. Don Root[J]. Journal of Guangxi Normal University(Natural Science Edition), 2024, 42(1): 147-155.

参考文献

[1] HAN M H, KIM K Y. Research progress on the identification and pharmacological activity of the active components of the Rhododendron species[J]. Biosciences Biotechnology Research Asia, 2021,18(3): 543-565. DOI: 10.13005/bbra/2939.
[2] 王刚, 邹准, 周艳林, 等.瑶药材搜山虎的化学成分研究[J]. 中草药, 2021, 52(21): 6466-6472. DOI: 10.7501/j.issn.0253-2670.2021.21.003.
[3] 刘义梅, 张乐华, 陈士林, 等.ITS2序列鉴别10种杜鹃属药用植物[J]. 中药材, 2011, 34(9): 1342-1345. DOI: 10.13863/j.issn1001-4454.2011.09.010.
[4] LI C J, WANG L Q, CHEN S N, et al. Diterpenoids from the fruits of Rhododendron mole[J]. Journal of Natural Products, 2000, 63(9): 1214-1217. DOI: 10.1021/np000009e.
[5] DENG X Q, LUO Y, LU M Q, et al. Unraveling the mechanism of Zhibaidihuang decoction against IgA nephropathy using network pharmacology and molecular docking analyses[J]. The Tohoku Journal of Experimental Medicine, 2023, 259(1): 37-47. DOI: 10.1620/tjem.2022.J088.
[6] SAFRAN M, DALAH I, ALEXANDER J, et al. GeneCards version 3: the human gene integrator[J]. Database, 2010, 2010:baq020. DOI: 10.1093/database/baq020.
[7] PIÑNERO J, RAMÍREZ-ANGÜITA J M, SAÜCH-PITARCH J, et al. The DisGeNET knowledge platform for disease genomics: 2019 update[J]. Nucleic Acids Research, 2020, 48(D1): D845-D855. DOI: 10.1093/nar/gkz1021.
[8] LIU X F, OUYANG S S, YU B, et al. PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach[J]. Nucleic Acids Research, 2010, 38(S2): 609-614. DOI: 10.1093/nar/gkq300.
[9] DAINA A, MICHIELIN O, ZOETE V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules[J]. Nucleic Acids Research, 2019, 47(W1): W357-W364. DOI: 10.1093/nar/gkz382.
[10] DONCHEVA N T, MORRIS J H, GORODKIN J, et al. Cytoscape StringApp: network analysis and visualization of proteomics data[J]. Journal of Proteome Research, 2019, 18(2): 623-632. DOI: 10.1021/acs.jproteome.8b00702.
[11] SZKLARCZYK D, GABLE A L, LYON D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Research, 2019, 47(D1): D607-D613. DOI: 10.1093/nar/gky1131.
[12] MABRY T J, SAKAKIBARA M, KING B. Asebotin and its aglucone from three species of Rhododendron[J]. Phytochemistry, 1975, 14(5/6): 1448-1450. DOI: 10.1016/s0031-9422(00)98660-6.
[13] KUBO I, MATSUMOTO A. Isolation of an insect-antifeedant, phloretin 4’-O-β-D-glucopyranoside, by rotation locular counter-current chromatography and determination of its preferred conformation insolution by nuclear magnetic resonance analysis[J]. Chemical and Pharmaceutical Bulletin, 1985, 33(9): 3817-3820. DOI: 10.1248/cpb.33.3817.
[14] 高毓涛, 杨秀伟, 艾铁民. 狗肝菜的化学成分研究[J]. 中草药, 2007, 38(1): 14-17. DOI: 10.3321/j.issn:0253-2670.2007.01.005.
[15] 付晓丽, 张立伟, 林文翰, 等. 满山红化学成分的研究[J]. 中草药, 2010, 41(5): 704-707.
[16] 戚进, 胡正芳, 刘志军, 等. 夏枯草的化学成分[J]. 中国天然药物, 2009, 7(6): 421-424. DOI: 10.3724/SP.J.1009.2009.00421.
[17] 张扩, 赵明, 王美娇, 等. 细叶杜香叶中三萜类化学成分研究[J]. 中草药, 2018, 49(6): 1250-1254. DOI: 10.7501/j.issn.0253-2670.2018.06.003.
[18] 郭盛, 段金廒, 赵金龙, 等. 酸枣果肉资源化学成分研究[J]. 中草药, 2012, 43(10): 1905-1909.
[19] 黄雪峰, 罗俊, 张勇, 等. 石刁柏的化学成分[J]. 中国天然药物, 2006,(3): 181-184.
[20] 卢文杰, 牙启康, 陈家源, 等. 黑草的化学成分研究[J]. 中草药, 2012, 43(6): 1079-1081.
[21] 魏丽娜, 赵静, 罗仓学, 等. 根皮素的制备、结构修饰及生理活性研究进展[J]. 食品与发酵工业, 2019,45(17): 278-285. DOI: 10.13995/j.cnki.11-1802/ts.020079.
[22] MAIA J L, LIMA-JÚNIOR R C P, MELO C M, et al. Oleanolic acid, a pentacyclic triterpene attenuates capsaicin-induced nociception in mice: possible mechanisms[J]. Pharmacological Research, 2006, 54(4): 282-286. DOI: 10.1016/j.phrs.2006.06.003.
[23] 王翔, 阎昭, 王旭, 等. 熊果酸纳米脂质体的镇痛作用和抗炎活性[J]. 山东医药, 2013, 53(29): 31-32,35. DOI: 10.3969/j.issn.1002-266X.2013.29.011.
[24] 贾忠建, 李国强. 黄花杜鹃化学成分研究[J]. 中草药, 1996, 27(5): 262-265.
[25] 冯夏, 赵善欢. 黄杜鹃有效成分作用机制的初步研究[J]. 广东农业科学, 1990(3): 40-41. DOI: 10.16768/j.issn.1004-874x.1990.03.015.
[26] 程东美, 胡美英, 张志祥. 黄杜鹃不同部位有效成分含量及对害虫拒食作用的研究[J]. 华南农业大学学报, 2000, 21(2): 25-27. DOI: 10.3969/j.issn.1001-411X.2000.02.008.
[27] RECIO M C, GINER R M, MÁÑEZ S, et al. Investigations on the steroidal anti-inflammatory activity of triterpenoids from Diospyros leucomelas[J]. Planta Medica, 1995, 61(1): 9-12. DOI: 10.1055/s-2006-957988.
[28] SHAO J P, XU R Y, LI M, et al. Glucocorticoid receptor inhibit the activity of NF-κB through p38 signaling pathway in spinal cord in the spared nerve injury rats[J]. Life Sciences, 2018, 208: 268-275. DOI: 10.1016/j.lfs.2018.07.026.
[29] CRONIN S J F, RAO S, TEJADA M A, et al. Phenotypic drug screen uncovers the metabolic GCH1/BH4 pathway as key regulator of EGFR/KRAS-mediated neuropathic pain and lung cancer[J]. Science Translational Medicine, 2022, 14(660): abj1531. DOI: 10.1126/scitranslmed.abj1531.
[30] MARTIN L J, SMITH S B, KHOUTORSHY A, et al. Epiregulin and EGFR interactions are involved in pain processing[J]. Journal of Clinical Investigation, 2017,127(9):3353-3366. DOI: 10.1172/JCI87406.
[31] WANG Y P, GAO W Q, SHI X Y, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin[J]. Nature, 2017, 547(7661): 99-103. DOI: 10.1038/nature22393.
[32] ROSE-JOHN S, JENKINS B J, GARBERS C, et al. Targeting IL-6 trans-signalling: past, present and future prospects[J]. Nature Reviews Immunology, 2023, 23(10):666-681. DOI: 10.1038/s41577-023-00856-y.
[33] 谭娟, 黄微, 陈善龙, 等. 熊果酸衍生物与查耳酮缀合物的合成及抗炎活性[J]. 药学学报, 2016, 51(6): 938-946. DOI: 10.16438/j.0513-4870.2015-1162.
[34] 成慧娟, 吕小平. PI3K-AKT信号转导通路与炎症性肠病关系的研究进展[J]. 广东医学, 2014, 35(2): 297-299. DOI: 10.13820/j.cnki.gdyx.2014.02.056.
[35] FANG Y, PENG X L, BU H L, et al. Chemokine CXCL10 regulates pain behaviors via PI3K-AKT signaling pathway in mice[J]. Neuropeptides, 2022, 93: 102243. DOI: 10.1016/j.npep.2022.102243.
[36] 刘婷莉, 郭元彪, 邓艺, 等. Hp感染性胃溃疡患者炎症活动度与血清TNF-α、IL-17表达水平的相关性[J]. 热带医学杂志, 2021, 21(9): 1154-1157. DOI: 10.3969/j.issn.1672-3619.2021.09.015.
[37] 王丽娜, 罗竹, 黄小朵, 等. 基于TNF-α/NF-κB信号通路对IPF炎症与焦亡的探讨[J]. 临床医药文献电子杂志, 2020, 7(46): 190-191. DOI: 10.16281/j.cnki.jocml.2020.46.131.
[38] YE Y J, ZHONG X, LI N, et al. Protective effects of liraglutide on glomerular podocytes in obese mice by inhibiting the inflammatory factor TNF-α-mediated NF-κB and MAPK pathway[J]. Obesity Research and Clinical Practice, 2019, 13(4): 385-390. DOI: 10.1016/j.orcp.2019.03.003.
[39] JI R R, NACKLEY A, HUH Y, et al. Neuroinflammation and central sensitization in chronic and widespread pain[J]. Anesthesiology, 2018, 129(2): 343-366. DOI: 10.1097/ALN.0000000000002130.
[40] 曾光, 陈芳, 邵峰, 等. 熊果酸对大鼠CIA模型关节TNF-α, IL-17, PGE2表达的影响[J]. 湖南中医药大学学报, 2018, 38(1): 13-16. DOI: 10.3969/j.issn.1674-070X.2017.01.004.
[41] 邓莉. 齐墩果酸对肿瘤坏死因子-α诱导的成纤维样滑膜细胞炎症因子表达的影响及其机制研究[D]. 泸州:西南医科大学, 2017.

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