Mechanism of Portulaca oleracea L. in the treatment of non-alcoholic fatty liver disease based on data analysis
-
摘要:
目的 探讨马齿苋治疗非酒精性脂肪肝(non-alcoholic fatty liver disease, NAFLD)的分子基础与作用机制。 方法 通过TCMSP、Drug Bank、Uniprot等数据库，筛选出马齿苋的有效活性成分及其作用靶点。利用Drugbank、OMMI、GeneCards等数据库找出与NAFLD相关的基因靶点，最后取两者交集。最后利用DAVID数据库进行KEGG和GO富集分析。 结果 通过筛选得出马齿苋有10种有效成分，其中槲皮素、山奈酚、木犀草素、β-谷固醇、β-胡萝卜素是主要活性成分。共得到85个关键交集靶点，其中肿瘤坏死因子(TNF)、半胱氨酸天冬氨酸蛋白酶(CASP)、Ser/Thr蛋白激酶(AKT1)、炎症趋化因子(CCL2)为重要靶点。DAVID富集分析显示，GO功能分析主要参与调控炎症反应(P < 0.001)、细胞缺氧(P < 0.001)、凋亡(P < 0.001)、相似蛋白质结合(P < 0.001)、蛋白质二聚化活性(P < 0.001)、细胞因子活性(P < 0.001)等方面。KEGG富集分析主要与TNF(P < 0.001)、细胞凋亡(P < 0.001)、TLR(P < 0.001)、NF-κB(P < 0.001)等信号通路有关。 结论 本研究通过初步探讨马齿苋治疗NAFLD的潜在靶点和相关信号通路，为进一步深入揭示其作用机制及开发马齿苋功能性食品提供了理论依据。 Abstract:Objective To explore the molecular mechanism of Portulaca oleracea L. in the treatment of non-alcoholic fatty liver (NAFLD). Methods With the use of the TCMSP and Drug Bank and Uniprot database, the effective activity of Portulaca oleracea L. was screened out ingredients and their potential targets. The Drug bank, OMMI and GeneCards databases were used in identifying gene targets related to NAFLD and intersection targets. Finally, the DAVID database was used in conducting KEGG and GO enrichment analyses for determining the potential signal pathways of Portulaca oleracea L. for NAFLD treatment. Results Portulaca oleracea L. had 10 effective active ingredients, of which quercetin, kaempferol, luteolin, β-sitosterol and β-carotene were the main active ingredients. A total of 85 key targets were identified after matching with NAFLD gene targets, and tumor necrosis factor (TNF), cysteine aspartic protease, Ser/Thr protein kinase and inflammatory chemokines were found to be important targets. DAVID enrichment analysis showed that GO functional analysis were mainly involved in inflammation (P < 0.001), cell hypoxia (P < 0.001), and apoptosis (P < 0.001), identical protein binding (P < 0.001), protein polymerisation activity (P < 0.001) and cytokine activity (P < 0.001). KEGG enrichment analysis mainly related to TNF (P < 0.001), apoptosis (P < 0.001), TLR (P < 0.001) and NF-κB signal pathway (P < 0.001). Conclusion This study preliminarily explores the potential targets and related signal pathways of Portulaca oleracea L. in NAFLD treatment and provides a theoretical basis for further revealing mechanisms for developing the functional food of Portulaca oleracea L. -
表 1 马齿苋的10种有效活性成分
分子ID 英文名 中文名 分子量 OB值(%) DL值 MOL001439 arachidonic acid 花生四烯酸 304.52 45.57 0.2 MOL003578 Cycloartenol 环烯醇 426.80 38.69 0.78 MOL002773 beta-carotene β-胡萝卜素 536.96 37.18 0.58 MOL000358 beta-sitosterol β-谷固醇 414.79 36.91 0.75 MOL000422 kaempferol 山奈酚 286.25 41.88 0.24 MOL005100 5, 7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one 5, 7-二羟基-2-(3-羟基-4-甲氧基苯基)苯并四氢吡喃-4-酮 302.30 47.74 0.27 MOL000006 luteolin 木犀草素 286.25 36.16 0.25 MOL006657 isobetanidin 异黄烷素 388.36 59.73 0.52 MOL006662 isobetanin_qt 异单宁_qt 388.36 30.16 0.52 MOL000098 quercetin 槲皮素 302.25 46.43 0.28 
下载: 导出CSV
表 2 马齿苋治疗NAFLD潜在靶点的GO功能分析
GO分析 ID 条目 靶点数 P值 生物过程(BP) 0006954 炎症反应 21 < 0.001 0071456 细胞缺氧反应 13 < 0.001 0043066 凋亡负调控 21 < 0.001 分子功能(CC) 0005615 细胞外空间 37 < 0.001 0005829 胞质溶胶 36 < 0.001 0009897 质膜外侧 10 < 0.001 细胞组成(MF) 0042802 相同的蛋白质结合 22 < 0.001 0042803 蛋白质均二聚活性 20 < 0.001 0005125 细胞因子活性 9 < 0.001
下载: 导出CSV
表 3 马齿苋治疗NAFLD相关信号通路的KEGG分析
ID 条目 靶点数 P值 hsa04668 TNF信号通路 20 < 0.001 hsa05200 癌症通路 31 < 0.001 hsa04932 非酒精性脂肪肝病(NAFLD) 19 < 0.001 hsa04210 细胞凋亡 12 < 0.001 hsa04620 TLR信号通路 14 < 0.001 hsa04064 NF-κB信号通路 13 < 0.001
下载: 导出CSV
-
[1] ESTES C, RAZAVI H, LOOMBA R, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease[J]. Hepatology, 2018, 67(1): 123-133. doi: 10.1002/hep.29466 [2] YOUNOSSI Z, ANSTEE Q M, MARIETTI M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(1): 11-20. doi: 10.1038/nrgastro.2017.109 [3] COBBINA E, AKHLAGHI F. Non-alcoholic fatty liver disease (NAFLD)-pathogenesis, classification, and effect on drug metabolizing enzymes and transporters[J]. Drug Metab Rev, 2017, 49(2): 197-211. doi: 10.1080/03602532.2017.1293683 [4] FANG Y L, CHEN H, WANG C L, et al. Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From "two hit theory" to "multiple hit model"[J]. World J Gastroenterol, 2018, 24(27): 2974-2983. doi: 10.3748/wjg.v24.i27.2974 [5] SAROSIEKJEZNACH-STEINHAGEN A, OSTROWSKA J, CZERWONOGRODZKA-SENCZYNA A, et al. Non-alcoholic liver disease-diagnosis and treatment[J]. Pol Merkur Lekarski, 2017, 43(257): 237-242. http://europepmc.org/abstract/MED/29231919 [6] CHEN D, YAO JN, LIU T, et al. Research and application of Portulaca oleracea in pharmaceutical area[J]. Chin Herb Med, 2019, 11(2): 150-159. doi: 10.1016/j.chmed.2019.04.002 [7] RAMADAN B K, SCHAALAN M F, TOLBA A M. Hypoglycemic and pancreatic protective effects of Portulaca oleracea extract in alloxan induced diabetic rats[J]. BMC Complement Altern Med, 2017, 17(1): 37. doi: 10.1186/s12906-016-1530-1 [8] SHANKER N, DEBNATH S. Impact of purslane (Portulaca oleracea L. )leaves extract to enhance the anti-oxidant potential of edible oils during heating[J]. J Oleo Sci, 2019, 68(4): 321-328. doi: 10.5650/jos.ess18126 [9] ZHENG G, MO F, LING C, et al. Portulaca oleracea L. alleviates liver injury in streptozotocin-induced diabetic mice[J]. Drug Des Devel Ther, 2017, 12: 47-55. doi: 10.2147/DDDT.S121084 [10] FARKHONDEH T, SAMARGHANDIAN S, AZIMI-NEZHAD M, et al. The hepato-protective effects of portulaca oleracea L. extract: Review[J]. Curr Drug Discov Technol, 2019, 16(2): 122-126. doi: 10.2174/1570163815666180330142724 [11] LUO T T, LU Y, YAN S K, et al. Network pharmacology in research of chinese medicine formula: methodology, application and prospective[J]. Chin J Integr Med, 2020, 26(1): 72-80. doi: 10.1007/s11655-019-3064-0 [12] SOROKINA M, STEINBECK C. Review on natural products databases: where to find data in 2020[J]. J Cheminform, 2020, 12(1): 20. doi: 10.1186/s13321-020-00424-9 [13] MIAO L, TAO H, PENG Y, et al. The anti-inflammatory potential of Portulaca oleracea L. (purslane) extract by partial suppression on NF-κB and MAPK activation[J]. Food Chem, 2019, 290(4): 239-245. http://www.onacademic.com/detail/journal_1000042276908999_424a.html [14] FARKHONDEH T, SAMARGHANDIAN S. The therapeutic effects of Portulaca oleracea L. in hepatogastric disorders[J]. Gastroenterol Hepatol, 2019, 42(2): 127-132. doi: 10.1016/j.gastrohep.2018.07.016 [15] 张超, 李昌平, 聂娇. 槲皮素对非酒精性脂肪肝模型大鼠硬脂酰辅酶A去饱和酶1和肝X受体α表达的影响[J]. 中国药理学与毒理学杂志, 2017, 31(8): 807-814. doi: 10.3867/j.issn.1000-3002.2017.08.005 [16] YANG H, YANG T, HENG C, et al. Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db/db mice[J]. Phytother Res, 2019, 33(12): 3140-3152. doi: 10.1002/ptr.6486 [17] REN J, LU Y, QIAN Y, et al. Recent progress regarding kaempferol for the treatment of various diseases[J]. Exp Ther Med, 2019, 18(4): 2759-2776. http://www.ncbi.nlm.nih.gov/pubmed/31572524 [18] ZHU Y, LIU R, SHEN Z, et al. Combination of luteolin and lycopene effectively protect against the "two-hit" in NAFLD through Sirt1/AMPK signal pathway[J]. Life Sci, 2020, 256: 117990. doi: 10.1016/j.lfs.2020.117990 [19] FRIEDMAN S L, NEUSCHWANDER-TETRI B A, RINELLA M, et al. Mechanisms of NAFLD development and therapeutic strategies[J]. Nat Med, 2018, 24(7): 908-922. doi: 10.1038/s41591-018-0104-9 -
点击查看大图
图(2) / 表(3)
计量
- 文章访问数: 125
- HTML全文浏览量: 87
- PDF下载量: 4
- 被引次数: 0
