Molecular Mechanism of <i>Phedimus aizoon </i>(Linnaeus)'t Hart<i>.</i> on Anti-inflammatory Effect Based on Network Pharmacology and Molecular Docking and Experiment Research

YANG Juan; DOU Jiahong; SUN Yuelong; WANG Xiaoying; ZHOU Weiwei; ZHANG Guobin; LIU Hongxin; YANG Peilong; LI Xiumei

doi:10.13386/j.issn1002-0306.2022050178

Volume 44 Issue 4

Feb. 2023

Turn off MathJax

Article Contents

Abstract

References

Science and Technology of Food Industry > 2023 > 44(4): 12-21. > DOI: 10.13386/j.issn1002-0306.2022050178

YANG Juan, DOU Jiahong, SUN Yuelong, et al. Molecular Mechanism of Phedimus aizoon (Linnaeus)'t Hart. on Anti-inflammatory Effect Based on Network Pharmacology and Molecular Docking and Experiment Research[J]. Science and Technology of Food Industry, 2023, 44(4): 12−21. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022050178.

Citation:

PDF (9892 KB)

Molecular Mechanism of Phedimus aizoon (Linnaeus)'t Hart. on Anti-inflammatory Effect Based on Network Pharmacology and Molecular Docking and Experiment Research

1.
Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
2.
Qinghai Leshuyuan Agricultural Science and Technology Co., Ltd., Xining 810000, China

More Information

Received Date: May 16, 2022
Available Online: December 06, 2022

Graphical Abstract

Abstract

Abstract

Objective: To study the molecular mechanism of Phedimus aizoon (Linnaeus)'t Hart. on anti-inflammatory effect by network pharmacology, molecular docking, and experiment research. Methods: The potential anti-inflammatory effect ingredients and targets were acquired from TCMSP, HERB, and other databases under the screening condition of oral bioavailability ≥30%. The inflammation-related targets were collected from GeneCards, OMIM, and other databases, and the protein-protein interaction (PPI) analysis to obtain the key anti-inflammatory effect targets. Meanwhile, GO annotation and KEGG signal pathway enrichment analysis of the key targets was analyzed using the David database. Moreover, this study verified the key targets predicted by AutoDock molecular docking. The key anti-inflammatory effect ingredients of Phedimus aizoon (Linnaeus)'t Hart. were analyzed using high-performance liquid chromatography (HPLC). The anti-inflammatory effect of the key ingredients was verified on the LPS-induced RAW264.7 cell model. Results: The results showed that there were five potent components corresponding to 130 related targets, and 421 inflammation-related targets, with 22 intersection anti-inflammatory targets, among which the key targets were PPARG, EGFR, TP53, etc. β-sitosterol and gallic acid (3,4,5-trihydroxy benzoic acid) were the main ingredients that can be anti-inflammatory. GO annotation and KEGG signal pathway enrichment analysis indicated that β-sitosterol and gallic acid played an anti-inflammatory role through multiple pathways such as transcription from RNA polymerase II promoter, positive regulation of neuron apoptotic process, and response to lipopolysaccharide, etc., as well as signal pathways including pathways in cancer, hepatitis B, TNF signaling pathway, MAPK signaling pathway, and other signaling pathways. Furthermore, the molecular docking analysis revealed that the key targets had good binding affinities with the key active ingredients. β-sitosterol and gallic acid as active ingredients in Phedimus aizoon (Linnaeus)'t Hart. were analyzed by HPLC. The experimental results showed that β-sitosterol and gallic acid could significantly reduce NO content, increase the content of IL-10 (P<0.05), and play an anti-inflammatory effect. Conclusion: This study revealed that Sedum aizoon L. would play an anti-inflammatory role by regulating multiple targets and multiple pathways, which laid a foundation for the research and application of Phedimus aizoon (Linnaeus)'t, Hart.
- Phedimus aizoon (Linnaeus)'t Hart.,
- anti-inflammatory,
- pharmacodynamic components,
- network pharmacology,
- molecular docking,
- mechanism

FullText(HTML)

References (43)

References

[1]	LI M, QI Z, HAO Y, et al. New adducts of iriflophene and flavonoids isolated from Sedum aizoon L. with potential antitumor activity[J]. Molecules,2017,22:1859. doi: 10.3390/molecules22111859
[2]	南京中医药大学. 中药大辞典[M]. 上海: 上海科学技术出版社, 2006. 在线查询版:http://www.zhongyaocai360.com/zhongyaodacidian/ The Nanjing University of Chinese Medicine. Dictionary of traditional Chinese medicine[M]. Shanghai: Shanghai Science and Technology Press, 2006. Online query version: http://www.zhongyaocai360.com/zhongyaodacidian/.
[3]	谭波, 何席呈, 李婷, 等. 景天三七化学成分及药理作用研究进展[J]. 中国民族民间医药,2018,27(17):49−52. [TAN B, HE X C, LI T, et al. Research progress on chemical constituents and medical functions of Sedum aizoon L J]. Chinese Journal of Ethnomedicine and Ethnopharmacy,2018,27(17):49−52.
[4]	中国科学院中国植物志委员会. 中国植物志[M]. 北京: 科学出版社, 1984: 128 Editorial Committee of Chinese Flora. Chinese academy of sciences[M]. Beijing: Science Press, 1984: 128.
[5]	GONG J, QIU S, WENG Q, et al. Effect of different drying methods on phenolic compounds and antioxidant capacity in different fractions of Sedum aizoon L.[J]. Journal of Food Processing and Preservation, 2020, 44(9): e14723.
[6]	XU T, WANG Z, LEI T, et al. New flavonoid glycosides from Sedum aizoon L.[J]. Fitoterapia,2015,101:125−132. doi: 10.1016/j.fitote.2014.12.014
[7]	LIN Z, FANG Y, HUANG A, et al. Chemical constituents from Sedum aizoon and their hemostatic activity[J]. Pharmaceutical Biology,2014,52:1429−1434. doi: 10.3109/13880209.2014.895019
[8]	XIONG Y, YI P, DU C, et al. A new adduct of iriflophene and flavonoid from Sedum aizoon L.[J]. Biochemical Systematics and Ecology,2020,92:104119. doi: 10.1016/j.bse.2020.104119
[9]	XU F, CAO S, WANG C, et al. Antimicrobial activity of flavonoids from Sedum aizoon L. against Aeromonas in culture medium and in frozen pork[J]. Food Science & Nutrition,2019,7:3224−3232.
[10]	LIU Z, MIN C, DONG H, et al. Improvement of adventitious root formation in Sedum aizoon L. and the production of flavonoids[J]. South African Journal of Botany,2021,137:483−491. doi: 10.1016/j.sajb.2020.10.024
[11]	黄安玉. 养心草水提乙酸乙酯部位止血和抗炎活性的筛选[D]. 福州: 福建中医药大学, 2014 HUANG A Y. Study on ethyl acetate parts of hemostatic and anti-inflammatory effect of Sedum aizoon L. activity screening [D]. Fuzhou: Fujian University of Traditional Chinese Medicine, 2014.
[12]	林珠灿, 张龙, 张睿卓, 等. 基于炎症细胞模型的景天三七醋酸乙酯部位抗炎活性及其HPLC指纹图谱的研究[J]. 中国药学(英文版),2015,24(10):647−653. [LIN Z C, ZHANG L, ZHANG R Z, et al. Anti-inflammatory effect of ethyl acetate extract of Sedum aizoon L. in LPS-stimulated RAW 264.7 macrophages and its HPLC fingerprint[J]. Journal of Chinese Pharmaceutical Sciences,2015,24(10):647−653.
[13]	韩宁娟, 方欢乐, 牛睿, 等. 横根费菜不同溶剂萃取部位止痒抗炎作用研究[J]. 西北药学杂志,2018,33(4):496−499. [HAN N J, FANG H L, NIU R, et al. Study on the antipruritic and anti-inflammatory effects of different polar fractions of Sedum kamtschaticum fish[J]. Northwest Pharmaceutical Journal,2018,33(4):496−499. doi: 10.3969/j.issn.1004-2407.2018.04.018
[14]	黄美雯, 杨华杰, 周晓春, 等. 网络药理学在民族药研究中的应用与展望[J]. 中国中药杂志,2019,44:3187−3194. [HUANG M W, YANG H J, ZHOU X C, et al. Advances on network pharmacology in ethnomedicine research[J]. China Journal of Chinese Materia Medica,2019,44:3187−3194. doi: 10.19540/j.cnki.cjcmm.20190711.201
[15]	解静, 高杉, 李琳, 等. 网络药理学在中药领域中的研究进展与应用策略[J]. 中草药,2019,50:2257−2265. [XIE J, GAO S, LI L, et al. Research progress and application strategy on network pharmacology in Chinese materia medica[J]. Chinese Traditional Herbal Drugs,2019,50:2257−2265. doi: 10.7501/j.issn.0253-2670.2019.10.001
[16]	姚凤, 周清燕, 熊瑛, 等. β-谷甾醇对脂多糖诱导的小鼠急性肺损伤的保护作用研究[J]. 中国农学通报,2015,31(2):55−61. [YAO F, ZHOU Q Y, XIONG Y, et al. Protective effects of β-sitosterol on acute lung injury induced by lipopolysaccharide in mice[J]. Chinese Agricultural Science Bulletin,2015,31(2):55−61.
[17]	BUI TTHL, BUI HT, NGUYEN PT, et al. A new phenolic component from Triticum aestivum sprouts and its effects on LPS-stimulated production of nitric oxide and TNF-α in RAW 264.7 cells[J]. Phytotherapy Research,2014,28:1064−1070. doi: 10.1002/ptr.5097
[18]	黄丽华, 侯林, 薛海南, 等. 没食子酸通过拮抗脂多糖诱导的TLR4/NF-κB活化抑制RAW264.7巨噬细胞炎性反应[J]. 细胞与分子免疫学杂志,2016,12(12):1610−1614. [HUANG L H, HOU L, XUE H N, et al. Gallic acid inhibits inflammatory response of RAW264.7 macrophages by blocking the activation of TLR4/NF-κB induced by LPS[J]. Chinese Journal of Cellular and Molecular Immunolo,2016,12(12):1610−1614. doi: 10.13423/j.cnki.cjcmi.007974
[19]	杨宇钦. PPARG/FABP4信号通路介导乳腺癌增殖侵袭能力的体外研究[D]. 广州: 南方医科大学, 2020 YANG Y Q. In vitro study on proliferation and invasion of breast cancer mediated by PPARG/FABP4 signal pathway [D]. Guangzhou: Southern Medical University, 2020.
[20]	SHI S, YU G, HUANG B, et al. PPARG could work as a valid therapeutic strategy for the treatment of lung squamous cell carcinoma[J]. PPAR Research,2020,2020:2510951.
[21]	ZHU W, QIN L. GOLM1-regulated EGFR/RTK recycling is a novel target for combating HCC metastasis[J]. Science China Life Science,2017,60:98−101. doi: 10.1007/s11427-016-0311-x
[22]	袁奕清, 胡小军. 芍药甘草汤加减对急性胃溃疡患者血清炎症因子、胃黏膜表皮生长因子及受体表达的影响[J]. 世界中西医结合杂志,2021,16(1):92−95, 99. [YUAN Y Q, HU X J. Effect of modified Shaoyao Gancao decoction on the expression of serum inflammatory factors, gastric mucosal epidermal growth factor, and receptor in patients with acute gastric ulcer[J]. World Journal of Integrated Traditional and Western Medicine,2021,16(1):92−95, 99.
[23]	贺小威, 徐玲. 细胞周期相关基因CDKN2A、TP53、RB1和BRCA2在恶性肿瘤中的研究进展[J]. 现代肿瘤医学,2018,26(1):153−157. [HE X W, XU L. Advances on the role of cell cycle-related genes CDKN2A, TP53, RB1 and RBCA2 in malignancies[J]. Journal of Modern Oncology,2018,26(1):153−157. doi: 10.3969/j.issn.1672-4992.2018.01.040
[24]	何庆南. 转录因子AP-1的研究进展[J]. 国外医学: 儿科学分册,1999,26:152−155. [HE Q N. Advances in the study of activator protein-1[J]. Foreign Medical Sciences (Section of Pediatrics),1999,26:152−155.
[25]	FARKHONDEH T, MEHRPOUR O, BUHRMANN C, et al. Organophosphorus compounds and MAPK signaling pathways[J]. International Journal of Molecular Sciences,2020,21:4258. doi: 10.3390/ijms21124258
[26]	CAITLYN NGUYEN-NGO C S, ANDREW LAI, JANE C WILLCOX, et al. Anti-inflammatory effects of gallic acid in human gestational tissues in vitro[J]. Reproduction,2020,160:561−578. doi: 10.1530/REP-20-0249
[27]	DEHGHANI M A, SHANKIBA MARAM N, MOGHIMIPOUR E, et al. Protective effect of gallic acid and gallic acid-loaded Eudragit-RS 100 nanoparticles on cisplatin-induced mitochondrial dysfunction and inflammation in rat kidney[J]. Biochimica et Biophysica Acta Molecular Basis of Disease,2020,1866:165911. doi: 10.1016/j.bbadis.2020.165911
[28]	LIN F, XU L, HUANG M, et al. Beta-sitosterol protects against myocardial ischemia/reperfusion injury via targeting PPARγ/NF-κB signalling[J]. Evidence-based Complementary and Alternative Medicine,2020,2020:2679409.
[29]	LIAO P, LAI M, HSU K, et al. Identification of β-sitosterol as in vitro anti-inflammatory constituent in Moringa oleifera[J]. Journal of Agricultural and Food Chemistry,2018,66:10748−10759. doi: 10.1021/acs.jafc.8b04555
[30]	YANG Q, YU D, ZHANG Y. β-sitosterol attenuates the intracranial aneurysm growth by suppressing TNF-α-mediated mechanism[J]. Pharmacology,2019,104:303−311. doi: 10.1159/000502221
[31]	李晓宇, 何兴祥. 炎症与肿瘤的关系研究进展[J]. 广东医学,2006,27(9):1427−1428. [LI X Y, HE X X. Research progress on the relationship between inflammation and tumor[J]. Guangdong Medical Journal,2006,27(9):1427−1428. doi: 10.3969/j.issn.1001-9448.2006.09.074
[32]	辛剑, 陈辉兵, 尚艺泰. p38MAPK信号通路抑制剂对TNF-α诱导的乳腺癌细胞凋亡的影响[J]. 中国妇幼保健, 2019, 34: 1375-1379 XIN J, CHEN H B, SHANG Y T. Effects of p38MAPK signaling pathway inhibitors on TNF-α-induced apoptosis of breast cancer cells[J]. Maternal and Child Health Care of China, 2019, 34: 1375-1379.
[33]	万星, 李相国, 李修贤, 等. Beta-谷甾醇通过抑制TNF-α-NF-κB和TβR1-Smad2/3信号通路抗小鼠肝纤维化损伤[J]. 中国药理学同胞, 2020, 36: 75-80 WAN X, LI X G, LI X X, et al. Beta-sitosterol inhibits hepatic fibrosis in mice by inhibiting TNF-α-NF-κB and Tβ R1-SMad2/3 signaling pathways[J]. Chinese Pharmacology Compatriots, 2020, 36: 75-80.
[34]	SHI Y X, HUANG C, YANG Z, et al. Impact of hepatitis B virus infection on hepatic metabolic signaling pathway[J]. World J Gastroenterol,2016,22:8161−8167. doi: 10.3748/wjg.v22.i36.8161
[35]	CHEN L, DENG H, CUI H, et al. Inflammatory responses and inflammation-associated diseases in organs[J]. Oncotarget,2018,9(6):7204−7218. doi: 10.18632/oncotarget.23208
[36]	刘明. 蛋白质与配体相互作用机理的分子模拟研究[D]. 北京: 北京工业大学, 2010 LIU M. Protein and ligand with molecular modeling approaches[D]. Beijing: Beijing University of Technology, 2010.
[37]	牟艳芳, 陈文璐, 周冰, 等. 基于网络药理学与分子对接技术探讨川蛭通络胶囊干预微循环障碍的机制研究[J]. 中草药,2021,52(24):7550−7560. [MOU Y F, CHEN W L, ZHOU B, et al. Mechanism of Chuan Zhi Tongluo capsules on microcirculation disturbance based on network pharmacology and molecular docking[J]. Chinese Traditional Herbal Drugs,2021,52(24):7550−7560.
[38]	雷欢, 邓琴, 刘子源, 等. 基于网络药理学和分子对接方法探讨香叶木素治疗高尿酸血症肾病的分子机制[J]. 山东医药,2022,62(14):9−13,24. [LEI H, DENG Q, LIU Z Y, et al. To explore the molecular mechanism of German lignin in the treatment of hyperuricemia nephropathy based on network pharmacology and molecular docking method[J]. Shandong Medical Journal,2022,62(14):9−13,24. doi: 10.3969/j.issn.1002-266X.2022.14.003
[39]	林珠灿. 景天三七止血、抗炎物质基础与质量评价的研究[D]. 南京: 南京中医药大学, 2014 LIN Z C. Studies on hemostatic and anti-inflammatory effective substances of Phedimus aizoon (Linnaeus)'t Hart. and its quality evaluation[D]. Nanjing: Nanjing University of Chinese Medicine, 2014.
[40]	付煜荣, 王至宝, 田嘉铭. 景天三七中没食子酸的提取[J]. 陕西中医,2006,27(9):1138−1139. [FU Y R, WANG Z B, TIAN J M. Extraction of gallic acid from Phedimus aizoon (Linnaeus)'t Hart doi: 10.3969/j.issn.1000-7369.2006.09.081 J]. Shaanxi Journal of Traditional Chinese Medicine,2006,27(9):1138−1139. doi: 10.3969/j.issn.1000-7369.2006.09.081
[41]	李乔, 于洋, 李明晓, 等. 费菜根茎化学成分的分离与鉴定[J]. 中国现代中药,2020,22(3):353−357. [LI Q, YU Y, LI M X, et al. Isolation and identification of the chemical constituents from the rhizome of Phedimus aizoon (Linnaeus)'t Hart doi: 10.13313/j.issn.1673-4890.20191203001 J]. Modern Chinese Medicine,2020,22(3):353−357. doi: 10.13313/j.issn.1673-4890.20191203001
[42]	余虹, 李逐波. 不饱和双键化合物与药物活性研究进展[J]. 解放军药学学报,2008(3):234−238. [YU H, LI Z B. Research progress in intestinal unsaturated double-bond compounds and drug activity[J]. Pharmaceutical Journal of Chinese People's Liberation Army,2008(3):234−238.
[43]	刘艳红, 冯锋, 谢宁, 等. 穿心莲内酯衍生物抗肿瘤、解热抗炎构效关系研究进展[J]. 西北药学杂志,2013,28(1):95−98. [LIU Y H, FENG F, XIE N, et al. Advances in research on the anti-tumor, antipyretic and anti-inflammatory activity of andrographolide derivatives[J]. Northwest Pharmaceutical Journal,2013,28(1):95−98.

Supplements (0)

Cited By

Cited by

Periodical cited type(6)

1.	洪梦杰，景奕文，于白音，张朝玉，石海英，常圣鑫. 基于网络药理学和分子对接探讨葛根素抗炎的关键靶点. 韶关学院学报. 2025(02): 41-46 .
2.	鲁森，王瑞，高雄，林慧纯，陈忠正，张媛媛，陈旭洁，黄秋颜，李斌，林晓蓉. 基于高分辨质谱和网络药理学探究南昆山毛叶红茶的抗炎机理. 食品工业科技. 2024(02): 30-39 . 本站查看
3.	李思蒙，田荣，殷明婧，谷巍. 基于网络药理学和分子对接探讨中药芫花治疗原发性痛经的作用机制. 亚热带植物科学. 2024(01): 31-39 .
4.	李镁娟，张军，张云数，李乾伟，张娜，刘梦娇，张人平. 网络药理学结合分子对接技术揭示芹菜籽抑制痛风的潜在分子机制. 食品与机械. 2024(03): 44-51 .
5.	张淼，黄菲，江思思，刘小芬. 闽台“一条根”类青草药次生代谢产物研究进展. 中国民族民间医药. 2023(16): 62-67 .
6.	殷春燕，董占军，陈江魁. 基于网络药理学和分子对接技术研究花生红衣多酚抗动脉粥样硬化的作用机制. 食品与发酵工业. 2023(20): 242-249 .