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基于网络药理学和分子对接技术探讨人参对牙周炎的潜在治疗机制
孙金梦, 张颖, 郑泽君, 丁晓玲, 孙敏敏, 丁刚
PDF(5943 KB)
PDF(5943 KB)
基于网络药理学和分子对接技术探讨人参对牙周炎的潜在治疗机制
), 张颖1, 郑泽君1, 丁晓玲2, 孙敏敏1(), 丁刚1()Potential mechanism of ginseng in the treatment of periodontitis based on network pharmacology and molecular docking
), Zhang Ying1, Zheng Zejun1, Ding Xiaoling2, Sun Minmin1(), Ding Gang1()目的 采用网络药理学和分子对接技术探讨人参治疗牙周炎的潜在作用机制。 方法 通过多种数据库获得人参、牙周炎的潜在靶点，利用VENNY获得人参-牙周炎交集靶点，在STRING平台形成蛋白质互作网络关系图，采用Cytoscape软件形成核心靶点图并构建人参-活性成分-靶点网络图，将核心靶点进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，通过分子对接技术分析人参活性成分治疗牙周炎的核心靶点。 结果 分析获得22个人参活性成分、591个人参活性成分潜在作用靶点、2 249个牙周炎基因靶点和145个人参-牙周炎交集靶点。人参对血管内皮生长因子A、表皮生长因子受体等核心靶点以及低氧诱导因子-1（HIF-1）信号通路、磷脂酰肌醇3-激酶-蛋白激酶B（PI3K-Akt）信号通路分子具有较强的结合活性。 结论 人参及其活性成分可通过调节HIF-1、PI3K-Akt等多条信号通路发挥治疗牙周炎的作用。
Objective To explore the mechanism of ginseng in the treatment of periodontitis based on network pharmacology and molecular docking technology. Methods Potential targets of ginseng and periodontitis were obtained through various databases. The intersection targets of ginseng and periodontitis were obtained by using VENNY, the protein-protein interaction network relationship diagram was formed on the STRING platform, the core target diagram was formed by Cytoscape software, and the ginseng-active ingredient-target network diagram was constructed. The selected targets were screened for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The core targets of ginseng’s active ingredients in treating periodontitis were analyzed by molecular docking technique. Results The 22 ginseng’s active ingredients, 591 potential targets of ginseng’s active ingredients, 2 249 periodontitis gene targets, and 145 ginseng-periodontitis intersection targets were analyzed. Ginseng had strong binding activity on core targets such as vascular endothelial growth factor A and epidermal growth factor receptor, as well as hypoxia induced-factor 1 (HIF-1) signaling pathway and phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway. Conclusion Ginseng and its active components can regulate several signaling pathways such as HIF-1 and PI3K-Akt, thereby indicating that ginseng may play a role in treating periodontitis through multiple pathways.
人参 / 牙周炎 / 网络药理学 / 分子对接 / 作用机制
ginseng / periodontitis / network pharmacology / molecular docking / mechanism
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| 1 | 孟焕新. 牙周病学[M]. 5版. 北京: 人民卫生出版社, 2020: 146-147. |
| 1 | Meng HX. Periodontology[M]. 5th ed. Beijing: People’s Medical Publishing House, 2020: 146-147. |
| 2 | Global oral health status report: towards universal heal-th coverage for oral health by 2030[R]. Geneva: World Health Organization, 2022: 37-40. |
| 3 | Figuero E, Han YW, Furuichi Y. Periodontal diseases and adverse pregnancy outcomes: mechanisms[J]. Periodontol 2000, 2020, 83(1): 175-188. |
| 4 | Lalla E, Papapanou PN. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases[J]. Nat Rev Endocrinol, 2011, 7(12): 738-748. |
| 5 | Sanz M, Del Castillo AM, Jepsen S, et al. Periodontitis and cardiovascular diseases: consensus report[J]. J Clin Periodontol, 2020, 47(3): 268-288. |
| 6 | Michaud DS, Liu Y, Meyer M, et al. Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study[J]. Lancet Oncol, 2008, 9(6): 550-558. |
| 7 | Schmidlin PR, Fachinger P, Tini G, et al. Shared microbiome in gums and the lung in an outpatient population[J]. J Infect, 2015, 70(3): 255-263. |
| 8 | Jungbauer G, St?hli A, Zhu X, et al. Periodontal microorganisms and Alzheimer disease—A causative relationship[J]. Periodontol 2000, 2022, 89(1): 59-82. |
| 9 | Tsai CY, Tang CY, Tan TS, et al. Subgingival microbiota in individuals with severe chronic periodontitis[J]. J Microbiol Immunol Infect, 2018, 51(2): 226-234. |
| 10 | Slots J. Periodontitis: facts, fallacies and the future[J]. Periodontol 2000, 2017, 75(1): 7-23. |
| 11 | Graziani F, Karapetsa D, Alonso B, et al. Nonsurgical and surgical treatment of periodontitis: how many options for one disease[J]. Periodontol 2000, 2017, 75(1): 152-188. |
| 12 | Bhatavadekar NB, Williams RC. Modulation of the host inflammatory response in periodontal disease management: exciting new directions[J]. Int Dent J, 2009, 59(5): 305-308. |
| 13 | Shergis JL, Zhang AL, Zhou W, et al. Panax ginseng in randomised controlled trials: a systematic review[J]. Phy-tother Res, 2013, 27(7): 949-965. |
| 14 | Fan W, Huang Y, Zheng H, et al. Ginsenosides for the treatment of metabolic syndrome and cardiovascular di-seases: pharmacology and mechanisms[J]. Biomed Pharmacother, 2020, 132: 110915. |
| 15 | Qi HY, Li L, Ma H. Cellular stress response mechanisms as therapeutic targets of ginsenosides[J]. Med Res Rev, 2018, 38(2): 625-654. |
| 16 | Li X, Liu J, Zuo TT, et al. Advances and challenges in ginseng research from 2011 to 2020: the phytochemistry, quality control, metabolism, and biosynthesis[J]. Nat P-rod Rep, 2022, 39(4): 875-909. |
| 17 | Oh SJ, Oh Y, Ryu IW, et al. Protective properties of ginsenoside Rb3 against UV-B radiation-induced oxidative stress in HaCaT keratinocytes[J]. Biosci Biotechnol Biochem, 2016, 80(1): 95-103. |
| 18 | Xing JJ, Hou JG, Ma ZN, et al. Ginsenoside Rb3 provi-des protective effects against cisplatin-induced nephrotoxicity via regulation of AMPK-/mTOR-mediated auto-phagy and inhibition of apoptosis in vitro and in vivo [J]. Cell Prolif, 2019, 52(4): e12627. |
| 19 | Liu X, Jiang Y, Fu W, et al. Combination of the ginseno-sides Rb3 and Rb2 exerts protective effects against myocardial ischemia reperfusion injury in rats[J]. Int J Mol Med, 2020, 45(2): 519-531. |
| 20 | Sun M, Ji Y, Zhou S, et al. Ginsenoside Rb3 inhibits osteoclastogenesis via ERK/NF?κB signaling pathway in vitro and in vivo [J]. Oral Dis, 2023, 29(8): 3460-3471. |
| 21 | Sun M, Ji Y, Li Z, et al. Ginsenoside Rb3 inhibits pro-inflammatory cytokines via MAPK/AKT/NF-κB pathways and attenuates rat alveolar bone resorption in response to Porphyromonas gingivalis LPS[J]. Molecules, 2020, 25(20): 4815. |
| 22 | 赵欢, 开国银, 韩冰. 基于网络药理学和分子对接的丹参饮抗结肠癌作用机制[J]. 中国药理学通报, 2022, 38(4): 598-605. |
| 22 | Zhao H, Kai GY, Han B. Study of Danshen decoction on colon cancer based on network pharmacology and molecular docking[J]. Chin Pharmacol Bull, 2022, 38(4): 598-605. |
| 23 | 宗阳, 丁美林, 贾可可, 等. 基于网络药理学和分子对接法探寻达原饮治疗新型冠状病毒肺炎(COVID-19)活性化合物的研究[J]. 中草药, 2020, 51(4): 836-844. |
| 23 | Zong Y, Ding ML, Jia KK, et al. Exploring active compounds of Da-Yuan-Yin in treatment of COVID-19 based on network pharmacology and molecular docking method[J]. Chin Tradit Herbal Drugs, 2020, 51(4): 836-844. |
| 24 | 唐萍, 唐芳婷, 王红, 等. 基于网络药理学及分子对接探讨人参治疗胃癌的作用机制[J]. 湖南中医杂志, 2023, 39(6): 162-169. |
| 24 | Tang P, Tang FT, Wang H, et al. Mechanism of action of Panax ginseng in treatment of gastric cancer: a study based on network pharmacology and molecular docking[J]. Hunan J Tradit Chin Med, 2023, 39(6): 162-169. |
| 25 | Chen W, Yao P, Vong CT, et al. Ginseng: a bibliometric analysis of 40-year journey of global clinical trials[J]. J Adv Res, 2020, 34: 187-197. |
| 26 | 刘丽, 李雅萍, 王娟, 等. 三七凝胶治疗牙周炎的初步研究[J]. 宁夏医学杂志, 2022, 44(12): 1074-1077. |
| 26 | Liu L, Li YP, Wang J, et al. Preliminary study on the curative effect of panax notoginseng gel on periodontitis[J]. Ningxia Med J, 2022, 44(12): 1074-1077. |
| 27 | 杨倩, 余占海, 杜建东, 等. 人参皂甙Rg-1对大鼠牙周组织中白介素6、骨钙素水平的影响[J]. 实用口腔医学杂志, 2009, 25(1): 22-25. |
| 27 | Yang Q, Yu ZH, Du JD, et al. Effects of ginsenoside Rg-1 on the expressions of interleukin-6, bone gla protein in periodontal tissues in periodontitis rats[J]. J Pract Stomatol, 2009, 25(1): 22-25. |
| 28 | Kim EN, Kim TY, Park EK, et al. Panax ginseng fruit has anti-inflammatory effect and induces ssteogenic differentiation by regulating Nrf2/HO-1 signaling pathway in vitro and in vivo models of periodontitis[J]. Antioxidants (Basel), 2020, 9(12): 1221. |
| 29 | G?lz L, Memmert S, Rath-Deschner B, et al. Hypoxia and P. gingivalis synergistically induce HIF-1 and NF-κB activation in PDL cells and periodontal diseases[J]. Mediators Inflamm, 2015, 2015: 438085. |
| 30 | Ng KT, Li JP, Ng KM, et al. Expression of hypoxia-inducible factor-1α in human periodontal tissue[J]. J Perio-dontol, 2011, 82(1): 136-141. |
| 31 | 唐宋, 张晓南. 牙周组织低氧环境与牙周炎发生发展的研究进展[J]. 同济大学学报(医学版), 2021, 42(2): 285-290. |
| 31 | Tang S, Zhang XN. Relationship between hypoxic environment in periodontal tissue and the development of pe-riodontitis[J]. J Tongji Univ (Med Sci), 2021, 42(2): 285-290. |
| 32 | Hirai K, Furusho H, Hirota K, et al. Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss[J]. Int J Oral Sci, 2018, 10(2): 12. |
| 33 | 施庆颜, 靳华, 蓝田, 等. 缺氧诱导因子1α在人慢性牙周炎牙龈组织中的表达[J]. 中国病理生理杂志, 2013, 29(9): 1668-1671. |
| 33 | Shi QY, Jin H, Lan T, et al. Expression of hypoxia-inducible factor 1α in human gingival tissues with chronic periodontitis[J]. Chin J Pathophysiol, 2013, 29(9): 1668-1671. |
| 34 | Wang C, Liu C, Liang C, et al. Role of berberine thermosensitive hydrogel in periodontitis via PI3K/AKT pathway in vitro [J]. Int J Mol Sci, 2023, 24(7): 6364. |
| 35 | Tian T, Chen L, Wang Z, et al. Sema3A drives alternative macrophage activation in the resolution of periodontitis via PI3K/AKT/mTOR signaling[J]. Inflammation, 2023, 46(3): 876-891. |
| 36 | Han Y, Wang X, Ma D, et al. Ipriflavone promotes proliferation and osteogenic differentiation of periodontal ligament cells by activating GPR30/PI3K/AKT signaling pa-thway[J]. Drug Des Devel Ther, 2018, 12: 137-148. |
| 37 | 万美钰, 窦德强. 基于网络药理学探究人参、红参与黑参治疗气虚的药效物质基础与机制[J]. 人参研究, 2023, 35(3): 2-8. |
| 37 | Wan MY, Dou DQ. Exploring the pharmacological substance basis and mechanism of ginseng, red ginseng, and black ginseng in treating qi deficiency based on network pharmacology[J]. Ginseng Res, 2023, 35(3): 2-8. |
| 38 | Sczepanik FSC, Grossi ML, Casati M, et al. Periodon-titis is an inflammatory disease of oxidative stress: we should treat it that way[J]. Periodontol 2000, 2020, 84(1): 45-68. |
| 39 | Bullon P, Newman HN, Obesity Battino M., me-llitus diabetes, atherosclerosis and chronic periodontitis : a shared pathology via oxidative stress and mitochondrial dysfunction[J]. Periodontol 2000, 2014, 64(1): 139-153. |
| 40 | Han X, Zhao S, Song H, et al. Kaempferol alleviates LD-mitochondrial damage by promoting autophagy: implications in Parkinson’s disease[J]. Redox Biol, 2021, 41: 101911. |
| 41 | Yang L, Gao Y, Bajpai VK, et al. Advance toward isolation, extraction, metabolism and health benefits of kaem-pferol, a major dietary flavonoid with future perspectives[J]. Crit Rev Food Sci Nutr, 2023, 63(16): 2773-2789. |
| 42 | Chen M, Xiao J, El-Seedi HR, et al. Kaempferol and atherosclerosis: from mechanism to medicine[J]. Crit Rev Food Sci Nutr, 2022. doi: 10.1080/10408398.2022.21212-61 . |
| 43 | Fossier L, Panel M, Butruille L, et al. Enhanced mitochondrial calcium uptake suppresses atrial fibrillation associated with metabolic syndrome[J]. J Am Coll Cardiol, 2022, 80(23): 2205-2219. |
| 44 | Xie C, Zhuang XX, Niu Z, et al. Amelioration of Alzheimer’s disease pathology by mitophagy inducers i-dentified via machine learning and a cross-species workflow[J]. Nat Biomed Eng, 2022, 6(1): 76-93. |
| 45 | Zhao J, Ling L, Zhu W, et al. M1/M2 re-polarization of kaempferol biomimetic NPs in anti-inflammatory therapy of atherosclerosis[J]. J Control Release, 2023, 353: 1068-1083. |
| 46 | Wang S, Shi X, Li J, et al. A small molecule selected from a DNA-encoded library of natural products that binds to TNF?α and attenuates inflammation in vivo [J]. Adv Sci (Weinh), 2022, 9(21): 2201258. |
| 47 | Behl T, Mehta K, Sehgal A, et al. Exploring the role of polyphenols in rheumatoid arthritis[J]. Crit Rev Food Sci Nutr, 2022, 62(19): 5372-5393. |
| 48 | Han X, Sun S, Sun Y, et al. Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease[J]. Autophagy, 2019, 15(11): 1860-1881. |
| 49 | Yang EJ, Kim GS, Jun M, et al. Kaempferol attenuates the glutamate-induced oxidative stress in mouse-derived hippocampal neuronal HT22 cells[J]. Food Funct, 2014, 5(7): 1395-1402. |
| 50 | Liu Z, Yao X, Sun B, et al. Pretreatment with kaempfe-rol attenuates microglia-mediate neuroinflammation by inhibiting MAPKs-NF-κB signaling pathway and pyroptosis after secondary spinal cord injury[J]. Free Radic Biol Med, 2021, 168: 142-154. |
| 51 | Xiao X, Hu Q, Deng X, et al. Old wine in new bottles: kaempferol is a promising agent for treating the trilogy of liver diseases[J]. Pharmacol Res, 2022, 175: 106005. |
| 52 | Kim MJ, Song YR, Kim YE, et al. Kaempferol stimulation of autophagy regulates the ferroptosis under the oxidative stress as mediated with AMP-activated protein kinase[J]. Free Radic Biol Med, 2023, 208: 630-642. |
| 53 | Wang H, Wang Z, Zhang Z, et al. β-Sitosterol as a promising anticancer agent for chemoprevention and chemotherapy: mechanisms of action and future prospects[J]. Adv Nutr, 2023, 14(5): 1085-1110. |
| 54 | Khan Z, Nath N, Rauf A, et al. Multifunctional roles and pharmacological potential of β-sitosterol: emerging evidence toward clinical applications[J]. Chem Biol Inte-ract, 2022, 365: 110117. |
| 55 | Zhang F, Liu Z, He X, et al. β-sitosterol-loaded solid lipid nanoparticles ameliorate complete Freund’s adjuvant-induced arthritis in rats: involvement of NF-кB and HO-1/Nrf-2 pathway[J]. Drug Deliv, 2020, 27(1): 1329-1341. |
| 56 | Babu S, Jayaraman S. An update on β-sitosterol: a potential herbal nutraceutical for diabetic management[J]. Bio-med Pharmacother, 2020, 131: 110702. |
| 57 | Ferrara N, Adamis AP. Ten years of anti-vascular endothelial growth factor therapy[J]. Nat Rev Drug Discov, 2016, 15(6): 385-403. |
| 58 | Han Y, You X, Xing W, et al. Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts[J]. Bone Res, 2018, 6: 16. |
| 59 | Ferrara N. Vascular endothelial growth factor: basic science and clinical progress[J]. Endocr Rev, 2004, 25(4): 581-611. |
| 60 | Huang Q, Li F, Liu X, et al. Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy[J]. Nat Med, 2011, 17(7): 860-866. |
| 61 | Nozaki K, Maltez VI, Rayamajhi M, et al. Caspase-7 activates ASM to repair gasdermin and perforin pores[J]. Nature, 2022, 606(7916): 960-967. |
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