Network Pharmacology-based Analysis of the Anti-atherosclerosis Mechanism of Scutellarin and Experimental Validation <i>in Vivo</i>

Li ZHANG; Yuting WANG; Jianing SHI; Dan YU; Renhua YANG; Zhiqiang SHEN; Jiang LONG; Peng CHEN

doi:10.12259/j.issn.2095-610X.S20220804

Volume 43 Issue 8

Jul. 2022

Turn off MathJax

Article Contents

Article Navigation > Journal of Kunming Medical University > 2022 > 43(8): 17-27

Li ZHANG, Yuting WANG, Jianing SHI, Dan YU, Renhua YANG, Zhiqiang SHEN, Jiang LONG, Peng CHEN. Network Pharmacology-based Analysis of the Anti-atherosclerosis Mechanism of Scutellarin and Experimental Validation in Vivo[J]. Journal of Kunming Medical University, 2022, 43(8): 17-27. doi: 10.12259/j.issn.2095-610X.S20220804

Citation:

Li ZHANG, Yuting WANG, Jianing SHI, Dan YU, Renhua YANG, Zhiqiang SHEN, Jiang LONG, Peng CHEN. Network Pharmacology-based Analysis of the Anti-atherosclerosis Mechanism of Scutellarin and Experimental Validation in Vivo[J]. Journal of Kunming Medical University, 2022, 43(8): 17-27. doi: 10.12259/j.issn.2095-610X.S20220804

Citation:

Li ZHANG, Yuting WANG, Jianing SHI, Dan YU, Renhua YANG, Zhiqiang SHEN, Jiang LONG, Peng CHEN. Network Pharmacology-based Analysis of the Anti-atherosclerosis Mechanism of Scutellarin and Experimental Validation in Vivo[J]. Journal of Kunming Medical University, 2022, 43(8): 17-27. doi: 10.12259/j.issn.2095-610X.S20220804

PDF( 4533 KB)

Network Pharmacology-based Analysis of the Anti-atherosclerosis Mechanism of Scutellarin and Experimental Validation in Vivo

doi: 10.12259/j.issn.2095-610X.S20220804

1.
School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products，Kunming Medical University，Kunming Yunnan 650500
2.
Dept. of Neurosurgery，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

Received Date: 2022-03-29
Available Online: 2022-07-21
Publish Date: 2022-07-28

Abstract

Abstract

Objective To analyze the potential molecular biological mechanism of scutellarin for the treatment of atherosclerosis （AS） based on network pharmacology. Methods The PubChem database was used to predict the potential targets of scutellarin, and the Disgenet and CeneCards databases were used to predict and screen the genes related to atherosclerosis, and the Cytoscape 3.7.0 software was used to establish and construct the component-target-disease network visualization network. The GO and KECG pathways were analyzed using the David database. In addition, an APOE^-/- mouse AS model was developed and treated with different concentrations of scutellarin, and the expression changes of the core targets were verified by RT-PCR. Results 1. Network pharmacological prediction results: the core targets of Scutellarin for AS treatment were tumor necrosis factor-α （TNF-α）, AKT serine/threonine kinase 1 （MAPK）, low density lipoprotein receptor （LDLR）, apolipoprotein E （APOE）, among other targets, with 106 in total. The key targets of Scutellarin are PI3K/AKT signaling pathway （hsa04151）, Ras signaling pathway （hsa04014） and MAPK signaling pathway （hsa04010）（P < 0.05）, which are involved in cell proliferation, inflammatory response, oxidative stress and apoptosis, to treat AS. 2. Results of in vivo experiments: compared with the model group, the mRNA expression of PI3K, AKT, mTOR and Bcl-2 was down-regulated and the mRNA expression of Bax and Caspase-3 was up-regulated in the Scutellarin group. In addition, compared with model group, Scutellarin down-regulated the contents of TNF-α and IL-1β in serum concentration-dependent （P < 0.05）. Conclusion Through network pharmacology screening and RT-PCR verification, Scutellarin inhibits the process of inflammatory response in a mouse model of AS by regulating the PI3K/AKT/mTOR signaling pathway.
- Network pharmacology,
- Scutellarin,
- Atherosclerosis,
- APOE^-/- mice AS model,
- PI3K\AKT\mTOR

FullText(HTML)

References(15)

References

[1]	Sun J J,Yin X W,Liu H H,et al. Rapamycin inhibits ox-LDL-induced inflammation in human endothelial cells in vitro by inhibiting the mTORC2/PKC/c-Fos pathway[J]. Acta Pharmacol Sin,2018,39(3):336-344. doi: 10.1038/aps.2017.102
[2]	Troidl K,Schubert C,Vlacil A K,et al. The lipopeptide MALP-2 promotes collateral growth[J]. Cells,2020,9(4):997. doi: 10.3390/cells9040997
[3]	Xi J Y,Rong Z. Scutellarin ameliorates high glucose-induced vascular endothelial cells injury by activating PINK1/Parkin-mediated mitophagy[J]. J Ethnopharmacol,2021,271:113855. doi: 10.1016/j.jep.2021.113855
[4]	Keeter,W C,Ma S,Stahr N,et al. Atherosclerosis and multi-organ-associated pathologies[J]. Semin Immunopathol,2022,44(3):363-374. doi: 10.1007/s00281-022-00914-y
[5]	Wu M F,Xu K Z,Guo YG,et al. Lipoprotein(a) and atherosclerotic cardiovascular disease:Current understanding and future perspectives[J]. Cardiovasc Drugs Ther,2019,33(6):739-748. doi: 10.1007/s10557-019-06906-9
[6]	Panes O,Gonzalez C,Hidalgo P,et al. Platelet tissue factor activity and membrane cholesterol are increased in hypercholesterolemia and normalized by rosuvastatin,but not by atorvastatin.[J]. Atherosclerosis,2017,257:164-171. doi: 10.1016/j.atherosclerosis.2016.12.019
[7]	Lee Y P,Cho Y,Kim E J,et al. Reduced expression of pyruvate kinase in kidney proximal tubule cells is a potential mechanism of pravastatin altered glucose metabolism[J]. Sci Rep,2019,9(1):5318. doi: 10.1038/s41598-019-39461-2
[8]	Ott B R,Daiello L A,Dahabreh I J,et al. Do statins impair cognition? A systematic review and meta-analysis of randomized controlled trials[J]. J Gen Intern Med,2015,30(3):348-358. doi: 10.1007/s11606-014-3115-3
[9]	Mo J,Yang R H,Li F,et al. Scutellarin protects against vascular endothelial dysfunction and prevents atherosclerosis via antioxidation[J]. Phytomedicine,2018,42:66-74. doi: 10.1016/j.phymed.2018.03.021
[10]	Zhou S,Ai Z,Li W,et al. Deciphering the pharmacological mechanisms of taohe-chengqi decoction extract against renal fibrosis through integrating network pharmacology and experimental validation In vitro and in vivo[J]. Front Pharmacol,2020,11(1):425.
[11]	何信用,王俊岩,宋囡,等. 基于网络药理学的葛根素治疗动脉粥样硬化潜在分子机制研究[J]. 中华中医药学刊,2020,38(9):116-120. doi: 10.13193/j.issn.1673-7717.2020.09.029
[12]	Fernandez-Hernando C,Jozsef L,Jenkins D,et al. Absence of akt1 reduces vascular smooth muscle cell migration and survival and induces features of plaque vulnerability and cardiac dysfunction during atherosclerosis[J]. Arterioscler Thromb Vasc Biol,2009,29(12):2033-2040. doi: 10.1161/ATVBAHA.109.196394
[13]	李敏静,郭莉,陈晔,等. 血府逐瘀汤含药血清对低氧诱导的大鼠肺动脉平滑肌细胞增殖及PI3K/AKT/mTOR信号通路的影响[J]. 中国中西医结合杂志,2020,40(7):836-841.
[14]	张莉,白林英,母凯茜,等. 灯盏乙素对小型猪动脉粥样硬化模型颈总动脉斑块组织中基质金属蛋白酶-1、2、9 表达的影响[J]. 中药药理与临床,2020,36(6):91-97.
[15]	Ashino T,Yamamoto M,Yoshida T,et al. Redox-sensitive transcription factor Nrf2 regulates vascular smooth muscle cell migration and neointimal hyperplasia[J]. Arterioscler Thromb Vasc Biol,2013,33(4):760-768. doi: 10.1161/ATVBAHA.112.300614

Relative Articles(20)

Relative Articles

[1]	Yi YANG, Shen SHEN, Mengxia WAN, Yongbo ZHANG. Preoperative Fasting Triglyceride-glucose Index as a Predictor of Contralateral New Silent Ischemic Brain Lesions after Carotid Artery Stenting. Journal of Kunming Medical University, 2024, 46(): 1-6.
[2]	Aiyun WANG, Yuting WANG, Jing CAI, Ruoyan NI, Caiying LUO, Zhuo YU, Peng CHEN. The Role of Intestinal Flora and Its Metabolites in The Development of Atherosclerosis. Journal of Kunming Medical University, 2024, 45(12): 1-7.
[3]	Liyuan WANG, Zhenting YANG, Qingling LI, Haiwen LI, Zhirong ZHAO, Yongrui YANG, Shude LI. Effects of Scutellarin on MMP2，MMP9 and TIMP-1 Protein in Liver of Obese Rats with Chronic Liver Injury by High Glucose and Fat Diet. Journal of Kunming Medical University, 2023, 44(4): 9-15. doi: 10.12259/j.issn.2095-610X.S20230408
[4]	Shaoyou DENG, Rong LI, Jintao LI, Yulan ZHAO, Peijin WANG, Hong ZHENG. Mechanism of Osteoking Improving Osteoarthritis based on Network Pharmacology and DDM Rats. Journal of Kunming Medical University, 2023, 44(7): 34-39. doi: 10.12259/j.issn.2095-610X.S20230701
[5]	Hualei DAI, Chengcheng HU, Guimin ZHANG, Siming TAO, Jiankun CHEN. Screening Biomarkers of Astragalus Membranaceus for Hypertensive Ventricular Remodeling Based on Network Pharmacology and Molecular Docking. Journal of Kunming Medical University, 2023, 44(8): 27-36. doi: 10.12259/j.issn.2095-610X.S20230819
[6]	Ranxi SHI, Tao YANG, Qing CHENG, Liangchen ZHAO, Jiahui GUO, Limei WANG. Mechanism of Dendrobium Officinale Against Inflammatory Aging Based on Network Pharmacology and Molecular Docking. Journal of Kunming Medical University, 2023, 44(11): 1-8. doi: 10.12259/j.issn.2095-610X.S20231101
[7]	Yongrui YANG, Liyuan WANG, Haiwen LI, Zhirong ZHAO, Rui PU, Guishuai WU, Shude LI. Scutellarin Ameliorates Liver Fibrosis in Nonalcoholic Fatty Liver Disease by Inhibiting NOX Expression. Journal of Kunming Medical University, 2022, 43(7): 38-45. doi: 10.12259/j.issn.2095-610X.S20220721
[8]	Hu ZHANG, Anrui PENG, Jiaji ZHONG, Bo HUANG, Peng BAI. The Application of Breviscapine on Graft Restenosis in Coronary Artery Bypass Grafting. Journal of Kunming Medical University, 2022, 43(1): 59-62. doi: 10.12259/j.issn.2095-610X.S20220136
[9]	Xiaohan WANG, Shanmao MOU, Cuifang HAO, Linlin REN, Min WANG, Tong ZHAO. Platelet-rich Plasma Promotes the Proliferation of Human Endometrial Mesenchymal Stem Cells (EnMSCs) through the PI3K/AKT/mTOR Signaling Pathway. Journal of Kunming Medical University, 2022, 43(1): 26-32. doi: 10.12259/j.issn.2095-610X.S20220126
[10]	Yanlong LIU, Xuefeng GUANG, Xiaolong YIN, Hailong DAI. Effects of miR-125a-3p on Atherosclerotic Plaque, M1/M2 Macrophages, MMP-9 and VEGF. Journal of Kunming Medical University, 2022, 43(9): 1-6. doi: 10.12259/j.issn.2095-610X.S20220915
[11]	Li ZHANG, Dan YU, Yu-ting WANG, Zhi-mei GOU, Ren-hua YANG, Bo HE, Zhi-qiang SHEN, Wen-ying CHAI, Peng CHEN. Effects of Scutellarin on Expressions of PKC and TNF-α in OX-LDL Injured RAW264.7 Cells in vitro. Journal of Kunming Medical University, 2021, 42(10): 1-7. doi: 10.12259/j.issn.2095-610X.S20211040
[12]	Ni Guang Hui , Tong Jun , Hu Zhi , Li Na , Chen Xian Lu , Miao Xuan , He Yue Feng . . Journal of Kunming Medical University, 2017, 38(05): 1-4.
[13]	Lan Dan Feng . . Journal of Kunming Medical University,
[14]	Guan Bing . . Journal of Kunming Medical University,
[15]	Hu Yan Jie . . Journal of Kunming Medical University,
[16]	Wang Ling . The Correlation between Lower Extremity Atherosclerosis and Bone Mineral Density in Type 2 Diabetes Mellitus Patients. Journal of Kunming Medical University,
[17]	. Therapeutic Effect of PAS Combination Therapy on 40 Patients with Atherosclerosis. Journal of Kunming Medical University,
[18]	. Evaluation of Atherosclerosis in Rheumatoid Arthritis Patients with High Lipid Levels by Ultrasonography. Journal of Kunming Medical University,
[19]	Deng Zi Yu . . Journal of Kunming Medical University,
[20]	Qiu Hong Mei . . Journal of Kunming Medical University,