基于网络药理学分析党参减轻大肠杆菌感染小鼠急性肺损伤的作用机制

doi:10.11843/j.issn.0366-6964.2023.08.040

Abstract

Abstract: The network pharmacology and related molecular biology experiments were used to explore the protective mechanism of Codonopsis pilosula on acute lung injury (ALI). The main chemical components of Codonopsis radix and related targets were mined through the network pharmacology database. The related targets of ALI were obtained through disease-related databases. protein interaction (PPI) network was constructed,and GO analysis and KEGG pathway enrichment analysis were performed on the mined data. The results showed that 8 compounds in Codonopsis pilosula could act on 303 targets, 1 522 targets related to ALI, 119 intersecting targets involved in ALI, 103 targets in PPI network including MAPK, NF-κB and TLR4. GO functional enrichment analysis showed 133 molecular functions, 79 biological processes and 523 cellular components, and KEGG showed 132 related pathways. The results were verified by Western blotting, ELISA and immunofluorescence. The results showed that Codonopsis pilosula polysaccharides pretreatment could down-regulate MAPK and NF-κB inflammatory signal pathways activation and TNF α and IL-1 β secretion in E.coli-induced macrophages. Furthermore, Codonopsis pilosula polysaccharide could down-regulate TNF α and IL-1β production, and down-regulate HMGB1 expression to reduce the lung injury in the E.coli-infected lungs of mice. In conclusion, Codonopsis pilosula could protect the lung by regulating disease-related targets of ALI through multiple pathways and biological processes.

Key words: acute lung injury, Codonopsis pilosula, network pharmacology, targets

CLC Number:

S853.74

GONG Zhiguo, ZHAO Jiamin, GU Baichen, REN Peipei, YU Zhuoya, BAI Yunjie, LIU Xinyu, WANG Chao, LIU Bo. Exploring the Mechanism of Codonopsis pilosula in Alleviation of Acute Lung Injury in Escherichia coli Infected Mice Based on Network Pharmacology[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(8): 3571-3581.

References 35

[1]	LUAN F, JI Y F, PENG L X, et al. Extraction, purification, structural characteristics and biological properties of the polysaccharides from Codonopsis pilosula:a review[J]. Carbohydr Polym, 2021, 261:117863.
[2]	DENG X L, FU Y J, LUO S, et al. Polysaccharide from radix codonopsis has beneficial effects on the maintenance of T-cell balance in mice[J]. Biomed Pharmacother, 2019, 112:108682.
[3]	张彦琼, 李梢. 网络药理学与中医药现代研究的若干进展[J]. 中国药理学与毒理学杂志, 2015, 29(6):883-892.ZHANG Y Q, LI S. Progress in network pharmacology for modern research of traditional Chinese medicine[J]. Chin J Pharmacol Toxicol, 2015, 29(6):883-892. (in Chinese)
[4]	KULKARNI H S, LEE J S, BASTARACHE J A, et al. Update on the features and measurements of experimental acute lung injury in animals:an official American thoracic society workshop report[J]. Am J Respir Cell Mol Biol, 2022, 66(2):e1-e14.
[5]	FU Y H, LIU B, LIU J H, et al. Geniposide, from Gardenia jasminoides Ellis, inhibits the inflammatory response in the primary mouse macrophages and mouse models[J]. Int Immunopharmacol, 2012, 14(4):792-798.
[6]	TOLLE L B, STANDIFORD T J. Danger-associated molecular patterns (DAMPs) in acute lung injury[J]. J Pathol, 2013, 229(2):145-156.
[7]	车玉虎, 刘志, 董雪松, 等. 大肠杆菌气管注入致急性肺损伤的实验研究[J]. 中国医科大学学报, 2006, 35(3):262-264.CHE Y H, LIU Z, DONG X S, et al. Acute lung injury induced by intratracheal instillation of Escherichia coli in rabbits[J]. J China Med Univ, 2006, 35(3):262-264. (in Chinese)
[8]	WU H Y, YANG J, SU E M, et al. Lipoxin A4 and platelet activating factor are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice[J]. PLoS One, 2014, 9(3):e93003.
[9]	KESHARI R S, SILASI-MANSAT R, ZHU H, et al. Acute lung injury and fibrosis in a baboon model of Escherichia coli sepsis[J]. Am J Respir Cell Mol Biol, 2014, 50(2):439-450.
[10]	SAFFARZADEH M, JUENEMANN C, QUEISSER M A, et al. Neutrophil extracellular traps directly induce epithelial and endothelial cell death:a predominant role of histones[J]. PLoS One, 2012, 7(2):e32366.
[11]	MOURATIS M A, MAGKRIOTI C, OIKONOMOU N, et al. Autotaxin and endotoxin-induced acute lung injury[J]. PLoS One, 2015, 10(7):e0133619.
[12]	GAO Z Z, ZHANG C, JING L R, et al. The structural characterization and immune modulation activitives comparison of Codonopsis pilosula polysaccharide (CPPS) and selenizing CPPS (sCPPS) on mouse in vitro and vivo[J]. Int J Biol Macromol, 2020, 160:814-822.
[13]	巩志国, 顾柏臣, 沈媛, 等. 布劳恩脂蛋白对大肠埃希氏菌感染导致的小鼠体内细胞因子分泌及死亡的调节作用[J]. 动物医学进展, 2022, 43(2):25-29.GONG Z G, GU B C, SHEN Y, et al. Regulation of Braun lipoprotein on cytokine secretion and death in Escherichia coli-infected mice[J]. Prog Vet Med, 2022, 43(2):25-29. (in Chinese)
[14]	WU J D, LIU B, MAO W, et al. Prostaglandin E2 regulates activation of mouse peritoneal macrophages by Staphylococcus aureus through toll-like receptor 2, toll-like receptor 4, and NLRP3 inflammasome signaling[J]. J Innate Immun, 2020, 12(2):154-169.
[15]	FLORIAN M, WANG J P, DENG Y P, et al. Gene engineered mesenchymal stem cells:greater transgene expression and efficacy with minicircle vs. plasmid DNA vectors in a mouse model of acute lung injury[J]. Stem Cell Res Ther, 2021, 12(1):184.
[16]	MEYER N J, GATTINONI L, CALFEE C S. Acute respiratory distress syndrome[J]. Lancet, 2021, 398(10300):622-637.
[17]	WHEELER A P, BERNARD G R. Acute lung injury and the acute respiratory distress syndrome:a clinical review[J]. Lancet, 2007, 369(9572):1553-1564.
[18]	张建军, 胡春玲. 中药党参研究的现代进展[J]. 甘肃高师学报, 2017, 22(3):39-43.ZHANG J J, HU C L. Advances of modern in studies on codonopsis pilosula[J]. Journal of Gansu Normal Colleges, 2017, 22(3):39-43. (in Chinese)
[19]	白娟, 邱桐. 党参治疗呼吸窘迫综合征的实验研究-肺泡-动脉血氧分压差和气-血屏障的变化[J]. 甘肃中医学院学报, 1994, 11(1):50-52.BAI J, QIU T. Effects of codonopsis on changes of alveolar-arterial oxygen gradient and blood-air barrier in rats with respiratory distress syndrome[J]. Journal Gansu College of TCM, 1994, 11(1):50-52. (in Chinese)
[20]	郭鹏翔, 杨扶德, 王志旺, 等. 党参对慢性阻塞性肺疾病小鼠肿瘤坏死因子-α与核转录因子-κB信号通路的影响[J]. 中国临床药理学杂志, 2022, 38(16):1930-1934, 1944.GUO P X, YANG F D, WANG Z W, et al. Effects of codonopsis radix on tumor necrosis factor-α/nuclear factor-κB signaling pathway in mice with chronic obstructive pulmonary disease[J]. The Chinese Journal of Clinical Pharmacology, 2022, 38(16):1930-1934, 1944. (in Chinese)
[21]	王玉冰. 党参对博莱霉素致间质性肺病大鼠的作用机制研究[D]. 济南:山东中医药大学, 2015.WANG Y B. The mechanism of Dangshen on bleomycin-induced interstitial lung disease of rats[D]. Ji'nan:Shandong University of Traditional Chinese Medicine, 2015. (in Chinese)
[22]	RICCIOTTI E, FITZGERALD G A. Prostaglandins and inflammation[J]. Arterioscler Thromb Vasc Biol, 2011, 31(5):986-1000.
[23]	VOGEL L K, SÆBØ M, HØYER H, et al. Intestinal PTGS2 mRNA levels, PTGS2 gene polymorphisms, and colorectal carcinogenesis[J]. PLoS One, 2014, 9(8):e105254.
[24]	RAWLINGS J S, ROSLER K M, HARRISON D A. The JAK/STAT signaling pathway[J]. J Cell Sci, 2004, 117(8):1281-1283.
[25]	LANDONI G, PIEMONTI L, MONFORTE A D A, et al. A multicenter phase 2 randomized controlled study on the efficacy and safety of reparixin in the treatment of hospitalized patients with COVID-19 Pneumonia[J]. Infect Dis Ther, 2022, 11(4):1559-1574.
[26]	HAO J, LV T G, XU L P, et al. Macrophage migration inhibitory factor is involved in antineutrophil cytoplasmic antibody-mediated activation of C5a-primed neutrophils[J]. BMC Immunol, 2019, 20(1):22.
[27]	BOHUSH A, NIEWIADOMSKA G, FILIPEK A. Role of mitogen activated protein kinase signaling in Parkinson's disease[J]. Int J Mol Sci, 2018, 19(10):2973.
[28]	FAN C, WU L H, ZHANG G F, et al. 4'-Hydroxywogonin suppresses lipopolysaccharide-induced inflammatory responses in RAW 264. 7 macrophages and acute lung injury mice[J]. PLoS One, 2017, 12(8):e0181191.
[29]	MING K, HE M, SU L L, et al. The inhibitory effect of phosphorylated Codonopsis pilosula polysaccharide on autophagosomes formation contributes to the inhibition of duck hepatitis A virus replication[J]. Poul Sci, 2020, 99(4):2146-2156.
[30]	郜艳雪, 时坤, 李健明, 等. 党参多糖对动物免疫调节作用研究进展[J]. 动物医学进展, 2019, 40(9):103-106.GAO Y X, SHI K, LI J M, et al. Advance on immunoregulation effect of Codonopsis pilosula polysaccharides[J]. Progress in Veterinary Medicine, 2019, 40(9):103-106. (in Chinese)
[31]	PEARSON J S, HARTLAND E L. The inflammatory response during enterohemorrhagic Escherichia coli infection[J]. Microbiol Spectr, 2014, 2(4):EHEC-0012-2013.
[32]	MENG Y, XU Y J, CHANG C, et al. Extraction, characterization and anti-inflammatory activities of an inulin-type fructan from Codonopsis pilosula[J]. Int J Biol Macromol, 2020, 163:1677-1686.
[33]	HOBBS S, REYNOSO M, GEDDIS A V, et al. LPS-stimulated NF-κB p65 dynamic response marks the initiation of TNF expression and transition to IL-10 expression in RAW 264.7 macrophages[J]. Physiol Rep, 2018, 6(21):e13914.
[34]	LOTZE M T, TRACEY K J. High-mobility group box 1 protein (HMGB1):nuclear weapon in the immune arsenal[J]. Nat Rev Immunol, 2005, 5(4):331-342.
[35]	CHEN S S, XIA J G, ZHANG Y, et al. IL35 attenuated LPS-induced acute lung injury by regulating macrophage polarization[J]. Mol Biol Rep, 2022, 49(7):5811-5820.

Exploring the Mechanism of Codonopsis pilosula in Alleviation of Acute Lung Injury in Escherichia coli Infected Mice Based on Network Pharmacology

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