Exploration of potential mechanisms for the treatment of ulcerative colitis by Solanum diphyllum L. based on network pharmacology and molecular docking

Abstract

Evidence of the advantages of Solanum nigrum L. for the treatment of ulcerative colitis is accumulating. However, research revealing the treatment of Solanum diphyllum L. against ulcerative colitis is scarce. In this study, the chemical components of the extract of Solanum diphyllum L. were characterized by LC-MS/MS, identifying 31 compounds by positive and negative total ion flow maps. A total of 425 component target genes and 1 900 disease target genes were obtained, and 121 intersection targets and 6 core targets were obtained after the intersection of the two genes by means of network pharmacology. GO analysis and KEGG analysis respectively obtained 20 signaling pathways such as anti-inflammation. The results of molecular docking showed that the chemical components could successfully dock with the target proteins of the disease such as SRC, EGFR, PTGS2, MMP9, HSP90AA1, ESR1. This study provided a scientific basis for the development and application of Solanum diphyllum L.

Keywords

LC-MS/MS / ulcerative colitis / Solanum diphyllum L. / network pharmacology / molecular docking

References

[1] Ordás I, Eckmann L, Talamini M, et al. Ulcerative colitis[J]. Lancet, 2023, 402 (10401): 571-584.

[2] Pituch-Zdanowska A, Dembiński Ł, Banaszkiewicz A. Old but fancy: Curcumin in ulcerative colitis-current overview[J]. Nutrients, 2022, 14 (24): 5249.

[3] Zhou J, Pan ZY, Zhao Y, et al. Physiological growth response of Solanum mongolicum seedlings to cadmium stress[J]. Plants of Guangxi, 2022, 42 (4): 628-638.

[4] Wan MLY, Co VA, El-Nezami H. Dietary polyphenol impact on gut health and microbiota[J]. Crit Rev Food Sci Nutr, 2021, 61 (4): 690-711.

[5] Rumpf J, Burger R, Schulze M. Statistical evaluation of DPPH, ABTS, FRAP, and Folin-Ciocalteu assays to assess the antioxidant capacity of lignins[J]. Int J Biol Macromol, 2023, 223: 123470.

[6] Ji YB, Wang SH, Gao SY, et al. Effect of solanine on sialic acid and sealing degree of tumor cell membrane in H22 tumor-bearing mice[J]. Chin Herb Med, 2005, 36 (1): 79.

[7] Marshall DC, Lyman SK, McCauley S, et al. Selective allosteric inhibition of MMP9 is efficacious in preclinical models of ulcerative colitis and colorectal cancer[J]. PLoS One, 2015, 10 (5): e0127063.

[8] Cho RL, Yang CC, Lee IT, et al. Lipopolysaccharide induces ICAM-1 expression via a c-Src/NADPH oxidase/ ROS-dependent NF-κB pathway in human pulmonary alveolar epithelial cells[J]. Am J Physiol Lung Cell Mol Physiol, 2016, 310 (7): L639-L657.

[9] Chelakkot C, Ghim J, Rajasekaran N, et al. Intestinal epithelial cell-specific deletion of PLD2 alleviates DSS- induced colitis by regulating occludin[J]. Sci Rep, 2017, 7 (1): 1573.

[10] Kim HG, Kim MY, Cho JY. Alisma canaliculatum ethanol extract suppresses inflammatory responses in LPS- stimulated macrophages, HCl/EtOH-induced gastritis, and DSS-triggered colitis by targeting Src/Syk and TAK1 activities[J]. J Ethnopharmacol, 2018, 219: 202-212.

[11] Chiou WF, Don MJ, Liao JF, et al. Psoralidin inhibits LPS- induced iNOS expression via repressing Syk-mediated activation of PI3K-IKK-IκB signaling pathways[J]. Eur J Pharmacol, 2011, 650: 102-109.

[12] Byeon SE, Yi YS, Oh J, et al. The role of src kinase in macrophage-mediated inflammatory responses[J]. Mediat Inflamm, 2012, 2012: 512926.

[13] Hardbower DM, Coburn LA, Asim M, et al. EGFR- mediated macrophage activation promotes colitis- associated tumorigenesis[J]. Oncogene, 2017, 36 (27): 3807-3819.

[14] Manieri N, Mack M, Himmelrich M, et al. Stappenbeck mucosally transplanted mesenchymal stem cells stimulate intestinal healing by promoting angiogenesis[J]. J Clin Invest, 2015, 125 (9): 3606-3618.

[15] Grimstad T, Kvivik I, Kvaløy JT, et al. Heat shock protein 90 and inflammatory activity in newly onset Crohn’s disease scand[J]. J Gastroenterol, 2018, 53 (12): 1453-1458.

[16] Li F, Boon ACM, Michelson AP, et al. Estrogen hormone is an essential sex factor inhibiting inflammation and immune response in COVID-19[J]. Sci Rep, 2022, 12 (1): 9462.

[17] Adachi A, Honda T, Egawa G, et al. Estradiol suppresses psoriatic inflammation in mice by regulating neutrophil and macrophage functions[J]. J Allergy Clin Immunol, 2022, 150 (4): 909-919.

[18] Ashrafizadeh M, Zarrabi A, Hushmandi K, et al. Association of the epithelial-mesenchymal transition (EMT) with cisplatin resistance[J]. Int J Mol Sci, 2020, 21 (11): 4002.

[19] Jin J, Zhong Y, Long J, et al. Ginsenoside Rg1 relieves experimental colitis by regulating balanced differentiation of Tfh/Treg cells[J]. Int Immunopharmacol, 2021, 100: 108133.

[20] Tolstanova G, Khomenko T, Deng X, et al. Neutralizing anti-vascular endothelial growth factor (VEGF) antibody reduces severity of experimental ulcerative colitis in rats: Direct evidence for the pathogenic role of VEGF J. pharmacol[J]. Exp Ther, 2009, 328: 749-757.

[21] Tolstanova G, Khomenko T, Deng XM, et al. New molecular mechanisms of the unexpectedly complex role of VEGF in ulcerative colitis[J]. Biochem Biophys Res Commun, 2010, 399 (4): 613-616.