Discussion on the mechanism of Salvia miltiorrhiza in treating pathological scars based on network pharmacology

doi:10.5246/jcps.2021.10.069

Abstract

Abstract:

In the present study, we aimed to explore the mechanism of Salvia miltiorrhiza in the treatment of pathological scars (PS) by network pharmacology. The active ingredients and drug targets of Salvia miltiorrhiza were screened out through TCMSP database, the disease targets of PS in GeneCards database were obtained, and Venn diagram analysis on drug targets and disease targets was performed, and the intersection was used as the target of Salvia miltiorrhiza for the treatment of PS. Cytoscape software was used to construct a drug-ingredient-target-disease network diagram. A protein-protein interaction network was constructed through String website, its key protein modules and hub genes were screened with Cytoscape software, and GO and KEGG enrichment analyses were performed in DAVID database. Fifty-nine active ingredients, 138 drug targets, and 90 targets of Salvia miltiorrhiza for the treatment of PS were screened out. Core ingredients, such as luteolin and tanshinone IIA, were obtained. The hub genes, such as VEGFA, TP53, JUN, STAT3, AKT1, MAPK1, and PTGS2, and signaling pathways, such as HIF-1, TNF, MAPK, PI3K-Akt, and Jak-STAT, were screened out. Salvia miltiorrhiza might improve PS hypoxia, inflammation, and balance of proliferation and apoptosis of fibroblasts by regulating HIF-1, TNF, MAPK, PI3K-Akt, and Jak-STAT signaling pathways. Moreover, it had the characteristics of multiple centers, multiple targets, and multiple pathways.

Key words: Pathological scar, Network pharmacology, Salvia miltiorrhiza

Supporting:

Hongzhuang Zhang, Zhiwei Yang, Jianghe Zhang, Yiming Zhang, Shike Hou, Zhenguo Wang, Li Yan, Dongli Fan. Discussion on the mechanism of Salvia miltiorrhiza in treating pathological scars based on network pharmacology[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(10): 813-821.

Figures/Tables 5

References 22

[1]	Yu, L.J.; Wang, X.J.; Long, X. Advances in mechanisms for prevention and treatment of pathological scars with mesenchymal stem cells. Acta Acad. Med. Sin. 2017, 39, 573–577.
[2]	Chiang, R.S.; Borovikova, A.A.; King, K.; Banyard, D.A.; Lalezari, S.; Toranto, J.D.; Paydar, K.Z.; Wirth, G.A.; Evans, G.R.D.; Widgerow, A.D. Current concepts related to hypertrophic scarring in burn injuries. Wound Repair Regen. 2016, 24, 466–477.
[3]	Huang, J.W.; Han, X.; Zhao, X.; Li, X.B.; Dong, X.Z.; An, L.F.; Ji, S.X.; Xia, X.H. Treatment and improvement of scar hyperplasia by panax notoginseng based on network pharmacology study on molecular mechanisms. Int. J. Trad. Chin. Med. 2019, 41, 1353–1359.
[4]	Xu, X.Q.; Yang, S.L.; Wang, J.; Lai, J.H.; Guo, S.Y.; Wang, F.; Chen, Q.F.; Shi, J. Multi-target analysis of Salvianolic acid B in the treatment of hypertrophic scar. J. Guangdong Pharm. Univ. 2019, 35, 523–528.
[5]	Wu, Z.Y.; Luo, S.J.; Jiang, L.M. Effect of cryptotanshinone on hypertrophic scar tissue of rabbit ear. Guangxi Med. 2008, 7, 1012–1013.
[6]	Lai, J.H.; Xu, X.Q.; Shi, J.; Guo, S.Y. Research progress on the formation mechanism of hypertrophic scar and treatment of Salvia miltiorrhiza. J. Guangdong Pharm. Univ. 2019, 35, 707–713.
[7]	Sun, G.F.; Zhang, X.F.; Chen, Y.F.; Feng, D.X. ShengjiYuhong ointment inhibits the proliferation and collagen secretion of human hypertrophic scar fibroblasts by down regulating TGF-β1/Smads. Lishizhen Med. Mater. Med. Res. 2016, 27, 1590–1593.
[8]	Guan, Z.Q.; Chen, G.S.; Feng, L.C.; Zhao, L.; Zhai, X.X. Analysis of traditional Chinese medicine treatment of pathological scar based on literature research. Chin. Arch. Tradit. Chin. Med. 2018, 36, 1803–1805.
[9]	Xu, J.P.; Wei, K.H.; Zhang, G.J.; Lei, L.J.; Yang, D.W.; Wang, W.L.; Han, Q.H.; Xia, Y.; Bi, Y.Q.; Yang, M.; Li, M.H. Ethnopharmacology, phytochemistry, and pharmacology of Chinese Salvia species: a review. J. Ethnopharmacol. 2018, 225, 18–30.
[10]	Shen, W.L. Protective effects of tanshinone IIA derivative on myocardial ischemia/reperfusion injury in rats. J. Chin. Pharm. Sci. 2018, 27, 1–13.
[11]	Chen, G.; Liang, Y.M.; Liang, X.; Li, Q.F.; Liu, D.L. Tanshinone IIA inhibits proliferation and induces apoptosis through the downregulation of survivin in keloid fibroblasts. Ann. Plast. Surg. 2016, 76, 180–186.
[12]	Chen, G.; Liang, Y.M.; Li Q.F. Effect of Tanshinone IIA on Cell Proliferation, Apoptosis and Cell Cycle of Fibroblasts Derived from Keloid. J. Tissue Enginee. Rec. Surgery. 2012, 8, 73–77.
[13]	Zhang, Y.F.; Wang, J.; Zhou, S.Z.; Xie, Z.B.; Wang, C.D.; Gao, Y.; Zhou, J.; Zhang, X.L.; Li, Q.F. Flavones hydroxylated at 5, 7, 3' and 4' ameliorate skin fibrosis via inhibiting activin receptor-like kinase 5 kinase activity. Cell Death Dis. 2019, 10, 124.
[14]	Ye, F.L. HIF-1α expresion in keloid and its corelation with angiogenesis, inflammatory response and apoptosis. J. Hainan Med. College. 2017, 23, 2442–2444+2448.
[15]	Wilgus, T.A. Vascular endothelial growth factor and cutaneous scarring. Adv. Wound Care. 2019, 8, 671–678.
[16]	Xu, X.Q.; Han, B.; Lai, J.H.; Lin, Y.J.; Shi, J. Effect and mechanism of tanshinone IIA on TGF-β1 induced human skin fibroblast proliferation. Chin. Herbal Med. 2020, 51, 4685–4690.
[17]	Ogawa, R. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis. Int. J. Mol. Sci. 2017, 18, 606.
[18]	Jundi, K.; Greene, C.M. Transcription of interleukin-8: how altered regulation can affect cystic fibrosis lung disease. Biomolecules. 2015, 5, 1386–1398.
[19]	Morris Jr, M.W.; Allukian III, M.; Herdrich, B.J.; Caskey, R.C.; Zgheib, C.; Xu, J.W.; Dorsett-Martin, W.; Mitchell, M.E.; Liechty, K.W. Modulation of the inflammatory response by increasing fetal wound size or interleukin-10 overexpression determines wound phenotype and scar formation. Wound Repair Regen. 2014, 22, 406–414.
[20]	Zhang, W.; Bai, X.Z.; Zhao, B.; Li, Y.; Zhang, Y.J.; Li, Z.Z.; Wang, X.J.; Luo, L.; Han, F.; Zhang, J.L.; Han, S.C.; Cai, W.X.; Su, L.L.; Tao, K.; Shi, J.H.; Hu, D.H. Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway. Exp. Cell Res. 2018, 370, 333–342.
[21]	Mari, W.; Alsabri, S.G.; Tabal, N.; Younes, S.; Sherif, A.; Simman, R. Novel insights on understanding of keloid scar: article review. J. Am. Coll. Clin. Wound Specialists. 2015, 7, 1–7.
[22]	Wei, B.; Fan, J.C.; Yan, L.; Luo Q.; Zhang, J.Y.; Hou, H.L.; Lv, X.Y.; Cao, R.; Wang, C.M. Effect of PTGS2 knockdown on gene expression profile of skin fibroblasts. Basic Med. Clinic. 2012, 32, 396–401.