Study on the mechanism of Rhinoceros Horn and Rehmannia Decoction in the treatment of systemic lupus erythematosus based on the method of network pharmacology

doi:10.5246/jcps.2023.05.030

Abstract

Abstract:

In the present study, we aimed to explore the mechanism of Rhinoceros Horn and Rehmannia Decoction in treating systemic lupus erythematosus (SLE). First, the active ingredients and their targets of the Chinese medicine components of Rhinoceros Horn and Rehmannia Decoction were searched through TCMSP, TCMID, and BATMAN-TCM databases, and then the drug targets were summarized. Then the disease targets of SLE were retrieved from CTD, OMIM, and TCMIP databases, and the intersection of drug targets and disease targets was analyzed. Cytoscape 3.7.1 software was used to construct a drug-component target-disease network. The protein-protein interaction (PPI) network of therapeutic targets was constructed on the String platform, and its key modules and hub genes were screened. GO and KEGG enrichment analyses were performed in the DAVID database. A total of 22 active ingredients, 209 drug targets, 284 disease targets, and 59 therapeutic targets were screened out. Drug-component-target-disease and PPI network analysis yielded core active ingredients, such as quercetin, kaempferol, and baicalein, and core targets, such as PTGS2, CASP3, MMP9, AKT1, JUN, CXCL8, FOS, and TP53. It mainly involves TNF, PI3K Akt, Toll-like receptor, T cell receptor, and apoptosis signal pathways. It can be seen that Rhinoceros Horn and Rehmannia Decoction may play the role of anti-inflammation, inhibition of abnormal immune response, and apoptosis by regulating inflammation, immunity, and apoptosis signaling pathways. It has the characteristics of multi-center, multi-target, and multi-pathway.

Key words: Systemic lupus erythematosus, Network pharmacology, Rhinoceros Horn and Rehmannia Decoction, Target

Supporting:

Mengya Wang, Kuanyou Zhang, Xin Chen, Hao Fu, Shouchun Peng. Study on the mechanism of Rhinoceros Horn and Rehmannia Decoction in the treatment of systemic lupus erythematosus based on the method of network pharmacology[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(5): 351-359.

Figures/Tables 5

References 24

[1]	Barnett, R. Systemic lupus erythematosus. Lancet. 2016, 387, 1711.
[2]	Chen, W.W.; Xiao, X.L.; Su, L.; Su, X.; Xia, J. Compound Shengdi Mixture from TLR-NF- κ B pathway regulates Th17/Treg balance in MRL/lpr mice. Chin. J. Tradit. Chin. Med. 2020, 10, 5270–5273.
[3]	Zhu, Y.L.; Wu, F. Overview of TCM syndrome types and changes of systemic lupus erythematosus. Chin. J. Tradit. Chin. Med. 2018, 07, 2973–2975.
[4]	Jiang, Z.; Tang, F.; Ma, W.K.; Lan, W.Y.; Fan, M.; Cai, X. Meta analysis of the clinical efficacy of Rhinoceros horn Rehmannia glutinosa decoction combined with anti rheumatic drugs in the treatment of heat toxic and intense systemic lupus erythematosus. J. Guizhou Univ. Tradit. Chin. Med. 2021, 03, 81–87.
[5]	Zhou, G.W.; Chen, Y.H.; Xia, P.; Gao, K.; Chen, J.M.; Guo, F. Study on the mechanism of Langchuangjing traditional Chinese medicine granules in treating systemic lupus erythematosus based on network pharmacology. Chin. J. Tradit. Chin. Med. 2020, 10, 122–127.
[6]	Fei, X.J.; Zhang, X.; Wang, Q.; Li, J.B.; Shen, H.; Wang, X.Y.; Liu, H.Q.; Tao, W.W. Xijiao Dihuang Decoction alleviates ischemic brain injury in MCAO rats by regulating inflammation, neurogenesis, and angiogenesis. Evid. Based Complement. Altern. Med. 2018, 2018, 5945128.
[7]	Liu, J.; Pei, T.; Mu, J.; Zheng, C.; Chen, X.; Huang, C.; Fu, Y.; Liang, Z.; Wang, Y. Systems Pharmacology Uncovers the Multiple Mechanisms of Rhinoceros horn Rehmannia glutinosa Decoction for the Treatment of Viral Hemorrhagic Fever. Evid. Based Complement. Altern. Med. 2016, 06, 9025036.
[8]	Huang, D.Y. Effect of Rhinoceros horn Rehmannia glutinosa Decoction on inflammatory factors and immunoglobulin in patients with systemic lupus erythematosus skin damage. Modern Med. Health Res. Elect. J. 2020, 08, 71–73.
[9]	Wang, F.S. Clinical efficacy of Rhinoceros horn Rehmannia glutinosa decoction combined with small dose of corticosteroids in the treatment of heat toxic and burning systemic lupus erythematosus. J. Pract. Chin. Med. 2021, 04, 100–102.
[10]	Zhou, X.G.; Li, H.W.; Wu, J.L. Effect of quercetin on LPE like mouse model induced by hypoglycane. Chin. J. Hospital Pharm. 2016, 21, 1869–1872.
[11]	Cheng, L.Y.; Tu, L.L.; Shi, H. p38MAPK’s effect on chronic prostatitis pain and the intervention of quercetin. China Modern Appl. Pharm. 2016, 08, 984–988.
[12]	Lin, F. Kaempferol enhances the suppressive function of Treg cells by inhibiting FOXP3 phosphorylation. Int. Immunopharmacol. 2015, 28, 859–865.
[13]	Ma, S.; Jin, Y.; Shi, Y.; Zhang, Y.D. Study on the effect of Hongban Qingtang on sIL-2R level and prognosis of patients with systemic lupus erythematosus. Sichuan Tradit. Chin. Med. 2019, 08, 141–143.
[14]	Kordulewska, N.K.; Cieślińska, A.; Fiedorowicz, E.; Jarmołowska, B.; Kostyra, E. High expression of IL-1RI and EP2 receptors in the IL-1β/COX-2 pathway, and a new alternative to non-steroidal drugs—osthole in inhibition COX-2. Int. J. Mol. Sci. 2019, 20, 186.
[15]	Chen, S.; Wang, Y.; Qin, H.; Lin, J.; Xie, L.; Chen, S.; Liang, J.; Xu, J. Downregulation of miR-633 activated AKT/mTOR pathway by targeting AKT1 in lupus CD4⁺ T cells. Lupus. 2019, 28, 510–519.
[16]	Ruchakorn, N.; Ngamjanyaporn, P.; Suangtamai, T.; Kafaksom, T.; Polpanumas, C.; Petpisit, V.; Pisitkun, T.; Pisitkun, P. Performance of cytokine models in predicting SLE activity. Arthritis Res. Ther. 2019, 21, 287.
[17]	Yu, Y.; Liu, L.; Hu, L.L.; Yu, L.L.; Li, J.P.; Rao, J.A.; Zhu, L.J.; Liang, Q.; Zhang, R.W.; Bao, H.H.; Cheng, X.S. Potential therapeutic target genes for systemic lupus erythematosus: a bioinformatics analysis. Bioengineered. 2021, 12, 2810–2819.
[18]	Oikonomidou, O.; Vlachoyiannopoulos, P.G.; Kominakis, A.; Kalofoutis, A.; Moutsopoulos, H.M.; Moutsatsou, P. Glucocorticoid receptor, nuclear factor kappaB, activator protein-1 and C-Jun N-terminal kinase in systemic lupus erythematosus patients. Neuroimmunomodulation. 2006, 13, 194–204.
[19]	Schonthaler, H.B.; Guinea-Viniegra, J.; Wagner, E.F. Targeting inflammation by modulating the Jun/AP-1 pathway. Transl. Psychiatry. 2011, 70, i109–i112.
[20]	Yang, Z.; Xie, R.F.; Zhong, M.H.; Xie, G.Q.; Fan, Y.S.; Zhao, T. Potential molecular mechanisms of Zhibai Dihuang wan in systemic lupus erythematosus based on network biology. Evid. Based Complement. Altern. Med. 2020, 2020, 7842179.
[21]	Teng, Z.; Lin, X.; Luan, C.; Sun, Y.; Li, X. The high expression of miR-564 in patients with systemic lupus erythematosus promotes differentiation and maturation of DC cells by negatively regulating TP53 expression in vitro. Lupus. 2021, 30, 1469–1480.
[22]	Zhou, Y.; Li, Z. Systemic lupus erythematosus and infection. Chin. J. Clin. (Electronic Edition). 2016, 21, 3271–3275.
[23]	Gong, X.B.; Li, H.; Li, SW.; Wang, B.S.; Yao, M.M. Network Pharmacological Analysis of Artemisia Annua in Treating Systemic Lupus Erythematosus. J. Clin. Chin. Med. 2021, 06, 1112–1118.
[24]	Li, J.; Wang, X.; Zhang, F.; Yin, H. Toll-like receptors as therapeutic targets for autoimmune connective tissue diseases. Pharmacol. Ther. 2013, 138, 441–451.