Advanced Search

Journal of Traditional Chinese Medicine >

2022 , Vol. 42 >Issue 2: 304 - 313

DOI: https://doi.org/10.19852/j.cnki.jtcm.20210707.001

Research Articles

Mechanism of Huashi Xingyu Qingre recipe (化湿行淤清热方) in treating oral lichen planus based on network pharmacology and clinical trial verification

  • Qianlan DENG ,
  • Yueting LU ,
  • Lijuan YAN ,
  • Hualin LU ,
  • Ruizhe JIN ,
  • Yanzhi XU ,
  • Jing SONG ,
  • Tiejun LIU
Expand
  • 1 Department of Stomatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China
    2 Department of Stomatology, Hebei Children's Hospital, Shijiazhuang 050000, China
    3 Department of Stomatology, Shijiazhuang Third Hospital, Shijiazhuang 050000, China
LIU Tiejun, Department of Stomatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050000, China. liutiejun1973@sohu.com, Telephone: +86-13831110771

Received date: 2021-01-05

  Accepted date: 2021-03-30

  Online published: 2021-07-07

Supported by

Proteomics Study on Differential Protein of Oral Lichen Planus and Chinese Medicine Intervention of Huashi Xingyu Qingre recipe(81273813);Effect of Huashi Xingyu Qingre recipe on Differential Protein Expression Of Oral Lichen Planus(2011013);Project of National Cancer Center Climbing Fund(NCC201803B006);Project of Health Department Research Fund of Hebei Province(20170691);Scientific Research Project of TCM administration in Hebei Province(2018138);Government-funded Outstanding Talents Project in 2020(2704016)

Fold

Abstract

OBJECTIVE: To identify the main active components and targets of Huashi Xingyu Qingre recipe (化湿行淤清热方, HXQR) and to investigate its mechanism in the treatment of oral lichen planus (OLP).

METHODS: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was searched to identify the active ingredients and corresponding targets of HXQR. Disease genes were obtained from the GeneCards database, and a “drug-disease regulatory network” was constructed using Cytoscape software and PERL programming language. The STRING database was used to build a protein-protein interaction network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms were analyzed using R software with a Bioconducter plugin. Finally, the results and the efficacy of HXQR in treating OLP were validated in a clinical trial that included enzyme-linked immunosorbent assay (ELISA) testing and observations of the post-treatment changes in clinical symptoms.

RESULTS: HXQR contained 167 active components and 261 targets, with 391 disease targets. The intersection of these two categories in a Venn diagram revealed 57 drug-disease common targets. A compound-target network was constructed and revealed that the six key pharmaceutical ingredients of HXQR were quercetin, luteolin, wogonin, kaempferol, beta-carotene, and baicalein. The protein-protein interaction network mainly involved core proteins such as ALB, interleukin-6, and AKT1. Drug-disease common targets were enriched in 1628 GO terms and 117 KEGG terms, mainly involving inflammatory responses, viral infections, and tumor-related pathways. ELISA testing indicated that HXQR inhibited the tumor necrosis factor (TNF) signaling pathway by reducing the expression of interleukin-6, matrix metalloproteinase-9, and intercellular adhesion molecule-1. The clinical symptoms of the patients with OLP were significantly improved after 8 weeks of treatment with HXQR.

CONCLUSION: HXQR treats OLP by regulating the TNF signaling pathway, resulting in a marked treatment effect with few adverse effects.

Key words： lichen planus, oral; network pharmacology; clinical trial; Huashi Xingyu Qingre recipe

Cite this article

Qianlan DENG , Yueting LU , Lijuan YAN , Hualin LU , Ruizhe JIN , Yanzhi XU , Jing SONG , Tiejun LIU . Mechanism of Huashi Xingyu Qingre recipe (化湿行淤清热方) in treating oral lichen planus based on network pharmacology and clinical trial verification[J]. Journal of Traditional Chinese Medicine, 2022 , 42(2) : 304 -313 . DOI: 10.19852/j.cnki.jtcm.20210707.001

References

1. Lozada-Nur F, Miranda C. Oral lichen planus: epidemiology, clinical characteristics, and associated diseases. Semin Cutan Med Surg 1997; 16: 273-7.
2. Alrashdan MS, Cirillo N, McCullough M. Oral lichen planus: a literature review and update. Arch Dermatol Res 2016; 308: 539-51.
3. Fitzpatrick SG, Hirsch SA, Gordon SC. The malignant transformation of oral lichen planus and oral lichenoid lesions: a systematic review. J Am Dent Assoc 2014; 145: 45-56.
4. Kurago ZB. Etiology and pathogenesis of oral lichen planus: an overview. Oral Surg Oral Med Oral Pathol Oral Radiol 2016; 122: 72-80.
5. Gu S, Pei J. Innovating Chinese herbal medicine: from traditional health practice to scientific drug discovery. Front Pharmacol 2017; 8: 381.
6. Li J, Lu C, Jiang M, et al. Traditional chinese medicine-based network pharmacology could lead to new multicompound drug discovery. Evid Based Complement Alternat Med 2012; 2012: 149762.
7. Hao da C, Xiao PG. Network pharmacology: a Rosetta Stone for Traditional Chinese Medicine. Drug Dev Res 2014; 75: 299-312.
8. Zhang GB, Li QY, Chen QL, et al. Network pharmacology: a new approach for chinese herbal medicine research. Evid Based Complement Alternat Med 2013; 2013: 621423.
9. Zhang B, Wang X, Li S. An integrative platform of TCM network pharmacology and its application on a herbal formula, Qing-Luo-Yin. Evid Based Complement Alternat Med 2013; 2013: 456747.
10. Ru J, Li P, Wang J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6: 13.
11. Stelzer G, Rosen N, Plaschkes I, et al. The genecards suite: from gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics 2016; 54: 1.30.1-1.30.33.
12. Doncheva NT, Morris JH, Gorodkin J, et al. Cytoscape StringApp: network analysis and visualization of proteomics data. J Proteome Res 2019; 18: 623-32.
13. Szklarczyk D, Morris JH, Cook H, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res 2017; 45: D362-8.
14. Walter W, Sanchez-Cabo F, Ricote M. GOplot: an R package for visually combining expression data with functional analysis. Bioinformatics 2015; 31: 2912-4.
15. Carullo G, Cappello AR, Frattaruolo L, et al. Quercetin and derivatives: useful tools in inflammation and pain management. Future Med Chem 2017; 9: 79-93.
16. Li Y, Yao J, Han C, et al. Quercetin, nflammation and immunity. Nutrients 2016; 8: 167.
17. Cheng SC, Huang WC, JH SP, et al. Quercetin inhibits the production of IL-1beta-induced inflammatory cytokines and chemokines in ARPE-19 cells via the MAPK and NF-kappa B signaling pathways. Int J Mol Sci 2019; 20: 2957.
18. Wang F, Ke Y, Yang L, et al. Quercetin protects human oral keratinocytes from lipopolysaccharide-induced injury by down-regulating microRNA-22. Hum Exp Toxicol 2020; 39: 1310-7.
19. Aziz N, Kim MY, Cho JY. Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies. J Ethnopharmacol 2018; 225: 342-58.
20. Abu-Elsaad N, El-Karef A. Protection against nonalcoholic steatohepatitis through targeting IL-18 and IL-1 alpha by luteolin. Pharmacol Rep 2019; 71: 688-94.
21. Fei J, Liang B, Jiang C, et al. Luteolin inhibits IL-1 beta-induced in flammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model. Biomed Pharmacother 2019; 109: 1586-92.
22. Yao ZH, Yao XL, Zhang Y, et al. Luteolin could improve cognitive dysfunction by inhibiting neuroinflammation. Neurochem Res 2018; 43: 806-20.
23. Velmurugan BK, Lin JT, Mahalakshmi B, et al. Luteolin-7-O-glucoside inhibits oral cancer cell migration and invasion by regulating matrix metalloproteinase-2 expression and extracellular signal-regulated kinase pathway. Biomolecules 2020; 10.
24. Wang W, Xia T, Yu X. Wogonin suppresses inflammatory response and maintains intestinal barrier function via TLR4-MyD88-TAK1-mediated NF-kappa B pathway in vitro. Inflamm Res 2015; 64: 423-31.
25. Lee SO, Jeong YJ, Yu MH, et al. Wogonin suppresses TNF-alpha-induced MMP-9 expression by blocking the NF-kappa B activation via MAPK signaling pathways in human aortic smooth muscle cells. Biochem Biophys Res Commun 2006; 351: 118-25.
26. Kang JW, Kim JH, Song K, et al. Kaempferol and quercetin, components of Ginkgo biloba extract (EGb 761), induce caspase-3-dependent apoptosis in oral cavity cancer cells. Phytother Res 2010; 24 Suppl 1: S77-82.
27. Yao H, Sun J, Wei J, et al. Kaempferol protects blood vessels from damage induced by oxidative stress and inflammation in association With the Nrf2/HO-1 signaling pathway. Front Pharmacol 2020; 11: 1118.
28. Aziz E, Batool R, Akhtar W, et al. Xanthophyll: health benefits and therapeutic insights. Life Sci 2020; 240: 117104.
29. Buajeeb W, Kraivaphan P, Amornchat C, et al. Reduction of micronuclei in oral lichen planus supplemented with beta-carotene. J Oral Sci 2008; 50: 461-7.
30. Wang J, Luo H, Yang L, et al. Baicalein induces apoptosis and reduces inflammation in LPS-stimulated keratinocytes by blocking the activation of NF-kappa B: implications for alleviating oral lichen planus. Cell Mol Biol (Noisy-le-grand) 2016; 62: 55-60.
31. Gu GM, Martin MD, Darveau RP, et al. Oral and serum IL-6 levels in oral lichen planus patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 98: 673-8.
32. Sun A, Chia JS, Chang YF, et al. Levamisole and Chinese medicinal herbs can modulate the serum interleukin-6 level in patients with recurrent aphthous ulcerations. J Oral Pathol Med 2003; 32: 206-14.
33. Wei W, Sun Q, Deng Y, et al. Mixed and inhomogeneous expression profile of Th1/Th2 related cytokines detected by cytometric bead array in the saliva of patients with oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol 2018; 126: 142-51.
34. Kumagai K, Horikawa T, Gotoh A, et al. Up-regulation of EGF receptor and its ligands, AREG, EREG, and HB-EGF in oral lichen planus. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010; 110: 748-54.
35. Fu J, Chen W, Sun Z. Gene expression of epidermal growth factor and epidermal growth factor receptor in oral lichen planus. Zhonghua Kou Qiang Yi Xue Za Zhi 2005; 40: 455-8.
36. Tobon-Arroyave SI, Villegas-Acosta FA, Ruiz-Restrepo SM, et al. Expression of caspase-3 and structural changes associated with apoptotic cell death of keratinocytes in oral lichen planus. Oral Dis 2004; 10: 173-8.
37. Weber B, Schlapbach C, Stuck M, et al. Distinct interferon-gamma and interleukin-9 expression in cutaneous and oral lichen planus. J Eur Acad Dermatol Venereol 2017; 31: 880-6.
38. Sugerman PB, Savage NW, Walsh LJ, et al. The pathogenesis of oral lichen planus. Crit Rev Oral Biol Med 2002; 13: 350-65.
39. Wang H, Guan X, Luo Z, et al. The association and potentially destructive role of Th9/IL-9 is synergistic with Th17 cells by elevating MMP9 production in local lesions of oral lichen planus. J Oral Pathol Med 2018; 47: 425-33.
40. Ma RJ, Tan YQ, Zhou G. Aberrant IGF1-PI3K/AKT/MTOR signaling pathway regulates the local immunity of oral lichen planus. Immunobiology 2019; 224: 455-61.
41. Wang J, Luo H, Xiao Y, et al. miR-125b inhibits keratinocyte proliferation and promotes keratinocyte apoptosis in oral lichen planus by targeting MMP-2 expression through PI3K/Akt/mTOR pathway. Biomed Pharmacother 2016; 80: 373-80.
42. Segura S, Rozas-Munoz E, Toll A, et al. Evaluation of MYC status in oral lichen planus in patients with progression to oral squamous cell carcinoma. Br J Dermatol 2013; 169: 106-14.
43. Bradley JR. TNF-mediated inflammatory disease. J Pathol 2008; 214: 149-60.
44. Yang S, Wang J, Brand DD, et al. Role of TNF-TNF receptor 2 signal in regulatory T cells and its therapeutic implications. Front Immunol 2018; 9: 784.
45. Zhou XJ, Sugerman PB, Savage NW, et al. Matrix metalloproteinases and their inhibitors in oral lichen planus. J Cutan Pathol 2001; 28: 72-82.
46. Chen X, Liu Z, Yue Q. The expression of TNF-alpha and ICAM-1 in lesions of lichen planus and its implication. J Huazhong Univ Sci Technolog Med Sci 2007; 27: 739-41.
47. Rhodus NL, Cheng B, Myers S, et al. A comparison of the pro-inflammatory, NF-kappa B-dependent cytokines: TNF-alpha, IL-1-alpha, IL-6, and IL-8 in different oral fluids from oral lichen planus patients. Clin Immunol 2005; 114: 278-83.
Options
Outlines

/

〈 〉