Rutin attenuates inflammation by downregulating AGE-RAGE signaling pathway in psoriasis: Network pharmacology analysis and experimental evidence

Mingxia Wang; Xiaoxuan Ma; Chunjie Gao; Yue Luo; Xiaoya Fei; Qi Zheng; Xin Ma; Le Kuai; Bin Li; Ruiping Wang; Jiankun Song

doi:10.1016/j.intimp.2023.111033

Rutin attenuates inflammation by downregulating AGE-RAGE signaling pathway in psoriasis: Network pharmacology analysis and experimental evidence

Int Immunopharmacol. 2023 Dec;125(Pt A):111033. doi: 10.1016/j.intimp.2023.111033. Epub 2023 Oct 27.

Authors

Mingxia Wang¹, Xiaoxuan Ma², Chunjie Gao¹, Yue Luo¹, Xiaoya Fei¹, Qi Zheng¹, Xin Ma³, Le Kuai⁴, Bin Li³, Ruiping Wang⁵, Jiankun Song⁶

Affiliations

¹ Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443, China.
² Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
³ Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China.
⁴ Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China.
⁵ Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443, China. Electronic address: w19830901@126.com.
⁶ Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443, China. Electronic address: 1607247615@qq.com.

PMID: 38149569
DOI: 10.1016/j.intimp.2023.111033

Abstract

Background: Jueyin granules (JYG) is effective against psoriasis, but its utility components are not clear. Rutin is the main monomer of JYG, its therapeutic effect and mechanism on psoriasis need to be further clarified.

Purpose: To explore the potential mechanisms of rutin on psoriasis through network pharmacology and experiments.

Methods: In vitro, cell viability was determined using the CCK8 assay, and inflammatory factors were identified using RT-qPCR. The hub genes and kernel pathways of action were identified by modular pharmacology analysis. In vivo, a BALB/c mice model of psoriasis was induced by Imiquimod (IMQ). The therapeutic effect and action pathway were detected through Western Blotting, RT-qPCR, histopathologic and immunohistochemical analysis.

Results: Rutin inhibited cell proliferation and expression of TNF-α and IL-6 in HaCaT cells. The hub genes include APP, INS, and TNF, while the kernel pathways contain the AGE-RAGE signaling pathway. In IMQ-induced psoriasis-like mice, rutin ameliorated skin lesions and inhibited cell proliferation. Rutin could attenuate inflammation by downregulating the AGE-RAGE signaling pathway.

Conclusion: This study suggests that rutin can reduce IMQ-induced psoriasis like skin inflammation in mice, and regulation of AGE-RAGE signaling pathway may be one of its potential anti-inflammatory mechanisms. Rutin has a promising therapeutic use for the treatment of psoriasis.

Keywords: AGE-RAGE signaling pathway; Network pharmacology; Psoriasis; Rutin.

MeSH terms

Animals
Disease Models, Animal
Imiquimod / pharmacology
Inflammation / chemically induced
Keratinocytes
Mice
Mice, Inbred BALB C
Network Pharmacology
Psoriasis* / chemically induced
Psoriasis* / drug therapy
Psoriasis* / pathology
Rutin* / pharmacology
Rutin* / therapeutic use
Signal Transduction
Skin / pathology

Substances

Rutin
Imiquimod