Exploring the Mechanism of Topical Application of Clematis Florida in the Treatment of Rheumatoid Arthritis through Network Pharmacology and Experimental Validation

Author:

Lei Ting12,Jiang Chang1,Zhao Li1,Zhang Jizhou1,Xiao Qing1,Chen Yanhong12,Zhang Jie1,Zhou Chunquan1,Wang Gong1,Han Jing1ORCID

Affiliation:

1. Institute of Materia Medica, Fujian Academy of Chinese Medical Science, Fuzhou 350003, China

2. Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China

Abstract

Clematis Florida (CF) is a folk medicinal herb in the southeast of China, which is traditionally used for treating osteoarticular diseases. However, the mechanism of its action remains unclear. The present study used network pharmacology and experimental validation to explore the mechanism of CF in the treatment of rheumatoid arthritis (RA). Liquid chromatography–mass spectrometry (LC-MS/MS) identified 50 main compounds of CF; then, their targets were obtained from TCMSP, ETCM, ITCM, and SwissTargetPrediction databases. RA disease-related targets were obtained from DisGeNET, OMIM, and GeneCards databases, and 99 overlapped targets were obtained using a Venn diagram. The protein–protein interaction network (PPI), the compound–target network (CT), and the compound–potential target genes–signaling pathways network (CPS) were constructed and analyzed. The results showed that the core compounds were screened as oleanolic acid, oleic acid, ferulic acid, caffeic acid, and syringic acid. The core therapeutic targets were predicted via network pharmacology analysis as PTGS2 (COX-2), MAPK1, NF-κB1, TNF, and RELA, which belong to the MAPK signaling pathway and NF-κB signaling pathway. The animal experiments indicated that topical application of CF showed significant anti-inflammatory activity in a mouse model of xylene-induced ear edema and had strong analgesic effect on acetic acid-induced writhing. Furthermore, in the rat model of adjuvant arthritis (AA), topical administration of CF was able to alleviate toe swelling and ameliorate joint damage. The elevated serum content levels of IL-6, COX-2, TNF-α, IL-1β, and RF caused by adjuvant arthritis were reduced by CF treatment. Western blotting tests showed that CF may regulate the ERK and NF-κB pathway. The results provide a new perspective for the topical application of CF for treatment of RA.

Funder

Fundamental Research Project for non-Profit Scientific Research Institutes in Fujian Province

Fujian Provincial Traditional Chinese Medicine Science and Technology Program

National Natural Science Foundation of China

Fujian Provincial Traditional Chinese Medicine Health Technology and Economic Integration Service Platform

Publisher

MDPI AG

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