Dictamnus dasycarpus turcz. Attenuates collagen-induced rheumatoid arthritis in DBA/1J mice through inhibiting IL-17 signaling pathway

Abstract

Ethnopharmacological relevance

Rheumatoid Arthritis (RA), a chronic inflammatory autoimmune condition, presents a substantial challenge to public health. Dictamnus dasycarpus Turcz. (D. dasycarpus) is a traditional Chinese medicinal plant recognized for its anti-inflammatory properties and is increasingly being utilized as a potential anti-RA agent, but the underlying mechanism is still unclear.

Aim of the study

The objective of this research is to elucidate the potential active components and therapeutic properties of D. dasycarpus in experimental RA-induced DBA/1J mice, and to uncover the pharmacological basis of its action.

Materials and methods

Surface plasmon resonance (SPR) was employed to ascertain the specificity of interactions between protein targets and D. dasycarpus active ingredients for treating RA. The extract of D. dasycarpus was obtained by HP-20 microresin column chromatography, and its chemical composition was assessed using UPLC-Orbitrap-MS. This study utilized a collagen-induced arthritis (CIA) mouse model for in vivo experimentation. Body weight, foot thickness measurements, arthritis scores, immune organ index, and serum antibody levels of mice were used as indicators to evaluate the effects of D. dasycarpus components in treating RA. The serum levels of inflammatory factors in mice were measured using a cytokine antibody microarray assay. Additionally, this study quantified the protein expression levels associated with inflammatory responses through a combination of immunohistochemical staining and western blotting analyses.

Results

This research investigated the interaction between D. dasycarpus active components and target proteins, including PTPN14, using a BIACORE system. The screened active components were identified as alkaloids through mass spectrometry. The UPLC-Orbitrap-MS analysis revealed that alkaloids were the predominant constituents in the 60% EtOH extract of D. dasycarpus. Alkaloid components significantly reduced the arthritis index, foot swelling, and serum antibody levels of IgG1, IgG 2a, and IgG 2b in CIA mice. Histological staining results indicated that alkaloid components mitigate disease exacerbations in CIA mice. Bioinformatics analysis and protein level detection results show that the therapeutic mechanism of D. dasycarpus in managing RA could be attributed to the suppression of the IL-17 signaling pathway.

Conclusion

This study was based on clarifying the therapeutic effect of D. dasycarpus on RA, identifies its effective chemical components as alkaloids. It systematically elucidates the pharmacological mechanisms of alkaloids in treating RA, thereby laying a crucial theoretical foundation for further exploration of the active constituents of D. dasycarpus.