Majoon Chobchini attenuates arthritis disease severity and RANKL-mediated osteoclastogenesis in rheumatoid arthritis

Snigdha Samarpita; Hari Madhuri Doss; Ramamoorthi Ganesan; Mahaboobkhan Rasool

doi:10.1007/s13205-021-02985-4

Majoon Chobchini attenuates arthritis disease severity and RANKL-mediated osteoclastogenesis in rheumatoid arthritis

3 Biotech. 2021 Oct;11(10):436. doi: 10.1007/s13205-021-02985-4. Epub 2021 Sep 17.

Authors

Snigdha Samarpita¹, Hari Madhuri Doss¹, Ramamoorthi Ganesan^{1

2}, Mahaboobkhan Rasool¹

Affiliations

¹ SMV 240, Immunopathology Lab, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore, Tamil Nadu 632 014 India.
² Present Address: Immunology Program, Department of Clinical Science, H. Lee Moffitt Cancer Center, Tampa, FL 33612 USA.

Abstract

Majoon Chobchini, a polyherbal Unani compound, has been used holistically in India to treat rheumatoid arthritis. However, the potential mechanism underlying the antiarthritic efficacy of Majoon Chobchini has not been elucidated so far. This study was aimed to explore the underlying molecular mechanism and scientifically validate the therapeutic basis of Majoon Chobchini in rheumatoid arthritis (RA). The anti-arthritic efficacy of Majoon Chobchini was demonstrated in vivo using complete Freund's adjuvant-induced arthritic rat model and adjuvant-induced arthritic fibroblast-like synoviocytes (AA-FLS). The expression of pro-inflammatory mediators and enzymes was evaluated in the serum and synovial tissues of adjuvant-induced arthritis (AIA) rats. In-vitro, AA-FLS, and bone marrow macrophages (BMMs) were co-cultured to evaluate the formation and activity of osteoclasts using TRAP staining analysis and pit formation assay, respectively. RANKL and OPG levels were detected using western blotting and qRT-PCR analysis. Furthermore, the involvement of JAK-STAT-3 signaling in the therapeutic efficacy of Majoon Chobchini was evaluated both in vivo and in vitro. Majoon Chobchini significantly reversed the physical symptoms in AIA rats with reduced expression of pro-inflammatory cytokines and enzymes. Notably, Majoon Chobchini alleviated cartilage degradation and bone erosion in AIA rats via inhibiting the activation of the JAK-STAT-3 signaling pathway in the AIA rats. Consistent with its effect in vivo, Majoon Chobchini decreased osteoclast inducing potential of AA-FLS and thus attenuated osteoclast formation and bone resorption in vitro. Taken together, our findings suggest that the JAK/STAT-3 signaling inhibition may underlie the mechanism through which Majoon Chobchini provides relief against RA symptoms.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-021-02985-4.

Keywords: Cartilage damage; Majoon Chobchini; Osteoclastogenesis; Rheumatoid arthritis; Synovial inflammation.