Therapeutic Effect of Matrine on Collagen-Induced Arthritis Rats and Its Regulatory Effect on RANKL and OPG Expression

Abstract

Objective. To investigate the effect of matrine on rats with collagen-induced arthritis (CIA) and its regulatory effect on receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) expression. Methods. Wistar rats ( n = 6 ) and CIA rats ( n = 30 ) were randomly divided into six groups: healthy, CIA control, low/medium/high matrine (25, 50, or 100 mg/kg, once per day for six weeks), and methotrexate (MTX) (2 mg/kg, once per week for six weeks). The degree of joint damage was evaluated by X-ray and HE staining. Bone marrow suppression was assessed by routine blood analysis. In addition, the levels of serum RANKL and OPG in the rats were measured by ELISA. Results. The level of joint swelling and degree of joint damage assessed by ankle swelling measurements, AI score, X-ray, and HE staining were alleviated in the CIA rats treated with MTX or different doses of matrine. Furthermore, no obvious inhibitory effect was observed on the bone marrow of the CIA rats, regardless of the dose of matrine or treatment with 2 mg/kg MTX ( P > 0.05 ). The levels of OPG in serum and the ratio of OPG/RANKL were higher, and RANKL expression was lower in the low/medium/high matrine group compared with that of the CIA control group. The serum levels of OPG and OPG/RANKL ratio increased with the matrine dose, while the opposite was observed for RANKL expression. Conclusion. Matrine treatment was associated with a lower degree of bone destruction, increased OPG expression and OPG/RANKL ratio, and decreased RANKL expression in CIA rats. Thus, matrine may represent a novel drug candidate for the treatment of RA.

Epimedii Folium and Ligustri Lucidi Fructus Promote Osteoblastogenesis and Inhibit Osteoclastogenesis against Osteoporosis via Acting on Osteoblast-Osteoclast Communication

“…The ratio of RANKL/OPG is usually used in reflecting the ability of osteoclastogenesis and the degree of OC-mediated bone resorption. A high RANKL/OPG ratio reflects an increase in bone loss, while a low ratio reflects a decrease in bone loss [ 64 ]. OBs also secrete a mass of TGF- β 1 considered as the core cytokine that dominate bone formation.…”

“…Same as the effect of OBs on OCs, OCs can influence the function of OBs through regulating cytokines such as TGF- β 1, BMP-2, IGF-1, and Atp6v0d2. TGF- β 1 is released from the bone matrix due to OC-mediated bone resorption and is activated in acidic environment resulting from activated OCs [ 64 ]. TGF- β 1 promotes BM-MSC proliferation, migration, and differentiation into OBs through Smad2/3 pathway and promotes OB proliferation and matrix maturation [ 66 , 67 ].…”

Evaluating the anti‐arthritic potential of walnut ( Juglans regia L.) in FCA induced Sprague Dawley rats

“…The drug MTX is commonly used in the treatment of RA. The level of RANKL was decreased whereas the OPG level was improved after MTX treatment (Li et al, 2021). Phenolic acids play an important role in the inhibition of osteoclastogenesis, thus preventing bone tissue loss.…”

Matrine, a potential drug for the treatment of rheumatoid arthritis

“…Li et al 53 observed in in vitro experiments that matrine inhibits the expression of TRAF6, interferes with its binding to receptor activator of nuclear factor‐κB (RANK), and inhibits the activation of NF‐κB, c‐Fos, and NFATc1 in a dose‐dependent manner, ultimately causing osteoclast activation disorders. In their subsequent study, Li et al 54 provided evidence that matrine alleviates bone degradation and enhances the expression of osteoprotegerin and the osteoprotegerin/RANK ligand ratio, while suppressing the expression of RANK ligand in rats with CIA. Both studies indicated that matrine inhibits the NF‐κB pathway.…”