Abstract
Boswellia serrata extracts have been traditionally employed for the treatment of inflammatory diseases. In the present study, we have evaluated the mechanism of activity of Boswellin Super® FJ (BSE), a standardized extract of B. serrata containing not less than 30% 3-acetyl-11-keto-β-boswellic acid along with other β-boswellic acids. The in vitro anti-inflammatory activities were carried out in RAW 264.7 macrophages or human peripheral blood mononuclear cells stimulated with bacterial lipopolysaccharides (LPS) and treated with 1.25-5μg/ml BSE. The anti-arthritic activity of the extract was evaluated in a rat model of collagen-induced arthritis. BSE at 40 and 80mg/kg and celecoxib 10mg/kg were orally dosed for 21days. BSE showed significant (p<0.05) inhibition of inflammation (TNF-α, IL-6, nitric oxide, and COX-2 secretion) and downregulates the mRNA levels of TNF-α, IL-6, IL1-β, and inducible nitric oxide synthase in macrophages. BSE treatment reduced the levels of phosphorylated-NF-κB (P65), suggesting an anti-inflammatory activity mediated by blocking this key signal transduction pathway. In addition, BSE showed inhibition (p<0.05) of collagenase, elastase, hyaluronidase enzymes, and a reduction in reactive oxygen species and matrix-degrading proteins in RAW 264.7 macrophages stimulated with LPS. BSE treatment significantly (p<0.05) reduced the arthritic index, paw volume, and joint inflammation comparable to celecoxib in collagen-induced arthritis (CIA) in rats. The circulating anti-collagen antibodies were reduced in BSE and celecoxib-treated animals as compared to the CIA. In confirmation with in vitro data, BSE showed a significant (p<0.05) dose-dependent effect on C-reactive protein, prostaglandin E2, and erythrocyte sedimentation rate, which is widely used as a blood marker of inflammation. Further, BSE treatment suppressed the cartilage oligomeric matrix protein and significantly enhanced the hyaluronan levels in synovial fluid. As observed by collagen staining in joints, the loss of matrix proteins was lower in BSE-treated animals, suggesting that BSE could preserve the extracellular matrix in RA. The extract showed inhibition of collagenase enzyme activity in vitro, further strengthening this hypothesis. BSE treatment was found to be safe, and rats displayed no abnormal behavior or activities. The results suggest that Boswellin Super® mediates its activity by preserving matrix proteins, reducing pro-inflammatory mediators, and oxidative stress.
Highlights
Rheumatoid arthritis (RA) is a chronic, inflammatory, and autoimmune disease, with a global prevalence estimated to range from 0.24–1% in different countries (Safiri et al, 2019)
The cell viability of peripheral blood mononuclear cells (PBMCs) and RAW 264.7 was not affected at concentrations up to 5 μg/ml (Figures 2A, 3A); all the cell-based assays were carried out at a maximum concentration of 5 μg/ml of Boswellin® Super (BSE)
The present study demonstrates that BSE, a standardized extract of Boswellia serrata containing 30% 3-acetyl-11-keto-β-boswellic acid, reduces inflammation, oxidative stress and, most importantly, preserves the matrix proteins by inhibiting the enzymes which hydrolyze these proteins
Summary
Rheumatoid arthritis (RA) is a chronic, inflammatory, and autoimmune disease, with a global prevalence estimated to range from 0.24–1% in different countries (Safiri et al, 2019) It is characterized by inflammation and swelling of the peripheral joints, pain, and articular cartilage damage. Monocytes recruited into the synovium secrete cytokines and chemokines, inducing synovial fibroblast proliferation, pro-inflammatory cytokine production, matrix-degrading enzymes secretion, and sustained synovial hypertrophy (Bartok and Firestein, 2010). The cytokines, such as the receptor activator of nuclear factor-kappa-β ligand and granulocyte-macrophage colony-stimulating factor, control the osteoclast differentiation. Abnormalities in the immune system leading to the presence of autoantibodies known as rheumatoid factors and immigration of T and B cells into the synovium are characteristic features of RA (Scherer et al, 2020)
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