BTEX-K Ameliorates Rheumatoid Arthritis Through Regulating the NF-κB and PPAR-γ Signaling Pathways in Incomplete Freund’s Adjuvant-Induced Arthritis Mice

TL;DR

BTEX-K reduces inflammation in arthritis by regulating key signaling pathways, offering potential for treating inflammatory arthritis symptoms.

Contribution

BTEX-K's novel anti-inflammatory mechanism through NF-κB and PPAR-γ pathways in arthritis models is newly demonstrated.

Findings

BTEX-K reduced NO, IL-6, TNF-α, and PGE2 production in LPS-treated cells without cytotoxicity.

BTEX-K suppressed iNOS and COX-2 protein expression and inhibited JNK phosphorylation.

BTEX-K restored IκB levels and suppressed NF-κB activation by maintaining PPAR-γ expression.

Abstract

Background/Objectives: Degenerative arthritis is a chronic inflammatory disease marked by tissue degradation and vascular fibrosis. Macrophages play a central role in the inflammatory response by releasing mediators such as nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and prostaglandin E2 (PGE2). This study aimed to investigate the anti-inflammatory potential of BTEX-K, a formulation of dried red ginseng combined with alpha-galactosidase, in lipopolysaccharide (LPS)-stimulated cells. Methods: LPS-treated immune cells were used to assess the anti-inflammatory effects of BTEX-K. The levels of NO, IL-6, TNF-α, and PGE2 were measured following BTEX-K treatment. The protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was evaluated. Cytotoxicity assays were conducted to determine whether the observed effects were due to cell viability loss. The involvement of MAPK signaling and NF-κB pathway modulation was examined by analyzing JNK phosphorylation, IκB degradation, and PPAR-γ expression. Results: BTEX-K significantly reduced the production of NO, IL-6, TNF-α, and PGE2 in LPS-treated cells without inducing cytotoxicity. The protein expression levels of iNOS and COX-2 were also suppressed. Furthermore, BTEX-K inhibited the LPS-induced phosphorylation of JNK in the MAPK pathway. It restored IκB levels and suppressed NF-κB activation by preventing the downregulation of PPAR-γ. Conclusions: BTEX-K demonstrates notable anti-inflammatory effects by inhibiting key inflammatory mediators and signaling pathways in immune cells. These findings support its therapeutic potential in mitigating inflammation-related symptoms, including pain, swelling, and redness, commonly seen in degenerative arthritis.

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