Arglabin as a potential drug in the treatment of Freund’s complete adjuvant-induced arthritis in rats

Abstract

Purpose: To investigate the anti-arthritic activity of arglabin in Freund's complete adjuvant-induced arthritis in rats, and the likely underlying mechanism. Methods: A total of 40 male albino Wistar rats weighing between 120 and 150 g were used for this study. The rats were divided into four groups of ten rats each: control group, arthritis group, arglabintreated group, and standard (STD) group. Chronic arthritis was induced by injecting Freund's complete adjuvant in the plantar region of the rats. Rats in the arglabin-treated group received 5 ng/g arglabin intraperitoneally (i.p.), while those in the STD group received 1.5 mg/kg indomethacin, p.o. for 4 weeks. The development of arthritis was assessed at 0, 7, 14, 21 and 28th day of protocol by measuring thermal hyperalgesia, mechanical nociceptive threshold, arthritic score and paw volume. Activities of liver alkaline phosphatase (ALP), alanine amino-transaminase (ALT) and aspartate amino-transaminase (AST), and the levels of inflammatory cytokines-tumor necrosis factor-α (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-6 and interleukin (IL)-1β were measured in the synovial fluid, while those of inflammatory mediators-thromboxane B2 (TXB2), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were determined in serum. The expressions of mRNAs of nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were also determined in rat synovial tissues. Results: Arglabin significantly decreased the paw swelling and arthritic scores, but significantly increased the paw withdrawal latency, when compared to the arthritis group (p < 0.05). It also attenuated the altered levels of inflammatory cytokines in arthritic rats, and significantly reduced the levels of inflammatory mediators, when compared to the arthritis group (p < 0.05). The expressions of mRNAs of NFkB, COX-2 and iNOS also significantly decreased in arglabin-treated group, relative to the arthritis group (p < 0.05). Conclusion: The anti-arthritic activity of arglabin is due to its effect on inflammatory pathway via decreases in the levels of inflammatory mediators and cytokines, and decrease in the expressions of NFkB, COX-2 and iNOS in the synovial tissues of arthritic rats.

Applications of Sesquiterpene Lactones: A Review of Some Potential Success Cases

“…Besides anticancer activity, arglabin (2) demonstrated in vivo anti-arthritis activity in a rat model. Arglabin (2) lowers the levels of inflammatory mediators and cytokines, and reduces expression of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), COX-2 (cyclooxygenase-2) and iNOS (inducible nitric oxide synthase) [79]. Abderrazak and co-authors [80] suggest that arglabin (2) is a compound with great potential in inflammation and atherosclerosis therapy.…”