Abstract. Phlomis younghusbandii Mukerjee (Labiatae) has been reported to be effective in the treatment of rheumatoid arthritis (RA). In the present study, the anti-inflammatory and anti-arthritic effects of phlomisoside F (PF), isolated from P. younghusbandii Mukerjee (Labiatae), were investigated in male Wistar rats subjected to carrageen-induced paw edema and complete Freund's adjuvant (CFA)-induced arthritis. Arthritis scores were evaluated by a 5-point ordinal scale (scores 0-4). Expression levels of TNF-α, IL-1β, IL-6, IL-10, COX-2 and 5-LOX were determined via ELISA and western blot assays. Subsequent to establishing the edema and arthritis models, oral administration of PF (5, 10 and 20 mg/kg) significantly inhibited mean edema rate, compared with the control group in carrageenan-induced paw edema assay. In addition, administration of PF (5, 10 and 20 mg/kg/day) for 28 days markedly exhibited an anti-arthritic activity by offsetting the body weight loss, inhibiting the paw edema, reducing the arthritis scores and the indices of thymus and spleen, inhibiting the expression levels of TNF-α, IL-1β, IL-6, COX-2 and 5-LOX, and increasing the expression of IL-10, when compared with the respective control group in CFA-induced arthritis assay. In conclusion, PF is a valuable anti-arthritic constituent of P. younghusbandii, and the present study results suggest that this herb may be used in the treatment of RA.

The proinflammatory cytokine tumor necrosis factor-α (TNF-α)-induced degradation of extracellular matrix (ECM), such as type II collagen in chondrocytes, plays an important role in the development of osteoarthritis (OA). Telmisartan, an angiotensin II (Ang-II) receptor blocker, is a licensed drug used for the treatment of hypertension. However, the effects of Telmisartan in tumor necrosis factor-α (TNF-α)-induced damage to chondrocytes and the progression of OA are unknown. In this study, we found that treatment with Telmisartan attenuated TNF-α-induced oxidative stress by reducing the levels of mitochondrial reactive oxygen species (ROS) and the production of protein carbonyl in human C28/I2 chondrocytes. Interestingly, Telmisartan inhibited TNF-α-induced expression and secretions of proinflammatory mediators such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and monocyte chemotactic protein 1 (MCP-1). Notably, stimulation with TNF-α reduced the levels of type II collagen at both the mRNA and the protein levels, which was rescued by the treatment with Telmisartan. Mechanistically, we found that Telmisartan restored TNF-α-induced reduction of SOX-9. Silencing of SOX-9 blocked the inhibitory effects of Telmisartan against TNF-α-induced degradation of type II collagen. These findings suggest that Telmisartan might be a potential and promising agent for the treatment of OA.