ABSTRACT
Background & objectives: Osteoarthritis (OA) is a degenerative disease characterized by joint pain and progressive loss of articular cartilage. Entada pursaetha has been traditionally used in the treatment of inflammatory disease, liver ailment, etc. In this study we investigated suppressive effect of ethanolic extract of E. pursaetha (EPE) on monosodium iodoacetate (MIA)-induced osteoarthritis pain and disease progression by histopathological changes in joints in a rat model. Methods: OA was induced in right knee of rat by intra-articular injection of 3 mg of MIA and characterized by pathological progression of disease and pain of affected joint. Spontaneous movements, mechanical, thermal and cold sensitivity were monitored at days 0 (before drug and MIA injection), 7, 14 and 21 of MIA administration. EPE (30, 100 and 300 mg/kg), vehicle or etoricoxib (10 mg/ kg; reference drug) were administered daily for 21 days by oral route. Results: EPE at various doses significantly reduced mechanical, heat, cold hyperalgesia and increased the horizontal and vertical movements in intra-articular MIA injected rats. EPE prevented the damage to cartilage structure and reduced the cellular abnormalities. Articular cartilage of rats treated with EPE at 300 mg/kg group was almost normal with well-developed smooth surface and chondrocytes were distributed individually or arranged in column. Interpretation & conclusions: the present findings showed that the EPE was not only able to mitigate pain and hyperalgesia but also inhibited MIA-induced cartilage degeneration in vivo. EPE may have the potential to become therapeutic modality in the treatment of osteoarthritis. However, further studies need to be done to confirm these findings in other models and clinical trials.
ABSTRACT
In the present investigation we have examined the hypothesis that calcium-dependent K+ channels (K(Ca)) are involved in the sodium nitroprusside (SNP)-induced vasodilatation of goat coronary artery. SNP (10(-9)-3 x 10(-6) M), added cumulatively, relaxed K+ (30 mM)-contracted coronary artery ring segments in a concentration-dependent manner with an EC50 of 1.32 x 10(-7) M (95% CL, 0.93-1.86 x 10(-7) M; n = 21). K(Ca) blocker, tetraethyl ammonium (1 mM) caused a rightward shift in the concentration-response curve of SNP with a corresponding increase in EC50 (1.62 x 10(-6) M; 95% CL, 0.44-6.02 x 10(-6) M, n = 4) of nitro vasodilator. Lowering of extra cellular Ca2+ in the physiological saline solution to 1/4 of normal selectively attenuated the vasorelaxant response of SNP, thereby causing an increase in its EC50 (2.4 x 10(-6) M; 95% CL, 1.23-4.68 x 10(-6) M, n = 4). Exposure of the tissues to high K+ (80 mM) solution, a protocol adopted to reduce the K+ gradient across the cell membrane, markedly inhibited the coronary artery relaxations induced by SNP (EC50, 2.54 x 10(-6) M; 95% CL, 1.31-4.91 x 10(-6) M, n = 4), when compared with tissues contracted with low K+ (30 mM) solution (EC50 7.9 x 10(-8); 95% CL, 4.4 x 10(-8)-1.44 x 10(-7) M, n = 6). The results suggested that a major component of SNP-induced relaxation of goat coronary artery was mediated by K(Ca) channels.