High‐dose Tiger‐Gian formula protects the knee joint from surgically induced osteoarthritis in rats

Aim Although the Tiger‐Gian formula (TGF) has proven clinically effective at improving the symptoms of knee osteoarthritis (KOA), the pharmacological effects and underlying mechanisms of TGF have not been examined in any animal model. This study assessed the effects of TGF in male Sprague‐Dawley rats with anterior cruciate ligament transection (ACLT) ‐induced KOA. Methods Thirty rats underwent ACLT surgery and were assigned to either the control group, ACLT alone, ACLT + low‐dose TGF (1000 mg/kg), ACLT + high‐dose TGF (3000 mg/kg), or ACLT + celecoxib (30 mg/kg). All rats were subjected to micro‐computed tomography (micro‐CT), weight‐bearing behavioral testing, and histological inspections of the knee joint for evidence of structural changes in articular bone, cartilage and synovium. Results After 6 weeks, force discrepancies in weight‐bearing distribution between the normal hind and postoperative limbs revealed superiority with high‐dose TGF (18.00 ± 5.93 g) and celecoxib (18.68 ± 5.29 g) versus both ACLT alone (41.29 ± 7.06 g) and low‐dose TGF (37.00 ± 7.40 g). Micro‐CT images revealed that high‐dose TGF and celecoxib similarly improved subchondral bone architecture, protected articular cartilage after ACLT, and downregulated proinflammatory cytokines interleukin‐1β and tumor necrosis factor‐α in the cartilage and synovial sections. Conclusion High‐dose TGF induced the smallest amount of KOA‐associated bone loss. Anti‐inflammatory, anti‐oxidative, and immunomodulatory effects of TGF were accompanied by reductions in proinflammatory cytokines and improvements in pain and function. TGF‐induced anti‐osteoporotic activity and inhibition of cartilage degradation were reflected by micro‐CT and histological analysis. The findings help to explain how TGF alleviates symptoms of KOA.