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Background  Prevalence of osteoarthritis (OA) is on rise on the global scale. At present there are no satisfactory pharmacological agents for treating OA. Our previous study showed that  Sida cordifolia  L. and  Zingiber officinale  Rosc. had protective effect on cartilage. Here, we describe the effect of OA-F2, a herbal formulation prepared using combination of these two plants in alleviating OA associated symptoms in a rat model of collagenase-induced OA.    Methods  OA was induced by intra-articular injection of collagenase type II in wistar rats. Diclofenac (10 mg/kg) was used as a reference control. Rats ( n  = 6) were divided into 6 groups: Healthy control (HC), osteoarthritic control (OAC), diclofenac (DICLO), OA-F2L (135 mg/kg), OA-F2M (270 mg/kg) and OA-F2H (540 mg/kg). The effects of the 20 days treatment were monitored by parameters like knee diameter, paw volume, paw retraction; serum C-reactive protein (CRP), alkaline phosphatase (ALP) and glycosaminoglycan (GAG). Radiography and histopathology of knee joint were also studied. Additionally, gene expression was studied from isolated synovium tissue proving anti-osteoarthritic potential of OA-F2.    Results  Oral administration of OA-F2 has significantly prevented knee swelling compared to OAC; OA-F2 and DICLO, significantly reduced paw volume compared to OAC. Paw latency was remarkably increased by OA-F2 compared to OAC. OA-F2L (−0.670,  p  < 0.001), M (−0.110,  p  < 0.05) and H (0.073) has markedly reduced levels of CRP compared to DICLO. OA-F2L ( p  < 0.05), M ( p  < 0.001) and H ( p  < 0.05) significantly reduced ALP levels, compared to DICLO. GAG release in the serum was also significantly lowered in OA-F2 treated group compared to DICLO. Radiological and histopathological observations showed cartilage protection by OA-F2. OA-F2 has upregulated SOD and GPx. Upregulated CAT expression was observed in OA-F2M and H. Considerable down-regulation of expression of MMP-3 and MMP-9 was observed in all the groups. Up-regulation of TIMP-1 was observed in rats treated with OA-F2L, H and DICLO.    Conclusion  OA-F2 has shown therapeutic effects in rat model of collagenase induced OA by demonstrating cartilage protection through controlling MMPs and improving anti-oxidant levels in arthritic synovium and is a potent candidate for further drug development and treatment for OA.

New herbal composition (OA-F2) protects cartilage degeneration in a rat model of collagenase induced osteoarthritis