Effect of ficus deltoidea, a medicinal plant, on cartilage protection in cartilage explant and postmenopausal rat models of osteoarthritis

      Purpose: In the light of global problem associated with osteoarthritis (OA), there is a huge demand on new alternative treatments for the disease. Developing therapeutics from plant-derived sources may exert favorable safety profiles and may reduce cost of therapies. We hypothesized that Ficus deltoidea or commonly known as mistletoe fig, a shrub native to the tropical climates of Asia, India, and Africa, has the beneficial effects on OA due to its anti-inflammatory and antioxidant properties. This study aims to evaluate the role of Ficus deltoidea (FD) leaves extract on OA through IL-1β-induced bovine cartilage explant and postmenopausal OA rat model induced by monosodium iodoacetate (MIA) with comparison to diclofenac as a common OA pharmacologic drug.
      Methods: In bovine cartilage explant culture, the recombinant bovine IL-1β (10 ng/mL) was added to the cartilage disks in DMEM/F12 media to induce proteoglycan degradation. FD leaves extract (20, 40, 80 μg/mL) or diclofenac (5 μg/mL) were simultaneously supplemented into the medium after IL-1β induction. The amount of proteoglycan released into the medium was determined and chondrocytes synthesis was evaluated by histological analysis. In in vivo experiment, thirty twelfth-week-old Sprague Dawley female rats were randomized into five groups. The rats were undergoing bilateral ovariectomy (OVX) and OA was induced by intra-articular injection of monosodium iodoacetate (MIA) into right knee joints after two weeks of OVX, excluding healthy group that received sham operation and intra-articular injection of normal saline. Healthy and OA non-treated groups were given deionized water while treatment groups were orally administered with FD (200, 400 mg/kg) leaves extract or diclofenac (5 mg/kg) once a day for 28 days. Serum levels of inflammation (IL-1β, PGE2) and cartilage degradation (PIINP, CTX-II) biochemical markers were assessed by enzyme-linked immunosorbent assay (ELISA). Evaluation on articular cartilage changes of the OA knees was determined by macroscopic and microscopic observations and scored by standard grading criteria.
      Results: In vitro study showed both FD leaves extract and diclofenac supplemented groups significantly inhibited proteoglycan loss and increased chondrocytes proliferation compared to non-treated group. Rats undergoing OVX and MIA-induction showed obvious articular cartilage degradation on macroscopic and microscopic observations. OA rats treated with FD leaves extract and diclofenac showed significantly less cartilage erosion particularly on femoral trochlea compared to non-treated OA rats. Serum levels of IL-1β, PGE2, PIINP, and CTX-II were elevated in OA rats and significantly reduced by FD leaves extract and diclofenac. FD leaves extract exerted no significant difference to diclofenac in reducing articular cartilage erosion, and levels of inflammation and cartilage degradation markers associated with OA in the rat model.
      Conclusions: Our findings suggested that FD leaves extract has the role on protecting OA joint destruction through inhibition of inflammation and articular cartilage degradation comparable to diclofenac. FD leaves extract may be a promising therapeutic candidate for the treatment of OA. Future investigation on therapeutic mechanism and clinical efficacy of the FD leaves extract on OA is needed.