Solanum xanthocarpum fruit extract promotes chondrocyte proliferation in vitro and protects cartilage damage in collagenase induced osteoarthritic rats (article reference number: JEP 114028).

ETHNOPHARMACOLOGICAL RELEVANCE: Osteoarthritis (OA), a degenerative joint disease, is characterized by cartilage erosion and matrix degradation. Solanum xanthocarpum Schrad. & Wendl. fruits (SXF) and leaves have long been used as folk remedy in the treatment of pain in rheumatism. AIM OF THE STUDY: This study was aimed to investigate the phytochemical components and protective benefits of SXF on in vitro chondrocytes proliferation, and in vivo suppression of collagenase-induced OA. MATERIALS AND METHODS: Phytochemical components in ethanolic SXF extract were evaluated using gas chromatography-mass spectrometry (GC-MS). Effect of SXF on in vitro cell proliferation of primary chondrocytes was determined by cell proliferation assay and cell cycle analysis by flow cytometry. OA was induced in the right knees of rats through intra-articular injection of collagenase type-II. To evaluate in vivo preventive function of SXF, body weight, blood ALP, histopathological changes in the knee joint, proteoglycan, and collagen content were determined. The mRNA expression of COL-2, MMP-3 and COX-2 genes through qRT-PCR was studied. Antioxidant activities, total phenolics and flavonoid contents of SXF were also examined. RESULTS: GC-MS analysis revealed that SXF constitutes 28 phytochemicals including flavonoids (3-methoxy apigenin, quercetin, luteolin), tannin (quinic acid), terpenes (oleanolic acid, lupeol, psi.psi carotene), phytosterols (campesterol, stigmasterol, ß-sitosterol), and ascorbic acid. In vitro studies demonstrated that SXF enhanced the cell proliferation in a dose-dependent manner and has no cytotoxic effect on primary chondrocytes. In vivo study suggests that SXF protects the cartilage destruction induced by collagenase. The histological study revealed that SXF restored the synthesis of collagen and proteoglycan, vital factors for cartilage restoration, and reduced the arthritic score. An up-regulation in COL-2 expression and suppression of MMP-3 and COX-2 were detected by qRT-PCR analysis. Thus, in vivo study suggests the protective effects of SXF on cartilage destruction induced by collagenase. CONCLUSIONS: Our results imply that SXF benefits and ameliorates OA by enhancing the chondrocytes proliferation and preventing the articular cartilage damage through the restoration of their structural molecules, arthritic score reduction, suppression of MMP-3 and COX-2 expression level and up regulation of COL-2 genes expression. These results suggest that SXF could be a promising alternative treatment candidate for osteoarthritis.

Antiosteoarthritic effect of Punica granatum L. peel extract on collagenase induced osteoarthritis rat by modulation of COL-2, MMP-3, and COX-2 expression.

Osteoarthritis (OA) is a chronic degenerative and musculoskeletal disorder. The toxicity associated with nonsteroidal antiinflammatory drugs (NSAIDs) limits its use in the management of OA. To ameliorate these toxicities, natural antioxidants can be used as substitutes for the management of OA. Therefore, this study is aimed to investigate the prophylactic mechanisms of Punica granatum L. peel (PGP) in collagenase-induced OA rat compared with indomethacin. OA was induced in female Sprague Dawley rats by intraarticular injection of collagenase type-II and treated with PGP (250 and 500 mg/kg body wt) and a positive control (PC) indomethacin (3 mg/kg body wt). The results demonstrated that PGP reduced the collagenase induced OA as compared with indomethacin treated group through reducing blood ALP (P < .001) and significantly (P < .001) inhibited cartilage erosion as indicated in histological slides with retention of collagen and proteoglycan content. Quantitative real-time PCR analysis revealed the considerable (P < .05) upregulation in the expression of COL-2 gene and downregulation of MMP-3 and COX-2 genes in the PGP treated group. The high phenolic content (633 ± 1.16 mg/GAE) and flavonoid content (420.3 ± 2.14 mg/RE) contribute to the strong antioxidant activity with IC50 value (320 ± 2.2 µg/mL) of DPPH free radical scavenging activity. These results need further validation in clinical studies and thus, PGP could be developed as a preventive drug treatment for OA.

2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents.

In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC50 values of 9.2 and 21.8 µmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.