Molecular Endocrinology Lab, Department of Zoology, University of Lucknow, Lucknow, 226007, Uttar Pradesh, India.
Department of Biotechnology, Era's Lucknow Medical College & Hospital, Era University, Lucknow, 226003, Uttar Pradesh, India.
J Ethnopharmacol. 2021 Jun 28;274:114028. doi: 10.1016/j.jep.2021.114028. Epub 2021 Mar 26.
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.
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.
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.
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, β-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.
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.
骨关节炎（OA）是一种退行性关节疾病，其特征为软骨侵蚀和基质降解。酸浆（Solanum xanthocarpum Schrad. & Wendl.）的果实和叶子一直以来都被民间用于治疗风湿病中的疼痛。
本研究旨在探究酸浆果实的植物化学成分及其对体外软骨细胞增殖的保护作用，并在体内抑制胶原酶诱导的 OA。
使用气相色谱-质谱联用技术（GC-MS）评估乙醇酸浆果实提取物中的植物化学成分。通过细胞增殖测定和流式细胞术进行细胞周期分析，确定酸浆果实对原代软骨细胞体外增殖的影响。通过关节内注射胶原酶 II 诱导大鼠右膝关节 OA，评估酸浆果实的体内预防作用。通过体重、血液碱性磷酸酶、膝关节组织学变化、糖胺聚糖和胶原蛋白含量，评估 SXF 的体内预防作用。通过 qRT-PCR 研究 COL-2、MMP-3 和 COX-2 基因的 mRNA 表达。还研究了 SXF 的抗氧化活性、总酚和类黄酮含量。
GC-MS 分析表明，SXF 由 28 种植物化学成分组成，包括类黄酮（3-甲氧基芹菜素、槲皮素、木樨草素）、鞣酸（奎宁酸）、萜类（齐墩果酸、羽扇豆醇、ψ.ψ 胡萝卜素）、植物固醇（菜油固醇、豆固醇、β-谷甾醇）和抗坏血酸。体外研究表明，SXF 以剂量依赖的方式增强细胞增殖，对原代软骨细胞无细胞毒性作用。体内研究表明，SXF 可保护胶原酶诱导的软骨破坏。组织学研究表明，SXF 恢复了胶原蛋白和糖胺聚糖的合成，这是软骨修复的重要因素，并降低了关节炎评分。qRT-PCR 分析显示 COL-2 表达上调，MMP-3 和 COX-2 表达下调。因此，体内研究表明 SXF 通过增强软骨细胞增殖和防止关节软骨损伤来保护胶原酶诱导的软骨破坏。
我们的结果表明，SXF 通过增强软骨细胞增殖、防止结构分子损伤、降低关节炎评分、抑制 MMP-3 和 COX-2 表达水平以及上调 COL-2 基因表达来改善 OA，从而对 OA 具有有益作用。这些结果表明，SXF 可能是骨关节炎的一种有前途的替代治疗候选物。
