比较含硫酸软骨素的药品或食品补充剂：它们的生物活性等效吗？

INTRODUCTION: Oral supplementation of chondroitin sulfate (CS) and glucosamine (GlcN), symptomatic slow-acting molecules, is recommended by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis and Musculoskeletal Diseases (ESCEO) and other European Union (EU) guidelines for the restoration of the articular cartilage surface in patients affected by osteoarthritis (OA). They are commercialized as pharmaceutical grade products and as food supplements in combination with plant extracts hyaluronic acid, methylsulfonylmethane, and other components. Food supplements do not need to undergo the strict regulatory controls of pharmaceutical grade products; thus, composition and contaminants that could be present may not be evidenced before commercialization and these uncertainties may give rise to concerns about the bioactivity of these formulations. METHODS: In this paper 10 different food supplements (FS) from diverse European countries were analyzed in comparison with two pharmaceutical grade products (Ph) using updated analytical approaches and biochemical cell-based assays. The purity, the titer, and the origin of CS in Ph and FS samples were initially assessed in order to successively compare the biological function. Both food supplements and pharmaceutical formulations were tested in vitro, using the same final CS concentration, on primary chondrocytes and synoviocytes in terms of (i) cell viability, (ii) activation of the NF-κB-mediated inflammation pathway, (iii) cartilage oligomeric matrix protein (COMP-2), IL-6, and IL-8 production. RESULTS: All the FS presented a certain insoluble fraction; the CS and the GlcN contents were lower than the declared ones in 9/10 and 8/10 samples, respectively. All FS contained keratan sulfate (KS) at up to 50% of the total glycosaminoglycan amount declared on the label. Primary cells treated with the samples diluted to present the same CS concentration in the medium showed cytotoxicity in 7/10 FS while Ph preserved viability and reduced NF-κB, COMP-2, and secreted inflammatory cytokines. CONCLUSION: Among all samples tested, the pharmaceutical grade products demonstrated effective modulation of biomarkers counteracting the inflammation status and improving viability and the physiological condition of OA human primary chondrocyte and synoviocyte cells. In contrast to that, most FS were cytotoxic at the tested concentrations, and only 3/10 of them showed similarities to Ph sample behavior in vitro. FUNDING: This work was partially supported by PON01_1226 NUTRAFAST, MIUR Ministero dell'Università e della Ricerca Scientifica. Bioteknet financed two short-term grants for graduate technicians. The journal's Rapid Service and Open Access fees were funded by IBSA CH.

简介：欧洲临床和经济骨质疏松症和骨关节炎和肌肉骨骼疾病学会（ESCEO）和其他欧盟（EU）指南建议口服补充硫酸软骨素（CS）和葡萄糖胺（GlcN），这是治疗骨关节炎（OA）患者关节软骨表面的症状性慢作用分子。它们以药品级产品和与植物提取物透明质酸、甲基磺酰甲烷和其他成分组合的食品补充剂形式销售。食品补充剂不需要经过药品级产品的严格监管控制；因此，在商业化之前，可能无法证明其成分和污染物的存在，这些不确定性可能会引起人们对这些配方生物活性的关注。

方法：本文比较了来自不同欧洲国家的 10 种不同的食品补充剂（FS）与两种药品级产品（Ph），使用更新的分析方法和生化细胞基检测。首先评估 Ph 和 FS 样品中的 CS 纯度、效价和来源，以相继比较其生物学功能。将食品补充剂和药品制剂以相同的最终 CS 浓度，在原代软骨细胞和滑膜细胞中进行体外测试，从以下方面评估其生物学功能：（i）细胞活力；（ii）NF-κB 介导的炎症途径的激活；（iii）软骨寡聚基质蛋白（COMP-2）、IL-6 和 IL-8 的产生。

结果：所有 FS 均呈现一定的不溶性成分；9/10 和 8/10 的样本中 CS 和 GlcN 的含量均低于声明值。所有 FS 均含有高达 50%标签上声明的糖胺聚糖总量的角蛋白硫酸盐（KS）。将样品稀释至培养基中呈现相同 CS 浓度的原代细胞在 7/10 的 FS 中表现出细胞毒性，而 Ph 则保持活力并降低 NF-κB、COMP-2 和分泌的炎症细胞因子。

结论：在所测试的所有样本中，药品级产品有效调节生物标志物，抑制炎症状态，改善 OA 患者原代软骨细胞和滑膜细胞的活力和生理状况。相比之下，大多数 FS 在测试浓度下具有细胞毒性，只有 3/10 的 FS 显示出与 Ph 样品在体外行为的相似性。

资助：本工作部分由 PON01_1226 NUTRAFAST、MIUR Ministero dell'Università e della Ricerca Scientifica 资助。Bioteknet 为研究生技术员提供了两项短期资助。该杂志的快速服务和开放获取费用由 IBSA CH 资助。