Quarta Stefano, Santarpino Giuseppe, Carluccio Maria Annunziata, Calabriso Nadia, Scoditti Egeria, Siculella Luisa, Damiano Fabrizio, Maffia Michele, Verri Tiziano, De Caterina Raffaele, Massaro Marika
Department of Biological and Environmental Sciences and Technologies (DISTEBA), University of Salento, 73100 Lecce, Italy.
Cardiovascular Center, Paracelsus Medical University, 90471 Nuremberg, Germany.
Pharmaceuticals (Basel). 2022 Oct 13;15(10):1263. doi: 10.3390/ph15101263.
Osteoarthritis (OA) is a joint disease characterized by inflammation of the synovium, angiogenesis, cartilage degradation, and osteophyte formation. DC. ex Meisn., Roxb., L., Bromelain and Escin () are plants which extracts, together to Bromelain and Escin () are traditionally used in OA. However, their mechanistic role remains unclear. We aimed to investigate whether these bioactives alone or in combination (as in Flonat Fast) can suppress TNF-α-induced inflammation, angiogenesis, and osteophyte formation using two cell models involved in OA: endothelial cells and monocytes. Each plant extract was evaluated for its polyphenol content, antioxidant activity, and toxicity. In endothelial cells and monocytes, expression of genes involved in OA was assessed, functional assays for inflammation and angiogenesis were performed, and impairment of reactive oxygen species production (ROS) was evaluated. Exposure of cells to the bioactives alone and in combination before cytokine stimulation resulted in differential counterregulation of several gene and protein expressions, including those for cyclooxygenases-2, metalloproteinase-9, transforming growth factor β1, and bone morphogenic protein-2. We demonstrated that these bioactives modulated monocyte adhesion to endothelial cells as well as cell migration and endothelial angiogenesis. Consistent with radical scavenging activity in the cell-free system, the bioactives curbed TNF-α-stimulated intracellular ROS production. We confirmed the potential anti-inflammatory and antiangiogenic effects of the combination of , , Curcuma, Bromelain, and Escin and provided new mechanistic evidence for their use in OA. However, further clinical studies are needed to evaluate the true clinical utility of these bioactives as supportive, preventive, and therapeutic agents.
骨关节炎（OA）是一种关节疾病，其特征在于滑膜炎症、血管生成、软骨降解和骨赘形成。DC. ex Meisn.、Roxb.、L.、菠萝蛋白酶和七叶皂苷（）是传统上用于OA的植物提取物，其与菠萝蛋白酶和七叶皂苷（）一起使用。然而，它们的作用机制尚不清楚。我们旨在研究这些生物活性物质单独使用或联合使用（如在Flonat Fast中）是否可以使用涉及OA的两种细胞模型（内皮细胞和单核细胞）来抑制TNF-α诱导的炎症、血管生成和骨赘形成。评估了每种植物提取物的多酚含量、抗氧化活性和毒性。在内皮细胞和单核细胞中，评估了参与OA的基因表达，进行了炎症和血管生成的功能测定，并评估了活性氧产生（ROS）的损伤。在细胞因子刺激之前，将细胞单独或联合暴露于生物活性物质中，导致对几种基因和蛋白质表达的不同反向调节，包括环氧化酶-2、金属蛋白酶-9、转化生长因子β1和骨形态发生蛋白-2的表达。我们证明这些生物活性物质调节单核细胞与内皮细胞的粘附以及细胞迁移和内皮血管生成。与无细胞系统中的自由基清除活性一致，这些生物活性物质抑制了TNF-α刺激的细胞内ROS产生。我们证实了姜黄、菠萝蛋白酶和七叶皂苷联合使用的潜在抗炎和抗血管生成作用，并为它们在OA中的应用提供了新的作用机制证据。然而，需要进一步的临床研究来评估这些生物活性物质作为支持性、预防性和治疗性药物的真正临床效用。
