Faculty of Medicine, University of Latvia, Raina Blvd. 19, Riga 1586, Latvia.
Faculty of Medicine, University of Latvia, Raina Blvd. 19, Riga 1586, Latvia.
Phytomedicine. 2019 Feb;53:86-95. doi: 10.1016/j.phymed.2018.09.029. Epub 2018 Sep 5.
Anthocyanidins are plant phytochemicals found at high concentrations in berries, vegetables and flowers. Anthocyanidins have been extensively investigated due to their antioxidative, antidiabetic and anti-inflammatory effects. Few studies show that anthocyanidins decrease obesity and improve bone density. However, the effects of anthocyanidins on tissue regeneration have not been sufficiently clarified. Human mesenchymal stem cells (MSCs) are multipotent adult stem cells responsible for the regeneration of fat, bone and cartilage. Although MSCs are often used for screening of biologically active compounds, so far, the effect of anthocyanidins on MSC differentiation has not been addressed.
The aim of this study was to analyse the effect of anthocyanidins malvidin, cyanidin and delphinidin on adipose tissue-derived MSC differentiation into adipocytes, osteocytes and chondrocytes.
Differentiation into adipocytes, osteocytes and chondrocytes was carried out in the defined cell culture conditions in the presence or absence of malvidin, cyanidin and delphinidin. The differentiation was confirmed by cytochemical staining and tissue-specific gene and protein expression. Antiobesity and anti-diabetes drug liraglutide was used as a reference drug in this study.
Delphinidin inhibited MSC adipogenesis and downregulated FABP4 and adiponectin genes. Malvidin induced a significantly higher accumulation of calcium deposits in MSCs comparing to untreated MSCs, as well as upregulated the osteocyte-specific gene BMP-2 and Runx-2 expression and induced BMP-2 secretion. Cyanidin and delphinidin demonstrated a chondrogenesis stimulating effect by upregulation of Col2a1 and aggrecan.
Altogether, our data show that anthocyanidins malvidin, cyanidin and delphinidin exert favourable effects on MSC osteogenesis and chondrogenesis whereas delphinidin inhibits adipogenesis. These results suggest that anthocyanidin effects on tissue regeneration could be further analysed in depth in vivo.
花色苷是一种植物类黄酮,在浆果、蔬菜和花卉中含量较高。花色苷具有抗氧化、抗糖尿病和抗炎作用,因此受到广泛研究。有少量研究表明花色苷可减少肥胖并提高骨密度。然而,花色苷对组织再生的影响尚未得到充分阐明。人骨髓间充质干细胞(MSCs)是多能成体干细胞,可用于脂肪、骨骼和软骨的再生。尽管 MSCs 常用于筛选具有生物活性的化合物,但迄今为止,花色苷对 MSC 分化的影响尚未得到解决。
本研究旨在分析花色苷矢车菊素、飞燕草素和锦葵素对脂肪组织来源的 MSC 向脂肪细胞、成骨细胞和软骨细胞分化的影响。
在存在或不存在矢车菊素、飞燕草素和锦葵素的情况下,在明确的细胞培养条件下进行向脂肪细胞、成骨细胞和软骨细胞的分化。通过细胞化学染色和组织特异性基因和蛋白表达来确认分化。本研究中使用抗肥胖和抗糖尿病药物利拉鲁肽作为参考药物。
锦葵素抑制 MSC 脂肪生成并下调 FABP4 和脂联素基因。与未经处理的 MSC 相比,矢车菊素可使 MSC 中钙沉积物的积累显著增加,同时上调成骨细胞特异性基因 BMP-2 和 Runx-2 的表达并诱导 BMP-2 分泌。飞燕草素和锦葵素通过上调 Col2a1 和聚集蛋白促进软骨生成。
总之,我们的数据表明,花色苷矢车菊素、飞燕草素和锦葵素对 MSC 成骨和软骨形成具有有利影响,而锦葵素抑制脂肪生成。这些结果表明,花色苷对组织再生的影响可以在体内进一步深入分析。