Coronarin D, a Metabolite from the Wild Turmeric, Curcuma aromatica, Promotes the Differentiation of Neural Stem Cells into Astrocytes.
Coronarin D, a Metabolite from the Wild Turmeric, Curcuma aromatica, Promotes the Differentiation of Neural Stem Cells into Astrocytes.
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DOI：
10.1021/acs.jafc.2c00020
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发表时间：
2022-03-16
影响因子：
6.1
通讯作者：
Nakao Y
中科院分区：
文献类型：
--
作者：
Otsuka S;Kawamura M;Fujino S;Nakamura F;Arai D;Fusetani N;Nakao Y
姜黄属植物在亚洲国家被广泛用作传统药物。这些植物含有生物活性化合物，具有神经保护特性或增加神经干细胞(NSCs)和神经元的活性。然而，姜黄中促进神经干细胞分化为星形胶质细胞的生物活性成分尚未见报道。在此，我们研究了姜黄提取物对胚胎干细胞来源神经干细胞体外分化的影响。野生姜黄提取物对神经干细胞向星形胶质细胞的分化有明显的促进作用。生测分离得到冠花素C(1)和D(2)，以及(E)-Labda-8(17)，12-二烯-15，16-Dial(3)作为生物活性化合物。冠花素D(2)可显著促进神经干细胞向星形胶质细胞的分化，其作用约为4倍(3.6 4±0.4 8)，并在基因和蛋白水平上增加胶质纤维酸性蛋白的表达水平，而化合物1和3的作用较弱，提示15-羟基-Δ12-γ-内酯部分具有重要的生物活性。此外，化合物2增加了pSTAT3阳性细胞的数量，提示化合物2通过JAK/STAT信号通路促进星形胶质细胞的分化。
Plants in the genus Curcuma have been widely used as traditional medicines in Asian countries. These plants contain bioactive compounds with neuroprotective properties or activities that increase neural stem cells (NSCs) and neurons. However, bioactive components in Curcuma that promote the differentiation of NSCs into astrocytes have not yet been reported. Here, the effects of Curcuma extracts on the in vitro differentiation of embryonic stem-cell-derived NSCs were evaluated. The extract of the wild turmeric, Curcuma aromatica, strongly promoted the differentiation of NSCs into astrocytes. Bioassay-guided isolation yielded coronarins C (1) and D (2), as well as (E)-labda-8(17),12-diene-15,16-dial (3) as the bioactive compounds. Coronarin D (2) markedly promoted the differentiation of NSCs into astrocytes up to approximately 4 times (3.64 ± 0.48) and increased the expression level of GFAP at the mRNA and protein level, while compounds 1 and 3 exhibited only weak effects, suggesting that the 15-hydroxy-Δ12-γ-lactone moiety is important for bioactivity. Moreover, compound 2 increased the number of pSTAT3-positive cells, suggesting that compound 2 promoted astrocytic differentiation through JAK/STAT signaling pathway.
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