College of Korean Medicine, Gachon University, Seongnam-si 13120, Republic of Korea.
Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung-si 25451, Republic of Korea.
Int J Mol Sci. 2023 Jan 20;24(3):2066. doi: 10.3390/ijms24032066.
This study aimed to synthesize and evaluate the anti-inflammatory activity of 3-substituted-indolin-2-one derivatives. Cell viability of 3-substituted-indolin-2-one derivatives was measured with the EZ-Cytox reagent; interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible NOS mRNA levels were measured using Taqman qRT-PCR; pro-inflammatory cytokine IL-6 and TNF-α levels were determined using ELISA kits; the phosphorylation of Akt, JNK, ERK, p38, p65, and IκB protein levels were measured by immunoblotting. Among the nineteen 3-substituted-indolin-2-one derivatives synthesized, 3-(3-hydroxyphenyl)-indolin-2-one showed the highest anti-inflammatory activity, inhibiting the nitric oxide production related to inflammation, suppressing the production of TNF-α and IL-6 in a concentration-dependent manner and mRNA expression. Moreover, 3-(3-hydroxyphenyl)-indolin-2-one significantly inhibited lipopolysaccharide (LPS)-induced signal pathways such as the Akt, MAPK, and NF-κB signaling pathways. Our findings revealed that a 3-substituted-indolin-2-one derivative, 3-(3-hydroxyphenyl)-indolin-2-one, possesses excellent anti-inflammatory activity and can be considered for future research.
本研究旨在合成和评估 3-取代吲哚啉-2-酮衍生物的抗炎活性。使用 EZ-Cytox 试剂测定 3-取代吲哚啉-2-酮衍生物的细胞活力；使用 Taqman qRT-PCR 测定白细胞介素 (IL)-6、肿瘤坏死因子 (TNF)-α 和诱导型一氧化氮合酶 mRNA 水平；使用 ELISA 试剂盒测定促炎细胞因子 IL-6 和 TNF-α 水平；通过免疫印迹测定 Akt、JNK、ERK、p38、p65 和 IκB 蛋白水平的磷酸化。在合成的十九个 3-取代吲哚啉-2-酮衍生物中，3-(3-羟基苯基)-吲哚啉-2-酮显示出最高的抗炎活性，抑制与炎症相关的一氧化氮产生，以浓度依赖的方式抑制 TNF-α 和 IL-6 的产生和 mRNA 表达。此外，3-(3-羟基苯基)-吲哚啉-2-酮显著抑制脂多糖 (LPS) 诱导的信号通路，如 Akt、MAPK 和 NF-κB 信号通路。我们的研究结果表明，3-取代吲哚啉-2-酮衍生物 3-(3-羟基苯基)-吲哚啉-2-酮具有优异的抗炎活性，可考虑用于未来的研究。
