BACKGROUND & AIMS:
:Anti-inflammatory and peroxisome proliferator-activated receptors (PPARs) transactivational effects of nine compounds (1 - 9) from the roots of Sophora flavescens were evaluated using NF-κB-luciferase, reverse transcriptase polymerase chain reaction, peroxisome proliferator response element (PPRE)-luciferase, and GAL-4-PPAR chimera assays. Compounds 4 and 8 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC₅₀ values of 4.0 and 4.4 μM, respectively. Furthermore, the transcriptional inhibitory function of these compounds was confirmed by a decrease in cyclooxgenase 2 and inducible nitric oxide synthase gene expression levels in HepG2 cells. Compounds 1, 3, 5, 6, 8, and 9 significantly activated the transcription of PPARs in a dose-dependent manner, with EC₅₀ values ranging from 1.1 to 13.0 μM. Compounds 1, 3, 5, 6, 8, and 9 exhibited dose-dependent PPARα transactivational activity, with EC₅₀ values in a range of 0.9 - 16.0 μM. Compounds 1, 3, 8, and 9 also significantly upregulated PPARγ activity in a dose-dependent manner, with EC₅₀ values of 10.5, 6.6, 15.7, and 1.6 μM, whereas compounds 1, 8, and 9 demonstrated transactivational PPARβ(δ) effects with EC₅₀ values of 11.4, 10.3, and 1.5 μM, respectively. These results provide a scientific rationale for the use of the roots of S. flavescens and warrant further studies to develop new agents for the prevention and treatment of inflammatory and metabolic diseases.
背景与目标:
: 使用NF-κ b-荧光素酶,逆转录酶聚合酶链反应,过氧化物酶体增殖物反应元件 (PPRE)-荧光素酶评估了苦参根中的9种化合物 (1 - 9) 的抗炎和过氧化物酶增殖物激活受体 (ppar) 反式激活作用。GAL-4-PPAR嵌合体分析。化合物4和8以剂量依赖的方式显着抑制了tnf α 诱导的HepG2细胞中的NF-κ b转录活性,其ic of值分别为4.0和4.4 μ m。此外,这些化合物的转录抑制功能被HepG2细胞中环氧合酶2和诱导型一氧化氮合酶基因表达水平的降低所证实。化合物1、3、5、6、8和9以剂量依赖性方式显着激活ppar的转录,其值范围为1.1至13.0 μ m。化合物1、3、5、6、8和9表现出剂量依赖性ppar α 反式激活活性,其值在0.9 - 16.0 μ m的范围内。化合物1、3、8和9也以剂量依赖的方式显着上调ppar γ 活性,其e of value为10.5、6.6、15.7和1.6 μ m,而化合物1、8和9表现出反式激活ppar β(δ) 效应,其e of value为11.4、10.3,和1.5 μ m,分别。这些结果为使用S. flavescens的根提供了科学依据,并需要进一步研究以开发用于预防和治疗炎症和代谢疾病的新药物。