秦皮(FraxinuschinensisRoxb。)在许多国家商业上用于医疗保健产品,用于改善肠道功能和痛风性关节炎。三种新的Secoippoidroids糖苷,(8E)-4\'\'-O-甲基木质素苷(1),(8E)-4\'\'-O-甲基木质素苷(2),和3\'\',4\'\'-二-O-甲基-去甲基橄榄苦苷(3),从白蜡树的茎皮中分离出来,连同23种已知化合物(4-26)。通过光谱分析(1D,2DNMR,IR,UV,和HRESIMS)。在分离的化合物中,(8E)-4\'\'-O-甲基木质素苷(1),(8E)-4\'\'-O-甲基木质素苷(2),3\'\',4\'\'-二-O-甲基去甲基橄榄苦苷(3),橄榄苦苷(6),aesculetin(9),isoscopetin(11),aesculetin二甲酯(12),fraxetin(14),酪醇(21),4-羟基苯乙酸乙酯(22),和()-松脂醇(24)抑制(IC50≤7.65μg/mL)人嗜中性粒细胞对甲酰基-L-甲硫酰基-L-氯酰基-L-苯丙氨酸/细胞松弛素B的产生(fMLP/CB)。化合物1、9、11、14、21和22抑制fMLP/CB诱导的弹性蛋白酶释放,IC50≤3.23μg/mL。此外,化合物2、9、11、14和21显示出有效的抑制作用,IC50值≤27.11μM,对抗脂多糖(LPS)诱导的一氧化氮(NO)的产生。众所周知的促炎细胞因子,肿瘤坏死因子-α(TNF-α)和白细胞介素6(IL-6),也被化合物1、9和14抑制。化合物1、9和14显示出对NO的抗炎作用,TNF-α,和IL-6通过抑制LPS激活的巨噬细胞中MAPKs和IκBα的激活。此外,化合物1,9和14通过提高精氨酸酶1和Krüppel样因子4(KLF4)的表达来刺激抗炎M2表型。上述结果表明,化合物1、9和14可被认为是进一步开发NO产生靶向抗炎剂的潜在化合物。
Qin Pi (Fraxinus chinensis Roxb.) is commercially used in healthcare products for the improvement of intestinal function and gouty arthritis in many countries. Three new secoiridoid glucosides, (8E)-4\'\'-O-methylligstroside (1), (8E)-4\'\'-O-methyldemethylligstroside (2), and 3\'\',4\'\'-di-O-methyl-demethyloleuropein (3), have been isolated from the stem bark of Fraxinus chinensis, together with 23 known compounds (4-26). The structures of the new compounds were established by spectroscopic analyses (1D, 2D NMR, IR, UV, and HRESIMS). Among the isolated compounds, (8E)-4\'\'-O-methylligstroside (1), (8E)-4\'\'-O-methyldemethylligstroside (2), 3\'\',4\'\'-di-O-methyldemethyloleuropein (3), oleuropein (6), aesculetin (9), isoscopoletin (11), aesculetin dimethyl ester (12), fraxetin (14), tyrosol (21), 4-hydroxyphenethyl acetate (22), and (+)-pinoresinol (24) exhibited inhibition (IC50 ≤ 7.65 μg/mL) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leuckyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 1, 9, 11, 14, 21, and 22 inhibited fMLP/CB-induced elastase release with IC50 ≤ 3.23 μg/mL. In addition, compounds 2, 9, 11, 14, and 21 showed potent inhibition with IC50 values ≤ 27.11 μM, against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation. The well-known proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), were also inhibited by compounds 1, 9, and 14. Compounds 1, 9, and 14 displayed an anti-inflammatory effect against NO, TNF-α, and IL-6 through the inhibition of activation of MAPKs and IκBα in LPS-activated macrophages. In addition, compounds 1, 9, and 14 stimulated anti-inflammatory M2 phenotype by elevating the expression of arginase 1 and Krüppel-like factor 4 (KLF4). The above results suggested that compounds 1, 9, and 14 could be considered as potential compounds for further development of NO production-targeted anti-inflammatory agents.