Journal Article

Secoiridoid Glucosides and Anti-Inflammatory Constituents from the Stem Bark of Fraxinus chinensis

Chang, Hao-Chiun, Chen, Jih-Jung, Sung, Ping-Jyun, Cheng, Ming-Jen, Chen, Chin-Yen, Wang, Shih-Wei, Liao, Kuang-Wen, Hwang, Tsong-Long

2020

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Animals / anti-inflammatory activity / Anti-Inflammatory Agents - chemistry / Anti-Inflammatory Agents - classification / Anti-Inflammatory Agents - isolation & purification / Anti-Inflammatory Agents - pharmacology / Chromatography / Cytochalasin B - antagonists & inhibitors / Cytochalasin B - pharmacology / Fraxinus - chemistry / Fraxinus chinensis / Gene Expression Regulation - drug effects / Gene Expression Regulation - immunology / Humans / Interleukin-6 - genetics / Interleukin-6 - immunology / Iridoid Glucosides - chemistry / Iridoid Glucosides - classification / Iridoid Glucosides - isolation & purification / Iridoid Glucosides - pharmacology / Kruppel-Like Factor 4 / Kruppel-Like Transcription Factors - genetics / Kruppel-Like Transcription Factors - immunology / Leukocyte Elastase - immunology / Leukocyte Elastase - metabolism / Lipopolysaccharides - antagonists & inhibitors / Lipopolysaccharides - pharmacology / MAP Kinase Kinase 4 - genetics / MAP Kinase Kinase 4 - immunology / Mice / Molecular Structure / N-Formylmethionine Leucyl-Phenylalanine - antagonists & inhibitors / N-Formylmethionine Leucyl-Phenylalanine - pharmacology / Neutrophils - cytology / Neutrophils - drug effects / Neutrophils - immunology / NF-KappaB Inhibitor alpha - genetics / NF-KappaB Inhibitor alpha - immunology / Nitric Oxide - antagonists & inhibitors / Nitric Oxide - metabolism / Oleaceae / p38 Mitogen-Activated Protein Kinases - genetics / p38 Mitogen-Activated Protein Kinases - immunology / Plant Bark - chemistry / Plant Extracts - chemistry / Primary Cell Culture / RAW 264.7 Cells / secoiridoid / stem bark / Structure-Activity Relationship / Superoxides - antagonists & inhibitors / Superoxides - metabolism / Tumor Necrosis Factor-alpha - genetics / Tumor Necrosis Factor-alpha - immunology