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

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

doi:10.3390/molecules25245911

Abstract

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.

Highlights

Fraxinus chinensis Roxb. (Oleaceae) is a deciduous tree distributed in China, Japan, Korea, Russia, and Vietnam [1]
Phosphorylation of JNK caused by LPS was most significantly inhibited by these compounds. These results suggest that the anti-inflammatory effects of compounds 1, 9, and 14 are through the inhibition of activation of Mitogen-activated protein kinases (MAPKs) and IκBα in LPS-activated macrophages
We further examined whether compounds 1, 9, and 14 enhanced the expression level of M2 macrophages

Summary

Introduction

Fraxinus chinensis Roxb. (Oleaceae) is a deciduous tree distributed in China, Japan, Korea, Russia, and Vietnam [1]. A number of secoiridoid glucosides [2,3,4,5,6], coumarins [5,6], phenylpropenoids [5,6], lignans [6], and benzofuran derivatives [6] have been reported from the genus Fruxinus. These derivatives have been reported to exhibit several biological activities, such as antidiabetic [4], anti-inflammatory [4], immunosuppressive [4], anticancer [4], and quinone reductase-inducing activities [6].

Methods

Results

Conclusion