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

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.

Identification of Key Biomarkers and Immune Infiltration in Systemic Juvenile Idiopathic Arthritis by Integrated Bioinformatic Analysis

“…In human, arginase one is constitutively expressed in polymorphonuclear neutrophils, and acts as a key regulator of innate immunity and adaptive immunity (Panfili et al, 2020). It is liberated from neutrophils in some inflammatory diseases such as glomerular acute immune complex inflammation, and it reduces the L-arginine bioavailability and downregulates the levels of NO through substrate competition, which in turn suppresses immune responses (Waddington et al, 1998;Munder, 2009;Chang et al, 2020;Sim et al, 2021). In the present study, ARG1 was found to be upregulated in sJIA patients, which may be attributed to the chronic arthritis of sJIA, since ARG1 is supposed to be an anti-inflammatory factor.…”

Advances in Research on Chemical Constituents and Their Biological Activities of the Genus Actinidia

“…A total of 16 related compounds (139)(140)(141)(142)(143)(144)(145)(146)(147)(148)(149)(150)(151)(152)(153)(154) have been obtained from kiwifruit plants (Fig. 7, Table 6).…”

“…Two coumarins were isolated from the roots of A. deliciosa and identified as fraxetin 260 and isoscopoletin 261 [150]. Compound 260 showed potent inhibition against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation with an IC 50 value of 10.11 ± 0.47 µM [151]. Esculin 263 and fraxin 264 were characterized from the stems and fruits of A. deliciosa (kiwifruit) and A. chinensis [152].…”

“… 258 Umbelliferone A. polygama [ 109 ] Leaves Anti-tumor (in vitro) [ 143 ] Anti-inflammatory (in vitro) [ 144 ] Antioxidant (in vitro) [ 149 ] Antidiabetic (in vitro and in vivo) [ 146 ] Immunomodulatory(in vitro) [ 148 ] 259 Esculetin A. arguta [ 135 ] Fruits Anti-tumor (in vitro) [ 154 ] Anti-oxidant and anti-inflammatory (in vivo) [ 155 ] 260 Fraxetin A . deliciosa [ 150 ] Roots Anti-inflammatory (in vitro) [ 151 ] Anti-tumor (in vitro) [ 156 ] 261 Isoscopoletin A . deliciosa [ 150 ] Roots Anti-inflammatory [ 151 ] 262 Isofraxoside A. chinensis [ 137 ] Roots 263 Esculin A .…”

“…deliciosa [ 150 ] Roots Anti-inflammatory (in vitro) [ 151 ] Anti-tumor (in vitro) [ 156 ] 261 Isoscopoletin A . deliciosa [ 150 ] Roots Anti-inflammatory [ 151 ] 262 Isofraxoside A. chinensis [ 137 ] Roots 263 Esculin A . deliciosa [ 152 ] Stems 264 Fraxin A .…”