Li-Chai Chen

Anti-Inflammatory and Analgesic Effects of the Marine-Derived Compound Comaparvin Isolated from the Crinoid Comanthus bennetti

To date, no study has been conducted to explore the bioactivity of the crinoid Comanthus bennetti. Here we report the anti-inflammatory properties of comaparvin (5,8-dihydroxy-10-methoxy-2-propylbenzo[h]chromen-4-one) based on in vivo experiments. Our preliminary screening for anti-inflammatory activity revealed that the crude extract of Comanthus bennetti significantly inhibited the expression of pro-inflammatory proteins in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Comaparvin isolated from crinoids significantly decreased the expression of inducible nitric oxide synthase (iNOS) protein and mRNA in LPS-stimulated macrophage cells. Moreover, our results showed that post-treatment with comaparvin significantly inhibited mechanical allodynia, thermal hyperalgesia and weight-bearing deficits in rats with carrageenan-induced inflammation. Comaparvin also attenuated leukocyte infiltration and iNOS protein expression in carrageenan-induced inflamed paws. These results suggest that comaparvin is a potential anti-inflammatory therapeutic agent against inflammatory pain.

Limonoids from the Seeds of Swietenia macrophylla and Their Anti-Inflammatory Activities.

A new limonoid, swietemacrophin (1), was isolated from the seeds of Swietenia macrophylla, together with five known compounds 2–6. The structure of 1 was determined through extensive 1D/2D-NMR and mass-spectrometric analyses. Swietemacrophin (1), humilinolide F (2), 3,6-O,O-diacetylswietenolide (3), 3-O-tigloylswietenolide (4), and swietemahonin E (5) exhibited inhibition (IC50 values ≤ 45.44 μM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). Compounds 1, 4, 5, and swietenine (6) showed potent inhibition with IC50 values ≤ 36.32 μM, against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation.

New Sesquiterpenoids and Anti-Platelet Aggregation Constituents from the Rhizomes of Curcuma zedoaria

Two new sesquiterpenoids—13-hydroxycurzerenone (1) and 1-oxocurzerenone (2)—have been isolated from the rhizomes of Curcuma zedoaria, together with 13 known compounds (3–15). The structures of two new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 13-hydroxycurzerenone (1), 1-oxocurzerenone (2), curzerenone (3), germacrone (4), curcolone (5), procurcumenol (6), ermanin (7), curcumin (8), and a mixture of stigmast-4-en-3,6-dione (12) and stigmasta-4,22-dien-3,6-dione (13) exhibited inhibition (with inhibition % in the range of 21.28%–67.58%) against collagen-induced platelet aggregation at 100 μM. Compounds 1, 5, 7, 8, and the mixture of 12 and 13 inhibited arachidonic acid (AA)-induced platelet aggregation at 100 μM with inhibition % in the range of 23.44%–95.36%.

New thymol derivatives and cytotoxic constituents from the root of Eupatorium cannabinum ssp. asiaticum.

Two new thymol (=5‐methyl‐2‐(1‐methylethyl)phenol) derivatives, 8,10‐didehydro‐9‐(3‐methylbutanoyl)thymol 3‐O‐tiglate (1) and 9‐O‐angeloyl‐8‐methoxythymol 3‐O‐isobutyrate (2), were isolated from the root of Eupatorium cannabinum ssp. asiaticum, together with six known compounds, 3–8. The structures of 1 and 2 were determined through extensive 1D/2D‐NMR and MS analyses. Among the isolates, 9‐acetoxy‐8,10‐epoxythymol 3‐O‐tiglate (3) was the most cytotoxic, with IC50 values of 0.02±0.01, 1.02±0.07, and 1.36±0.12 μg/ml, respectively, against DLD‐1, CCRF‐CEM, and HL‐60 cell lines. In addition, 10‐acetoxy‐9‐O‐angeloyl‐8‐hydroxythymol (4) and eupatobenzofuran (6) exhibited cytotoxicities, with IC50 values of 1.14±0.16 and 2.63±0.22, and 7.63±0.94 and 2.31±0.14 μg/ml, respectively, against DLD‐1 and CCRF‐CEM cell lines.

A New Chalcone and Antioxidant Constituents of Glycyrrhiza glabra

A new chalcone, glycyglabrone (1), has been isolated from the roots of Glycyrrhiza glabra, together with three known compounds, licoagrochalcone B (2), licochalcone C (3), and kanzonol Y (4). The structure of the new compound 1 was determined through spectroscopic and MS analyses. Glycyglabrone (1) and licochalcone C (3) exhibited potent free radical scavenging activity, with IC0.200 values of 4.6 ± 0.6 and 8.2 ± 0.9 μM, respectively, in the diphenylpicrylhydrazyl radical (DPPH) decoloration assay.

New Cytotoxic 24-Homoscalarane Sesterterpenoids from the Sponge Ircinia felix

Two new 24-homoscalarane sesterterpenoids, felixins F (1) and G (2), were isolated from the sponge Ircinia felix. The structures of new homoscalaranes 1 and 2 were elucidated by extensive spectroscopic methods, particularly with one-dimensional (1D) and two-dimensional (2D) NMR, and, by comparison, the spectral data with those of known analogues. The cytotoxicity of 1 and 2 against the proliferation of a limited panel of tumor cell lines was evaluated and 1 was found to show cytotoxicity toward the leukemia K562, MOLT-4, and SUP-T1 cells (IC50 ≤ 5.0 μM).

Cholest-4-en-3-one attenuates TGF-β responsiveness by inducing TGF-β receptors degradation in Mv1Lu cells and colorectal adenocarcinoma cells

Abstract Purpose: The transforming growth factor-beta (TGF-β) pathway is an important in the initiation and progression of cancer. Due to a strong association between an elevated colorectal cancer risk and increase fecal excretion of cholest-4-en-3-one, we aim to determine the effects of cholest-4-en-3-one on TGF-β signaling in the mink lung epithelial cells (Mv1Lu) and colorectal cancer cells (HT29) in vitro. Methods: The inhibitory effects of cholest-4-en-3-one on TGF-β-induced Smad signaling, cell growth inhibition, and the subcellular localization of TGF-β receptors were investigated in epithelial cells using a Western blot analysis, luciferase reporter assays, DNA synthesis assay, confocal microscopy, and subcellular fractionation. Results: Cholest-4-en-3-one attenuated TGF-β signaling in Mv1Lu cells and HT29 cells, as judged by a TGF-β-specific reporter gene assay of plasminogen activator inhibitor-1 (PAI-1), Smad2/3 phosphorylation and nuclear translocation. We also discovered that cholest-4-en-3-one suppresses TGF-β responsiveness by increasing lipid raft and/or caveolae accumulation of TGF-β receptors and facilitating rapid degradation of TGF-β and thus suppressing TGF-β-induced signaling. Conclusions: Our results suggest that cholest-4-en-3-one inhibits TGF-β signaling may be due, in part to the translocation of TGF-β receptor from non-lipid raft to lipid raft microdomain in plasma membranes. Our findings also implicate that cholest-4-en-3-one may be further explored for its potential role in colorectal cancer correlate to TGF-β deficiency.

Naphthofuranone derivatives and other constituents from Pachira aquatica with inhibitory activity on superoxide anion generation by neutrophils

Two new naphthofuranone derivatives, 11-hydroxy-2-O-methylhibiscolactone A (1) and O-methylhibiscone D (2), have been isolated from the stems of Pachira aquatica, together with 18 known compounds (3-20). The structures of two new compounds were determined through spectroscopic and MS analyses. Among the isolated compounds, 11-hydroxy-2-O-methylhibiscolactone A (1), isohemigossylic acid lactone-7-methyl ether (4), gmelofuran (6), and 5-hydroxyauranetin (8) exhibited inhibition (IC50≤28.84μM) of superoxide anion generation by human neutrophils in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP).

New Labdane-Type Diterpenoid and Cytotoxic Constituents of Hedychium coronarium

A new labdane-type diterpenoid, hedychiumin (1), has been isolated from the aerial part of Hedychium coronarium, together with five known compounds, (+)-coronarin A (2), (E)-15,16-bisnorlabda-8(17),11-dien-13-one (3), calcaratarin A (4), β-sitostenone (5), and stigmasta-4,22-dien-3-one (6). The structure of the new compound 1 was determined through spectroscopic and MS analyses. Among the isolates, hedychiumin (1) exhibited cytotoxicity, with IC50 value of 4.74 μg/mL, against P388D1 cell line.