Journal of Natural Medicines最新文献

Three new biflavonoids (1–3) and two known flavonoids (4, 5) were isolated from Xylia kerrii collected in Thailand. Compounds 1–5 showed selective cytotoxicity against the rheumatoid fibroblast-like synovial MH7A cell line, and these compounds showed weak cytotoxicity against the human lung synovial fibroblast WI-38 VA13 sub 2 RA cell line. Notably, compound 1 was highly selective toward MH7A cells with an IC₅₀ value of 6.9 μM, whereas the IC₅₀ value for WI-38 VA13 sub 2 RA cells was > 100 μM. The western blotting analysis of MH7A cells treated with compound 1 showed increased CDKN2A /p16INK4A and caspase-8 levels.

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Mountain caviar is a fruit of Kochia scoparia that contains momordin Ic as a major saponin constituent. Its extract (MCE) has been shown to suppress blood glucose elevations in the human oral glucose tolerance test (OGTT) as well as increases in blood glucose in OGTT, gastric emptying (GE), and glucose incorporation in the small intestine in rats. However, the effects of MCE and momordin Ic on glucose absorption in mice and these action mechanisms have not been examined for more than 2 decades. Therefore, we herein investigated the effects of MCE, its saponin fraction, and momordin Ic on blood glucose elevations in mice. Mouse blood glucose elevation tests were performed on carbohydrate-loaded mice. The mountain caviar saponin fraction significantly delayed blood glucose elevations in glucose-, sucrose-, and soluble starch-loaded mice. In glucose-loaded mice, the saponin fraction, MCE, and momordin Ic significantly suppressed rapid glucose elevations after glucose loading, but not sucrose loading. A mouse GE study was performed by loading with glucose and phenolphthalein solution. Momordin Ic and MCE strongly suppressed mouse GE. Intestinal glucose absorption was evaluated by the incorporation of 2-deoxyglucose (2-DG) into Caco-2 cell layers and mouse duodenum wall vesicles. The results obtained showed that momordin Ic inhibited the incorporation of 2-DG into Caco-2 cells and mouse duodenum vesicles. Collectively, these results suggest that MCE, particularly the principal saponin, momordin Ic, preferably suppressed glucose-induced blood glucose elevations and delayed carbohydrate-induced glucose elevations in mice. The underlying mechanism was found to involve the suppression of GE and intestinal glucose absorption.

Graphical Abstract

The relative configuration of the epoxide functionality in pinofuranoxin A (1), α-alkylidene-β-hydroxy-γ-methyl-γ-butyrolactone with trans-epoxy side chain isolated by Evidente et al. in 2021, was revised by DFT-based spectral reinvestigations and stereo-controlled synthesis. The present investigation demonstrates the difficulty of the configurational elucidation of the stereogenic centers on the conformationally flexible acyclic side-chains. Sharpless’s enantioselective epoxidations and dihydroxylations were quite effective in the reinvestigations of the configurations. As our syntheses made all diastereomers available, these would be quite effective in the next structure-biological activity relationship studies.

Graphical Abstract

Baicalin and berberine are biologically active constituents of the crude drugs Scutellaria root and Coptis rhizome/Phellodendron bark, respectively. Baicalin and berberine are reported to combine together as a 1:1 complex that forms yellow precipitates by electrostatic interaction in decoctions of Kampo formulae containing these crude drugs. However, the structural basis and mechanism for the precipitate formation of this compound–compound interaction in aqueous solution remains unclarified. Herein, we searched for berberine derivatives in the Coptis rhizome that interact with baicalin and identified the chemical structures involved in the precipitation formation. Precipitation assays showed that baicalin formed precipitates with berberine and coptisine but not with palmatine and epiberberine. Thus, the 2,3-methylenedioxy structure may be crucial to the formation of the precipitates, and electrostatic interaction is necessary but is not sufficient. In this multicomponent system experiment, palmatine formed a dissociable complex with baicalin and may competitively inhibit the formation of berberine and coptisine precipitation with baicalin. Therefore, the precipitation formed by berberine and baicalin was considered to be caused by the aggregation of the berberine–baicalin complex, and the 2,3-methylenedioxy structure is likely crucial to the aggregation of the complex.

Graphic abstract

In this study, nine triterpene glycosides including seven previously undescribed compounds (1–7), were isolated from leaves of Cryptolepis buchananii R.Br. ex Roem. and Schult. using various chromatographic methods. The chemical structures of the compounds were elucidated to be 3-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosyluncargenin C 28-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl ester (1), 3-O-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyluncargenin C 28-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl ester (2), 3-O-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyluncargenin C 28-O-β-d-glucopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl ester (3), 3-O-β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosylhederagenin 28-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl ester (4), 3-O-β-d-glucopyranosylarjunolic acid 28-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl ester (5), 3-O-β-d-glucopyranosyl-(1 → 2)-β- d-glucopyranosyl-6β,23-dihydroxyursolic acid 28-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl ester (6), 3-O-β-d-glucopyranosyl-6β,23-dihydroxyursolic acid 28-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl ester (7), asiatic acid 28-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl ester (8), and 3-O-β-d-glucopyranosylasiatic acid 28-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl ester (9), through infrared, high-resolution electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance spectral analyses. The isolates inhibited nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells, with half-maximal inhibitory concentration (IC₅₀) values of 18.8–58.5 µM, compared to the positive control compound, dexamethasone, which exhibited an IC₅₀ of 14.1 µM.

Graphical abstract

Methanol extract of the Cnidium officinale Makino rhizome, which is used as a crude drug Cnidium Rhizome (Cnidii Rhizoma; “Senkyu” in Japanese) and is listed in the Japanese Pharmacopoeia XVIII, showed intracellular triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells. Thirty-five constituents, including two new alkylphthalide glycosides, senkyunosides A (1) and B (2), and a neolignan with a new stereoisomeric structure (3), were isolated in the extract. Their stereostructures were elucidated based on chemical and spectroscopic evidence. Among the isolates, several alkylphthalides, (Z)-3-butylidene-7-methoxyphthalide (9) and senkyunolides G (10), H (14), and I (15), and a polyacetylene falcarindiol (26), were found to show significant activity without any cytotoxicity at 10 μM.

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A novel trimeric monoterpenoid indole alkaloid, vincarostine A (1) consisting of an aspidosperma-iboga-aspidosperma type skeleton, was isolated from the whole plant of Catharanthus roseus. The structure including absolute stereochemistry was elucidated on the basis of 2D NMR data and CD spectrum. Vincarostine A (1) showed anti-malarial activity.

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Oxomollugin is a degraded product of mollugin and was found to be an active compound that inhibits LPS-induced NF-κB activation. In this study, we investigated the inhibitory activity of oxomollugin, focusing on TLR4 signaling pathway, resulting in NF-κB activation. Oxomollugin inhibited the LPS-induced association of essential factors for initial activation of TLR4 signaling, MyD88, IRAK4 and TRAF6. Furthermore, oxomollugin showed suppressive effects on LPS-induced modification of IRAK1, IRAK2 and TRAF6, LPS-induced association of TRAF6-TAK1/TAB2, and followed by IKKα/β phosphorylation, which critical in signal transduction leading to LPS-induced NF-κB activation. The consistent results suggested that oxomollugin inhibits LPS-induced NF-κB activation via the suppression against signal transduction in TLR4 signaling pathway.

The activities of oxomollugin reported in this study provides a deeper understanding on biological activity of mollugin derivatives as anti-inflammatory compounds.

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