Journal of Natural Medicines最新文献

Boletus bicolor is a kind of wild edible boletus, which is widely distributed in China. We have isolated the protein D1 from B. bicolor, and found that protein D1 has a significant inhibitory effect on the growth and proliferation of lung cancer A549 cells both in vitro and in vivo. In this paper, we found that miR-34a plays an important role in inhibiting the proliferation of A549 cells. miR-34a is the functional target of protein D1 against A549 cells. Protein D1 induces the positive feedback regulation of miR-34a and p53, which further regulates downstream Bcl-2 and CDK6, and inhibits the proliferation of A549 cells.

Two previously undescribed specialized metabolites, erecricins F (1) and G (2), along with two known metabolites, erectumins A (3) and B (4), were isolated from the aerial parts of Hypericum erectum Thunb. (Hypericaceae). Detailed spectroscopic analyses revealed erecricin F (1) to be a C₃₀ meroterpene with four isoprene units, and erecricin G (2) to be a prenylated acylphloroglucinol biogenetically related to 1. The relative configurations of erecricins F (1) and G (2) were assigned by NOESY analysis and GIAO NMR calculation, while their absolute configurations were deduced by comparison of the ECD spectra with TDDFT calculated spectra. The relative configurations of 3 and 4 were also elucidated by the similar method as for 1 and 2. Erecricins F (1) and G (2) and erectumins A (3) and B (4) were evaluated for their inhibitory effect against IL-1β release from LPS-stimulated murine microglial cells and anti-ferroptosis activity using human hepatoma Hep3B cells.

Resin glycosides, characteristic of plants of the Convolvulaceae family, are well-known purgative constituents found in traditional medicinal crude drugs, such as Rhizoma Jalapae, Rhizoma Jalapae Braziliensis, Orizaba Jalapa Tuber, and Pharbitidis Semen. The isolated compounds exhibited a wide range of biological activities, including antibacterial, ionophoric, anti-inflammatory, antiviral, and multidrug-resistance-modulating properties, as well as cytotoxicity against cancer cells. Ipomoea lacunosa L. (Convolvulaceae) is an herbaceous vine native to the United States. Four new acylated glycosidic acid methyl esters (1-4) and one new glycosidic acid (5) were isolated from the methanol extract of the plant seed. The structures of 1-5 were elucidated using spectroscopic data in conjunction with our previous studies on the components of the crude resin glycoside fraction from I. lacunosa seeds. Compounds 1 and 2 were identified as heptaglycosides, 3 as an octaglycoside, and 4 as a nonaglycoside, all sharing methyl 3S,11S-dihydroxytetradecanoate as a common aglycone. The saccharide moieties were partially acylated by glycosidic acid, 7S-hydroxydecanoic acid 7-O-β-D-quinovopyranoside, and organic acids, including (E)-2-methylbut-2-enoic, 2S-methylbutyric, and 2R-methyl-3R-hydroxybutyric acids. Compound 5 was identified as a triglycoside with a new aglycone, 4,11-dihydroxyhexadecanoic acid, which is the first glycosidic acid with a hydroxyl group at C-4 of the aglycone moiety.

Fe(II)/αKG-dependent oxygenases are multifunctional oxidases responsible for the formation of unique natural product skeletons. Studies of these enzymes are important because the knowledge of their catalytic functions, enzyme structures, and reaction mechanisms can be used to create non-natural enzymes through mutation and synthesize non-natural compounds. In this review, I will introduce the research we have conducted on two fungal Fe(II)/αKG-dependent oxygenases, TlxI-J and TqaL. TlxI-J is the first Fe(II)/αKG-dependent oxygenase type enzyme heterodimer that catalyzes consecutive oxidation reactions, hydroxylation followed by retro-aldol or ketal formation, to form the complex skeletons of meroterpenoids. TqaL is the first naturally occurring aziridine synthase, and I will discuss the mechanism of its unique C-N bond formation in nonproteinogenic amino acid biosynthesis. This review will advance research on the discovery of new enzymes and the analysis of their functions by reviewing the structures and functions of these extraordinary Fe(II)/αKG-dependent oxygenases, and promote their use in the synthesis of new natural medicines.

Since the coronavirus disease 2019 (COVID-19) outbreak, research has been conducted on treatment and countermeasures against the causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the development of new seeds is urgently needed because viruses have the characteristic of becoming resistant through mutation. We hypothesize that endophytes produce antiviral substances to combat foreign viruses in host plants. According to this hypothesis, the seeds of therapeutic agents for infectious diseases could be obtained from endophytes by culture experiments. This report found that Aspergillus sp. endophyte isolated from Catharanthus roseus produced ( +)-eupenoxide and its 3-ketone form with anti-SARS-CoV-2 activity. In addition, ( +)-eupenoxide-3,6-diketon was discovered as a new compound with potent 3C-like protease inhibitory activity (IC₅₀: 0.048 μM) by synthesis based on ( +)-eupenoxide. This finding could be an important evidence that endophytic fungi symbiosis with medicinal plants is useful as antiviral producers.

A new diterpenoid, carneadiol (1), with an unprecedented tricyclic carbon skeleton, was isolated from the culture extracts of Nocardia carnea IFM 12324. The structure of compound 1 was elucidated using spectral studies, including various NMR data. The absolute configuration of 1 was determined using X-ray crystallographic analysis with the crystalline sponge method. The biosynthetic gene of compound 1 was deduced, and it was observed that the mRNA of the gene involved in terpenoid cyclization increased significantly in the strain producing compound 1.

Two new cerebrosides, raphimanosides A (1) and B (2), and a new ceramide, raphimanide (3), were isolated from the aerial parts of Raphidiocystis mannii Hook. f., along with ten known compounds (4-13). Their structures were fully established, based on extensive analyses of ¹H, ¹³C, DEPT, 2D NMR, ESIMS, and HRESIMS data and chemical conversion. Subsequently, methanol extract, ethyl acetate, and n-butanol soluble portions and the isolated compounds 1-9, 12, and 13 were assayed for their cytotoxic effects against three human cancer cell lines (MCF-7, HeLa and A549). None of the new compounds demonstrated efficacy against the tested cell lines. In contrast, the methanol extract, ethyl acetate soluble portion, and compounds 6, 7, 9, 12, and 13 showed moderate to low activities against different tested cell lines. Ethyl acetate soluble portion and compounds 13 and 7 were the most potent samples with the IC₅₀ value of 41.25 μg/mL, 36.76 μM, and 13.16 μM against MCF-7, HeLa, and A549 cell lines, respectively. To the best of our knowledge, this is the inaugural investigation into the chemical constituents of the genus Raphidiocystis, offering novel insights into the chemotaxonomy of this hitherto poorly understood genus.

Steroids are physiologically important compounds for animals, plants, and fungi, and they have significantly contributed to drug discovery for many years. Fungi mainly biosynthesize ergostane-type steroids such as ergosterol. However, after the basic skeleton is biosynthesized, chemical transformations can lead to the cleavage or rearrangement of the fundamental skeleton of steroids. The cleaved (seco) and rearranged (abeo) steroids are chemically and pharmacologically intriguing because they often exhibit biological activities. As ergostane-type steroids including the normal, seco, and abeo types have been isolated from the mushrooms of the Pleurotus genus, this review focuses on them as a resource of ergostane-type steroids, providing their distribution, structure determination, and biological activity.

Non-Hodgkin lymphomas (NHL), including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), and follicular lymphoma (FL), predominantly arise from B cells undergoing germinal center (GC) reactions. The transcriptional repressor B-cell lymphoma 6 (BCL6) is indispensable for GC formation and contributes to lymphomagenesis via its BTB domain-mediated suppression of target genes. Dysregulation of BCL6 underpins the pathogenesis of GC-derived NHL. While pharmacological targeting the BCL6-BTB domain has shown therapeutic promise, natural product-based inhibitors remain underexplored. In this study, resveratrol, a polyphenolic compound derived from grapes, was identified as a potent BCL6 inhibitor through a comprehensive screen of traditional Chinese medicine monomers using Homogeneous Time-Resolved Fluorescence (HTRF) assay. As a BCL6 natural inhibitor, resveratrol effectively disrupted the BCL6/SMRT interaction, reactivated suppressed gene expression, and inhibited the proliferation of GC-derived NHL cells. It also exhibited synergistic efficacy when combined with EZH2 and PRMT5 inhibitors. In vivo, resveratrol suppressed GC formation, reduced follicular helper T-cell frequencies, impaired class-switch recombination, and disrupted immunoglobulin affinity maturation. Furthermore, it markedly inhibited the progression of GC-derived NHL in animal models. Our findings demonstrate that resveratrol functions as a natural BCL6 inhibitor with significant therapeutic potential for the treatment of GC-derived NHL.

In the preliminary screening, falcarinol and falcarindiol, C₁₇ polyacetylenes from the roots of Glehnia littoralis F. Schmidt ex Miq (Umbelliferae), displayed cytotoxic activity both against oxaliplatin-sensitive/resistant colorectal cancer (CRC) and gefitinib-sensitive/resistant non-small cell lung cancer (NSCLC) cells. In this study, 13 polyacetylenes including a new (3R,11R)-11-hyroxy-isofalcarinolone (1) were isolated from G. littoralis, and the chemical structures were elucidated through NMR, HRMS, and optical rotation analysis as well as DP4 plus calculation. (3S,8S)-Oplopandiol (5) showed cytotoxic activities against oxaliplatin-sensitive and -resistant CRC (HCT116 and HCT116-OxR) cells. Unexpectedly, (3R,8S)-falcarindiol (3) and (3S)-falcarinol (12), newly purified from G. littoralis, did not show cytotoxic activity. It was confirmed that both falcarinol and falcarindiol, previously evaluated, were decomposed, which seems to be the cause of inconsistent biological results. These findings indicated that C₁₇ polyacetylene could be a good starting compound for the development of anticancer leads against drug-resistant CRC and NSCLC cells, however, the stability of C₁₇ polyacetylens should be considered for further studies.