RESUMO
An OSMAC strategy was used to study secondary metabolites and anti-inflammatory activities of the endophytic fungus Penicillium herquei JX4 hosted in Ceriops tagal. The PDB ferment of fungus P. herquei JX4 was isolated, purified, and identified by using silica gel column chromatography, gel column chromatography, octadecylsilyl(ODS) column chromatography, and semi-preparative high-performance liquid chromatography. Two new pinophol derivatives, pinophol H(1) and pinophol I(2) were isolated and identified, and they were evaluated in terms of the inhibitory activities against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse macrophage RAW264.7 cells. The results showed that compound 1 had significant inhibitory activity on NO production, with an IC_(50) value of 8.12 µmol·L~(-1).
Assuntos
Óxido Nítrico , Penicillium , Penicillium/química , Camundongos , Animais , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Endófitos/química , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/químicaRESUMO
Background: Crohn's disease (CD) is a chronic inflammatory bowel disease with significant morbidity, affecting millions worldwide. The intricacies of immune responses in CD, especially post-treatment, remain a vital area of exploration. While memory T (Tm)-cell subsets play a pivotal role in adaptive immunity, their specific function in patients with CD after treatment is not well-understood. This study aims to investigate the effect and function of Tm-cell subsets in these patients, addressing a crucial knowledge gap in the context of CD therapeutics. Methods: A total of eight patients diagnosed with CD were selected based on predefined inclusion criteria. All patients were treated with either anti-inflammatory agents, immunosuppressive drugs, or a combination of both. For comparison, healthy donors were enrolled based on exclusion of autoimmune or inflammatory diseases. Peripheral blood mononuclear cells (PBMCs) and lymphocytes were isolated from blood and lymph node tissue respectively. The phenotype and cytokine production of T lymphocytes from both CD patients and healthy donors were analyzed using flow cytometry. Statistical comparisons of the outcomes between CD patients and healthy donors were made using Mann-Whitney test (two-tailed) and Student t-test. Results: Post-treatment CD patients exhibited an altered T cell distribution with a notable increase in CD8+ T cells in PBMCs (P=0.0005), and altered frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes (MLNs). Tm cells showed decreased interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) production, with significant alterations in the frequency of IFN-γ-producing CD8+ stem cell-like Tm (Tscm) cells in lesions of the MLNs from patients with CD (CD-M-Lys) compared to healthy MLNs from patients with CD (N-M-Lys) (P=0.0152). Differences in tissue-resident Tm (Trm)-cell subset frequencies were observed between the MLNs and small intestinal mucosa in CD patients. Conclusions: The treatments with anti-inflammatory agents and/or immunosuppressive drugs have a significant effect on the frequency and function of Tm-cell subsets. Clinically, these findings suggest a potential therapeutic avenue in modulating Tm-cell responses, which might be particularly beneficial for conditions where immune response modulation is crucial. Further clinical studies are warranted to explore the full therapeutic implications of these findings.
RESUMO
Three new indole alkaloids, named talatensindoids A-C (1-3), together with two known biogenetically related indole alkaloids tryptamine (4) and L-tryptophan (5) were isolated from the Talaromyces assiutensis JTY2 based on the guidance of OSMAC approach. The structures of these indole alkaloids were determined by comprehensive spectroscopic analyses. The absolute configuration of 3 was confirmed by X-ray crystallographic analysis. Compound 1 represent the rare example of a chlorine-substituted indole alkaloid from natural products. The inhibitory activity of compounds 1-5 against two phytopathogenic fungi and three phytopathogenic bacteria was evaluated. Compound 1 exhibited broad spectrum antibacterial activities.
Assuntos
Alcaloides Indólicos , Testes de Sensibilidade Microbiana , Talaromyces , Talaromyces/química , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/isolamento & purificação , Cristalografia por Raios X , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Bactérias/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Conformação Molecular , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , Fungos/efeitos dos fármacos , Fungos/químicaRESUMO
Two rare 5/5/5/6 four-ring system iridoids, allamancinsâ A and B (1 and 2) together with one known biogenetically related iridoid derivative, 3-O-methyallamancin (3) were isolated from the flowers of Plumeria alba L. The structures of these iridoid derivatives were determined by comprehensive spectroscopic analyses. The absolute configuration of 1 was confirmed by X-ray crystallographic analysis. The inhibitory activities of compoundsâ 1-3 against nitric oxide (NO) production induced and three cancer cell lines were evaluated inâ vitro. Compoundsâ 1 and 3 showed inhibitory activities on NO production with IC50 values of 18.3±0.12 and 22.1±0.14â µM, respectively. Compoundsâ 1-3 showed moderate inhibitory activities against cancer cell lines of A549, Hela and MCF-7.
Assuntos
Apocynaceae , Iridoides , Humanos , Iridoides/farmacologia , Iridoides/química , Células HeLa , Apocynaceae/química , Óxido Nítrico/metabolismo , Cristalografia por Raios X , Estrutura MolecularRESUMO
Two new anthraquinone derivatives sapranquinones A and B (1 and 2) together with two known biogenetically related anthraquinone derivatives (3 and 4) were isolated from the stems of Saprosma crassipes H. S. Lo. The structures of these compounds were elucidated using comprehensive spectroscopic methods. Compounds 1-4 were evaluated for their antibacterial activities and compounds 1 and 3 had a broad spectrum antibacterial activity against Staphylococcus albus, Escherichia coli, Bacillus cereus, Micrococcus tetragenus, and Micrococcus luteus with MIC values ranging from 1.25 to 5 µg/mL.