Journal of Natural Medicines最新文献

Seven new saponins (1-7) isolated from Stenocereus eruca (Cactaceae) and four new saponins (8-11) isolated from Polaskia chichipe (Cactaceae)　are described. Their structures were elucidated using high-resolution mass spectrometry and nuclear magnetic resonance analysis including ¹H and ¹³C NMR, DEPT, HMQC, HMBC, H2BC, DQF-COSY, HSQC-TOCSY, phase sensitive TOCSY, 1D-TOCSY, phase sensitive NOESY, and ROESY experiments. One saponin required J-resolved spectroscopy experiments due to its complex ¹H NMR spectrum. The inhibitory activity of Aβ aggregation, and protective effects on SH-SY5Y neuroblastoma cells against Aβ toxicity, were evaluated. Only 7 showed weak inhibitory activity of Aβ aggregation at 100 µM compared to the control group. No compounds showed obvious protective effects, but 8 possessed a very weak protective effect on SH-SY5Y cells. The acetylation of the C-16, C-22, and C-30 hydroxyl groups could be important for inhibitory activity of Aβ aggregation and protective effects on SH-SY5Y cells against Aβ toxicity.

Natural phenolic acid compounds have been extensively studied for their anti-inflammatory properties, particularly in the context of inflammation-associated diseases. In this study, we investigated the anti-inflammatory effects of trans-cinnamic acid on neutrophil accumulation during inflammatory processes using both in vivo and in vitro approaches. For the in vivo experiments, LPS-induced pleurisy was used in mice pretreated with trans-cinnamic acid. Inflammatory parameters, including plasma leakage, leukocyte infiltration, and proinflammatory cytokine levels (IL-6 and TNF-α), were quantified in the pleural exudate. In vitro, the effects of trans-cinnamic acid on neutrophil chemotaxis toward CXCL1 were assessed using the Boyden chamber assay. Additionally, human endothelial EA.hy926 cells were stimulated with TNF-α to evaluate neutrophil adhesion and the expression of the adhesion molecule ICAM-1 following trans-cinnamic acid treatment. Pretreatment with trans-cinnamic acid significantly inhibited LPS-induced pleurisy in mice by reducing protein-rich exudate formation, neutrophil infiltration, and local concentrations of TNF-α and IL-6. In vitro, trans-cinnamic acid did not alter CXCL1-induced neutrophil chemotaxis, nor the secretion of CXCL8 produced by TNF-α-stimulated EA.hy926 cells. However, it markedly reduced neutrophil adhesion to TNF-α-activated EA.hy926 cells. This reduction was associated with the downregulation of ICAM-1 expression at both the mRNA and protein levels. Overall, these findings demonstrated that trans-cinnamic acid exerted anti-inflammatory effects by inhibiting vascular permeability and leukocyte recruitment, particularly through the suppression of ICAM-1-mediated neutrophil adhesion to endothelial cells. These results support trans-cinnamic acid as a promising candidate for the development of new therapeutic agents targeting inflammatory diseases.

Liver fibrosis is a significant global health threat, and Carthamus tinctorius L., a traditional herb used for liver ailments, contains flavonoids with diverse pharmacological properties. This study explored the effects and mechanisms of total flavonoids from Carthamus tinctorius L. (TFCTL) on hepatic fibrosis in mice and TGF-β1-induced activation of hepatic stellate cells (HSCs). Using LC-MS/MS, TFCTL's composition was characterized, and models of liver fibrosis in mice and HSC-T6 cell activation in vitro were established. Techniques such as CCK-8, Western blotting, RT-qPCR, and immunofluorescence revealed that TFCTL inhibited HSC-T6 activation and proliferation by promoting YAP phosphorylation and degradation via increased MST1 and LATS1 expression, suppressing Hippo pathway target genes. TFCTL also improved liver fibrosis pathology in mice, primarily through the Hippo/YAP pathway. These results underscore the anti-fibrotic potential of TFCTL, establishing it as a highly promising candidate for the treatment of liver fibrosis.

Two new mycobactins, U (1) and V (3), were isolated with ferric-1 (2) and ferric-3 (4) from the culture extracts of Mycolicibacterium septicum IFM 12283. The structures of compounds 1-4 were elucidated via spectral studies, including various NMR analyses. The absolute configurations of compounds 1-4 were deduced by comparing their circular dichroism (CD) spectra with those of mycobactin H (5) and ferric-mycobactin H (6). These compounds exhibited cytotoxicity against the MH7A rheumatoid fibroblast-like synovial cell line.

Glycyrrhetinic acid (GA) and glycyrrhizin (GL), active ingredients derived from Glycyrrhiza, Glycyrrhizae Radix (The Japanese Pharmacopia), exhibit various pharmacological effects, such as anti-inflammatory and anti-allergic activities, and a side effect of licorice-induced pseudoaldosteronism. GA is also produced as a metabolite of GL in gastrointestinal bacterial flora when Glycyrrhiza-containing Kampo medicines are orally administered. The present study aimed to confirm that a galacturonic-glycyrrhizin (gala-GL), an analog of GL contained in Glycyrrhiza, contributes to gastrointestinal GA production as well as GL. Gala-GL was hydrolyzed to GA by the intestinal flora, although the hydrolysis rate was slower than that of GL. This is the first report to reveal hydrolyzation of gala-GL into GA in the intestinal flora. The gala-GL content in the 16 Kampo extracts containing 1.0-4.0 g/daily dose of Glycyrrhiza and 8 commercially available Shakuyakukanzoto (SKT) products containing 2.0-4.8 g/daily dose of Glycyrrhiza were 2.2-9.5 and 2.9-7.2 mg/daily dose, respectively. The gala-GL contents corresponded to 7.3-10.9% and 8.0-9.4% of the total GL contents (sum of GL and gala-GL) for the Kampo extracts and SKT products, respectively. These results suggest that gala-GL also can be as sources of gastrointestinal GA, although the contents in Glycyrrhiza-containing Kampo medicines and the hydrolytic rate of conversion to GA in intestinal bacterial flora were much smaller than those of GL.

Despite the rising prevalence of food allergies (FAs) in recent decades, existing therapeutic drugs remain inadequate. Therefore, the development of novel therapeutic strategies for FAs is urgently needed. Baicalein, a flavonoid from Scutellariae baicalensis, has been reported to ameliorate ovalbumin (OVA)-induced FA responses by inducing regulatory T cells (Tregs) in a mouse model. Here, we examined the effects of five traditional Japanese herbal medicines (Kampo medicines) containing Scutellariae radix on Treg induction and FA responses. All five Kampo medicines significantly enhanced the transcriptional activity of Foxp3, a master regulator of Tregs, in a recombinant human Jurkat cell line transfected with a Foxp3-luciferase reporter. Among them, Ogonto exerted the strongest effect. In addition, Ogonto significantly increased Foxp3 gene expression in Jurkat T cells and upregulated the expression of Ten-eleven translocation 2 (TET2) and TET3, demethylating enzymes that contribute to the stable expression of Foxp3. In our HPLC analysis, the Ogonto preparation used in this study was found to contain baicalin, the glycosylated form of baicalein. We next used an OVA-induced FA mouse model to evaluate the effects of Ogonto administration on allergic symptoms and the proportion of Tregs in the mesenteric lymph nodes (mLNs). Ogonto ameliorated OVA-induced diarrhea and rectal hypothermia and reduced OVA-specific immunoglobulin E levels. Furthermore, Ogonto increased the proportion of CD4⁺Foxp3⁺ Tregs in the mLNs of FA mice. These results suggest that Ogonto suppresses the development of FA by increasing Tregs.