RESUMEN
Hepatic diseases pose a significant threat to community health, impacting the quality of life and longevity of millions worldwide. Despite revolutionary advancements in treatment, liver diseases remain a pressing issue, necessitating the development of more effective therapeutic approaches. Here, we conducted a comprehensive multi-omics analysis to investigate the underlying mechanism of Swertiamarin in alleviating hepatic injuries induced by CCl4 in mice. We divided 100 Kunming mice into five groups: RC (control), RM (CCl4), RD (15â¯mg/Kg Swertiamarin), RZ (30â¯mg/Kg Swertiamarin), and RG (60â¯mg/Kg Swertiamarin). Animals in groups RD, RZ, and RG received daily Swertiamarin via gavage, while those in groups RM, RD, RZ, and RG were treated with CCl4 solution intraperitoneally every four days, nine times in total. Our findings revealed that mice in the RM group exhibited slightly lower average weights compared to other groups, along with significantly higher liver weight (p<0.0001) and liver index (p<0.0001). Pathological analysis indicated liver damage characterized by cell degeneration, inflammatory cell infiltration, and hepatic fibrosis in the CCl4-induced group. In contrast, Swertiamarin supplementation mitigated these effects, reducing denatured cells, inflammatory cells, and collagenous fibers in the liver. Serum analysis showed elevated levels of TNF-α (p<0.001), IL-6 (p<0.05), ALT (p<0.001), AST (p<0.0001), MDA (p<0.001), and Hyp (p<0.001) in CCl4-induced animals, along with lower levels of T-AOC (p<0.001), GSH-px (p<0.0001), SOD (p<0.001), and CAT (p<0.01). Microbiome analysis revealed significant differences among groups, with pathogenic taxa such as Arthrinium and Aureobasidium, and probiotic Saccharomyces showing notable variations. Metabolomics analysis identified numerous differentially abundant metabolites, with Swertiamarin-treated animals exhibiting distinct profiles. Our findings highlight the potential of Swertiamarin ameliorating CCl4-induced liver toxicity through modulation of antioxidant capacity, inflammatory response, gut microbiota, and metabolites. These insights may inform the development of novel therapies for liver injury.
Asunto(s)
Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas , Glucósidos Iridoides , Hígado , Pironas , Animales , Pironas/farmacología , Glucósidos Iridoides/farmacología , Ratones , Hígado/efectos de los fármacos , Hígado/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Masculino , Metabolómica , Estrés Oxidativo/efectos de los fármacos , Multiómica , Animales no ConsanguíneosRESUMEN
The liver is a well-known organ contributing to digestion, hemostasis and detoxification, while liver injury is a world-widely distributed health problem with limited treatment choices. We detected the protective effect of Abrus cantoniensis Hance (ACH) on Carbon tetrachloride-induced (CCl4) liver injury in mice. Fifty ICR (Institute of Cancer Research) animals were grouped into five groups of control (a), CCl4 (d), ACH (25 mg/kg) treated group (c), ACH (50 mg/kg) treated group (b), and ACH (100 mg/kg) treated group (e). Mice in groups d, c, b, and e were given CCl4 every four days, and treated animals received daily ACH supplementation. The results showed that the daily body weights in CCl4-induced animals were slightly lower; however, the weight of ACH-treated mice increased, particularly in the higher dose group. Treatment with CCl4 led to increased liver weight and liver indices in mice, whereas supplementation with ACH reduced both liver weights and liver indices in animals. Histo-pathological analysis indicated that CCl4 led to inflammatory cell infiltration and hepatocellular degeneration, with collagenous fibers proliferation in ICR animals. In contrast, supplementation with ACH prominently decreased inflammatory cells and degeneration of hepatocytes and inhibited collagen fiber hyperplasia. Furthermore, the levels or concentrations of AST (p < 0.0001), ALT (p < 0.0001), MDA (p < 0.0001), IL-1ß (p < 0.01), TNF-α (p < 0.01) and IL-6 (p < 0.01) were significantly higher in CCl4 induced ICR animals in group d. However, mice treated with ACH showed lower levels or concentrations of those indices in dose dependent manner. The levels of GSH-px (p < 0.0001), CAT (p < 0.0001) and SOD (p < 0.0001) were significantly reduced in CCl4 group; however, all these three enzymes exhibited significant (p < 0.05) increase in animals supplemented with ACH in dose dependent manner. The microbiome sequencing generated 1,168,327 filtered reads in the mice samples. A notable difference was observed in the composition of 6 phyla and 37 genera among the five ICR animal groups. Supplementation with ACH increased the abundance of beneficial genera of Coprococcus, Blautia and Clostridium, while concurrently decreased the presence of pathogenic genera of Mycoplasma and Helicobacter. In conclusion, we revealed that Abrus cantoniensis Hance has the potential to relieve liver damage induced by CCl4, through the reduction of inflammation, enhancement of antioxidant capacity, and regulation of intestinal microbiota.
Asunto(s)
Abrus , Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatopatías , Ratones , Animales , Ratones Endogámicos ICR , Hígado , Inflamación/inducido químicamente , Enfermedad Hepática Inducida por Sustancias y Drogas/patologíaRESUMEN
Plant-derived phytochemicals have recently drawn interest in the prevention and treatment of diabetes mellitus (DM). The seeds of Moringa oleifera Lam. are widely used in food and herbal medicine for their health-promoting properties against various diseases, including DM, but many of their effective constituents are still unknown. In this study, 6 new phenolic glycosides, moringaside B-G (1-6), together with 10 known phenolic glycosides (7-16) were isolated from M. oleifera seeds. The structures were elucidated by 1D and 2D NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data analysis. The absolute configurations of compounds 2 and 3 were determined by electronic circular dichroism (ECD) calculations. Compounds 2 and 3 especially are combined with a 1,3-dioxocyclopentane moiety at the rhamnose group, which are rarely reported in phenolic glycoside backbones. A biosynthetic pathway of 2 and 3 was assumed. Moreover, all the isolated compounds were evaluated for their inhibitory activities against α-glucosidase. Compounds 4 and 16 exhibited marked activities with IC50 values of 382.8 ± 1.42 and 301.4 ± 6.22 µM, and the acarbose was the positive control with an IC50 value of 324.1 ± 4.99 µM. Compound 16 revealed better activity than acarbose.
Asunto(s)
Glicósidos , Moringa oleifera , Glicósidos/farmacología , alfa-Glucosidasas , Acarbosa , Semillas , Fenoles/farmacologíaRESUMEN
Four new monomeric sorbicillinoids, trichillinoids A - D (1-4), along with two known dimeric sorbicillinoids (5 and 6), and five known monomeric sorbicillinoids (7-11), were obtained from the marine-fish-derived fungus Trichoderma sp. G13. They were structurally characterized on the basis of comprehensive spectroscopic investigations (NMR, HRESIMS, and ECD). Compounds 1-4 displayed moderate anti-inflammatory activities, according to inhibiting the production of NO in RAW264.7 cells activated with IC50 values ranging from 14 to 20 µM.