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1.
Drug Des Devel Ther ; 16: 4343-4364, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36583115

RESUMEN

Purpose: Shaoyao decoction (SYD) is a traditional Chinese medicine used to treat ulcerative colitis (UC). The exact mechanism of action of SYD in UC treatment is still unclear. Here, we examined the therapeutic effects of SYD in mice with dextran sulfate sodium (DSS)-induced colitis and explored the underlying mechanism. Methods: The experimental group was divided into normal control, UC, and SYD treatment groups. The UC model of C57BL/6 mice was induced using 3% (w/v) DSS for 7 days. SYD was orally administered for 7 days. The proximal and distal colonic metabolic profiles were detected using quadrupole-time-of-flight mass spectrometry-based untargeted metabolomics. Results: SYD significantly increased weight, reduced disease activity index scores, and ameliorated colon length shortening and pathological damage in mice. In the distal colon, SYD increased the abundance of phosphatidic acid and lysophosphatidylethanolamine and decreased the abundance of lactosylceramide, erythrodiol 3-palmitate, and lysophosphatidylcholine. In the proximal colon, SYD increased the abundance of palmitic acid, cyclonormammein, monoacylglyceride, 13S-hydroxyoctadecadienoic acid, and ceanothine C and decreased the abundance of tetracosahexaenoic acid, phosphatidylserine, and diglyceride. Conclusion: Our findings revealed that SYD could alleviate UC by regulating metabolic dysfunction, which provides a reference for further studies on SYD.


Asunto(s)
Colitis Ulcerosa , Colitis , Animales , Ratones , Sulfato de Dextran/efectos adversos , Sulfato de Dextran/metabolismo , Ratones Endogámicos C57BL , Colitis/tratamiento farmacológico , Colon , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Metabolómica , Modelos Animales de Enfermedad
2.
Drug Des Devel Ther ; 16: 3739-3776, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36324421

RESUMEN

Background: Traditional Chinese medicine (TCM) has the advantage of multi-component and multi-target, which becomes a hot spot in the treatment of numerous diseases. Shaoyao decoction (SYD) is a TCM prescription, which is mainly used to treat damp-heat dysentery clinically, with small side effects and low cost. However, its mechanism remains elusive. The purpose of this study is to explore the mechanism of SYD in the treatment of mice with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) through metabolomics and network pharmacology, and verify through molecular docking and immunohistochemistry, so as to provide a scientific basis for the role of SYD in the treatment of UC. Materials and Methods: Firstly, DSS-induced UC models were established and then untargeted metabolomics analysis of feces, livers, serum and urine was performed to determine biomarkers and metabolic pathways closely related to the role of SYD. Besides, network pharmacology was applied to screen the active components and UC-related targets, which was verified by molecular docking. Finally, metabonomics and network pharmacology were combined to draw the metabolite-pathway-target network and verified by immunohistochemistry. Results: Metabolomics results showed that a total of 61 differential metabolites were discovered in SYD-treated UC with 3 main metabolic pathways containing glycerophospholipid metabolism, sphingolipid metabolism and biosynthesis of unsaturated fatty acids, as well as 8 core targets involving STAT3, IL1B, IL6, IL2, AKT1, IL4, ICAM1 and CCND1. Molecular docking demonstrated that the first five targets had strong affinity with quercetin, wogonin, kaempferol and baicalein. Combined with metabolomics and network pharmacology, sphingolipid signaling pathway, PI3K/AKT-mTOR signaling pathway and S1P3 pathway were identified as the main pathways. Conclusion: SYD can effectively ameliorate various symptoms and alleviate intestinal mucosal damage and metabolic disorder in DSS induced UC mice. Its effect is mainly related to sphingolipid metabolism, PI3K/AKT-mTOR signaling pathway and S1P3 pathway.


Asunto(s)
Colitis Ulcerosa , Medicamentos Herbarios Chinos , Ratones , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Medicamentos Herbarios Chinos/química , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Metabolómica , Serina-Treonina Quinasas TOR , Esfingolípidos
3.
J Anim Sci ; 99(1)2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33515478

RESUMEN

This study investigated the different addition levels of iron (Fe) in growing-finishing pigs and the effect of different Fe levels on growth performance, hematological status, intestinal barrier function, and intestinal digestion. A total of 1,200 barrows and gilts ([Large White × Landrace] × Duroc) with average initial body weight (BW; 27.74 ± 0.28 kg) were housed in 40 pens of 30 pigs per pen (gilts and barrows in half), blocked by BW and gender, and fed five experimental diets (eight replicate pens per diet). The five experimental diets were control diet (basal diet with no FeSO4 supplementation), and the basal diet being supplemented with 150, 300, 450, or 600 mg/kg Fe as FeSO4 diets. The trial lasted for 100 d and was divided into the growing phase (27 to 60 kg of BW) for the first 50 d and the finishing phase (61 to 100 kg of BW) for the last 50 d. The basal diet was formulated with an Fe-free trace mineral premix and contained 203.36 mg/kg total dietary Fe in the growing phase and 216.71 mg/kg in the finishing phase based on ingredient contributions. And at the end of the experiment, eight pigs (four barrows and four gilts) were randomly selected from each treatment (selected one pig per pen) for digesta, blood, and intestinal samples collection. The results showed that the average daily feed intake (P = 0.025), average daily gain (P = 0.020), and BW (P = 0.019) increased linearly in the finishing phase of pigs fed with the diets containing Fe. On the other hand, supplementation with different Fe levels in the diet significantly increased serum iron and transferrin saturation concentrations (P < 0.05), goblet cell numbers of duodenal villous (P < 0.001), and MUC4 mRNA expression (P < 0.05). The apparent ileal digestibility (AID) of amino acids (AA) for pigs in the 450 and 600 mg/kg Fe groups was greater (P < 0.05) than for pigs in the control group. In conclusion, dietary supplementation with 450 to 600 mg/kg Fe improved the growth performance of pigs by changing hematological status and by enhancing intestinal goblet cell differentiation and AID of AA.


Asunto(s)
Alimentación Animal , Hierro de la Dieta , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Peso Corporal , Dieta/veterinaria , Suplementos Dietéticos , Femenino , Porcinos
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