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1.
Future Med Chem ; : 1-12, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39157857

RESUMEN

Aim: Investigating a novel compound, DMPNP, for treating colitis in mice, a key issue in inflammatory bowel diseases (IBD). Methods: Mice with induced colitis received DMPNP (50, 100, 150 mg/kg) or sulfasalazine (SUL), evaluated via tissue assessment, Disease Activity Index (DAI), myeloperoxidase (MPO), nitric oxide (NO) levels and cytokine analysis. Results: DMPNP significantly reduced colitis symptoms, inflammation and oxidative stress at higher doses, with marked improvements in DAI, MPO, NO and cytokines, comparable to SUL results. Conclusion: DMPNP shows potent anti-inflammatory and immunomodulatory properties, indicating potential as an IBD therapeutic. Further clinical trials are suggested to validate these outcomes.


This article focuses on a study testing a new compound, DMPNP, for treating colitis, a challenging aspect of inflammatory bowel disease (IBD). The researchers aimed to determine if DMPNP could alleviate colitis symptoms and serve as an effective treatment option.The study involved mice with induced colitis symptoms, treated with different doses of DMPNP (50, 100, 150 mg/kg). For comparison, another group received sulfasalazine (SUL), a standard IBD medication. The evaluation focused on colon tissue health, disease severity through the Disease Activity Index (DAI) and levels of myeloperoxidase (MPO) and nitric oxide (NO), which are markers of inflammation and oxidative stress. Additionally, the effect of DMPNP on immune cell production and inflammatory gene expression was assessed.The results were encouraging. Mice treated with DMPNP showed significant improvements, particularly at higher doses. Symptoms like inflammation, tissue damage and ulceration in the colon reduced noticeably. The DAI scores, indicative of colitis severity, were substantially lower in the DMPNP group, suggesting reduced disease intensity. Also, decreases in MPO and NO levels indicated less oxidative stress and inflammation. The compound also mirrored sulfasalazine's effects in reducing inflammatory cell and gene production.These findings are crucial as they indicate DMPNP's potential as a new treatment for colitis and possibly other IBD forms. Its effectiveness in reducing inflammation and regulating the immune response, akin to existing treatments but possibly with different advantages, highlights its promise. The study paves the way for more in-depth research and eventual human trials to confirm DMPNP's safety and efficacy in IBD treatment.

2.
Arch Physiol Biochem ; : 1-11, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38445617

RESUMEN

CONTEXT: Type 2 Diabetes Mellitus (T2D) is a significant health concern worldwide, necessitating novel therapeutic approaches beyond conventional treatments. OBJECTIVE: To assess isorhamnetin's potential in improving insulin sensitivity and mitigating T2D characteristics through oxidative and glycative stress modulation. MATERIALS AND METHODS: T2D was induced in mice with a high-fat diet and streptozotocin injections. Isorhamnetin was administered at 10 mg/kg for 12 weeks. HepG2 cells were used to examine in vitro effects on stress markers and insulin sensitivity. Molecular effects on the PGK1 and AKT signalling pathway were also analyzed. RESULTS: The administration of isorhamnetin significantly impacted both in vivo and in vitro models. In HepG2 cells, oxidative and glycative stresses were markedly reduced, indicating a direct effect of isorhamnetin on cellular stress pathways, which are implicated in the deterioration of insulin sensitivity. Specifically, treated cells showed a notable decrease in markers of oxidative stress, such as malondialdehyde, and advanced glycation end products, highlighting isorhamnetin's antioxidant and antiglycative properties. In vivo, isorhamnetin-treated mice exhibited substantially lower fasting glucose levels compared to untreated T2D mice, suggesting a strong hypoglycemic effect. Moreover, these mice showed improved insulin responsiveness, evidenced by enhanced glucose tolerance and insulin tolerance tests. The molecular investigation revealed that isorhamnetin activated PGK1, leading to the activation of the AKT signalling pathway, crucial for promoting glucose uptake and reducing insulin resistance. This molecular action underscores the potential mechanism through which isorhamnetin exerts its beneficial effects in T2D management. DISCUSSION: The study underscores isorhamnetin's multifaceted role in T2D management, emphasizing its impact on oxidative and glycative stress reduction and molecular pathways critical for insulin sensitivity. CONCLUSION: Isorhamnetin presents a promising avenue for T2D treatment, offering a novel approach to enhancing insulin sensitivity and managing glucose levels through the modulation of key molecular pathways. Further research is needed to translate these findings into clinical practice.

3.
Inflammopharmacology ; 32(3): 2035-2048, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38520575

RESUMEN

The aim of this investigation was to explore the protective impacts and mechanisms of Anastatica hierochuntica essential oil (EOAH) against dextran sulfate sodium (DSS)-induced experimental colitis in mice. EOAH demonstrated a reduction in DSS-induced body weight decline, disease activity index (DAI), colon length reduction, colonic tissue damage, and myeloperoxidase (MPO) activity. The essential oil significantly mitigated the production of pro-inflammatory agents including TNF-α, IL-1ß, and IL-12. Further analysis revealed that EOAH's anti-inflammatory effects involved the regulation of NF-κB and PPARγ pathways, as well as the inhibition of NLRP3 activation in colitis mice. Notably, EOAH treatment elevated the levels of beneficial commensal bacteria such as Lactobacillus and Bifidobacteria, while reducing Escherichia coli levels in the mice's feces. In addition, EOAH restored the expression of occludin and ZO-1 proteins in colonic tissues affected by ulcerative colitis (UC). These findings indicate that supplementing with EOAH might offer a novel therapeutic approach for UC prevention.


Asunto(s)
Antiinflamatorios , Colitis , Sulfato de Dextran , Aceites Volátiles , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/administración & dosificación , Ratones , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/metabolismo , Antiinflamatorios/farmacología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/metabolismo , FN-kappa B/metabolismo , Masculino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL
5.
Heliyon ; 8(8): e10400, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36090223

RESUMEN

Background: Ceratonia siliqua L. (Leguminosae) has neuroprotective, mutagenic, hypotensive, anti-bacterial, hypoglycaemic, and anti-inflammatory effects through extracts from its leaves. Therefore, the aim of this study is to assess the anti-nociceptive activity of ethanol extracts of Ceratonia siliqua leaves. Methods: Ethanol extract of Ceratonia siliqua leaves were studied using well-established animal models of inflammation and pain. A hot plate latency assay (55 °C) was used to assess the analgesic effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extracts in addition to paw licking time in early and late phase using a formalin-induced paw licking assay test. Paw oedema induction using carrageenan and cotton pellet granuloma assays were used to assess the anti-inflammatory effect of 10, 31.6, 100, and 316 mg/kg doses of ethanol extract. Results: The ethanol extract of Ceratonia siliqua leaves reduces paw licking time in early and late phase after formalin injection. The same effect was also observed when the hotplate test was performed. Ethanol extract of Ceratonia siliqua leaves caused dose dependent inhibition in paw oedema after the injection of carrageenan and cotton pellet granuloma in mice. These effects were not antagonized when opioid receptors were blocked by naloxone (5 mg/kg). The preliminary phytochemical analysis of the ethanol extract of Ceratonia siliqua leaves showed the presence of tannins, alkaloids, flavonoids and terpenoids. Conclusion: The present data indicate that ethanol extract of Ceratonia siliqua leaves might possess anti-inflammatory and anti-nociception properties and should be considered for further therapeutic research.

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