Discovery of a New Anti-Inflammatory Agent from Anemoside B4 Derivatives and Its Therapeutic Effect on Colitis by Targeting Pyruvate Carboxylase

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(9), С. 7385 - 7405

Опубликована: Апрель 30, 2024

Anemoside B4 (AB4), a triterpenoidal saponin from Pulsatilla chinensis, shows significant anti-inflammatory activity, and may be used for treating inflammatory bowel disease (IBD). Nevertheless, its application is limited due to high molecular weight pronounced water solubility. To discover new effective agents IBD, we synthesized 28 AB4 derivatives evaluated their cytotoxic activities in vitro. Among them, A3–6 exhibited significantly superior activity compared AB4. It showed improvement the symptoms of DSS-induced colitis mice, with notably lower oral dose Furthermore, discovered that bound pyruvate carboxylase (PC), then inhibited PC reprogramming macrophage function, alleviated colitis. These findings indicate promising therapeutic candidate colitis, potential target

Язык: Английский

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Fasting-Induced Molting Impacts the Intestinal Health by Altering the Gut Microbiota

Animals, Год журнала: 2024, Номер 14(11), С. 1640 - 1640

Опубликована: Май 31, 2024

Fasting-induced molting (FIM) is a common method used to improve the laying performance of aged hens. Nevertheless, this approach may impose various stresses on chickens, such as disruptions in intestinal flora and inflammation issues within intestines. However, impact an imbalance health during FIM process remains elusive. Therefore, injury, microbiome, metabolome were analyzed individually integrated elucidate process. The findings indicated that fasting resulted notable reduction villus height villus/crypt ratio, coupled with elevated levels permeability. During period, microbiota compositions changed. abundance Escherichia_Shigella increased, while Ruminococcaceae_UCG-013 Lactobacillus decreased. was positively correlated Citrinin Sterobilin, which lead inflammation. exhibited positive correlations Lanthionine reduced Glutathione, thereby reducing This study screened probiotics, Ruminococcaceae UCG-013 Lactobacillus, influence gut providing experimental basis for improving

Язык: Английский

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Accelerating repair of infected bone defects through post-reinforced injectable hydrogel mediated antibacterial/immunoregulatory microenvironment at bone-hydrogel interface

Carbohydrate Polymers, Год журнала: 2024, Номер 351, С. 123082 - 123082

Опубликована: Ноя. 29, 2024

Язык: Английский

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The Multifaceted Impact of Bioactive Lipids on Gut Health and Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(24), С. 13638 - 13638

Опубликована: Дек. 20, 2024

Bioactive lipids have a multifaceted role in health and disease are recognized to play an important part gut immunity conditions such as inflammatory bowel colon cancer. Advancements lipidomics, enabled by mass spectrometry chromatographic techniques, enhanced our understanding of lipid diversity functionality. lipids, including short-chain fatty acids, saturated omega-3 sphingolipids, exhibit diverse effects on inflammation immune regulation. Short-chain acids like butyrate demonstrate anti-inflammatory properties, enhancing regulatory T cell function, barrier integrity, epigenetic regulation, making them promising therapeutic targets for Conversely, promote disrupting homeostasis, triggering oxidative stress, impairing Omega-3 counteract these effects, reducing supporting balance. Sphingolipids complex roles, modulating trafficking inflammation. They can exert protective or exacerbate colitis depending their source context. Additionally, eicosanoids also prevent pathology through prostaglandin defense against damage epithelial barriers. This review underscores the importance dietary shaping highlights potential use strategies managing

Язык: Английский

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Advances in the prerequisite and consequence of STING downstream signalosomes

Medical Review, Год журнала: 2024, Номер 4(5), С. 435 - 451

Опубликована: Май 7, 2024

Abstract The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is an evolving DNA-sensing mechanism involved in innate immunity and pathogen defense that has been optimized while remaining conserved. Aside from recognizing pathogens through conserved motifs, these receptors also detect aberrant or misplaced self-molecules as possible signs perturbed homeostasis. Upon binding external self-derived DNA, a mobile secondary messenger 2′3′-cyclic (cGAMP) produced by cGAS turn activates its adapter STING the endoplasmic reticulum (ER). Resting-state activated protein finely restricted multiple degradation machineries. post-translational changes protein, along with regulatory machinery secret routes, limit onset, strength sustention signal. experiences conformational shift relocates TBK1 ER to perinuclear vesicles containing transcription factors, provoking activity IRF3/IFN-I NF-κB pathways, well initiate number cellular processes have shown alter immune landscape cancer, such autophagy, NLRP3 inflammasome, stress, cell death. signal thus serves potent activator for mobilization yet triggers immune-mediated pathology tissues. Recent advances established vital role surveillance tumorigenic process. This review provides overview disparate outcomes cancer attributed actions pleiotropic coordinated downstream signalosomes, underlying mechanisms function pathologies, providing therapeutic implications new approaches hunt next generation immunotherapy base on STING.

Язык: Английский

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Emerging roles of antimicrobial peptides in innate immunity, neuronal function, and neurodegeneration

Trends in Neurosciences, Год журнала: 2024, Номер 47(11), С. 949 - 961

Опубликована: Окт. 9, 2024

Язык: Английский

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Sesquiterpene lactones from Cichorium intybus exhibit potent anti-inflammatory and hepatoprotective effects by repression of NF-κB and enhancement of NRF2

Journal of Ethnopharmacology, Год журнала: 2025, Номер 343, С. 119439 - 119439

Опубликована: Фев. 2, 2025

Язык: Английский

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Inulin Hydrogel Loaded with Self-Assembled Nanoparticles of Curcumin and Glycyrrhizic Acid for Inflammatory Bowel Disease Treatment Via Anti-Inflammation, Antioxidation, and Microbiota Modulation

Опубликована: Янв. 1, 2025

Язык: Английский

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Cooperation of TRADD- and RIPK1-dependent cell death pathways in maintaining intestinal homeostasis

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 22, 2025

Язык: Английский

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Daily Vitamin D3 Versus Stoss Vitamin D3 for Correction of 25OHD Deficiency in Children with Inflammatory Bowel Disease, a Randomised Controlled Trial

Digestive Diseases and Sciences, Год журнала: 2025, Номер unknown

Опубликована: Фев. 28, 2025

Vitamin D deficiency is common in Paediatric Inflammatory Bowel Disease (PIBD) and has been implicated disease pathogenesis exacerbation. Current guidelines recommend oral vitamin supplementation when 25OHD levels are below 50 nmol/L. Supplementation comes two forms: either a daily supplement of low dose D3 (2000 IU) for several months or single high D3-termed 'stoss' therapy, with no consensus regarding optimum treatment. A randomised controlled trial was conducted children prior diagnosis PIBD (< nmol/L), comparing 2000 IU to stoss protocol (oral dosage 400,000 3–12 years age 800,000 > 12 years). Children were followed months, biochemistry (25OHD, calcium, magnesium, phosphate, parathyroid hormone, haemoglobin, haematocrit, platelets, albumin), stool markers (calprotectin, S100A12), anthropometrics (weight, height, body mass index) as well clinical indices (Paediatric Crohn's Activity Index, Ulcerative Colitis Index) medication use collected at 3, 6, 9 months. 74 aged 5–18 completed the study. Both significantly increased from baseline values One patient had level 263 nmol/L normal serum calcium. There difference biochemical, between groups any time point, nor there correlation calprotectin activity scores. Stoss non-inferior raising also 6 groups.

Язык: Английский

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