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, Journal Year: 2024, Volume and Issue: 67(9), P. 7385 - 7405

Published: April 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

Language: Английский

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

Animals, Journal Year: 2024, Volume and Issue: 14(11), P. 1640 - 1640

Published: May 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

Language: 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, Journal Year: 2025, Volume and Issue: 343, P. 119439 - 119439

Published: Feb. 2, 2025

Language: 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

Published: Jan. 1, 2025

Language: Английский

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

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 22, 2025

Language: 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, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

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The effect of vitamin E supplementation on serum low-density lipoprotein oxidization: A systematic review and meta-analysis of clinical trials

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177491 - 177491

Published: March 1, 2025

Language: Английский

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Regulation of intestinal health by Lactobacillus rhamnosus GG during fasting-induced molting in laying hens

Poultry Science, Journal Year: 2025, Volume and Issue: unknown, P. 105057 - 105057

Published: March 1, 2025

Language: Английский

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Synergistic Anti-Inflammatory Effects of Pomegranate Peel–Hawthorn Combinations in Ulcerative Colitis: Network Pharmacology Prediction and Experimental Validation

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(4), P. 243 - 243

Published: April 1, 2025

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by complex pathogenesis involving dysregulated immunity and gut microbiota imbalance, demanding innovative therapeutic strategies. This study investigates the synergistic potential of pomegranate peel–hawthorn combinations their active constituents (ellagic acid maslinic acid) through an integrative approach combining network pharmacology, in vitro/in vivo experiments, analysis. Network pharmacology identified 61 shared targets (p < 0.05 for pathway enrichment) revealed complementary mechanisms: peel primarily modulated AGE-RAGE/PI3K-Akt pathways, while hawthorn targeted IL-17/NF-κB signaling. Experimental validation demonstrated potent anti-inflammatory effects (combination index 1), with optimal reducing nitric oxide production 52.35% (herbal extracts, p 0.05) 74.4% (active monomers, 0.05). In DSS-induced UC mice, combinatorial therapies significantly suppressed pro-inflammatory cytokines (TNF-α: 204.78 vs. 446.52 pg/mL group, 0.05; IL-6: 33.19 64.86 pg/mL, 0.05), restored colonic SOD activity (72.31 50.10 U/mg·prot 0.01), alleviated histopathological damage, outperforming monotherapeutics. Gut analysis recovery α-diversity indices normalized Bacteroidota/Bacillota ratios. Mechanistically, MAPK/NF-κB signaling cascades, p-p38/p38 0.01 group) p-ERK1/2/ERK1/2 phosphorylation. These findings establish that formulations exert multi-modal inhibition mitigation oxidative stress, restoration microbiota, offering scientifically validated management rooted traditional medicine principles.

Language: Английский

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Anti-Inflammatory Effect of Dendrobium officinale Extract on High-Fat Diet-Induced Obesity in Rats: Involvement of Gut Microbiota, Liver Transcriptomics, and NF-κB/IκB Pathway

Antioxidants, Journal Year: 2025, Volume and Issue: 14(4), P. 432 - 432

Published: April 3, 2025

The growing prevalence of obesity is being increasingly acknowledged as a major public health issue. This mainly stems from the excessive intake dietary fats. Dendrobium officinale (DO), recognized an herb with dual roles food and medicine, renowned for its diverse health-promoting effects. Nevertheless, specifics antiobesity anti-inflammatory properties underlying mechanisms are still obscure. present study shows that treatment extract (DOE) alleviates obesity, liver steatosis, inflammation, oxidative stress in rats obese due to high-fat diet (HFD). Firstly, respect HFD rats, higher doses DOE significantly reduced TG, TC, LDL-C, blood glucose, AST ALT, along lipid droplets. Meanwhile, supplementation induced by ROS MDA increased levels GSH-Px SOD tissues. Furthermore, integrated analysis transcriptomic microbiomic data revealed modulated inflammatory responses through NF-κB/IκB pathway. regulatory mechanism was evidenced corresponding changes protein expression both NF-κB IκB. Additionally, found modulate gut microbiota composition specifically reducing relative abundance Bilophila while increasing beneficial bacterial populations, particularly genera Akkermansia Roseburia. These findings suggest may help retain homeostasis improve metabolic regulating inflammation intestine, thereby providing protection against related syndromes. Our demonstrates DOE, natural botanical extract, can effectively facilitate prevention or syndrome precision interventions.

Language: Английский

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