Vincamine exerts hepato-protective activity during colon ligation puncture-induced sepsis by modulating oxidative stress, apoptosis, and TNFα/Nrf-2/Keap-1 signaling pathways

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 23, 2024

Abstract Sepsis is a pathological and biochemical disorder induced by numerous infections, leading to critical illness high mortality rate worldwide. Vincamine an indole alkaloid compound obtained from the leaves of Vinca minor. The present study aims investigate hepato-protective activity vincamine during colon ligation puncture (CLP)-induced sepsis at molecular level. was using CLP model. Liver function enzymes such as ALT AST were analyzed. hepatic antioxidant status (SOD GSH), lipid peroxidation (MDA), pro-inflammatory cytokines (TNFα, IL-6, IL-1β), bax, bcl2, cleaved caspase 3 proteins estimated. Nrf-2 Keap-1 protein expression evaluated western blotting. Histopathological investigation liver tissues also performed. CLP-induced led injury through elevation enzymes. Oxidative stress initiated via suppression GSH content SOD MDA. inflammatory condition activated upregulation TNFα, IL-1β, downregulation proteins. apoptosis activation bax inhibition bcl2 expression. However, significantly improved histological abnormalities decreased (ALT AST). It ameliorated oxidative stress, evidenced reducing MDA increasing content. Moreover, reduced increased Additionally, it upregulated downregulated exhibited potential cross-connection antioxidant, anti-inflammatory, anti-apoptotic activities modulating TNFα/IL-6/IL-1β/Nrf-2/Keap-1 regulating bax/bcl2/cleaved signaling pathways.

Language: Английский

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Nicorandil mitigates arsenic trioxide‐induced lung injury via modulating vital signalling pathways SIRT1/PGC‐1α/TFAM, JAK1/STAT3, and miRNA‐132 expression

British Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 181(17), P. 3215 - 3231

Published: May 13, 2024

Nicorandil, a selective opener of potassium channels, used to treat angina, has drawn attention for its potential in mitigating lung injury, positioning it as promising therapeutic approach drug-induced toxicity. This study aimed explore the protective role nicorandil arsenic trioxide (ATO)-induced injury and elucidate underlying mechanistic pathways.

Language: Английский

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Vincamine alleviates intrahepatic cholestasis in rats through modulation of NF-kB/PDGF/klf6/PPARγ and PI3K/Akt pathways

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2024, Volume and Issue: 397(10), P. 7981 - 7994

Published: May 18, 2024

Abstract The defect in the hepatobiliary transport system results an impairment of bile flow, leading to accumulation toxic compounds with subsequent liver disorders. Vincamine, a plant indole alkaloid that is utilized as dietary supplement, has been known for its promising pharmacological activities. For first time, present study was planned estimate, at molecular level, potentiality vincamine against alfa-naphthyl isothiocyanate (ANIT)-induced hepatic cholestasis. Liver function tests were analyzed. Hepatic activity SOD and levels GSH MDA assessed. contents bax, bcl2, NF-kB, PPARγ, catalase, heme-oxygenase-1, NTCP, BSEP evaluated using ELISA. mRNA IL-1β, IL-6, TNFα, PDGF, klf6, PPARγ , P53 examined qRT-PCR. PI3K, Akt cleaved caspase-3 proteins assessed western blotting. Histopathological analyses performed hematoxylin & eosin staining. ANIT-induced cholestasis elevated tests, including AST, ALT, GGT, ALP, total bilirubin. ANIT reduced protein expression NTCP transporters. It induced inflammatory genes, IL-1β PDGF NF-kB genetic level suppressed anti-inflammatory klf6 . Also, antioxidant markers during induction such GSH, SOD, heme-oxygenase-1 PI3K/Akt pathway, while elevated. Furthermore, gene, bax caspase 3 activated, bcl2 inhibited. histopathological analysis showed degeneration hepatocytes cellular infiltrates. However, treatment modulated all these markers. improved tests. inhibited activated pathway. Additionally, it proteins. More interestingly, better outcomes on alterations by ANIT. Vincamine alleviated dysfunction intrahepatic through efficacies modulation NF-kB/PDGF/klf6/PPARγ pathways.

Language: Английский

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Insights into the Role of Glutathione Peroxidase 3 in Non-Neoplastic Diseases

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 689 - 689

Published: June 13, 2024

Reactive oxygen species (ROSs) are byproducts of normal cellular metabolism and play pivotal roles in various physiological processes. Disruptions the balance between ROS levels body’s antioxidant defenses can lead to development numerous diseases. Glutathione peroxidase 3 (GPX3), a key component system, is an oxidoreductase enzyme. GPX3 mitigates oxidative damage by catalyzing conversion hydrogen peroxide into water. Beyond its function, vital regulating metabolism, modulating cell growth, inducing apoptosis facilitating signal transduction. It also serves as significant tumor suppressor cancers. Recent studies have revealed aberrant expression several non-neoplastic diseases, associating it with multiple pathological This review synthesizes current understanding regulation, highlighting extensive noncancerous Additionally, this paper evaluates potential diagnostic biomarker explores emerging therapeutic strategies targeting enzyme, offering avenues for future clinical treatment conditions.

Language: Английский

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Phytochemicals in Cancer Therapy: Modulating Cell Cycle, Angiogenesis, and Epithelial-Mesenchymal Transition

Revista Brasileira de Farmacognosia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

Language: Английский

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Alkaloids from the genus Vinca L. (Apocynaceae): a comprehensive biological and structural review

Phytochemistry Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: March 29, 2025

Language: Английский

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Elucidating the causal associations and mechanisms between circulating immune cells and idiopathic pulmonary fibrosis: new insights from Mendelian randomization and transcriptomics

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 17, 2025

Growing evidence indicates an association between circulating immune cell phenotypes and idiopathic pulmonary fibrosis (IPF). Although studies have attempted to elucidate the causal relationship two, further clarification of specific mechanisms linkages is warranted. We aimed conduct a two-sample Mendelian randomization (MR) analysis with transcriptomics data cells IPF explore potential biomarkers. first explored bidirectional using MR analysis. Genome-wide for phenotype were obtained from publicly available databases. A standardized instrumental variable screening process was used select single nucleotide polymorphisms (SNPs) inclusion in MR. Five methods represented by IVW assess effects. Subsequently, SNP-nearest genes combined subjected multiple bioinformatics analyses such as TIMER, WGCNA, functional enrichment analysis, protein-protein interaction ROC identify Finally, single-cell RNA sequencing (scRNA-seq) validate our findings The study identified 27 causally associated IPF, which 20 decreased risk developing 7 increased risk. CTSB (AUC=0.98), IL10 (AUC=0.83), AGER (AUC=0.87) promising biomarkers IPF. Single showed differences CD14+ CD16+ monocytes, monocytes Granulocyte-monocyte progenito group healthy control group. three hub highly expressed subsets patients. It underscores feasibility Our demonstrates associations through genetic identifies CTSB, IL10, These provide guidance future clinical basic research.

Language: Английский

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Idiopathic pulmonary fibrosis microenvironment: Novel mechanisms and research directions

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 155, P. 114653 - 114653

Published: April 14, 2025

Language: Английский

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Structural Modification and Optimisation of Hyperoside Oriented to Inhibit TGF-β-Induced EMT Activity in Alveolar Epithelial Cells

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(5), P. 584 - 584

Published: May 2, 2024

Pulmonary fibrosis (PF) is a disease characterised by diffuse nonspecific alveolar inflammation with interstitial fibrosis, which clinically manifests as dyspnoea and significant decline in lung function. Many studies have shown that the epithelial–mesenchymal transition (EMT) plays pivotal role pathogenesis of pulmonary fibrosis. Based on our previous findings, hypericin (Hyp) can effectively inhibit process EMT to attenuate Therefore, series hyperoside derivatives were synthesised via modifying structure hyperoside, subsequently evaluated for A549 cytotoxicity. Among these, pre-screening eight inhibits EMT. In this study, we efficacy Z6, most promising derivative, reversing TGF-β1-induced EMTs inhibiting EMT-associated migration cells. After treatment cells Z6 48 h, RT-qPCR Western blot results showed inhibited epithelial supressing morphological changes cells, up-regulating E-cadherin (p < 0.01, p 0.001), down-regulating Vimentin 0.001). This significantly reduced mobility transforming growth factor β1 (TGF-β1)-stimulated 0.001) assessed wound closure, while increasing adhesion rate conclusion, suggest derivatives, especially compound are potential lead compounds treating therefore deserve further investigation.

Language: Английский

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Pulmonary Fibrosis and Diabetes Mellitus: Two coins with the same face

Archives of Internal Medicine Research, Journal Year: 2024, Volume and Issue: 07(01)

Published: Jan. 1, 2024

Idiopathic pulmonary fibrosis (IPF) constitutes a long-term disease with complex pathophysiology composed of multiple molecular actors that lead to the deposition extracellular matrix, loss function and ultimately patient's death. Despite approval pirfenidone nintedanib for treatment disease, lung transplant is only solution fully recover respiratory capacity gain quality life. One risk factors development IPF pre-existing condition diabetes mellitus. Both, mellitus, share similar pathological damage mechanisms, including inflammation, endoplasmic reticulum stress, mitochondrial failure, oxidative senescence signaling from glycated proteins through receptors. In this critical review article, we provide information about interrelationship, examining mediators play an essential role in both diseases identify targets interest potential drugs. We findings clinical trials progression how novel molecules may be used stop process. The results highlight importance early detection addressing therapeutic simultaneously achieve better efficacy potentially reverse fibrosis.

Language: Английский

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