Monotropein mitigates methotrexate-induced liver injury by activating autophagy and inhibiting ferroptosis DOI Creative Commons

Jinman Du,

Qiong Zou, Yi Shen

et al.

Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 121, P. 106413 - 106413

Published: Aug. 18, 2024

Methotrexate (MTX) is effective for the therapy of cancer, lupus erythematosus, rheumatoid arthritis, psoriasis and other diseases. However, hepatotoxicity MTX often leads to withdrawal discontinuation drugs, then limits its clinical application. Monotropein (MON), an iridoid glycosides distributing in many edible medicinal plants, has been exhibited prevent liver kedney injury induced by chemicals related The current study aimed assess potential beneficial effects MON mitigating MTX-induced together with delineating implicated mechanisms. A model mice BRL 3A cells were developed explore hepatoprotection MON. GEO WGCNA analysis conducted predict possible mechanism on injury. results demonstrated that can decrease serum levels AST ALT, increase activities antioxidant SOD GSH, improve morphological alteration tissue, reduce accumulation lipids hepatocytes tissue treated MTX. Moreover, our also activate autophagy as assessed autophagosome formation, expression protein autophagy, inhibit ferroptosis evaluated mitochondrial integrity, Fe2+level key changes, CQ (inhibitor autophagy) RSL-3 (the activator ferroptosis) reversed injured Therefore, attenuates activating inhibiting ferroptosis. These findings provide new insights into a healthy ingredient functional food.

Language: Английский

Geographical variation in metabolite profiles and bioactivity of Thesium chinense Turcz. revealed by UPLC-Q-TOF-MS-based metabolomics DOI Creative Commons
Fang Zhang, Guanglei Zhang, Cong Wang

et al.

Frontiers in Plant Science, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

This study aims to investigate the impact of geographical origin on metabolite composition and bioactivity Thesium chinense Turcz. (TCT), a member Apiaceae family renowned for its wide range pharmacological properties, including antioxidant, antimicrobial, anti-inflammatory effects. In this study, we investigated whole plants TCT from different regions in China, aiming explore variation TCT. A non-targeted metabolomics approach was employed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Principal component analysis (PCA) partial least squares discriminant (PLS-DA) were utilized identify differentiate profiles. We bioactivity, antioxidant activity, total flavonoid content (TFC), characteristic compounds sourced regions. further metabolic differences quality characteristics various origins. PCA PLS-DA analyses indicated that samples origins could be clearly distinguished. The revealed 54 differential metabolites, predominantly flavonoids alkaloids. KEGG pathway significant variations biosynthesis pathways flavanols among samples. Anhui province exhibited highest TFC strongest activities, while Jilin showed lowest. strong correlation observed between origins, suggesting is significantly influenced by provenance. Additionally, activities validated, showing predictive relationship TFC. research highlights potential discerning subtleties plant metabolomes, contributing advancement traditional Chinese medicine integration into modern healthcare practices.

Language: Английский

Citations

0
Chemical characterization of Siraitia grosvenorii granules and their efficacy and mechanism of action on PM2.5-induced acute lung injury DOI Creative Commons
Qi Shao, Yan D. Zhao, Yaohong Shi

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 290, P. 117702 - 117702

Published: Jan. 1, 2025

Language: Английский

Citations

0
[ DOI
Haonan Xu, Fang Zhang, Yuying Huang

et al.

PubMed, Journal Year: 2025, Volume and Issue: 45(2), P. 285 - 295

Published: Feb. 20, 2025

To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify shared targets genes TCT AAD, key signaling pathways binding between active components in core protein targets. In a Kunming mouse model AAD established by intragastric administration lincomycin hydrochloride, effects daily gavage 1% carboxymethyl cellulose sodium or gel solutions at 1.5 g/kg 3 (n=10) on body weight observed. HE staining, ELISA, 16S rRNA sequencing, Western blotting examine pathologies, expression levels IL-6 TNF-α, changes gut microbiota, expressions EGFR, p-EGFR, PI3K, p-PI3K, Akt, p-Akt colon tissues mice. We identified total 66 68 including STAT3 PIK3CA. suggested that was mediated primarily through PI3K/Akt pathway. Molecular showed EGFR had highest affinity with coniferin, EGFR-coniferin complex maintained stable conformation 10 ns, whose stability also confirmed Gibbs free energy analysis. models treatment significantly improved colonic tissue morphology, decreased TNF-α IL-6, increased microbiota diversity, modulated relative abundances genera Lactobacillus Bacteroides. markedly reduced p-PI3K can alleviate mice modulating composition, regulating EGFR/PI3K/Akt pathway, reducing TNF‑α expressions.

Language: Английский

Citations

0
The integration of metabolites from Forsythia suspensa and gut microbiota ameliorates drug-induced liver injury: network pharmacology and molecular docking studies DOI Creative Commons
Yanni Wang, Xiaotian Peng, Bo Qian

et al.

Artificial Cells Nanomedicine and Biotechnology, Journal Year: 2025, Volume and Issue: 53(1), P. 105 - 121

Published: March 7, 2025

This study integrates metabolites from Forsythia suspensa (FS) and gut microbiota GM to assess combined therapeutic efficacy against drug-induced liver injury (DILI) using network pharmacology molecular docking. Metabolites of FS were retrieved the NPASS gutMGene databases, respectively. Relevant targets for DILI-related identified through public databases. The PPI KEGG pathway analysis employed identify hub key signalling pathways. Furthermore, we performed a docking assay on active verify pharmacological concept. physicochemical properties toxicity assessed in silico platforms. 19 final recognized as proteins responsible alleviation DILI by metabolites, with ESR1 emerging central target network. estrogen pathway, particularly involving ESR1, ESR2 JUN genes, was mediator effects. Four (baicalein, luteolin, lunularin 2,3-bis(3,4-dihydroxybenzyl)butyrolactone) two (pinoresinol isolariciresinol) non-toxic, promising candidates. In conclusion, may exert potent synergistic effect modulation pathway.

Language: Английский

Citations

0
Fabrication of sodium alginate/polyvinyl alcohol@ ZnNPs with SPI scaffold for evaluation of immune-stimulating and liver-protective effects in methotrexate-treated rats DOI
Rasha S. Mohamed, Engy M. Akl, Sawsan Dacrory

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143514 - 143514

Published: April 1, 2025

Language: Английский

Citations

0
Potential Hepatoprotective Effects of Chamaecyparis lawsoniana against Methotrexate-Induced Liver Injury: Integrated Phytochemical Profiling, Target Network Analysis, and Experimental Validation DOI Creative Commons

Eman Fikry,

Raha Orfali, Shaimaa S. El-Sayed

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(12), P. 2118 - 2118

Published: Dec. 14, 2023

Methotrexate (MTX) therapy encounters significant limitations due to the concern of drug-induced liver injury (DILI), which poses a challenge its usage. To mitigate deleterious effects MTX on hepatic function, researchers have explored plant sources discover potential hepatoprotective agents. This study investigated ethanolic extract derived from aerial parts Chamaecyparis lawsoniana (CLAE) against DILI, specifically focusing MTX-induced hepatotoxicity. UPLC-ESI-MS/MS was used identify 61 compounds in CLAE, with 31 bioactive determined through pharmacokinetic analysis. Network pharmacology analysis revealed 195 DILI targets for compounds, including TP53, IL6, TNF, HSP90AA1, EGFR, IL1B, BCL2, and CASP3 as top targets. In vivo experiments conducted rats acute MTX-hepatotoxicity that administering CLAE orally at 200 400 mg/kg/day ten days dose-dependently improved attenuated oxidative stress, inflammation, apoptosis, reversed disarrayed histological features induced by MTX. general, findings present provide evidence favor capabilities thereby justifying need additional preclinical clinical investigations.

Language: Английский

Citations

4
Monotropein mitigates methotrexate-induced liver injury by activating autophagy and inhibiting ferroptosis DOI Creative Commons

Jinman Du,

Qiong Zou, Yi Shen

et al.

Journal of Functional Foods, Journal Year: 2024, Volume and Issue: 121, P. 106413 - 106413

Published: Aug. 18, 2024

Methotrexate (MTX) is effective for the therapy of cancer, lupus erythematosus, rheumatoid arthritis, psoriasis and other diseases. However, hepatotoxicity MTX often leads to withdrawal discontinuation drugs, then limits its clinical application. Monotropein (MON), an iridoid glycosides distributing in many edible medicinal plants, has been exhibited prevent liver kedney injury induced by chemicals related The current study aimed assess potential beneficial effects MON mitigating MTX-induced together with delineating implicated mechanisms. A model mice BRL 3A cells were developed explore hepatoprotection MON. GEO WGCNA analysis conducted predict possible mechanism on injury. results demonstrated that can decrease serum levels AST ALT, increase activities antioxidant SOD GSH, improve morphological alteration tissue, reduce accumulation lipids hepatocytes tissue treated MTX. Moreover, our also activate autophagy as assessed autophagosome formation, expression protein autophagy, inhibit ferroptosis evaluated mitochondrial integrity, Fe2+level key changes, CQ (inhibitor autophagy) RSL-3 (the activator ferroptosis) reversed injured Therefore, attenuates activating inhibiting ferroptosis. These findings provide new insights into a healthy ingredient functional food.

Language: Английский

Citations

0