ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2023
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IF 6.8
Wei-yu Guo,Ding-yan Lu,Zhi-zhong Guan,Lin Zheng,Shuai-shuai Chen,Ting Liu
To investigate the impact of the ethanoic fractions of Periploca forrestii Schltr. (P. forrestii) in ameliorating the liver injury caused by fluoride ingestion and to explore the potential mechanisms. Initially, an in vitro fluorosis cell model was constructed using the human normal liver cell line (L-02) induced by fluoride. Cell viability was assessed using the CCK-8 assay kit. The lactate dehydrogenase (LDH) assay kit was utilized to measure LDH content in the cell supernatant, while the malonic dialdehyde (MDA) assay kit was employed to determine MDA levels within the cells. Subsequently, a fluorosis rat model was established, and LDH content in the cell supernatant was measured using the LDH assay kit. Various parameters, including MDA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and reactive oxygen species (ROS) content within the cells, were detected using appropriate assay kits. Additionally, cell apoptosis rate was determined using the Annexin V-FITC/PI cell apoptosis assay kit. The protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase-3, Cleaved Caspase-3, Caspase-9, and Cleaved Caspase-9 were analyzed through Western blotting. Compared to the model group, the ethanolic fraction D of P.forrestii (Fr.D) increased cell viability ( P < 0.01) and decreased LDH and MDA levels ( P < 0.01). In the high-dose Fr.D treatment group of fluoride-poisoned rats, serum ALT, AST, LDH and MDA levels significantly decreased ( P < 0.01). Results from rat primary cells exhibited that the Fr.D administration group exhibited significantly higher cell survival rates than the fluoride group ( P < 0.01). Similarly, primary rat cells treated with Fr.D showed enhanced cell viability ( P < 0.05) and reduced apoptosis rate, LDH, MDA, SOD, GSH-Px, CAT, and ROS levels ( P < 0.05) compared to the model group. Western blot analysis indicated that the Fr.D treatment group elevated the Bcl-2/Bax protein expression ratio and reduced Caspase-3 and Caspase-9 activation levels ( P < 0.01) compared to the model group. The results suggest that components within the Fr.D from Periploca forrestii may alleviate fluoride-induced liver injury by potentially counteracting oxidative stress and cell apoptosis.
研究领域:
药理学
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毒理学
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细胞生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 18
·13695
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IF 5.6
Jia Sun,Zuying Zhou,Yang Zhou,Ting Liu,Yueting Li,Zipeng Gong,Yang Jin,Lin Zheng,Yong Huang
The purpose of this study was to elucidate the metabolic action patterns ofP. forrestiiagainst rheumatoid arthritis (RA) using metabolomics, and to obtain its potential effective substances for treating RA. First, the therapeutic effects ofP. forrestiiagainst RA were confirmed; second, the chemical composition ofP. forrestiiwas analyzed, and 17 prototypes were absorbed into blood; subsequently, plasma metabolomics studies using UPLC-Triple-TOF-MS/MS and GC-MS were performed to disclose the metabolomics alterations in groups, which revealed 38 altered metabolites after drug intervention. These metabolites were all associated with the arthritis pathophysiology process (−log(p) > 1.6). Among them, sorted by variable important in projection (VIP), the metabolites affected (VIP ≥ 1.72) belonged to lipid metabolites. Finally, Pearson’s analysis between endogenous metabolites and exogenous compounds was conducted to obtain potential pharmacological substances for theP. forrestiitreatment of RA, which showed a high correlation between five blood-absorbed components andP. forrestii-regulated metabolites. This information provides a basis for the selection of metabolic action modes forP. forrestiiclinical application dosage, and potential pharmacological substances that exerted anti-RA effects ofP. forrestiiwere discovered. The study provided an experimental basis for further research on pharmacoequivalence, molecular mechanism validation, and even the development of new dosage forms in the future.Keywords:Periploca forrestiiSchltr.;rheumatoid arthritis;network pharmacology;metabolomics;pharmacodynamic substances
研究领域:
药理学
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代谢组学
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风湿病学
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中医药
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DOI
PubMed
高影响因子
Journal of Inflammation Research
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2025
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IF 4.1
Shuaishuai Chen,Weina Xue,Zhongxiu Wu,Dingyan Lu,Lin Zheng,Meng Zhou,Yongjun Li,Yonglin Wang,Ting Liu
Objective: The total flavonoids of Periploca forrestii Schltr. (TFPF) exhibit notable anti-rheumatoid arthritis (RA) properties, highlighted by their inhibitory action on TNF-α. This study investigates the specific compounds of TFPF responsible for TNF-α inhibition and delineates their mechanism of action.Methods: L929 cells and luciferase-based assays were used to assess anti-TNF-α activity. Additionally, MH7A cells and Wistar rats were employed to establish in vitro and in vivo models of RA. Chemical chromatography, thermal proteome profiling (TPP), molecular docking, surface plasmon resonance (SPR), cellular thermal shift assays (CETSA), drug affinity responsive target stability tests (DARTS), and transcriptomic analysis were used to study the potent molecules of TFPF and their protein targets and pathways. H&E staining, immunofluorescence staining, ELISA, and Western blot were employed for pharmacodynamic and mechanism studies of these potent molecules.Results: TFPF mitigated cellular injury in L929 cells and inhibited luciferase expression, both of which were induced by TNF-α. Among the eight compounds identified, quercetin exhibited the most potent anti-TNF-α activity. Quercetin improved cellular injury and reduced the cell apoptosis rate in L929 cells treated with TNF-α. TPP revealed the interaction between quercetin and TNF-α, which was verified by molecular docking, SPR, CETSA, and DARTS assays. Transcriptomic analysis highlighted the TNF signaling pathway, suggesting that quercetin may target TNF-α to inhibit the activation of the NF-κB signaling pathway. Quercetin inhibited luciferase expression, suppressed the phosphorylation of IκBα and p65, blocked p65 nuclear translocation, and reduced the mRNA expression of COX-2, INOS, IL-6, and IL-1β. Moreover, quercetin decreased inflammation and joint damage in RA.Conclusion: Quercetin, a compound of TFPF, interacts with and inhibits the activity of TNF-α, thereby suppressing the TNF-α/NF-κB signaling pathway and alleviating the symptoms of RA. These findings position quercetin as a promising TNF-α inhibitor for the treatment of RA.
研究领域:
药理学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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