INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Ye Wang,Shao-jie Chen,Ting Ma,Qiu Long,Lan Chen,Ke-xin Xu,Yu Cao
Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.
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高影响因子
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
·
2024
·
IF 4.8
Yiming Ni,Xinghua Chen,Yiqun Jia,Long Chen,Mingmei Zhou
Currently, the hepatoprotective activity of taxifolin, a flavonoid isolated from Pseudotsuga taxifolia , has been reported in many animal models. However, whether the protective effect of taxifolin on the liver is related to its effect on lipidomics is unclear. Based on the significant therapeutic effect of taxifolin on CCl 4 induced subacute hepatic injury, we observed the intervention of taxifolin by lipidomics. The results demonstrate that taxifolin can effectively reverse the damage caused by CCl 4 , which including hepatocyte vacuolization and necrosis. Lipomic profiling based on liquid chromatography-mass spectrometry showed that taxifolin was able to restore lipidomic changes caused by CCl 4 , including the levels of lysophosphatidylserine (LPS), phosphatidylcholine (PC), coenzyme (Co), phosphatidylglyceride (PG), phosphatidylserine (PS), dimethylphosphatidylethanolamine (dMePE), ceramide (Cer), sphingosine (So), triglycerides (TG), and monogalactosyl diacylglycerol (MGDG) in the rat liver, and phosphatidylcarbinol (PMe) and phosphatidylethanolamine (PE), plant sphingosine (phSM), glucose ceramide (CerG1), TG, and diglycerides (DG) in serum. Spearman's correlation analysis showed that CerG1, phSM, PE, and PMe in serum, and Cer, dMePE, PG, PS, So, TG, and MGDG in liver were positively correlated with serum levels of aspartate transaminase, alanine transaminase, and liver index; while TG, DG in serum, and Co, LPS, PC in liver were negatively correlated with the parameters. In total, 43 and 34 lipid molecules were altered by taxifolin treatment in the liver and serum, respectively, mainly including glycerophosphoglycerols, glycerophosphocholines, glycerophosphoethanolamines, and linoleic acids and derivatives. Our findings help to provide novel insights into the mechanism of the hepatoprotective effect of taxifolin from a lipidomics approach.
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高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
·
IF 7.419
Qiteng Ding,Kecheng Chen,Xinglong Liu,Chuanbo Ding,Yingchun Zhao,Shuwen Sun,Yiwen Zhang,Jinping Zhang,Shuang Liu,Wencong Liu
Purpose Taxifolin (TAX) is a flavanol compound with hepatoprotective effect, but its application is severely limited by its poor water solubility and low oral bioavailability. Therefore, it is important to urgently find a method to improve the oral bioavailability of TAX. Methods In this study, hydroxypropyl methylcellulose acetate succinate modified taxifolin liposomes (HPMCAS-TAX-Lips) were prepared by a thin-film dispersion method, and a series of physicochemical properties of the liposomes were studied. The cumulative in vitro release rates of free TAX, taxifolin liposomes (TAX-Lips), and HPMCAS-TAX-Lips in the simulated gastrointestinal fluid were measured by in vitro release experiments, and the effect of HPMCAS-TAX-Lips on the human hepatoellular carcinomas (HepG2) cells was detected by MTT assay. Finally, the hepatoprotective mechanism of HPMCAS-TAX-Lips was explored through in vivo experiments. Results The results showed that the particle size of HPMCAS-TAX-Lips was 100.44 ± 2.85 nm, the zeta potential was − 51.13 ± 0.57 mV, the PDI was 0.170 ± 0.088, and the EE was 87.9 ± 3.73%. The in vitro release results showed that the cumulative release rates of TAX-Lips and HPMCAS-TAX-Lips in simulated gastric fluid for 24 h were 92.60 ± 5.31% and 66.91 ± 1.20%, respectively. The cumulative release rates in simulated intestinal fluid for 24 h were 72.61 ± 4.38% and 53.94 ± 3.2%, respectively. The results of cytotoxicity experiments proved that HPMCAS-TAX-Lips had a significant inhibitory effect on HepG2 cells. In vivo experiments further showed that HPMCAS-TAX-Lips significantly improved the survival rate of lipopolysaccharide (LPS)/ D -galactosamine ( D -GalN)-induced acute liver injury mice and exerted hepatoprotective effects by regulating the expression of autophagy proteins and inhibiting the activation of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathway. Conclusion This study proved the significant hepatoprotective effect of HMPCAS-TAX-Lips and provided a new idea for the application of TAX.
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高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2018
·Vol. 42
·期 5
·e12607
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IF 1.552
Zaizhi Liu,Mengxia Wei,Guoqiang Cui,Xinyu Yang,Huiyan Gu,Lei Yang
Double experimental designs, Plackett–Burman design coupled with Box–Behnken design, were used to optimize the simultaneous extraction process of arabinogalactan and taxifolin from Larix gmelinii by ultrasonic microwave synergistic extraction (UMSE) method. The optimal extraction conditions were determined with the extraction yields of 223.40 ± 7.82 mg/g for larch arabinogalactan and 125.02 ± 5.30 mg/g for taxifolin. Compared to conventional methods, UMSE method showed the merits of higher extraction efficiency, saving time, and energy. The molar ratio of galactose to arabinose is found to be 6:1 through the monosaccharide composition analysis of larch arabinogalactan. The obtained taxifolin structure was identified by mass spectrometry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance. Interestingly, larch arabinogalactan and taxifolin showed completely opposite influences on α-amylase, α-glycosidase, and pancreatic lipase; it was inferred that larch arabinogalactan could act as an inhibitor while taxifolin as an accelerator. Practical applications In this study, response surface methodology of Plackett–Burman design and Box–Behnken design performed well to obtain the optimal conditions and satisfactory extraction yields for the extraction of arabinogalactan and taxifolin from Larix gmelinii by ultrasonic microwave synergistic extraction method, which could be a good paradigm for the efficient isolation of bioactive substances from plant matrix in the field of separation science. Meanwhile, the results from the evaluation of the effects of two target compounds on activities of α-amylase, α-glycosidase, and pancreatic lipase in vitro revealed that larch arabinogalactan and taxifolin enjoyed the completely opposite influences on the three digestive enzymes, namely larch arabinogalactan could act as an inhibitor while taxifolin an accelerator. These results will facilitate the application of larch arabinogalactan and taxifolin in the food and pharmaceutical industries.
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高影响因子
危险品化学品经营许可证（带存储）