Food & Function
·
2020
·Vol. 11
·期 8
·7217-7230
·
IF 4.171
Konglong Feng,Xiaoai Zhu,Guo Liu,Qixin Kan,Tong Chen,Yunjiao Chen,Yong Cao
Citrus peel essential oil (CPEO) contains abundant volatile compounds and exhibits fragrance properties and beneficial pharmacological effects on humans. Herein, we aimed to investigate the effects of CPEO on the prevention of hypercholesterolemia and hepatic steatosis in high-fat diet-fed rats and identify its possible regulatory mechanisms in lipid metabolism by combining lipidomics with gene expression analysis. CPEO at effective supplementation levels of 0.5% and 0.75% significantly ameliorated hypercholesterolemia and hepatic steatosis, including decreased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), hepatic TC and triglyceride (TG) levels, and hepatic lipid droplet accumulation. Lipidomics analysis revealed that the total levels of fatty acid (FFA), TG and cholesteryl ester (CE) classes in the liver tissue were remarkably decreased after 0.75% CPEO supplementation some of which (3 TGs and 4 CEs) might emerge as potential lipid biomarkers in response to the effects of CPEO. Furthermore, these lipidomics findings were associated with downregulation of lipogenesis-related genes SREBP-1c, ACC and FAS and upregulation of bile acid biosynthesis-related genes LXRα, CYP7A1 and CYP27A1 in the liver. This study indicated that CPEO could effectively prevent hypercholesterolemia and hepatic steatosis, possibly because of its mediation of lipid and cholesterol homeostasis by altering liver lipid metabolites and regulating lipid metabolism-related genes.
研究领域:
营养学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Yun Leng,Tianyi Xie,Yufeng Tao,Yuting Zeng,Qing Zhu,Lei Wang
ELABELA (ELA), an endogenous peptide, exhibits antioxidant and anti-inflammatory properties in the heart and kidney. This study aimed to explore the therapeutic potential of ELA in hyperuricemia (HUA) and its underlying mechanism. Male C57BL/6 mice were used to induce HUA via oral administration of adenine and potassium oxonate for 14 days. 32 or 11 amino-acid ELA peptides (ELA32 or ELA11) were intraperitoneally injected into HUA mice. Compared with the HUA group, both ELA peptides significantly reduced serum UA levels, as well as hepatic expression and activity of XOD. ELA32 also decreased BUN, serum creatinine, AST, ALT and cholesterol levels while ELA11 diminished BUN and serum creatinine. Furthermore, both ELA peptides modulated bile acid (BA) synthesis, primarily through suppression of CYP27A1. Hepatic BA profiling revealed that HUA increased levels of taurochenodeoxycholic acid (TCDCA), whereas ELA treatment elevated levels of taurocholic acid (TCA), tauroursodeoxycholic acid (TUDCA), and tauro-β-muricholic acid (T-βMCA). ELA32 additionally promoted accumulation of cholic acid (CA) and taurodeoxycholic acid (TDCA). In human hepatocytes HepG2, both ELA peptides reduced H 2 O 2 -induced protein levels of XOD and CYP27A1, while enhanced FXR expression. CYP27A1 deficiency mimicked the effects of ELA32 on XOD and FXR expression under H 2 O 2 stimulation. Moreover, TCA, TUDCA, TCDCA, CA and TDCA reversed H 2 O 2 -mediated regulation of XOD and FXR expression. These findings suggest that both ELA32 and ELA11 alleviate HUA in mice primarily by inhibiting XOD expression through CYP27A1-regulated BA metabolism. Our study suggests that ELA has therapeutic potential for the treatment of HUA.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-22
·
IF 10.2
Zhu Li,Li Hongjiao,Li Jiyu,Zhong Yuan,Wu Shuai,Yan Meng,Ni Sheng,Zhang Kun,Wang Guixue,Qu Kai,Yang Deqin,Qin Xian,Wu Wei
A disorder of cholesterol homeostasis is one of the main initiating factors in the progression of atherosclerosis (AS). Metabolism and removal of excess cholesterol facilitates the prevention of foam cell formation. However, the failure of treatment with drugs (e.g. methotrexate, MTX) to effectively regulate progression of disease may be related to the limited drug bioavailability and rapid clearance by immune system. Thus, based on the inflammatory lesion “recruitment” properties of macrophages, MTX nanoparticles (MTX NPs) camouflaged with macrophage membranes (MM@MTX NPs) were constructed for the target to AS plaques. MM@MTX NPs exhibited a uniform hydrodynamic size around ~ 360 nm and controlled drug release properties (~ 72% at 12 h). After the macrophage membranes (MM) functionalized “homing” target delivery to AS plaques, MM@MTX NPs improved the solubility of cholesterol by the functionalized β-cyclodextrin (β-CD) component and significantly elevate cholesterol efflux by the loaded MTX mediated the increased expression levels of ABCA1, SR-B1, CYP27A1, resulting in efficiently inhibiting the formation of foam cells. Furthermore, MM@MTX NPs could significantly reduce the area of plaque, aortic plaque and cholesterol crystals deposition in ApoE−/− mice and exhibited biocompatibility. It is suggested that MM@MTX NPs were a safe and efficient therapeutic platform for AS.Graphical Abstract
研究领域:
纳米技术
·
药学
·
心血管疾病
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrition & Metabolism
·
2022
·Vol. 19
·期 1
·1-9
·
IF 4.654
Qiu Fubin,Li Rui,Gu Siyu,Zhao Yimin,Yang Linxue
Background Iron and vitamin D (VD) is essential to health. Previous studies have shown that iron homeostasis has a potential effect on VD metabolism, but the mechanism is not fully understood.ObjectivesTo explore the relationship between VD metabolism and iron metabolism, as well as the regulatory mechanism of iron on VD metabolism.Methods 40 male rats were fed adaptively for 7 days and randomly divided into control (C, n = 6 normal diet) group and model (M, n = 24 iron deficient diet) by simple randomization, the latter was used to establish iron deficiency anemia (IDA) model. After 6 weeks of feeding, the M group was randomly divided into: iron deficiency group (DFe), low iron group (LFe), medium iron group (MFe) and high iron group (HFe) by block randomization. Different doses of iron dextran (based on iron content (100 g·bw·d)): 0, 1.1, 3.3 and 9.9 mg) were given respectively. After 4 weeks, the rats were anesthetized with 8% chloral hydrate, Blood (collected from the abdominal aorta), liver and kidney tissues were collected. The serum and tissues were separately packed and frozen at -80℃ for testing.Results The results showed that the levels of hemoglobin (Hb), red blood cell (RBC), serum iron (SI), liver iron, and kidney iron in DFe group were lower than those in the other four groups, while the levels of total iron-binding capacity (TIBC), transferrin (TF) and transferrin receptor (Tfr) in DFe group were higher than those in other groups; The serum levels of 25-(OH)D3 and 1,25-(OH)2D3 in DFe group were significantly lower than those in C group (P < 0.05). The correlation analysis showed that the levels of 25-(OH)D3 and 1,25-(OH)2D3 were negatively correlated with TIBC, TF and Tfr no correlation with SI. Western blotting, immunofluorescence, and q-PCR results showed that compared with C group, the protein and gene expressions of CYP2R1, CYP27A1, and CYP24A1 in DFe group were down-regulated, and the expression of CYP27B1 protein and gene was up-regulated in DFe group.Conclusion Iron may be involved in the metabolism of VD3 by regulating the expression of VD3 hydroxylase, suggesting that appropriate iron supplementation might promote the activation of VD3.
研究领域:
营养学
·
生物化学
·
药理学
·
动物生理学
✓ 已验证
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2019
·
IF 5.574
Rinkiko Suguro,Xiao-cong Pang,Zhong-wen Yuan,Si-yao Chen,Yi-Zhun Zhu,Ying Xie
Silybin (SB) is widely used to treat chronic liver diseases , especially this compound is much efficient for the treatments of alcoholic and non-alcoholic steatohepatitis (NASH). However, low bioavailability seriously limits wide-application of SB in biomedical niche. Prior to this study, we found that tangeretin (TG) could remarkably increase the bioavailability of SB by the inhibition of efflux transporters, which encourges us to therapeutical discovery of SB and TG combitional use against NASH. Here, we revealed that TG is capable of improving hepatic-protective activity of SB in mice with NASH by interfering liver oxidative stress, inflammation, and lipid accumulation. In addition, TG was observed to enhance the exposural level of SB in the plasma and liver of mice. Our metabolome assay confirmed that amino acid metabolism and lipid biosynthesis mostly accounted for combitional use of SB and TG to teat NASH in mice, basically biosynthesis of unsaturated fatty acids was mostly affected. Notably, significant inhibitions in fatty acid generating and transporting proteins such as G6PD, FABP4, LPL and CD36/FAT, and cholesterol metabolism enzyme CYP27A1 as well as nuclear transcription factors FXR , PPAR-γ, and LXR were illustrated to decipher therapeutic mechanisms of SB and TG against experimental NASH . Taken together, the strategy based combitional use of SB and TG has a potential-capacity to treat NASH.
研究领域:
肝病学
·
药理学
·
代谢组学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）