DRUG DEVELOPMENT RESEARCH
·
2020
·Vol. 81
·期 4
·526-533
·
IF 1.902
Dong Liu,Hailong Qin,Bixian Yang,Bin Du,Xuelin Yun
Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) and accumulation of the extracellular matrix. There are limitations in the current therapies for liver fibrosis. Recently, oridonin was shown to induce apoptosis in HSCs. Thus, we aimed to determine the roles of oridonin in chronic liver injury and fibrosis. Liver fibrosis was induced by CCl 4 in mice injected intraperitoneally with oridonin for 6 weeks. The administration of oridonin significantly attenuated liver injury and reduced ALT levels. In addition, Sirius Red staining and the expression of α-smooth muscle actin (α-SMA) were significantly reduced by oridonin in murine livers with fibrosis. The expression of NLRP3, caspase-1, and IL-1β was downregulated with the oridonin treatment. Furthermore, the expression of F4/80 in liver tissues was also decreased by oridonin treatment. These results demonstrate that oridonin ameliorates chronic liver injury and fibrosis. Mechanically, oridonin may inhibit the activity of the NLRP3 inflammasome and inflammation in the liver. These results highlight the potential of oridonin as a therapeutic agent for liver fibrosis.
研究领域:
药理学
·
肝病学
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Zixia Hu,Yanjia Zhao,Yi Yang,Wei Li,Rong Tan,Linhua Zhao,Xiaolin Tong,Ying Peng,Jiang Zheng
Background Dioscorea bulbifera L. (DBL) is a common herbal medicine where furanoterpenoid diosbulbin B (DSB) is a major component responsible for its hepatotoxicity . The metabolic oxidation of the furan moiety of DSB, resulting in covalent binding to hepatic protein , is considered to initiate its liver injury. Purpose We aimed to develop a mechanism-based plasma protein adduction-based biomarker to determine DBL exposure and to predict the onset of hepatotoxicity induced by DBL. Methods Rats were intragastrically treated with DBL extract, and the plasma samples were collected. Plasma ALT and AST were measured with commercial kits. Plasma protein modification was determined by immunoblot assay. Assessment of DSB-induced protein adduction was achieved by LC-MS/MS analysis of complete proteolytic digestion of adducted protein to pyrroline derivative A4 using pronase enzyme . The structure of the resulting pyrroline derivatives was confirmed by NMR. Results Plasma protein of rats treated with DBL extract was covalently modified by the metabolite of DSB. Pyrroline derivative A4 was detected in proteolytic digestion of plasma obtained from rats administered DBL extract. The protein adduction elevated with the increase in the dosage of DBL extract. A detectable level of plasma was observed 10 days after withdrawal of DBL extract post 30-day continuous administration. In addition, the elevation trend of plasma ALT was found to be proportional to the accumulation trend of pyrroline derivative A4. Conclusion DSB-derived plasma protein adduction correlated well with the exposure of DBL in rats. The protein adduction may be used as a good biomarker for diagnosis of DBL-induced liver injury and a useful indicator for DBL medication plans.
研究领域:
药理学
·
毒理学
·
分析化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Pengchao Xie,Yan Peng,Liyan Qiu
To explore effective therapeutic strategy on nonalcoholic fatty liver disease (NAFLD), the amphiphilic oligochitosan derivative containing ursodeoxycholic acid (UDCA) was synthesized and named as UBC, which could self-assemble and encapsulate exenatide (Exe) to obtain Exe-UBC nano-vesicle. Exe-UBC could be uptaken by fatty-acid cultured cells and release UDCA and Exe responsive to the high esterase concentration. In vitro experiments demonstrated that Exe-UBC activated the expression level of SIRT1 with inhibited expression of PGC-1β and PPAR-γ and consequently exerted synergistic bioaction immediately on reducing lipidosis. After a month of Exe-UBC treated through intravenous injection, the body weight of high-fat diet feeding C57BL/6 mice recovered to ordinary level, and their lipid contents in the liver declined significantly. The recovery in hepatic function indexes like TG , AST , and ALT further revealed the superiority of Exe-UBC vesicles. These results suggested that the co-delivery of UDCA and Exe via Exe-UBC could be a potent platform for NAFLD treatment.
研究领域:
药学
·
生物技术
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2022
·
IF 4.336
Hong-shuang Liu,Man-yu Zhou,Xi Zhang,Ya-lan Li,Jing-wei Kong,Xin Gao,Dong-yu Ge,Jia-jing Liu,Pei-guang Ma,Gui-ying Peng,Yan Liao
The hepatic protective role of Sagittaria sagittifolia polysaccharide (SSP) and its possible mechanism were discussed in mice and L02 hepatocytes injured by heavy metals mixture of Cd + Cr (VI) + Pb + Mn + Zn + Cu. After 30-day intervention, blood and liver samples were collected for the relevant assessments. Methyl thiazolyl tetrazolium (MTT) assay showed 24 h was the best protecting point and the SSP protection at 1 mg/mL was strongest in L02 hepatocytes. SSP can alleviated hepatic injury, as evidenced by significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the malondialdehyde (MDA) content, also increased the superoxide dismutase (SOD) activity and glutathione (GSH), total sulphydryl (T-SH) contents. SSP effectively reduced pathological damage of mice and accumulation of heavy metals in liver, as well as decreased the level of reactive oxygen species (ROS) in L02 hepatocytes. After SSP treatment, the protein expressions or gene transcription of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD( P )H dehydrogenase, quinone 1 (NQO1) and heme oxygenase1 (HO-1) decreased in L02. The protein expression of Nrf2 and NQO1 were increased while HO-1 was decreased in liver. Besides, SSP can attenuates apoptosis through reducing the protein expression of Bcl-2-associated X protein (Bax) and caspase-3, and increasing B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl). SSP protects against six-heavy-metal-induced hepatic injury in mice and L02 hepatocytes. Supported by Nrf2 gene silencing, the mechanisms may correlate with activating Nrf2 pathway to mitigate oxidative stress and apoptosis.
研究领域:
药理学
·
毒理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry A
·
2022
·Vol. 10
·期 25
·13286-13297
·
IF 14.511
Yaoguang Chen,Xiu Liu,Zhengqi Lao,Kang Yang,Fuzhen Li,Ling Chen,Kancheng Mai,Zishou Zhang
Inspired by the results of molecular dynamics simulation, a novel binary poly(ethylene-alt-2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) maleate) (PETM) and single-walled carbon nanotube (SWNT) nanocomposite thin film is first prepared and used as a flexible radical electrode. Benefiting from the enhanced affinity of PETM for SWNTs, a three-dimensional homogeneous co-continuous phase network structure is achieved in the PETM/SWNT electrode, which contributes to its high electrical conductivity, outstanding mechanical properties, and long-term deformation endurance. More importantly, the PETM/SWNT electrode exhibits a remarkable long-cycle life (96% capacity retention after 2000 cycles) and exceptional rate capability (almost unchanged capacity ranging from 5 to 50C). Additionally, a pouch cell based on the PETM/SWNT electrode demonstrated a stable operating voltage to power LED light strips under variant bending angles. These findings have practical significance towards designing high-performance flexible organic radical batteries.
研究领域:
材料科学
·
能源技术
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2017
·Vol. 8
·期 9
·3259-3270
·
IF 3.247
Xiaozhou Zhou,Shiguo Chen,Xingqian Ye
The anti-obesity effects of different proanthocyanidin extracts (PE) from Chinese bayberry (Myrica rubra Sieb.et Zucc.) leaves were evaluated in a high-fat (HF) diet-induced obese rat model. The leaves of Chinese bayberry (LCB), a non-desaccharified proanthocyanidin extract (NDPE), and a desaccharified proanthocyanidin extract (DPE) were compared with orlistat, a conventional anti-obesity drug used as a positive control. The rats from all of the PE-treated groups showed obvious weight loss, with the greatest weight loss in the DPE group (P < 0.05). Compared to the HF group, almost all of the PE-treated groups showed significantly reduced levels of serum TC, TG, AST, ALT, ALP, LDL-C, ADP and a LEP/ADP ratio, and increased levels of HDL-C and LEP. Furthermore, the expression levels of SIRT1, PPAR-γ, C/EBP-α, BMP4 and UCP1 were investigated in the liver, kidney, epididymis and abdominal adipose tissue. Compared to the HF group, PPAR-γ and C/EBP-α levels were significantly reduced and SIRT1, BMP4 and UCP1 levels were significantly upregulated in the DPE-treated group. Our results suggested that PE exerted its anti-obesity effects by upregulating the expression of SIRT1, thus inducing the deacetylation of PPAR-γ and downregulating the expression of C/EBP-α, and also upregulating the expression of BMP4 to boost the levels of brown fat.
研究领域:
药理学
·
营养学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2014
·
IF 3.63
Demei Xu,Lihua Hu,Chuanyang Su,Xiaomin Xia,Pu Zhang,Juanli Fu,Wenchao Wang,Duo Xu,Hong Du,Qiuling Hu,Erqun Song,Yang Song
This study investigated the protective effects of curcumin on tetrachloro- p -benzoquinone (TCBQ)-induced hepatotoxicity in mice. TCBQ-treatment causes significant liver injury (the elevation of serum AST and ALT activities, histopathological changes in liver section including centrilobular necrosis and inflammatory cells), oxidative stress (the elevation of TBAR level and the inhibition of SOD and catalase activities) and inflammation (up-regulation of iNOS , COX-2, IL-1β, IL-6, TNF-α and NF-κB). However, these changes were alleviated upon pretreatment with curcumin. Interestingly, TCBQ has no effect on caspase family genes or B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) protein expressions, which implied that TCBQ-induced hepatotoxicity is independent of apoptosis. Moreover, curcumin was shown to induce phase II detoxifying/antioxidant enzymes HO-1 and NQO1 through the activation of nuclear factor erythroid-derived 2-like 2 (Nrf2). In summary, the protective mechanisms of curcumin against TCBQ-induced hepatoxicity may be related to the attenuation of oxidative stress, along with the inhibition of inflammatory response via the activation of Nrf2 signaling.
研究领域:
药理学
·
毒理学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2022
·
IF 3.973
Mingyu Zhang,Yaodong Hu,Wei Li,Chen Sun,Chunjing Guan,Ying Peng,Jiang Zheng
2,6-Dimethylphenol (2,6-DMP) is an environmental pollutant found in industrial wastewater. Exposure to 2,6-DMP is of increasing concern as it endangered reportedly some aquatic animals. In this study, we investigated the metabolic activation and hepatotoxicity of 2,6-DMP. 2,6-DMP was metabolized to an o-quinone methide intermediate in vitro and in vivo. The electrophilic metabolite was reactive to the sulfhydryl groups of glutathione, N-acetyl cysteine, and cysteine. NADPH was required for the formation of the reactive metabolite. The quinone methide intermediate reacted with cysteine residues to form hepatic protein adduction. A single dose of 2,6-DMP induced marked elevation of serum ALT and AST in mice. Both the protein adduction and hepatotoxicity of 2,6-DMP showed dose dependency.
研究领域:
毒理学
·
环境科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Tingting Yan,Yuying Zhang,Hengyu Lu,Jun Zhao,Chengrong Wen,Shuang Song,Chunqing Ai,Jingfeng Yang
An alcohol-induced liver injury model was induced in C57BL/6 mice to assess the protective efficacy of Enteromorpha prolifera polysaccharides (EP) against liver damage. Histological alterations in the liver were examined following hematoxylin-eosin (H&E) staining. Biochemical assay kits and ELISA kits were employed to analyze serum and liver biochemical parameters, as well as the activity of antioxidant enzymes and alcohol metabolism-related enzymes. The presence of oxidative stress-related proteins in the liver was detected using western blotting. Liquid chromatography and mass spectrometry were used to profile serum metabolites in mice. The findings demonstrated that EP-H (100 mg/Kg) reduced serum ALT and AST activity by 2.31-fold and 2.32-fold, respectively, when compared to the alcohol-induced liver injury group. H&E staining revealed a significant attenuation of microvesicular steatosis and ballooning pathology in the EP-H group compared to the model group. EP administration was found to enhance alcohol metabolism by regulating metabolite-related enzymes (ADH and ALDH) and decreasing CYP2E1 expression. EP also modulated the Nrf2/HO-1 signaling pathway to bolster hepatic antioxidant capacity. Furthermore, EP restored the levels of lipid metabolites (Glycine, Butanoyl-CoA, and Acetyl-CoA) to normalcy. In summary, EP confers protection to the liver through the regulation of antioxidant activity and lipid metabolites in the murine liver.
研究领域:
药理学
·
毒理学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2025
·
IF 3.6
Duan Yunping,Liu Hui,Zhang Weichuan,Pei Zhuo,Huang Yong
In this study, 360 healthy juvenile largemouth bass, averaging body weights of 11.26 ± 0.49 g, were randomly assigned to four experimental groups. These groups were exposed to water environments containing different concentrations of cadmium (Cd): 0 mg/L for the control (Con) group, 0.9804 mg/L for the low-cadmium (LCd) group, 1.9608 mg/L for the medium-cadmium (MCd) group, and 9.804 mg/L for the high-cadmium (HCd) group, over a duration of 21 days, to study how different levels of Cd impact the liver. Ultrastructural changes manifest as nuclear deformation, blurred cell membrane boundaries, mitochondrial swelling, matrix dissolution, cristae rupture, and disappearance. TUNEL analysis indicates that the apoptotic rate of hepatocytes increases with increasing Cd concentration. Compared with the Con group, serum biochemical results showed that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glucose (GLU), and urea (UREA) were significantly elevated in the HCd group. With increasing Cd concentration, the activities of hepatic catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH) were significantly altered, accompanied by a reduction in ATP content and an increase in the malondialdehyde (MDA) levels. Analysis of inflammatory gene expression showed upregulation of pro-inflammatory genes (IL-1β, TNF-α, and IL-6) and downregulation of the anti-inflammatory gene IL-10. In addition, significant changes in the mRNA levels of apoptosis-related genes were observed in these Cd-exposed groups. Collectively, these findings consistently indicate that Cd exposure can lead to liver injury in largemouth bass by inducing oxidative stress, inflammatory responses, and apoptosis. Graphical
研究领域:
环境毒理学
·
水生毒理学
·
生物化学
·
分子生物学
·
生态毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2018
·
IF 5.091
Jibo Dou,Qiang Huang,Hongye Huang,Defu Gan,Junyu Chen,Fengjie Deng,Yuanqing Wen,Xiaoli Zhu,Xiaoyong Zhang,Yen Wei
A novel ternary composite consisting of Mg/Al layered double hydroxides (LDH), polydopamine (PDA) and poly(methyl vinyl ether- alt -maleic anhydride) (PMVE-MA) was fabricated by a facile combination of mussel-inspired chemistry and a ring-opening reaction. Dopamine can serve as a “minimalist mimic” of mussel adhesive protein to form a layer of polydopamine (PDA) on the LDH surface under rather mild conditions (including air atmosphere, aqueous solution, and catalyst free). Subsequently, the PMVE-MA brushes were immobilized onto the PDA modified LDH via a ring-opening reaction. The morphology and chemical compositions of the as-prepared samples were characterized by SEM, TEM, FT-IR, TGA , and XPS. To evaluate the adsorption performance of the PMVE-MA modified LDH ( [email protected] @PMVE-MA) composites, the obtained samples were used as adsorbents for the removal of copper ions (Cu 2+ ) from an aqueous solution. The results demonstrated that the [email protected] @PMVE-MA composites showed a significant improvement in the adsorption efficiency towards Cu 2+ , and the adsorption capacity of the [email protected] @PMVE-MA composites was found to be 2 times higher than that of pristine LDH. Adsorption kinetics showed that the experimental data were fitted well by the pseudo-second-order kinetic model. Equilibrium data could be best described by the Langmuir isotherm model, with the maximum monolayer adsorption capacity of 193.78 mg/g. Thermodynamic studies indicated that the adsorption of Cu 2+ onto the [email protected] @PMVE-MA composites is an endothermic and spontaneous process. Importantly, it can be easily regenerated by low-cost reagents, and exhibited high removal efficiencies after four cycles of adsorption-desorption. These results suggest that the [email protected] @PMVE-MA nanocomposites are good candidate for Cu 2+ removal from aqueous solutions.
研究领域:
材料科学
·
环境化学
·
表面化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2022
·
IF 3.973
Si-wei Rao,Yuan-yuan Duan,Dong-sheng Zhao,Cheng-jun Liu,Shao-hua Xu,Dong Liang,Feng-xiang Zhang,Wei Shi
Matrine (MT) is a major bioactive compound extracted from Sophorae tonkinensis. However, the clinical application of MT is relatively restricted due to its potentially toxic effects, especially hepatotoxicity. Although MT-induced liver injury has been reported, little is known about the underlying molecular mechanisms. In this study, transcriptomics and metabolomics were applied to investigate the hepatotoxicity of MT in mice. The results indicated that liver injury occurred when the administration of MT (30 or 60 mg/kg, i.g) lasted for 2 weeks, including dramatically increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), etc. The metabolomic results revealed that steroid biosynthesis, purine metabolism, glutathione metabolism, and pyruvate metabolism were involved in the occurrence and development of MT-induced hepatotoxicity. Further, the transcriptomic data indicated that the downregulation of NSDHL with CYP51, FDFT1, and DHCR7, involved in steroid biosynthesis, resulted in a lower level of cholic acid. Besides, Gstps and Nat8f1 were related to the disorder of glutathione metabolism, and HMGCS1 could be treated as the marker gene of the development of MT-induced hepatotoxicity. In addition, other metabolites, such as taurine, flavin mononucleotide (FMN), and inosine monophosphate (IMP), also made a contribution to the boosting of MT-induced hepatotoxicity. In this work, our results provide clues for the mechanism investigation of MT-induced hepatotoxicity, and several biomarkers (metabolites and genes) closely related to the liver injury caused by MT are also provided. Meanwhile, new insights into the understanding of the development of MT-induced hepatotoxicity or other monomer-induced hepatotoxicity were also provided.
研究领域:
药理学
·
毒理学
·
分子生物学
·
系统生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）