Scientific Reports
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2023
·Vol. 13
·期 1
·1-9
·
IF 4.6
Zhang Lijun,Liu Chuhe,Yin Liufang,Huang Cheng,Fan Shengjie
Hepatic fibrosis is a late stage process of many chronic liver diseases. Blocking the fibrosis process will be beneficial to the treatment and recovery of the diseases. Mangiferin has many pharmacological activities. Recently, it has been reported that mangiferin may relieve tissue fibrosis, including renal, myocardial, pulmonary fibrosis via anti-inflammatory and anti-oxidative effects in animal models. Here, we investigate the effects of mangiferin on CCl4-induced liver fibrosis and the underlying mechanism in mice. Thirty-two male C57BL/6 mice were randomly divided into 4 groups (n = 8 in each group), injected with carbon tetrachloride (10% CCl4) for 8 weeks, and oral administrated with mangiferin (50 mg/kg or 100 mg/kg) from the fifth week. The serum levels of ALT, AST were analyzed to evaluate liver function. H&E, Masson’s trichrome and Sirius red staining were used to assess liver morphology and the degree of liver fibrosis. Quantitative RT-PCR and Western blot were used to assay the gene expression and protein levels. The results showed that mangiferin alleviated the serum levels of AST, ALT, ALP, TBA and TBIL, reduced liver lesions, prevented hepatic parenchymal necrosis, and ameliorated collagen accumulation in the liver of CCl4-treated mice. Meanwhile, mangiferin inhibited the expression of inflammatory genes IL-6 and IL-1β, fibrogenic genes α-SMA, TGF-β and MMP-2 and bile acid metabolism genes ABCB4, ABCB11, SULT2A1 in the liver of CCl4-treated mice. Furthermore, mangiferin reduced collagen accumulation and HSCs activation, inhibited the p-IκB and p-p65 protein levels. Our results suggest that mangiferin could alleviate liver fibrosis in CCl4-treated mice through inhibiting NF-κB signaling, and mango consuming may have beneficial effects to hepatic fibrosis.
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2018
·
IF 3.909
Yao Xu,Huiyan Jiang,Congyong Sun,Michael Adu-Frimpong,Wenwen Deng,Jiangnan Yu,Ximing Xu
In this study, two polysaccharide fractions (RRP1: Mw = 5.5 kDa, and RRP2: Mw = 425.7 kDa) were isolated from Rhodiola rosea to investigate their antioxidation and hepatoprotective effects. Physicochemical analysis showed that RRP1 was composed of mannose, rhamnose, galacturonic acid, glucose, galactose and arabinose with a relative molar ratio of 0.69:0.11:0.15:1:0.51:7.5 and RRP2 was consisted of mannose, rhamnose, galacturonic acid, glucose, galactose and arabinose (relative molar ratio = 0.15:0.19:1.01:0.18:0.47:1). Periodate oxidation and Smith degradation analysis revealed that, in RRP1, part of the arabinose and glucose residues were 1 → 3,6/1 → 3/1 → 2,3/1 → 3,4/1 → 2,4/1 → 2,3,4-linked, and the mannose, rhamnose and galactose residues were 1 → 2,6/1 → 6/1 → 2/1→/1 → 4,6/1 → 4-linked. In RRP2, the rhamnose, glucose and galactose residues were linked by 1 → 3,6/1 → 3/1 → 2,3/1 → 3,4/1 → 2,4/1 → 2,3,4 linkages, and the arabinose and mannose residues were 1 → 2/1 → 6/1 → 4-linked. The methylation analysis confirmed the structure information of the two fractions. Importantly, fraction RRP1 demonstrated stronger antioxidative activities than RRP2 by scavenging DPPH, hydroxyl and superoxide anion radicals in vitro. Correspondently, RRP1 showed more significant effects than RRP2 on decreasing the levels of ALT, AST and MDA, and increasing the GSH, SOD and CAT levels in the CCl 4 -treated mice. These data demonstrated that the polysaccharide RRP1 could be developed as a promising candidate for preventing and treating liver damage induced by toxic chemicals.
研究领域:
药理学
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生物化学
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DOI
PubMed
高影响因子
ACS Omega
·
2025
·
IF 4.3
Mingmin Li,Liang Qi,Jin Huang,Haonan Li,Wei Cheng,Zihan Shi,Xianxing Jiang,Yifeng Zhou,Wanxiang Jiang
Liver fibrosis can progress to cirrhosis and hepatocellular carcinoma. Currently, there is no effective drug for liver fibrosis. The peptide 6 (T6) is an endogenous peptide derived from human intrauterine adhesion tissues and has antifibrotic potential. Here, to improve the long-term efficacy and activity of T6, we conducted the rational modified of T6 through studying structure–activity, and synthesized a series of analogues. Among them, S6 and S6-FA exhibited optimal antihepatic fibrosis activity, and S6-FA had a stronger long-acting effect than T6 and S6. The two analogues inhibited the expression of α-SMA and Collagen 1 in TGF-β-induced LX2 cells model and CCl4-induced mouse model of liver fibrosis. Besides, we discovered that S6 and S6-FA remarkably reduced the AST and ALT serum levels. Mechanistic studies have demonstrated that analogues inhibited liver fibrosis through inhibiting Erk, Smad and P65 pathways. This study provided that the novel peptide S6 and S6-FA is potential candidate compounds for treating liver fibrosis.
研究领域:
医学
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药理学
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DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
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2020
·
IF 2.274
Lei-Lei Zhu,Ji-Duo Shen,Bao-Ying Wang,Shuai-Fei Lu,Bai Ming,Er-Ping Xu,Yu-Cheng Li,Xiao-Yan Fang
Depression is a highly prevalent mental disease and increasingly become a global public health problem. Recent studies have shown that the dysfunction of liver was associated with depression. However, the previous studies have not been fully explained the relationship between depression and liver injury. The present study was aimed to investigate whether chronic liver injury could induce depressive-like behavior. Chronic liver injury was induced by intraperitoneal injection of carbon (CCl 4 ), D-galactosamine (D-GalN) and thioacetamide (TAA), respectively. And the results showed that the serum activities of ALT in CCl 4 , D-GalN and TAA groups were significantly increased in both male and female mice compared with the control group, while the activities of AST increased only in CCl 4 group. Meanwhile, H&E staining showed that CCl 4 , D-GalN and TAA induced hepatocytes injury in both male and female mice. Moreover, the sucrose preference was significantly decreased and the immobility time in forced swimming test and tail suspension test were significantly prolonged in CCl 4 and D-GalN group compared with control group. Our findings demonstrated that chronic liver injury induced by CCl 4 and D-GalN could induce depressive-like behaviors in mice.
研究领域:
医学
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神经科学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2017
·
IF 3.526
Yi Kuang,Yan Lin,Kai Li,Wei Song,Shuai Ji,Xue Qiao,Qingying Zhang,Min Ye
Background Licorice and its constituents, especially licorice flavonoids have been reported to possess significant hepatoprotective activities. However, previous studies mainly focus on the extract and major compounds, and few reports are available on other licorice compounds. Purpose This work aims to evaluate the in vitro hepatoprotective activities of licorice compounds and screen active compounds, and to establish the structure–activity relationship. Methods A compound library consisting of 180 compounds from three medicinal licorice species, Glycyrrhiza uralensis , G. glabra and G. inflata was established. HepG2 cells were incubated with the compounds, together with the treatment of 0.35% CCl 4 for 6 h and 14 mM APAP for 24 h, respectively. Results A total of 62 compounds at 10 µM showed protective effects against CCl 4 to improve cell viability from 52.5% to >60%, and compounds 5 (licoflavone A), 104 (3,4-didehydroglabridin), 107 (isoliquiritigenin), 108 (3,4,3′,4′-tetrahydroxychalcone), and 111 (licochalcone B) showed the most potent activities, improving cell viability to >80%. And 64 compounds showed protective effects against APAP to improve cell viability from 52.0% to >60%, and compounds 47 (derrone), 76 (xambioona), 77 ((2S)-abyssinone I), 107 (isoliquiritigenin), 118 (licoagrochalcone A), and 144 (2′- O -demethybidwillol B) showed the most potent activities, improving cell viability to >80%. Preliminary structure–activity analysis indicated that free phenolics compounds especially chalcones showed relatively stronger protective activities than other types of compounds. Conclusion Compounds 5, 76, 104, 107, 111, 118 and 144 possess potent activities against both CCl 4 and APAP, and 5, 76 and 118 were reported for the first time. They could be the major active compounds of licorice for the treatment of liver injury.
研究领域:
药理学
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细胞生物学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2019
·
IF 6.044
Juan-Juan Cao,Qing-Qing Lv,Bao Zhang,Han-Qing Chen
Two polysaccharide fractions (TSP-1 and TSP-2) with molecular weights of 833.6 kDa and 81.6 kDa were isolated from Toona sinensis leaves (Meliaceae) by hot water extraction, DEAE Cellulose-52 chromatography and Sephacryl S-400 gel permeation chromatography. Structural analysis indicated that TSP-1 and TSP-2 consisted of Man p , Glc p A, Glc p , Gal p , Xyl p and Ara f with different molar ratios. Methylation and NMR analysis revealed that the backbone of TSP-1 might consist of 1,6-linked-Glc p , 1,3,6-linked-Man p and 1,6-linked-Gal p , while TSP-2 was mainly composed of 1,3,5-linked-Ara f , 1,6-linked-Glc p , 1,4-linked-Xyl p and 1,6-linked-Gal p . Congo red assay indicated that TSP-1 and TSP-2 had no triple-helix structure, which was consistent with the results of AFM. In vivo hepatoprotective activity showed that TSP-1 and TSP-2 could improve CCl 4 -induced mice liver injury by reducing the activities of AST, ALT and the level of MDA, increasing the activities of SOD, GSH-Px, and CAT and the level of GSH in liver and decreasing the expression levels of TNF-α and IL-6 in liver. These results suggest that TSP-1 and TSP-2 have promising potential to serve as hepatoprotective agents.
研究领域:
药理学
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生物化学
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植物科学
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DOI
PubMed
高影响因子
STAR Protocols
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2023
·
IF 0
Jie Zhang,Xiao-Tong Lin,Lei Fang,Chuan-Ming Xie
Summary FBXO45, an E3 ubiquitin ligase highly expressed in liver tumors, is positively correlated with poor survival of hepatocellular carcinogenesis (HCC) patients, but whether FBXO45 drives HCC tumorigenesis remains largely unclear. Here, we describe a protocol that shortens the observation period for HCC tumorigenesis to assess the effects of FBXO45 in a DEN/CCl 4 -induced HCC mouse model. We describe steps for chemical induction of HCC in FBXO45-overexpressing mice, followed by tissue collection and pathology assessment via quantitative real-time PCR, histology, and immunohistochemistry. For complete details on the use and execution of this protocol, please refer to Lin et al. (2021). 1
研究领域:
癌症生物学
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分子生物学
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病理学
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DOI
PubMed
CATALYSIS LETTERS
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2018
·Vol. 149
·期 3
·665-671
·
IF 2.911
Lyu Xinyu,Wang Wencheng,Sun Yiqun,Zhao Qian,Qiu Tao
Abstract An ionic liquid catalyzed Friedel–Crafts alkylation reaction of substituted benzenes with CCl 4 was developed. The reaction proceeded efficiently under mild conditions, gave corresponding trichloromethylarenes with diversity functional groups in moderate to good yields. The influence of Lewis acidity of ionic liquids on the conversion of the alkylation reaction has been investigated. Notably, the probable mechanism of this reaction has been proposed with the assistance of 27 Al NMR spectroscopy. It was noteworthy that the predominance of [Al 2 Cl 7 ] − species in EmimCl–AlCl 3 , N = 0.67 could be detected by 27 Al NMR spectral analysis, and [AlCl 4 ] − was generated at the beginning of reaction. Additionally, it was found that [AlCl 4 ] − could be transformed into [Al 2 Cl 7 ] − when the reaction finished. Some control experiments confirmed that the interaction between Lewis acidic species [Al 2 Cl 7 ] − of the ionic liquid and CCl 4 led to the change in speciation of aluminum during the alkylation reactions. Graphical Abstract
研究领域:
有机化学
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催化化学
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DOI
高影响因子
JOURNAL OF PHYSICAL CHEMISTRY A
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2017
·
IF 2.847
Peiwen Wang,Nan Zhao,Yizhen Tang
Methyl iodine (CH3I) and carbon tetrachloride (CCl4) are both important volatile precursors for atmospheric ozone destruction. CH3I and CCl4 can act as halogen bond donors to form molecular complexes with atmospheric organic species, such as 2,5-dihydrofuran, tetrahydrofuran, and acetone. This study characterized the halogen bonds in the CH3I and CCl4 complexes using matrix isolation infrared spectroscopy and density functional theory calculations. With the combination of vibrational frequencies in spectra and the calculated interaction energies, frequencies and atoms-in-molecules analyses, we confirmed the formation of halogen-bonded complexes. CH3I as a halogen-bond donor is comparable or slightly weaker than CCl4, and furans involving ether oxygens are better halogen acceptors than acetone. The results help to understand the possibilities of formation of atmospheric molecular complexes that may influence the atmospheric chemical activities and enhance the aerosol formation.
研究领域:
物理化学
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大气化学
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光谱学
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量子化学计算
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分子间作用力
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环境化学
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DOI
高影响因子
PHARMACEUTICAL BIOLOGY
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2015
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IF 1.241
Cong Li,Li-Tao Yi,Di Geng,Yuan-Yuan Han,Lian-jin Weng
Context: The roots of Berchemia lineate (L.) DC. (Rhamnaceae) have been long used as a remedy for the treatment of some diseases in Guangxi Province, China.Objective: The present study investigates the hepatoprotective effect of Berchemia lineate ethanol extract (BELE) on CCl4-induced acute liver damage in mice.Materials and methods: Effect of BELE administrated for 7 consecutive days was evaluated in mice by the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), albulin (ALB), globulin (GLB), and total protein (TP) levels, as well as liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Moreover, histopathological examinations were also taken.Results: Compared with the model group, administration of 400 mg/kg BELE for 7 d in mice significantly decreased the serum ALT (56.25 U/L), AST (297.67 U/L), ALP (188.20 U/L), and TBIL (17.90 mol/L), along with the elevation of TP (64.67 g/L). In addition, BELE (100, 200, and 400 mg/kg, i.g.) treated mice recorded a dose-dependent increment of SOD (291.17, 310.32, and 325.67 U/mg prot) and reduction of MDA (7.27, 6.77, and 5.33 nmol/mg prot) levels. Histopathological examinations also confirmed that BELE can ameliorate CCl4-induced liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation.Discussion and conclusion: The results indicated that BELE possessed remarkable protective effect against acute hepatotoxicity and oxidative injuries induced by CCl4, and that the hepatoprotective effects of BELE may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.
研究领域:
药理学
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肝病学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2025
·
IF 5.1
Yifang Wang,Yihua Zhang,Yinting He,Shixun Zhang,Bo Huang,Yarong Wang,Weibin Lin,Weicheng Xiao,Zhenzhuang Zou,Guozhen Cui
Background: Liver disease is a global health issue requiring effective therapeutic interventions. Although the individual hepatoprotective properties of glutathione, Ganoderma lucidum extract, and vitamin C are well-documented, their combined effects remain to be elucidated.Objective: This study aims to investigate the hepatoprotective potential of a functional food formula named GGV to mitigate acute liver injury induced in mice.Methods: GGV was orally administered in a mouse model of carbon tetrachloride (CCl4)-induced acute liver injury. Liver function was assessed by measuring serum and hepatic biomarkers. Gut microbiota composition and diversity were evaluated using 16S rRNA gene sequencing. Serum metabolomic profiling was conducted using UPLC-Q/TOF-MS.Results and conclusion: GGV administration significantly ameliorated CCl4-induced liver dysfunction, exhibiting greater efficacy than its individual components. Gut microbiota analysis revealed that GGV treatment restored the microbial diversity and composition disrupted by CCl4 exposure. Metabolomic profiling further indicated that GGV normalized phospholipid, fatty acid, and bile acid levels. Correlation analysis identified specific microbial genera associated with serum bile acid profiles, suggesting that the hepatoprotective effects of GGV are mediated through modulation of gut microbiota composition and metabolites. Taken together, these findings support the potential of GGV as a promising dietary intervention for promoting liver health through the liver-microbiota-gut axis.
研究领域:
药理学
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
Biology-Basel
·
2026
·Vol. 15
·期 5
·
IF 4.3
Li Gao,Hui Tian,Xiangli Bai,Yanwen Zhang
This study aimed to investigate the effect and underlying mechanism ofTaxus cuspidataseed oil (TCSO) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. A mouse model of hepatic fibrosis was established by CCl4induction, and the model mice were subsequently treated orally with high dose or low dose TCSO for eight weeks. The degree of liver fibrosis and the mechanism of action were assessed through organ indices, serum biochemical markers, oxidative stress levels, histopathological examination, and molecular biological analyses. The results demonstrated that TCSO significantly reduced serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). Concurrently, it decreased the concentrations of liver fibrosis markers, including procollagen III (PC III), collagen IV (IV-C), hyaluronic acid (HA), and laminin (LN), and reduced hepatic collagen deposition. Furthermore, TCSO enhanced the activities of the antioxidants superoxide dismutase (SOD) and glutathione (GSH) while inhibiting the production of the lipid peroxidation product malondialdehyde (MDA), and it ameliorated histopathological alterations in liver tissue. Additionally, TCSO markedly downregulated the expression of key fibrogenic proteins, such as transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinases-1 (TIMP-1), thereby effectively suppressing the progression of hepatic fibrosis. In conclusion, TCSO ameliorates hepatic fibrosis in mice by reducing hepatotoxic enzyme activity and collagen deposition, enhancing antioxidant capacity, and downregulating the expression of fibrosis-related proteins.
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PubMed
高影响因子
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