Food & Function
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2020
·Vol. 11
·期 5
·4582-4590
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IF 4.171
Xiaohua Lei,Qiang Liu,Qiang Liu,Zhenyu Cao,Ju Zhang,Tao Kuang,Yu Fang,Guoxing Liu,Ke Qian,Jie Fu,Huihui Du,Zhiqiang Liu,Zhihong Xiao,Changzhu Li,Xundi Xu
Liver fibrosis is a common part of the pathological development of many chronic liver diseases. As liver fibrosis progresses, it may lead to cirrhosis, portal hypertension, liver decompensation, liver tumours, and death. Camellia oil (Camellia oleifera Abel.) is widely used as an edible oil in China. It has a wide range of biological activities and is used as a traditional medicine to treat conditions such as burns and stomach pains. However, whether camellia oil can ameliorate liver fibrosis remains unclear. We constructed a liver fibrosis model induced by carbon tetrachloride (CCl4) and then confirmed the role of camellia oil in liver fibrosis by biochemical examination, histopathological morphology, immunohistochemistry, and western blot analysis. We found that camellia oil ameliorated histopathological lesions, improved liver function and antioxidant capacity, decreased the expression of TGF-β1 and α-SMA proteins, and downregulated the expression of the pro-apoptotic proteins in CCl4-induced liver fibrosis. Therefore, these results suggest that camellia oil attenuates CCl4-induced liver fibrosis in mice, and its mechanism may function via reduction of hepatocyte apoptosis to inhibit hepatic stellate cell (HSC) activation. Camellia oil may provide a potential new treatment for liver fibrosis as an auxiliary treatment by addition of the edible oil to the daily diet.
研究领域:
药理学
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肝病学
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病理学
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DOI
PubMed
高影响因子
WORLD JOURNAL OF GASTROENTEROLOGY
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2020
·
IF 3.665
Xiao Meng,Guo-Yi Tang,Pin-He Liu,Chan-Juan Zhao,Qing Liu,Hua-Bin Li
BACKGROUND Many natural products confer health benefits against diverse diseases through their antioxidant activities. Carbon tetrachloride (CCl 4 ) is often used in animal experiments to study the effects of substances on liver injury and the related mechanisms of action, among which oxidative stress is a major pathogenic factor. AIM To compare antioxidant and hepatoprotective activities of ten herbs and identify and quantify phytochemicals for the one with strongest hepatoprotection. METHODS The antioxidant activity of ten medicinal herbs was determined by both ferric-reducing antioxidant power and Trolox equivalent antioxidant capacity assays. The total phenolic and flavonoid contents were determined by Folin–Ciocalteu method and aluminum chloride colorimetry, respectively. Their effects on CCl 4 -induced oxidative liver injury were evaluated and compared in a mouse model by administrating each water extract (0.15 g/mL, 10 mL/kg) once per day for seven consecutive days and a dose of CCl 4 solution in olive oil (8%, v/v, 10 mL/kg). The herb with the strongest hepatoprotective performance was analyzed for the detailed bioactive components by using high-performance liquid chromatography-electrospray ionization source-ion trap tandem mass spectrometry. RESULTS The results revealed that all tested herbs attenuated CCl 4 -induced oxidative liver injury; each resulted in significant decreases in levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and triacylglycerols. In addition, most herbs restored hepatic superoxide dismutase and catalase activities, glutathione levels, and reduced malondialdehyde levels. Sanguisorba officinalis ( S. officinalis ) L., Coptis chinensis Franch., and Pueraria lobata (Willd.) Ohwi root were the three most effective herbs, and S. officinalis L. exhibited the strongest hepatoprotective effect. Nine active components were identified in S. officinalis L. Gallic acid and (+)-catechin were quantified (7.86 ± 0.45 mg/g and 8.19 ± 0.57 mg/g dried weight, respectively). Furthermore, the tested herbs displayed a range of in vitro antioxidant activities proportional to their phenolic content; the strongest activities were also found for S. officinalis L. CONCLUSION This study is of value to assist the selection of more effective natural products for direct consumption and the development of nutraceuticals or therapeutics to manage oxidative stress-related diseases.
研究领域:
药理学
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肝病学
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天然产物化学
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DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
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2012
·Vol. 22
·期 5
·2524-2530
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IF 1.271
Guo Yibing,Zheng Cheng,Xu Wen,Si Yongxing,Dou Sufeng,Yang Yumin
Abstract Salidroside, a phenylpropanoid glycoside isolated from a traditional Chinese medicinal plant Rhodiola rosea L. displays a broad spectrum of pharmacological properties. It has been found to play a hepatoprotective role in liver diseases through inhibiting apoptosis of hepatocytes and proliferation of hepatic stellate cells, decreasing serum aminotransferase, reversing hepatic fibrosis, and improving liver function. In this study as an ongoing study on the discovery and development of new hepatoprotective agents, about 12 novel glycosides were synthesized, and 2,2-diphenyl-1-picrylhydrazyl radical scavenge activity of each glycoside was evaluated. 2-(3,4,5-trihydroxyphenyl)ethyl β- d -glucopyranoside ( 4g ) and 2-(3,4,5-trihydroxyphenyl)ethyl β- d -galactopyranoside ( 4h ) exhibited significant activity prior to salidroside with an IC 50 value of 38.05 and 35.85 μM, respectively. The hepatoprotective effect of compounds 4g and 4h on CCl 4 -induced cytotoxicity in LO2 cells was assessed for further research. Graphical abstract 2-(3,4,5-Trihydroxyphenyl)ethyl β- d -glucopyranoside ( 4g ) and 2-(3,4,5-trihydroxyphenyl)ethyl β- d -galactopyranoside ( 4h ) exhibited significant hepatoprotective activity prior to salidroside.
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高影响因子
Hepatology International
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2019
·Vol. 14
·期 1
·145-160
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IF 5.49
Zhao Jing,Han Ming,Zhou Li,Liang Pu,Wang Yun,Feng Shenghu,Lu Hongping,Yuan Xiaoxue,Han Kai,Chen Xiaofan,Liu Shunai,Cheng Jun
Background This study aimed to investigate the roles and mechanisms of tenofovir alafenamide fumarate (TAF)/tenofovir disoproxil fumarate (TDF) in treating liver fibrosis. Methods The effects of TAF/TDF on carbon tetrachloride (CCl 4 )-induced liver fibrosis in C57BL/6 wild-type or nonstructural protein 5A transactivated protein 9 (NS5ATP9) knockout mice were studied. The differentiation, activation, and proliferation of LX-2 cells after TAF/TDF treatment were tested in vitro. The expression of NS5ATP9 and activities of transforming growth factor-β1 (TGFβ1)/Sekelsky mothers against decapentaplegic homolog 3 (Smad3) and NF-κB/NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were detected in TAF/TDF-treated mice and LX-2 cells. The genes related to extracellular matrix accumulation were detected in vivo and in vitro after NS5ATP9 silencing or knockout. Results TAF/TDF significantly inhibited CCl 4 -induced liver fibrosis in mice, and regulated the differentiation, activation, and proliferation of hepatic stellate cells (HSCs). Furthermore, TAF/TDF suppressed the activities of TGFβ1/Smad3 and NF-κB/NLRP3 inflammasome signaling pathways in vivo and in vitro. NS5ATP9 inhibited liver fibrosis through TGFβ1/Smad3 and NF-κB signaling pathways. TAF/TDF upregulated the expression of NS5ATP9 in vivo and in vitro. Finally, TAF/TDF could only show marginal therapeutic effects when NS5ATP9 was silenced and knocked out in vivo and in vitro. Conclusions TAF/TDF prevented progression and promoted reversion of liver fibrosis through assembling TGFβ1/Smad3 and NF-κB/NLRP3 inflammasome signaling pathways via upregulating the expression of NS5ATP9. TAF/TDF also regulated the differentiation, activation, and proliferation of HSCs. The findings provided strong evidence for the role of TAF/TDF as a new promising therapeutic strategy in liver 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
AAPS Journal
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2017
·Vol. 19
·期 6
·1703-1714
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IF 3.423
Cao Mingnan,Wang Huixia,Guo Limei,Yang Simin,Liu Chun,Khor Tin Oo,Yu Siwang,Kong Ah-Ng
Oxidative stress is an important pathogenic factor in various hepatic diseases. Nuclear factor-erythroid 2-related factor-2 (Nrf2), which coordinates the expression of an array of antioxidant and detoxifying genes, has been proposed as a potential target for prevention and treatment of liver disease. Dibenzoylmethane (DBM) is a minor ingredient in licorice that activates Nrf2 and prevents various cancers and oxidative damage. In the present study, the mechanisms by which DBM activates Nrf2 signaling were delineated, and its protective effect against carbon tetrachloride (CCl 4 )-induced liver injury was examined. DBM potently induced the expression of HO-1 in cells and in the livers of mice, but this induction was diminished in Nrf2-deficient mice and cells. Overexpression of Nrf2 enhanced DBM-induced HO-1 expression, while overexpression of a dominant-negative fragment of Nrf2 inhibited this induction. DBM treatment resulted in dissociation from Keap1 and nuclear translocation of Nrf2. Moreover, DBM activated Akt/protein kinase B, mitogen-activated protein kinases, and AMP-activated protein kinase and increased intracellular calcium levels. Inhibition of JNK, AMPK, or intracellular calcium signaling significantly suppressed the induction of HO-1 expression by DBM. Finally, DBM treatment significantly inhibited CCl 4 -induced acute liver injury in wild-type but not in Nrf2-deficient mice. Taken together, our results revealed the mechanisms by which DBM activates Nrf2 and induces HO-1 expression, and provide molecular basis for the design and development of DBM and its derivatives for prevention or treatment of liver diseases by targeting Nrf2.
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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毒理学
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
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2022
·Vol. 66
·期 9
·2100892
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IF 6.575
Ying Li,Haiming Hu,Huabing Yang,Aizhen Lin,Hui Xia,Xue Cheng,Mingwang Kong,Hongtao Liu
Scope Vine tea ( Ampelopsis grossedentata ), a traditional Chinese tea, has displayed various biological activities. The authors aim to investigate the effect of Vine Tea ( Ampelopsis grossedentata ) extract (VTE) on carbon tetrachlorid (CCl 4 )induced acute liver injury (ALI) in mice and to explore the underlying role of gut microbiota during the treatment. Methods and Results C57BL/6J mice injected with CCl 4 are treated with VTE for 6 weeks. By using H&E staining, immunofluorescence staining, quantitative real-time (qRT)-PCR, and western blot, it is shown that VTE treatment significantly ameliorates hepatocyte necrosis, alleviates the mRNA levels of toll-like receptor 4 ( Tlr4) , interleukin (Il)-6 , inducible nitric oxide synthase (iNOS) , acetyl-CoA carboxylase 1 (Acc1) , and increases the mRNA levels of peroxisome proliferator-activated receptor gamma (Ppar-γ) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (Hmg-coar) compared to the CCl 4 group. Also, VTE abrogates the decreased mRNA expressions of zonula occludens-1 (Zo-1) , Occludin , and Mucin1 in colon tissues. Using microbial 16S rDNA sequencing, VTE treatment significantly downregulates the abundances of some harmful intestinal bacteria like Helicobacter and Oscillibacter . In contrast, VTE upregulates the contents of several beneficial bacteria, such as Ruminococcaceae_UCG-014 and Eubacterium_fissicatena_group . Further, VTE fails to improve ALI in the mice with gut microbiota depletion using antibiotic treatment. Conclusions The studies suggest that VTE exhibits a protective effect against CCl 4 -induced ALI in mice by alleviating hepatic inflammation, suppressing intestinal epithelial barrier injury, and restoring gut microbiota dysbiosis.
研究领域:
药理学
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微生物学
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肝病学
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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
Drug Design Development and Therapy
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2022
·
IF 4.319
Rong Xu,Siyan Qiu,Jie Zhang,Xiaoli Liu,Ling Zhang,Haizhu Xing,Min You,Man Wang,Yuting Lu,Peng Zhang,Jing Zhu
Background: Silibinin (Sil), a flavonoid lignan-like natural compound derived from milk thistle seeds, has been used to treat hepatic diseases, including early-phase hepatocirrhosis and fatty liver, for many years. However, its poor water solubility limits its gastrointestinal absorption and bioavailability. It clinical use has been limited due to its slow onset of action. Faced with this problem, research on the derivatives of silibinin has been receiving much attention. Purpose: A series of silibinin derivatives with good biosafety and higher hepatoprotective activity were obtained by a safe, efficient and green chemical synthesis method. Patients and methods: First, the carbonyl group in the structure of silibinin was used to obtain silibinin Schiff base derivatives by dehydration condensation with the carboxyl group in the sulfur-containing amino acid. Next, relevant experiments were performed to characterize the structure, physical form and solubility of the derivatives. Then, toxicity tests of the derivatives were performed in LO-2 cells and SD rats to evaluate their biosafety. Finally, the anti-inflammatory and antiapoptotic activities were observed using a carbon tetrachloride (CCl 4 )-induced acute liver injury model in C57BL/6J mice using silibinin as a control. Results: The studies showed that SS and ST behaved as amorphous substances and showed a significant increase in solubility compared to silibinin. These two derivatives showed low toxicity in biosafety tests and higher bioactivity (anti-inflammatory and anti-apoptotic) than silibinin against acute liver injury induced by CCl 4 . Conclusion: Two silibinin derivatives (SS and ST) obtained by the Schiff base reaction improved the solubility of the silibinin parent nucleus in biological media with the help of the hydrophilic and amorphous morphology of the ligand. The low toxicity in vivo and in vitro ensures the biosafety of the derivatives. The hepatoprotective activity (anti-inflammatory and anti-apoptotic) was significantly improved compared to silibinin.
研究领域:
药理学
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肝病学
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药物化学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2023
·
IF 5.2
Yanping Fan,Meilan Xue,Tianhu Shan,Yixian Bai,Huaqi Zhang,Man Liu,Peng Wang,Xi Liang,Hui Liang
Alcoholic liver fibrosis (ALF) is a reversible pathological change in the liver caused by chronic alcohol consumption and is associated with the activation of hepatic stellate cells . Recent findings suggest that niacin can lower triglyceride levels and exert potent antioxidant effects in liver damage. However, the therapeutic effects and molecular mechanisms of niacin in liver fibrosis remain unclear. Therefore, this study aimed to investigate the effects and mechanisms of niacin in ALF using in vivo and in vitro experiments. To establish a murine model of ALF, male C57BL/6N mice were fed a Lieber–DeCarli liquid diet containing 4 % (vol/vol) ethanol and injected with carbon tetrachloride twice weekly (2 mL/kg) for 8 weeks. L-02 and LX2 cells were treated with 400 μM acetaldehyde for 24 h to establish an in vitro ALF model. Serum parameters were examined to investigate the protective effects of niacin against ALF, and network pharmacology was used to identify potential targets and pathways of niacin. Niacin protects against ALF by suppressing the serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase , and alkaline phosphatase . Additionally, niacin treatment ameliorated liver fibrosis by improving the antioxidant system, inhibiting heat shock protein 90 (HSP90) activation, promoting signal transducer and activator of transcription 3 (STAT3) ubiquitination , and suppressing the JAK1/STAT3 signaling pathway . Collectively, this study provides experimental evidence that niacin protects against ALF by downregulating the HSP90/JAK1/STAT3 signaling pathway.
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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细胞生物学
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DOI
高影响因子
Science China-Life Sciences
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2020
·Vol. 64
·期 3
·443-451
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IF 4.611
Luan Dongrui,Zhao Zengteng,Xia Dandan,Zheng Qiuling,Gao Xiaonan,Xu Kehua,Tang Bo
Sodium selenite has alleviating effects on liver fibrosis; however, its therapeutic molecular mechanism remains unclear. Herein, hydrogen selenide, a major metabolite of Na 2 SeO 3 , was tested to uncouple the sulfilimine bond in collagen IV, the biomarker of liver fibrosis. A mouse model of liver fibrosis was constructed via a CCl 4 -induced method, followed by the administration of 0.2 mg kg −1 Na 2 SeO 3 via gavage three times per week for 4 weeks. Changes in H 2 Se, NADPH, and H 2 O 2 levels were monitored in real time by using NIR-H 2 Se, DCI-MQ-NADPH, and H 2 O 2 probes in vivo , respectively. H 2 Se continuously accumulated in the liver throughout the Na 2 SeO 3 treatment period, but the levels of NADPH and H 2 O 2 decreased. The expression of collagen IV was analyzed through Western blot and liquid chromatography-mass spectrometry. Results confirmed that the sulfilimine bond of collagen IV in the fibrotic mouse livers could be broken by H 2 Se with the Na 2 SeO 3 treatment. Therefore, the therapeutic effect of Na 2 SeO 3 on liver fibrosis could be mainly attributed to H 2 Se that uncoupled the sulfilimine bond to induce collagen IV degradation. This study provided a reasonable explanation for the molecular mechanism of the in vivo function of Na 2 SeO 3 and the prevention of liver fibrosis by administering inorganic selenium.
研究领域:
药理学
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生物化学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
·
IF 4.8
Yusi Qin,Ning Wang,Xinlu Yuan,Juanjuan Luo,Junnan Wan,Yiting Zhao,Cunfang Wang,Xiaoning Zhang
This work investigated the protective effects of high Fischer's ratio oligopeptides from goat ( Capra hircus ) whey protein (HFO) against CCl 4 -induced acute liver injury in vivo and their underlying mechanism of action. The results showed that HFO inhibited the rise of serum transaminases (including alanine aminotransferase and aspartate aminotransferase), leading to an increase in the levels of superoxide dismutase and glutathione peroxidase and inhibition of malondialdehyde content, thus ameliorating the CCl 4 -induced liver lesions. Moreover, the levels of cytokines, tumor necrosis factor-α, interleukin-6, and interleukin-1β decreased significantly, indicating that HFO alleviates the CCl 4 -induced inflammatory response by reducing the levels of inflammatory factors in mice. Additionally, Western blot analysis showed that HFO treatment significantly promoted the expression of IkappaB-alpha antibody and inhibited the expression of phosphorylated p65, suggesting that the anti-inflammatory activity is one of the reasons for the hepatoprotective effects of HFO. In conclusion, HFO can potentially be used as a component of functional foods with a particular focus on treating chemical liver injury.
研究领域:
药理学
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毒理学
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免疫学
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生物化学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING SCIENCE
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2026
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IF 5.1
Jiejun Ye,Aqiang Chu,Yidan Zhou,Yan Xu,Shenxiang Zhang
Zinc-chlorine (Zn-Cl 2 ) battery with high discharge voltage, attractive theoretical energy density and inherently low-cost active materials provides affordable and scalable solutions for stationary energy storage. However, the Zn-Cl 2 battery suffers from rapid capacity decay and low coulombic efficiency (CE), primarily due to uncontrolled overflow of Cl 2 gas from the electrolyte. Solvents with high chlorine solubility like CCl 4 combine high chlorine storage capacity, delivering a theoretical volumetric capacity of up to 97 Ah L −1 , but at the cost of suffering from water-oil interfacial instability. In this work, we designed a wettability-tailored membrane electrode with CNT and Pt nanoparticle that stabilizes the two-phase interface and exhibits electrocatalytic activity. Moreover, leveraging the abundant and low-cost chloride in seawater, we replace deionized water with seawater. When using a seawater-based electrolyte, the Zn-Cl 2 flow battery delivers 600 stable cycles (over 220 h) with an average CE of 88.37%. Notably, it maintains 1420 stable cycles (over 544 h) at 0 °C, accompanied by an average CE of 91.94% and a capacity retention of 94.1%. This work establishes a new paradigm for the design of interface regulation strategies in Zn-Cl 2 flow batteries, providing a feasible approach for high-capacity, seawater-based energy storage systems suitable for coastal low-temperature applications.
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DOI
高影响因子
BIOORGANIC CHEMISTRY
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2022
·
IF 5.307
Tingting Ma,Huanli Cheng,Tongxi Li,Yifan Chen,Tianying Cai,Junjie Bai,Ziming Wu,Xianming Xia,Tiancheng Liang,Yichao Du,Wenguang Fu
Background Although liver fibrosis is a key pathologic process in many liver diseases, therapeutic approaches for inhibiting liver fibrosis are still very limited. N-Acetyl- l -tryptophan ( l -NAT) has a hepatoprotective effect via inhibiting the destruction of liver cells, enhancing cell viability and reducing the inflammation. However, the effect of l -NAT on liver fibrosis is not determined. Purpose The present study investigated the effect of l -NAT on liver fibrosis and explored it potential molecular mechanism. Methods To address this concern, this study was carried out via fibrotic mice model induced by CCl 4 and many approaches such as various histological staining methods, western blot assay, etc. Result l -NAT decreased the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in fibrotic mice model induced by carbon tetrachloride (CCl 4 ). Histological staining showed that l -NAT ameliorated liver injury and fibrosis, and reduced the expression of α-smooth muscle actin (α-SMA) and Collagen I protein. l -NAT also attenuated apoptosis by down-regulating the level of pro-apoptotic protein Bax and up-regulating that of anti-apoptotic protein Bcl-2. Moreover, l -NAT inhibited the expressions of TGF-β1/SMAD and matrix metalloproteinase 9 (MMP9) proteins, and reversed the expression of YAP1 protein in CCl 4 -induced liver fibrosis. Conclusion These results clearly demonstrated that l -NAT attenuated CCl 4 -induced liver fibrosis in mice, and this protective mechanism might relate to TGF-β1/SMAD and Hippo/YAP1 signaling pathway. Thus, this study provided data basis for the prevention and treatment of liver fibrosis.
研究领域:
药理学
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肝病学
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分子生物学
✓ 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）