Nutrients
·
2016
·Vol. 8
·期 12
·799
·
IF 3.759
Shu-Fang Xia,Guo-Wei Le,Peng Wang,Yu-Yu Qiu,Yu-Yu Jiang,Xue Tang
Myricetin is an effective antioxidant in the treatment of obesity and obesity-related metabolic disorders. The objective of this study was to explore the regressive effect of myricetin on pre-existing hepatic steatosis induced by high-fat diet (HFD). C57BL/6 mice were fed either a standard diet or a HFD for 12 weeks and then half of the mice were treated with myricetin (0.12% in the diet,w/w) while on their respective diets for further 12 weeks. Myricetin treatment significantly alleviated HFD-induced steatosis, decreased hepatic lipid accumulation and thiobarbituric acid reactive substance (TBARS) levels, and increased antioxidative enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Microarray analysis of hepatic gene expression profiles showed that myricetin significantly altered the expression profiles of 177 genes which were involved in 12 biological pathways, including the peroxisome proliferator activated receptor (PPAR) signaling pathway and peroxisome. Further research indicated that myricetin elevated hepatic nuclear Nrf2 translocation, increased the protein expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), reduced the protein expression of PPARγ, and normalized the expressions of genes that were involved in peroxisome and the PPAR signaling pathway. Our data indicated that myricetin might represent an effective therapeutic agent to treat HFD-induced hepatic steatosis via activating the Nrf2 pathway and the PPAR signaling pathway.Keywords:myricetin;hepatic steatosis;Nrf2;PPARγ;oxidative stress
研究领域:
药理学
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分子生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
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2020
·
IF 2.365
Wen Yuan,Meixing Yan,Yitong Wang,Xia Liu,Yanling Gong
This study was aimed at evaluating the potential of peach gum (PG) and gelatin in the microencapsulation of eugenol and the intervention of eugenol microcapsules on hepatic steatosis in vitro. Response surface method (RSM) was used to optimize the encapsulation conditions of eugenol microcapsules. The microcapsules were characterized by scanning electron microscopy (SEM), dynamic Light Scattering (DLS), Fourier transform infrared spectroscopy (FT-IR) and release behavior in vitro was determined. The effect of eugenol microcapsules on free fatty acids (FFA) treated hepatocellular cells (HepG2) cells was evaluated by oil red O staining and intracellular total cholesterol (TC) and triglyceride (TG) determination. The results showed that the optimal encapsulation conditions were as follows: the PG-gelatin ratio was 1.6:1.4, the core-wall ratio was 1.6:1.4, the pH was 4 and the emulsification speed was 9000 r/min. The optimized microcapsules were smooth spherical with a size of about 3.09 ± 0.58 μm and the encapsulation was confirmed by FT-IR. In vitro release behavior showed that eugenol microcapsules could be released stably in a neutral environment for 72 h. Oil red O staining showed that 50 and 100 μM eugenol microcapsules could significantly inhibit the lipid accumulation and reduce the TC and TG in steatotic HepG2 cells induced by FFA. Therefore, PG and gelatin can be used as excellent carriers for the microencapsulation of volatile compounds in the field of biomedical industry, and eugenol microcapsules is a promising preparation for the treatment of nonalcoholic fatty liver disease (NAFLD).
研究领域:
药理学
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生物医学工程
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肝脏疾病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 45
·期 11
·e13976
·
IF 2.72
Longkai Shi,Emad Karrar,Xingguo Wang
Non-alcoholic fatty liver disease (NAFLD) is a chronic hepatopathy caused by disordered lipid metabolism in the liver. Sesamol, a phenolic compound derived from sesame oil, has been shown to inhibit obesity, hyperlipidemia, and atherosclerosis in previous investigations. However, the preventive effect of sesamol against hepatic steatosis and oxidative stress in NAFLD has not been well-studied. In this work, sesamol was observed to alleviate lipid accumulation and oxidative stress in high oleic acid (300 μM)/cholesterol (25 μM) induced HepG2 cells, thus indicating that sesamol was involved in regulating hepatic lipid metabolism and oxidative injury. Mechanism studies found that the activated peroxisome proliferator-activated receptors (PPAR) signaling pathway by sesamol intervention up-regulated gene and protein expressions related to fatty acid oxidation and cholesterol efflux and catabolism, thus accelerating lipid consumption and reducing intracellular lipid accumulation in the process of NAFLD. These data suggested that sesamol can effectively ameliorate hepatic steatosis and sesamol riched sesamol oil may be a potential agent for finding therapeutic strategies to treat the NAFLD. Practical applications Sesamol and sesamol-rich sesame oil have received much attention due to their performance on hepatic lipid regulation. The results of this study indicate that sesamol treatment could ameliorate hepatic steatosis by inhibiting lipid accumulation and oxidative stress, thus demonstrating that sesamol and sesame oil can be used for functional foods and nutraceutical applications in the future. In addition, the present work provides knowledge of the effects of sesamol on NAFLD and involved mechanisms, and further supplies nutritional guidelines for sesame oil consumption.
研究领域:
营养学
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分子生物学
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医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Weiting Hu,Wenyu Gong,Fan Yang,Rui Cheng,Gerong Zhang,Lu Gan,Yikun Zhu,Weiwei Qin,Ying Gao,Xing Li,Jing Liu
Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and is a promising therapeutic option for type 2 diabetes mellitus (T2DM). Nevertheless, its effect and underlying mechanism on hepatic steatosis remain ambiguous. Herein, we explored the impact of tirzepatide on improving hepatic steatosis in diabetic mice, with a particular focus on the gut microbiota and bile acids (BAs) using animal models. The tirzepatide effectively reduced body weight, improved insulin resistance, decreased serum and hepatic lipid levels, and mitigated liver injury. Compared to semaglutide, tirzepatide exhibited superior efficacy in reducing hepatic lipid accumulation. 16S rRNA gene sequencing and targeted metabolomics of BAs revealed that tirzepatide ameliorated gut microbiota dysbiosis and BAs metabolism in diabetic mice. Notably, tirzepatide observably increased the abundance of beneficial genera such as Akkermansia , elevated the ratio of farnesoid X receptor (FXR) antagonists (glycoursodeoxycholic acid: GUDCA, β-muricholic acid: β-MCA, hyodeoxycholic acid: HDCA, ursodeoxycholic acid: UDCA) to natural agonists (cholic acid: CA, lithocholic acid: LCA, chenodeoxycholic acid: CDCA, glycocholic acid: GCA, taurodeoxycholic acid: TDCA), and reduced FXR expression in intestinal tissues. In conclusion, tirzepatide attenuated hepatic steatosis in diabetic mice and regulated the gut microbiota and BAs metabolism, which may help to provide a novel therapeutic approach and therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD).
研究领域:
药理学
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代谢组学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2020
·Vol. 64
·期 14
·2000105
·
IF 5.309
Yanan Chen,Hao Zhang,Yueping Chen,Yuying Zhang,Mingming Shen,Peilu Jia,Shuli Ji,Tian Wang
Scope Endoplasmic reticulum (ER) stress is widely recognized as a critical factor linked to lipid metabolic disorders in nonalcoholic fatty liver disease. However, its pathogenesis remains elusive, and therapeutic options are limited. This study investigates the potential of resveratrol (RSV) to alleviate hepatic steatosis and injury in a tunicamycin (TM)-induced murine ER stress model and provides detailed evidence. Methods and Results Male C57BL/6J mice were orally administered either RSV or vehicle for 2 weeks before the TM challenge. Results indicated that TM induced ER morphological damage and severe unfolded protein reaction (UPR), accompanied by increases in lipid accumulation, oxidative damage, and inflammatory response. Administering RSV decreased the expression of ER stress markers, partially normalized the active levels of UPR sensors, and facilitated sirtuin 1 activity in the liver under ER stress. Notably, the TM-induced hepatic steatosis was also alleviated by RSV, possibly by regulating the expression pattern of genes involving lipid oxidation and delivery. Consistently, RSV attenuated the TM-induced increases in lipid peroxidation, hepatocyte apoptosis, and the overactivation of inflammatory signals. Conclusion RSV may have an auxiliary therapeutic potential to prevent the development of steatosis and its progression to steatohepatitis in the liver by alleviating severe ER stress.
研究领域:
医学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nutrients
·
2023
·Vol. 15
·期 14
·3200
·
IF 5.9
Wen Liu,Min Zhu,Meng Gong,Wen Zheng,Xin Zeng,Qing Zheng,Xiaoyu Li,Fudong Fu,Yingyi Chen,Jingqiu Cheng,Zhiyong Rao,Yanrong Lu,Younan Chen
Obesity is a recognized epidemic worldwide, and the accumulation of excess free saturated fatty acids (SFAs) in cells induces cellular lipotoxic damage and increases the risk of a wide spectrum of metabolic diseases including type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have been reported to combat SFA-induced cellular damage. However, the comparative studies of the two types of unsaturated fatty acids (UFAs) are still limited. We investigated the effects of different MUFAs and PUFAs in the human hepatocyte line L-02 cells in vitro, and in high-fat-diet (HFD)-induced obese C57BL/6 mice in vivo. The results of the in vitro study showed that SFAs induced significant cellular lipotoxic damage, but the combination of MUFAs/PUFAs with SFAs significantly improved the impaired cell viability. Particularly, oleic acid (OA) was superior to eicosapentaenoic acid (EPA), Docosahexaenoic acid (DHA), and arachidonic acid (AA) in terms of its anti-apoptotic effect and inhibition of endoplasmic reticulum (ER) stress. In vivo, both olive-oil-enriched (HFD + OO) and fish-oil-enriched high-fat diets (HFD + FO) reduced hepatic steatosis and improved insulin sensitivity in obese mice. However, FO induced an abnormal increase in serum aspartate aminotransferase (AST) and an increase in the oxidative stress indicator Malondialdehyde (MDA). Liver-targeted lipidomic analysis showed that liver lipid metabolites under the two types of UFA dietary interventions differed from the HFD group, modulating the abundance of some lipid metabolites such as triglycerides (TGs) and glycerophospholipids. Furthermore, the FO diet significantly increased the abundance of the associated FA 20:5 long-chain lipid metabolites, whereas the OO diet regulated the unsaturation of all fatty acids in general and increased the abundance of FA 18:1 in the overall lipid metabolites, especially TGs, which may primarily contribute to the FO, and OO drove protection in NAFLD.Keywords:obesity;insulin resistance;hepatic steatosis;unsaturated fatty acids;targeted lipidomics
研究领域:
营养学
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代谢学
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脂质生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxins
·
2021
·Vol. 13
·期 11
·802
·
IF 4.546
Qian-Wen Zheng,Xu-Fen Ding,Hui-Jun Cao,Qian-Zhi Ni,Bing Zhu,Ning Ma,Feng-Kun Zhang,Yi-Kang Wang,Sheng Xu,Tian-Wei Chen,Ji Xia,Xiao-Song Qiu,Dian-Zhen Yu,Dong Xie,Jing-Jing Li
Ochratoxin A(OTA) is considered to be one of the most important contaminants of food and feed worldwide. The liver is one of key target organs for OTA to exert its toxic effects. Due to current lifestyle and diet, nonalcoholic fatty liver disease (NAFLD) has been the most common liver disease. To examine the potential effect of OTA on hepatic lipid metabolism and NAFLD, C57BL/6 male mice received 1 mg/kg OTA by gavage daily. Compared with controls, OTA increased lipid deposition and TG accumulation in mouse livers. In vitro OTA treatment also promoted lipid droplets accumulation in primary hepatocytes and HepG2 cells. Mechanistically, OTA prevented PPARγ degradation by reducing the interaction between PPARγ and its E3 ligase SIAH2, which led to activation of PPARγ signaling pathway. Furthermore, downregulation or inhibition of CD36, a known of PPARγ, alleviated OTA-induced lipid droplets deposition and TG accumulation. Therefore, OTA induces hepatic steatosis via PPARγ-CD36 axis, suggesting that OTA has an impact on liver lipid metabolism and may contribute to the development of metabolic diseases.Keywords:fatty liver disease;lipid metabolism;OTA;PPARKey Contribution:The in vitro and in vivo study reveal that OTA induces hepatic steatosis via PPARγ-CD36 axis. OTA prevents PPARγ from ubiquitination-mediated degradation by reducing the expression of the E3 ligase SIAH2 and SIAH2-PPARγ interaction.
研究领域:
毒理学
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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
PLoS One
·
2024
·Vol. 19
·期 3
·e0301133
·
IF 2.9
Suye Ran,Lingyu Song,Hong Yang,Jiangnan Yu,Yunhuan Zhen,Qi Liu
Purpose
Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), which has a high risk of cirrhosis, liver failure, and hepatocellular carcinoma. Piperine (Pip) is an extract of plants with powerful anti-inflammatory effects, however, the function of Pip in NASH remains elusive. Here, we aim to explore the role of Pip in NASH and to find the possible mechanisms.
Methods
Methionine and choline-deficient (MCD) diets were used to induce steatohepatitis, methionine- and choline-sufficient (MCS) diets were used as the control. After Pip treatment, H&E staining, Oil Red O staining, hepatic triglyceride (TG) content and F4/80 expression were performed to analysis liver steatosis and inflammation; Masson’s staining, COL1A1 and α-SMA were detected liver fibrosis. Lipopolysaccharide (LPS) -treated AML12 cells were used to as the cell model to induce pyroptosis. Then, pyroptosis-related proteins, IL-1β and LDH release were detected in vivo and in vitro . Finally, NF-κB inhibitor, BAY11-7082, was used to further demonstrate the mechanism of Pip in NASH.
Results
The study found that Pip alleviated liver steatosis, inflammation, hepatocyte injury, and fibrosis in mice fed with MCD diets. Moreover, the pyroptosis markers (NLRP3, ASC, caspase-1 p20, and GSDMD), IL-1β and LDH release were decreased by Pip treatment. NF-κB activation was suppressed by Pip treatment and pyroptosis-related proteins were down regulated by BAY11-7082.
Conclusion
Pip ameliorates NASH progression, and the therapeutical effect was associated with inhibition of hepatocyte pyroptosis induced by NF-κB.
研究领域:
药理学
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肝病学
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免疫学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY
·
2024
·Vol. 34
·期 4
·e23123
·
IF 3
Yuqiu Fu,Deyue Zang,Baiyou Lin,Qiming He,Yujie Xie,Baoliang Zhang,Yao Liu,Yi Jin,Yonghong He,Tian Guan
Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disorder affecting approximately 25.2% of the global population, posing risks of liver fibrosis, cancer, and metabolic disturbances. Despite its increasing prevalence, many facets of NAFLD's pathogenesis remain elusive, and there are currently no approved therapeutic drugs, underscoring the critical need for a comprehensive understanding of its pathophysiology to enable early diagnosis and intervention. Experimental animal studies play a pivotal role in elucidating the mechanisms underlying NAFLD and in the exploration of novel pharmacotherapies. Despite the widespread integration of deep learning techniques in human histopathology, their application to scrutinize histological features in animal models warrants exploration. This study presents a pioneering NAFLD assessment system leveraging IFNet and ResNet34 architectures. This automated system adeptly identifies inflammatory cell foci and hepatic steatosis in histopathology sections of rat livers. Remarkably, our approach achieved an impressive 95.6% accuracy in the assessment of hepatic steatosis and 77.7% in the evaluation of inflammation cell foci. By introducing a novel histopathology scoring system, our methodology mitigated subjective variations inherent in traditional pathologist evaluations, concurrently streamlining time and labor costs. This system ensured a standardized and precise assessment of rat liver histology in NAFLD and represented a significant stride toward enhancing the efficiency and objectivity of experimental outcomes.
研究领域:
病理学
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医学影像分析
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实验动物模型
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肝脏疾病研究
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Endocrinology
·
2023
·
IF 5.2
Tingwan Du,Lian Xiang,Jingjing Zhang,Chunmei Yang,Wenxin Zhao,Jialu Li,Yong Zhou,Ling Ma
Introduction The study aimed to explore the association of serum 25(OH)D 3 and hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) patients and to determine whether the effect of vitamin D (VD) is mediated by activation of the peroxisome proliferator-activated receptor α (PPARα) pathway. Methods The study contained a case-control study, in vivo and in vitro experiments. A case-control study was conducted to compare serum parameters between NAFLD patients and controls and to evaluate the association of 25(OH)D 3 and NAFLD. In vivo study, male Wistar rats were randomly divided into control and model groups, fed a standard chow diet and a high-fat diet (HFD), respectively, for 7 weeks to generate an NAFLD model. Then, the rats were treated with VD and a PPARα antagonist (MK886) for 7 weeks. Tissue and serum were collected and assessed by biochemical assays, morphological analysis, histological analysis, and western blot analysis. In vitro , HepG2 cells were incubated with oleic acid (OA) to induce steatosis, which was evaluated by staining. HepG2 cells were pretreated with MK886 followed by calcitriol treatment, and differences in lipid metabolism-related proteins were detected by western blot. Results NAFLD patients were characterized by impaired liver function, dyslipidemia, and insulin resistance. Serum 25(OH)D 3 was negatively associated with alanine aminotransferase (ALT) in NAFLD. VD deficiency was a risk factor for patients with no advanced fibrosis. Adequate VD status (25(OH)D 3 >20 ng/mL) had a protective effect in patients after adjustment for confounding variables. NAFLD rats showed hyperlipidemia with severe hepatic steatosis, systematic inflammation, and lower serum 25(OH)D 3 . VD treatment ameliorated hepatic steatosis both in NAFLD rats and OA-induced HepG2 cells. Further, MK886 inhibited the anti-steatosis effect of VD. Conclusion The study revealed that an adequate VD level may act as a protective factor in NAFLD and that VD may alleviate hepatic steatosis via the PPARα signaling pathway.
研究领域:
肝病学
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内分泌学
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营养学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIVER INTERNATIONAL
·
2025
·Vol. 45
·期 4
·e70053
·
IF 5.2
Peng Ma,Hao Ou,Junze Cai,Yuanli Zhang,Yu Ou
Background & Aims G protein-coupled receptors (GPCRs) are important potential drug targets for the treatment of metabolic disorders. The D2 dopamine receptor (DRD2), a GPCR receptor, is a member of the dopamine receptor family. However, the role of DRD2 in regulating lipid metabolism, especially in hepatic steatosis, is unclear. Methods Eight-week male mice were fed HFHC/MCD to induce the MASH model. AAV2/8 containing the TBG promoter was used to knock down and overexpress DRD2 in mouse liver. Co-immunoprecipitation, Western lotting, immunofluorescence, and immunohistochemistry were used to investigate the mechanisms and screen DRD2 antagonists. Results The study found that activation of PKC leads to the elevation and internalisation of DRD2 in a high-fat environment. Knockdown of DRD2 in mouse liver can effectively interfere with the progression of MASH, while overexpression of DRD2 significantly aggravates the process of MASH. The study on the mechanism of DRD2 regulating lipid metabolism found that the internalisation of DRD2 could lead to dephosphorylation of pAKT (T308) by binding to β-arrestin2 and pAKT, thereby inducing ubiquitin-dependent degradation of AMPK and exacerbating steatosis. L-741626, a DRD2 antagonist, was found to interfere with the internalisation of DRD2 in a high-fat environment. It has been shown that L-741626 can treat MASH by regulating the AKT-AMPK signalling axis in vitro and in vivo. Conclusions In conclusion, this study demonstrated that internalisation of DRD2 in a high-fat environment aggravated MASH progression through the AKT-AMPK signalling axis. Furthermore, L-741626, as a DRD2 antagonist, has the potential to treat MASH.
研究领域:
代谢性疾病
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肝病学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Herbal Medicines
·
2023
·
IF 3.8
Mingning Ding,Fei Zhou,Yijie Li,Chuanyang Liu,Yiqing Gu,Jianzhi Wu,Guifang Fan,Yajing Li,Xiaojiaoyang Li
Objective Cassiae Semen (CS, Juemingzi in Chinese) has been used for thousands of years in ancient Chinese history for relieving constipation, improving liver function as well as preventing myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease (NAFLD). Methods High-performance liquid chromatography (HPLC) was used to identify the major components of CS water extract. Mice were fed with a high-fat and sugar-water (HFSW) diet to induce hepatic steatosis and then treated with CS. The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining. Additionally, the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid (OAPA)-treated HepG2 cells were measured. The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism. Results Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C, emodin and rhein were simultaneously identified in CS extract. CS not only improved the diet-induced hepatic steatosis in vivo , as indicated by decreased number and size of lipid droplets, hepatic and serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes. These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase (FASN) and the activation of autophagy-related signaling, including AMP-activated protein kinase (AMPK), light chain 3-II (LC3-II)/ LC3-1 and autophagy-related gene5 (ATG5). Conclusion Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy, which might become a promising therapeutic strategy for relieving NAFLD.
研究领域:
药理学
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肝病学
·
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）