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
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分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2026
·
IF 6.4
Gaoxuan Shao,Chenceng Sun,Chenhao Ye,Ying Liu,Jiashu Pan,Yujing Liu,Lu Lu,Lei Wang,Zemin Lin,Fan Yang,Guang Ji,Hanchen Xu
Luteolin significantly reduces tumor burden and fibrosis in a MASH-HCC mouse model. • Luteolin attenuates hepatic lipid accumulation by inhibiting de novo lipogenesis. • The protective effects of luteolin are mediated via the AMPK/ACC signaling pathway. • Inhibition of AMPK abolishes the lipid-lowering benefits of luteolin in hepatocytes. Aims Metabolic dysfunction-associated steatohepatitis (MASH) is a primary driver of hepatocellular carcinoma (HCC), yet effective therapeutic interventions remain limited. While luteolin is known for its anti-inflammatory properties, its efficacy and underlying mechanism in the MASH-HCC transition are not fully understood. This study investigated the protective effects of luteolin against MASH-HCC and the role of the AMPK/ACC signaling pathway in this process. Materials and methods In vivo , a MASH-HCC mouse model was established using diethylnitrosamine (DEN) combined with a high-fat, high-cholesterol (HFHC) diet. Mice were treated with vehicle or luteolin (50 or 100 mg/kg) for 26 weeks. Progression was monitored via serum alpha-fetoprotein (AFP), histological analysis, and Western blotting. In vitro , HepG2 and Huh-7 cells were challenged with cholesterol and treated with luteolin. The AMPK inhibitor BAY-3827 was employed to verify whether the metabolic benefits of luteolin were pathway-dependent. Key findings Luteolin treatment significantly reduced tumor burden, lowered serum AFP levels, and attenuated hepatic lipid accumulation and fibrosis in MASH-HCC mice. In vitro results mirrored these findings, showing that luteolin reduced cholesterol-induced lipid loading. Mechanistically, luteolin increased the phosphorylation of AMPK and its downstream target, ACC. Furthermore, pharmacological inhibition of AMPK with BAY-3827 abolished the lipid-lowering effects of luteolin in hepatic cells, confirming that its therapeutic benefits are mediated through AMPK activation. Significance Luteolin suppresses the progression of MASH to HCC by activating the AMPK/ACC signaling pathway and subsequently inhibiting de novo lipogenesis. These findings highlight luteolin as a promising potential therapeutic candidate for the prevention and treatment of MASH-related liver cancer. Download: Download high-res image (314KB) Download: Download full-size image
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DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 11
·10033-10046
·
IF 4.171
Xiaodong Ge,Chang'e Wang,Huiling Chen,Tingting Liu,Ligen Chen,Ying Huang,Feng Zeng,Bin Liu
Luteolin (LU) is a flavonoid compound and metformin hydrochloride (MH) is a kind of drug. Studies have shown that both LU and MH have the function of hypoglycemic effect. However, there are few reports indicating that LU cooperated with MH (LU·MH) can relieve lipid metabolism disorders and optimize intestinal flora compositions of high-fat diet mice. In this research, we investigated the effects of LU, MH and LU·MH on lipid metabolism disorders and intestinal flora composition in high-fat diet mice. The study found that compared with high-fat diet (HFD) alone, LU, MH and LU·MH could significantly reduce the lipid metabolism disorder. Furthermore, compared with LU or MH alone, the biochemical indicators of LU·MH were significantly improved and the results of the histopathological section also showed that LU·MH has stronger liver repair ability. It revealed that the potential mechanisms of the LU·MH alleviating lipid metabolism disorders were involved in the simultaneous regulation of SREBP-1c/FAS and SREBP-1c/ACC/Cpt-1. In addition, LU·MH could regulate the intestinal flora compositions. This includes significantly reducing the ratio of Firmicutes and Bacteroidetes(F/B) and at the family level, increasing the relative abundance of Lachnospiraceae, Helicobacteraceae, Marinifilaceae and Peptococcaceae to relieve lipid metabolism disorders. In conclusion, the work found that LU·MH regulates the signal pathway of SREBP-1c/FAS and SREBP-1c/ACC/Cpt-1 simultaneously and decreases the ratio of F/B, as well as increases the relative abundance of certain microbiota to alleviate the lipid metabolism disorders of HFD-fed mice.
研究领域:
药理学
·
营养学
·
微生物学
·
代谢性疾病
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2020
·
IF 2.985
Peng Ma,Rongrong Huang,Jingyao Jiang,Yuan Ding,Tingting Li,Yu Ou
C-phycocyanin (C-PC) is a kind of photosynthetically assisted pigment, which is ubiquitous in cyanobacteria cells. We investigated the effect of C-PC on non-alcoholic fatty liver disease (NAFLD) and its mechanism. Through oil red O staining, TC/TG detection, liver SOD/MDA detection and liver H&E staining, we found that C-PC could significantly reduce the lipid accumulation in the steatosis L02 cells and the liver of non-alcoholic steatohepatitis (NASH) mice, and improve the antioxidant capacity of liver. The results of Western Blotting showed that C-PC upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes ACC and FAS expression levels. Furthermore, C-PC also upregulated the expression of transcription factor PPARα , which was regulated by AMPK, and its target genes CPT1 level. In addition, C-PC could promote AMPK phosphorylation in hepatocytes while increasing the phosphorylation level of ACC in vivo and in vitro. Besides, C-PC could also improve the liver inflammatory infiltration by upregulated the expression of PPARγ and downregulated the expression of CD36 , IL6 and TNFα . These results indicate that C-PC may improve hepatic lipid accumulation and inflammation in the non-alcoholic fatty liver mice by activating AMPK pathway of hepatocytes. The finding provides important help for the research and development of C-PC in the nutraceuticals and therapeutics of NAFLD.
研究领域:
药理学
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肝病学
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营养保健品
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
·
2021
·
IF 4.698
Xixi Song,Minghui Wang,Hongchao Jiao,Jingpeng Zhao,Xiaojuan Wang,Hai Lin
Ghrelin, classically known as a central appetite-stimulating hormone, has recently been recognized to play an important role in peripheral tissue energy metabolism. In chicken, contrary to mammal, ghrelin acts as an anorexia signal, increased by fasting and further elevated after refed. In the present study, the effect of ghrelin on glucose/lipid utilization by peripheral tissues was investigated. Injection of exogenous acyl ghrelin reduced plasma triglyceride and glucose levels of chickens at both fasting and fed status. In the in vitro cultured chicken primary hepatocytes, adipocytes, and myoblasts, ghrelin suppressed glucose uptake , stimulated fatty acids uptake and oxidation , and decreased TG content. In hepatocyte, ghrelin increased the activities of LPL and HL, and upregulated the expression levels of gene ACC , CPT1 , and PPARα . Ghrelin treatment markedly increased the protein level of p-ACC, PPARγ, PGC1α, and CPT1 in hepatocytes, adipocytes and myoblasts. Inhibition of AMPK activity by Compound C had no influence on glucose uptake by hepatocyte, adipocyte, and myoblast, but further amplified the stimulated fatty acid uptake of adipocyte by ghrelin. The present result demonstrates that ghrelin facilitates the uptake and oxidation of fatty acid and cut down the utilization of glucose by the liver, muscle, and adipose tissues. The result suggests that ghrelin functions as a signal of fatty acid oxidation. The study provides a vital framework for understanding the intrinsic role of ghrelin as a crucial factor in the concerted regulation of metabolic substrate of hepatocytes, adipocytes, and myoblasts.
研究领域:
内分泌学
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代谢
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动物生理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Wei Ye,Lei Wang,Ye Fan,Li Ma,Zaohong Chen,Jinmeng Zhang,Rong Zeng,Xiang Liu
Metabolic dysfunction-associated steatotic liver disease (MASLD) progression closely involves ferroptosis. Using high-fat diet-challenged mice and free fatty acid (FFA)-treated HepG2 cells, we demonstrate that oleanolic acid (OA) ameliorates MASLD and suppresses ferroptosis─an effect validated by the ferroptosis activator Erastin. Supported by network pharmacology, mechanistic analyses reveal that OA exerts synergistic efficacy via a dual-axis network. First, molecular docking, cellular thermal shift assay (CETSA), and molecular dynamics (MD) simulations confirm that OA directly binds PTGS2, mitigating lipid peroxidation and inflammatory mediator release. Second, OA activates the AMPK/ACC metabolic signaling pathway, inhibiting ACC through phosphorylation to correct lipid metabolism disorders, and its antiferroptotic effect can be blocked by AMPK inhibitors. This study first elucidates OA’s therapeutic mechanism against MASLD via “metabolic correction + oxidative inhibition,” outlining a novel strategy for targeting hepatic ferroptosis.
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产品关联
DOI
PubMed
高影响因子
AAPS Journal
·
2025
·Vol. 27
·期 1
·1-14
·
IF 3.7
Wan Zhijie,Yuan Ming,Liu Ziao,Cai Yuan,He Hua,Hao Kun
The rising prevalence of metabolic-associated steatotic liver disease emphasizes the need to understand its lipid metabolism. Dapagliflozin may improve hepatic steatosis but could also increase the risk of ketoacidosis by elevating β-hydroxybutyrate (KB) levels. This study investigates dapagliflozin's effects on hepatic lipid metabolism and quantifies KB levels in vivo . Male Sprague–Dawley rats were fed either a normal diet or a high-fat diet (HFD) for 12 weeks. The HFD rats were then divided into four subgroups to receive vehicle, 0.5 mg/kg, 1 mg/kg, and 3 mg/kg of dapagliflozin for four weeks. Free fatty acids (FFA) and KB levels were monitored, while protein and gene expression were analyzed. And a dynamic model of KB was developed for humans based on preclinical data. Dapagliflozin decreased body weight and visceral fat in HFD rats, increasing KB by upregulating CPT1a, HMGCS2, and HMGCL, and downregulating ACC. These changes correlated with reduced liver/fat index, liver pathology score, and oil-red staining area. A pharmacokinetic/pharmacodynamic (PK/PD) model was created from preclinical data to quantify KB levels in rats and validated in humans. Dapagliflozin reduces hepatic steatosis by enhancing fatty acid β-oxidation and ketogenesis and inhibiting fat synthesis. A dynamic model accurately predicts ketone body levels in treated individuals. Graphical
研究领域:
药理学
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代谢性疾病
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肝病学
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营养科学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Biobased Materials and Bioenergy
·
2017
·Vol. 11
·期 4
·282-290
·
IF 0.975
Zhang Panpan,Yuan Bo,Xu Mengke,Cao Xiaoying,Xue Lingwei,Jiang Jihong
This study aims to investigate the plant growth promoting bacteria (PGPB) in the medicinal plant Pinellia ternata (P. ternata), and evaluate the effect of PGPB on the growth and alkaloid content of P. ternata. Bacteria were isolated from P. ternate, and 16S
rRNA gene sequencing of partial isolates was carried out. 23 kinds of representative bacteria were classified into 7 genera: Acinetobacter, Bacillus, Enterobacter, Pseudomonas, Kosakonia, Rhizobium and Stenotrophomonas. The results of the plant growth promotion screening showed that
23 strains could produce different levels of Indole-3-acetic acid (IAA), 1-aminocyclopropane-1-carboxylicacid deaminase (ACC), biofilm and certain enzymes. Potential PGPB were selected to evaluate their abilities to promote the growth of wheat. The results indicated that strain PtB01 (Rhizobium
nepotum) and PtB24 (Bacillus methylotrophicus) significantly promoted the growth of the wheat seedlings. These two strains and their co-culture group were inoculated on P. ternata aseptic seedlings. It was found that these strains increased shoot length by 194%, root length
by 307%, leaf area by 232%, fresh weight by 231%, dry weight by 165%, and the number of fibrous roots by 200%. We also designed a novel organic silica hybrid monolithic column through silicon dioxide modification and tested the influence of two strains on the alkaloid in P. ternata
aseptic seedlings. The result showed that the content of alkaloid was increased by 140% after inoculation PGPB in P. ternata. PGPB from the medicinal plant P. ternata promoted the growth of the host plant and influenced the alkaloid content of P. ternata.
研究领域:
微生物学
·
生药学
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分析化学
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植物科学
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DOI
高影响因子
Food Science and Human Wellness
·
2022
·
IF 8.022
Peng Ma,Rongrong Huang,Yu Ou
Soy glycinin derived octapeptide (SGP8) is a peptide obtained from degradation of the soy glycinin, whose amino acid sequence is IAVPGEVA. To determine the effect of SGP8 on non-alcoholic fatty liver disease (NAFLD), steatosis HepG2 cells were induced by 1 mmol/L free fatty acid (FFA) and C57BL/6J mice were fed with methionine-choline deficient (MCD) diet for 3 weeks to establish NAFLD model. The results of oil red O staining and total cholesterol (TC)/triglyceride (TG) contents showed that SGP8 could significantly reduce the lipid content of steatosis HepG2 cells. In vivo , SGP8 lowered plasma alanine aminotransferase (ALT) and low density lipoprotein (LDL) content, normalized hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) production, and reduced the severity of liver inflammation. The results of Western blotting showed that SGP8 increased expression of Sirtuin-1 (SIRT1) and phosphorylation level of AMP activated protein kinase (AMPK) in hepatocytes. Through activation of SIRT1/AMPK pathway, SGP8 downregulated the expression of sterol regulatory element binding protein 1c (SREBP-1c) and its target genes ACC and FAS expression levels, and increased the phosphorylation level of acetyl CoA carboxylase (ACC). Furthermore, SGP8 also upregulated the expression of transcription factor peroxisome proliferator activated receptor α (PPARα), which was regulated by SIRT1/AMPK pathway, and its target gene CPT1 level. In conclusion, SGP8 might improve NAFLD by activating the SIRT1/AMPK pathway. Our data suggest that SGP8 may act as a novel and potent therapeutic agent against NAFLD.
研究领域:
药理学
·
分子生物学
·
肝病学
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DOI
高影响因子
Chinese Journal of Natural Medicines
·
2025
·
IF 4.9
Qian Chen,Shuying Zhang,Xuanxi Jiang,Jie Liao,Xin Shao,Xin Peng,Zheng Wang,Xiaoyan Lu,Xiaohui Fan
Coptis chinensis Franch. and Panax ginseng C. A. Mey. are traditional herbal medicines with millennia of documented use and broad therapeutic applications, including anti-diabetic properties. However, the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus (T2DM) and its underlying mechanism remain unclear. The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1, exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes. This combination demonstrated significant synergistic effects in improving glucose tolerance, reducing fasting blood glucose (FBG), the weight ratio of epididymal white adipose tissue (eWAT), and the homeostasis model assessment of insulin resistance (HOMA-IR) in leptin receptor-deficient (db/db) mice. Subsequently, a T2DM liver-specific network was constructed based on RNA sequencing (RNA-seq) experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions (PPIs). The network recovery index (NRI) score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components. The research identified that activated adenosine 5’-monophosphate-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling in the liver played a crucial role in the synergistic treatment of T2DM, as verified by western blot experiment in db/db mice. These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice, surpassing the efficacy of individual treatments. The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
研究领域:
药理学
·
植物学
·
分子生物学
·
系统生物学
·
内分泌学
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转录组学
·
民族药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2019
·
IF 4.259
Zhang Jian-Mei,Sun Yin-Shuang,Zhao Li-Qin,Chen Tian-Tian,Fan Mei-Na,Jiao Hong-Chao,Zhao Jing-Peng,Wang Xiao-Juan,Li Fu-Chang,Li Hai-Fang,Lin Hai
The impact of gut microbiota and its metabolites on fat metabolism have been widely reported in human and animals. However, the critical mediators and the signal transductions are not well demonstrated. As ovipara, chicken represents a specific case in lipid metabolism that liver is the main site of lipid synthesis. The aim of this study is to elucidate the linkage of gut microbiota and fat synthesis in broiler chickens. The broilers were subjected to dietary treatments of combined probiotics (Animal bifidobacterium: 4 × 108 cfu/kg; Lactobacillus plantarum: 2 × 108 cfu/kg; Enterococcus faecalis: 2 × 108 cfu/kg; Clostridium butyrate: 2 × 108 cfu/kg, PB) and guar gum (1 g/kg, GG), respectively. Results showed that dietary supplementation of PB and GG changed the cecal microbiota diversity, altered short chain fatty acids (SCFAs) contents, and suppressed lipogenesis. In intestinal epithelial cells (IECs), SCFAs (acetate, propionate, and butyrate) up-regulated the expression of glucagon-like peptide-1 (GLP-1) via mitogen-activated protein kinase (MAPK) pathways, mainly via the phospho - extracellular regulated protein kinase (ERK) and phospho-p38 mitogen activated protein kinase (p38 MAPK) pathways. GLP-1 suppressed lipid accumulation in primary hepatocytes with the involvement of (AMP)-activated protein kinase/Acetyl CoA carboxylase (AMPK/ACC) signaling. In conclusion, the result suggests that SCFAs-induced GLP-1 secretion via MAPK pathway, which links the regulation of gut microbiota on hepatic lipogenesis in chickens.
研究领域:
动物营养学
·
微生物学
·
分子生物学
·
生理学
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产品关联
DOI
PubMed
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-PLANT
·
2023
·Vol. 59
·期 1
·61-73
·
IF 2.6
Li Xiaofang,Fang Pingping,Li Mingxuan,Xu Pei
Structural analogs of enzyme substrates involved in plant hormone biosynthesis can either inhibit or enhance hormone-related responses depending on their specific chemical characteristics. Ethylene is an important gaseous phytohormone regulating a myriad of physiological and developmental processes. The substrate of the ethylene biosynthesis key enzyme ACC oxidase (ACO), 1-aminocyclopropane-1-carboxylate acid (ACC), is the direct precursor of ethylene. Previous studies have identified a series of ACC analogs as ethylene antagonists competitively binding with ACO. Here, this study identified methyl 1-aminocyclopropanecarboxylate (methyl-ACC), a structural analog of ACC, as an agonist of ethylene response in plants. Methyl-ACC triggered enhanced ethylene-related responses in plants similar to the effects of ACC, such as restrained root elongation, increased root hair number, promoted dark-induced leaf senescence, and accelerated ripening of postharvest tomato fruit. A higher amount of ethylene release was detected from the tomato leaves treated with methyl-ACC than from the mock control. These bioactivities of methyl-ACC render it a potential plant growth regulator (PGR) for the agricultural and postharvest industries. RT-qPCR revealed a generally upregulated expression of the ethylene biosynthesis genes in detached tomato leaves under methyl-ACC treatment. In vivo and in vitro enzymatic activity analyses showed that methyl-ACC had no obvious effect on the total ACO activity in detached tomato leaves nor on the activity of recombinant SlACO1, the predominantly expressed ACO family member in this tissue. This study offers a promising new PGR and adds to the current knowledge on the structure–function-regulation relationship of compounds associated with ethylene biosynthesis. The mechanism by which methyl-ACC exerts its function is discussed.
研究领域:
植物生理学
·
植物生物化学
·
农业科学
·
分子生物学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）