JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Jing Zhou,Ji Zhang,Jiayi Li,Yiqiu Guan,Ting Shen,Fu Li,Xueqin Li,Xiaojun Yang,Weicheng Hu
Ginsenoside F2 (GF2) is a protopanaxdiol saponin from Panax ginseng leaves and possesses many potential pharmacological properties. GF2 may prevent obesity by directly binding to the peroxisome proliferator-activated receptor-γ (PPARγ) and inhibiting adipocyte differentiation. However, the mechanism by which GF2 alleviates obesity is unknown. We therefore explored the anti-adipogenesis and anti-obesity effects of GF2 in vitro and in vivo. GF2 inhibited differentiation and reduced the triglyceride (TG) content of 3T3-L1 preadipocytes in the early stage of adipogenesis. Administration of GF2 (50 and 100 mg/kg) to obese mice for 4 weeks reduced the body weight gain, weight of adipose tissues, adipocyte size, and total cholesterol, TG, and AST levels in serum. RNA sequencing and real-time quantitative PCR indicated that GF2 decreased the expression levels of adipokines, including PPARγ, fatty acid synthase, and adiponectin. KEGG enrichment and western blot analyses demonstrated that GF2 accelerated the phosphorylation of AMPK and ACC in vitro and in vivo. Moreover, GF2 promoted the biosynthesis of mitochondria in 3T3-L1 adipocytes and increased the expression of antioxidant enzymes such as SOD and GSH-Px in the liver of obese mice. Therefore, GF2 suppressed adipogenesis and obesity by regulating the expression of adipokines and activating the AMPK pathway. Hence, the findings suggest that GF2 may have potential therapeutic implications to treat obesity.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2020
·
IF 3.343
Gang Wang,Yang Yu,Yu-Zhu Wang,Pei-Hao Yin,Ke Xu,Heng Zhang
In this study, isoliquiritigenin (ISL) incorporated nanoliposomes were prepared and their effects on colorectal cancer (CRC) cell lines were investigated. Herein, we sought to explore the anti-cancer mechanisms of ISL loaded nanoliposomes (ISL-NLs) on AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathways mediated glycolysis. Also, the key targets such as caveolin 1 (CAV1), glucose transporters and Akt/mTOR that promote glycolysis, and are activated via the induction of α-enolase (ENO1), fructose bisphosphate aldolase A (ALDOA) and monocarboxylate transporter 4 (MCT4) expressions were also investigated. It was shown that ISL-NLs significantly suppressed the proliferation and glucose uptake of CRC cell by potentially regulating the glycolysis and lactate targets as well as pathways that formed the basis of the anti-CRC effects of ISL-NLs. The mechanism underlying this effect was further validated via the regulation of some key targets such as ENO1, ALDOA, lactate dehydrogenase A (LDHA) and MCT4 in glycolysis coupled with cellular myelocytomatosis oncogene (c-myc), hypoxia-inducible factor 1-alpha (HIF-1α) in protein kinase B/mTOR (Akt/mTOR) pathways. Moreover, the AMPK proteins were identified to be up-regulated while the lactic acid production was suppressed by ISL-NLs in the CRC cells, indicating that ISL-NLs had an inhibitory effect on AMPK mediated glycolysis and lactate production. Altogether, these results have provided insights into the mechanism underlying the key role that liposomal ISL played in the multiple inhibition of AMPK and Akt/mTOR mediated glycolysis and lactate generation, which may be regulated as the alternative metabolic pathways of CRC as well as serve as adjuvant therapy for the disease.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2020
·
IF 2.971
Yucheng Li,Baoying Wang,Jiduo Shen,Ming Bai,Erping Xu
Context Berberine is an alkaloid that possesses various pharmacologic effects.Objective To explore the mechanism of berberine to improve insulin sensitivity in fructose-fed mice.Materials and methods Sixty male ICR mice were randomly divided into 6 groups (10 mice in each group): control, fructose, pioglitazone (10 mg/kg) and berberine (50, 100, and 200 mg/kg). Except for the control group, the mice received 20% fructose drinking for 10 weeks. Pioglitazone and berberine were orally administered once daily during the last 4 weeks. The insulin sensitivity was evaluated using an oral glucose tolerance test (OGTT). The serum levels of fasting glucose and insulin, blood lipids, and hormones were determined. The hepatic AMP and ATP contents were detected using high performance liquid chromatography (HPLC) analysis, and the protein expression was examined by immunoblotting.Results Berberine significantly reversed the insulin resistance induced by fructose, including lowering fasting insulin levels (from 113.9 to 67.4) and area under the curve (AUC) during OGTT (from 1310 to 1073), decreasing serum leptin (from 0.28 to 0.13) and increasing serum adiponectin levels (from 1.50 to 2.80). Moreover, berberine enhanced the phosphorylation levels of protein kinase B (PKB/AKT; 2.27-fold) and glycogen synthase kinase-3β (GSK3β; 2.56-fold), and increased hepatic glycogen content (from 0.19 to 1.65). Furthermore, berberine upregulated the protein expression of peroxisome proliferator activated receptor gamma coactivator 1α (PGC1α; 2.61-fold), phospho-AMP-activated protein kinase (p-AMPK; 1.35-fold) and phospho-liver kinase B1 (p-LKB1; 1.41-fold), whereas it decreased the AMP/ATP ratio (from 4.25 to 1.82).Conclusion The present study demonstrated the protective effects of berberine against insulin resistance induced by fructose. Our findings may provide an experimental basis for the application of berberine in the treatment of insulin resistance.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2019
·
IF 4.18
Dan Chen,Ya-Xian Wu,Yu-bao Qiu,Bin-bin Wan,Gang Liu,Jun-liang Chen,Mu-dan Lu,Qing-feng Pang
Background Hypoxia is commonly existed in tumors and lead to cancer cell chemo/radio-resistance. It is well-recognized that tumor hypoxia is a major challenge for the treatment of various solid tumors . Hyperoside (quercetin-3-O-galactoside, Hy) possesses antioxidant effects and has been reported to protect against hypoxia/reoxygenation induced injury in cardiomyocytes . Therefore, Hy may be attractive compound applicable to hypoxia-related diseases . Purpose This study was designed to determine the role of Hy in hypoxia-induced proliferation of non-small cell lung cancer cells and the underlying mechanism. Study Design and Methods A549, a human non-small cell lung cancer (NSCLC) cell line, was used in the present study. 1% O 2 was used to mimic the in vivo hypoxic condition of NSCLC. The potential mechanisms of Hy on hypoxia-induced A549 survival and proliferation, as well as the involvement of AMPK/HO-1 pathway were studied via CCK-8 assay, EdU staining, flow cytometry, qRT-PCR and western blot . Results We showed that pretreatment with Hy suppressed hypoxia-induced A549 survival and proliferation in dose-dependent manner. In terms of mechanism, hypoxia-treated A549 showed the lower AMPK phosphorylation and the reduced HO-1 expression, which were reversed by Hy pretreatment. Both AMPK inhibitor (Compound C) and HO-1 activity inhibitor (Zinc protoporphyrin IX) abolished Hy-evoked A549 cell death under hypoxia stimuli. Of note, Ferrous iron contributed to Hy-induced A549 cell death under hypoxia, while Hy had no effect on lipid peroxidation under hypoxia. Conclusion Taken together, our results highlighted the beneficial role of Hy against hypoxia-induced A549 survival and proliferation through ferrous accumulation via AMPK/HO-1 axis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2022
·Vol. 396
·期 4
·683-692
·
IF 3.195
Huang Hui,Xue Jie,Xie Tao,Xie Mei-Lin
Osthole is a natural coumarin substance that has an inhibitory effect on hepatic cancer, but its radiosensitization effect on hepatoma cells has not been reported. This study aimed to investigate the effect of osthole. Human HCC-LM3 and SK-Hep-1 hepatoma cells were used and treated with or without osthole, irradiation, or their combination; the cell survival, migration, colony formation, DNA damage repair, intracellular lactic acid content, and glycolysis-related glycogen synthase kinase-3β (GSK-3β), p-GSK-3β, AMP-activated protein kinase (AMPK), p-AMPK, mammalian target of rapamycin (mTOR), p-mTOR, glucose transporter-1 (GLUT-1), GLUT-3, and pyruvate kinase isozyme type M2 (PKM2) protein expressions were determined. Compared with the irradiation group, the osthole plus irradiation group could further decrease the survival rate, migration, colony formation, and DNA damage repair of both hepatoma cells, indicating a synergistic effect of the combination treatment. Moreover, the combination of osthole and irradiation could decrease the content of intracellular lactic acid, ratios of intracellular p-GSK-3β/GSK-3β and p-mTOR/mTOR proteins, and expressions of intracellular GLUT-1/3 and PKM2 proteins, and increase the ratio of intracellular p-AMPK/AMPK proteins. Osthole can increase the radiosensitivity of hepatoma cells, and its radiosensitization mechanisms may be related to glycolytic inhibition by attenuating the GSK-3β/AMPK/mTOR pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2025
·
IF 4
Hanju Fan,Meng Yan,Yongshuai Jing,Ziyan Li,Yaqian He,Zhiwei Li,Junna Song,Lanfang Wu
Crataegus pinnatifida is the dried fruit of Crataegus pinnatifida . Crataegus pinnatifida polysaccharides (CPPs) eluted with water as the mobile phase (CPPs-H-1) is one of the important active components. CPPs-H-1 has anti-oxidation and blood lipid regulation activities in vitro. Therefore, we investigated the effects of CPPs-H-1 on nonalcoholic fatty liver disease (NAFLD) in C57/BL6J mice. As a result, CPPs-H-1 inhibited the rapid growth of body weight and alleviated the liver injury caused by high-fat diets, significantly reducing the liver index and blood lipid levels in the model group, inhibiting the production of inflammation and cytokines, and inhibiting oxidative stress. CPPs-H-1 also enhanced intestinal barrier function. At the phylum level, CPPs-H-1 reduced the ratio of Firmicutes to Bacteroides (F/B) and regulated the content of short-chain fatty acids (SCFAs). The CPPs-H-1 may regulate intestinal flora composition, and improve intestinal barrier function, ultimately delaying the progression of NAFLD in mice. Also, CPPs-H-1 improved NAFLD progression by enhancing the Amp-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor α (PPARα) signaling pathway to enhance fatty acid oxidation. All these results confirm that CPPs-H-1 plays a multi-pathway and multi-target role in the improvement of NAFLD.
研究领域:
营养学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Linghui Song,Panpan Chen,Baimei Shi,Aihua Qu,Chuanlai Xu,Hua Kuang,Maozhong Sun
Autophagy is a key regulator in a diverse range of human diseases. Here, chiral copper sulfide (CuS) nanoparticles (NPs) modified with penicillamine are fabricated, which exhibited a circular dichroism (CD) spectrum between 300 and 1000 nm and a fluorescence peak at 680 nm. The experimental data showed that D -CuS NPs exhibited chirality-dependent autophagy induction, outperforming L -CuS NPs, and targeted breast cancer cells with 228.4 times higher affinity for CD81 receptor. The mechanism is revealed that chiral NPs specifically bound to CD81 receptor to open mechanosensitive calcium channels and motivated the calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMPK pathway, which enhanced Atg1/Unc-51-like autophagy activating kinase 1 (ULK1) activity to promote autophagy. In vivo experiments confirmed the selective accumulation of D -CuS NPs in tumors, induction of autophagy, and successful treatment of the tumor. Therefore, chiral CuS NPs show great potential for modulating biological processes and improving tumor treatment.
研究领域:
纳米医学
·
肿瘤学
·
分子生物学
·
细胞自噬
·
生物材料
·
转化医学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2025
·
IF 14.1
Ningxi Wu,Anwen Yin,Xiang Yu,Mingxin Wang,Jiahui Zhang,Kerong Liu,Yutong Hou,Minkai Cao,Yiting Zhang,Xiaoxiao Zhang,Yao Gao,Xirong Guo,Le Zhang,Yun Li
Exclusive breastfeeding reduces the risk of childhood obesity, potentially through metabolic programming of adipose tissue during lactation. However, the underlying mechanisms remain unclear. Using a mouse model, it is shown that mixed formula feeding disrupts brown adipose tissue (BAT) morphology, mitochondrial integrity, and thermogenic capacity, resulting in greater fat accumulation and glucose intolerance after weaning under a high-fat diet. By contrast, BAT from exclusively breastfed mice preserved enhanced thermogenic function for up to 12 weeks after transplantation into recipient mice. Transcriptomic analysis revealed that AMPK activation is sustained in BAT from exclusively breastfed mice but markedly diminished in mixed-fed counterparts. Pharmacological inhibition of AMPK abolished the long-term metabolic benefits conferred by exclusive breastfeeding. Mechanistically, breast milk–derived extracellular vesicles enriched in miR-125a-5p enhanced AMPK signaling by targeting HIF1AN. AMPK-induced α-ketoglutarate (αKG) production proved essential for BAT development and thermogenesis, and αKG supplementation rescued impaired BAT function in mixed-fed mice. In conclusion, exclusive breastfeeding imprints a thermogenic memory in BAT via the HIF1AN/AMPK/αKG signaling axis, thereby conferring long-term metabolic protection to offspring.
研究领域:
发育生物学
·
代谢学
·
内分泌学
·
分子生物学
·
营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Zhou Fei,Ding Mingning,Gu Yiqing,Fan Guifang,Liu Chuanyang,Li Yijie,Sun Rong,Wu Jianzhi,Li Jianchao,Xue Xiaoyong,Li Hongjuan,Li Xiaojiaoyang
Nonalcoholic fatty liver disease (NAFLD), manifested as the aberrant accumulation of lipids in hepatocytes and inflammation, has become an important cause of advanced liver diseases and hepatic malignancies worldwide. However, no effective therapy has been approved yet. Aurantio-obtusin (AO) is a main bioactive compound isolated from Cassia semen that has been identified with multiple pharmacological activities, including improving adiposity and insulin resistance. However, the ameliorating effects of AO on diet-induced NAFLD and underlying mechanisms remained poorly elucidated. Our results demonstrated that AO significantly alleviated high-fat diet and glucose-fructose water (HFSW)-induced hepatic steatosis in mice and oleic acid and palmitic acid (OAPA)-induced lipid accumulation in hepatocytes. Remarkably, AO was found to distinctly promote autophagy flux and influence the degradation of lipid droplets by inducing AMPK phosphorylation. Additionally, the induction of AMPK triggered TFEB activation and promoted fatty acid oxidation (FAO) by activating PPARα and ACOX1 and decreasing the expression of genes involved in lipid biosynthesis. Meanwhile, the lipid-lowing effect of AO was significantly prevented by the pretreatment with inhibitors of autophagy, PPARα or ACOX1, respectively. Collectively, our study suggests that AO ameliorates hepatic steatosis via AMPK/autophagy- and AMPK/TFEB-mediated suppression of lipid accumulation, which opens new opportunities for pharmacological treatment of NAFLD and associated complications.
研究领域:
药理学
·
肝病学
·
代谢疾病
✓ 已验证
DOI
PubMed
高影响因子
AAPS Journal
·
2017
·Vol. 19
·期 6
·1703-1714
·
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
·
肝病学
·
分子生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 6
Juan Tao,Yuning Wei,Mengyu Zhao,Zirong Dong,Zibo Wei,Shuyan Li,Jiaxin Zhao,Jinlong Yang,Jianping Qi
D100B is a first-in-class small-molecule activator of AMP-activated protein kinase (AMPK) that specifically targets the lysosomal pool, enabling precise metabolic regulation with lower systemic toxicity. Despite its favorable solubility and stability, D100B exhibits extremely poor oral bioavailability due to strong mucoadhesion and extensive retention within the intestinal mucus. Electrostatic and hydrophobic interactions between D100B and mucin were found to severely hinder its diffusion and epithelial absorption. To overcome this limitation, a PEGylated self-nanoemulsifying system (PSNE) was developed to reduce mucin binding and enhance mucus penetration. The optimized PSNE displayed uniform nanoscale droplets, sustained drug release, and significantly improved diffusion in simulated mucus. In Caco-2/HT29-MTX co-culture monolayers, PSNE significantly enhanced epithelial transport, while pharmacokinetic evaluation demonstrated a 2.66-fold increase in oral bioavailability compared with the unformulated drug. Overall, this study establishes a mucus-barrier-focused formulation strategy that may be applicable for improving the oral delivery of amphiphilic compounds whose absorption is compromised by mucus-mediated retention
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2026
·
IF 8.2
Xinyi Zeng,Deijian Peng,Yunlong Shen,Li Tang,Tianlu Ran,Ziheng Pan,Hui Liu
Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by the abnormal aggregation of amyloid-β (Aβ). Bletilla striata polysaccharide (BSP), the primary active component of the traditional Chinese medicine Bletilla striata , exhibits various pharmacological effects including hemostatic, antioxidant, anti-inflammatory, and immunomodulatory activities. This study aimed to systematically investigate the protective effects and molecular mechanisms of BSP in Caenorhabditis elegans AD model. We found that BSP effectively alleviated the paralysis phenotype in AD worms, with optimal efficacy observed at a concentration of 100 μg/mL. Furthermore, BSP significantly extended the lifespan of both wild type and AD worms, reduced lipofuscin deposition and egg-laying capacity, improved neuromuscular function, learning ability, and stress resistance, and lowered the level of oxidative stress in vivo. Additionally, BSP treatment markedly suppressed Aβ aggregation in AD worms.Transcriptomic analysis revealed that BSP significantly regulates the autophagy pathway. In combination with genetic experiments, we further elucidated that BSP coordinates the insulin and AMPK signaling pathways to modulate autophagy, thereby reducing abnormal autophagosome accumulation and restoring autophagic homeostasis. Notably, the neuroprotective effects of BSP were completely abolished in mutants of key insulin signaling pathway genes ( daf-2 , age-1 , akt-1 , akt-2 , daf-16 ) and the AMPK homologous gene aak-2 , indicating that its efficacy is associated with the insulin/AMPK-autophagy regulatory axis. This study reveals the mechanism by which BSP ameliorates AD pathology through multi-target and multi-pathway regulation of autophagy, providing a new theoretical basis for its development as a candidate therapeutic agent for AD and further highlighting the potential medical value of Bletilla striata in combating AD.
✓ 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）