Biomaterials Research
·
2025
·
IF 9.6
Zijian Dai,Wanting Yin,Jiahao Li,Lingjun Ma,Fang Chen,Qun Shen,Xiaosong Hu,Yong Xue,Junfu Ji
Quercetin as a flavonoid polyphenol in nature has shown great anti-obesity effects. Due to its poor stability in chemical structure and low intestinal absorption, the in vivo bioavailability of quercetin is considered to be the main challenge for applications. To achieve the oral quercetin administration, chitosan was successfully trimethylated (TMC) to coat the quercetin-loaded zein nanoparticles (Zein-Q), which were designed as the core–shell structure for enhancing the intestinal absorption in this study. TMC-Zein-Q was demonstrated to protect quercetin from degradation and showed the sustained-release effect in an in vitro drug release experiment. The nanoparticles were found to reversibly open tight junctions between intestinal epithelial cells and help to increase quercetin uptake via the paracellular pathway in Caco-2 cells. In addition, the delivery system also showed stronger intestinal permeability and mucoadhesion in vivo, which improved the bioavailability of quercetin in cellular and animal experiments. After 10 weeks of intervention, TMC-Zein-Q could effectively suppress weight gain, improve serum lipid levels, and ameliorate hepatic steatosis and glucose tolerance in high-fat diet (HFD) mice by mediating the AMPK pathway. Consequently, this work successfully constructed TMC-Zein-Q for oral quercetin delivery, providing a novel and feasible strategy for the treatment of obesity via the oral route.
研究领域:
药剂学
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营养学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2020
·
IF 3.701
Xing Zhang,Wen Shi,Hui He,Ruge Cao,Tao Hou
Val-Phe-Val-Arg-Asn (VFVRN) has been identified and screened from lipid-lowering chickpea peptides (ChPs) previously. This work explored its lipid-lowering mechanisms by using a high-fat diet C57BL/6J mice model and 3T3-L1 preadipocyte cell model. Administration of VFVRN to hyperlipidemic mice significantly decreased the levels of total cholesterol (TC) and total triglyceride (TG) in liver and serum (P < 0.05), and increased the fecal triglyceride excretions. The expressions of sterol regulatory element-binding protein (SREBP)-2, liver X receptor (LXR)α, peroxisome proliferator-activated receptors (PPAR)α and their related target genes were regulated via AMP-activated protein kinase (p-AMPK) pathway in liver. Compared with model group, the levels of PPARα and PPARγ in 10 mg/kg VFVRN group were up-regulated by 36.96% and 36.49% in adipose tissues, while LXRα and ATP binding cassette G5/8 transporters (ABGC5/8) were lowered by 87.26% and 145% in small intestine respectively. Moreover, VFVRN promoted 3T3-L1 preadipocyte apoptosis by regulating the expressions of BaX, Caspase-3 and Bcl-2.
研究领域:
营养学
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分子生物学
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药理学
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DOI
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 105
·期 4
·e70097
·
IF 3.3
Wei-fang Song,Sheng-nan Li,Rui-xin Yao,Qiu-yan Jiang,Ting Shi,Dan-dan Fan,Hai-juan Zhang,Wen-hui Zhang,Rui-jun Wang
The primary objective aims to evaluate the therapeutic efficacy of echinacoside in ameliorating hepatic steatosis and exploring its role in modulating autophagic flux through AMP-activated protein kinase (AMPK) signaling, positioning it as a potential treatment for non-alcoholic fatty liver disease (NAFLD). A well-established NAFLD rat model was employed, administering varying concentrations of echinacoside. Biochemical parameters, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alongside liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), were measured to assess liver function. To elucidate the molecular mechanisms, western blot analyses were performed to assess the expressions of p-AMPK, total AMPK, and key autophagy markers LC-3 I/II and Beclin-1. Echinacoside significantly improved the lipid profile by lowering plasma TG, TC, and LDL-C levels while increasing HDL-C. It also reduced serum ALT, AST, and ALP activities, demonstrating hepatoprotective effects. Notably, echinacoside reversed the p-AMPK levels in NAFLD rats in a dose-dependent manner, with the highest dosage showing the strongest effect. This was accompanied by increased expression of LC-3 I/II and Beclin-1. Echinacoside is expected to be a therapeutic drug for NAFLD by activating AMPK activity and enhancing autophagy to improve liver function. These findings suggest its clinical potential, with autophagy modulation via the AMPK pathway as a possible therapeutic mechanism for NAFLD treatment.
研究领域:
药理学
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代谢生物学
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肝脏疾病研究
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Jiaxin Li,Lianghua Xie,Zishan Dou,Yiyang Zhou,Jianling Mo,Wei Chen
Cultured meat technology is expected to solve problems such as resource shortages and environmental pollution, but the muscle fiber differentiation efficiency of cultured meat is low. Genipin is the active compound derived from Gardenia jasminoides Ellis, which has a variety of activities. Additionally, genipin serves as a noncytotoxic agent for cross-linking, which is suitable as a foundational scaffold for in vitro tissue regeneration. However, the impact of genipin on myoblast differentiation remains to be studied. The research revealed that genipin was found to improve the differentiation efficiency of myoblasts. Genipin improved mitochondrial membrane potential by activating the AMPK signaling pathway of myoblasts, promoting mitochondrial biogenesis, and mitochondrial network remodeling. Genipin activated autophagy in myoblasts and maintained cellular homeostasis. Autophagy inhibitors blocked the pro-differentiation effect of genipin. These results showed that genipin improved the differentiation efficiency of myoblasts, which provided a theoretical basis for the development of cultured meat technology.
研究领域:
细胞生物学
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分子生物学
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再生医学
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DOI
PubMed
高影响因子
GERONTOLOGY
·
2024
·
IF 3.1
Liang Yu,Zhou Yiming,Zhou Can,Cai Xinqi,Liu Li,Wei Fang,Li Guolin
Introduction: While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of sertraline on healthspan remain to be elucidated. Here, we explored the role of sertraline in the lifespan and healthspan of Caenorhabditis elegans. Methods: The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. Results: Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. Conclusion: Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways
研究领域:
生物化学
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分子生物学
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衰老研究
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Lulu Zhao,Yongbo Peng,Jing Huang,Nishang Liu,Xinrong Zou,Junnan Li,Yunpeng Fan,Ping Li,Liling Tang,Jisheng Wang,Yajun Zeng,Yi Wu,Gaohui Zhu
Polysaccharides are the major bioactive composition of Polygonatum sibiricum ( P. sibiricum ). However, the structural and functional identifications of these polysaccharides were still limited. Herein, we isolated a novel P. sibiricum polysaccharides (PSPF) and explored its potential function and mechanism in alleviating hyperlipidemia. PSPF were purified by diethylaminoethyl-sepharose fast flow (DEAE-Sepharose FF) and cross-linked dextran gel LH-20 (Sephadex LH-20) column chromatography, and identified by gel-permeation chromatography, methylation analysis, fourier transform infrared spectrometer (FT-IR), nuclear magnetic resonance (NMR), and gas chromatography–mass spectrometry (GC–MS). Their molecular weight (Mw), polysaccharide composition, and chemical structure were characterized. Furthermore, egg yolk emulsion-induced acute hyperlipidemia mouse model was constructed to evaluate the lipid-lowering efficacy and the underlying mechanism of PSPF. It was found that PSPF, with the Mw of 3592 Da, were prepared and mainly consisted of fructan with →1)-β-D-Fru f -(2 → main chain and →6)-β-D-Fru f -(2 → side chains. In addition, PSPF supplements efficiently reduced liver lipid accumulation, alleviated hepatocyte steatosis, and upregulated the AMP-activated protein kinase (AMPK) pathway, thereby enhancing fatty acid oxidation and decomposition. These results indicate that PSPF may serve as the potential dietary supplements for lipid reduction.
研究领域:
生物化学
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营养学
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药理学
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产品关联
DOI
PubMed
高影响因子
World Journal of Diabetes
·
2024
·Vol. 15
·期 12
·2338
·
IF 4.2
Lu-Sha Cen,Yi Cao,Yi-Mai Zhou,Jing Guo,Jing-Wen Xue
BACKGROUND Shikonin is a natural remedy that is effective at treating diabetic wounds. NFAT5 is a potential therapeutic target for diabetes, and mitochondrial function is essential for wound healing. However, the relationship among Shikonin, NFAT5, and mitochondrial function has not been thoroughly studied. Here, we offer new perspectives on the advantages of shikonin for managing diabetes. AIM To assess the therapeutic mechanism of shikonin in diabetic wounds, its relationship with NFAT5, and its protection of mitochondrial function. METHODS Hypertonic cell and diabetic wound mouse models were established. NFAT5 expression was measured through western blotting and immunofluorescence, in vivo and in vitro . Mitochondrial function was evaluated using reactive oxygen species (ROS) detection and JC-1 and Calcein AM dyes. Mitochondrial structures were observed using transmission electron microscopy. The NFAT5/AMPK pathway was analyzed using a transfection vector and an inhibitor. The effect of shikonin on cells under hypertonic conditions via the NFAT5/AMPK pathway was assessed using western blotting. RESULTS Shikonin treatment preserved HaCaT cell viability, while significantly reducing cyclooxygenase-2 expression levels in a high-glucose environment ( P < 0.05). Additionally, shikonin maintained mitochondrial morphology, enhanced membrane potential, reduced membrane permeability, and decreased ROS levels in HaCaT cells under hyperosmolar stress. Furthermore, shikonin promoted wound healing in diabetic mice ( P < 0.05). Shikonin also inhibited NFAT5, in vivo and in vitro ( P < 0.05). Shikonin treatment reduced NFAT5 expression levels, subsequently inhibiting AMPK expression in vitro ( P < 0.05). Finally, shikonin inhibited several key downstream molecules of the NFAT5/AMPK pathway, including mammalian target of rapamycin, protein kinase B, nuclear factor kappa-light-chain-enhancer of activated B cells, and inducible nitric oxide synthase ( P < 0.05). CONCLUSION Shikonin protects mitochondria via the NFAT5/AMPK-related pathway and enhances wound healing in diabetes.
研究领域:
药理学
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内分泌学
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细胞生物学
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分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
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
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肿瘤学
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分子生物学
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细胞自噬
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生物材料
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转化医学
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产品关联
DOI
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2023
·Vol. 103
·期 12
·5839-5848
·
IF 4.1
Xuan Yao,Anqi Wang,Bo Gao,Yu Xue,Xueling Zhao,Xuanyu Wang,Rui Wang,Min Zhuang,Changqing Wei,Weidong Cheng,Jian Zhang,Padraig Strappe,Zhongkai Zhou
BACKGROUND Ageing and associated cognitive impairments are becoming serious issues around the world. In this study, the physiological properties of three kinds of complexes of fatty acid (capric, stearic and oleic acid, respectively) and de-branched starch molecules were investigated via a d -galactose-induced ageing model. This study revealed differences in the regulation of cognitive impairment and brain damage following intervention of different complexes, which might highlight a potent approach for the prevention of this chronic disease. RESULTS Data indicated that three complexes improved response time and cognitive function and the bio-parameter markers associated with oxidative stress in ageing rats. Among them, the complexes prepared from de-branched starch–oleic acid showed a greater improvement compared to others. In addition, de-branched starch–capric acid complex showed a higher improvement in the morphology of colon cells and hippocampal neuronal cells. The consumption of de-branched starch–capric acid and –oleic acid complexes generated more short-chain fatty acids in the gut. More importantly, the complexation of de-branched starch with either caprate or stearate enhanced gut Akkermansia . Therefore, it was proposed that the richness in Akkermansia and gut metabolites might be associated with reduced damage of the hippocampal neuronal cells induced by the ageing progress. Moreover, the AMPK (AMP-activated protein kinase) pathway was activated in liver in de-branched starch–capric acid complex diet. In summary, de-branched starch–capric acid complex exhibited a greater effect on the attenuation of ageing-induced cognitive impairment. CONCLUSION This study might highlight a new approach for intervening in the cognitive impairment during the ageing progress via a food supply. © 2023 Society of Chemical Industry.
研究领域:
营养学
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老年医学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Cancer Communications
·
2018
·Vol. 38
·期 1
·1-14
·
IF 0
Huang Yanjun,Zhou Sichun,He Caimei,Deng Jun,Tao Ting,Su Qiongli,Darko Kwame Oteng,Peng Mei,Yang Xiaoping
Background In previous studies, we have shown that the combination of metformin and gefitinib inhibits the growth of bladder cancer cells. Here we examined whether the metformin analogue phenformin, either used alone or in combination with gefitinib, could inhibit growth of bladder cancer cells.Methods The growth-inhibitory effects of phenformin and gefitinib were tested in one murine and two human bladder cancer cell lines using MTT and clonogenic assays. Effects on cell migration were assessed in a wound healing assay. Synergistic action between the two drugs was assessed using CompuSyn software. The potential involvement of AMPK and EGFR pathways in the effects of phenformin and gefitinib was explored using Western blotting.Results In MTT and clonogenic assays, phenformin was > 10-fold more potent than metformin in inhibiting bladder cancer cell growth. Phenformin also potently inhibited cell migration in wound healing assays, and promoted apoptosis. AMPK signaling was activated; EGFR signaling was inhibited. Phenformin was synergistic with gefitinib, with the combination of drugs showing much stronger anticancer activity and apoptotic activation than phenformin alone.Conclusion sPhenformin shows potential as an effective drug against bladder cancer, either alone or in combination with gefitinib.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
Journal of Diabetes
·
2023
·
IF 4.5
Guangwei Yang,Zitian Liu,Shuohui Dong,Xiang Zhao,Zheng Ge,Zhiqiang Cheng,Xiang Zhang,Kexin Wang
Background Diabetic cardiomyopathy is a serious complication of obesity with type 2 diabetes and is a major cause of mortality. Metabolic surgery, such as duodenal-jejunal bypass (DJB), can effectively improve diabetic cardiomyopathy; however, the underlying mechanisms remain elusive. Oxidative stress is one of the pivotal mechanisms of diabetic cardiomyopathy. Our objective was to investigate the effect and potential mechanisms of DJB on oxidative stress in the heart of diabetic cardiomyopathy rats. Methods High-fat diet combined with intraperitoneal injection of streptozotocin was used to establish diabetic cardiomyopathy rats. DJB was performed on diabetic cardiomyopathy rats, and high glucose and palmitate were used to simulate diabetic cardiomyopathy in H9C2 cells in vitro. Sera from different groups of rats were used for experiments in vivo and in vitro. Results DJB effectively improved oxidative stress and activated the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway to increase endothelial nitric oxide synthase (eNOS) phosphorylation level and the expression of antioxidative system-related proteins and genes in the heart of diabetic cardiomyopathy rats. AMPK agonists and serum from DJB rats activated the AMPK pathway to increase eNOS phosphorylation level and the expression of antioxidative system-related proteins and genes and decreased the content of reactive oxygen species in H9C2 cells, but this improvement was almost eliminated by the addition of AMPK inhibitors. Conclusions DJB activates eNOS and enhances the antioxidant system by activating the AMPK pathway—and not solely by improving blood glucose—to improve oxidative stress in the heart of diabetic cardiomyopathy rats.
研究领域:
外科手术
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糖尿病
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心脏病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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.
研究领域:
药理学
·
分子生物学
·
细胞生物学
·
代谢
✓ 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）