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匹配条件： “Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway (AMPK)” ，找到相关结果约1000条。
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基于AMPK通路探究功能性消化不良的中医药治疗
Research Progress on Mechanisms of Traditional Chinese Medicine in the Treatment of Functional Dyspepsia Based on the AMPK Signaling Pathway  [PDF]
文越, 周雪雷
Traditional Chinese Medicine (TCM) , 2026, DOI: 10.12677/tcm.2026.151041
Abstract: 功能性消化不良(FD)是一种常见的胃肠功能性疾病，全球患病率较高，其病理机制涉及胃肠动力障碍和内脏高敏性等多重因素，临床治疗仍面临难以彻底根治的困境。近年来，腺苷酸活化蛋白激酶(AMPK)信号通路被证实可以通过影响Cajal间质细胞(ICCs)的自噬、促进ghrelin释放以及抗氧化应激等途径调节胃肠运动改善FD。本综述旨在系统性地探讨中医药通过干预AMPK信号通路来防治FD的机制，并试图揭示其在临床治疗、基础科研及新药研发领域的新视角和研究潜力。
Functional dyspepsia (FD) is a common gastrointestinal functional disorder with a high global prevalence. The pathological mechanisms involve multiple factors such as gastrointestinal dysmotility and visceral hyperalgesia, and clinical treatment still faces the dilemma of difficulty in complete cure. In recent years, the AMP-activated protein kinase (AMPK) signaling pathway has been shown to regulate gastrointestinal motility and improve FD through influencing autophagy of interstitial cells of Cajal (ICCs), promoting ghrelin release, and antioxidant stress, among other pathways. This review aims to systematically explore the mechanisms of traditional Chinese medicine in preventing and treating FD by interfering with the AMPK signaling pathway, and attempts to reveal its new perspectives and research potential in the field of clinical treatment, basic scientific research, and drug development.
Vitamin D Insufficiency Exacerbates Adipose Tissue Macrophage Infiltration and Decreases AMPK/SIRT1 Activity in Obese Rats
Eugene Chang,Yangha Kim
- , 2017, DOI: 10.3390/nu9040338
Abstract: Obesity is recognized as a state of chronic low-grade systemic inflammation due to adipose tissue macrophage infiltration and production of proinflammatory adipokines. Decreased vitamin D status is associated with obesity. The specific aim of the present study is to investigate the effects of vitamin D on obesity-induced adipose tissue inflammation. Male Sprague-Dawley rats were randomized and fed a normal diet (NOR, 1000 IU vitamin D/kg diet), a 45% high-fat diet (HF, 1000 IU vitamin D/kg diet), or a 45% high-fat diet containing 25 IU vitamin D/kg diet (HF+LVD) for 12 weeks. The vitamin D-insufficient diet (HF+LVD) led to vitamin D inadequacy as determined by serum 25(OH)D level, 68.56 ± 7.97 nmol/L. The HF+LVD group exacerbated HF-increased adipocyte size, adipogenic gene expression of PPARγ, adipose tissue macrophage recruitment, and proinflammatory cytokine IL-6 and TNFα levels in epididymal white adipose tissue. In addition, vitamin D insufficiency significantly decreased mRNA levels of β-oxidation-related genes such as CPT1α, PGC1α, PPARα, VLCAD, LCAD, MCAD, and UCP1. Moreover, significant decrements of SIRT1 and AMPK activity were noted in obese rats fed with a vitamin D-insufficient diet. The observed deleterious effects of vitamin D insufficiency on adipose tissue expansion, immune cell infiltration and inflammatory status suggest vitamin D plays a beneficial role in adipocyte metabolic metabolism and obesity progression. SIRT1 and AMPK activity may play a role in the mechanism of vitamin D action
Caffeic Acid Targets AMPK Signaling and Regulates Tricarboxylic Acid Cycle Anaplerosis while Metformin Downregulates HIF-1α-Induced Glycolytic Enzymes in Human Cervical Squamous Cell Carcinoma Lines
Karolina Bukowska-Strakova,Kinga A. Kocemba-Pilarczyk,Malgorzata Tyszka-Czochara,Marcin Majka
- , 2018, DOI: 10.3390/nu10070841
Abstract: The small molecules, natural antioxidant Caffeic Acid (trans-3,4-Dihydroxycinnamic acid CA) and anti-diabetic drug Metformin (Met), activate 5′-adenosine monophosphate-activated protein kinase (AMPK) and interfere with metabolic reprogramming in human cervical squamous carcinoma cells. Here, to gain more insight into the ability of CA, Met and the combination of both compounds to impair aerobic glycolysis (the “Warburg effect”) and disrupt bioenergetics of cancer cells, we employed the cervical tumor cell lines C-4I and HTB-35/SiHa. In epithelial C-4I cells derived from solid tumors, CA alleviated glutamine anaplerosis by downregulation of Glutaminase (GLS) and Malic Enzyme 1 (ME1), which resulted in the reduction of NADPH levels. CA treatment of the cells altered tricarboxylic acid (TCA) cycle supplementation with pyruvate via Pyruvate Dehydrogenase Complex (PDH), increased ROS formation and enhanced cell death. Additionally, CA and CA/Met evoked intracellular energetic stress, which was followed by activation of AMPK and the impairment of unsaturated FA de novo synthesis. In invasive HTB-35 cells, Met inhibited Hypoxia-inducible Factor 1 (HIF-1α) and suppressed the expression of the proteins involved in the “Warburg effect”, such as glucose transporters (GLUT1, GLUT3) and regulatory enzymes of glycolytic pathway Hexokinase 2 (HK2), 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4 (PFKFB4), Pyruvate Kinase (PKM) and Lactate Dehydrogenase A (LDH). Met suppressed the expression of c-Myc, BAX and cyclin-D1 (CCND1) and evoked apoptosis in HTB-35 cells. In conclusion, both small molecules CA and Met are capable of disrupting energy homeostasis, regulating oxidative metabolism/glycolysis in cervical tumor cells in regard to specific metabolic phenotype of the cells. CA and Met may provide a promising approach in the prevention of cervical cancer progression
二甲双胍对胰腺癌和胰腺癌干细胞中ALDH1表达的作用
吴少璇,张亚娜,樊青霞,池艳艳,王峰,马望
- , 2017, DOI: 10.3971/j.issn.1000-8578.2017.03.005
Abstract: 摘要 目的 观察二甲双胍对胰腺癌PANC-1细胞和胰腺癌干细胞中ALDH1表达的影响，探讨其作用机制。方法 采用CCK-8和Western blot检测不同浓度二甲双胍对胰腺癌PANC-1细胞的增殖及ALDH1和p-mTOR蛋白表达的影响。Western blot、免疫荧光法及qRT-PCR检测二甲双胍、雷帕霉素以及联合用药组PANC-1细胞中ALDH1、4EBP1、p-mTOR蛋白及mRNA的表达。超低黏附培养板悬浮培养胰腺癌细胞后观察干细胞成球数目的改变以及Western blot检测干细胞ALDH1的表达；建立胰腺癌裸鼠移植瘤模型比较PANC-1细胞以及胰腺癌成球细胞的成瘤能力。结果 二甲双胍抑制胰腺癌PANC-1细胞的增殖，且呈时间剂量依赖性，最佳干预时间为48 h，IC50约为20 mmol/L；与对照组相比，二甲双胍、雷帕霉素和联合用药组ALDH1、4EBP1、p-mTOR的ALDH1的蛋白表达以及mRNA水平明显降低（P<0.05）。胰腺癌成球细胞的体外成瘤能力以及ALDH1的表达比PANC-1细胞组显著增高；相比于对照组，二甲双胍、雷帕霉素和联合用药组胰腺癌细胞的成球能力以及胰腺癌干细胞中ALDH1的表达均显著降低（P<0.05）。结论 二甲双胍以及雷帕霉素均能显著抑制胰腺癌PANC-1细胞和胰腺癌干细胞ALDH1的表达，其作用机制可能是通过抑制mTOR通路
AICAR Antiproliferative Properties Involve the AMPK-Independent Activation of the Tumor Suppressors LATS 1 and 2
Beno？t Pinson,Beno？t Viollet,Bertrand Daignan-Fornier,Chloé Philippe,Jim Dompierre,Michel Moenner,Véronique Pantesco
- , 2018, DOI: 10.1016/j.neo.2018.03.006
Abstract: AICAR (Acadesine) is a pharmacological precursor of purine nucleotide biosynthesis with anti-tumoral properties. Although recognized as an AMP mimetic activator of the protein kinase AMPK, the AICAR monophosphate derivative ZMP was also shown to mediate AMPK-independent effects. In order to unveil these AMPK-independent functions, we performed a transcriptomic analysis in AMPKα1/α2 double knockout murine embryonic cells. Kinetic analysis of the cellular response to AICAR revealed the up-regulation of the large tumor suppressor kinases (Lats) 1 and 2 transcripts, followed by the repression of numerous genes downstream of the transcriptional regulators Yap1 and Taz. This transcriptional signature, together with the observation of increased levels in phosphorylation of Lats1 and Yap1 proteins, suggested that the Hippo signaling pathway was activated by AICAR. This effect was observed in both fibroblasts and epithelial cells. Knockdown of Lats1/2 prevented the cytoplasmic delocalization of Yap1/Taz proteins in response to AICAR and conferred a higher resistance to the drug. These results indicate that activation of the most downstream steps of the Hippo cascade participates to the antiproliferative effects of AICAR
Inhibitory effect of resveratrol on proliferation of vascular smooth muscle cells induced by angiotensin Ⅱ and its underlying mechanism
Pan GAO,Liang-yi SI,Qiang XU,Xiao-mei WANG
Medical Journal of Chinese People's Liberation Army , 2013,
Abstract: Objective 　To explore the effect of resveratrol on proliferation of vascular smooth muscle cells (VSMCs) as induced by angiotensin Ⅱ (Ang Ⅱ) and its underlying mechanism. Methods 　VSMCs of rat's thoracic aorta were primarily cultured in vitro. For detecting the effects of resveratrol on Ang Ⅱ-induced VSMC proliferation, the cultured cells were divided into a control group, Ang Ⅱ group (1μmol/L), gradient concentrations of resveratrol groups, and Ang Ⅱ + gradient concentration of resveratrol groups. The gradient concentrations of resveratrol were set as 10, 30 and 100μmol/L. Cells in each group were treated for 0, 6, 12 and 24h, respectively. VSMC proliferation was detected by cell count assay, and the viability of the VMSC was measured by MTT assay. For detecting the effects of compound C [adenine monophosphate-activated protein kinase (AMPK) inhibitor] on biological effects of VSMCs, the cultured cells were divided into a control group, Ang Ⅱ group, resveratrol + Ang Ⅱ group and compound C + resveratrol + Ang Ⅱ group. The protein expression of proliferated cell nuclear antigen (PCNA) in each group was detected by Western blotting after being treated for 24 hours. Results 　Compared with control group, the cell viability and cell number in Ang Ⅱ group were significantly increased (P<0.05) after Ang Ⅱ stimulation for 6, 12 and 24 hours. Compared with Ang Ⅱ group, the cell vitality and cell number were significantly decreased in different concentrations of resveratrol + Ang Ⅱ groups (P<0.05). On the other hand, compared with the control group, the expression of PCNA protein in Ang Ⅱ group was significantly increased (P<0.05); as compared with Ang Ⅱ group, the expression of PCNA protein in resveratrol + Ang Ⅱ group was significantly decreased (P<0.05); as compared with resveratrol + Ang Ⅱ, the cell number, cell viability, and PCNA protein expression in compound C + resveratrol + Ang Ⅱ group was significantly increased (P<0.05). Conclusion 　Resveratrol can inhibit Ang Ⅱ stimulated cell proliferation through activation of AMPK.
Metformin attenuates motility, contraction, and fibrogenic response of hepatic stellate cells in vivo and in vitro by activating AMP-activated protein kinase
Chun-Qing Zhang,Dong-Xiao Meng,Li-Ping Ling,Qian Ding,Xiao Li,Ying Wu,Zhen Li
- , 2018, DOI: 10.3748/wjg.v24.i7.819
Abstract:
5'-Monophosphate-activated protein kinase (AMPK) improves autophagic activity in diabetes and diabetic complications
Fan Yao,Ming Zhang
- , 2016, DOI: 10.1016/j.apsb.2015.07.009
Abstract: Diabetes mellitus (DM), an endocrine disorder, will be one of the leading causes of death world-wide in about two decades. Cellular injuries and disorders of energy metabolism are two key factors in the pathogenesis of diabetes, which also become the important causes for the process of diabetic complications. AMPK is a key enzyme in maintaining metabolic homeostasis and has been implicated in the activation of autophagy in distinct tissues. An increasing number of researchers have confirmed that autophagy is a potential factor to affect or induce diabetes and its complications nowadays, which could remove cytotoxic proteins and dysfunctional organelles. This review will summarize the regulation of autophagy and AMPK in diabetes and its complications, and explore how AMPK stimulates autophagy in different diabetic syndromes. A deeper understanding of the regulation and activity of AMPK in autophagy would enhance its development as a promising therapeutic target for diabetes treatment
AMPK-associated signaling to bridge the gap between fuel metabolism and hepatocyte viability
Yoon Mee Yang, Chang Yeob Han, Yoon Jun Kim, Sang Geon Kim
World Journal of Gastroenterology , 2010,
Abstract: The adenosine monophosphate-activated protein kinase (AMPK) and p70 ribosomal S6 kinase-1 pathway may serve as a key signaling flow that regulates energy metabolism; thus, this pathway becomes an attractive target for the treatment of liver diseases that result from metabolic derangements. In addition, AMPK emerges as a kinase that controls the redox-state and mitochondrial function, whose activity may be modulated by antioxidants. A close link exists between fuel metabolism and mitochondrial biogenesis. The relationship between fuel metabolism and cell survival strongly implies the existence of a shared signaling network, by which hepatocytes respond to challenges of external stimuli. The AMPK pathway may belong to this network. A series of drugs and therapeutic candidates enable hepatocytes to protect mitochondria from radical stress and increase cell viability, which may be associated with the activation of AMPK, liver kinase B1, and other molecules or components. Consequently, the components downstream of AMPK may contribute to stabilizing mitochondrial membrane potential for hepatocyte survival. In this review, we discuss the role of the AMPK pathway in hepatic energy metabolism and hepatocyte viability. This information may help identify ways to prevent and/or treat hepatic diseases caused by the metabolic syndrome. Moreover, clinical drugs and experimental therapeutic candidates that directly or indirectly modulate the AMPK pathway in distinct manners are discussed here with particular emphasis on their effects on fuel metabolism and mitochondrial function.
磷酸腺苷激活的蛋白激酶在慢性应激诱发小鼠非酒精性脂肪肝中的作用
杨政华,寇兴瑞,杜格致,黄俊龙,张友磊
- , 2017, DOI: 10.16781/j.0258-879x.2017.12.1521
Abstract: 目的 探讨磷酸腺苷激活的蛋白激酶（AMPK）及其激动剂5-氨基咪唑-4-甲酰胺核苷酸（AICAR）在慢性应激诱发小鼠非酒精性脂肪肝（NAFLD）中的作用。方法 建立小鼠慢性应激模型，设对照组、应激组、应激加AICAR给药组和AICAR给药组，每组6只。采用ELISA法检测小鼠血浆促炎性细胞因子（肿瘤坏死因子α，γ干扰素）浓度，采用自动生化分析仪检测小鼠血浆丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆固醇、三酰甘油、游离脂肪酸的水平，采用苏木精-伊红染色和油红O染色检测肝细胞脂肪变性，采用蛋白质印迹法检测肝组织AMPK蛋白表达；然后用AICAR处理慢性应激小鼠并检测上述指标的变化。结果 慢性应激导致小鼠肝细胞脂肪变性，肝功能损害（ALT、AST水平升高，P<0.01），血浆促炎性细胞因子浓度升高（P<0.05），血浆游离脂肪酸水平升高（P<0.01）以及肝组织AMPK蛋白表达降低（P<0.01）。AICAR改善了肝细胞脂肪变性，并缓解了上述指标的变化。结论 慢性应激可能通过AMPK信号通路诱发NAFLD，AMPK激动剂AICAR可缓解慢性应激导致的NAFLD。
Objective To investigate the role of adenosine monophosphate-activated protein kinase (AMPK) and its agonist 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR) in mice with chronic stress-induced non-alcoholic fatty liver disease (NAFLD). Methods BABL/c mice were randomly divided into control group, stress group, stress plus AICAR group (ST+A group) and AICAR group. The mouse models of chronic stress was established in the stress and ST+A groups, and the mice were injected with AICAR 500 mg/kg in the ST+A and AICAR groups. Before and after treating with AICAR, the levels of pro-inflammatory cytokines (tumor necrosis factor α[TNF-α] and interferon γ[IFN-γ]) in plasma of mice were detected by ELISA, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol, triglyceride and free fatty acid in plasma were determined by automatic biochemical analyzer, the hepatic steatosis was detected by hematoxylin-eosin (H-E) staining and Oil Red O staining, and the expression of AMPK protein in liver tissues was detected by Western blotting. Results Chronic stress caused liver function damage (the levels of ALT and AST were significantly increased, P<0.01) and liver steatosis in mice, the levels of pro-inflammatory cytokines (P<0.05) and free fatty acid (P<0.01) were significantly increased and the liver AMPK protein expression was significantly decreased (P<0.01). AICAR improved the liver cell steatosis, and alleviated the changes of above indicators. Conclusion Chronic stress may induce NAFLD through AMPK signaling pathway, and AMPK agonist AICAR can alleviate NAFLD caused by chronic stress
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