Introduction
Heterotic structure of AMPK
Regulation of AMPK activity
Regulation of macrophage activation
Role of AMPK in macrophage polarisation and anti-inflammation
Role of AMPK in macrophage-related diseases
Atherosclerosis
Insulin resistance
Cancer
AMPK enhancers | Experimental design | Applications/outcomes of the study | References |
---|---|---|---|
Astragalus membranaceus | Model: murine ANA-1 macrophages | Injection of Astragalus membranaceus extracts suppressed the production of interleukin-6 by activating autophagy through the AMPK–mTOR pathway in lipopolysaccharide-stimulated macrophages | [136] |
Calcium-binding protein 39 | Model: murine primary chondrocyte cell line (ATDC5) and macrophage cell line (RAW264.7) | Overexpression of calcium-binding protein 39 promoted macrophage polarisation from the ‘M1’ to the ‘M2’ phenotype and alleviated chondrocyte damage in osteoarthritis by activating the AMP-activated protein kinase/sirtuin-1 axis | [137] |
Moderate l-lactate | Model: male C57BL/6 mice fed a high-fat diet | Moderate administration of l-lactic acid inhibited the M1 polarisation of adipose tissue macrophages by activating the GPR132–PKA–AMPKα1 signalling pathway to alleviate insulin resistance | [111] |
2-Deoxy-d-glucose (2-DG) | Model: bone marrow-derived macrophages (BMDMs) from C57BL/6 (B6) mice | 2-DG treatment decreased M2 polarisation in mice with tumours and allergic airway inflammation via the AMPK–Hif-1α pathway | [138] |
Non-lethal sonodynamic therapy (NL-SDT) | Model: Mouse model of AS and bone marrow transplantation (BMT) | Non-lethal sonodynamic therapy facilitated the M1-to-M2 transition in advanced atherosclerotic plaques by activating the ROS–AMPK–mTORC1–autophagy pathway | [59] |
β-Hydroxyisovalerylshikonin (β-HIVS) | Model: murine macrophage cell line (RAW264.7) and BMDMs | β-HIVS inhibited M1 polarisation and promoted M2 polarisation through the AMPK/Nrf2 pathway, alleviating sepsis in mice | [139] |
Human recombinant annexin A1 (hrANXA1) | Model: male C57BL/6 mice, alx/fpr2/3GFP/GFP mice, AnxA1−/− mice and BMDMs | AnxA1 promoted macrophage skewing to accelerate muscle regeneration through the AANXA1/FPR2/AMPK axis | [10] |
Vitamin B6 (VitB6) | Model: wild-type (WT) B129 mice and DOK3-knockout (DOK3−/−) mice | VitB6 inhibited macrophage activation through the AMPK–DOK3 pathway to prevent LPS-induced acute pneumonia in mice | [140] |
Metformin | Model: adult male ICR mice, SRA1-KO mice and BMDMs | Metformin decreased plasma HMGB1 accumulation and attenuated CIPN via the AMPK/p38/SR-A1 signalling pathway | [141] |
Astragaloside IV | Model: the human lung cancer cell lines A549 and H1299, the human monocyte cell line THP-1 and Lewis lung cancer (LLC) cells | AS-IV inhibited lung cancer progression and metastasis by blocking M2 polarisation partially through the AMPK signalling pathway | [77] |
Ac2-26, a pharmacophore N-terminal peptide of ANXA1 | Model: male C57BL/6J mice with tMCAO/R and murine BV2 microglial cells | Annexin A1 protected against cerebral ischaemia–reperfusion injury by modulating microglia/macrophage polarisation via the FPR2/ALX-dependent AMPK–mTOR pathway | [142] |
Alginate oligosaccharides (AOSs) | Model: murine RAW264.7 cells and BMDMs | AOSs inhibited LPS-mediated inflammatory responses and attenuated dextran sodium sulphate (DSS)-induced colitis by activating AMPK signalling and suppressing NF-κB activation | [143] |
Apoptotic extracellular vesicles (ApoEVs) | Model: mouse bone marrow MSCs and BMDMs | ApoEVs inhibited the polarisation of macrophages to the proinflammatory phenotype via the AMPK/SIRT1/NF-κB pathway and suppressed the formation of adjacent osteoclasts by reducing the secretion of TNF-α | [144] |
Metformin | Model: 10-week-old male C57BL/6J mice and bone marrow-derived macrophages (BMMs) | Metformin attenuated osteoclast-mediated abnormal subchondral bone remodelling and alleviated osteoarthritis via the AMPK/NF-κB/ERK signalling pathway | [145] |
2-DG | Model: male Sprague-Dawley (SD) rats and RAW264.7 macrophages | 2-DG promoted macrophage polarisation from the M1 to the M2 phenotype via the AMPK/NF-κB pathway to ameliorate adjuvant-induced arthritis | [146] |
Baicalein | Model: HUVECs (human), RAW264.7 macrophages (murine) and MOVAS (murine) | Baicalein targeted the inflammation-associated AMPK/Mfn-2/MAPK signalling pathway to exert anti-atherosclerotic effects | [147] |
Mogrol (MG) | Model: human colonic epithelial cells NCM460 | Mogrol alleviated ulcerative colitis by promoting AMPK activation | [148] |
Fisetin | Model: male C57BL/6J mice and RAW264.7 macrophages | Fisetin mitigated hepatic ischaemia–reperfusion injury by regulating the GSK3β/AMPK/NLRP3 inflammasome pathway | [149] |
Nitazoxanide and tizoxanide | Model: wild-type C57BL/6J mice, ApoE−/− mice and RAW264.7 macrophages | Nitazoxanide and tizoxanide inhibited the activation of the NLRP3 inflammasome in macrophages through the AMPK/IκBα/NF-κB pathway. Nitazoxanide inhibited the formation of atherosclerotic plaques in ApoE−/− mice fed a Western diet | [150] |
Galanin | Model: male C57BL/6 mice and the murine macrophage cell lines J774A.1 (ATCC TIB67) and RAW264.7 | Galanin ameliorated liver inflammation and fibrosis in mice by activating AMPK/ACC signalling and modifying the inflammatory phenotype of macrophages | [151] |
Metformin | Model: male C57BL/6J ApcMin/+ mice and the human monocytic myeloid cell line THP-1 | Metformin-induced activation of AMPK decreased the abundance of MDSCs and M2 macrophages by downregulating the mevalonate pathway | [135] |
Calycosin-7-glucoside (CG) | Model: male db/db mice (age, 6–8 weeks) and RAW264.7 macrophages | Calycosin-7-glucoside promoted the polarisation of M2 macrophages and accelerated the healing of diabetic wounds in db/db mice through the ROS/AMPK/STAT6 pathway | [152] |
Oleoylethanolamide | Model:mmacrophages derived from THP-1 cells | Oleoylethanolamide stabilised atherosclerotic plaques by regulating macrophage polarisation via the AMPK–PPARα pathway | [153] |
Bushen Huoxue decoction | Model: RAW264.7 cells (FH0328) and THP-1 cells (FH0112) | Bushen Huoxue decoction suppressed the M1 polarisation of macrophages and prevented LPS-induced inflammatory bone loss by activating the AMPK pathway | [154] |
Saxagliptin | Model: diabetic rats (STZ) and human THP-1 monocytes | Saxagliptin regulated M1/M2 macrophage polarisation via the CaMKKβ/AMPK pathway to alleviate non-alcoholic fatty liver disease (NAFLD) | [155] |
Polo-like kinase 1 (PLK1) | Model: ApoE−/− mice and THP-1 macrophages | PLK1 inhibited lipid accumulation in macrophages and mitigated atherosclerosis by promoting ABCA1- and ABCG1-dependent cholesterol efflux via the AMPK/PPARγ/LXRα pathway | [156] |
Empagliflozin | Model: male C57BL/6J mice (weight, 20–25 g) | Empagliflozin significantly ameliorated NAFLD-related liver injury by enhancing hepatic macrophage autophagy via the AMPK/mTOR signalling pathway and inhibiting IL-17/IL-23 axis-mediated inflammatory responses | [157] |
Impressic acid (IPA) | Model: murine RAW264.7 macrophages | IPA attenuated LPS-induced inflammatory responses by activating the AMPK/GSK3β/Nrf2 axis in macrophages | [158] |
Salicylates | Model: murine RAW264.7 macrophages | Salicylates ameliorated dextran sodium sulphate-induced colitis by activating AMPK targeting the β1 subunit in macrophages | [159] |
Gallic acid (GA) | Model: the human hepatoma cell line HepG2, murine hepatoma cell line Hepa1-6 and murine RAW264.7 macrophages | GA inhibited lipid accumulation via the AMPK pathway and suppressed apoptosis and macrophage-mediated inflammation in hepatocytes | [160] |
IL-37 | Model: six-week-old female C57BL/6 mice (infected with S. japonicum) | IL-37 alleviated hepatic granuloma caused by Schistosoma japonicum infection by promoting the expression of phosphorylated AMPK in macrophages and inducing M2 polarisation | [161] |
5-Amino-1-β-d-ribofuranosyl-imidazole-4-carboxamide (AICAR) | Model: male C57BL/6 mice and bone marrow-derived macrophages (BMMs) | AMPKα2 subunit directly contributed to AICAR-induced macrophage polarisation at the inflamed site of the paw. AICAR reduced peripheral inflammation by inducing macrophage polarisation | [162] |
Irisin | Model: murine RAW264.7 macrophages | Irisin-induced M2 polarisation enhanced osteogenesis in osteoblasts; this effect might be associated with AMPK activation | [163] |
Geniposide combined with notoginsenoside R1 (GN combination) | Model: eight-week-old male ApoE−/− mice (n = 10) | GN combination attenuated inflammation and apoptosis in atherosclerosis via the AMPK/mTOR/Nrf2 signalling pathway | [164] |
Adiponectin (APN) | Model: Sprague-Dawley pups | APN ameliorated GMH-induced brain injury by regulating M1/M2 microglia polarisation via the adipoR1/APPL1/AMPK/PPARγ signalling pathway in neonatal rats | [165] |