Table 1 AMPK activators affect macrophage-related diseases through the AMPK pathway

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]