Table 3.

Role of AMPK enhancers/inducers on inflammation and related disorders.

AMPK Enhancers	Experimental Design	Applications/Outcomes of the Experiment	References
Name of the Component: Xanthohumol Dose: 10 or 50 mg/kg	Model: Wild-type (WT) and Nrf2−/− (knockout) C57BL/6 mice	-Induction of AMPK reduced ROS and cytokine secretion. -Txnip/NLRP3 inflammasome and NF-κB signaling pathways were also found to be inhibited.	[206]
Name of the Component: Metformin Dose: 200 mg/kg	Model: Six months older male Wister rats	-The treatment reduced cellular levels of nuclear factor-κB, Tumor Necrosis Factor-α and Cyclooxygenase-2 through AMPK pathway.	[203]
Name of the Component: AICAR Dose: 11 pM	Model: Endothelial cells	-Induction of AMPK demonstrated an anti-inflammatory pathway linking with PARP-1, and Bcl-6 pathways.	[16]
Name of the Component: Retinoic acid Dose: 10 µM	Model: BALB/c mice	-The treatment inhibited tissue factor and HMGB1 via modulation of AMPK activity in TNF-α activated endothelial cells and LPS-injected mice.	[194]
Name of the Component: Cilostazol Dose: 0.1% Cilostazol with chow food	Model: Sprague Dawley rats	-Induction of AMPK inhibited NF-κB activation, as well as the induction of iNOS mRNA and protein expression, within the aortas of LPS-treated rats.	[227]
Name of the Component: 2,3,4’,5-tetrahydroxystilbene-2-O-β-d-glucoside (THSG) Dose: 10, 20, 40, 80, and 100 µM	Model: Mouse primary microglia and cell culture	-LPS-induced NF-κB activation and neuro-inflammatory response (TNF-α, IL-6, and PGE2) activating AMPK/Nrf2 pathways.	[215]
Name of the Component: Ginseng Saponin Metabolite Rh3	Model: N/A	-Rh3 exerts an anti-inflammatory effect in microglia by modulating AMPK and its downstream signaling pathways such as phosphatidylinositol 3-kinase (PI3K)/Akt and JAK1/STAT1.	[228]
Name of the Component: Quercetin, Luteolin and EGCG Dose: 10 µmol/l each	Model: EA.hy-926 cells	-The treatment inhibited ER stress-associated TXNIP and NLRP3 inflammasome activation, and therefore protected endothelial cells from inflammation and apoptosis.	[207]
Name of the Component: Luteolin Dose: 100 µM	Model: HepG2 hepatocarcinoma cells	-AMPK activity was found to be critical for the inhibition of intracellular ROS in turn mediate NF-κB signaling.	[216]
Name of the Component: Methotrexate and A769662 Dose: N/A	Model: Human monocytes and bone marrow-derived macrophages	-Methotrexate-induced AMPK activation was associated with a reduction in the production of pro-inflammatory cytokines (IL-6, IL-1 β, and TNF-α) in response to LPS and TNF stimulation.	[198]
Name of the Component: Metformin Dose: 5 µM	Model: Wild type C57/Bl6 mice	-Metformin specifically inhibited LPS-induced IL-1β production and boosts IL-10 induction via AMKPα1- and or AMPKβ1 pathways.	[199]
Name of the Component: LY294002 and or CP-690550 Dose: 20 µM	Model: C57BL/6J mice	- AMPKα1 is required for IL-10 activation of the PI3K/Akt/mTORC1 and STAT3-mediated anti-inflammatory pathways.	[200]
Name of the Component: Lindenenyl acetate Dose: 20 µM	Model: The immortalized HPDL cell line	-Inducible nitric oxide synthase (iNOS) derived nitric oxide (NO) and cyclooxygenase-2 (COX-2) derived prostaglandin E2 (PGE2) production were found to be downregulated with the association with AMPK induction.	[202]
Name of the Component: Emodin Dose: 0-80 µM	Model: Mouse primary microglia and cell culture	-The approach effectively inhibited the production of pro-inflammatory cytokines, TNF-α and IL-6, and reduced the level of IκBα phosphorylation with the involvement of AMPK/Nrf2 Activation.	[229]
Name of the Component: Monascin and Ankaflavin Dose: 10 µM	Model: Mouse liver cell FL83B	-AMPK suppressed the production of inflammatory cytokines, including IL-6, TNF-α, and TGF-β.	[195]
Name of the Component: Flufenamic Acid Dose: 50 µM	Model: NRK-52E cells	-The strategy significantly suppressed nuclear factor- activity and inducible nitric-oxide synthase expression triggered by interleukin-1 and tumor necrosis factor- α.	[230]
Name of the Component: Xanthohumol Dose: 5 µM	Model: CHO-ARE-LUC cells	-Inhibition of GSK3β or mTOR is not involved in the observed AMPK boost, and -AMPK also enhanced the activity of the Nrf2/HO-1 signaling pathway.	[209]
Name of the Component: Genetically induced or Ghrelin Dose: 100 nM	Model: GHS-R knockout mice	-Ghrelin induction activated AMPK in primary endothelial cells showed potential activity in atherosclerosis by reducing inflammatory and proinflammatory cytokines.	[226]
Name of the Component:AMP mimetic ZMP Dose: 100 µM	Model: Vascular endothelial cells	-AMPK-mediated JAK-STAT signaling inhibition suppressed either by the IL-6Rα or in IL-6.	[231]
Name of the Component: Berberine and SB203580 Dose: 10 µM and 10 µM	Model: Sprague-Dawley rats	-The therapy reduced cleaved caspase 3, iNOS, Collagen-II, chondrocyte apoptosis and ameliorated cartilage degeneration via activating AMPK signaling and suppressing p38 MAPK activity.	[204]
Name of the Component: trans-caryophyllene (TC) Dose: 50 µM	Model: Rat cortical neurons/glia	-TC reduced cerebral ischemic injury via activation of the AMPK-CREB pathway.	[232]
Name of the Component: Mangiferin Dose: 0.1, 1, 10 μmol/L	Model: EA.hy926 cells	-The treatment ameliorated endothelial dysfunction by inhibition of ER stress-associated TXNIP/NLRP3 inflammasome activation and increased IL-1β secretion. in the endothelial cells	[208]
Name of the Component: Wogonin Dose: 10–100 μM	Model: Human glioma cell lines	-The strategy blocked cell cycle progression at the G1 phase and induced apoptosis by inducing p53 expression and further upregulating p21 expression.	[233]
Name of the Component: Ilexgenin A Dose: 80 mg/kg	Model: Sprague-Dawley rats and ICR male mice	-The treatment prevented NLRP3 inflammasome activation by down-regulation of NLRP3 and cleaved caspase-1 induction, and -reduced IL-1β secretion was also noticed associate with AMPK activation.	[234]
Name of the Component: CRPE55IB Dose: 40 µM	Model: Isolated primary microglia cultures	-CRPE55IB inhibited LPS-induced NF-κB activation and neuro-inflammatory response in microglia upregulating AMPK/Nrf2 pathways.	[210]
Name of the Component: Resveratrol Dose: 0.1 or 10 µM	Model: RAW 264.7 macrophage cells	-Enhancement of AMPK suppressed LPS-induced NF-κB-dependent COX-2 activation in RAW 264.7 macrophage cells.	[12]
Name of the Component: RSVA314 and RSVA405 Dose: 3 μM each	Model:C57BL/6 females cell cultures	-Enhancers of AMPK potently inhibited mTOR signaling, activated autophagy, and triggered Aβ clearance by the lysosomal system.	[235]
Name of the Component: Ursolic Acid Dose: 2.5 mM to 10 mM dose-dependently	Model:3T3-L1 pre-adipocytes	-Ursolic Acid inhibited CEBPα and β-actin in the fat cells via LKB1/AMPK pathways.	[51]
Name of the Component: Nitric oxide (NO) Dose: 100 mmol/L	Model: Human endothelial cells	- An inhibition of the IKK kinase and decreased NF-κB activation and TNF-α expression were observed with AMPKα2 phosphorylation.	[236]