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Metformin inhibits NLRP3. 108 / 108
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"We show that metformin inhibited NLRP3 inflammasome activation and interleukin (IL)-1beta production in cultured and alveolar macrophages along with inflammasome independent IL-6 secretion, thus attenuating lipopolysaccharide (LPS) - and SARS-CoV-2-induced ARDS."
| PMC
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"In SARS-CoV-2-infected mice, metformin has also been shown to inhibit the activation of the NLRP3 inflammasome and its-mediated lung inflammation [149]."
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"On the contrary, by inhibiting the activation of NLRP3 inflammasome, metformin induces M2 polarization in macrophages and promotes wound healing in rat dorsal skin (175)."
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"To determine whether short-term metformin treatment inhibits NLRP3-dependent inflammation in vivo we used the alum-induced peritonitis model ( Guarda et al., 2011 )."
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"Metformin inhibited NLRP3 inflammasomes activation and suppressed diabetes accelerated atherosclerosis in apoE -/- mice, which at least partially through activation of AMPK and regulation of thioredoxin-1 and thioredoxin-interacting protein."
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"Similarly, metformin, a frontline medication for type 2 diabetes, effectively prevents the activation of the TXNIP/NLRP-3 inflammasome by mitigating ER stress and activating AMPK in macrophages."
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"Sustained metformin administration reduces macrophage NLRP3 inflammasome activation in diabetic individuals and in non myeloid cells via an AMP activated protein kinase (AMPK)-dependent and poorly defined mechanism."
| PMC
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"In isolated rat hearts subjected to I/R, metformin reduced the size of the infarct and inhibited cardiac fibrosis through the reduction of proinflammatory cytokines (TNF-α, IL-6, IL-1β) and the suppression of the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome [11]."
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"In addition, metformin, a drug widely used for diabetes, was reported to indirectly inhibit the NLRP3 inflammasome via the regulation of the mechanistic target of rapamycin mechanistic target of rapamycin kinase (mTOR) protein, which is related to the reduction in the mortality of COVID-19 and type 2 diabetes mellitus (T2DM) patients [149]."
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"Metformin inhibits NLRP3 inflammasome activation."
| PMC
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"In addition, various studies have suggested that metformin inhibits NLRP3 inflammasome activity, thereby suppressing IL-1beta secretion and reducing inflammation [27,28]."
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"To determine whether short-term metformin treatment inhibits NLRP3 dependent inflammation invivo we used the alum induced peritonitis model."
| PMC
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"The suppression of NLRP3 by metformin was mainly attributed to the activation of the autophagy [68]."
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"Metformin stimulates mitophagy by activating AMPK, and mitophagy limits NLRP3 inflammasome activation."
| PMC
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"Another study showed that metformin inhibits the NLRP3 pathway in diabetic mice through an AMPK/mTOR-dependent pathway."
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"Specifically, in LPS-induced ALI models, the drug metformin can significantly reduce endothelial cell pyroptosis by inhibiting NLRP3 activity (Zhang et al., 2022)."
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"In addition, Ppargc1a induction with the plasmid and metformin can attenuate NLRP3 inflammasome and thus improve mitochondrial dynamics and morphology in the event of kidney fibrosis [43] ."
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"These results further confirm that inhibition of mtROS production is not required for metformin inhibition of NLRP3 inflammasome activation."
| PMC
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"Metformin was also seen to inhibit NLRP3 through the regulation of regulation of thioredoxin-1/thioredoxin-interacting protein ( Tang et al., 2019 )."
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"Furthermore, after stimulation with the mTOR inhibitor rapamycin, additional metformin treatment could still downregulate Nek7 and NLRP3."
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"Metformin and resveratrol could suppress dynamin‐related protein 1 activity and prevent activation of the NLRP3 inflammasome by limiting ER stress to reverse the damage process and protect mitochondrial integrity."
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"In addition, metformin inhibits the expression of inflammatory signaling pathways, including NLRP3 inflammasome and NF-κB activated in COVID-19 [35]."
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"[55] Besides, metformin a first-line drug in the management of T2DM, acts through activation of AMP-activated protein kinase (AMPK) and blocking of mitochondrial complex I. [56] Metformin inhibits NLRP3 inflammasome through AMPK activation and autophagy with mTOR pathway inhibition in dilated cardiomyopathy."
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"Although metformin attenuated mtROS accumulation in macrophages treated with the NLRP3 activators ATP and nigericin, this effect was not important for inhibition of NLRP3 inflammasome activation which was not reversed by treatment of metformin incubated macrophages with the mtROS generators mitoParaquat and DMNQ."
| PMC
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"In addition, Guo et al [XREF_BIBR] found that the pioglitazone metformin complex preparation could reduce inflammation, inhibit activation of the NLRP3 inflammasome, and reduce the release of IL-1beta in the treatment of PCOS."
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"Metformin is used for treating type 2 diabetes either alone or in combination with other hypoglycemic agents.122 Yang et al reported that metformin blocks the NLRP3 inflammasome through inhibition of the AMPK/mTOR pathway, and improves cardiac fibrosis in mice with diabetic cardiomyopathy.123 Empaglifozin (EMPA) selectively inhibits the sodium-glucose co-transporter 2."
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"Overall, metformin inhibited the activation of NLRP3 inflammasome, decreased cartilage degradation, reversed subchondral bone remodelling and inhibited chondrocyte pyroptosis."
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"It has been reported that Metformin can promote autophagy via the above pathway to inhibit the activation of NLRP3 inflammatory corpuscle and play a protective role in the heart (96)."
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"Our findings suggest that metformin attenuates central sensitization in CM by regulating the activation of microglia and NLRP3 inflammasome through the TREM2-SYK pathway."
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"[55] Besides, metformin a first-line drug in the management of T2DM, acts through activation of AMP-activated protein kinase (AMPK) and blocking of mitochondrial complex I. [56] Metformin inhibits NLRP3 inflammasome through AMPK activation and autophagy with mTOR pathway inhibition in dilated cardiomyopathy."
| DOI
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"Metformin inhibited the activation of TNF-α, IL-6, IL-1β, and NLRP3 inflammasome, reduced the size of MI and myocardial fibrosis, enhanced the activity of myocardial cells, reduced the activity of LDH, inhibited pyroptosis and inflammation (107)."
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"Metformin and resveratrol protected mitochondrial integrity by inhibiting Drp1 activity and prevented NLRP3 inflammasome activation by suppressing ER stress, and thereby protected adipose function from high glucose insult."
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"Additionally, compared with the control group, metformin supply reduced the activation of NLRP3 (P < 0.05)."
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"Overall, our findings discovered that metformin may deactivate the S100A8/A9-NLRP3-IL-1β pathway as well as NLRP3 inflammasome to lessen the damage to lung tissue in septic young mice."
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"Our data report that metformin effectively inhibits the activation of TNC microglia and NLRP3 while alleviating the inflammatory response.Studies have demonstrated that LPS stimulation causes an elevation of TREM2 expression in mouse primary cultured microglia and facilitates neuroinflammatory processes [50]."
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"In patients with T2DM, an upregulation of IL-18, IL-1β, and caspase-1 expression is detected, and the anti-diabetic drug metformin can impair the activation of the NLRP3 inflammasome, resulting in a decrease of mature IL-1β level via AMPK-mediated signaling pathway[45]."
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"Based on the aforementioned findings, we hypothesize that metformin can decrease the occurrence of OA chondrocyte pyrolysis by inhibiting the NLRP3 inflammasome, inhibiting cartilage degradation, promoting cartilage anabolism and inhibiting cartilage catabolism."
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"Metformin inhibited the activation of NLRP3 inflammasome, decreased cartilage degradation, improved subchondral bone remodelling and inhibited chondrocyte pyroptosis."
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"Similarly, metformin, by activating AMPK/autophagy and subsequently inhibiting the NLRP3 inflammasome, possesses cardioprotective and anti-inflammatory effects [8]."
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"Metformin has also been revealed to inhibit NLRP3(22)."
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"Moreover, metformin inhibited LPS-induced upregulation of the TRPV1/NLRP3 signaling pathway in microglial cell line, an effect that can be reversed by the TRPV1-specific agonist capsaicin."
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"It has been shown that metformin is able to decrease the activation of NLRP3 in various tissues (Lee et al., 2013; Bullón et al., 2016; Li et al., 2016)."
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"We provide evidence that metformin inhibits the NLRP3 inflammasome priming and activation in microglia."
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"Among the last ones, a remarkable effect of metformin in preventing LPS-induced IL-1β mRNA levels was found, thus further supporting our in vitro study showing that metformin highly inhibits NLRP3 inflammasome priming in microglia.Under brain pathological conditions, microglial checkpoints pathways sense the environment to prevent overreaction to external stimuli."
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"Metformin, the most widely used drug for treating T2D, can inhibit NLRP3 by activating AMPK (AMP activated protein kinase), thus increasing autophagy activity to promote the clearance of inflammasomes via inhibiting the mTOR pathway and alleviating the symptoms in diabetic cardiomyopathy."
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"Metformin reduces the activity of NLRP3 inflammasomes by inhibiting the expression of Nek7, and significantly reduces experimental diabetic periodontitis in vivo and in vitro (Zhou et al., 2019)."
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"Metformin prevented an activation of NLRP3 and ameliorated the inflammatory responses in patients with diabetes (30)."
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"Furthermore, metformin has been reported to inhibit NLRP3-dependent inflammation via the AMPK/mTOR pathway in DCM ( Yang et al., 2019 )."
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"Interestingly, even glucose in high concentrations activates NLRP3 inflammasome in trophoblasts, and a recent study showed that metformin inhibits NLRP3 through the AMPK/mTOR pathway."
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"Metformin also inhibited the interaction of TXNIP and NLRP3 [XREF_BIBR]."
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"Furthermore, metformin activated phosphorylated AMPK, decreased pro inflammatory cytokines, TNF-alpha, IL-6 and IL-1beta, and decreased NLRP3 inflammasome activation."
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"71 Metformin and empagliflozin, two well-known antidiabetic drugs, inhibited NLRP3 inflammasome and decelerated the development of diabetic cardiomyopathy but via different mechanisms."
| PMC
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"A previous study reported that metformin can suppress NLRP3-dependent inflammation through the AMPK/mTOR pathway in diabetic cardiomyopathy ( Yang et al., 2019 )."
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"However, NLRP3 could also be inhibited by glyburide, dioscin, metformin and resveratrol, preventing the bone loss from the progress of pyroptosis."
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"Recently, Yang F et al. demonstrated that metformin can suppress the NLRP3 inflammasome through the AMPK/mTOR/autophagy pathway."
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"Another potential effect of metformin is preventing the activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome (Wiernsperger et al., 2022)."
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"The current study found that metformin can decrease the occurrence of chondrocyte pyroptosis by affecting the activation of NLRP3 inflammasome, and that it can ultimately delay the progression of OA."
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"In the same experiment, metformin was also shown to increase the production of IL-10, inhibit the activation of NLRP 3 inflammasome and decrease caspase-1 activation."
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"In addition, Yang et al. verified that metformin could inhibit the NLRP3 inflammasome by activating the AMPK and mTOR pathway in diabetic cardiomyopathy."
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"Metformin Inhibits NLR Family Pyrin Domain Containing 3 ( NLRP ) - Relevant Neuroinflammation via an Adenosine-5 ' - Monophosphate-Activated Protein Kinase ( AMPK ) - Dependent Pathway to Alleviate Early Brain Injury After Subarachnoid Hemorrhage in Mice ."
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"Another study found that metformin inhibits the activation of the NLRP3 inflammasome and attenuates acute respiratory distress syndrome by targeting the electron transport chain complex 1 independent of the AMPK or NF-kB pathways (39)."
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"The classic oral hypoglycemic drug metformin inhibited NLRP3 inflammasome by the AMPK/mTOR pathway in DCM ( Yang et al., 2019 ), which is why metformin was used as a positive control in this study."
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"More importantly, the administration of metformin reversed piperine-induced inhibition on NLRP3 inflammasome and recovered pyroptosis in HK-2 cells, implying the essential role of AMPK signaling in re[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The diabetes drug metformin indirectly inhibits NLRP3 by regulating mTOR, and its use is significantly associated with reduced mortality among patients with COVID-19 and type 2 diabetes."
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"Metformin was also recently shown to inhibit NLRP3 activation and lung inflammation in SARS-CoV-2-infected mice ."
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"Then, further research is needed into whether metformin inhibits NLRP3 activation through mitochondrial autophagy."
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"Metformin can inhibit the NLRP3 inflammasome activation in apolipoprotein E (apoE) -/- mice and inhibit diabetes accelerated AS, at least in part by activating AMPK and regulating thioredoxin-1 and thioredoxin interacting protein."
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"We further found that metformin significantly suppressed NLRP3 inflammasome activation, subsequent caspase-1 cleavage, and interleukin-1beta secretion in both peripheral macrophages and central hippocampus."
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"A recent study by Yang F. et al., in 2019, further emphasized the role of AMPK activators in diabetic cardiomyopathy benefit and reported metformin-mediated NLRP3 inflammasome inhibition via AMPK/mTOR pathway [57]."
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"Metformin inhibits the activation of STING and NLRP3 in hypothalamic microglia of obese mice."
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"Besides several infectious diseases, metformin has also been discovered to prevent NLRP3 inflammasome activity both in periodontitis (Li et al., 2016) and psoriasis (Tsuji et al., 2020)."
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"AICAR and metformin are potent autophagy activators and inhibit Aβ-induced NLRP3 over activation [81] ."
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"Recently, Yang et al. demonstrated that metformin suppressed NLRP3 inflammasome through AMPK/mTOR/autophagy pathways in diabetic cardiomyopathy [34]."
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"Additionally, metformin inhibits the NLRP3 inflammasome, decreasing IL-1β release by stabilizing mitochondrial function and reducing reactive oxygen species (ROS), a mechanism confirmed in metabolic disease models but applicable to infection-related inflammation (Xian et al., 2021)."
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"As shown in Figures 2D–G, the percentage of NLRP3- and caspase-1-positive cells was markedly increased in the pulmonary endothelium of lung tissues following the LPS challenge, but the supplementation of metformin significantly decreased active NLRP3 and caspase-1-positive cells."
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"These results indicate that metformin can inhibit NLRP3 inflammasome activation in apoE -/- mice and inhibit diabetes accelerated AS, at least in part by activating AMPK and regulating thioredoxin-1 and thioredoxin interaction protein."
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"Metformin, a diabetes drug under investigation for its potential to extend HS and LS, activates AMPK and inhibits the NLRP3 inflammasome (Zhou et al., 2001; Barzilai et al., 2016; Yang et al., 2019)."
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"Furthermore, after stimulation with the mTOR inhibitor rapamycin, additional metformin treatment could still downregulate Nek7 and NLRP3."
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"Besides, Metformin inhibits NLRP3 activation through the AMPK/mTOR signaling pathway and promotes M2-type polarization of Mp, and is beneficial to Non-DW healing (Qing et al., 2019)."
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"Metformin also inhibits ROS accumulation and NLRP3 inflammasome activation stimulated by high glucose in macrophages which is blocked by compound C."
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"Metformin also inhibits the NLRP3 inflammasome and retards renal fibrosis via PGC-1α activating in adenine-fed and UUO mice."
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"In order to indicate whether metformin and atorvastatin could inhibit NLRP3 inflammasome activation, the expression levels of NLRP3 and its downstream molecules (caspase-1 and IL-1beta) were detected by Western blot assay."
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"It has been shown that metformin inhibits NLRP3 activation in other disease models (Jia et al. 2020; Xian et al. 2021)."
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"In our study, we observed that Metformin significantly suppressed accumulation of the NLRP3 inflammasome and activation of Caspase-1."
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"By repeating the same assays on macrophages with AMPKα gene silencing, we found that AMPK was involved in metformin mediated NLRP3 inflammasome deactivation but not downregulation of NLRP3 and pro-IL-[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Metformin reduced the activity of NLRP3 in primary urothelial cells."
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"Metformin also inhibits NLRP3 inflammasome (141)."
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"Combined Administration of Metformin and Atorvastatin Inhibited NLRP3 Inflammasome in H9C2 Cells Exposed to Palmitate via Toll Like Receptor 4/NF-kappaB Signaling Pathway."
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"Combined Treatment With Metformin and Atorvastatin Inhibited Activation of NLRP3 Inflammasome in Heart Tissues of db/db Mice."
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"Therefore, metformin can inhibit the activation of NLRP3 inflammasome and the focal death of chondrocytes, thereby delaying the progress of OA (149)."
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"But the therapeutically relevant concentration of metformin to glucose metabolism should be explored in future.Overall, our data suggested that metformin could reduce NLRP3 inflammasome activity in ox[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"A number of scholars pointed out that metformin could inhibit NLRP3 inflammasome by activating the AMPK and mTOR signaling pathway."
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"Metformin Inhibits the NLRP3 Inflammasome via AMPK/mTOR-dependent Effects in Diabetic Cardiomyopathy."
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"The aim of this study was to investigate whether metformin can inhibit the NLRP3 inflammasome by activating the AMPK/mTOR pathway in DCM."
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"These results show that metformin reduces NLRP3 protein expression and activation via AMPK and PP2A in oxLDL-induced macrophages ( 71 ) ."
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"In addition, metformin or resveratrol attenuated OGD/R-induced upregulation of TXNIP and NLRP3 activation, whereas SIRT6 deficiency abolished the effects of metformin or resveratrol on the expression of TXNIP and NLRP3 inflammasome signaling (Fig. 6B)."
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"These results confirmed that metformin activated p-AMPK and autophagy, thus inhibiting the NLRP3 inflammasome."
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"Metformin inhibits the NLRP3 pathway via AMPK/mTOR-dependent effects in diabetic mice."
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"Metformin, a specific activator of AMPK, inhibited the NLRP3 inflammasome and boosted M2 macrophage polarization to accelerate wound healing [ 36 ]."
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"HTR-8 cells were pre-treated with 1000 nM insulin for 48 h and metformin for an additional 24 h. Western blot analyses demonstrated that metformin — across a range of concentrations — suppressed IR-induced increases in NLRP3, cleaved caspase-1, and GSDMD-NT (Fig. 5A-D)."
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"Our study verified that metformin could inhibit the NLRP3 inflammasome via AMPK/mTOR signaling in DCM (Fig. 8)."
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"AMPK activator metformin inhibits NLRP3 inflammasome through the activation of the mTOR pathway, in addition to mediating autophagy and alleviating pyroptosis in type 2 diabetes."
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"Therefore, we demonstrated that metformin inhibits the NLRP3 pathway via mitochondrial complex I/AMPK/mTOR-dependent effects in diabetic mice.In conclusion, our findings strongly demonstrate that metformin possesses cardioprotective and anti-inflammatory effects by activating AMPK/autophagy and subsequently inhibiting the NLRP3 inflammasome in DCM."
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"PGC-1alpha induction with the plasmid and metformin improved mitochondrial dynamics and morphology and attenuated the NLRP3 inflammasome and cell injury."
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"171 Moreover, hypoglycemic agent metformin reduced chondrocyte pyroptosis in an OA rat model by inhibiting NLRP3."
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"In addition to decreasing IL-1β production, metformin also reduces the effects of existing IL-1β by inhibiting activation of the NLRP3 inflammasome (167)."
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"For instance, metformin activates autophagy and suppresses NLRP3 inflammasome activity, reducing plaque progression [23]."
| PMC
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"For example, metformin, a first-line drug for diabetes treatment, inhibited the activation of NLRP3 inflammasome and cardiomyocyte pyroptosis (209–211), reducing myocardial ischemia-reperfusion injury (210)."
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