ml265  (MedChemExpress)

Journal: Frontiers in Pharmacology

Article Title: Macrophage PKM2 depletion ameliorates hepatic inflammation and acute liver injury in mice

doi: 10.3389/fphar.2025.1546045

Figure Lengend Snippet: Pharmacological PKM2 antagonist effectively attenuates ALI in mice. (A) Scheme diagram depicting C57BL/6J mice pre-treated with ML265 (30 mg/kg), a PKM2 antagonist, were challenged with APAP (300 mg/kg) for indicated time. n = 5-7 per group. (B) Serum levels of ALT of APAP-induced mice after ML265 treatment. (C) Representative images and quantification of livers, H&E-, IHC of cleaved caspase 3- for ML265- or vehicle-treated mice after 24 h of APAP induction (300 mg/kg). Necrotic region was enclosed in dotted lines. (D) Immunofluorescence staining for iNOS and CD206 of ML265- or vehicle-treated mice after 24 hours of APAP induction (300 mg/kg). (E) The mRNA levels of Tnfa , Il1b and Il6 in ML265- or vehicle-treated mice after 24 h of APAP induction. (F) Kaplan-Meier survival curve comparing percent survival of mice pre-treated with ML265 or vehicle after induction of ALF by APAP (750 mg/kg). n = 7 per group. Scale bar: 100 μm. *P < 0.05; **P < 0.01; ***P < 0.001. Error bars depict the standard deviations.

Article Snippet: To investigate the therapeutic effect of PKM2 antagonist on APAP-induced ALI and ALF, 6-8-week-old male C57BL/6J mice were pretreated with single i.p. injection of ML265 (30 mg/kg; MedChemExpress, USA), and then were subjected to 300 mg/kg or 750 mg/kg APAP induction, for analysis of liver injury and survival respectively.

Techniques: Immunofluorescence, Staining

Journal: European journal of pharmacology

Article Title: Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation.

doi: 10.1016/j.ejphar.2022.175352

Figure Lengend Snippet: Fig. 1. Quercetin (Que) attenuates lipopolysaccharide (LPS)-induced lung injury. (A) Representative images of hematoxylin and eosin staining for endotoxin-induced lung injury at 18 h after LPS treatment with or without Que treatments, at 200x and 400x magnification (upper and lower panels, respectively). (B) Histopathological lung injury score in the 4 groups. (C) The serum lactate levels were determined. (D) The degree of Evans blue dye leakage in lung tissue was determined. (E) Percentage of neutrophils in the BALF. (F) Percentage of lymphocytes in the BALF. (G) BALF TNFα levels determined by ELISA. (H) BALF IL-6 levels determined by ELISA. (I) BALF IL-1β levels determined by ELISA. (J) Another set of animals were exposed to LPS and treated with vehicle or Que, or ML265, the percent survival rate was expressed as a Kaplan–Meier survival curves, n = 10. All data were expressed as mean ± SD, n = 5–10/per group. *p < 0.05 was considered significant, **p < 0.01, ***p < 0.001.

Article Snippet: To investigate mechanisms that limit PKM2 dimer formation, the small molecule inhibitor ML265 (50 mg/kg, dissolved in 2% DMSO, then dissolved in 30% PEG 300 + 2% Tween 80 + 66% ddH2O, i.p.) (Selleck, USA) was administered 30 min before LPS exposure.

Techniques: Staining, Enzyme-linked Immunosorbent Assay

Journal: European journal of pharmacology

Article Title: Quercetin protects against LPS-induced lung injury in mice via SIRT1-mediated suppression of PKM2 nuclear accumulation.

doi: 10.1016/j.ejphar.2022.175352

Figure Lengend Snippet: Fig. 4. Prevention of PKM2 nuclear accumulation could attenuate lipopolysaccharide (LPS)-induced inflammatory injury and decrease NLRP3 activation in mice. (A) Representative images of hematoxylin and eosin staining for endotoxin-induced lung injury at 18 h after LPS treatment with or without ML265 treatments, at 200x and 400x magnification (upper and lower panels, respectively). (B) Histopathological lung injury score in the 4 groups. (C) Serum lactate levels were deter mined. (D) Real-time RT-PCR measuring NLRP3, SIRT1, IL-1β, and IL18 mRNA expression levels in lung tissues. (E) Real-time RT-PCR measuring NLRP3, SIRT1, PKM2, IL-1β, and IL18 mRNA expression levels shown in the seven groups in J774A.1 cells. (F) The immunoblotting assay showing the protein levels of NLRP3, SIRT1, GSDMD, ASC, cleaved-caspase1 and nuclear PKM2 under LPS exposure with or without ML265 treatments in lung tissues. Quantitative analysis of NLRP3 (G), SIRT1 (H), and nuclear PKM2(I) under LPS exposure with or without ML265 treatments. All data are expressed as mean ± SD. n = 3–6/per group. ns P > 0.05, *P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: To investigate mechanisms that limit PKM2 dimer formation, the small molecule inhibitor ML265 (50 mg/kg, dissolved in 2% DMSO, then dissolved in 30% PEG 300 + 2% Tween 80 + 66% ddH2O, i.p.) (Selleck, USA) was administered 30 min before LPS exposure.

Techniques: Activation Assay, Staining, Quantitative RT-PCR, Expressing, Western Blot