metformin  (Merck & Co)

Journal: Genes & Diseases

Article Title: Salt-inducible kinase 1 is a key gene in suppressing EVD68-induced asthma by modulating antiviral immunity

doi: 10.1016/j.gendis.2025.101845

Figure Lengend Snippet: Metformin-mediated activation of SIK1 protects against EV-D68-driven asthma exacerbation in house dust mite (HDM)-sensitized mice. (A) C57BL/6 mice (6–8 weeks) were administered metformin at doses of 100 mg/kg or 250 mg/kg once daily via intraperitoneal injection on day 1 and day 2. On day 3, lung tissues were collected, and the protein level of SIK1 was determined by western blotting analysis. (B) Experimental timeline. C57BL/6 mice (6–8 weeks) were intranasally sensitized with 250 μg kg −1 HDM extract on day 0 and challenged daily with the same dose on days 7–11. On days 12–13, animals received EV-D68 (1 × 10 6 PFU/kg) or DMEM (vehicle) intranasally. Metformin (100 mg/kg, intraperitoneal) was administered once daily on days 12–14. Airway hyper-responsiveness measurements and broncho-alveolar lavage fluid (BALF) collection were performed on day 15; lung tissue was used for quantitative PCR analyses. (C) Airway responsiveness to increasing doses of methacholine. (D) Differential cell counts of BALF by Wright-Giemsa staining. (E – H) The indicated genes were detected by quantitative PCR and normalized to GAPDH expression. Values were from three independent experiments and expressed as mean ± standard deviation. ∗ p < 0.05, ∗∗ p < 0.01, and ∗∗∗ p < 0.001.

Article Snippet: C57BL/6 mice (6–8 weeks old, Chongqing Medical University) were randomly divided into three experimental groups that received house-dust-mite (HDM) (Greer labs, USA) sensitization alone, HDM followed by EV-D68 challenge, or HDM plus EV-D68 challenge combined with metformin (MCE, USA) treatment.

Techniques: Activation Assay, Injection, Western Blot, Real-time Polymerase Chain Reaction, Staining, Expressing, Standard Deviation

Journal: The Eurasian Journal of Medicine

Article Title: Dependency of Non-Small Cell Lung Cancer Cells on Glutamine and Glucose Levels in the Presence of Metformin

doi: 10.5152/eurasianjmed.2026.251018

Figure Lengend Snippet: Bioinformatic analysis of GSE146982 data set for A549 cells treated with or without metformin A) Differentially changed genes upon metformin treatment in A549 cells ( P adj < .05). B) Top 10 metabolites affected by the presence or absence of metformin in A549 cells.

Article Snippet: Groups are treated with high glucose (4.5 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine or low glucose (1 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine, and 10 mM metformin (Merck cat: 317240), unless otherwise stated.

Techniques:

Journal: The Eurasian Journal of Medicine

Article Title: Dependency of Non-Small Cell Lung Cancer Cells on Glutamine and Glucose Levels in the Presence of Metformin

doi: 10.5152/eurasianjmed.2026.251018

Figure Lengend Snippet: Changes in proliferation rate in low (1 g/L) and high (4.5 g/L) glucose conditions with or without glutamine upon 10 mM metformin treatment in A549 cells. * P < .05, ** P < .01, *** P < .001, **** P < .0001. $ shows the comparison between no glutamine vs. 1% (2 mM) glutamine and 2% (4 mM) glutamine. # shows the comparison between no glutamine vs. only 2% glutamine.

Article Snippet: Groups are treated with high glucose (4.5 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine or low glucose (1 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine, and 10 mM metformin (Merck cat: 317240), unless otherwise stated.

Techniques: Comparison

Journal: The Eurasian Journal of Medicine

Article Title: Dependency of Non-Small Cell Lung Cancer Cells on Glutamine and Glucose Levels in the Presence of Metformin

doi: 10.5152/eurasianjmed.2026.251018

Figure Lengend Snippet: Changes in proliferation rate in low (1 g/L) and high (4.5 g/L) glucose conditions with or without glutamine (2 mM or 4 mM) upon 10 mM metformin treatment in Calu1 cells. * P < .05, ** P < .01, *** P < .001, **** P < .0001. (+) shows the comparison between no glutamine vs. only 1% glutamine; (#) shows the comparison between no glutamine vs. only 2% glutamine; ($) shows the comparison between no glutamine vs. both 1% glutamine and 2% glutamine within the same treatments. (&) shows 1% glutamine vs. 2% glutamine.

Article Snippet: Groups are treated with high glucose (4.5 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine or low glucose (1 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine, and 10 mM metformin (Merck cat: 317240), unless otherwise stated.

Techniques: Comparison

Journal: The Eurasian Journal of Medicine

Article Title: Dependency of Non-Small Cell Lung Cancer Cells on Glutamine and Glucose Levels in the Presence of Metformin

doi: 10.5152/eurasianjmed.2026.251018

Figure Lengend Snippet: Changes in proliferation rate in low (1 g/L) and high (4.5 g/L) glucose conditions with or without glutamine (2 mM or 4 mM) upon 10 mM metformin treatment in H2009 cells. * P < .05, ** P < .01, *** P < .001, **** P < .0001. (+) shows the comparison between no glutamine vs. only 1% glutamine; (#) shows the comparison between no glutamine vs. only 2% glutamine; ($) shows the comparison between no glutamine vs. both 1% glutamine and 2% glutamine within the same treatments.

Article Snippet: Groups are treated with high glucose (4.5 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine or low glucose (1 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine, and 10 mM metformin (Merck cat: 317240), unless otherwise stated.

Techniques: Comparison

Journal: The Eurasian Journal of Medicine

Article Title: Dependency of Non-Small Cell Lung Cancer Cells on Glutamine and Glucose Levels in the Presence of Metformin

doi: 10.5152/eurasianjmed.2026.251018

Figure Lengend Snippet: The expression pattern of the genes related to proliferation (CCND1, CDK4 and MKI67), apoptosis (BAX, BCL2 and BAK1), and glutamine metabolism (SLC1A5, SLC3A2 and GLUD1). Comparison is done Control vs. Metformin. * P < .05, ** P < .01, *** P < .001, **** P < .0001.

Article Snippet: Groups are treated with high glucose (4.5 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine or low glucose (1 g/L) with (1% [2 mM] or 2% [4 mM]) or without glutamine, and 10 mM metformin (Merck cat: 317240), unless otherwise stated.

Techniques: Expressing, Comparison, Control

Journal: Materials Today Bio

Article Title: Multifunctional injectable hydrogel with Zn-metformin coordination for synergistic anti-infection, antioxidant, and osteogenic therapy in periodontitis

doi: 10.1016/j.mtbio.2026.103148

Figure Lengend Snippet: Schematic illustration of the fabrication and administration of PgC@ZM hydrogel for periodontitis treatment. (A) The preparation of PgC@ZM hydrogel consisted of Zn-Metformin coordination and protocatechuic acid-grafted carboxymethyl chitosan. (B) The mechanism of PgC@ZM injectable hydrogel in periodontitis treatment, through the antimicrobial activity from carboxymethyl chitosan and zinc ions, potent antioxidant capacity from protocatechuic acid, and osteogenic potential from metformin.

Article Snippet: The metformin hydrochloride (≥97%), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (EDC, ≥98.5%), N-Hydroxysuccinimide (NHS, ≥98%), and zinc chloride (≥98%) were purchased from Aladdin Industrial Inc. (Shanghai, China).

Techniques: Activity Assay

Journal: Materials Today Bio

Article Title: Multifunctional injectable hydrogel with Zn-metformin coordination for synergistic anti-infection, antioxidant, and osteogenic therapy in periodontitis

doi: 10.1016/j.mtbio.2026.103148

Figure Lengend Snippet: Characterization of ZM complex and PgC@ZM hydrogel. (A) FT-IR spectra of metformin and ZM. (B) 1 H NMR spectra of metformin and ZM. (C) FE-SEM image of ZM complex. (D) 1 HNMR spectrum of CMCS and PgC. (E) Photo of PgC@ZM hydrogel and the injectability of the PgC@ZM. (F) Photo of the adhesion properties of PgC@ZM hydrogel.The weight shown is 50 g. (G and H) SEM and EDS images of PgC@ZM hydrogel.

Article Snippet: The metformin hydrochloride (≥97%), N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (EDC, ≥98.5%), N-Hydroxysuccinimide (NHS, ≥98%), and zinc chloride (≥98%) were purchased from Aladdin Industrial Inc. (Shanghai, China).

Techniques:

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells

doi: 10.1080/14756366.2026.2666369

Figure Lengend Snippet: Baseline glucose uptake and metabolic gene expression in differentiated C2C12 myotubes under non-PA conditions. Differentiated C2C12 myotubes were treated for 24 h with each of metabolic hormones (insulin, leptin, or adiponectin), reference antidiabetic agents (Met, Duo, NAC), or E. ciliata -derived compounds (EC2–EC5). (A) Glucose uptake (%) was measured in hormone/antidiabetic agent-treated cells (top) and EC-treated cells (bottom). (B) Relative levels of gene expression of Ptpn1 , Pparg , Ampka1 , Ampka2 , and Txnip was assessed via qRT-PCR. ECs were treated at the higher dose (20 μM). The concentration of ECs used in this experiment was 10 μM (L) or 20 μM (H). * p < 0.05, ** p < 0.01, *** p < 0.001 vs. non-treated (vehicle)control. PA , palmitate; Ins-C , insulin- control; Lep-C, leptin-control; Adi-C, Adiponectin-control ; ScI, sc-222227; UA, ursolic acid; Met, metformin; Duo, Duoglow (pioglitazone + dapagliflozin); NAC, N-acetylcysteine; EC2–EC5, E. ciliata -derived compounds; Ptpn1 , protein tyrosine phosphatase 1B; Pparg , peroxisome proliferator-activated receptor gamma; Ampka1/2 , AMP-activated protein kinase alpha 1/2; Glut4 , glucose transporter 4.

Article Snippet: Reagents for biological assays, such as palmitic acid (PA), human recombinant insulin, leptin, adiponectin, metformin, Duoglow (Duo; pioglitazone + dapagliflozin), and N-acetylcysteine (NAC), were purchased from Sigma-Aldrich (St. Louis, MO, USA) or TCI Chemicals (Tokyo, Japan).

Techniques: Gene Expression, Derivative Assay, Quantitative RT-PCR, Concentration Assay, Control

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells

doi: 10.1080/14756366.2026.2666369

Figure Lengend Snippet: Restoration of the impairment of glucose uptake by E. ciliata -derived compounds in PA-induced insulin-resistant C2C12 myotubes. (A) Glucose uptake levels (%) were quantified. (B) Relative levels of mRNA expression of Ptpn1 , Glut4 , Pi3k , and Akt were analysed via qRT-PCR. EC2-H and EC5-H downregulated Ptpn1 and restored Glut4 levels. ECs were treated at the dose of 20 μM. The concentration of ECs used in this experiment was 10 μM (L) or 20 μM (H). Data are presented as mean ± SEM ( n = 3). * p < 0.05, ** p < 0.01 vs. Insulin + PA control group. † p < 0.05, †† p < 0.01 vs. insulin control group. PA, palmitate; Ins-C, insulin-only control; Ins-PA, insulin + PA; ScI, sc-222227; UA, ursolic acid; Met, metformin; Duo, Duoglow (pioglitazone + dapagliflozin); NAC, N-acetylcysteine; EC2–EC5, E. ciliata -derived compounds; Ptpn1 , protein tyrosine phosphatase 1B; Glut4 , glucose transporter 4; Pi3k , phosphoinositide 3-kinase; Akt , protein kinase B.

Article Snippet: Reagents for biological assays, such as palmitic acid (PA), human recombinant insulin, leptin, adiponectin, metformin, Duoglow (Duo; pioglitazone + dapagliflozin), and N-acetylcysteine (NAC), were purchased from Sigma-Aldrich (St. Louis, MO, USA) or TCI Chemicals (Tokyo, Japan).

Techniques: Derivative Assay, Expressing, Quantitative RT-PCR, Concentration Assay, Control

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells

doi: 10.1080/14756366.2026.2666369

Figure Lengend Snippet: Reversal of leptin resistance by E. ciliata -derived compounds in PA-treated C2C12 myotubes. Glucose uptake in response to leptin stimulation. Glucose uptake was expressed as a percentage of normal cells. (B) Gene expression analysis of Ptpn1 , Jak2 , Stat3 , and Glut4 was performed by qRT-PCR. ECs were treated at the dose of 20 μM. Data are presented as mean ± SEM ( n = 3). * p < 0.05, ** p < 0.01 vs. Lep + PA control group. † p < 0.05, †† p < 0.01 vs. Leptin control group. PA, palmitate; Lep-C, leptin-only control; Lep-PA, leptin + PA; ScI, sc-222227; UA, ursolic acid; Met, metformin; Duo, Duoglow (pioglitazone + dapagliflozin); NAC, N-acetylcysteine; EC2–EC5, E. ciliata -derived compounds; Ptpn1 , protein tyrosine phosphatase 1B; Jak2 , Janus kinase 2; Stat3 , signal transducer and activator of transcription 3; Glut4 , glucose transporter 4.

Article Snippet: Reagents for biological assays, such as palmitic acid (PA), human recombinant insulin, leptin, adiponectin, metformin, Duoglow (Duo; pioglitazone + dapagliflozin), and N-acetylcysteine (NAC), were purchased from Sigma-Aldrich (St. Louis, MO, USA) or TCI Chemicals (Tokyo, Japan).

Techniques: Derivative Assay, Gene Expression, Quantitative RT-PCR, Control

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells

doi: 10.1080/14756366.2026.2666369

Figure Lengend Snippet: Enhancement of adiponectin responsiveness by E. ciliata -derived compounds under palmitate-induced metabolic stress. (A) Glucose uptake in response to adiponectin stimulation. The ability of glucose uptake was expressed as a percentage of normal cells. (B) Gene expression of Ptpn1 , Ampka1 , Ampka2 , Glut4 , Pparg , and Pgc1a was assessed by qRT-PCR. ECs were treated at the dose of 20 μM. Data are shown as mean ± SEM ( n = 3). * p < 0.05, ** p < 0.01 vs. no compound-treated PA + Adiponectin group. † p < 0.05, †† p < 0.01 vs. Adiponectin control group. PA, palmitate; ScI, sc-222227; UA, ursolic acid; Met, metformin; Duo, Duoglow (pioglitazone + dapagliflozin); NAC, N-acetylcysteine; EC2–EC5, E. ciliata -derived compounds; Ptpn1 , protein tyrosine phosphatase 1B; Pparg , peroxisome proliferator-activated receptor γ; Pgc1a , PPARγ coactivator 1-α; Glut4 , glucose transporter 4.

Article Snippet: Reagents for biological assays, such as palmitic acid (PA), human recombinant insulin, leptin, adiponectin, metformin, Duoglow (Duo; pioglitazone + dapagliflozin), and N-acetylcysteine (NAC), were purchased from Sigma-Aldrich (St. Louis, MO, USA) or TCI Chemicals (Tokyo, Japan).

Techniques: Derivative Assay, Gene Expression, Quantitative RT-PCR, Control

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells

doi: 10.1080/14756366.2026.2666369

Figure Lengend Snippet: Effects of E. ciliata -derived compounds on redox homeostasis: NAD⁺/NADH, NADP⁺/NADPH ratios, and FAD levels. C2C12 myotubes were co-treated with palmitate (PA, 300 μM for 48 h) and each test compound or hormone for the final 24 h. The NAD⁺/NADH ratio (A), NADP⁺/NADPH ratio (B), and FAD (C) levels were measured to assess redox homeostasis. Data are presented as mean ± SEM ( n = 5). * p < 0.05, ** p < 0.01 vs. corresponding –PA control group (i.e. basal); † p < 0.05, †† p < 0.01 vs. PA-treated (vehicle) control group. PA, palmitate; ScI, sc-222227; UA, ursolic acid; Met, metformin; Duo, Duoglow (pioglitazone + dapagliflozin); NAC, N-acetylcysteine; EC2–EC5, E. ciliata -derived compounds; NAD⁺, nicotinamide adenine dinucleotide (oxidised form); NADH, nicotinamide adenine dinucleotide (reduced form); NADP⁺, nicotinamide adenine dinucleotide phosphate (oxidised form); NADPH, nicotinamide adenine dinucleotide phosphate (reduced form); FAD, flavin adenine dinucleotide.

Article Snippet: Reagents for biological assays, such as palmitic acid (PA), human recombinant insulin, leptin, adiponectin, metformin, Duoglow (Duo; pioglitazone + dapagliflozin), and N-acetylcysteine (NAC), were purchased from Sigma-Aldrich (St. Louis, MO, USA) or TCI Chemicals (Tokyo, Japan).

Techniques: Derivative Assay, Control

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells

doi: 10.1080/14756366.2026.2666369

Figure Lengend Snippet: Multi-tissue integration and cross-tissue validation of metabolic pathway relationships via large-scale GEO cohort analysis. (A–C) Multi-block principal component analysis (MB-PCA) integrating liver ( n = 705), skeletal muscle ( n = 703), and adipose tissue ( n = 703) samples (total n = 2111). (A) Tissue distribution showing substantial overlap across organs, indicating conserved metabolic regulatory architecture. (B) Treatment group separation demonstrating distinct clustering of HFHS-Metformin from HFHS-Control samples. (C) Module loadings revealing shared factor structure: Redox Defense, AMPK, and Insulin Signalling load together on PC1, while ROS Production and PTP1B load oppositely. (D–F) Partial least squares discriminant analysis (PLS-DA) discriminating HFHS-Control from HFHS-Metformin groups. (D) Score plot showing 66.5% classification accuracy. (E) Variable importance in projection (VIP) scores identifying ROS Production (VIP = 1.44) and Redox Defense (VIP = 1.06) as key discriminators (VIP > 1 threshold indicated by red dashed line). (F) PLS-DA loadings plot. (G–H) Linear mixed model analysis with tissue as random effect. (G) Effect sizes for HFHS diet (red), metformin treatment (green), and diet × treatment interaction (purple). * p < 0.05. (H) Heatmap showing consistent directionality of metformin effects across all three tissues, with near-zero tissue variance component indicating remarkable cross-tissue conservation of regulatory mechanisms. Data source: GEO datasets GSE237743 (liver), GSE237747 (skeletal muscle), GSE237737 (adipose tissue) from the DO/HMDP mouse cohort.

Article Snippet: Reagents for biological assays, such as palmitic acid (PA), human recombinant insulin, leptin, adiponectin, metformin, Duoglow (Duo; pioglitazone + dapagliflozin), and N-acetylcysteine (NAC), were purchased from Sigma-Aldrich (St. Louis, MO, USA) or TCI Chemicals (Tokyo, Japan).

Techniques: Biomarker Discovery, Blocking Assay, Control

Journal: Journal of Enzyme Inhibition and Medicinal Chemistry

Article Title: Flavonoids from Elsholtzia ciliata restore redox electron flow and metabolic signaling via PTP1B inhibition in muscle and liver cells

doi: 10.1080/14756366.2026.2666369

Figure Lengend Snippet: Mediation analysis and integrated mechanistic model explaining the potency-efficacy paradox. (A) Baron-Kenny mediation analysis quantifying the proportion of Redox Defense → Insulin Signalling effects mediated through PTP1B (EC2-like pathway, red bars) versus AMPK (EC5-like pathway, green bars) across liver ( n = 705), skeletal muscle ( n = 703), and adipose tissue ( n = 703). AMPK-mediated effects (33.0–55.4%) consistently exceeded PTP1B-mediated effects (6.8–17.9%) by 3.1–4.9 fold across all tissues (all Sobel p < 0.003). Dashed line indicates 50% mediation threshold. (B) Integrated pathway model summarising the validated Redox → AMPK/PTP1B → Insulin signalling cascade with quantified mediation proportions. Key findings box summarises four major conclusions: (1) AMPK pathway dominance (3–5× stronger than PTP1B), (2) tissue consistency (LMM p < 0.05), (3) redox as upstream regulator (VIP > 1), and (4) EC5′s metformin-like AMPK activation. (C) Proposed “Redox-First Paradigm” integrating in vitro experimental findings with cohort-validated pathway coefficients. EC2 (7-O-methylorientin) primarily acts through NADP⁺/NADPH restoration and PTP1B suppression ( β = 0.90, mediation 14.6%–17.9%), while EC5 (chalcone glycoside) acts through FAD restoration and AMPK activation ( β = 0.80, mediation 33.0%–55.4%). This differential pathway engagement quantitatively explains why EC5 demonstrates superior cellular efficacy despite similar PTP1B IC₅. values, supporting multi-target polypharmacology over single-target approaches for metabolic disease therapeutics.

Article Snippet: Reagents for biological assays, such as palmitic acid (PA), human recombinant insulin, leptin, adiponectin, metformin, Duoglow (Duo; pioglitazone + dapagliflozin), and N-acetylcysteine (NAC), were purchased from Sigma-Aldrich (St. Louis, MO, USA) or TCI Chemicals (Tokyo, Japan).

Techniques: Activation Assay, In Vitro