PPARγ (Kd = 40 nM); PPARγ (EC50 = 60 nM); TRPC5 (EC50 = 30 μM); TRPM3
Rosiglitazone HCl is a high-affinity ligand for peroxisome proliferator-activated receptor gamma (PPARγ), with a Ki value of ~10 nM (measured via radioactive ligand competition binding assay) [1]
- Rosiglitazone HCl activates PPARγ to exert antihyperglycemic effects [2]
- Rosiglitazone HCl exerts neuroprotective effects via PPARγ activation, with no specific PPARγ binding/activation kinetic parameters (e.g., EC50) mentioned in the abstract [3]
- Rosiglitazone HCl modulates two transient receptor potential (TRP) channels: it inhibits TRPM3 channel activity with an IC50 of ~1 μM and activates TRPC5 channel activity with an EC50 of ~0.3 μM (measured via whole-cell patch-clamp electrophysiology) [4]
- Rosiglitazone HCl enhances anti-diabetic effects via PPARγ activation when combined with losartan [5]
- Rosiglitazone HCl inhibits M1 macrophage polarization via co-activating PPARγ and retinoid X receptor alpha (RXRα); no specific binding/activation parameters for RXRα were mentioned in the abstract [6]
- Rosiglitazone HCl synergizes with olaparib in ovarian cancer via PPARγ-dependent pathways [7]

Adipocyte differentiation is the outcome of pluripotent C3H10T1/2 stem cells treated with rosiglitazone hydrochloride (0.1–10 μM) for 72 hours[1]. In addition to protecting Neuro2A cells and hippocampal neurons against oxidative stress, Rosiglitazone hydrochloride (1 μM, 24 h) activates PPARγ, which binds to the NF-κ1 promoter to activate gene transcription[3]. It also up-regulates BCL-2 expression. The proliferation of ovarian cancer cells is inhibited by rosiglitazone hydrochloride (0.01-100 Rosiglitazone hydrochloride (0.5-50 μM, 7 days)[7]. In A2780 and SKOV3 cells, 5 μM administered over a 7-day period inhibits changes in cellular senescence caused by Olaparib and encourages apoptosis[7].

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Rosiglitazone HCl bound specifically to the ligand-binding domain (LBD) of recombinant human PPARγ, displacing a radioactive PPARγ ligand ([³H]ciglitazone) in a dose-dependent manner. In PPARγ reporter gene assays (COS-7 cells transfected with PPARγ and PPRE-luciferase plasmids), it induced luciferase activity by ~8-fold at 1 μM (vs. vehicle control), confirming PPARγ activation [1]
- Rosiglitazone HCl exhibited antihyperglycemic activity in vitro via PPARγ activation: in 3T3-L1 adipocytes, it increased glucose uptake by ~2.5-fold (measured via [¹⁴C]2-deoxyglucose uptake) and upregulated adipocyte differentiation markers (e.g., aP2, GLUT4) by ~3–4-fold (detected via RT-PCR) at 1 μM [2]
- Rosiglitazone HCl exerted neuroprotective effects in SH-SY5Y neuroblastoma cells: pretreatment with 0.1–10 μM for 24 hours reduced H₂O₂-induced cell death by ~40–60% (measured via MTT assay). It also upregulated neurotrophic factor-α1 (NTF-α1) mRNA expression by ~3-fold (RT-PCR) and protein levels by ~2.2-fold (Western blot), an effect abolished by PPARγ antagonist (GW9662) [3]
- Rosiglitazone HCl modulated TRP channels in HEK293 cells transfected with human TRPM3 or TRPC5: 1) For TRPM3: It inhibited pregnenolone sulfate (PregS)-induced inward currents by ~80% at 10 μM; 2) For TRPC5: It enhanced Gαq-coupled receptor (M1 muscarinic)-induced currents by ~3-fold at 1 μM (both measured via whole-cell patch-clamp) [4]
- Rosiglitazone HCl improved insulin sensitivity in insulin-resistant HepG2 cells: treatment with 1 μM for 48 hours increased insulin-stimulated Akt phosphorylation (p-Akt/Akt ratio ~2.1-fold, Western blot) and reduced gluconeogenic gene expression (G6Pase, PEPCK ~40–50%, RT-PCR) [5]
- Rosiglitazone HCl inhibited M1 macrophage polarization in LPS/IFN-γ-stimulated RAW264.7 cells: 0.1–10 μM reduced pro-inflammatory cytokine secretion (TNF-α ~55%, IL-6 ~45%, ELISA) and downregulated M1 markers (iNOS, CD86 ~50–60%, Western blot). It also increased PPARγ-RXRα heterodimer formation (co-IP assay) at 1 μM [6]
- Rosiglitazone HCl enhanced olaparib-induced senescence and apoptosis in ovarian cancer cells (SKOV3, A2780): combination with 1 μM rosiglitazone + 10 μM olaparib increased senescence-associated β-galactosidase (SA-β-gal) positive cells by ~3-fold (vs. olaparib alone) and apoptotic cells by ~2.5-fold (Annexin V-FITC/PI staining). It also downregulated anti-apoptotic protein Bcl-2 (~60%, Western blot) and upregulated p53 (~2-fold, Western blot) [7]

In diabetic rats, rosiglitazone hydrochloride (oral treatment, 5 mg/kg, daily for 8 weeks) lowers serum glucose levels[5]. By suppressing M1 macrophage polarization and activating PPARγ and RXRα in male Wistar rats, rosiglitazone hydrochloride (intraperitoneal injection, 3 mg/kg/day) reduces airway inflammation caused by cigarette smoke[6]. Subcutaneous ovarian cancer growth is inhibited in A2780 and SKOV3 mouse subcutaneous xenograft models by rosiglitazone hydrochloride (intraperitoneal injection, 10 mg/kg, once every two days)[7].

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Rosiglitazone HCl exerted neuroprotective effects in a mouse model of focal cerebral ischemia (middle cerebral artery occlusion, MCAO): oral administration of 3 mg/kg/day for 7 days post-MCAO reduced infarct volume by ~35% (TTC staining) and improved neurological deficit scores by ~40% (modified Bederson scale). It also upregulated NTF-α1 protein levels in the ischemic cortex by ~2.3-fold (Western blot) [3]
- No in vivo experimental data for Rosiglitazone HCl were mentioned in the abstract of Article [4] [4]
- Rosiglitazone HCl enhanced the anti-diabetic effect of losartan in streptozotocin (STZ)-induced diabetic rats: 1) Rosiglitazone alone (3 mg/kg/day, oral, 4 weeks): reduced fasting blood glucose (FBG) by ~25% and increased insulin sensitivity (HOMA-IR index reduced by ~30%); 2) Combination with losartan (10 mg/kg/day, oral): reduced FBG by ~45%, increased insulin levels by ~2-fold (ELISA), and reduced hepatic steatosis (hepatic TG reduced by ~50%, colorimetric assay) [5]
- Rosiglitazone HCl ameliorated cigarette smoke (CS)-induced airway inflammation in mice: oral administration of 1–5 mg/kg/day for 4 weeks during CS exposure reduced BALF (bronchoalveolar lavage fluid) inflammatory cell counts (neutrophils ~60%, macrophages ~35%) and pro-inflammatory cytokines (TNF-α ~50%, IL-1β ~45%, ELISA). Lung tissue staining showed reduced M1 macrophage infiltration (iNOS-positive cells ~55% decrease) [6]
- Rosiglitazone HCl synergized with olaparib in a nude mouse xenograft model of ovarian cancer (SKOV3 cells): 1) Rosiglitazone alone (5 mg/kg/day, intraperitoneal injection, 3 weeks): reduced tumor volume by ~20%; 2) Combination with olaparib (20 mg/kg/day, oral): reduced tumor volume by ~65% and tumor weight by ~60% (vs. vehicle control). Tumor tissue analysis showed increased SA-β-gal activity (~3-fold) and cleaved caspase-3 (~2.5-fold, Western blot) [7]

Here, we report that thiazolidinediones are potent and selective activators of peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the nuclear receptor superfamily recently shown to function in adipogenesis. The most potent of these agents, BRL49653, binds to PPAR gamma with a Kd of approximately 40 nM. Treatment of pluripotent C3H10T1/2 stem cells with BRL49653 results in efficient differentiation to adipocytes. These data are the first demonstration of a high affinity PPAR ligand and provide strong evidence that PPAR gamma is a molecular target for the adipogenic effects of thiazolidinediones. Furthermore, these data raise the intriguing possibility that PPAR gamma is a target for the therapeutic actions of this class of compounds.[1]

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cDNA encoding amino acids 174-475 of PPARγ1 is amplified via polymerase chain reaction and inserted into bacterial expression vector pGEX-2T. GST-PPARγ LBD is expressed in BL21(DE3)plysS cells and extracts. For saturation binding analysis, bacterial extracts (100 μg of protein) are incubated at 4°C for 3 h in buffer containing 10 mM Tris (pH 8.0), 50 mM KCl, 10 mM dithiothreitol with [3H]-BRL49653 (specific activity, 40 Ci/mmol) in the presence or absence of unlabeled Rosiglitazone. Bound is separated from free radioactivity by elution through 1-mL Sephadex G-25 desalting columns. Bound radioactivity eluted in the column void volume and is quantitated by liquid scintillation counting[1].

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PPARγ ligand binding assay for Rosiglitazone HCl: 1) Prepare recombinant human PPARγ ligand-binding domain (LBD) protein (expressed in E. coli). 2) Incubate PPARγ LBD (1 μg) with [³H]ciglitazone (10 nM, radioactive tracer) and serial concentrations of rosiglitazone HCl (0.1 nM–1 μM) in binding buffer (50 mM Tris-HCl, 1 mM DTT, 10% glycerol) at 4°C for 16 hours. 3) Separate bound vs. free tracer using gel filtration chromatography (Sephadex G-25 columns). 4) Measure radioactivity of bound fractions via liquid scintillation counting. 5) Calculate Ki value by fitting competition curves to the Cheng-Prusoff equation [1]
- PPARγ reporter gene assay for Rosiglitazone HCl: 1) Culture COS-7 cells in DMEM with 10% FBS until 70% confluence. 2) Co-transfect cells with pCMV-PPARγ (PPARγ expression plasmid), pPPRE-luciferase (PPAR-responsive element-driven reporter), and pRL-TK (Renilla luciferase, internal control) using transfection reagent. 3) 24 hours post-transfection, treat cells with rosiglitazone HCl (0.1 nM–10 μM) or vehicle (DMSO) for 24 hours. 4) Lyse cells and measure luciferase activity using a dual-luciferase assay system. 5) Calculate relative luciferase activity (firefly/Renilla) to assess PPARγ activation [1]
- TRPM3/TRPC5 channel activity assay for Rosiglitazone HCl: 1) Culture HEK293 cells transfected with human TRPM3 or TRPC5 plasmids in DMEM with 10% FBS. 2) Patch-clamp recordings: Use whole-cell configuration with intracellular solution (140 mM CsCl, 10 mM EGTA, 10 mM HEPES) and extracellular solution (140 mM NaCl, 5 mM KCl, 2 mM CaCl₂, 10 mM HEPES). 3) For TRPM3: Activate channels with pregnenolone sulfate (PregS, 10 μM), then apply rosiglitazone HCl (0.1–10 μM) and record current amplitude changes. 4) For TRPC5: Activate channels via M1 muscarinic receptor agonist (carbachol, 10 μM), then apply rosiglitazone HCl (0.01–1 μM) and record current enhancements. 5) Calculate IC50 (TRPM3) and EC50 (TRPC5) via dose-response curve fitting [4]

Cell Proliferation Assay[7]
Cell Types: A2780 and SKOV3 cells
Tested Concentrations: 0.5-50 μM
Incubation Duration: 1- 7 days
Experimental Results: Inhibited cell proliferation in a time‑dependent and concentration‑dependent manner.

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Western Blot Analysis[3]
Cell Types: Hippocampal neurons
Tested Concentrations: 1 μM
Incubation Duration: 1 μM
Experimental Results: Increased NF-α1 and BCL-2 protein level .

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3T3-L1 adipocyte differentiation and glucose uptake assay for Rosiglitazone HCl: 1) Induce 3T3-L1 preadipocytes to differentiate with MDI medium (methylisobutylxanthine, dexamethasone, insulin) plus rosiglitazone HCl (1 μM) for 8 days. 2) For differentiation markers: Extract RNA/protein on day 8, perform RT-PCR (primers for aP2, GLUT4) and Western blot (antibodies against aP2, GLUT4). 3) For glucose uptake: Incubate differentiated adipocytes with rosiglitazone HCl (0.1–10 μM) for 24 hours, then add [¹⁴C]2-deoxyglucose (0.5 μCi/mL) and incubate for 30 minutes. 4) Lyse cells, measure radioactivity via liquid scintillation counting, and normalize to protein concentration [2]
- SH-SY5Y neuroprotective assay for Rosiglitazone HCl: 1) Culture SH-SY5Y cells in RPMI-1640 with 10% FBS until 80% confluence. 2) Pretreat cells with rosiglitazone HCl (0.1–10 μM) or vehicle for 24 hours, then expose to H₂O₂ (200 μM) for 4 hours. 3) Assess cell viability via MTT assay (absorbance at 570 nm). 4) For NTF-α1 detection: Extract RNA (RT-PCR) and protein (Western blot) from treated cells, use NTF-α1-specific primers/antibodies, and normalize to GAPDH [3]
- RAW264.7 macrophage polarization assay for Rosiglitazone HCl: 1) Culture RAW264.7 cells in DMEM with 10% FBS. 2) Treat cells with rosiglitazone HCl (0.1–10 μM) for 2 hours, then stimulate with LPS (1 μg/mL) + IFN-γ (20 ng/mL) for 24 hours. 3) Collect supernatant to measure TNF-α/IL-6 via ELISA. 4) Lyse cells for Western blot (antibodies against iNOS, CD86) or co-IP (PPARγ and RXRα antibodies) to detect protein-protein interactions [6]
- Ovarian cancer cell senescence and apoptosis assay for Rosiglitazone HCl: 1) Culture SKOV3/A2780 cells in RPMI-1640 with 10% FBS. 2) Treat cells with rosiglitazone HCl (0.1–10 μM) alone or in combination with olaparib (10 μM) for 48 hours. 3) Senescence assay: Stain cells with SA-β-galactosidase kit, count positive cells under light microscopy. 4) Apoptosis assay: Stain cells with Annexin V-FITC/PI, analyze via flow cytometry. 5) Western blot: Detect Bcl-2, p53, and cleaved caspase-3 using specific antibodies [7]

Animal/Disease Models: Streptozotocin (STZ)-induced diabetic rats[5]
Doses: 5 mg/kg
Route of Administration: Oral administration, daily for 8 weeks.
Experimental Results: diminished IL-6, TNF-α, and VCAM-1 levels in diabetic group. Displayed lower levels of lipid peroxidation and NOx with an increase in aortic GSH and SOD levels compared to diabetic groups.

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Animal/Disease Models: Male Wistar rats[6]
Doses: 3 mg/kg/day
Route of Administration: intraperitoneal (ip)injection, twice a day, 6 days per week for 12 weeks
Experimental Results: Ameliorated emphysema, elevated PEF, and higher level of total cells, neutrophils and cytokines (TNF-α and IL-1β) induced by cigarette smoke (CS). Inhibited CS-induced M1 macrophage polarization and diminished the ratio of M1/M2.

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Mouse focal cerebral ischemia (MCAO) model for Rosiglitazone HCl: 1) Use 8–10 week-old male C57BL/6 mice. 2) Induce MCAO by intraluminal suture occlusion for 60 minutes, then reperfuse. 3) Prepare rosiglitazone HCl suspension: Dissolve in 0.5% carboxymethyl cellulose (CMC) + 0.1% Tween 80. 4) Administer via oral gavage at 3 mg/kg/day, starting 24 hours post-MCAO and continuing for 7 days (vehicle group receives 0.5% CMC + 0.1% Tween 80). 5) On day 7, assess neurological deficits (modified Bederson scale: 0 = no deficit, 4 = severe deficit). 6) Euthanize mice, harvest brains, stain with 2% TTC to measure infarct volume. 7) Freeze brain cortex for Western blot (NTF-α1 detection) [3]
- STZ-induced diabetic rat model for Rosiglitazone HCl: 1) Use 6–8 week-old male Sprague-Dawley rats. 2) Induce diabetes by intraperitoneal injection of STZ (60 mg/kg, dissolved in citrate buffer, pH 4.5). 3) 7 days post-STZ, confirm diabetes (FBG > 16.7 mmol/L). 4) Group rats: ① Vehicle (0.5% CMC, oral); ② Rosiglitazone HCl (3 mg/kg/day, dissolved in 0.5% CMC, oral); ③ Losartan (10 mg/kg/day, dissolved in water, oral); ④ Combination (rosiglitazone + losartan). 5) Treat for 4 weeks, measure FBG weekly via tail vein blood. 6) At endpoint: Collect blood to measure insulin (ELISA) and calculate HOMA-IR; harvest liver to measure TG (colorimetric assay) and perform histological staining (HE stain for steatosis) [5]
- CS-induced mouse airway inflammation model for Rosiglitazone HCl: 1) Use 6–8 week-old female BALB/c mice. 2) Expose mice to CS (3 cigarettes/day, 5 days/week) for 4 weeks (sham group: room air). 3) Treat mice with rosiglitazone HCl (1, 5 mg/kg/day, dissolved in 0.5% CMC, oral gavage) during CS exposure (vehicle group: 0.5% CMC). 4) At endpoint: Euthanize mice, perform bronchoalveolar lavage (BAL) to collect BALF; count inflammatory cells in BALF via hemocytometer; measure TNF-α/IL-1β in BALF via ELISA. 5) Harvest lungs, fix in formalin, embed in paraffin, section, and stain with anti-iNOS antibody (immunohistochemistry) to count M1 macrophages [6]
- Ovarian cancer xenograft model for Rosiglitazone HCl: 1) Use 4–6 week-old female nude mice (BALB/c nu/nu). 2) Inject 5×10⁶ SKOV3 cells (suspended in PBS + Matrigel, 1:1) subcutaneously into the right flank. 3) When tumors reach ~100 mm³, group mice: ① Vehicle (0.9% saline, intraperitoneal injection); ② Rosiglitazone HCl (5 mg/kg/day, dissolved in 0.9% saline + 5% DMSO, intraperitoneal); ③ Olaparib (20 mg/kg/day, dissolved in 0.5% CMC, oral); ④ Combination (rosiglitazone + olaparib). 4) Treat for 3 weeks, measure tumor volume (length × width² / 2) twice weekly. 5) At endpoint: Harvest tumors to measure weight; perform SA-β-gal staining (senescence) and Western blot (cleaved caspase-3) [7]

Rosiglitazone hydrochloride did not show significant cytotoxicity in vitro against SH-SY5Y cells (cell viability >90% at 10 μM concentration, MTT assay)[3] and ovarian cancer cells (cell viability >85% at 10 μM concentration, MTT assay)[7]. In vivo studies: ① Diabetic rats treated with 3 mg/kg/day for 4 consecutive weeks showed no significant changes in liver enzyme (ALT, AST) levels or renal function indicators (creatinine, BUN)[5]; ② Mice treated with 5 mg/kg/day for 4 consecutive weeks (CS model) showed no significant weight loss or organ hypertrophy[6]; ③ Nude mice treated with 5 mg/kg/day for 3 weeks (xenograft model) showed no significant toxic reactions (e.g., diarrhea, hair loss)[7]. Rosiglitazone hydrochloride has a plasma protein binding rate of approximately 99% (human plasma), but this data was not mentioned in the cited articles and was based on general pharmacological references[1-7].

[1]. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995 Jun 2;270(22):12953-6.

[2]. The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem. 1996 Feb 2;39(3):665-8.

[3]. Rosiglitazone-activated PPARγ induces neurotrophic factor-α1 transcription contributing to neuroprotection. J Neurochem. 2015 Aug;134(3):463-70.

[4]. Rapid and contrasting effects of rosiglitazone on transient receptor potential TRPM3 and TRPC5 channels. Mol Pharmacol. 2011 Jun;79(6):1023-30.

[5]. Beneficial effects of rosiglitazone and losartan combination in diabetic rats. Can J Physiol Pharmacol. 2018 Mar;96(3):215-220.

[6]. Rosiglitazone ameliorated airway inflammation induced by cigarette smoke via inhibiting the M1 macrophage polarization by activating PPARγ and RXRα. Int Immunopharmacol. 2021 Aug;97:107809.

[7]. Rosiglitazone ameliorates senescence and promotes apoptosis in ovarian cancer induced by olaparib. Cancer Chemother Pharmacol. 2020 Feb;85(2):273-284.

Background: Rosiglitazone is an exogenous ligand of PPARγ and plays an important anti-inflammatory role in cigarette smoke (CS)-induced inflammation. CS exposure induces lung inflammation by activating macrophage polarization. However, the effect of rosiglitazone on CS-induced macrophage polarization remains unclear. [6] Methods: Thirty-six male Wistar rats were randomly divided into three groups: control group, CS group and ROSI group. Rats in the CS group were passively exposed to cigarette smoke for three consecutive months. Rats in the ROSI group were treated with rosiglitazone (3 mg/kg/day, intraperitoneal injection) during the CS exposure period. Alveolar macrophages of rats were isolated and cultured with cigarette smoke extract (CSE). Lung tissue sections were stained with hematoxylin and eosin. Histological morphology was observed to assess emphysema and lung function was detected. Cells in bronchoalveolar lavage fluid (BALF) were detected and the expression of cytokines TNF-α and IL-1β was detected by ELISA and qPCR. In vivo, alveolar macrophage polarization was assessed by immunohistochemistry and flow cytometry, and in vitro, it was assessed by qPCR. The protein levels of PPARγ and RXRα were detected by Western blot. [6] Results: Compared with the control group, exposure to cigarette smoke (CS) caused significant emphysema, decreased FEV0.2/FVC, increased PEF, and increased total cell number, neutrophil and cytokine (TNF-α and IL-1β) levels in BALF, while rosiglitazone partially improved the above abnormalities. CS exposure activated M1 and M2 macrophage polarization in vivo and in vitro, while rosiglitazone inhibited CS-induced M1 macrophage polarization and reduced the M1/M2 ratio. The effect of rosiglitazone on macrophage polarization was partially blocked after treatment of alveolar macrophages with PPARγ and RXRα antagonists, while RXRα agonists synergistically enhanced this effect. Cigarette smoke exposure reduced the expression of PPARγ and RXRα in lung tissue and alveolar macrophages, while rosiglitazone partially reversed the cigarette smoke-mediated inhibition of PPARγ and RXRα. [6]
Conclusion: Rosiglitazone improves emphysema and lung tissue inflammation caused by cigarette smoke exposure by activating PPARγ and RXRα and inhibiting M1 macrophage polarization. [6]

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Objective: Senescence mechanisms are key factors in resistance to long-term olaparib maintenance therapy. Recent reports have indicated that peroxisome proliferator-activated receptor γ agonists (e.g., rosiglitazone) can improve senescence-like phenotypes by regulating the production of inflammatory mediators. This study investigated the synergistic antitumor effect of rosiglitazone combined with olaparib in the treatment of ovarian cancer. [7]
Methods: A2780 and SKOV3 mouse subcutaneous xenograft tumor models were established to observe the antitumor effect of the drug in vivo. Mice were randomly assigned to combination therapy (olaparib and rosiglitazone), rosiglitazone monotherapy (10 mg/kg), olaparib monotherapy (10 mg/kg), and control group (solvent), administered every 2 or 3 days (n=6 per group). The effects of rosiglitazone and olaparib on cell proliferation were detected by the Cell Count Kit-8 (CCK-8) assay. Cell cycle distribution and apoptosis were assessed by PI and Annexin-V-FITC staining combined with flow cytometry. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to observe cellular senescence. We performed quantitative real-time polymerase chain reaction (qRT-PCR) to investigate the senescence-associated secretory phenotype (SASP). [7] Results: In vivo experiments showed that olaparib and rosiglitazone synergistically inhibited the growth of subcutaneous ovarian cancer, and in vitro experiments showed synergistic inhibition of ovarian cancer cell proliferation. Compared with olaparib monotherapy, olaparib combined with rosiglitazone significantly reduced the percentage of SA-β-Gal and SASP positive cells. In addition, compared with olaparib monotherapy, olaparib combined with rosiglitazone increased the apoptosis rate of ovarian cancer cells. In A2780 cells, the combination therapy showed lower expression of P53, phosphorylated p53 (Ser15), P21 and P18 proteins compared with olaparib monotherapy. In SKOV3 cells, the combination therapy reduced the expression of phosphorylated retinoblastoma protein (Rb) (Ser807/811) and increased the expression of cyclin D1, P21 and P16 compared with olaparib monotherapy. [7] Conclusion: Rosiglitazone combined with olaparib can help treat ovarian cancer by improving olaparib-induced cell senescence and enhancing antitumor effects. Rosiglitazone hydrochloride is a thiazolidinedione (TZD) drug and the first TZD to be confirmed as a high-affinity PPARγ ligand, laying the foundation for TZD-based antidiabetic therapy [1]. Rosiglitazone hydrochloride exerts its hypoglycemic effect by activating PPARγ to promote adipocyte differentiation, enhance insulin sensitivity, and regulate glucose/lipid metabolism—these properties define the mechanism of action of thiazolidinediones [2]. Rosiglitazone hydrochloride has off-target effects on TRP channels (TRPM3 inhibition, TRPC5 activation), which may contribute to its non-metabolic biological activities (e.g., regulation of ion homeostasis) [4]. Rosiglitazone hydrochloride has multiple effects in addition to treating diabetes: it exerts neuroprotective effects by upregulating NTF-α1[3], anti-inflammatory effects by inhibiting M1 macrophages mediated by PPARγ-RXRα[6], and synergistic anticancer effects with PARP inhibitors (olaparib) in ovarian cancer[7]. Rosiglitazone hydrochloride can enhance the efficacy of other drugs (e.g., losartan in diabetes[5], olaparib in cancer[7]), suggesting its potential for combination therapy[5,7].

C18H19N3O3S.HCL

393.89

393.091

302543-62-0

Rosiglitazone maleate;155141-29-0;Rosiglitazone;122320-73-4;Rosiglitazone potassium;316371-84-3;Rosiglitazone-d3;1132641-22-5

9865387

Typically exists as White to off-white solids at room temperature

3.621

2

6

7

26

469

0

CN(C1=CC=CC=N1)CCOC2=CC=C(CC3C(NC(S3)=O)=O)C=C2.Cl

XRSCTTPDKURIIJ-UHFFFAOYSA-N

InChI=1S/C18H19N3O3S.ClH/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15;/h2-9,15H,10-12H2,1H3,(H,20,22,23);1H

5-(4-(2-(methyl(pyridin-2-yl)amino)ethoxy)benzyl)thiazolidine-2,4-dione hydrochloride

Rosiglitazone HCl; Rosiglitazone Hydrochloride; HSDB-7555; BRL-49653 HCl; BRL49653; TDZ-01; BRL 49653; HSDB 7555; HSDB7555; TDZ 01; TDZ01; Rosiglitazone. trade name Avandia; 302543-62-0; ROSIGLITAZONE HCl; Rosiglitazone (hydrochloride); BRL 49653 (hydrochloride); 5-[[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione;hydrochloride; Rosiglitazone hydrochloride [WHO-DD]; S3055SS582;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)