Rosiglitazone (BRL 49653) potassium is a potent and selective PPARγ agonist (EC 50: 60 nM, Kd: 40 nM), administered orally. It also serves as an activator of TRPC5 (EC 50: 30 μM) and an inhibitor of TRPM3. This compound, widely used in research, has shown promise in investigating obesity, diabetes, senescence, and ovarian cancer [1] [2] [4] [7].
体外活性
Rosiglitazone potassium (0.1-10 μM, 72 h) results in pluripotent C3H10T1/2 stem cell differentiation to adipocytes [1]. Rosiglitazone potassium (1 μM, 24 h) activates PPARγ, which binds to NF-α1 promoter to activate gene transcription in neurons [3]. Rosiglitazone potassium (1 μM, 24 h) protects Neuro2A cells and hippocampal neurons against oxidative stress, and up-regulates BCL-2 expression in an NF-α1-dependent manner [3]. Rosiglitazone potassium (0.01-100 μM, 15 min) inhibits TRPM3 with IC 50 values of 9.5 and 4.6 μM against nifedipine- and PregS-evoked activity respectively [4]. Rosiglitazone potassium (0.5-50 μM, 7 days) inhibits ovarian cancer cell proliferation [7]. Rosiglitazone potassium (5 μM, 7 days) suppresses Olaparib induced alterations of cellular senescence and promotes apoptosis in A2780 and SKOV3 cells [7]. Cell Proliferation Assay [7] Cell Line: A2780 and SKOV3 cells Concentration: 0.5-50 μM Incubation Time: 1-7 days Result: Inhibited cell proliferation in a time dependent and concentration dependent manner. Western Blot Analysis [3] Cell Line: Hippocampal neurons Concentration: 1 μM Incubation Time: 24 h Result: Increased NF-α1 and BCL-2 protein level.
体内活性
Rosiglitazone potassium (oral administration, 5 mg/kg, daily for 8 weeks) decreases the serum glucose in diabetic rats [5]. Rosiglitazone potassium (intraperitoneal injection, 3 mg/kg/day) ameliorates airway inflammation induced by cigarette smoke via inhibiting the M1 macrophage polarization by activating PPARγ and RXRα in male Wistar rats [6]. Rosiglitazone potassium (intraperitoneal injection, 10 mg/kg, once every 2 days) inhibits subcutaneous ovarian cancer growth in A2780 and SKOV3 mouse subcutaneous xenograft models [7]. Animal Model: Streptozotocin (STZ)-induced diabetic rats [5] Dosage: 5 mg/kg Administration: Oral administration, daily for 8 weeks. Result: Decreased 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. Animal Model: Male Wistar rats [6] Dosage: 3 mg/kg/day Administration: Intraperitoneal injection, twice a day, 6 days per week for 12 consecutive weeks Result: 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 decreased the ratio of M1/M2.
