Irsogladine (irsogladine maleate) is a PDE4 inhibitor and muscarinic acetylcholine receptor binder. IM (irsogladine maleate) treatment (300 and 500 mg/kg/day) resulted in a dose-dependent reduction of angiogenesis in wild-type mice by 21 and 45.3%, in tPA-deficient mice by 42.6 and 46%, and in uPA-deficient mice by 27.2 and 46% , respectively[3]. Irsogladine maleate suppresses intestinal polyp formation in Min mice partly through the NF-jB signaling pathway, thus reducing oxidative stress[4]. IM up-regulates GJIC (gap junctional intercellular communication) between PC (pancreatic cancer) cells via regulation of the PKA pathway[5]. The mucosal protective effects afforded by irsogladine maleate on gastric injury induced by indomethacin are mediated by inhibition of mucosal proinflammatory cytokine production and neutrophil infiltration, leading to suppression of mucosal inflammation and subsequent tissue destruction[6].
Irsogladine/伊索拉定 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HCT-15 cells
100 μM and 200 μM
24 hours
To evaluate the effects of irsogladine maleate on NF-κB transcriptional activity. Results showed that 100 μM and 200 μM irsogladine maleate decreased NF-κB transcriptional activity by 22% and 29%, respectively.
Oncotarget. 2016 Feb 23;7(8):8640-52
Human induced pluripotent stem cell-derived 2D monolayer crypt-villus structural small intestine (2D-hiPSC-SI)
16 µg/mL
48 hours
To evaluate the effect of Irsogladine on 2D-hiPSC-SI under normal conditions, results showed that Irsogladine significantly increased Mki67 and Muc2 mRNA expression.
Medicina (Kaunas). 2022 Dec 31;59(1):92
RAW 264.7 macrophages
100 and 10 μM
24 hours
To evaluate the effects on cAMP levels, cytokine release, ROS and NO production in LPS-stimulated RAW 264.7 macrophages. Results showed that compounds 1 and 2 increased cAMP levels, reduced TNF-α and IL-1β release, and decreased ROS production.
Inflamm Res. 2017 Jan;66(1):79-95
Irsogladine/伊索拉定 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6-ApcMin/+ mice
Familial adenomatous polyposis model
Dietary administration
5 ppm and 50 ppm
8 weeks
To evaluate the inhibitory effects of irsogladine maleate on intestinal polyp formation. Results showed that 5 ppm and 50 ppm irsogladine maleate reduced the number of intestinal polyps to 69% and 66% of the untreated control value, respectively. Additionally, mRNA levels of NF-κB downstream targets, such as IL-1β and IL-6, were significantly decreased, and the levels of oxidative stress-related markers, reactive carbonyl species, in the livers of Min mice were clearly reduced.
Oncotarget. 2016 Feb 23;7(8):8640-52
Male Hos: Donryu rats
Indomethacin-induced gastric mucosal injury model
Oral
1 mg/kg, 3 mg/kg, 10 mg/kg
Single dose, lasted for 4 hours
To investigate the mucosal protective effect and the mechanisms of action of the anti-ulcer drug irsogladine maleate in gastric injury induced by indomethacin in rats. Results showed that irsogladine maleate significantly reduced the number and severity of gastric mucosal lesions and decreased the levels of proinflammatory cytokines (TNF-α, IL-1β, IL-8) and MPO in gastric mucosa.
World J Gastroenterol. 2008 Aug 14;14(30):4784-90
ICR mice
Ethanol/HCl-induced gastric ulcer model
Oral
1 mg/kg and 10 mg/kg
Pretreatment 1 hour before
IM significantly reduced the extent of ethanol/HCl mixture-induced gastric ulceration, exhibiting dose-related gastroprotection.
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