Isoastragaloside I

Isoastragaloside I is a natural compound found in Astragalus membranaceus, with oral activity and multiple biological activities such as anti-inflammatory and antioxidant properties. Isoastragaloside I inhibits Akt, NF-κB, MAPKs and PI3K, enhances the activity of hepatic FXR, regulates the TGF-β/Smads signaling pathway, and upregulates antioxidant molecules downstream of Nrf2. Isoastragaloside I inhibits the expression of NO, TNF-α, iNOS, COX-2, IL-1β and VCAM-1, and reduces intracellular ROS levels. Isoastragaloside I attenuates blood-brain barrier disruption, restores intestinal barrier function, increases β-cell mass, improves glucose homeostasis, and elevates circulating adiponectin levels. Isoastragaloside I can be used for the study of neuroinflammation-related neurodegenerative diseases, cholestatic liver disease, and diabetes^[1][2][3][4]. In Vitro:Isoastragaloside I (ISO I) (25-100 μM; 24 h) has no cytotoxic effect on BV-2 microglial cells^[1].
Isoastragaloside I (25-100 μM; 2 h pre-treatment, followed by 20 h LPS stimulation) dose-dependently inhibits LPS-induced nitric oxide and TNF-α secretion from BV-2 microglial cells^[1].
Isoastragaloside I (100 μM; 2 h pre-treatment, followed by 20 h LPS stimulation) inhibits LPS-induced expression of iNOS and COX-2 proteins in BV-2 microglia and phosphorylation of NF-κB, IκBα, p38, JNK and ERK1/2^[1].
Isoastragaloside I (100 μM; 2 h pre-treatment, followed by 20 h LPS stimulation) downregulates LPS-induced TNF-α, IL-1β, and iNOS mRNA expression in BV-2 microglial cells^[1].
Isoastragaloside I (100 μM; 2 h pre-treatment, followed by 20 h LPS stimulation) inhibits LPS-induced transactivation of NF-κB in BV-2 microglia. It blocked LPS-induced nuclear translocation of phosphorylated NF-κB in BV-2 microglia^[1].
Isoastragaloside I (100 μM; 2 h pre-treatment, followed by 5-30 min LPS stimulation) suppresses LPS-induced phosphorylation of PI3K and Akt in BV-2 microglial cells^[1].
Isoastragaloside I (ISOI) (25-100 μM; 2 h pre-incubation, 1-24 h co-treatment with LPS) pre-treatment prevents LPS-induced TEER reduction in bEnd.3 cells^[3].
Isoastragaloside I (25-100 μM; 2 h pre-incubation, 24 h co-treatment with LPS) pre-treatment mitigates LPS-induced Na+F− exudation in bEnd.3 cells, reduced ROS accumulation, and restored the expression of tight junction proteins (ZO-1, occludin, claudin-5)^[3].
Isoastragaloside I (25-100 μM; 2 h pre-incubation, 24 h co-treatment with LPS) pre-treatment reduces LPS-induced JAWS II monocyte adhesion to bEnd.3 cells^[3].
Isoastragaloside I pre-treatment reduces LPS-induced mRNA expression of IL-1β, TNF-α, VCAM-1, and ICAM-1 in bEnd.3 cells^[3].
Isoastragaloside I (100 μM; 2 h pre-incubation, 24 h co-treatment with LPS) pre-treatment suppresses LPS-induced VCAM-1 protein expression in bEnd.3 cells and restored LPS-depleted Nrf2, HO-1, and NQO1 protein expression in bEnd.3 cells^[3].
Isoastragaloside I (25-100 μM; 24 h) activates Nrf2 transactivation in HEK293T cells^[3].
Isoastragaloside I (100 μM; 2 h pre-incubation, 24 h co-treatment with LPS) pre-treatment enhances LPS-reduced Nrf2 nuclear translocation in bEnd.3 cells^[3].
Isoastragaloside I (100 μM; 2 h pre-incubation, 12 or 24 h co-treatment with LPS after Nrf2 siRNA transfection) pre-treatment's ability to restore the expression of tight junction proteins and VCAM-1 in LPS-stimulated bEnd.3 cells, which depends on the Nrf2 signaling pathway, as silencing Nrf2 eliminates this effect^[3].
Isoastragaloside I (10 μM) inhibits pancreatic ductal organoid growth in vitro, while low doses do not alter organoid cell proliferation^[4]. In Vivo:Isoastragaloside I (IAS I) (20-50 mg/kg; p.o.; daily; 4 weeks) dose-dependently alleviates DDC-induced cholestatic liver disease in C57BL/6J mice, with significant improvements in liver injury, fibrosis, inflammation, bile acid metabolism and intestinal barrier function^[2].
Isoastragaloside I (IAS-I) (0.5-5 mg/kg; intravenous injection; days 0-21) significantly increases the mass of small islets by approximately 60% in healthy mice; it also alleviates symptoms and increases small islet mass in both type 1 and type 2 diabetic mice^[4].