Isoandrographolide is an orally active NLRP3 inflammasome inhibitor and AKT / GSK-3β / β-catenin pathway inhibitor. Isoandrographolide inhibits the expression of NLRP3, ASC, and caspase-1, and reduces the levels of phosphorylated AKT, phosphorylated GSK-3β, and β-catenin. Isoandrographolide alleviates inflammatory responses, reduces collagen deposition, suppresses epithelial-mesenchymal transition (EMT), induces differentiation of leukemia cells, inhibits the growth of leukemia cells, protects lung and kidney tissues, regulates cytokine levels, and also exhibits hepatoprotective effects. Isoandrographolide can be used in studies related to silicosis, murine myeloid leukemia, renal tubulointerstitial fibrosis, and non-alcoholic fatty liver disease [1] [2] [3] [4].
In Vivo, Isoandrographolide (25-50 mg/kg; i.g.; daily; 28 days) dose-dependently ameliorates silica-induced silicosis in Mus musculus by inhibiting NLRP3 inflammasome activation, reducing pulmonary inflammation and fibrosis, and suppressing EMT[1]. Isoandrographolide (25-100 mg/kg; i.g.; daily; 7 days) dose-dependently ameliorates tubulointerstitial fibrosis in UUO-induced mice[3]. Isoandrographolide (25 mg/kg; p.o.; daily; 28 days) reduces plasma hepatotoxicity marker enzyme levels (ALT, AST) in HFD-fed rats with NAFLD[4].
In Vitro, Isoandrographolide (0.1-100 μM; 48 h) exhibits no significant cytotoxicity to A549 cells[1]. Isoandrographolide (0.15-0.6 μM; 24 h) dose-dependently suppresses silica + LPS-induced migratory capacity of A549 cells[1]. Isoandrographolide (0.15-0.6 μM; 24 h) dose-dependently downregulates silica + LPS-induced elevations in α-SMA, Col-III, FN, NLRP3, ASC and caspase-1 protein expression as well as IL-6, IL-1β and TGF-β1 mRNA expression in A549 cells[1]. Isoandrographolide (5-50 μM; 48 h) potently induces phagocytosis and inhibits growth of mouse myeloid leukemia (M1) cells[2]. Isoandrographolide binds to PPARα with a binding energy of -8.52 kcal/mol and an inhibition constant of 0.566 μM, demonstrating strong interaction with the target protein[4]. Isoandrographolide (100-500 μM; 24 h) reduces HepG2 cell viability in a concentration-dependent manner, with a GI25 of 878.18 μM[4]. Isoandrographolide (12.5-50 μM; 24 h) reduces lipid accumulation, triglyceride levels, LDH leakage, and transaminase levels in PO-BSA induced steatotic HepG2 cells in a concentration-dependent manner[4].
References:
[1]. Song Z, et al. Isoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in mice. Int Immunopharmacol. 2022;105:108539.
[2]. Matsuda T, et al. Cell differentiation-inducing diterpenes from Andrographis paniculata Nees. Chem Pharm Bull (Tokyo). 1994;42(6):1216-1225.
[3]. Guan Z. Isoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathway. Int Immunopharmacol. 2022;112:109201.
[4]. Toppo E, et al. Hepatoprotective effect of selected isoandrographolide derivatives on steatotic HepG2 cells and High Fat Diet fed rats. Eur J Pharmacol. 2021;899:174056.
In Vivo, Isoandrographolide (25-50 mg/kg; i.g.; daily; 28 days) dose-dependently ameliorates silica-induced silicosis in Mus musculus by inhibiting NLRP3 inflammasome activation, reducing pulmonary inflammation and fibrosis, and suppressing EMT[1]. Isoandrographolide (25-100 mg/kg; i.g.; daily; 7 days) dose-dependently ameliorates tubulointerstitial fibrosis in UUO-induced mice[3]. Isoandrographolide (25 mg/kg; p.o.; daily; 28 days) reduces plasma hepatotoxicity marker enzyme levels (ALT, AST) in HFD-fed rats with NAFLD[4].
In Vitro, Isoandrographolide (0.1-100 μM; 48 h) exhibits no significant cytotoxicity to A549 cells[1]. Isoandrographolide (0.15-0.6 μM; 24 h) dose-dependently suppresses silica + LPS-induced migratory capacity of A549 cells[1]. Isoandrographolide (0.15-0.6 μM; 24 h) dose-dependently downregulates silica + LPS-induced elevations in α-SMA, Col-III, FN, NLRP3, ASC and caspase-1 protein expression as well as IL-6, IL-1β and TGF-β1 mRNA expression in A549 cells[1]. Isoandrographolide (5-50 μM; 48 h) potently induces phagocytosis and inhibits growth of mouse myeloid leukemia (M1) cells[2]. Isoandrographolide binds to PPARα with a binding energy of -8.52 kcal/mol and an inhibition constant of 0.566 μM, demonstrating strong interaction with the target protein[4]. Isoandrographolide (100-500 μM; 24 h) reduces HepG2 cell viability in a concentration-dependent manner, with a GI25 of 878.18 μM[4]. Isoandrographolide (12.5-50 μM; 24 h) reduces lipid accumulation, triglyceride levels, LDH leakage, and transaminase levels in PO-BSA induced steatotic HepG2 cells in a concentration-dependent manner[4].
References:
[1]. Song Z, et al. Isoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in mice. Int Immunopharmacol. 2022;105:108539.
[2]. Matsuda T, et al. Cell differentiation-inducing diterpenes from Andrographis paniculata Nees. Chem Pharm Bull (Tokyo). 1994;42(6):1216-1225.
[3]. Guan Z. Isoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathway. Int Immunopharmacol. 2022;112:109201.
[4]. Toppo E, et al. Hepatoprotective effect of selected isoandrographolide derivatives on steatotic HepG2 cells and High Fat Diet fed rats. Eur J Pharmacol. 2021;899:174056.