Deoxyandrographolide

Deoxyandrographolide is an orally active lactone found in the Andrographis paniculata Nees. Deoxyandrographolide shows a K_D of 38.4 μM of HDAC1. Deoxyandrographolide enhances GLUT4 plasma membrane translocation, activates PI3K and AMPK-dependent signaling pathways, suppresses fasting blood glucose, serum insulin, triglycerides, and LDL-cholesterol levels. Deoxyandrographolide enhances HDAC1 expression via inhibited ubiquitination degradation, represses H3K4me3, improves chromosome stability, and restrains aging biomarkers p16, p21, γH2A.X, p53 and ROS production. Deoxyandrographolide interacts with Foot-and-Mouth Disease Virus 3Cpro active site, inhibits protease and IFN-antagonist activity, derepresses ISG expression, and inhibits viral replication. Deoxyandrographolide can be used for the researches of type 2 diabetes mellitus, vascular senescence and virus infection^[3]. In Vitro:Deoxyandrographolide (2.5-25 μM; 1-24 h) dose- and time-dependently stimulates glucose uptake in L6 myotubes, and its effects are additive to Insulin without reducing cell viability^[1].
Deoxyandrographolide (10 μM; 16 h) does not alter total cellular GLUT4 or GLUT1 protein levels in L6 myotubes, either alone or in combination with Insulin^[1].
Deoxyandrographolide (10-25 μM; 16 h) dose-dependently promotes GLUT4 translocation to the plasma membrane in L6-GLUT4myc myotubes, with a 1.23-fold increase at 25 μM for 16 h, and potentiates Insulin-induced GLUT4 translocation^[1].
Deoxyandrographolide (10 μM; 16 h) stimulates glucose uptake in L6 myotubes via a PI-3-K-dependent pathway, and activates downstream signaling by increasing Akt and insulin receptor-β phosphorylation, with synergistic effects when combined with insulin^[1].
Deoxyandrographolide (10-25 μM; 16 h) activates the AMPK pathway in L6 myotubes, as shown by increased AMPKα and ACC phosphorylation, and this pathway contributes to its ability to promote GLUT4 translocation^[1].
Deoxyandrographolide (7.94-250 μM; 24 h) is non-toxic to rat aorta endothelial cells at concentrations up to 200 μM and to human microvascular endothelial cells at concentrations up to 125 μM after 24 h of incubation^[2].
Deoxyandrographolide (50-150 μM; 48 h) inhibits Angiotensin II-induced upregulation of p16 and p21 mRNA in rat aorta endothelial cells and human microvascular endothelial cells^[2].
Deoxyandrographolide (25-150 μM; 48 h) inhibits Angiotensin II-induced p53 upregulation in rat aorta endothelial cells, restores angiotensin II-reduced HDAC1 levels in human microvascular endothelial cells, and reduces Angiotensin II-induced H3K4me3 upregulation in rat aorta endothelial cells^[2].
Deoxyandrographolide (50-100 μM; 48-60 h) at 50 and 100 μM reduces angiotensin II-induced γH2A.X and p21 upregulation, and at 100 μM reduces angiotensin II-induced ubiquitin upregulation in rat aorta endothelial cells^[2].
Deoxyandrographolide (6.75-200 μM) binds directly to recombinant human HDAC1 protein with a K_D of 38.4 μM, as measured by bio-layer interferometry^[2].
Deoxyandrographolide (50-150 μM; 24 h) reduces angiotensin II-induced reactive oxygen species accumulation in wild-type rat aorta endothelial cells, but this effect is abolished in HDAC1-knockdown rat aorta endothelial cells^[2].
Deoxyandrographolide (50-150 μM; 48 h) fails to inhibit angiotensin II-induced γH2A.X upregulation in HDAC1-knockdown rat aorta endothelial cells^[2].
Deoxyandrographolide (100 μM; 48 h) modulates gene expression related to chromosome stability, cell cycle, senescence, and inflammation in angiotensin II-treated rat aorta endothelial cells^[2].
Deoxyandrographolide (1-150 μM; 24 h) inhibits replication of FMDV serotype A in BHK-21 cells with an EC₅₀ of 36.47 μM and a selective index of 9.22^[3].
Deoxyandrographolide (1-100 μM; 16 h) inhibits the protease activity of FMDV 3Cpro in HEK 293T cells with an IC₅₀ of 25.58 μM and IC₉₀ of 122.88 μM^[3].
Deoxyandrographolide (25.58-122.88 μM; 24 h) interferes with the IFN-antagonist activity of FMDV 3Cpro in HEK 293T cells, significantly upregulating the expression of interferon-stimulating genes ISG15, ISG56, Mx-1, OAS-1, and PKR^[3].
Deoxyandrographolide (0.1-250 μM; 24 h) exhibits mild cytotoxicity in BHK-21 cells (CC₅₀ = 332.3 μM) and HEK 293T cells (CC₅₀ = 651.40 μM) with non-cytotoxic CC₁₀ concentrations of 81.05 μM and 155.55 μM, respectively^[3]. In Vivo:Deoxyandrographolide (100 mg/kg; p.o.; single dose) produces significant antihyperglycemic activity in Streptozotocin (HY-13753)-induced diabetic rats, lowering blood glucose by 20.2% at 5 hours and 24.3% at 24 hours^[1].
Deoxyandrographolide (100 mg/kg; p.o.; daily; 15 days) significantly reduces blood glucose, improves glucose tolerance, and normalizes lipid and insulin profiles in genetically diabetic db/db mice, including a 36.6% improvement in fasting blood glucose^[1].