Andrographolide

5508-58-7

C20H30O5

H2O : < 0.1 mg/mL (insoluble); DMSO : 50 mg/mL (142.67 mM; Need ultrasonic)

Autophagy; NF-kappaB

Andrographolide is a NF-kappaB inhibitor, which inhibits NF-kappaB activation through covalent modification of a cysteine residue on p50 in endothelial cells without affecting IkappaBalpha degradation or p50/p65 nuclear translocation. IC50 & Target: NF-kappaB1/p50^[1] In Vitro: Andrographolide (AP) concentration-dependently suppresses receptor activator of nuclear factor kappa B ligand (RANKL)-mediated osteoclast differentiation and bone resorption in vitro and reduces the expression of osteoclast-specific markers. Andrographolide attenuates inflammation by inhibition of TNFalpha-induced NF-kappaB activation through covalent modification of reduced Cys⁶² of p50, without affecting IkappaBalpha degradation or p50/p65 nuclear translocation. Andrographolide also inhibits the ERK/MAPK signalling pathway without affecting p38 or JNK signalling. Andrographolide inhibits osteoclast differentiation of RAW 264.7 cells in a concentration-dependent manner. Andrographolide suppresses osteoclast formation in a concentration-dependent manner without any obvious cytotoxic effects, in both BMMs and RAW 264.7 cells. Andrographolide treatment substantially reduces the area of bone resorption. Only approximately 30% of the bone resorption observed in the control group is achieved after treatment with 2.5?uM Andrographolide. Osteoclastic bone resorption is almost completely inhibited after treatment with 10?uM Andrographolide^[1]. In Vivo: Treatment with Andrographolide (5 or 30?mg/kg) reduces the extent of bone loss induced by LPS. Moreover, Andrographolide slightly increases the BMD and cortex thickness compared to LPS treatment. Histological examination confirms the protective effects of Andrographolide on LPS-induced bone loss. LPS injection leads to inflammatory bone erosion and increased numbers of TRAP-positive osteoclasts^[1].