Deoxyandrographolide is a natural compound extracted from A. paniculata; potently inhibit the growth of liver (HepG2 and SK-Hep1) and bile duct (HuCCA-1 and RMCCA-1) cancer cells.IC50 value:Target: Anticancer natural compoundin vitro: Treatment with 14-DAG activated AMPK through induction of cyclic AMP-protein kinase A pathway. 14-DAG controlled ethanol-induced hepatosteatosis by interfering with dysregulation of lipid metabolism. In conclusion, our results indicated that 14-DAG was capable of preventing the development of fatty liver through AMPK-mediated regulation of lipid metabolism [1]. 14-DAG down-regulated the formation of death-inducing signalling complex, resulting in desensitization of hepatocytes to TNF-alpha-induced apoptosis. Pretreatment of hepatocytes with 14-DAG accentuated microsomal Ca-ATPase activity through induction of NO/cGMP pathway [2]. 14-DAP, in concentrations between 10-100 microM, reduced the extracellular acidification rate and the intracellular alkalinization in a dose-dependent manner. In addition, 14-DAP reduced PAF-induced calcium flux in the presence of extracellular calcium, and tyrosine phosphorylation of a 44 kDa protein corresponding to the MAPK(ERK1) [3]. in vivo: Half of the ethanol-fed animals received 14-deoxyandrographolide (14-DAG) treatment for the last 4 weeks of study. protective effect of 14-DAG against ethanol-induced hepatic injury is based on its ability to reduce oxidative stress through cNOS dependent improvement of redox status. 14-DAG mediated activation of adenylate cyclase-cAMP signaling leading to up-regulation of cNOS may provide a promising approach in the prevention of liver diseases during chronic alcoholism [4].
[1]. Mandal S, et al. 14-Deoxyandrographolide alleviates ethanol-induced hepatosteatosis through stimulation of AMP-activated protein kinase activity in rats. Alcohol. 2014 Mar;48(2):123-32. [2]. Roy DN, et al. 14-Deoxyandrographolide desensitizes hepatocytes to tumour necrosis factor-alpha-induced apoptosis through calcium-dependent tumour necrosis factor receptor superfamily member 1A release via the NO/cGMP pathway. Br J Pharmacol. 2010 Aug;160(7):1823-43. [3]. Burgos RA, et al. 14-deoxyandrographolide as a platelet activating factor antagonist in bovine neutrophils. Planta Med. 2005 Jul;71(7):604-8. [4]. Mandal S, et al. 14-Deoxyandrographolide targets adenylate cyclase and prevents ethanol-induced liver injury through constitutive NOS dependent reduced redox signaling in rats. Food Chem Toxicol. 2013 Sep;59:236-48.