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.

British Journal of Pharmacology
D N RoyT Biswas

Abstract

Andrographis paniculata (AP) has been found to display hepatoprotective effect, although the mechanism of action of the active compounds of AP in this context still remains unclear. Here, we evaluated the hepatoprotective efficacy of 14-deoxyandrographolide (14-DAG), a bioactive compound of AP, particularly its role in desensitization of hepatocytes to tumour necrosis factor-alpha (TNF-alpha)-induced signalling of apoptosis. TNF-alpha-mediated ligand receptor interaction in hepatocytes in the presence of 14-DAG was studied in vitro in primary hepatocyte cultures, with the help of co-immunoprecipitation, confocal microscopy and FACS analysis. Events associated with 14-DAG-induced TNFRSF1A release from hepatocytes were determined using immunoblotting, biochemical assay and fluorimetric studies. Pulse-chase experiments with radiolabelled TNF-alpha and detection of apoptotic nuclei by terminal transferase-mediated dUTP nick-end labelling were performed under in vivo conditions. 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/cG...Continue Reading

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Citations

Sep 4, 2013·Biochimica Et Biophysica Acta·Dipanwita SenguptaGobinda Chandra Sadhukhan
Jun 15, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Samir MandalTuli Biswas
Nov 7, 2019·Brazilian Journal of Microbiology : [publication of the Brazilian Society for Microbiology]·Moumita MajumdarDijendra Nath Roy
Jan 1, 2014·TheScientificWorldJournal·Md Sanower HossainK M Hafizur Rahman

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