Safety evaluation of Andrographis paniculata Nilavembu extract in preclinical models

Abstract

newline Andrographis paniculata (Burm.f.) Nees is a medicinal herb that contains the newlineactive ingredients such as andrographolide, deoxyandrographolide, 11, 12-didehydro- newline14-deoxy-andrographolide, neoandrographolide, andrographiside, newlinedeoxyandrographiside, andropanoside, etc. The extract of Andrographis paniculata newlinewas known for various pharmacological properties such as analgesic, anticancer, newlineantidiabetic, antiinflammatory, antipyretic, antiviral, etc. As the toxicity studies newlineconducted on Andrographis paniculata extract or andrographolide alone are limited, newlinethe following toxicity studies were conducted, such as in silico prediction of PD, PK newlineand toxicities, genotoxicity, repeated dose toxicity studies and teratology study in rats newlineto assess the safety of its use and to determine the acceptable daily intake. newlineVarious in silico predictions for the target identification, pharmacokinetics, newlinetoxicities were performed using online/offline tools for the four active ingredients newline(Andrographolide, Neoandrographolide, Andrograpanin, and 14-Deoxy-11,12- newlinedidehydroandrographolide) quantified in the A. paniculata extract. The major predicted targets were NEK6 (a serine/threonine-protein kinase that has an effect on newlinemitotic cell progression) and Cytochrome P450 (involved in drug metabolism). ADME newlineprediction indicated that the ingredients may have good intestinal absorption but may newlinenot have adequate bioavailability, which could be due to the rapid clearance by CYP newlineand UGT. The active ingredients of A. paniculata were predicted to have low toxicity newlinepotential, with chances of nephrotoxicity and immunotoxicity. Developmental toxicity newlinewas predicted for neoandrographolide and 14-deoxy,1-12-didehydro-andrographolide, newlineand they were predicted to be non-genotoxic. newlineThe genotoxicity potential of Andrographolide and Andrographis paniculata newlineextract was studied by Ames mutagenicity assay and in vitro chromosomal aberration newlineassay in CHO-K1 cell line, and they were found to be non-genotoxic. The newlineclastogenicity of Andrographis paniculata extract was studied