In vitro and In silico Cytotoxic Activity of Aconitum heterophyllum Phytoniosomes and its Ethanolic Root Extract: A Comparative Study

Abstract

The present study aimed to investigate the comparative in vitro and in silico antioxidant and anti-proliferative activity of ethanolic root extract of Aconitum heterophyllum and Aconitum heterophyllum roots loaded phytoniosomes. Initially the ethanolic root extract of Aconitum heterophyllum and Aconitum heterophyllum roots loaded phytoniosomes were prepared and their antioxidant potential were studied in terms of 2,2-diphenyl-1-picrylhydrazyl, super oxide, hydroxyl radical scavenging by employing in vitro method. Assessment of anti-proliferative activity of MCF-7 human breast cancer cell lines was performed using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay and trypan blue exclusion assay. In silico docking was performed using Auto Dock Schrodinger Glide to identify the suitable antagonistic ligand which can inhibit the proteins breast cancer gene 1, breast cancer gene 2 and human epidermal growth factor receptor 2 to exert the cytotoxic effect. In the present study a concentration dependent cytotoxic activity was observed for both the extract. However, the enhanced cytotoxic activity observed for Aconitum heterophyllum roots loaded phytoniosomes extract may be due to the increased bioavailability of phytochemicals in the form of phytoniosomes. IC50 values were for the Aconitum heterophyllum roots loaded phytoniosomes calculated and it was found to be 43.81 μg/ml, 50.46 μg/ml respectively for 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide and trypan blue assay. Among the 21 phyto components identified in the gas chromatography-mass spectrometry analysis molecular docking analysis revealed the antagonistic nature of phytoligands namely α-D-Glucopyranoside,β-D-Fructofuranosyl and pyrrlidine,2α-1-pyrrolidinoformyl has the ability to inhibit the three tumour progressive proteins namely breast cancer gene 1, breast cancer gene 2 and human epidermal growth factor receptor 2 and their amino acid interactions were comparable to the positive drug Doxorubicin. Based on these studies the Aconitum heterophyllum loaded phytoniosomes can be a novel drug delivery tool in treating breast cancer.