Background and PurposeWithanolides are naturally occurring chemical compounds. They are secondary metabolites produced via oxidation of steroids and structurally consist of a steroid-backbone bound to a lactone or its derivatives. They are known to protect plants against herbivores and have medicinal value including anti-inflammation, anti-cancer, adaptogenic and anti-oxidant effects. Withaferin A (Wi-A) and Withanone (Wi-N) are two structurally similar withanolides isolated from Withania somnifera, also known as Ashwagandha in Indian Ayurvedic medicine. Ashwagandha alcoholic leaf extract (i-Extract), rich in Wi-N, was shown to kill cancer cells selectively. Furthermore, the two closely related purified phytochemicals, Wi-A and Wi-N, showed differential activity in normal and cancer human cells in vitro and in vivo. We had earlier identified several genes involved in cytotoxicity of i-Extract in human cancer cells by loss-of-function assays using either siRNA or randomized ribozyme library.Methodology/Principal FindingsIn the present study, we have employed bioinformatics tools on four genes, i.e., mortalin, p53, p21 and Nrf2, identified by loss-of-function screenings. We examined the docking efficacy of Wi-N and Wi-A to each of the four targets and found that the two closely related phytochemicals have differential binding properties to the selected cellular targets that can potentially instigate differential molecular effects. We validated these findings by undertaking parallel experiments on specific gene responses to either Wi-N or Wi-A in human normal and cancer cells. We demonstrate that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells. Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells. The present molecular docking analyses and experimental evidence revealed important insights to the use of Wi-A and Wi-N for cancer treatment and development of new anti-cancer phytochemical cocktails.
In this work the structural, electric and magnetic characteristics of 0.2(Ni0.8 Zn0.2Fe2O4 (NZF))-0.8 (Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT)) multiferroic composite is investigated. The constituent phases were synthesized by sol-gel process, and mixed in an appropriate ratio to form the composite. The XRD data and Rietveld refinement confirm that the composite exists in cubic+tetragonal+orthorhombic mixed phases. The P-E loop of the composite shows a finite loop opening with a decrease in the polarization compared to the pure BCZT. The M-H loops show a saturated loop at an applied field ∼ 1 kOe and the values of magnetization decreased nearly by four orders, compared to the pure NZF.
Lead-free Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT) ceramic has been prepared by solgel synthesis method. The effect of sintering temperature on the structure of BCZT ceramic was investigated. X-ray Diffraction studies show the suppression of secondary phase TiO2 with an increase in sintering temperature. The formation oftetragonal-orthorhombic morphotropic phase boundary is observed at the sintering temperature of 1350 °C. Polarization (P) versus electric field (E) measurementshows a remnant polarization of 1.32 µC/cm2 and coercive field of 4.33 kV/cm.
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