Exploring the antioxidant, anticancer and antimicrobial potential of Amaranthus viridis L. collected from Fayoum depression: Phytochemical, and biological aspects

Amaranthus viridis (AV) is an invasive weed designated for natural antioxidants. In the current endeavor, A. viridis aerial parts and soil samples were collected from six districts of Fayoum depression (FD), Egypt and were subjected to chemical and biological examination. Where, the organic extracts of the aerial parts of the six distinctive samples (AV1-AV6), were subjected to LC-HRESI-MS-assisted chemical profiling. Multivariate analysis of MS data revealed good clustering of A. viridis collected from three sites (1, 2 and 6) and empowered the hypothesis of chemical composition analogy among extracts AV1, AV2 and AV6. On the other hand, extracts AV3, AV4 and AV5 were not resemblant to each other and were apart from AV1, AV2 and AV6. Similarly, multivariate analysis of physico-chemical properties of A. viridis-associated soil samples showed good clustering of the same three sites (1, 2 and 6). The total phenolics contents (TPC) and total antioxidant capacity (TAC) were promising in all extracts, and they could be arranged in the order of AV6 ˃ AV2 ˃ AV5 ˃ AV3 ˃ AV4 ˃ AV1. Moreover, the uniqueness of AV2, AV3 and AV4 extracts lies in guttiferic acid and the high content of alkaloids that granted the privilege of cytotoxicity toward human liver cancer cell line (HepG2) and human metastatic breast cancer cell line (MDA-MB-231). Regarding the antimicrobial activity, AV1 and AV6 showed the highest antibacterial activity against S. aureus meanwhile AV2, AV3 and AV5 depicted the highest values in case of S. typhi and E. coli. Also, the study revealed that AV1, AV4, and AV6 reflects their prodigious minimum inhibitory concentration (MIC) values against E. coli, S. aureus, and S. typhi. In terms of antifungal activity, AV6 extract recorded as the most inhibition performance against A. flavus and A. niger, whereas AV2 and AV5 inhibited C. albicans the least. According to biofilm activity, AV4 and AV5 were superior, remarkably against E. coli and B. subtilis respectively. Interestingly, the AV6 extract performed exceptionally well as an antibiofilm agent against P. aeruginosa. The potency of some extracts rather than others may rely on possible relationships between soil physicochemical characteristics and chemical composition of A. viridis which contributed to the observed biological properties. Such factors should be taken into consideration in assessing quality control of medicinal plants

Inhibition of Drp1 orchestrates the responsiveness of breast cancer cells to paclitaxel but insignificantly relieves paclitaxel-related ovarian damage in mice

Abstract Chemoresistance and chemotherapy-related ovarian damage are well-reported in breast cancer (BC) young patients. Herein, the inhibition of the mitochondrial fission was invested to explore its chemosensitizing role in Paclitaxel (PTX)-resistant cells, and its ability to restore the ovarian integrity in mice receiving PTX or cisplatin chemotherapy. To establish these aims, PTX-resistance was generated in BC cells, which were treated with PTX in combination with Drp1 deficiency, via mdivi-1, or Drp1-specific siRNA transfection. Furthermore, the alterations in the ovarian structure and the endocrine-related hormones were explored in mice receiving repetitive doses of PTX or cisplatin. We found that combining PTX with mdivi-1 improved cell responsiveness to PTX, induced apoptosis- and autophagy-mediated cell death, and relieved cellular oxidative stress. Additionally, the expression of PCNA1 and cyclin B1 genes were downregulated, meanwhile, p53, p21, and mitochondrial fusion proteins (Mfu1&Mfu2) were increased. The in vivo investigations in mice demonstrated that PTX induced gonadotoxic damage similar to cisplatin, whereas dual treatment of mice with PTX+ mdivi-1 failed to restore their normal follicular count and the circulating levels of E2 and AMH hormones. These results suggested that combining Drp1 inhibition with PTX resensitized breast cancer cells to PTX but failed to offer enough protection against chemotherapy-related gonadotoxicity