Cancer is one of the leading causes of death worldwide. Regardless of advances in understanding the molecular mechanics of cancer, its treatment is still lacking and the death rates for many forms ... Graphical abstract

Moringa oleifera is known as a ‘natural nutrition of the tropics’ because it provides vital nutritional supplements and a variety of pharmacological benefits. The focus of this study was to elucidate the dose dependent effects of Moringa oleifera leaf (MOL) extract on the growth of the human osteoblast-like osteosarcoma SaOS-2 cell line and primary osteoblast cells. Trypan blue & tetrazolium assay, intracellular ROS generation, chromatin condensation, cell cycle analysis, alkaline phosphatase (ALP), mineralization, and osteogenic gene expression were tested on both treated and untreated osteosarcoma SaOS-2 cells. As revealed by cell viability assay, growth activity was observed at concentrations 25 and 50 μg/mL of MOL extract, whereas 100 and 200 μg/mL doses decreased the proliferation activity, resulting in ROS production and chromatin condensation. Cell cycle study revealed that MOL extract at 50 and 100 μg/mL concentrations arrested the cells in the G2/M phase. Low doses increased the ALP levels, mineralization, and expression of the bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (Runx2) genes in osteoblast-like SaOS-2 cells, however, high doses inhibited the proliferation properties of MOL extract. Through AutoDock Vina and iGEMDOCK 2.1, the interaction of active components of MOL, such as β-sitosterol, quercetin and kaempferol, with BMP2 and Runx2 proteins revealed a reasonable binding affinity. Moreover, these components did not show any Lipinski's rule of five violation and showed predictable pharmacokinetic properties. The results of the biphasic dose-response of MOL extract on the growth activity of osteoblast-like SaOS-2 cells and in silico binding interface, may provide a therapeutic and/or preventive implication in prospective drug development.

Drug-loaded, brain-targeted nanocarriers could be a promising tool in overcoming the challenges associated with Alzheimer's disease therapy. These nanocargoes are enormously flexible to functionali... Graphical abstract

Beclin1 is the mammalian orthologue of yeast Atg6/vacuolar protein sorting-30 (VPS30). Beclin1 interacts with various biological macromolecules like ATG14, BIF-1, NRBF2, RUBICON, UVRAG, AMBRA1, HMGB1, PINK1, and PARKIN. Such interactions promote Beclin1-PI3KC3 complex formation. Autophagy is blocked in apoptosis owing to the breakdown of Beclin1 by caspase whereas autophagy induction inhibits effector caspase degradation, therefore, blocks apoptosis. Thus, the Beclin1 is an essential biomolecular species for cross-regulation between autophagy and apoptosis. Various studies carried out in neurodegenerative animal models associated with aggregated proteins have confirmed that multifunctional Beclin1 protein is necessary for neuronal integrity. The role of Beclin1 protein has been investigated and was reported in various human neurodegeneration disorders. This chapter aims to provide an insight into the role of Beclin1 in the development of neurodegenerative disorders.

Background: Salvadora persica (S. persica), commonly known as ‘Miswak,’ has been used in ethnotraditional applications since ancient times. This study was formulated to examine bioactive phenolics and flavonoids from the hydroethanolic extract of S. persica bark, anticancer activity, and in silico binding interaction analysis with key therapeutic targets of triple-negative breast cancer (TNBC) cells. Methods: UHPLC was used to identify the phytochemicals in S. persica bark extract. Cell death was analyzed by MTT assay in TNBC MDA-MB-231 and MDA-MB-468 cells. Moreover, cellular apoptosis, ROS generation, MMP, and cell cycle checkpoints were also carried out. AutoDock Tools 1.5.7 and PyRx 0.8 tools were used for molecular binding interaction analysis. Results: Phytochemical analysis revealed the presence of total phenolic and total flavonoid content of 26.90 ± 0.46 μg GAE/mg and 54.51 ± 0.42 μg QE/mg of bark extract, respectively. UHPLC analysis confirmed the presence of fumaric acid, chlorogenic acid, rutin, and quercetin in the extract. S. persica significantly reduced cell viability of MDA-MB-231 and MDA-MB-468 cells with an IC₅₀ value of 144 and 128 μg/mL, respectively. S. persica extract elevated ROS generation, loss of MMP, late apoptosis induction, and G2/M-phase cell cycle arrest, while it did not show any significant effect against normal kidney Vero cells. Molecular docking studies revealed that rutin showed strong binding affinity towards EGFR with B.E. = −9.8 and −9.5 Kcal/mol; FGFR1 with B.E. = −7.4 and −7.5 Kcal/mol; FGFR4 with B.E. = −7.5 and −7.9 Kcal/mol; and csGRP78 with B.E. = −9.0 and −9.3 Kcal/mol, using Autodock Vina and PyRx tools, respectively. SwissADME and drug-likeness analysis confirmed acceptable drug-like characteristics and favorable pharmacokinetic profiles of the identified molecules. Conclusions: This study highlighted the potential of phytochemicals from S. persica bark as promising compounds for the development of novel anticancer therapeutics.