Molecular oxygen, a basic component of aerobic metabolism, is an inevitable component of all living organisms. However, a portion of the oxygen used by the cells is converted to several harmful reactive oxygen species (ROS) and free radicals. In low/moderate concentrations, free radicals serve as beneficial compounds and are involved in normal physiological functions. Excessive free radical generation results in oxidative stress, with the prime targets being the fundamental building blocks of cell, such as lipids, protein, and DNA. Oxidative damage to these molecules leads to growth arrest, senescence, or apoptosis which play crucial role in the development of several pathological conditions of humans. A growing body of recent literature suggests that scavenging these ROS alleviates the diseases completely. The documented literature suggests that many herbal extracts possess antioxidant effects. Among them, brahmi (Bacopa monneiri) has received increasing attention as a traditional medicine for treatment of several disorders. Previous research has shown that Bacopa monneiri is used to cure various ailments such as cardiovascular diseases, cancer, neurodegenerative diseases, and diabetes, among others. The present review focuses on the therapeutic potential of Bacopa monneiri in the management of diseases that are caused by oxidative stress and ROS by acting as a free radical scavenger.
: Leukotrienes are one of the major eicosanoid lipid mediators being produced as a result of oxidative transformation of arachidonic acid. Subsequently, they get converted into various cellular signaling hormones by a series of enzymes of myeloid origin to mediateor debilitate inflammation. Interestingly, the available literature demonstrates the pivotal role of eicosanoids in neurodegenerative, obesity, diabetes, cardiovascular diseases and cancers as well. The aberrant metabolism of arachidonic acid by LOX pathway is a common feature of epithelial derived malignancies and suggests the contributory role of dietary fats in carcinogenesis. The enzymes and receptors of the LOX pathway play a significant role in cell proliferation, differentiation and regulation of apoptosis through multiple signaling pathways and have been reported to be involved in various cancers including prostate, colon, lung and pancreatic cancers. So far, leukotriene receptor antagonists and 5-LOX inhibitors have reached up to the clinical trials for treating various diseases. Keeping its various roles in cancer, the review highlights the components of the leukotriene synthesizing machinery, emerging opportunities for pharmacological intervention, and the probability of considering lipoxygenases and leukotriene receptors as good candidates for clinical chemoprevention studies.
Glioblastoma is the malignant tumor affecting the central nervous system. Despite the advancement in treatment modalities, presence of blood-brain barrier, recurrence after surgical removal, resistance to radiotherapy and chemotherapy remain the major obstacles for long term survival of the patients. In this context, finding suitable therapeutics which have anticancer potential and are nontoxic might be useful to improve the overall survival of GBM. Plant products are safer, nontoxic and cheaper when compared to the chemotherapeutic drugs in trend which are expensive and highly toxic, owing to their systemic effects. Bacoside A (BA) is one such plant constituent isolated from Bacopa monnieri which offers neuroprotection and possesses anticancer potential. The present investigation elucidates the specific interaction of BA with various cell surface receptors, signal transduction proteins, effector proteins and transcription factors involved in glioblastoma signalling such as EGFR/Ras/Raf/MAPK pathway, Notch signalling and Wnt-beta catenin signalling through molecular docking studies. The interaction between BA and the target proteins of glioblastoma were analysed through the Glide module (Version 6.5) of Schrodinger Suite (2015) software. According to the results of molecular docking, jagged-1 ligands interact with BA with stronger affinity and Frizzled receptors interact with least affinity in terms of glide score. The results indicate that BA interacts well with the polar amino acids such as Asn, Trp, Arg, Ser, Thr, Tyr, Gln, Asp, Lys and Glu. The ligand also showed interactions with specific hydrophobic amino acids such as Val, Ala and Leu in all the protein targets studied. The in vitro cytotoxicity studies reveal the cytotoxic potential of BA on the U87MG glioblastoma cell line. This study warrants further investigation to elucidate modulations on cell signalling pathways resulting from the specific BA-target interactions in glioblastoma.
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