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Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer’s and Parkinson’s disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.

Background Our previous reports demonstrated the prospects of a new series of imidazoles as a source of alternative anti-parasite treatments, thus warranting further studies that include toxicity profiling. Objective In this study, we evaluated three imidazoles: bis-imidazole (compound 1), phenyl-substituted 1H-imidazole (compound 2), and thiopene-imidazole (compound 3) for cellular toxicity and possible mechanisms. Methods The three (3) compounds were assessed for in vitro cytotoxic action. Additionally, we probed likely mechanistic actions of these imidazoles. Findings showed dose-dependent cellular toxicity by these imidazoles. Results In the presence of antioxidant (Trolox), cytotoxicity was improved for compounds 2 and 3 but not for compound 1. Meantime, compound 7 promoted reactive oxygen species (ROS) production, which was abated in the presence of a standard antioxidant (Trolox). Additionally, the three (3) imidazoles impaired mitochondrial membrane potential (MMP). While MMP was not restored after treatment removal, the addition of antioxidant (Trolox) improved MMP for compounds 2 and 3 treatment. Additionally, compound 1 elevated expression of hypoxia-inducing factor 1-alpha (HIF-1α). This may not be unconnected with the capacity of compound 1 to cause oxidative stress. Conclusion We show evidence that supports the cytotoxic action of imidazoles involves likely impairment to redox balance and mitochondrial membrane potential. The findings help our understanding of the mechanistic action of these imidazoles in living cells, and altogether may boost their prospects as new and alternative anti-protozoans.

Breast cancer (BC) is one of the most common and recurring diseases and the second leading cause of death in women. Despite prevention, diagnostics, and therapeutic options such as radiation therapy and chemotherapy, the number of occurrences increases every year. Therefore, novel therapeutic drugs targeting specifically different checkpoints should be developed against breast cancer. Among drugs that can be developed to treat breast cancer, natural products, such as plant-derived compounds, showed significant anti-breast cancer properties. These substances belong to different chemical classes such as flavonoids, terpenoids, phenolic acids, and alkaloids. They exert their in vitro and in vivo cytotoxic activities against breast cancer cell lines via different mechanisms, including the inhibition of extrinsic and intrinsic apoptotic pathways, the arrest of the cell cycle, and the activation of autophagy. Moreover, they also exhibit anti-angiogenesis and antimetastatic action. Moreover, chemoprevention effects of these bioactive compounds were signaled only for certain drugs. Therefore, the aim of this review is to highlight the pharmacological actions of medicinal plants and their bioactive compounds on breast cancer. Moreover, the role of these substances in breast cancer chemoprevention was also discussed.

Background Therapeutic options for toxoplasmosis are limited. This fact underscores ongoing research efforts to identify and develop better therapy. Previously, we reported the anti-parasitic potential of a new series of derivatives of imidazole. Objective In the current investigation, we attempted the investigation of the possible action mechanism of few promising anti-parasite imidazole derivatives namely C1 (bis-imidazole), C2 (phenyl-substituted 1H-imidazole) and C3 (thiophene-imidazole) Methods We evaluated if oxidative stress, hypoxia as well as metabolic reprogramming of host l -tryptophan pathway form part of the parasite growth inhibition by imidazoles. Anti-parasite assay was performed for imidazoles at concentrations ranging from 0 to 10 μM, while pyrimethamine was used as reference drug to validate assay. Results Imidazole compounds restricted parasite growth dose-dependently. However, in the presence of an antioxidant (Trolox), l -tryptophan and/or CoCl2 (chemical inducer of hypoxia), the growth inhibitory efficacy of imidazoles was appreciably abolished. Further, imidazole treatment led to elevated level of reactive oxygen species, while reducing parasite mitochondrial membrane potential compared with control. In contrast, imidazole had no effect on host HIF-1α level suggesting its exclusion in the anti-parasite action. Conclusion Taken together, imidazole-based compounds might restrict parasite growth by causing oxidative stress. The findings provide new insight on the likely biochemical mechanisms of imidazoles as prospective anti-parasite therapy. Data gives new perspective that not only underscores the anti-parasite prospects of imidazoles, but implicates the host l -tryptophan pathway as a feasible treatment option for T. gondii infections.