Reactive oxygen species (ROS) are widely known as highly reactive signalling and transcription factors. They have shown beneficial effects at low concentrations to regulate multiple cellular processes like proliferation, differentiation, migration, necrosis, and autophagy. Elevated levels of ROS destroys the physiological functions by cross-linking with lipids, protein, and DNA, which lead to several diseases, including cancer, cardiovascular, diabetes, arthritis, neurological disorders and others metabolic diseases. Thus, quenching of excess ROS is very necessary to counter their deleterious effects. To deplete their increased concentration, there are so many endogenous as well as exogenous antioxidants are available, including both enzymatic and non-enzymatic antioxidants. In this review, we have discussed the numerous sources that generate several type of free radical/non- radical species such as superoxide and nitric oxide, singlet oxygen, nitroxyl anion, nitrosyl cation, hypochlorous acid, etc. In terms of molecular mechanism, we also discussed the role of endogenous (enzymatic, and non-enzymatic) and exogenous antioxidants (vitamins, plant-derived and other small molecules), including ascorbic acids, β-carotene, α-tocopherol, α-lipoic acid, coenzyme Q10, melatonin, and flavonoids (quercetin, luteolin, kaempferol, epicatechin, catechin, daidzein, genistein, and rutin, etc.) in scavenging of ROS. This review described sources and generation of ROS, associated diseases, and antioxidants, mainly focusing on molecular mechanisms. In addition, signaling pathways such as NF-κB, MAPKs, and Keap1-Nrf2-ARE etc., which affects physiological functions of ROS, are also discussed in details. Graphical abstract

In the 21st century, plant-derived metal nanoparticles (PDMNPs) have gained considerable interest because of their tremendous and remarkable potential as therapeutic agents as well as development of less expensive, safer, and easier biomedical equipment. PDMNPs are synthesized from metal salts or oxides by using plant extracts because plants have diversified bioactive compounds that can act as reducing and stabilizing agents at the time of nanoparticle synthesis. Besides, PDMNPs take advantages over the nanoparticles synthesized by other methods because of their low cost, environmental friendliness, and sustainability. The present review explains the synthesis of PDMNPs, their characterization techniques, and oxidative stress-mediated pharmacological effects. The mode of actions for antioxidant, antimicrobial, and anticancer properties has also been critically explored. Due to the plethora of data on plant-derived nanoparticles and their pharmacological properties, we have highlighted PDMNPs’ shape, size, metals of use, and experimental findings regarding their antioxidant, anti-microbial, and anticancer properties in a tabulated form for studies conducted in the last five years, from 2018 to 2022. Because of our review study, we, herein, contemplate that the scientific community as a whole will get a greater comprehension of PDMNPs and their numerous therapeutic applications in a single window.

Urogenital schistosomiasis is caused by Schistosoma haematobium (S. haematobium) infection, which has been linked to the development of bladder cancer. In this study, three repurposing drugs, ivermectin, arteether and praziquantel, were screened to find the potent drug-repurposing candidate against the Schistosoma-associated bladder cancer (SABC) in humans by using computational methods. The biology of most glutathione S-transferases (GSTs) proteins and vascular endothelial growth factor (VEGF) is complex and multifaceted, according to recent evidence, and these proteins actively participate in many tumorigenic processes such as cell proliferation, cell survival and drug resistance. The VEGF and GSTs are now widely acknowledged as an important target for antitumor therapy. Thus, in this present study, ivermectin displayed promising inhibition of bladder cancer cells via targeting VEGF and GSTs signaling. Moreover, molecular docking and molecular dynamics (MD) simulation analysis revealed that ivermectin efficiently targeted the binding pockets of VEGF receptor proteins and possessed stable dynamics behavior at binding sites. Therefore, we proposed here that these compounds must be tested experimentally against VEGF and GST signaling in order to control SABC. Our study lies within the idea of discovering repurposing drugs as inhibitors against the different types of human cancers by targeting essential pathways in order to accelerate the drug development cycle.

Polo-like kinase-1 (PLK-1) is an essential mitotic serine/threonine (Ser/Thr) kinase that belongs to the Polo-like kinase (PLK) family and is overexpressed in non-small cell lung cancer (NSCLC) via promotion of cell division. Therefore, PLK-1 may act as a promising target for the therapeutic cure of various cancers. Although a variety of anti-cancer drugs, both synthetic and naturally occurring, such as volasertib, onvansertib, thymoquinone, and quercetin, are available either alone or in combination with other therapies, they have limited efficacy, especially in the advanced stages of cancer. To the best of our knowledge, no anticancer agent has been reported from marine algae or microorganisms to date. Thus, the aim of the present study is a high-throughput virtual screening of phlorotannins, obtained from edible brown algae, using molecular docking and molecular dynamic simulation analysis. Among these, Pentafuhalol-B (PtB) showed the lowest binding energy (best of triplicate runs) against the target protein PLK-1 as compared to the reference drug volasertib. Further, in MD simulation (best of triplicate runs), the PtB-PLK-1 complex displayed stability in an implicit water system through the formation of strong molecular interactions. Additionally, MMGBSA calculation (best of triplicate runs) was also performed to validate the PtB-PLK-1 complex binding affinities and stability. Moreover, the chemical reactivity of PtB towards the PLK-1 target was also optimised using density functional theory (DFT) calculations, which exhibited a lower HOMO-LUMO energy gap. Overall, these studies suggest that PtB binds strongly within the pocket sites of PLK-1 through the formation of a stable complex, and also shows higher chemical reactivity than the reference drug volasertib. The present study demonstrated the inhibitory nature of PtB against the PLK-1 protein, establishing its potential usefulness as a small molecule inhibitor for the treatment of different types of cancer.