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Introduction: Aging leads to significant structural and functional changes in blood vessels, which disrupt their normal function and impact cardiovascular health. Current research is actively exploring the NRF2 antioxidative pathway, recognizing its role in protecting cells by preserving their antioxidant defenses against damage. However, there has been limited exploration into the role of the NRF2 pathway in vascular aging. The primary objective of this study was to determine whether age-related changes in the aorta are associated with variations in the baseline levels of antioxidant enzymes, with a particular emphasis on how the NRF2 pathway operates in the aortic wall., Methods: A group of healthy aging female SD rats was compared with their younger counterparts. Various assessments were conducted, including measuring blood pressure, analyzing serum lipid profiles, examining aortic tissue, and assessing the expression of antioxidant enzymes., Results: The results revealed significant differences in both blood pressure and serum lipid levels between the aged and younger rats. The examination of the aorta in older rats showed structural alterations, increased apoptosis, and the accumulation of fatty deposits. In the older rats, levels of SOD-1 (superoxide dismutase) and GSS (glutathione synthetase) were lower, whereas NRF2, KEAP-1 (Kelch-like ECH-associated protein 1), and HO-1 (Heme oxygenase 1) were higher., Discussion: This study advances our understanding of how aging affects the antioxidant system in blood vessels, particularly in relation to the regulation of the NRF2/HO-1 pathway in the aorta. These findings suggest that targeting the NRF2/HO-1 pathway could present anovel therapeutic approach for addressing age-related vascular issues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Asad, Qian, Wang, Asad, Gao, Cao, Huang, Bin Jardan, Shah, Wondmie, Bourhia, Lu and Zhu.)

Aldose reductase (AR) is an important target in the development of therapeutics against hyper-glycemia-induced health complications such as retinopathy, etc. In this study, we employed a combination of structure-based drug design, molecular simulation, and free energy calculation approaches to identify potential hit molecules against anti-diabetic (anti-hyperglycemic)-induced health complications. The 3D structure of aldoreductase was screened for multiple compound libraries (1,00,000 compounds) and identified as ZINC35671852, ZINC78774792 from the ZINC database, Diamino-di nitro-methyl dioctyl phthalate, and Penta-o-galloyl-glucose from the South African natural compounds database, and Bisindolylmethane thiosemi-carbazides and Bisindolylme-thane-hydrazone from the Inhouse database for this study. The mode of binding interactions of the selected compounds later predicted their aldose reductase inhibitory potential. These com-pounds interact with the key active site residues through hydrogen bonds, salt bridges, and π-π interactions. The structural dynamics and binding free energy results further revealed that these compounds possess stable dynamics with excellent binding free energy scores. The structures of the lead inhibitors can serve as templates for developing novel inhibitors, and in vitro testing to confirm their anti-diabetic potential is warranted. The current study is the first to design small molecule inhibitors for the aldoreductase protein that can be used in the development of therapeutic agents to treat diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shahab, Zheng, Alshabrmi, Bourhia, Wondmie and Mohammad Salamatullah.)

Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability. Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C -80, C-120,C -150, C -200 ns) revealed strong hydrogen bonding in the complexes and showed -12.9, -11.6, and -11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis. Conclusion: Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zafar, Safder, Imran Afridi, Riaz, -ur-Rehman, Unar, Un Nisa, Gaafar, Bourhia, Wondmie, Sharma and Kumar.)

Alzheimer's disease (AD) is more commonly found in women than in men as the risk increases with age. Phytochemicals are screened in silico from Punica granatum peels for their antioxidant activity to be utilized for Alzheimer's disease. Alzheimer's disease is inhibited by the hormone estrogen, which protects the brain from the bad effects of amyloid beta and acetylcholine (ACh), and is important for memory processing. For the purpose, a library of about 1,000 compounds from P. granatum were prepared and studied by applying integrated computational calculations like 3D-QSAR, molecular docking, MD simulation, ADMET, and density functional theory (DFT). The 3D-QSAR model screened the active compounds B25, B29, B35, B40, B45, B46, B48, B61, and B66 by the field points and activity atlas model from the prepared library. At the molecular level, docking was performed on active compounds for leading hit compounds such as B25 and B35 that displayed a high MolDock score, efficacy, and compatibility with drug delivery against the antioxidant activity. Optimization of the structure and chemical reactivity parameter of the hit compound was calculated by DFT. Moreover, ADMET prediction was evaluated to check the bioavailability and toxicity of the hit compound. Hesperidin (B25) is found to be a hit compound after the whole study and can be synthesized for potent drug discovery in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Parveen, Batool, Shafiq, Rashid, Sultan, Wondmie, Bin Jardan, Brogi and Bourhia.)

The present work aimed at characterizing the phytochemical composition of Haplophyllum tuberculatum essential oil (HTEO), assessing its antifungal activity against various fungal strains, evaluating its insecticidal and repulsive properties against Callosobruchus maculatus , and determine its antioxidant capacity. To this end, Gas chromatography-mass spectrometry analysis detected 34 compounds in HTEO, with β -Caryophyllene being the major constituent (36.94%). HTEO demonstrated predominantly modest antifungal effects, however, it sustains notable activity, particularly against Aspergillus flavus , with an inhibition rate of 76.50% ± 0.60%. Minimum inhibitory concentrations ranged from 20.53 ± 5.08 to 76.26 ± 5.08 mg/mL, effectively inhibiting fungal growth. Furthermore, the antifungal, and antioxidant activities of HTEO were evaluated in silico against the proteins Aspergillus flavus FAD glucose dehydrogenase, and beta-1,4-endoglucanase from Aspergillus niger , NAD(P)H Oxidase. Moreover, HTEO displayed strong insecticidal activity against C. maculatus , with contact and inhalation tests yielding LC 50 values of 30.66 and 40.28 μL/100g, respectively, after 24 h of exposure. A dose of 5 μL/100g significantly reduced oviposition (48.85%) and inhibited emergence (45.15%) compared to the control group. Additionally, HTEO exhibited a high total antioxidant capacity of 758.34 mg AAE/g EO, highlighting its antioxidant potential. Insilico results showed that the antifungal activity of HTEO is mostly attributed to γ -Cadinene and p-Cymen-7-ol, while antioxidant is attributed to α -Terpinyl isobutyrate displayed. Overall, HTEO offers a sustainable and environmentally friendly alternative to synthetic products used to manage diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Agour, Mssillou, Allali, Chebaibi, El Abdali, El Barnossi, Bin Jardan, Wondmie, Nafidi, Bourhia, Bari, Lyoussi and Derwich.)

Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins in its life cycle is ongoing due to the paucity of drugs in clinical use against the virus. Consequently, this study was aimed at evaluating the potentials of natural phenolics against the Main protease (Mpro) and the receptor binding domain (RBD) using molecular modeling techniques including molecular docking, molecular dynamics (MD) simulation, and density functional theory (DFT) calculations. To this end, thirty-five naturally occurring phenolics were identified and subjected to molecular docking simulation against the proteins. The results showed the compounds including rosmarinic acid, cynarine, and chlorogenic acid among many others possessed high binding affinities for both proteins as evident from their docking scores, with some possessing lower docking scores compared to the standard compound (Remdesivir). Further subjection of the hit compounds to drug-likeness, pharmacokinetics, and toxicity profiling revealed chlorogenic acid, rosmarinic acid, and chicoric acid as the compounds with desirable profiles and toxicity properties, while the study of their electronic properties via density functional theory calculations revealed rosmarinic acid as the most reactive and least stable among the sets of lead compounds that were identified in the study. Molecular dynamics simulation of the complexes formed after docking revealed the stability of the complexes. Ultimately, further experimental procedures are needed to validate the findings of this study., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shafiq, Mehroze, Sarwar, Arshad, Parveen, Rashid, Farooq, Rafiq, Wondmie, Bin Jardan, Brogi and Bourhia.)