Diabetes mellitus, a complex metabolic disorder, presents a growing global health challenge. In 2021, there were 529 million diabetics worldwide. At the super-regional level, Oceania, the Middle East, and North Africa had the highest age-standardized rates. The majority of cases of diabetes in 2021 (>90.0%) were type 2 diabetes, which is largely indicative of the prevalence of diabetes in general, particularly in older adults (K. L. Ong, et al., Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021, Lancet, 2023, 402(10397), 203–234). Nowadays, slowing the progression of diabetic complications is the only effective way to manage diabetes with the available therapeutic options. However, novel biomarkers and treatments are urgently needed to control cytokine secretion, advanced glycation end products (AGEs) production, vascular inflammatory effects, and cellular death. Emerging research has highlighted the intricate interplay between reactive oxygen species (ROS) and protein aggregation in the pathogenesis of diabetes. In this scenario, the main aim of this paper is to provide a comprehensive review of the current understanding of the molecular mechanisms underlying ROS-induced cellular damage and protein aggregation, specifically focusing on their contribution to diabetes development. The role of ROS as key mediators of oxidative stress in diabetes is discussed, emphasizing their impact on cellular components and signaling. Additionally, the involvement of protein aggregation in impairing cellular function and insulin signaling is explored. The synergistic effects of ROS and protein aggregation in promoting β-cell dysfunction and insulin resistance are examined, shedding light on potential targets for therapeutic intervention.

Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in patients with type 2 diabetes mellitus. In search of new inhibitors of amylin aggregation, we undertook the chemical analyses of five marine macroorganisms encountered in high populations in the Red Sea and selected a panel of 10 metabolites belonging to different chemical classes to evaluate their ability to inhibit the formation of amyloid deposits in the human amylin peptide. The thioflavin T assay was used to examine the kinetics of amyloid aggregation, and atomic force microscopy was employed to conduct a thorough morphological examination of the formed fibrils. The potential ability of these compounds to interact with the backbone of peptides and compete with β-sheet formation was analyzed by quantum calculations, and the interactions with the amylin peptide were computationally examined using molecular docking. Despite their structural similarity, it could be observed that the hydrophobic and hydrogen bond interactions of pyrrolidinones 9 and 10 with the protein sheets result in one case in a stable aggregation, while in the other, they cause distortion from aggregation.

Albumin, the most abundant plasma protein, has emerged as a promising carrier in drug delivery because of its exceptional biocompatibility, stability, and ligand-binding capacity. This chapter explored the role of albumin-based drug delivery systems and focused on their mechanism, recent innovations, and applications. Albumin can bind endogenous and exogenous molecular facilities for transport and controlled release of therapeutic agents, improve drug bioavailability, and minimize adverse effects. It has a long circulatory half-life facilitated by the neonatal Fc receptor (FcRn). This ensures a prolonged, systematic exposure, which makes it a viable option for targeted and sustained drug release. A chapter delves into a multiple drug-binding mechanism, including covalent and noncovalent interactions, nanoparticle formulation, and nanoparticles. The albumin nanoparticles (ABNPs) are particularly significant in modern therapeutics, controlled drug release, enhanced solubility, and tumor targets through receptor-mediated uptake and enhanced permeability and retention (EPR) effects. Through preparation techniques, like desolvation, emulsification, and high-pressure homogenization (NAB™ technology), they optimized an albumin nanoparticle for the enhancement of therapeutic efficacy. A clinical application of the albumin-based system extended beyond oncology, with notable success in diabetes, neurodegenerative disorders, and infectious diseases. The engineered albumin variant and albumin-drug conjugates expand the versatility of precision medicine. Challenges like stability, manufacturing scalability, and the drug-albumin interactions required continued refinement of albumin’s role in drug delivery.

Ephedra foeminea Forssk. is a medicinal plant traditionally used across various cultures and recognized for its historical significance in herbal medicine. It has been used as an herbal infusion to treat multiple respiratory diseases, headaches, and nasal congestion, as well as to prevent and manage breast cancer. In order to evaluate the validity of this ancestral knowledge, we aimed to investigate hot aqueous extracts of E. foeminea branches and fruits firstly by using untargeted metabolomic analysis, characterizing the chemical profiles of hot aqueous extracts from E. foeminea branches and fruits through the use of nuclear magnetic resonance, gas chromatography–mass spectrometry, and liquid chromatography–mass spectrometry. Subsequently, two in vitro studies were conducted to assess the anticancer and antioxidant potentials of the extracts. Antioxidant activity was evaluated using a 2,2-diphenyl-1-picrylhydrazyl assay and a total phenolic content assay. Anticancer activity was evaluated by assessing cytotoxicity using the MTT assay on MCF-7 (human breast cancer) and HeLa (cervical cancer) cell lines. Additionally, molecular docking was performed to explore the interactions between compounds identified in E. foeminea and selected cancer-related proteins, as well as the main protease of SARS-CoV-2. The results revealed that the branch extract exhibited superior antioxidant activity compared to the fruit extract, which was associated with a higher phenolic content in the branch extract (49.5 ± 0.7 mg GAE/g). The fruit extract exhibited greater cytotoxicity against MCF-7 cells, suggesting potential anticancer activity. Molecular docking analysis identified henryoside, guajavarin, and neohancoside as the most active compounds with anticancer and antiviral properties. These findings support the traditional use of E. foeminea Forssk. and highlight its potential as a source of bioactive compounds for further research into therapeutic applications.