Applications of Antioxidants in Metabolic Disorders and Degenerative Diseases: Mechanistic Approach

Department of Zoology, Science College, King Saud University, Riyadh 11451, Saudi Arabia Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea 410028, Romania The Institute of Genetics and Animal Breeding, Polish Academy of Sciences, Jastrzębiec, 05-552 Magdalenka, Poland Institute of Neurobiology, Bulgarian Academy of Sciences, 23 Acad. G. Bonchev Str., 1113 Sofia, Bulgaria Department of Pharmacognosy, University of Vienna, Vienna, Austria

Oxidative stress (resulting from redox homeostasis imbalance between prooxidative and antioxidant systems) is a major player in the pathogenesis of many inflammatory, metabolic, cardiovascular, degenerative, and neoplastic diseases [1]. To counteract this pathological mechanism, exogenous antioxidants act interactively, even synergistically, with the endogenous antioxidant defense system to restore or maintain redox homeostasis [2]. For example, some phytochemicals (e.g., epigallocatechin gallate, resveratrol, phytosterol, myricetin, and gingerol) directly influence the numerous pathways of molecular signal transduction (cell proliferation/migration, inflammation cascade, metabolic disorders, and oxidative stress) [3,4]. Further, many foods in the human diet-vegetables, fruits, juices, and beverages-contain antioxidants [5,6]. Epidemiological studies have shown that long-lasting consumption of antioxidants through food intake has the potential to protect against multiple diseases, including cancer, diabetes, and neurodegenerative and cardiovascular diseases. In this special issue, several studies described different molecular mechanisms for the alleviation of oxidative stress and the prevention of disorders related to ageing and metabolic and degenerative disorders.
In a cardiovascular research-focused work, I. Peluso and colleagues explored the effects of frequent vegetable consumption on the clinical, antioxidant, and immunological markers in individuals at risk of cardiovascular diseases. J. Li and his team examined the role of the milk fat globule (epidermal growth factor 8) as an antioxidant against neuroinflammation. K. Feng et al. explored the therapeutic effect of curcumin in the anterior cruciate ligament crossing on the osteoarthritis rat model and studied the specific mechanisms by which curcumin inhibits chondrocyte apoptosis, triggered by tertiary butyl hydroperoxide. N. A. Stefanova et al. depicted the suppression of Alzheimer's disease-like pathology progression using mitochondria-targeted antioxidant (SkQ1) in a transcriptome profiling study. Bridging oncology and angiology, M. Alasvand et al. highlighted the effects of some alkaloids on the angiogenesis process that influences cellular invasion and tumor growth.
In the field of ophthalmology, S. Bungău et al. presented an overview of the role, mechanisms, and potential synergistic effects of polyphenols (e.g., anthocyanins, ginkgo biloba, resveratrol, and quercetin) and carotenoids (e.g., lutein, zeaxanthin, and mezoxanthin) in the prevention and therapy of age-related ocular pathologies. C.-C. Chang et al. reported that melatonin significantly inhibited H 2 O 2 -induced retinal pigment epithelium (RPE) cell damage and apoptosis, increased the mitochondrial membrane potential, and augmented the autophagy effect. S. Satish et al. concluded that the molecule ZLN005 (a selective PGC-1α transcriptional regulator) increases PGC-1α expression in the human RPE and protects cells against death by three major biological prooxidants. In the same study, they demonstrated that PGC-1α is the critical mediator of ZLN005 antioxidant effects.
In a diabetes research-focused work, A. E. Zayed et al. explored the protective effects of Ginkgo biloba and magnetised water against nephrotoxicity associated with type 2 diabetes mellitus in rats. In the same vein, R. Jimenez et al. In the same field, T. Albrahim and M. A. Binobead showed how Moringa leaf extract could ameliorate the biochemical changes, oxidative stress, hepatic injury, and PCNA and P53 alterations, induced by vetsin (monosodium glutamate) administration. Moreover, W. Tang et al. demonstrated the potential of Hugan Qingzhi tablet (a lipidlowering and anti-inflammatory formula) in preventing and treating fatty nonalcoholic liver diseases in rats, along with its modulatory effect on the intestinal microbiota. Similarly, M. A. Dkhil et al. studied the effects of Indigofera oblongifolia leaf extract (IE) on the hepatic oxidative status, as well as the expression of apoptotic and inflammatory genes in blood-stage murine malaria. They concluded that IE protects the liver tissue from damages caused by P. chabaudi, via anti-inflammatory and antioxidant mechanisms.
In the field of neuromuscular disease, P. Xu et al. demonstrated that after transplantation, the overexpression of BRCA1 in the neural stem cells enhances functional recovery and cell survival into the experimental ischemic stroke, reducing oxidative stress and cell apoptosis. Based on the works mentioned above, the main objective of many studies remains to understand how oxidants act on molecular targets and the pathogenesis of related diseases. The results of these researches are aimed at characterizing novel preventive interventions and suggesting optimal therapeutic schemes.

Conflicts of Interest
All guest editors declare that there is no conflict to declare.