Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM). Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar male rats (n = 60) were randomly allocated into four groups; Control, Diabetic (streptozotocin (STZ)-treated rats where diabetes was induced by intraperitoneal injection of STZ, 65 mg/kg), Diabetic + TQ (diabetic rats treated with TQ (50 mg/kg) orally once daily), and TQ (non-diabetic rats treated with TQ) for 12 weeks. Results revealed that TQ significantly improved the sperm parameters with a reduction in nitric oxide (NO) and malondialdehyde (MDA) levels in testicular tissue. Also, it increased testicular reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity. Interestingly, TQ induced downregulation of testicular inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-κB) and significantly upregulated the aromatase protein expression levels in testicles in comparison with the diabetic rats. In conclusion, TQ treatment exerted a protective effect against reproductive dysfunction induced by diabetes not only through its powerful antioxidant and hypoglycemic effects but also through its downregulation of testicular iNOS and NF-κB along with upregulation of aromatase expression levels in diabetic rats.

Quercetin was fed to groups of broiler chickens at concentrations of 200, 400, and 800 ppm, and a control group was supplemented with a basal diet. Results revealed that quercetin dietary supplementation numerically improved the growth performance traits and significantly increased (p < 0.05) the European production efficiency factor (EPEF) in the 200 ppm group. The total coliforms and Clostridium perfringens were decreased (p < 0.05) in quercetin-supplemented groups. Conversely, Lactobacillus counts were increased (p < 0.05), due to improvement of the gut microbiota environment in quercetin-supplemented groups. Moreover, the mRNA expression of intestinal Cu/Zn-superoxide dismutase (SOD1), glutathione peroxidase (GSH-Px) and nutritional transporters, including glucose transporter 2 (GLUT2), peptide transporter 1 (PEPT1), and fatty acid synthase (FAS) genes, were significantly upregulated in quercetin-supplemented groups. Quercetin enhanced intestinal morphometry. We can suggest quercetin supplementation in broiler chickens by levels between 200 and 400 ppm to enhance their development and gut environment.

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1β, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.

The focus on nanotechnology for improved bioavailability and drug delivery is of increasing importance for control of different human diseases. Therefore, numerous nanoformulations have been developed for the oral bioavailability of different drugs. This review introduces applications of nanomedicine to enhance the biological activities of thymoquinone (TQ) to control different diseases in several in vivo studies as a preliminary investigation for human disease treatment with nano-TQ. Nano-TQ effectively augments the anticancer roles of doxorubicin by upregulation of P53 and downregulation of Bcl2 and potentiates paclitaxel’s apoptosis in MCF-7 breast cancer cells. Moreover, nano-TQ protects against diabetes, inflammation, CNS, and hepatotoxicity, mainly by enhancement of organs’ antioxidant status. We summarize the pros and cons of several FDA approved nanoparticle-based therapeutics and discuss the roadblocks in clinical translation, along with potential nano-TQ strategies to overcome these roadblocks. From this review, we can conclude that nano-TQ may be considered as a promising nutraceutical for human health.

Interactions of the receptor for advanced glycation end product (RAGE) and its ligands in the context of their role in diabetes mellitus, inflammation, and carcinogenesis have been extensively investigated. This review focuses on the role of RAGE-ligands and anti-RAGE drugs capable of controlling cancer progression. Different studies have demonstrated interaction of RAGE with a diverse range of acidic (negatively charged) ligands such as advanced glycation end products (AGEs), high-mobility group box1 (HMGB1), and S100s, and their importance to cancer progression. Some RAGE-ligands displayed effects on anti- and pro-apoptotic proteins through upregulation of the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-κB) pathways, while downregulating p53 in cancer progression. In addition, RAGE may undergo ligand-driven multimodal dimerization or oligomerization mediated through self-association of some of its subunits. We conclude our review by proposing possible future lines of study that could result in control of cancer progression through RAGE inhibition.

Supplementation of exogenous enzymes in chickens has been widely practiced, yet mechanisms responsible are not fully delineated. To investigate the effects of the dietary lysozyme on the growth performance and immunity of broiler chickens, a total of 120 one-day-old Ross 308 chicks were randomly allocated into four groups, each having three replicates (30 birds/group). The chicks were fed the starter (1–21 d) and grower (22–35 d) diets supplemented with 0 (control), 70 (LYZ70), 90 (LYZ90) and 120 (LYZ120) g of lysozyme 10%^® per ton of basal diet for five weeks. The results revealed significant improvement in the growth performance and gut environment. There were significant decreases (P < 0.05 or 0.01) in the harmful fecal Coliform and Clostridia and an increase (P ˂ 0.05) in the beneficial Lactobacillus in the lysozyme-supplemented groups, especially in LYZ90. Moreover, the mRNA expressions of Cu, Zn-superoxide dismutase (SOD1), glutathione peroxidase (GSH-Px), interferon-gamma (IFN-γ), interleukin-10 (IL-10), and interleukin-18 (IL-18) were upregulated in response to lysozyme supplementation. In comparison to control, LYZ90 fed birds had a significant increase (P < 0.01) in the GSH-Px gene expression that enhances the antioxidant status of the gut. Expression of the biomarkers involved in the gut non-specific immunity indicated significant increases in the mRNA expression of INF-γ (P < 0.001), IL-10 (P < 0.001), and IL-18 (P < 0.05) in LYZ90 group. Also, serum globulin levels were significantly elevated (P ˂ 0.05) in lysozyme-supplemented groups. Histologically, the intestinal villi length and crypts depth were also enhanced (P ˂ 0.05) by dietary lysozyme supplementation. In conclusion, supplementation of broiler chickens with exogenous lysozyme, especially at 90 g of lysozyme per ton of basal diet dose rate, improved the growth performance, gut antioxidant status, and nonspecific immunity of broiler chickens.