Comparative evaluation of hesperetin-loaded graphene oxide nanosheets (Hsp-GO) as a drug delivery system for colon cancer: synthesis and anticancer efficiency assessment.

BACKGROUND: Graphene oxide nanosheets (GONS) are recognized for their role in enhancing drug delivery and effectiveness in cancer treatment. With colon cancer being a prevalent global issue and the significant side effects associated with chemotherapy, the primary treatment for colon cancer alongside surgery, there is a critical need for novel therapeutic strategies to support patients in combating this disease. Hesperetin (HSP), a natural compound found in specific fruits, exhibits anti-cancer properties. The aim of this study is to investigate the effect of GONS on the LS174t colon cancer cell line. METHODS: In this study, an anti-cancer nano-drug was synthesized by creating a hesperetin-graphene oxide nanocomposite (Hsp-GO), which was subsequently evaluated for its efficacy through in vitro cell toxicity assays. Three systems were investigated: HSP, GONS, and HSP-loaded GONS, to determine their cytotoxic and pro-apoptotic impacts on the LS174t colon cancer cell line, along with assessing the expression of BAX and BCL2. The morphology and properties of both GO and Hsp-GO were examined using scanning electron microscopy (SEM), X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR). RESULTS: The Hsp-GO nanocomposite displayed potent cytotoxic and pro-apoptotic effects on LS174t colon cancer cells, outperforming individual treatments with HSP or GONS. Cell viability assays showed a significant decrease in cell viability with Hsp-GO treatment. Analysis of BAX and BCL2 expression revealed elevated BAX and reduced BCL2 levels in Hsp-GO treated cells, indicating enhanced apoptotic activity. Morphological analysis confirmed successful Hsp-GO synthesis, while structural integrity was supported by X-ray diffraction and FTIR analyses. CONCLUSIONS: These study highlight the potential of Hsp-GO as a promising anti-cancer nano-drug for colon cancer therapy.

Fine characterization and microbiota assessment as keys to understanding the positive effect of standardized natural citrus extract on broiler chickens.

The objective of this study was to investigate the effect and composition of a standardized natural citrus extract (SNCE) on both broiler chickens' growth performances and intestinal microbiota. A total of 930 one-day-old males were randomly assigned to three dietary treatments: a control treatment (CTL) in which broiler chickens were fed with a standard diet and two citrus treatments in which broiler chickens were fed with the same standard diet supplemented with 250 ppm and 2,500 ppm of SNCE, respectively. Each dietary treatment was composed of 10 experimental units (pen) of 31 broiler chickens each. Growth performances such as feed consumption, body weight, and feed conversion ratio (FCR) were recorded weekly until day 42. Litter quality was also weekly recorded while mortality was daily recorded. One broiler chicken was randomly selected from each pen (10 chickens/group) and ceca samples were collected for microbiota analysis at day 7 and 42. Chromatographic methods were used to determine molecules that enter into the composition of the SNCE. Results from the characterization of SNCE allowed to identify pectic oligosaccharides (POS) as a major component of the SNCE. In addition, 35 secondary metabolites, including eriocitrin, hesperidin, and naringin, were identified. The experiment performed on broiler chickens showed that the final body weight of broiler chickens fed diets supplemented with SNCE was higher than those fed the CTL diets (P < 0.01). Broiler cecal microbiota was impacted by age (P < 0.01) but not by the dietary supplementation of SNCE. Results indicate that SNCE allowed enhancing chickens' performances without any modulation of the cecal microbiota of broiler chickens. The characterization of SNCE allowed to identify compounds such as eriocitrin, naringin, hesperidin, and POS. Thus, opening new horizons for a better understanding of the observed effect on broiler chickens' growth performances.

Citrus extracts are increasingly being used in animal nutrition to enhance animal growth performances. Most of the available studies indicate an effect of these extracts on microbiota. However, citrus extracts can vary a lot. Indeed, the composition of citrus extract depends on parameters such as the citrus species, the extraction methods, and the inclusion rate. This variation is very important to take into consideration before using a citrus extract. The objective here was to evaluate a commercially available standardized natural citrus extract in terms of composition and effect on broiler chickens' performances and microbiota. Results showed that standardized natural citrus extract positively affects the final weight of broilers, but no effect was observed on chickens' caecal microbiota. The characterization of the standardized natural citrus extract reveals pectic oligosaccharides as major compounds as well as 35 others molecules. Most of these compounds are well described for their beneficial effect on animals' performances and health. In conclusion, the standardized natural citrus extract showed beneficial effects on broilers' performances. These effects are not correlated with broilers microbiota modulation and may be explained by the composition of the product.

Dynamic assessment of the relationship between oxidative stress and apoptotic pathway in embryonic fibroblast cells exposed to glycidamide: possible protective role of hesperidin.

Worldwide research is being conducted to determine the level of acrylamide (ACR) that humans are exposed to from food and environmental sources. Glycidamide (GA) is an important epoxide metabolite of ACR, and its cytotoxicity is stronger than ACR. In this study, it was aimed to elucidate the effects and underlying mechanisms of GA on the induction of apoptosis in embryonic fibroblast cells. The toxicogenomic profile of GA was studied in terms of both apoptotic and oxidative stress. Embryonic fibroblast cells were exposed to GA (1 and 1000 µM) in the presence and absence of hesperidin (Hes) (20 µM) or vitamin C (VitC) (50 µM) for 24 h. Cell viability, cytotoxicity, lipid peroxidation, hydroxyl radicals, hydrogen peroxide, antioxidant enzyme levels and gene expressions, apoptotic, and oxidative stress-related gene expressions were measured in embryonic fibroblast cells. The results showed that GA induced cytotoxicity and diminished the expression levels of apoptotic genes. Furthermore, GA increased the levels of oxidative stress markers and significantly changed the oxidative stress-related gene expression. It has been determined that antioxidant molecules are considerably suppressed in GA-induced toxicity at both gene and enzyme levels. In addition to these results, when VitC, which is known to have strong antioxidant properties in eliminating the toxic effects of GA, is taken as reference, it has been proven that Hes has stronger antioxidant properties compared to VitC. Finally, GA-induced apoptosis in embryonic fibroblast cells is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent oxidative stress and Hes has antioxidant properties with strong effects.

An assessment of the ameliorative role of hesperidin in Drosophila melanogaster model of cadmium chloride-induced toxicity.

Cadmium chloride (CdCl2) is an important heavy metal widely regarded as an environmental contaminant. Hesperidin, a flavanone glycoside found in citrus fruits, has an established properties against free radicals, apoptosis, and inflammation. The present study investigated the protective actions of hesperidin on CdCl2-induced oxidative damage and inflammation in Drosophila melanogaster. For 7 consecutive days via their diet regimen, the flies were exposed to CdCl2 alone (0.05 mM) or in combination with hesperidin (50 and 100 µM). Exposure to CdCl2 significantly (p < 0.05) increased mortality rate of flies, whereas the survived flies demonstrated significant oxidative toxicity from decreased activities of catalase and Glutathione S-transferase (GST) and Total Thiol (T-SH) and Non-Protein Thiols (NPSH) levels as well as accumulation of Nitric Oxide (NO (nitrite/nitrate)), protein carbonyl and Hydrogen Peroxide (H2O2). However, hesperidin-supplemented diet improved Acetylcholinesterase (AChE) activity, mitochondrial metabolic rate (cell viability), locomotor activity, and amelioration of oxidative damage and lipid peroxidation induced by CdCl2. The hesperidin diet supplement boosted the antioxidant milieu and ameliorated the oxidative damage in the treated flies. Overall, the findings revealed that hesperidin improved antioxidative protective capacity in Drosophila melanogaster model of CdCl2-induced toxicity. This suggests hesperidin as a potential therapeutic agent against oxidative stress disorders due to exposure to CdCl2 and or related toxicants.

Radiation shielding parameters of some antioxidants using Monte Carlo method.

In this paper, radiation shielding parameters such as mass attenuation coefficients and half value layer (HVL) of some antioxidants are investigated using MCNPX (version 2.4.0). The validation of the generated MCNPX simulation geometry for antioxidant structures is provided by comparing the results with standard WinXcom data for radiation mass attenuation coefficients of antioxidants. Very good agreement between WINXCOM and MCNPX was obtained. The results from the validated geometry were used to calculate the shielding parameters of different antioxidants. The radiation attenuation properties of each antioxidant were compared with each other. The results showed that, on average, the highest and the lowest radiation mass attenuation coefficients were observed on hesperidin and delphinidin chloride, respectively. It can be concluded that Monte Carlo simulation is a strong tool and an alternate method where experimental investigations are not possible and a standard simulation setup can be used in further studies for different biological structures. It can also be concluded that the obtained results from this study are very useful for radiology and radiotherapy applications where antioxidants are frequently used.

Biological activity assessment of a novel contraceptive antimicrobial agent.

Microbicides are a new category of compounds being developed as a prophylactic approach for the prevention of transmission of sexually transmitted diseases (STDs), including the human immunodeficiency virus (HIV). These are primarily being developed as women-controlled methods, with the target of designing new compounds or formulations that can be used without the knowledge of a male partner. Microbicide screening can be initially based on their hyaluronidase-inhibiting (HI) activity, as this enzyme plays a major role in the sperm and microbe penetration into the substrate. Derivatives of hesperidin, a citrus flavonoid glycoside, have been reported in the literature for their HI effects. Hesperidin was thereby sulphonated under strictly controlled conditions and the active fraction isolated and characterized, based on its HI activity. This derivative was screened for antimicrobial and enzyme-inhibitory activities, specifically for the reproductive tract. Sulphonated hesperidin (SH) was found to completely inhibit the sperm enzymes hyaluronidase, giving an indication toward its contraceptive effects. It was also been found to inhibit various sexually transmitted pathogens, including Chlamydia trachomatis, Neisseria gonorrhoea, HIV, and Herpes Simplex virus type 2 (HSV-2). Its safety assessment was based on its noninterference in sperm motility and its penetration through the cervical mucus, and no effect on the growth of lactobacilli, the normal vaginal flora. It was also found to be nontoxic to the HIV substrate cells (MT2 cells). The study concludes that sulphonated hesperidin can be developed as a potential microbicide for a dual prophylaxis of contraception and transmission of STDs and AIDS.