Pterostilbene induces apoptosis in hepatocellular carcinoma cells: Biochemical, pathological, and molecular markers.

Worldwide, hepatocellular carcinoma (HCC) is considered the sixth most prevalent cancer and ranked third in causes leading to death. Pterostilbene (PTE), a dimethylated analog of resveratrol, is a phytochemical found in fruits such as blueberries and grapes, and is known for its anticancer effect. The current study intended to investigate the effect of PTE on HepG2 cells. Cell viability, colony-forming potential, lipid peroxidation, catalase enzyme (CAT), superoxide dismutase (SOD), and caspase 3 activities, histone release, and expression levels of mTOR, S6K1, p53, and STAT3 proteins were assessed in PTE-treated HepG2 cells. In addition, the cellular and ultrastructural alterations were evaluated by light and transmission electron microscopy. PTE induced a significant reduction in HepG2 viability in a dose-dependent manner (IC50 of PTE = 74 ± 6 µM), accompanied by a decrease in colony formation potential. PTE-treated cancer cells exhibited a decrease in lipid peroxidation and CAT activity, and an increase in histone release, caspase-3, and SOD activities. Ultrastructurally, PTE-treated cells exhibited notable cell shrinkage, reduced number of filopodia, increased vacuolization, apoptotic bodies, accumulation of lipid droplets, enlarged mitochondria, dilated endoplasmic reticulum, pyknotic nuclei, and cellular fragmentation. mTOR, S6K1, and STAT3 levels were downregulated, however p53 level was modulated in PTE-treated cells. The anticancer potential of PTE might be related to its ability to alter the ultrastructure morphology, reduce mitotic activity, and modulate some key protein required for cell proliferation, suggesting its potential to trigger cancer cells towards apoptosis.

Effect of Epigallocatechin-3-gallate on Stress-Induced Depression in a Mouse Model: Role of Interleukin-1ß and Brain-Derived Neurotrophic Factor.

Epigallocatechin 3-gallate (EGCG) is a natural polyphenolic antioxidant in green tea leaves with well-known health-promoting properties. However, the influence of EGCG on a chronic animal model of depression remains to be fully investigated, and the details of the molecular and cellular changes are still unclear. Therefore, the present study aimed to investigate the antidepressant effect of EGCG in mice subjected to chronic unpredictable mild stress (CUMS). After eight consecutive weeks of CUMS, the mice were treated with EGCG (200 mg/kg b.w.) by oral gavage for two weeks. A forced swimming test (FST) was used to assess depressive symptoms. EGCG administration significantly alleviated CUMS-induced depression-like behavior in mice. EGCG also effectively decreased serum interleukin-1ß (IL-1ß) and increased the mRNA expression levels of brain-derived neurotrophic factor (BDNF) in the hippocampal CA3 region of CUMS mice. Furthermore, electron microscopic examination of CA3 neurons in CUMS mice showed morphological features of apoptosis, loss or disruption of the myelin sheath, and degenerating synapses. These neuronal injuries were diminished with the administration of EGCG. The treatment effect of EGCG in CUMS-induced behavioral alterations was comparable with that of clomipramine hydrochloride (Anafranil), a tricyclic antidepressant drug. In conclusion, our study demonstrates that the antidepressive action of EGCG involves downregulation of serum IL-1ß, upregulation of BDNF mRNA in the hippocampus, and reduction of CA3 neuronal lesions.

Combination of docosahexaenoic acid and Ginko biloba extract improves cognitive function and hippocampal tissue damages in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by a progressive loss of memory and other cognitive functions among elder people. Nowadays, natural antioxidants have been used to recover the quality of life for those with AD. In this study, we investigated, for the first time, the combined effect of docosahexaenoic acid (DHA) and Ginkgo bilobastandardized extract (EGb761) on AD mice. AD was induced in adult male albino mice with AlCl3 (20 mg/kg b.w, i.g.) and D-galactose (D-gal; 120 mg/kg, i.p.) for 90 days. 30 days after induction, mice were treated with DHA (200 mg/kg b.w., i.g.) and EGb761 (200 mg/kg b.w., i.g.) for two months. Our data revealed that the dual treatment of DHA and EGb761 significantly improved cognitive memory and spatial learning abilities in AD-induced mice. The drug treatments preserved the hippocampal CA3 architecture and restored neuronal ultrastructural alterations. Expression of protein phosphatase 2A (PP2A), the most implicated protein phosphatase in AD neurodegeneration, was highly upregulated in the CA3 hippocampus of AD mice treated with DHA and EGb761. Intriguingly, TNF-α expression was significantly reduced in the same group. In conclusion, our findings proved that the combined effect of DHA and EGb761 tended to be potent against the neurodegenerative effect of AlCl3 and D-gal. The applied treatment enhanced neuronal survival and cognitive functions via upregulation of PP2A and restoration of TNF-α expression.

Ameliorative effects of colostrum against DMBA hepatotoxicity in rats.

Colostrum, the sole diet for newborns, is an emerging nutraceutical. To date, the chemopreventive effect of Bovine Colostrum against liver injury induced by the potent carcinogen, 7,12-dimethyl-Benz[a]anthracene (DMBA) is unexplored. Humans are daily exposed to DMBA which is a highly lipophilic environmental organic pollutant. The study aimed to investigate the hepatoprotective role of Bovine Colostrum against DMBA-induced hepatotoxicity using a rat model. Fifty male rats were divided into five groups; GI (control), GII (olive oil, vehicle for DMBA), GIII (DMBA), GIV (DMBA + Bovine Colostrum), GV (Bovine Colostrum). After 12 weeks, body weight changes and mortality were calculated. Histological and ultrastructural examinations of liver tissue were performed. Expressions of p53, TGFß2, TNF-α, S6K2, and c20orf20 were assessed by RT-PCR. Post-treatment with Bovine Colostrum increased both the body weight and the survival rate of rats treated with DMBA. In addition, remarkable protection against the pathological effect of DMBA was noted. Ultrastructurally, Bovine Colostrum ameliorated/prevented most of the toxic effects of DMBA on hepatocytes, including irregularities of nuclear envelope, clumping, and margination of heterochromatin aggregates, segregated nucleoli, and mitochondrial pleomorphism. Bovine Colostrum administration down-regulated p53, C20orf20, and S6K2 mRNA levels, and up-regulated TNF-α and TGFß2. In conclusion, Bovine Colostrum have a protective effect against DMBA-induced toxicity on the liver of albino rats. Consequently, Bovine Colostrum may prevent polycyclic aromatic hydrocarbons-induced hepatotoxicity and may be useful in promoting human health if supplemented in the diet.

Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic ß-cells of streptozotocin-induced diabetic rats.

BACKGROUND: The present study investigated the effects of Nigella sativa aqueous extract and oil, as well as thymoquinone, on serum insulin and glucose concentrations in streptozotocin (STZ) diabetic rats. METHODS: Rats were divided into five experimental groups (control, untreated STZ-diabetic, and aqueous extract-, oil-, or thymoquinone-treated diabetic rats). Treated rats received 2 mL/kg, i.p., 5%N. sativa extract, 0.2 mL/kg, i.p., N. sativa oil, or 3 mg/mL, i.p., thymoquinone 6 days/week for 30 days. Serum insulin and glucose concentrations, superoxide dismutase (SOD) levels, and pancreatic tissue malondialdehyde (MDA) were determined. Electron microscopy was used to identify any subcellular changes. RESULTS: Diabetes increased tissue MDA and serum glucose levels and decreased insulin and SOD levels. Treatment of rats with N. sativa extract and oil, as well as thymoquinone, significantly decreased the diabetes-induced increases in tissue MDA and serum glucose and significantly increased serum insulin and tissue SOD. Ultrastructurally, thymoquinone ameliorated most of the toxic effects of STZ, including segregated nucleoli, heterochromatin aggregates (indicating DNA damage), and mitochondrial vacuolization and fragmentation. The aqueous extract of N. sativa also reversed these effects of STZ, but to a lesser extent. The N. sativa oil restored normal insulin levels, but failed to decrease serum glucose concentrations to normal. CONCLUSIONS: The biochemical and ultrastructural findings suggest that N. sativa extract and thymoquinone have therapeutic and protect against STZ-diabetes by decreasing oxidative stress, thus preserving pancreatic ß-cell integrity. The hypoglycemic effect observed could be due to amelioration of ß-cell ultrastructure, thus leading to increased insulin levels. Consequently, N. sativa and thymoquinone may prove clinically useful in the treatment of diabetics and in the protection of ß-cells against oxidative stress.

Effects of water pollution in Lake Mariut on gonadal free amino acid compositions in Oreochromis niloticus fish.

In the present report, we have determined the gonadal free amino acid compositions in Oreochromis niloticus collected from three sites in Lake Mariut: SE basin (less polluted), main basin (moderately polluted) and SW basin (highly polluted), in an attempt to develop sensitive biomarker to evaluate pollution effects from multiple sources. Variations of free amino acids (FAAs) were apparent in the polluted sites; total FAAs in testes and ovaries exhibited significant increases as compared to the less polluted site. This increase was attributed to increases in all individual amino acids including essential and non-essential ones. ANOVA indicated significant changes in all testicular FAAs, excluding phenylalanine. Levels of non-essential amino acids showed obvious alterations in ovaries. However, the increase in most essential amino acids, although insignificant, yet it was quite observable. In addition, the ratio of essential to non-essential amino acids was insignificantly decreased in gonads. This may be indicative of changes in protein metabolism.