Resveratrol Attenuates Copper and Zinc Homeostasis and Ameliorates Oxidative Stress in Type 2 Diabetic Rats

Diabetes is a common metabolic disorder characterized by elevated blood glucose level. Trace element homeostasis causes disturbances in diabetes due to hyperglycemia. Superoxide dismutase (SOD), an antioxidant enzyme, contains zinc and copper ions as its cofactors. Defects in SOD level and activity have been observed in diabetes. Resveratrol (RSV) has displayed hypoglycemic effects and is proven to improve oxidative stress. The aim of the present study was to examine the possible effects of RSV on blood glucose level, serum copper and zinc levels, SOD, and a number of other oxidative markers in type 2 diabetic rats. Diabetes was induced in male Wistar rats with administration of streptozotocin and nicotine amide. The studied groups containing six animals per group were as follows: group 1 normal control group; group 2 diabetic control group; groups 3, 4, and 5 diabetic rats that received 1, 5, and 10 mg/kg body weight of RSV, respectively for 30 days. Serum glucose, copper, zinc, SOD activity, total oxidant status (TOS) as well as thiol groups were all measured. Blood glucose in RSV treated groups significantly decreased. Similarly, copper significantly decreased in diabetic groups treated with RSV. Treatment with 10 mg/kg RSV resulted in significantly increased serum zinc. Furthermore, Cu/Zn ratio was observed to decrease in treated groups compared with untreated diabetic control group. RSV treated groups revealed an increased level of SOD activity as well as improved oxidative status. In summary, the results showed that RSV has potential hypoglycemic effect, attenuates trace element homeostasis, and consequently increases SOD activity level.     

Phytochemical Variation within Aerial Parts of Ferula cupularis Populations,an Endangered Medicinal Plant from Iran

Ferula cupularis (Boiss.) Spalik et S. R. Downie is an endangered endemic Iranian medicinal plant with occurrence restricted to Fars and Kohkilooyeh Boyerahmad provinces, Iran. F. cupularis is cited for strong antibacterial activity, usages in foodstuffs preservation, and has long been used by local peoples for ulcer treatment. In this research, the aerial parts of F. cupularis wild populations were collected from three natural habitats: Eqlid-Kaftar (FC1), Kakan (FC2), and Sepidan-Komohr (FC3), to assess phytochemical diversity and antioxidant activity. The quantity of essential oil (EO) ranged remarkably from 0.42 to 0.72 % v/w among the populations. Results obtained from the EO analysis by GC-FID and GC/MS detected up to 56 compounds. α-Pinene (21.65–31.53 %), sabinene (4.74–11.39 %), phellandrene (1.78–5.1 %), δ-3-carene (1.85–7.18 %), limonene (4.12–7.45 %), (Z)-β-ocimene (9.08–17.64 %), and elemicin (0.23–5.74 %) were the major compounds of EOs varied significantly among the populations. Moreover, total phenol content (250.54 to 387.45 mg gallic acid/100 g dry weight (DW)) and flavonoids (34.38 to 41.12 mg quercetin/100 g DW) of methanolic extracts varied substantially among the populations. Antioxidant activities of F. cupularis EOs and extracts were assessed by DPPH (2,2,1-diphenyl-1-picrylhydrazyl) radical scavenging method. EOs exhibited EC₅₀ values ranging from 8.88 to 9.67 μg mL⁻¹ and the EC₅₀ values for the extract ranged from 941.36 to 1335.96 μg mL⁻¹ within the populations. Results demonstrated significantly different levels of antioxidant capacities among the studied populations. Monitoring the data, the population collected from Eqlid-Kaftar (FC1) was selected as the most potent population concerning the highest EO content and antioxidant activity level. The obtained data provided new insights for an initial source of breeding plans and ultimately massive production for food and pharmaceutical industries.     

Defining the role of 17β-estradiol in human endometrial stem cells differentiation into neuron-like cells

Human endometrial stem cells (hEnSCs) that can be differentiated into various neural cell types have been regarded as a suitable cell population for neural tissue engineering and regenerative medicine. Considering different interactions between hormones, growth factors, and other factors in the neural system, several differentiation protocols have been proposed to direct hEnSCs towards specific neural cells. The 17β-estradiol plays important roles in the processes of development, maturation, and function of nervous system. In the present research, the impact of 17β-estradiol (estrogen, E2) on the neural differentiation of hEnSCs was examined for the first time, based on the expression levels of neural genes and proteins. In this regard, hEnSCs were differentiated into neuron-like cells after exposure to retinoic acid (RA), epidermal growth factor (EGF), and also fibroblast growth factor-2 (FGF2) in the absence or presence of 17β-estradiol. The majority of cells showed a multipolar morphology. In all groups, the expression levels of nestin, Tuj-1 and NF-H (neurofilament heavy polypeptide) (as neural-specific markers) increased during 14 days. According to the outcomes of immunofluorescence (IF) and real-time PCR analyses, the neuron-specific markers were more expressed in the estrogen-treated groups, in comparison with the estrogen-free ones. These findings suggest that 17β-estradiol along with other growth factors can stimulate and upregulate the expression of neural markers during the neuronal differentiation of hEnSCs. Moreover, our findings confirm that hEnSCs can be an appropriate cell source for cell therapy of neurodegenerative diseases and neural tissue engineering.     

Vanadium complex: an appropriate candidate for killing hepatocellular carcinoma cancerous cells

Hepatocellular carcinoma (HCC) is a prevalent human malignancy which its drug resistance is increasing world-wide. This project was designed to assess the anti-cancer effects of 4-bromo-2-(((5-chloro-2-hydroxyphenyl) imino) methyl) phenol ([IV(L)] complex) on the HepG2 cell line and also L929 cells, as normal cells. HepG2 and L929 cells were cultured in RPMI culture medium and the survival rates of the cells were determined after 24 and 48 h using MTT assay to find IC50 concentration of vanadium m, [IV(L)] complex. The early apoptosis and necrosis/late apoptosis were determined by means of annexin V/PI apoptosis detection kit. The results revealed that vanadium m, [IV(L)] complex induce early apoptosis higher in HepG2 cell line than L929 cells. The rates of necrosis/late apoptosis were also induced in HepG2 cells more than L929 cells. Based on the results, vanadium m, [IV(L)] complex might be considered as a safe new drug for treatment of HCC with low side effects on control liver cells.