The present study evaluated the antidiabetic and antioxidant effects of oleanolic acid (OA) from Ligustrum lucidum Ait (LLA) in alloxan-induced diabetic rats. OA in the alloxan-induced diabetic rats showed significant hypoglycemic activity by lowering blood glucose (at doses of 60 and 100 mg/kg for 40 days). The levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-c) in the OA-treated diabetic rats were lower, and the high-density lipoprotein cholesterol (HDL-c) level was higher than in the control diabetic rats. A significant reduction in the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels of diabetic rats following OA treatment was also observed. Furthermore, OA treatment decreased the malondialdehyde (MDA) level, but increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activities of the liver and kidney in diabetic rats. These results indicate that OA could protect the liver function avoiding alloxan-induced damage; OA had hypoglycemic, hypolipidemic and antioxidant efficacy in the diabetic rats. The antioxidant ability of OA might be one of the mechanisms of its hypoglycemic and hypolipidemic effects.

Palmitic acid (PA), the main component of dietary saturated fat, has been known to increase in patients with obesity, and PA-induced lipotoxicity may contribute to obesity-related male infertility. Melatonin has beneficial effects on reproductive processes; however, the effect and the underlying molecular mechanism of melatonin's involvement in PA-induced cytotoxicity in the testes are poorly understood. Our findings showed that lipotoxicity was observed in mouse testes after long-term PA treatment and that melatonin therapy restored spermatogenesis and fertility in these males. Moreover, melatonin therapy suppressed PA-induced apoptosis by modulating apoptosis-associated proteins such as Bcl2, Bax, C-Caspase3, C-Caspase12, and CHOP in type B spermatogonial stem cells. Changes in the expression of endoplasmic reticulum (ER) stress markers (p-IRE1, p-PERK, ATF4) and intracellular Ca 2+ levels showed that melatonin relieved PA-induced ER stress. Mechanistically, melatonin stimulated the expression and nuclear translocation of SIRT1 through its receptors and prevented PA-induced ROS production and mitochondrial dysfunction via SIRT1 signaling pathway. Furthermore, melatonin promoted SIRT1-mediated p53 deacetylation, thereby relieving G2/M arrest in response to PA-stimulated DNA damage. Collectively, these findings indicate that melatonin protects the testes from PA-induced lipotoxicity through the activation of SIRT1, which alleviates oxidative stress, ER stress, mitochondrial dysfunction, and DNA damage.

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A number of studies have shown that baicalein shows high antitumor activity in vitro and in vivo. In this study, the inhibitory effect of baicalein on human cervical cancer HeLa cells was studied in vitro. HeLa cells were treated with high (100 µg/ml) and low (50 µg/ml) doses of baicalein, and cell growth inhibition rates were examined by the MTT assay. The morphological changes of apoptotic cells were observed under the light and electron microscope, while the rate of cell apoptosis was examined by flow cytometry. The expression of apoptosis-related proteins was analyzed by western blot, and caspase-3 activation was examined by a caspase-3 activity assay and spectrophotometry. The results demonstrated that baicalein inhibits the proliferation of HeLa cells and induces apoptosis in a caspase-3-dependent pathway, through downregulation of the B-cell lymphoma 2 (Bcl-2) protein and upregulation of the Bcl-2-associated X protein (Bax), Fas, Fas ligand (FasL) and caspase-8. Thus, we conclude that baicalein induces apoptosis of HeLa cells via the mitochondrial and the death receptor pathways. Cell apoptosis in HeLa cells was most likely promoted by the activation of the proteolytic enzyme caspase-3 in both pathways.

Lycium barbarum is one of the traditional oriental medicines. It has been reported to reduce blood glucose levels. In this study, the effect of Lycium barbarum polysaccharide (LBP) on the improvement of insulin resistance and lipid profile was studied in rats, a model for non-insulin dependent diabetes mellitus (NIDDM). The rats were divided into three groups: control, NIDDM control, and NIDDM+LBP. Diabetes model groups were made by feeding high-fat diet and subjecting to i.p. streptozotocin (50 mg/kg). LBP treatment for 3 weeks resulted in a significant decrease in the concentration of plasma triglyceride and weight in NIDDM rats. Furthermore, LBP markedly decreased the plasma cholesterol levels and fasting plasma insulin levels, and the postprandial glucose level at 30 min during oral glucose tolerance test and significantly increased the Insulin Sensitive Index in NIDDM rats. In the present study, we have tested that LBP can alleviate insulin resistance and the effect of LBP is associated with increasing cell-surface level of glucose transporter 4 (GLUT4) in skeletal muscle of NIDDM rats. Under insulin stimulus, GLUT4 content in plasma membrane in NIDDM control rats was significantly lower than that of control (p<0.01), and GLUT4 content in the plasma membrane in NIDDM+LBP rats was higher than that of NIDDM control rats (p<0.01). In conclusion, LBP can ameliorate insulin resistance, and the mechanism may be involved in increasing cell-surface level of GLUT4, improving GLUT4 trafficking and intracellular insulin signaling.

The accumulation of reactive oxygen species is detrimental to the health of the ovarian follicle. The protective, antioxidant properties of melatonin, an endogenous component of porcine follicular fluid, on apoptosis of granulosa cells were evaluated in this study. Porcine granulosa cells from medium-sized (3-5 mm), healthy follicles were cultured in serum-free conditions with melatonin (0, 0.01, 0.1, 1.0, 10, and 100 ng/mL) with or without its receptor antagonist, luzindole, followed by evaluation of apoptotic markers in the treated cells. Results revealed that endogenous, intrafollicular melatonin concentration decreased as follicular atresia progressed, whereas the percentage of apoptotic granulosa cells increased. Spontaneous apoptosis of granulosa cells, triggered by serum deprivation in vitro, was remarkably blocked by melatonin (1.0 ng/mL melatonin, 32.7 ± 0.5%, vs. control, 47.0 ± 1.0%; P < 0.05). Treatment with 1.0 ng/mL of melatonin also significantly elevated MT2, SOD1, and GPX4 while lowering FASL, CHOP, and GRP78 mRNA abundance compared to the untreated control. The anti-apoptotic effect and some changes of apoptotic-relevant genes in granulosa cells invoked by melatonin supplementation were markedly blocked by luzindole, suggesting that melatonin could prevent the apoptosis of porcine granulosa cells during follicular atresia via its membrane receptors and its free-radical-scavenging activity. These findings provide new insights into the regulatory mechanism of melatonin in follicular atresia-related functions. Mol. Reprod. Dev. 83: 692-700, 2016 © 2016 Wiley Periodicals, Inc.

Extraction parameters of flavonoids from Ipomoea batatas leaf (FIBL) and anti-diabetic activity of FIBL on alloxan induced diabetic mice were studied. The optimal extraction parameters of FIBL were obtained by single factor test and orthogonal test, as follows: ethanol concentration 60 %, ratio of solvent to raw material 30 , extraction temperature 75 ℃ and extraction time 1.5 h , while extraction yield of FIBL was 5.94 %. FIBL treatment (50, 100, and 150 mg/ kg body weight) for 28 days resulted in a significant decrease in the concentration of fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) in diabetes mellitus mice. Furthermore, FIBL significantly increased body weight (bw) and serum high-density lipoprotein cholesterol (HDL-c) level. The data demonstrated FIBL at the dose of 100 mg/kg bw exhibited the optimal effect.The above results suggest that FIBL can control blood glucose and modulate the metabolism of blood lipid in diabetes mellitus mice.

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