Citrus peel flavonoids improve lipid metabolism by inhibiting miR-33 and miR-122 expression in HepG2 cells.

Citrus plants are rich in flavonoids and beneficial for lipid metabolism. However, the mechanism has not been fully elucidated. Both citrus peel flavonoid extracts (CPFE) and a mixture of their primary flavonoid compounds, namely, nobiletin, tangeretin and hesperidin, citrus flavonoid purity mixture (CFPM), were found to have lipid-lowering effects on oleic acid-induced lipid accumulation in HepG2 cells. The carnitine palmitoyltransferase 1α (CPT1α) gene was markedly increased, while the fatty acid synthase (FAS) gene was significantly decreased by both CPFE and CFPM in oleic acid-treated HepG2 cells. Flavonoid compounds from citrus peel suppressed miR-122 and miR-33 expression, which were induced by oleic acid. Changes in miR-122 and miR-33 expression, which subsequently affect the expression of their target mRNAs FAS and CPT1α, are most likely the principal mechanisms leading to decreased lipid accumulation in HepG2 cells. Citrus flavonoids likely regulate lipid metabolism by modulating the expression levels of miR-122 and miR-33.

AMPK activation is involved in hypoglycemic and hypolipidemic activities of mogroside-rich extract from Siraitia grosvenorii (Swingle) fruits on high-fat diet/streptozotocin-induced diabetic mice.

Previous studies suggested the anti-diabetic effect of mogrosides in type 1 diabetes. To evaluate the potential effect of mogrosides in type 2 diabetes, we herein investigated the hypoglycemic and hypolipidemic effects and the underlying mechanism of mogroside-rich extract (MGE) using a high-fat diet in combination with streptozotocin (STZ)-induced diabetic model. MGE feeding for 5 weeks did not result in any obvious impact on the body weight and energy intake, but caused a moderate decrease of organ index in diabetic mice. MGE-supplemented diabetic mice showed a notable reduction of fasting blood glucose (FBG), glycated serum protein (GSP), serum insulin, homeostasis model assessment-insulin resistance (HOMA-IR), and serum atherogenic lipid profiles in a dose-dependent manner, whereas significant increases in the anti-atherogenic lipid profile, insulin sensitivity, glucose and insulin tolerance capacity with high dose (300 mg kg-1) MGE were observed (P < 0.01). Besides, hepatocyte polymorphism, lipid accumulation and steatosis were ameliorated and restored to near normal at the high dose. Furthermore, hepatic 5'AMP-activated protein kinase (AMPK) signaling was dose-dependently activated. Accordingly, the mRNA levels of hepatic gluconeogenic and lipogenic genes were downregulated and fat oxidation-associated genes were upregulated. These findings suggest that the hypoglycemic and hypolipidemic activities of MGE are probably attributed to the attenuation of insulin resistance and activation of hepatic AMPK signaling.

Antiglycation and antioxidant activities of mogroside extract from Siraitia grosvenorii (Swingle) fruits.

Siraitia grosvenorii (Swingle) is one kind of medical and edible plants with various health-promoting properties. Recently, its hypoglycemic and antidiabetic activities have been reported, but the underlying mechanism remains to be explored. The current study was aimed to investigate the antioxidant and antiglycation activities of mogroside extract (MGE) from Siraitia grosvenorii (Swingle). The results showed that compared to glycated BSA, MGE at middle (125 µg/mL) and high dose (500 µg/mL) significantly inhibited BSA glycation evidenced by decreased fluorescent AGEs formation, protein carbonyls and Nε-(carboxymethyl) lysine (CML) level at 500 µg/mL by 58.5, 26.7 and 71.2%, respectively. Additionally, the antiglycative activity of MGE (500 µg/mL) was comparable to aminoguanidine (AG) at the equal concentration. However, the inhibitory effect of MGE on glycation-induced increase of fructosamine level and decrease of thiol level was not remarkable. MGE was a potent peroxide radicals scavenger (851.8 µmol TE/g), moderate DPPH and ABTS radicals scavenger with IC50 1118.1 and 1473.2 µg/mL, respectively, corresponding to positive controls ascorbic acid of IC50 9.6 µg/mL, and trolox of IC50 47.9 µg/mL, respectively, and mild reducing power. These findings suggest that MGE may serve as a new promising antiglycative agent against diabetic complications by inhibiting protein glycation and glycoxidation.

Pectin plays an important role on the kinetics properties of polyphenol oxidase from honeydew peach.

Polyphenol oxidase (PPO) was purified from peach pulp by a three-step column chromatographic procedure. The kinetics properties of the PPO fractions obtained from different purification steps were compared. All the fractions showed high affinities for (+)-catechin and (-)-epicatechin. The optimum pHs and optimum temperatures for all the fractions were the same. However, the fraction that contained pectin was more sensitive to the change of pH, and it had a lower affinity for the substrates and a higher thermostability than the fractions without pectin. In addition, the protein impurities in PPO fractions might have no effect on the properties of PPO. l-Cysteine and glutathione were effective for the inhibition of all the PPO fractions, while NaF inhibited moderately. However, the pectin could reduce the inhibition effects of those inhibitors.

Protective effect of flavonoid extract from Chinese bayberry (Myrica rubra Sieb. et Zucc.) fruit on alcoholic liver oxidative injury in mice.

To evaluate the beneficial effects of Chinese bayberry (Myrica rubra Sieb. et Zucc.) flavonoid extract (CBFE) on chronic alcohol-induced liver oxidative injury in mice, experimental mice were pretreated with different doses of CBFE (50-200 mg/kg) for 4 weeks by gavage feeding. Biochemical markers and enzymatic antioxidants from serum, liver tissue, mitochondria and microsomes were examined. Our results showed that the activities of TC, TG, L-DLC in serum, the activity of CYP2E1 in microsomes, and the levels of MDA in liver tissue and mitochondria, decreased significantly (P < 0.05) in the CBFE-treated group compared with the alcohol group. On the contrary, the activities of ALT, AST, and H-DLC in serum, enzymatic antioxidants GSH-Px, SOD and GST in liver tissue and mitochondria, and HO-1 in microsomes rose markedly (P < 0.05). Histopathological examination revealed that CBFE (200 mg/kg) pretreatment noticeably prevented alcohol-induced hepatocyte apoptosis and fatty degeneration. It was suggested that the hepatoprotective effects exhibited by CBFE on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

Reactive oxygen species scavenging activities and inhibition on DNA oxidative damage of dimeric compounds from the oxidation of (-)-epigallocatechin-3-O-gallate.

The dimeric catechins dehydrotheasinensin A (2) and theacitrin C (3) were prepared from the oxidation of (-)-epigallocatechin-3-O-gallate (EGCG, 1), and their antioxidant activity was investigated using a chemiluminescence (CL) method in vitro. Both compounds showed significant inhibitory effects on reactive oxygen species (O(2)(-), H(2)O(2) and *OH) and DNA oxidative damage, with 2 being more potent than 3 and EGCG itself.

[Biodegradation of nicotine in tobacco extracts for making reconstituted tobacco by strain DN2].

The purpose of the study is to use O. intermedium DN2 to degrade nicotine in tobacco extracts for making reconstituted tobacco. Firstly, we studied the effects of various factors on degradation of nicotine in the extracts by strain DN2. When we added 0.1% yeast extract into the extracts, adjusted its pH value to 7.0 by ammonia solution, inoculated 15% cultures and maintained fermentation temperature of 30 degrees C, the degradation rate of nicotine by strain DN2 was the fastest. Furthmore, under these conditions, we studied the degradation rates of nicotine in three fed batches culture which carried out in a 30-L reactor, the result showed that the average degradation rate of nicotine by strain DN2 was 140.55 mg/L/h, which was much higher than that reported in other studies. These results indicated that strain DN2 may be useful for reducing nicotine content of reconstituted tobacco.

Mogrosides extract from Siraitia grosvenori scavenges free radicals in vitro and lowers oxidative stress, serum glucose, and lipid levels in alloxan-induced diabetic mice.

This study evaluated the supplementation of a mogrosides extract (MG) from fruits of Siraitia grosvenori on reducing oxidative stress, hyperglycemia, and hyperlipidemia in alloxan-induced diabetic mice. The oxygen free radical scavenging activity of MG was also assessed in vitro. After induction of diabetes, a significant increase in the levels of serum glucose, total cholesterol (TC), triacylglycerol (TG), and hepatic malondialdehyde (MDA) as well as a reduction in the level of hepatic high-density lipoprotein cholesterol (HDL-C) associated with diminution of the corresponding antioxidant enzymes, such as glutathione peroxidase (GSH-Px) and superoxide dismutase, were observed in all diabetic mice. Treatment of diabetic mice with MG (100, 300, and 500 mg/kg ) for 4 weeks significantly decreased serum glucose, TC, TG, and hepatic MDA levels (P < .05), whereas it increased serum HDL-C level and reactivated the hepatic antioxidant enzymes (P < .05) in alloxan-induced diabetic mice (P < .05). The hypoglycemic, hypolipidemic, and antioxidative activities of MG (100 mg/kg treatment) were all higher compared with all other diabetic groups and were similar to that observed for XiaoKeWan-pill (894 mg/kg; Guangzhou Zhongyi Pharmaceutical Co., Ltd., Guangzhou, China), a Chinese traditional antidiabetic drug. Antioxidant capacity evaluated in vitro showed that MG and mogroside V, which was the main component of MG, possessed strong oxygen free radical scavenging activities. These results demonstrate that the extract may have capacity to inhibiting hyperglycemia induced by diabetes, and the data suggest that administration of the extract may be helpful in the prevention of diabetic complications associated with oxidative stress and hyperlipidemia. We conclude that the extract should be evaluated as a candidate for future studies on diabetes mellitus.

Effect of Momordica grosvenori on oxidative stress pathways in renal mitochondria of normal and alloxan-induced diabetic mice. Involvement of heme oxygenase-1.

BACKGROUND: Oxidative stress plays an important role in the pathogenesis of diabetes and diabetic nephropathy. Momordica grosvenori (MG), a traditional medicinal herb used as substitute sugar for obese and diabetes, exhibits anti-oxidative activity in vitro. AIM OF THE STUDY: This study investigated the effect of MG on renal mitochondrial lipid peroxidation, anti-oxidative defense system, and a potent oxidative stress-responsive protein, heme oxygenase-1 (HO-1) of nondiabetic and alloxan-diabetic mice in different stages of diabetes. METHODS: Male Balb/c mice were rendered diabetic by a single intra-peritoneal injection of alloxan (200 mg/kg), while control mice received sham saline injection. Control and diabetic mice were further subdivided according to their treatments: control (saline), low dose MG (150 mg/kg) and high dose MG (300 mg/kg), which were administered immediately after confirmation of hyperglycemia by gavage daily over an 8-week period. Mice were killed by cervical dislocation at 4th and 8th week, respectively, and serum and renal tissues were harvested. Serum glucose, lipid profile and renal function were evaluated; renal homogenate were subjected to determination of malondialdehyde (MDA) and glutathione (GSH) concentration, manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GSH-Px) and HO-1 activities, together with Mn-SOD and HO-1 mRNA expression; paraffin-embedded renal tissues was used for routine histopathological examination. RESULTS: Short-term diabetes caused hyperglycemia and intensified oxidative stress in renal mitochondrial demonstrated by higher MDA and lower GSH levels than control group, accompanied by increased mRNA expression and activity of HO-1 and Mn-SOD, and augmented GSH-Px activity. Low dose of MG administration ameliorated hyperglycemia, inhibited HO-1 and Mn-SOD mRNA expression and reduced HO-1, Mn-SOD, GSH-Px activities. Diabetic mice did not demonstrate early symptoms of diabetic nephropathy until 8th week, characterized by hyperglycemia, hyperlipidemia, and renal damage. A progressive increment in MDA level and decrease in GSH level, as well as reduced mRNA expression and activity of Mn-SOD and HO-1 in the kidney were observed. Low dose of MG attenuated diabetic nephropa- thy symptoms partially, inhibited lipid peroxidation, up-regulated HO-1 and Mn-SOD mRNA expression, and increased HO-1 activity. Conclusions The study confirmed the involvement of oxidative stress in the development of diabetes mediated by the pro- and antioxidant role of HO-1, and pointed to the possible anti-oxidative mechanism of the anti-diabetic and nephroprotective action of MG.