Antioxidant Activity of Graptopetalum paraguayense E. Walther Leaf Extract Counteracts Oxidative Stress Induced by Ethanol and Carbon Tetrachloride Co-Induced Hepatotoxicity in Rats.

(1) Background: Graptopetalum paraguayense E. Walther is a traditional Chinese herbal medicine. In our previous study, 50% ethanolic G. paraguayense extracts (GE50) demonstrated good antioxidant activity. (2) Methods: To investigate the hepatoprotective effects of GE50 on ethanol and carbon tetrachloride (CCl4) co-induced hepatic damage in rats, Sprague-Dawley rats were randomly divided into five groups (Control group; GE50 group, 0.25 g/100 g BW; EC group: Ethanol + CCl4, 1.25 mL 50% ethanol and 0.1 mL 20% CCl4/100 g BW; EC + GE50 group: Ethanol + CCl4 + GE50; EC + silymarin group: ethanol + CCl4 + silymarin, 20 mg/100 g BW) for six consecutive weeks. (3) Results: Compared with the control group, EC group significantly elevated the serum aspartate aminotransferase (AST), alanine aminitransferase (ALT), and lactate dehydrogenase (LDH). However, GE50 or silymarin treatment effectively reversed these changes. GE50 had a significant protective effect against ethanol + CCl4 induced lipid peroxidation and increased the levels of glutathione (GSH), vitamin C, E, total antioxidant status (TAS), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione S-transferases (GST). Furthermore, in EC focal group, slight fat droplet infiltration was observed in the livers, while in the GE50 or silymarin treatment groups, decreased fat droplet infiltration. HPLC phytochemical profile of GE50 revealed the presence of gallic acid, flavone, genistin, daidzin, and quercetin. (4) Conclusions: The hepatoprotective activity of GE50 is proposed to occur through the synergic effects of its chemical component, namely, gallic acid, flavone, genistin, daidzin, and quercetin. Hence, G. paraguayense can be used as a complementary and alternative therapy in the prevention of alcohol + CCl4-induced liver injury.

Anti-inflammatory effect of water extracts of Graptopetalum paraguayense supplementation in subjects with metabolic syndrome: a preliminary study.

BACKGROUND: Many studies have demonstrated that Graptopetalum paraguayense has good antioxidant ability; however, few studies have examined its anti-inflammatory effect. The study aimed to investigate the anti-inflammatory effects of water extracts of G. paraguayense (WGP, 4 g day(-1)) in subjects with metabolic syndrome (MS). Intervention was administered for 12 weeks. Levels of inflammatory markers [high sensitivity C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6)] and antioxidant enzymes activities were measured. RESULTS: Forty-two subjects completed the 12 week intervention study (placebo, n = 19; WGP, n = 23). After 12 weeks supplementation, subjects in WGP group had significantly lower levels of inflammatory markers than the baseline (P < 0.05) and the placebo group (CRP, P = 0.07; TNF-α, P = 0.04; IL-6, P = 0.03). The changes in levels of the inflammatory markers were significantly decreased in WGP group (CRP, P = 0.04; TNF-α, P = 0.06; IL-6, P = 0.01) compared to the placebo group. Levels of inflammatory markers were significantly negatively correlated with the antioxidant enzymes activities after supplementation. CONCLUSION: This study demonstrated a significant reduction in inflammatory status in MS after WGP supplementation. WGP may exert an anti-inflammatory effect on MS in addition to its antioxidant ability.

Effects of water extracts of Graptopetalum paraguayense on blood pressure, fasting glucose, and lipid profiles of subjects with metabolic syndrome.

This study was aimed to investigate the effects of water extracts of Graptopetalum paraguayense (WGP, 4 g/d) on blood pressure, blood glucose level, and lipid profiles in subjects with metabolic syndrome (MS). Participants with MS (n = 54) were randomly assigned to the placebo (n = 28) and WGP groups (n = 26), and the intervention was administered for 12 weeks. Systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose (FG), lipid profiles (total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein (HDL-C)), and antioxidant enzymes activities (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) were measured. Forty-two subjects completed the study (placebo, n = 19; WGP, n = 23). FG, SBP, and LDL-C levels were significantly lower and HDL-C level and antioxidant enzymes activities (CAT and SOD) were significantly higher after WGP supplementation. Blood pressure, FG, and lipid profiles were significantly correlated with antioxidant enzymes activities after supplementation (P < 0.05). The present study demonstrated a significant reduction in blood pressure, blood glucose, and lipid profiles and an increase in antioxidant enzymes activities in subjects with MS after WGP supplementation. Taken together, the antioxidative capacity of WGP might exert a beneficial effect on MS. This trial is registered with ClinicalTrials.gov NCT01463748.

Relationships between inflammation, adiponectin, and oxidative stress in metabolic syndrome.

Metabolic syndrome (MS) represents a cluster of physiological and anthropometric abnormalities. The purpose of this study was to investigate the relationships between the levels of inflammation, adiponectin, and oxidative stress in subjects with MS. The inclusion criteria for MS, according to the Taiwan Bureau of Health Promotion, Department of Health, were applied to the case group (n = 72). The control group (n = 105) comprised healthy individuals with normal blood biochemical values. The levels of inflammatory markers [high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), adiponectin, an oxidative stress marker (malondialdehyde), and antioxidant enzymes activities [catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were measured. Subjects with MS had significantly higher concentrations of inflammatory markers and lower adiponectin level, and lower antioxidant enzymes activities than the control subjects. The levels of inflammatory markers and adiponectin were significantly correlated with the components of MS. The level of hs-CRP was significantly correlated with the oxidative stress marker. The IL-6 level was significantly correlated with the SOD and GPx activities, and the adiponectin level was significantly correlated with the GPx activity. A higher level of hs-CRP (≥1.00 mg/L), or IL-6 (≥1.50 pg/mL) or a lower level of adiponectin (<7.90 µg/mL) were associated with a significantly greater risk of MS. In conclusion, subjects suffering from MS may have a higher inflammation status and a higher level of oxidative stress. A higher inflammation status was significantly correlated with decreases in the levels of antioxidant enzymes and adiponectin and an increase in the risk of MS.

Effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, and homocysteine) in patients with coronary artery disease.

OBJECTIVE: The purpose of this study was to investigate the effects of coenzyme Q10 supplementation on inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and homocysteine) in patients with coronary artery disease (CAD). METHODS: Patients with CAD (n = 51) were randomly assigned to a placebo group (n = 14) or one of two coenzyme Q10-supplemented groups (60 mg/d, Q10-60 group, n = 19; 150 mg/d, Q10-150 group, n = 18). The intervention was administered for 12 wk. Plasma coenzyme Q10 concentration, inflammatory markers (hs-CRP, IL-6, and homocysteine), malondialdehyde, and superoxide dismutase activities were measured. RESULTS: Forty subjects with CAD completed the intervention study. The plasma coenzyme Q10 concentration increased significantly in the Q10-60 and Q10-150 groups (P < 0.01). After 12 wk of intervention, the inflammatory marker IL-6 (P = 0.03) was decreased significantly in the Q10-150 group. Subjects in the Q10-150 group had significantly lower malondialdehyde levels and those in the Q10-60 (P = 0.05) and Q10-150 (P = 0.06) groups had greater superoxide dismutase activities. Plasma coenzyme Q10 was inversely correlated with hs-CRP (r = -0.20, P = 0.07) and IL-6 (r = -0.25, P = 0.03) at baseline. After supplementation, plasma coenzyme Q10 was significantly correlated with malondialdehyde (r = -0.35, P < 0.01) and superoxide dismutase activities (r = 0.52, P < 0.01). However, there was no correlation between coenzyme Q10 and homocysteine. CONCLUSION: Coenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the inflammatory marker IL-6 in patients with CAD.

In vitro and in vivo safety of aqueous extracts of Graptopetalum paraguayense E. Walther.

ETHNOPHARMACOLOGICAL RELEVANCE: Graptopetalum paraguayense E. Walther, a widely consumed vegetable in Taiwan, has many biological effects and has been used in folk medicine to alleviate hepatic disorders, exert diuretic effects, and relieve pain and infections. However, little data exist regarding its safety. MATERIALS AND METHODS: Two genotoxicity assays were performed: chromosomal aberration of Chinese hamster ovary (CHO-K1 cells) (in vitro) and micronucleus assay in mice (in vivo). Acute oral toxicity and 28-day repeated feeding toxicity tests were performed by oral gavage in Sprague-Dawley (SD) rats. RESULTS: GWE did not increase micronucleus ratios in vivo, and by chromosome aberration assay, GWE was safe up to 1.2mg/ml with regard to clastogenicity. Chromatid breakage was observed at high concentrations (2.5 and 5.0mg/ml) of GWE. GWE had no acute lethal effect at the maximum dose (5g/kg bw) in rats. In the 28-day study, there were no adverse effects on body weight, feed consumption, hematology, blood biochemical parameters, organ weight, or pathology. CONCLUSION: The acute toxicity study showed that the LD(50) of GWE was greater than the tested dose (up to 1g/kg bw) in SD rats. In the subacute toxicity study, the no observed adverse effect level (NOAEL) of GWE in rats was 1g/kg bw. The in vivo study of mammalian erythrocyte micronuclei confirmed the Ames test results, demonstrating that GWE has no mutagenicity. High doses of GWE require further examination due to its clastogenic potential.

Coenzyme Q10 supplementation reduces oxidative stress and increases antioxidant enzyme activity in patients with coronary artery disease.

OBJECTIVE: The purpose of this study was to investigate the effect of coenzyme Q10 supplementation on oxidative stress and antioxidant enzyme activity in patients with coronary artery disease (CAD). METHODS: This was an intervention study. Patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery or receiving percutaneous transluminal coronary angioplasty (n = 51) were randomly assigned to the placebo group (n = 14) or one of the two coenzyme Q10-supplemented groups (60 mg/d, n = 19 [Q10-60 group]; 150 mg/d, n = 18 [Q10-150 group]). Intervention was administered for 12 wk. Patients' blood samples were analyzed every 4 wk for plasma coenzyme Q10 concentrations, malondialdehyde (MDA), and antioxidant enzyme (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase) activity. RESULTS: Forty-three subjects with CAD completed intervention study. Plasma coenzyme Q10 concentration increased significantly after coenzyme the Q10-150 intervention (P < 0.01). The MDA levels were significantly lower than baseline in the Q10-150 group at week 4 (P = 0.03). The Q10-150 group had significantly lower MDA levels than the placebo group at week 8 (P = 0.03). With respect to antioxidant enzyme activity, subjects in the Q10-150 group had significantly higher CAT (P = 0.03) and SOD (P = 0.03) activity than the placebo group at week 12. The plasma coenzyme Q10 concentration was significantly correlated with MDA levels (r = -0.35, P = 0.02) and CAT (r = 0.43, P = 0.01) and SOD activity (r = 0.39, P = 0.01). The ratio of plasma coenzyme Q10 to total cholesterol was significantly correlated with SOD activity (r = 0.39, P = 0.02). The ratio of plasma coenzyme Q10 to low-density lipoprotein was significantly correlated with CAT (r = 0.35, P = 0.04) and SOD (r = 0.45, P = 0.01) activity. However, there was no relation between coenzyme Q10 concentration and glutathione peroxidase activity. CONCLUSION: Coenzyme Q10 supplements at a dose of 150 mg can decrease oxidative stress and increase antioxidant enzyme activity in patients with CAD. A higher dose of coenzyme Q10 supplements (>150 mg/d) might promote rapid and sustainable antioxidation in patients with CAD.

Hepatoprotection of chlorella against carbon tetrachloride-induced oxidative damage in rats.

The effects of 80% ethanolic chlorella extracts (GPE) on carbon tetrachloride (CCl(4))-induced hepatic damage were investigated in Sprague-Dawley rats. The rats were orally treated with GPE (0.5 g/kg body weight) or silymarin (0.2 g/kg body weight) over four consecutive weeks with administration of CCl(4) (20% CCl(4), 0.5 ml/rat twice a week). The GPE had a significant protective effect against liver injuries, as well as oxidative stress induced by CCl(4), resulting in reduced lipid peroxidation and improved serum biochemical parameters such as aspartate aminotransferase and alanine aminotransferase. The reduced levels of glutathione, vitamin C, superoxide dismutase, and catalase in the CCl(4)-treated rats were significantly increased by treatment with GPE. Furthermore, the activity of GPE was comparable to the standard drug silymarin. In conclusion, chlorella may be useful as a hepatoprotective agent against chemical-induced liver damage in vivo.

In vitro antioxidant and antiproliferative activity of the stem extracts from Graptopetalum paraguayense.

This study was aimed to evaluate the antioxidant abilities of water (SGWE), 50% ethanolic (SGE50) and 95% ethanolic (SGE95) extracts from the stem of Graptopetalum paraguayense, and the extract with the highest antioxidant activity was assayed for its inhibitory effect on proliferation of human hepatoma (Hep G2) cell line. Antioxidant abilities of extracts were assessed their radical-scavenging abilities and effects on Fe/ascorbate-induced lipid peroxidation in a liposome model system. The results of this study showed that antioxidant activities were increased with the increase of the extracts concentrations, and the activities correlated with both the total phenol and anthocyanin contents. A comparison of the 50% inhibition concentration (IC(50)) values of different antioxidant reactions revealed that SGWE was the more effective at scavenging superoxide anion radical and preventing lipid peroxidation than SGE50 and SGE95 (p<0.05). The flow cytometry results indicated that SGWE lowered cell viability, and induced G1 phase arrest and apoptosis in Hep G2 cells. These results demonstrated the antioxidant and anti-hepatoma potential of stem of Graptopetalum paraguayense.