Gyeong-Min Do

Du-zhong (Eucommia ulmoides Oliver) leaf extract mediates hypolipidemic action in hamsters fed a high-fat diet.

This study examined the effect of a Du-zhong (Eucommia ulmoides Oliver) leaf extract (0.175 g/100 g diet) that was supplemented with a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) on hyperlipidemic hamsters. Hamsters fed with Du-zhong leaf extract for 10 weeks showed a smaller size of epididymal adipocytes compared to the control group. The supplementation of the Du-zhong leaf extract significantly lowered the plasma levels of triglyceride, total cholesterol, LDL-cholesterol, non HDL-cholesterol, and free fatty acid, whereas it elevated the HDL-cholesterol/total cholesterol ratio and apolipoprotein A-I levels. The hepatic cholesterol concentration was lower in the Du-zhong group than in the control group. The plasma total cholesterol concentration was positively correlated with hepatic HMG-CoA reductase activity (r = 0.547, p < 0.05) and hepatic cholesterol concentration (r = 0.769, p < 0.001). The hepatic fatty acid synthase and HMG-CoA reductase activities were significantly lowered by a Du-zhong leaf extract supplement in high fat-fed hamsters. Hepatic fatty acid synthase activity was positively correlated with plasma fatty acid concentration (r = 0.513, p < 0.05) that was lower in the Du-zhong group. These results demonstrate that the Du-zhong leaf extract exhibits antihyperlipidemic properties by suppressing hepatic fatty acid and cholesterol biosynthesis with the simultaneous reduction of plasma and hepatic lipids in high fat-fed hamsters.

Supplementation of SK1 from Platycodi Radix Ameliorates Obesity and Glucose Intolerance in Mice Fed a High-Fat Diet

This study investigated the beneficial effects of SK1 on obesity and insulin resistance in C57BL/6 mice, which were fed a high-fat diet (37% calories from fat). SK1 is an edible saponin-rich compound from Platycodi radix. The mice were supplemented with two doses of SK1 (0.5% and 1.0%, wt/wt) for 9 weeks. The body weight, visceral fat mass, and adipocyte area were significantly decreased in the SK1 supplemented-groups in a dose-dependent manner compared to the high-fat group. The SK1 supplement significantly lowered plasma triglycerides, total cholesterol, and free fatty acid levels, whereas it significantly elevated the fecal excretion of lipids in the diet-induced obese mice. Supplementation of SK1 decreased the triglyceride and cholesterol levels and the accumulation of lipid droplets in the liver compared to the high-fat control group. High-fat diet induced glucose intolerance and insulin resistance with the elevation of blood glucose levels compared to the normal group; however, the SK1 supplement significantly improved postprandial glucose levels and insulin resistance index. After 9 weeks of being fed a high-fat diet, the mice presented with significantly increased activities of hepatic fatty acid synthase, fatty acid beta-oxidation, and glucokinase; however, both 0.5% and 1.0% SK1 supplementation normalized these activities. Notably, SK1 supplementation effectively diminished the ratio of fatty acid biosynthesis to fatty acid oxidation compared to the high-fat group. These results indicate that SK1 exhibits a potential anti-obesity effect and may prevent glucose intolerance by reducing body weight and fat accumulation, increasing fecal lipid excretions, and regulating hepatic lipid and glucose metabolism in high-fat fed mice.

Actions of Ferulic Acid and Vitamin E on Prevention of Hypercholesterolemia and Atherogenic Lesion Formation in Apolipoprotein E-Deficient Mice

This study was carried out to investigate whether dietary vitamin E and ferulic acid (FA) can exert possible interactions on preventions of hypercholesterolemia and atherogenic lesion formation in C57BL/65 apolipoprotein E-deficient (apo E(-/-)) mice. Four-week-old male apo E(-/-) mice were randomly divided into three groups and given one of three types of Western diets with various amounts of vitamin E (0.02%, 0%, or 0.2%) for 15 weeks. FA was added to vitamin E-free Western diet and vitamin E-rich Western diet at the 0.02% level. The plasma total cholesterol concentration was significantly lowered when FA was added to the vitamin E-free and vitamin E-rich Western diet as compared to the normal vitamin E Western diet (0.02% vitamin E), and this was accompanied with a decreased hepatic acyl-coenzyme A:cholesterol acyltransferase activity. The hepatic and erythrocyte thiobarbituric acid-reactive substances levels were significantly lowered when FA was added to the vitamin E-rich Western diet, which was attributable to increased activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and paraoxonase. Accordingly, vitamin E and/or FA are beneficial for prevention of hypercholesterolemia and atherogenesis in apo E(-/-) mice. In particular, dietary FA exhibited an anti-atherosclerotic property, and this effect was synergistically enhanced with the vitamin E supplement.

Acanthopanax koreanum Nakai modulates the immune response by inhibiting TLR 4-dependent cytokine production in rat model of endotoxic shock

The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/10 µg/kg body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.

Protective effects of Acanthopanax divaricatus vat. albeofructus and its active compound on ischemia-reperfusion injury of rat liver

In the present study, the potential antioxidant and anti-inflammatory effects of Acanthopanax divaricatus vat. albeofructus (AE) and acanthoside-D (AD) isolated from AE against hepatic ischemia-reperfusion (I/R) injury were investigated in a rat model. Male Sprague-Dawley rats (200-220 g) were randomized into seven groups: normal controls; sham-operated controls; I/R injury model; I/R injury model with AE pretreatment at 150, 300, and 600 mg/kg body weight; and I/R injury model with AD pretreatment at 600 μg/kg body weight (equivalent to high dose of AE). The AE and AD pretreatments were administered orally for 2 weeks prior to I/R injury surgery. All rats recovered for 1 week with AE and AD treatment after surgery. Compared to the normal control groups, the I/R injury model group without supplemental treatment showed a significantly lower level of serum superoxide dismutase (SOD) and significantly higher levels of tumor necrosis factor-alpha (TNF-α, interleukin (IL)-6, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), as well as lactate dehydrogenase (LDH) activity. The I/R-induced decrease in SOD and increases in TNF-α and IL-6 were resolved, at least partially, by AE and AD treatments, as evidenced by significantly higher antioxidant activities and significantly lower inflammatory cytokine levels in the treatment groups as compared to the I/R injury model group. The AE and AD treatment groups also showed significantly higher levels of serum IL-10 than I/R injury model group. Histological examination revealed that the AE and AD treated groups had less extensive liver necrosis than I/R injury model group. Concomitantly, AE lowered the I/R-induced increases in AST, ALT, ALP levels and LDH activity. In conclusion, AE and AD are capable of alleviating I/R-induced hepatic injury by inhibiting inflammatory cell infiltration, thereby mitigating the release of inflammatory cytokines and balancing the oxidant-antioxidant status mediated by p38 MAPK and JNK/SAPK signaling.

Acanthopanax divaricatus var. chiisanensis reduces blood pressure via the endothelial nitric oxide synthase pathway in the spontaneously hypertensive rat model

In this study, we investigated the antihypertensive effects of Acanthopanax divaricatus var. chiisanensis extract (AE) and its active compound, acanthoside D (AD), on arterial blood pressure (BP) in vivo and endothelial function in vitro. We hypothesized that AE has antihypertensive effects, which is attributed to enhancement of endothelial function via the improvement of nitric oxide synthesis or the angiotensin II (Ang II) response. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs) were randomly divided into 7 groups and then fed the following diets for 14 weeks: WKY fed a normal diet (WN); SHR fed a normal diet (SN); SHR fed a high-cholesterol (HC) diet (SH); SHR fed a HC diet with AE of 150, 300, 600 mg/kg body weight (SH-L, SH-M, SH-H); and SHR fed an HC diet with AD of 600 μg/kg body weight (SH-D). Blood pressure was significantly reduced in the SH-H compared with the SH from week 10 until week 14; BP was also significantly decreased in the SHR fed a HC diet with AE of 300 at week 14. Aortic wall thickness showed a tendency to decrease by AE and AD treatment. The SH-H showed increased endothelial nitric oxide synthase (eNOS) expression in the intima and media, compared with the SH. Furthermore, a significant increase in intracellular nitric oxide production was induced by AE and AD treatment in human umbilical vein endothelial cells. A significant increase of phospho-eNOS was found with a high dose of AE in human umbilical vein endothelial cells but not with AD. These results suggest that AE can regulate BP and improve endothelial function via eNOS-dependent vasodilation.