• Journal of Ginseng Research
• /
• v.29 no.1
• /
• pp.44-48
• /
• 2005

The purpose of this study was to investigate the biological activities of water soluble browning reaction products(WS-BRPs) isolated from korean red ginseng. Antioxidative activities of WS-BRPs were examined with the various systems. Three different fractions prepared by os moly tic treatment of WS-BRP(fraction L, S-l and S-2) were found to have an ability to donate hydrogen to DPPH and also exhibited the inhibitory activities in lipid peroxidation, consumption of oxygen and protein oxidation of mitochondrial fraction. Especially, L had the strongest activity of these three WS­BRPs in scavenging free radicals. Lipid peroxidation showed the antioxidant effect on linoleic acid oxidation inhibition ratio of $22.5\%,\;31.7\%,\;31.9\%\;and\;33.5\%$, respectivity. And the consumption of oxygen was strongly inhibited by $49.52\%,\;62,44,\;97.54\%$. But three WS-BRPs showed weak inhibitory activity on lipid peroxidation in rat hepatic microsomes.

• YAKHAK HOEJI
• /
• v.59 no.2
• /
• pp.49-54
• /
• 2015

In the present study we evaluated comparative herb-drug interaction potential of red ginseng total powder, ginsenoside Rg1, and Rb1 by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, red ginseng total powder inhibited significantly activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and testosterone 6-beta hydroxylation by CYP3A4, but the $IC_{50}$ values were higher than $556{\mu}g/ml$. Activities of CYP2B6, CYP2C9, CYP2D6 and CYP3A4 were inhibited by ginsenoside Rb1. Also, activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and testosterone 6-beta hydroxylation by CYP3A4 were inhibited by ginsenoside Rg1. The $IC_{50}$ values of ginsenoside Rb1 and Rg1 were higher than $200{\mu}g/ml$. Based on $IC_{50}$ values against CYP isoforms, ginsenosides-drug interactions by CYP inhibition may be very low in clinical situations.

• Journal of Ginseng Research
• /
• v.43 no.4
• /
• pp.539-549
• /
• 2019

Background: 20(S)-Protopanaxadiol (PPD), the aglycone part of 20(S)-protopanaxadiol ginsenosides, possesses antidepressant activity among many other pharmacological activities. It is currently undergoing clinical trial in China as an antidepressant. Methods: In this study, an ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass tandem mass spectrometry method was established to identify the metabolites of PPD in human plasma and urine following oral administration in phase IIa clinical trial. Results: A total of 40 metabolites in human plasma and urine were identified using this method. Four metabolites identified were isolated from rat feces, and two of them were analyzed by NMR to elucidate the exact structures. The structures of isolated compounds were confirmed as (20S,24S)-epoxydammarane-12,23,25-triol-3-one and (20S,24S)-epoxydammarane-3,12,23,25-tetrol. Both compounds were found as metabolites in human for the first time. Upon comparing our findings with the findings of the in vitro study of PPD metabolism in human liver microsomes and human hepatocytes, metabolites with m/z 475.3783 and phase II metabolites were not found in our study whereas metabolites with m/z 505.3530, 523.3641, and 525.3788 were exclusively detected in our experiments. Conclusion: The metabolites identified using ultra-performance liquid chromatography coupled with triple quadrupole time-of-flight mass spectrometry in our study were mostly hydroxylated metabolites. This indicated that PPD was metabolized in human body mainly through phase I hepatic metabolism. The main metabolites are in 20,24-oxide form with multiple hydroxylation sites. Finally, the metabolic pathways of PPD in vivo (human) were proposed based on structural analysis.

• Journal of Preventive Medicine and Public Health
• /
• v.32 no.1
• /
• pp.88-94
• /
• 1999

Objectives. In order to gain a better understanding of the mechanism of DMF toxicity, recent studies have focused on hepatic drug metabolizing enzymes. In this study, we investigated the effects of DMF on the induction of P450 and the activities of other related enzymes in rat liver microsomes. Methods. DMF was administered to male Sprague Daweley rats by intraperitoneal injection at 0(control), 450(D1), 900(D2), 1,800(D3) mg DMF/kg body weight in olive oil once a day for three days. Hepatic P450 was measured by method of Omura and Sato. We evaluated selective assays for the three drug metabolizing cytochrome P450 isoenzymes 1A1, 2B1 and 2E1. Results. The content of microsomal protein, P450 and b5 were tended to be decreased in DMF treated group, but they were not statistically significant. The activity of NADPH-cytochrome P450 reductase was significantly increased dose dependently(p<0.01), but the activity of NADH-b5 reductase was decreased in the treated group(p<0.01). The activities of PROD and EROD were not significant between control and treated group. The activities of pNPH in the DMF treated groups were higher than that of the control group(p<0.01). When Western immunoblottings were carried out utilizing three monoclonal antibodies which were specific against P4501A1/1, P4502B1/2 and P4502E1, the strong density band corresponding to P4502E1 was observed with the microsomes obtained from the rats treated with DMF. But there were no significant increased in the P4501A1/2 and P4502B1/2 band densities in immunoblotting. Conclusions. These result suggested that P4502E1 was inducible by DMF and P4502E1 isozyme might be responsible for the hydroxylation of DMF to HMMF.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.32 no.7
• /
• pp.1082-1087
• /
• 2003

This study was designed to investigate the effects of butanol (BuOH) fraction of pine (Pinus densiflora Sieb et Zucc) needle extract on membrane fluidity (MF), basal and induced oxygen radicals (BOR and IOR), lipid peroxide (LPO) and oxidized protein (OP) as an oxidative stress, and lipofuscin (LF) in liver membranes of Sprague-Dawley male rats. The rats were fed basic diets (control group) and experimental diets (BuOH-25, BuOH-50 and BuOH-100) prepared with 25, 50 and 100 mg added to basic diet for 45 days. MFs were significantly increased (about 16∼22%) in mitochondria of BuOH-50 and BuOH-100 groups compared with control group (p<0.01∼0.001) BOR and IOR formations in mitochondria were significantly decreased (11∼17% and 11∼28%, respectively) in these three BuOH groups (p<0.05∼0.001), while BOR and IOR formations in microsomes were significantly decreased (11∼24%) in BuOH-50 and BuOH-100 groups, and (15∼24%) in these three BuOH groups compared with control group (p<0.05∼0.001; p<0.01-0.001). LPO levels were significantly decreased (9% and 9∼13%, respectively) in mitochondria of BuOH-100 and microsomes of BuOH-50 and BuOH-100 groups (p<0.05∼0.01), whereas OP levels were significantly decreased (10∼12%) in mitochondria of BuOH-50 and BuOH-100 groups compared with control group (p<0.05). LF formations were significantly decreased (8∼9%) in BuOH-50 and BuOH-100 groups (p<0.05). These results suggest that butanol fraction of pine needle extract may playa effective role in an attenuating an oxidative stress and increasing a membrane fluidity.

• Korean Journal of Food Science and Technology
• /
• v.33 no.1
• /
• pp.128-134
• /
• 2001

Male Sprague-Dawley rats received either a cholesterol diet(Control group) or cholesterol diets supplemented with the water-soluble extract of stem bark from Morus alba(M group) or Cudrania tricuspidata(C group) at the level of 1% for 2 weeks. Concentrations of total cholesterol and phospholipid in serum of C group and triglyceride in serum of M group were lower than those of control group. Concentration of cholesterol in liver of M and C groups has a tendency to be lower than that of control group. Antioxidative activities of water-soluble extracts from stem bark of Morus alba and Cudrania tricuspidata on the peroxidation of lipid in tissues of rats were also studied in vivo by measuring the formation of thiobarbituric acid reactive substances (TBARS). Concentration of TBARS in kidney of M and C groups was significantly lower than control group. However, concentration of TBARS in liver and brain of C and M groups was significantly higher than in control group. The result that concentration of nonheme ion was significantly increased in liver of the mulberry supplemented groups comparision to control group, suggested that enhanced concentration of nonheme ion was associated with enhanced peroxidation of lipid in this group. Concentration of TBARS in microsomes of liver and brain in control group induced with $Fe^{2+}$/ascorbate increased by reaction time at $37^{\circ}C$, whereas this observation in liver did not occurred in C and M groups. This study suggested that water-extract from stem bark of Morus alba and Cudrania tricuspidata exert hypotriglycerolemic effect as well as antioxidative effect in kidney and liver microsomes in rats fed a cholesterol diet.

• Journal of Life Science
• /
• v.31 no.5
• /
• pp.488-495
• /
• 2021

The aim of this study was to investigate the possible antioxidant effect of Spirodela polyrhiza (SP) on rats fed a high fat and high cholesterol diet supplemented with either 5% (SPA group) or 10% (SPB group) SP for 4 weeks. The hepatic SOD activity of the HF group significantly decreased compared to that of the N group, but that of the SPA and SPB groups significantly increased. The GPx activity of the SPA and SPB groups in the liver was significantly greater than that of the HF group, and the hepatic catalase activity of the SPA and SPB groups significantly increased compared to the HF group. The hepatic superoxide radical content of the mitochondria and microsomes of the HF group significantly increased compared to that of the N group, but the contents were reduced in the group that took SP powder. The hepatic hydrogen peroxide content in the cytosol and mitochondria of the SP powder group was lower than in the HF group. The carbonyl content in the mitochondria and microsomes of the SPA and SPB groups was significantly lower than in the HF group. The TBARS values in the liver significantly decreased in the SPA and SPB groups. Spirodela polyrhiza was thus effective in reducing oxidative stress by regulating the hepatic antioxidant enzymes and the free radicals in rats fed high fat and high cholesterol diets.

• Tuberculosis and Respiratory Diseases
• /
• v.73 no.5
• /
• pp.258-265
• /
• 2012

Background: Vitamin D can translocate a vitamin D receptor (VDR) from the nucleus to the cell membranes. The meaning of this translocation is not elucidated in terms of a role in pathogenesis of chronic obstructive pulmonary disease (COPD) till now. VDR deficient mice are prone to develop emphysema, suggesting that abnormal function of VDR might influence a generation of COPD. The blood levels of vitamin D have known to be well correlated with that of lung function in patients with COPD, and smoking is the most important risk factor in development of COPD. This study was performed to investigate whether cigarette smoke extracts (CSE) can inhibit the translocation of VDR and whether mitogen activated protein kinases (MAPKs) are involved in this inhibition. Methods: Human alveolar basal epithelial cell line (A549) was used in this study. 1,25-$(OH_2)D_3$ and/or MAPKs inhibitors and antioxidants were pre-incubated before stimulation with 10% CSE, and then nucleus and microsomal proteins were extracted for a Western blot of VDR. Results: Five minutes treatment of 1,25-(OH2)D3 induced translocation of VDR from nucleus to microsomes by a dose-dependent manner. CSE inhibited 1,25-$(OH_2)D_3$-induced translocation of VDR in both concentrations of 10% and 20%. All MAPKs inhibitors did not suppress the inhibitory effects of CSE on the 1,25-$(OH_2)D_3$-induced translocation of VDR. Quercetin suppressed the inhibitory effects of CSE on the 1,25-$(OH_2)D_3$-induced translocation of VDR, but not in n-acetylcysteine. Conclusion: CSE has an ability to inhibit vitamin D-induced VDR translocation, but MAPKs are not involved in this inhibition.

• Journal of Life Science
• /
• v.23 no.9
• /
• pp.1126-1132
• /
• 2013

Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular system. CYP2J2 plays important roles in the metabolism of endogenous metabolites and therapeutic drugs, such as arachidonic acid, astemizole, ebastine, and terfenadine. CYP2J2 is also overexpressed in human cancer tissues and cancer cell lines and may represent a potential target for therapy of human cancers. In this study, 10 natural products obtained from plants and microorganisms were screened as potential CYP2J2 inhibitors. Among them, thelephoric acid showed strong inhibition of astemizole O-demethylation activity ($IC_{50}=3.23{\mu}M$) in a dose-dependent manner. Evaluation of the substrate dependency of the inhibitory activity of thelephoric acid showed that it strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}=5.32{\mu}M$) and terfenadine hydroxylation ($IC_{50}=3.27{\mu}M$) in a substrate nondependent manner. The present data suggest that this compound might be a potential candidate for further evaluation for anticancer activity.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.34 no.1
• /
• pp.21-26
• /
• 2005

Although the sesame lignans, sesamol, have been shown to possess antioxidative activity, less is known about the metabolism and antioxidative properties of sesamol, a major constituent of sesame oil. To determine the ability of sesamol to act as an antioxidant in vivo, we fed rats a diet containing 0.5% sesamol for 3 wk and studied its metabolism and its effects on oxidative stress. Body weight gain and weight of liver, kidneys were significantly higher in the rats fed sesamol than in rats fed the control diets. GST and GST-Px activities in rat liver microsomes were higher in rats fed sesamol and CAT activities were found to be significantly increased in rats fed sesamol. The formation of TBARS was decreased in the liver of rat fed the 0.5% sesamol diet than in controls. We detected sesamol metabolites in liver and kidneys of rats fed sesamol and its metabolites were present as conjugated glucuronides and sulfates. In contrast, not detected sesamol peak in other organs such as colon, small intestine and pancreas.