• Journal of Microbiology and Biotechnology
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• 제25권5호
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• pp.579-588
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• 2015

Fungi of the genus Pestalotiopsis have drawn attention for their capability to produce an array of bioactive secondary metabolites that have potential for drug development. Here, we report the determination of a polyketide derivative compound, pestalotiollide B, in the culture of the saprophytic fungus Pestalotiopsis microspora NK17. Structural information acquired by analyses with a set of spectroscopic and chromatographic techniques suggests that pestalotiollide B has the same skeleton as the penicillide derivatives, dibenzodioxocinones, which are inhibitors of cholesterol ester transfer protein (CETP), and as purpactins A and C', inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Strain NK17 can make a fairly high yield of pestalotiollide B (i.e., up to 7.22 mg/l) in a constitutive manner in liquid culture. Moreover, we found that a putative histone deacetylase gene, designated as hid1, played a role in the biosynthesis of pestalotiollide B. In the hid1 null mutant, the yield of pestalotiollide B increased approximately 2-fold to 15.90 mg/l. In contrast, deletion of gene hid1 led to a dramatic decrease of conidia production of the fungus. These results suggest that hid1 is a modulator, concerting secondary metabolism and development such as conidiation in P. microspora. Our work may help with the investigation into the biosynthesis of pestalotiollide B and the development for new CETP and ACAT inhibitors.

• 대한한방내과학회지
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• 제30권2호
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• pp.338-354
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• 2009

Objective : Gamijihwang-tang(GJT) has been used as a therapeutic agent for hyperlipidemia in oriental medicine for several years. This study was performed to investigate the effects of GJT on hyperlipidemia in rats using diverse biological methods. Method : Hyperlipidemia was induced by a hyper-lipidemic diet fed for 4 weeks. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, and glucose were measured in the serum after an oral administration of GJT. Lipid peroxidase, SOD, catalase, ACAT, and HMG-CoA were measured in liver after oral administration of GJT. Result: 1. GJT showed safety against cytotoxicity and toxicity in liver. 2. GJT significantly decreased rat's body and liver weight. 3. GJT significantly decreased serum total cholesterol and LDL-cholesterol, but increased serum HDL-cholesterol. 4. GJT significantly decreased serum triglyceride and glucose. 5. GJT significantly decreased lipid peroxidation and increased SOD and catalase in liver. 6. GJT significantly decreased ACAT and HMG-CoA reductase of cholesterol manifestation in liver. Conclusions : These results suggest that GJT might be effective in treatment and prevention of hyperlipidemia.

• 대한한방내과학회지
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• 제31권3호
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• pp.526-538
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• 2010

Objective : This study was performed to investigate the effect of Sunhwangigagambang(SHG) on hyperlipidemia in SD rats induced by high cholesterol diet. Method : After treatment with SHG, cytotoxicity, body weight, liver weight, AST, ALT, ALP, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, glucose, albumin, total protein in serum, malondialdehyde, and gene expression for ACAT and HMG-CoA reductase in hepatic tissue were analyzed. Result : 1. SHG didn't show any cytotoxicity in both human fibroblast cell line and SD rats. 2. SHG significantly inhibited the increase of liver weight by high cholesterol diet compared to the control group. 3. SHG significantly ameliorated the increase of total cholesterol, LDL-cholesterol, and triglyceride and reduction of HDL-cholesterol compared to the control group. 4. SHG significantly reduced glucose level in serum compared to the control group. 5. SHG significantly reduced malondialdehyde in hepatic tissue compared to the control group. 6. SHG significantly down-regulated gene expression of ACAT and HMG-CoA reductase compared to the control group. Conclusion : These results suggest that SHG might be effective in treatment and prevention of hyperlipidemia.

• 대한한방내과학회지
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• 제38권3호
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• pp.367-375
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• 2017

Objective: To investigate the effect of Artemisiae Iwayomogii Herba, Curcumae Radix, and Aurantii Fructus Immaturus complex extract (ACA) on dyslipidemia-related factor expression and anti-oxidation in HepG2 cells. Method: After treatment with ACA in the HepG2 cells, DPPH, ABTS radical scavenging activity, ROS production, and glutathione (GSH) production were measured. The free fatty acid, lipid peroxidation (MDA), ACAT1, and HMG-CoA reductase mRNA expression were measured in the HepG2 cells after treatment with ACA. Results: 1. DPPH, ABTS radical scavenging activity increased in an ACA concentration-dependent manner. 2. ACA significantly decreased ROS production in comparison to the control group. 3. ACA significantly increased glutathione production. 4. ACA significantly decreased free fatty acid and lipid peroxidation (MDA) in the HepG2 cells. 5. ACA decreased the mRNA expression of ACAT1 and HMG-CoA reductase. Conclusion: These results suggest that Artemisiae Iwayomogii Herba, Curcumae Radix, and Aurantii Fructus Immaturus complex extract (ACA) inhibits dyslipidemia-related factor expression and that it is effective in anti-oxidation. A future in vivo experiment with ACA is needed to investigate the effect on anti-dyslipidemia. It is expected that ACA is effective in anti-dyslipidemia and applied to cardiovascular disease, ischemic heart disease, stroke, etc.

• 동의생리병리학회지
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• 제32권1호
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• pp.13-23
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• 2018

This study was performed to investigate the antioxidant and antidyslipidemic effects of Artemisiae iwayomogii Herba, Curcumae longae Radix and Plantaginis Semen complex extract(ACP) on HepG2 cells. We measured total polyphenols, total flavonoids, radical scavenging activity, and ABTS radical scavenging activity of ACP to evaluate its antioxidant activity. HepG2 cells were treated with ACP. Then, we evaluated ROS production; intracellular GSH content; GPx, GR, SOD, and catalase activities; free fatty acids and MDA levels; and mRNA expression levels of ACAT1 and HMG-CoA reductase. Results: ACP contains polyphenols and flavonoids and increased the DPPH and ABTS radical scavenging activities in HepG2 cells in a dose dependent manner. Also, ACP significantly reduced ROS production in HepG2 cells compared to the control group and significantly increased the GSH content, and elevated the enzyme activities of GPx, GR, and catalase in HepG2 cells compared to the control group. In addition, ACP reduced the mRNA expression of ACAT1 and HMG-CoA reductase in HepG2 cells compared to that in the control group. Conclusion: These results suggest that ACP has an antioxidant effect and may suppress the expression of dyslipidemia - associated genes and thus may be useful for the improvement of dyslipidemia.

• 대한본초학회지
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• 제20권2호
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• pp.91-102
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• 2005

Objectives : By examining the effects of Jwa Kum-Whan composed of Coptidis Rhizoma and Evodiae Fructus by the ratio of 6:1 the effects of Soo Ryeon-Whan and composed of Coptidis Rhizoma and Evodiae Fructus by the ratio of 1:1 on hyperlipidemia, the present study attempted to reveal the change of effects based on the ratio of combination. Methods : Jwa Kum-Whan and Soo Ryeon-Whan were injected to rats suffered from induced hyperlipidemia, and then its influence on lipid. During the cultivation of hepatocytes, Jwa Kum-Whan and Soo Ryeon-Whan were added to culture media, and the expression of the enzymes relevant to fat metabolism of hepatocytes was examined. Results : 1. Jwa Kum-Whan significantly decreased total cholesterol(Tc), triglyceride(TG), and LDL-cholesterol(LDLc) of rats suffering from hyperlipidemia induced by high cholesterol diet. Soo Ryeon-Whan decreased LDLc, but had no significant on Tc and TG. 2. Jwa Kum-Whan increased the expression of cholesterol esterase, LDL-receptor, diacylglycerol acyltransferase (DGAT), acylCoA-cholesterol-acyltransferase (ACAT), peroxisome proliferator activated receptor gamma $(PPAR{\gamma})$, peroxisome proliferator activated receptor alpha $(PPAR{\alpha})$ of cultivated hepatocytes. In addition, Soo Ryeon-Whan increased the expression of cholesterol esterase, LDL-Receptor, DGAT, $PPAR{\gamma},\;PPAR{\alpha}$ of cultivated hepatocytes, but had no significant effects on the expression of ACAT. Conclusion : Both Jwa Kum-Whan and Soo Ryeon-Whan were composed of Coptidis Rhizoma and Evodiae Fructus, but the fonner is more effective in hyperlipidemia.

• Preventive Nutrition and Food Science
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• 제6권2호
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• pp.122-125
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• 2001

A potential mechanism through which the jujube extract might produce a cholesterol-lowering effect was compared with that of tangerine peel extract in vivo. Two extracts were prepared using ethanol. Male rats were fed a high cholesterol (1%, w/w) lab chow with jujube extract (1.2%) or tangerine peel extract (6.3%, w/w) for 3 weeks. Activities of hepatic HMG-CoA reductase (289.6$\pm$12.9 and 296.7$\pm$11.6 nmole/min/mg vs. 347.9$\pm$17.5 nmole/min/mg) and ACAT (554.8$\pm$18.2 and 451.7$\pm$19.4 nmole/min/mg vs. 602.6$\pm$21.4 nmole/min/mg) were significantly lowered by both supplements compared to the control group. These two supplements also substantially reduced the concentrations of plasma cholesterol (103.3$\pm$15.9 and 101.6$\pm$19.4 mg/dL vs. 141.6$\pm$18.1 mg/dL) and triglyceride (61.3$\pm$5.5 and 55.5$\pm$3.9 mg/dL vs. 96.0$\pm$4.2 mg/dL). The inhibition of HMG-CoA reductase resulting from the supplementation of jujube or tangerine extracts could count for the reduction in plasma cholesterol. Accordingly, lipid-lowering action of both supplements appears to be similar in high-cholesterol fed rats.

• 대한유전성대사질환학회지
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• 제12권2호
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• pp.104-107
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• 2012

본 연구는 신생아 대사 이상 질환에 대한 광범위 스크리닝으로 매우 희귀한 아미노산 대사 이상 질환 중 하나인 Alpha-methylacetoacetic aciduria의 국내 첫 증례를 경험했기에 이를 보고하는 바이다. 신생아 스크리닝의 광범위한 시행으로 인해 향후 우리나라에도 알려지지 않은 희귀 유전성 대사 질환의 보고가 증가할 것으로 예측된다. 이 환자들에 대한 적절한 관리를 통해 질환의 자연경과와 장기적 예후에 대한 관찰이 필요하다.

• Archives of Pharmacal Research
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• 제28권5호
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• pp.550-556
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• 2005

The flower of Campsis grandiflora K. Schum. Was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and H$_2$O. From the EtO Ac fraction, seven triterpenoids were isolated through the repeated silica gel, ODS column chromatographies and preparative HPLC. From the result of physico- chemical data including NMR, MS and IR, the chemical structures of the compounds were determined as 3${\beta}$-hydroxyolean-12-en-28-oic acid (oleanolic acid, 1), 3${\beta}$-hydroxyurs-12-en-28-oic acid (ursolic acid, 2), 3${\beta}$-hydroxyurs-12-en-28-al (ursolic aldehyde, 3), 2${\alpha}$,3${\beta}$-dihydroxyolean-12-en-28-oic acid (maslinic acid, 4), 2${\alpha}$,3${\beta}$-dihydroxyurs-12-en-28-oic acid (corosolic acid, 5), 3${\beta}$,23-dihydroxyurs-12- en-28-oic acid (23-hydroxyursolic acid ,6) and 2${\alpha}$,3${\beta}$,23-trihydroxyolean-12-en-28- oic acid (arjunolic acid, 7). These teriterpenoids were isolated for the first time from this plant. Also, compounds 4, 5, 6, and 7 revealed relatively high hACAT-1 inhibitory activity with the value of 46.2${\pm}$1.1, 46.7${\pm}$0.9, 41.5${\pm}$1.3 and 60.8${\pm}$1.1% at the concentration of 100${\mu}$g/mL, respectively.

• 대한한방부인과학회지
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• 제31권2호
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• pp.49-67
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• 2018

Objectives: This study was conducted to assess the effects of Hwanggimacmundong-tang extract (HM) on obese rats with estrogen deficiency. Methods: The experiments were performed with ovariectomized rats as estrogen-deficient obesity model. Rats were grouped NC (Normal Control Group; sham operation group), OC (Obesity Control Group; estrogen-deficient group), HML (20 mg/kg/day), HMH (100 mg/kg/day). HM was administered orally for six weeks. Body weights and serum lipid level were measured, and real-time PCR was performed to estimate the effect of HM on gene expression in liver. Results: HM decreased the total cholesterol and triglyceride in serum. And HM increased leptin, CPT1 gene expression in liver tissue of obese rats with estrogen deficiency. However HM decreased $PPAR{\gamma}$, $PGC-1{\alpha}$, HMGCR, CYP8B1, LPL, ACAT1, ACAT2, ApoB, ACOX gene expression in liver tissue of obese rats with estrogen deficiency. Conclusions: It is concluded that HM reduced total cholesterol and triglyceride in serum, and regulate gene expression related to lipid metabolism. These results indicate Hwanggimacmundong-tang that might have potential for treatment of obesity and complications during the menopause caused by estrogen-deficiency.