• Title/Summary/Keyword: C metabolism

Search Result 1,823, Processing Time 0.029 seconds

In vitro inhibitory effects of Yangguksanhwa-tang and Taeumjowi-tang on CYP450 isozymes (양격산화탕과 태음조위탕 추출물의 in vitro CYP450 효소 활성 억제 효과)

  • Ha, Hye-Kyung;Jin, Seong-Eun;Shin, Hyeun-Kyoo
    • Journal of Society of Preventive Korean Medicine
    • /
    • v.16 no.3
    • /
    • pp.129-137
    • /
    • 2012
  • Objective : Herb-drug interactions have become an important issue because of the consumption of herbal remedies has increased in the world. Yangguksanhaw-tang (Liang ge san huo-tang) and Taeumjowi-tang (Tai yin tiao wei-tang) are typical herbal formulas on Sasang constitution medicine (four-constitution medicine). This study was aimed at evaluating the effects of Yangguksanhaw-tang and Taeumjowi-tang on drug metabolizing enzymes, cytochrome P450 (CYP450) isozymes. Methods : Vivid$^{(R)}$ CYP450 Screening Kits were used to measure of CYP3A4, CYP2C19, CYP2D6 and CYP2E1 activities. This method is based on the use of fluorescent CYP450 substrates that are efficiently metabolized by specific CYP450 isozymes to yield a product with altered fluorescent properties. The percent inhibitions of CYP450s by herbal formulas were calculated. Results : Yangguksanhaw-tang inhibited CYP2C19 and CYP2E1 activities higher than that other CYP450 isozymes. The $IC_{50}$ values of CYP2C19 and CYP2E1 were 159.83 ${\mu}g/mL$ and 261.40 ${\mu}g/mL$, respectively. The CYP2E1 activity was inhibited ($IC_{50}=215.17{\mu}g/mL$) higher than that other CYP450 isozymes by Taeumjowi-tang. Conclusions : These results suggest that Yangguksanhaw-tang may inhibit the metabolism of co-administered drugs whose primary route of metabolism is via CYP2C19 or CYP2E1. Taeumjowi-tang could inhibit the metabolism of co-administered drugs, which are substrates for CYP2E1. Therefore, co-administration of the herbal formulas and other conventional drugs should be undertaken with care.

Economic Evaluation of Rosuvastatin and Atorvastatin for the Treatment of Dyslipidemia from a Korean Health System Perspective (이상지질혈증 환자에게 사용되는 Rosuvastain과 Atorvastatin의 경제성 평가)

  • Suh, Sunghwan;Jung, Chang Hee;Hong, Soon-Jun;Kim, Jung-Sun;Song, Byung Ju;Sohn, Hyun Soon;Choi, Sung Hee
    • Journal of Lipid and Atherosclerosis
    • /
    • v.5 no.1
    • /
    • pp.61-77
    • /
    • 2016
  • Objective: This study aims to analyze cost-effectiveness of two most-commonly used statins from the perspective of the Korean national health system. Methods: The scope of the analysis included rosuvastatin (5 mg, 10 mg, and 20 mg) and atorvastatin (10 mg, 20 mg, 40 mg, and 80 mg). Effectiveness was defined as percentage (%) and absolute (mg/dL) reductions of low-density lipoprotein cholesterol (LDL-C) from the baseline. They were derived from published randomized controlled studies for rosuvastatin and atorvastatin. Effectiveness was defined as reductions in LDL-C levels per mg dose of the drugs. The annual direct medical costs including drug acquisition costs and monitoring costs over the one-year time horizon were calculated for each alternative. The average cost-effectiveness ratios (ACERs) and incremental cost-effectiveness ratios (ICERs) for each statin dose were calculated. Results: The ACERs for all doses of rosuvastatin (5 mg, 10 mg, and 20 mg) were lower than those for all doses of atorvastatin (10 mg, 20 mg, 40 mg, and 80 mg). Rosuvastatin 10 mg was the most cost-effective statin for LDL-C reduction. In cost-effectiveness analyses for corresponding doses of rosuvastatin and atorvastatin, rosuvastatin was the superior strategy which suggests both higher effectiveness and lower costs than atorvastatin. However, we have to consider this analysis is highly influenced by current price of statins in each market. Conclusion: For reduction of LDL-C levels in Korean patients with dyslipidemia, rosuvastatin 10mg is the most cost-effective statin in the current Korean market.

Development of a Label-Free LC-MS/MS-Based Glucosylceramide Synthase Assay and Its Application to Inhibitors Screening for Ceramide-Related Diseases

  • Fu, Zhicheng;Yun, So Yoon;Won, Jong Hoon;Back, Moon Jung;Jang, Ji Min;Ha, Hae Chan;Lee, Hae Kyung;Shin, In Chul;Kim, Ju Yeun;Kim, Hee Soo;Kim, Dae Kyong
    • Biomolecules & Therapeutics
    • /
    • v.27 no.2
    • /
    • pp.193-200
    • /
    • 2019
  • Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z $588.6{\rightarrow}264.4$ for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625-160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.

Effects of Gamiolnyeo-jeon on Lipid Metabolism and Blood Glucose Level in db/db Mice (가미옥녀전(加味玉女煎)이 db/db 마우스 당뇨(糖尿)모델에서 지질대사(脂質代謝)와 항당뇨(抗糖尿) 효능(效能)에 미치는 영향(影響))

  • Sim, Boo-Yong;Kim, Dong-Hee
    • The Korea Journal of Herbology
    • /
    • v.31 no.2
    • /
    • pp.39-45
    • /
    • 2016
  • Objectives : Abnormal regulation of glucose and impaired lipid metabolism that result from a defective or deficient insulin are the key etiological factor in type 2 diabetes mellitus. The our study investigated the effects of Gamioknyeo-jeon (GO) on blood glucose and lipid metabolism improved by it in db/db mice (a murine model of type 2 diabetes mellitus).Methods : The animals were divided into 3 groups: Normal groups were not-treated C57BL/6 mice; Control groups were treated orally with DW in db/db mice; GO groups were treated orally with GO (200 ㎎/㎏/day) in db/db mice. After mice were treated with GO for 5 weeks, we measured AST, ALT, creatinine, BUN, body weight, food intake, blood glucose, insulin and lipid levels (total cholesterol, HDL cholesterol, and LDL cholesterol and atherogenic index(AI) and cardiac risk factor(CRF).Results : Serum AST, ALT, creatinine, BUN levels were not changed by GO do not show any toxic effects. GO groups were decreased in body weight, food intake and blood glucose level among compared to Control groups. Also, GO groups were found to have atherogenic Index and cardiac risk factor as well as lipid metabolism improvement (total cholesterol and LDL cholesterol decrease). Finally, GO groups were increased the insulin compared to Normal and control groups.Conclusions : We suggest that GO may have the control effects of diabetes mellitus by improving blood glucose control and lipid metabolism.

Development of Biologically Active Compounds from Edible Plant Sources-XX. Isolation of Lipids from the Roots of Brassica campestris ssp rapa (식용식물자원으로부터 활성물질의 탐색-XX. 순무(Brassica campestris ssp rapa)뿌리로부터 지질화합물의 분리)

  • Bang, Myun-Ho;Lee, Dae-Young;Han, Min-Woo;Oh, Young-Jun;Chung, Hae-Gon;Jeong, Tae-Sook;Choi, Myung-Sook;Lee, Kyung-Tae;Baek, Nam-In
    • Applied Biological Chemistry
    • /
    • v.50 no.3
    • /
    • pp.233-237
    • /
    • 2007
  • The roots of Brassica campestris ssp rapa were extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and $H_{2}O$. From the EtOAc and n-BuOH fractions, five compounds were isolated through the repeated silica gel column chromatographies. From the result of spectroscopic data including NMR and MS, the chemical structures of the compounds were determined as palmitic acid methyl ester (1), linolenic acid methyl ester (2), linoleic acid methyl ester (3), ${\beta}-sitosterol$ (4) and daucosterol (5).

Effect of Recombinant Porcine Somatotropin(rPST) Administration on Pig Health (유전공학 Porcine Somatotropin의 투여가 돼지의 건강에 미치는 영향)

  • Lee Chang-Woo;Bak Ung-Bok;Chang Byoung-Sun;Kim Nam-Joong;Lee Byung-Gueon
    • Journal of Veterinary Clinics
    • /
    • v.9 no.1
    • /
    • pp.333-366
    • /
    • 1992
  • Safety of recombinant porcine somatotropin administration on pig was studied using 32 Landrace x Yorkshire crossbred pigs. The starting body weight ranged from 55.5kg to 65.3kg. Eight pigs were allotted to each low dose group of sustained releasing rPST(SL), high dose group of sustained releasing rPST(SH), daily injection group of rPST(DI), and control group(C). Pigs in SL group and SH group were injected subcutaneously twice in 3 week-interval with 1000$\mu\textrm{g}$ and 2000$\mu\textrm{g}$ of sustained releasing rPST per kg body weight, respectively. Pigs in DI group were injected intramuscularly with 100$\mu\textrm{g}$ of rPST everyday for 6 weeks. Blood was collected from anterior vena cava just before the first treatment, and at four weeks and six weeks of experiment. Hematological parameters and blood chemical parameters indicating liver function, kidney function, electrolyte metabolism, mineral metabolism and lipid metabolism were determined. Necropsy and urinalysis were performed after final blood collection. The results were summarized as follows, and it is concluded that rPST administration does not affect pig health negatively. 1. rPST administration did not affect kidney function as manisfested by BUN, creatinine and urinalysis. 2. rPST administration did not affect liver function as manisfested by total protein, albumin, serum AST activity serum ALT activity serum ALP activity, serum LDH activity, serum GGT activity and serum SDH activity. 3. rPST administration did not affect skeletal muscle, cardiac muscle and brain as manifasted by serum AST activity and serum LDH activity. 4. rPST administration increased blood glucose level within normal range. 5. rPST administration did not affect lipid metabolism as manisfested by triglyceride, cholesterol, and phospholipid concentrati on. 6. rPst administration dia not affect mineral metabolism as manisfested by calcium, phosphorus, magnesium and iron concentration. 7. rPST administration did not affect electrolyte metabolism as manisfested by Na, K, chloride concentration. 8. rPST administration did not affect erythrocyte count, leukocyte count, thrombocyte count, and plasma fibrinogen level.

  • PDF

Effects of Cervi Cornu Aqua-Acupuncture on Lipid Metabolisms and Osteoporosis in Ovariectomized Rats (녹용약침자극(鹿茸藥鍼刺戟)이 난소적출(卵巢摘出) 흰쥐의 지질(脂質) 및 골대사(滑代謝)에 미치는 영향(影響))

  • Abadjieva, Daniela K.;Kang, Sung-Keel
    • The Journal of Korean Medicine
    • /
    • v.17 no.2 s.32
    • /
    • pp.168-177
    • /
    • 1996
  • In order to study the effect of aqua-acupuncture with Cervi Cornu (C.C.) extract solution manufactured by water-alcohol method on the lipid metabolism and osteoporosis, C.C. aqua-acupuncture was carried out every two days for 60 days on the corresponding bilateral loci of Shinsu (BL23), Taejo (BL11), and Hyonjong (GB39) from the 10th day after the ovariectomy for induced osteoporosis and thereafter the level of serum triglyceride, LDL, Ca, phosphorus and osteocalcin, as well as urine hydroxyproline were measured in the ovariectomized rats. The rats being studied were divided into a normal group (sham operation group), a control group (ovariectomized group), and a C.C. aqua-acupuncture group (group with C.C. aqua-acupunctured to the points of Shinsu, Taejo, and Hyonjong every two days for 60 days from the 10th day after the ovariectomy). The following results were obtained: 1. The serum triglyceride indicated an inhibited increase with statistical significance in the C.C. aqua-acupuncture group compared with the control group. 2. The serum LDL indicated an inhibited increase without any statistical significance in the C.C. aqua-acupuncture group compared with the control group. 3. The serum Ca showed an inhibited decrease without any statistical significance in the C.C. aqua-acupuncture group compared with the control group. 4. The serum phosphorus showed an inhibited decrease with statistical significance in the C.C. aqua-acupuncture group compared with the control group. 5. The serum osteocalcin indicated an inhibited decrease without any statistical significance in the C.C. aqua-acupuncture group compared with the control group. 6. The urine hydroxyproline showed an inhibited increase with statistical significance in the C.C. aqua-acupuncture group compared with the control group.

  • PDF

Nucleotide Sequence and Cloning of sfs4, One of the Genes Involved in the CRP-Dependent Expression of E. coli mal Genes. (CRP 의존성 maltose 대사 촉진 유전자 sfs4의 클로닝 및 염기배열 결정)

  • Chung, Soo-Yeol;Cho, Moo-Je;Jeong, Hee-Tae;Choi, Yong-Lark
    • Applied Biological Chemistry
    • /
    • v.38 no.2
    • /
    • pp.111-117
    • /
    • 1995
  • In Escherichia coli, CRP forms a complex with cAMP and acts as a transcriptional regulator of many genes, including sugar metabolism operons. The E. coli MK2001, which is introduced the altered crp, is functional in the expression of lac, ara and man, in the absence of cAMP. However, the expression of mal gene is fully activated by the addition of cAMP or cGMP. The object of the study is cloning of the sfs (sugar fermentation stimulation) genes, which was involved in regulation of mal gene expression with the altered crp gene, and structural analysis and characterization of the genes at the molecular level. We have cloned 5 different E. coli genes which stimulate the maltose metabolism in a crp, cya::km (MK2001) background. Newly identified genes were designated as sfs. One of the sfs genes (pPC1), located at the 53.2 min map position on the E. coli chromosome, was further analyzed. Expression of the genes, which is involved in maltose metabolism, malQ (amylomaltase), was increased to 5.8-fold in the presence of a plasmid, pAP5, containing the subcloned sfs4 gene. The nucleotide seguence of a common 2,126 bp segment of the pPCM1 was determined and two open reading frames (ORF1 and ORF2) were detected. The ORF1 encodes the sfs4 gene and ORF2 encodes a truncated protein. Potential CRP binding site is located in the upstream of the putative promoter in the regulatory region. Expression of the cloned sfs4 gene was positively regulated by the cAMP-CRP complex.

  • PDF

Effect of the Water Soluble Extracts from Velvet Antler on Lipid Metabolism and Blood Components in Rats (수용성 녹용 추출물이 랫드의 지방대사 및 혈액성분에 미치는 영향)

  • Cui, Xang Soon;Kim, Hye In;Cho, Seong Koo
    • Journal of Animal Science and Technology
    • /
    • v.50 no.3
    • /
    • pp.417-428
    • /
    • 2008
  • An experiment was conducted with 80 male rats for 4 weeks to investigate the effect of water soluble extracts(WSE) from different sections of farmed Elk(Cervus elaphus) antler on lipid metabolism and hematology. Antlers were divided into four sections of tip, upper, middle and base. Water soluble extract(35g/60ml) was prepared from each section of antler, and was administered orally to male Sprague- Dawley rats(10ml/kg body weight) once a day. Administration of WSE from upper, middle and base sections of antler decreased(P<0.0027) AST values at 3 weeks of feeding, however AST value was decreased(P< 0.0136) in the WSE of base section compared to that of control at 4 weeks of feeding. Administration of antler WSE for 4 weeks decreased total cholesterol in visceral fat(P<0.0035) and liver(P<0.0003) at 4 weeks of feeding compared to those of control. Feeding antler WSE for 4 weeks increased the compositions of C14:0(P<0.0037), C16:1(P<0.0061), C18:1(P<0.0066), C18:2(P< 0.0069) and C18:3(P<0.0035) in the visceral fat compared with that of control.

SREBP-1c Ablation Protects Against ER Stress-induced Hepatic Steatosis by Preventing Impaired Fatty Acid Oxidation (지방산 산화 장애 제어를 통한 SREBP-1c 결핍의 소포체 스트레스 유발 비알콜성지방간 보호작용)

  • Lee, Young-Seung;Osborne, Timothy F.;Seo, Young-Kyo;Jeon, Tae-Il
    • Journal of Life Science
    • /
    • v.31 no.9
    • /
    • pp.796-805
    • /
    • 2021
  • Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.