• Title/Summary/Keyword: primary metabolism

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Review about using Herbal medicine on steroid tapering and steroid overuse in Skin disease (피부과 영역에서 steroid 테이퍼링 및 남용 완화를 위한 한약 사용에 대한 고찰)

  • Han, Chang-Yi;Kim, Jun-Dong;Kang, Dong-Won;Kim, Kyu-Seok;Kim, Yoon-Bum
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.33 no.3
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    • pp.115-124
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    • 2020
  • Objectives : The purpose of this study is to investigate the effect and side effects of steroids on dermatitis and skin barrier through lipid metabolism. And to propose using Herbal medicine to suppress Steroid rebound and prevent side effects. Methods : We reviewed recent studies about the relationship between dermatitis, skin lipid, steroid, and herbal medicine through Google scholar. Results : In various inflammatory skin diseases, the corticosteroid is selected as the primary drug due to its strong anti-inflammatory and immunosuppressive effect. However, long-term use of steroids has a variety of side effects, especially lipid metabolism disruption, which aggravates skin barrier damage underlying various skin diseases and is more susceptible to inflammatory reactions. Conclusions : Herbal medicine is used as a comprehensive approach, and it can be used to reduce the frequency of steroid exposure by protecting against barrier damage by controlling anti-inflammatory, antioxidant, and systemic/sebaceous lipid metabolism and stratum corneum protein differentiation.

Metabolic Topography of Parkinsonism

  • Kim, Jae-Seung
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.2
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    • pp.141-151
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    • 2007
  • Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson diorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkisonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, an assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of parkisonism.

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
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    • v.16 no.3
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    • pp.129-137
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    • 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.

Comprehensive Lipid Profiling Recapitulates Enhanced Lipolysis and Fatty Acid Metabolism in Intimal Foamy Macrophages From Murine Atherosclerotic Aorta

  • Jae Won Seo;Kyu Seong Park;Gwang Bin Lee;Sang-eun Park;Jae-Hoon Choi;Myeong Hee Moon
    • IMMUNE NETWORK
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    • v.23 no.4
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    • pp.28.1-28.20
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    • 2023
  • Lipid accumulation in macrophages is a prominent phenomenon observed in atherosclerosis. Previously, intimal foamy macrophages (FM) showed decreased inflammatory gene expression compared to intimal non-foamy macrophages (NFM). Since reprogramming of lipid metabolism in macrophages affects immunological functions, lipid profiling of intimal macrophages appears to be important for understanding the phenotypic changes of macrophages in atherosclerotic lesions. While lipidomic analysis has been performed in atherosclerotic aortic tissues and cultured macrophages, direct lipid profiling has not been performed in primary aortic macrophages from atherosclerotic aortas. We utilized nanoflow ultrahigh-performance liquid chromatography-tandem mass spectrometry to provide comprehensive lipid profiles of intimal non-foamy and foamy macrophages and adventitial macrophages from Ldlr-/- mouse aortas. We also analyzed the gene expression of each macrophage type related to lipid metabolism. FM showed increased levels of fatty acids, cholesterol esters, phosphatidylcholine, lysophosphatidylcholine, phosphatidylinositol, and sphingomyelin. However, phosphatidylethanolamine, phosphatidic acid, and ceramide levels were decreased in FM compared to those in NFM. Interestingly, FM showed decreased triacylglycerol (TG) levels. Expressions of lipolysis-related genes including Pnpla2 and Lpl were markedly increased but expressions of Lpin2 and Dgat1 related to TG synthesis were decreased in FM. Analysis of transcriptome and lipidome data revealed differences in the regulation of each lipid metabolic pathway in aortic macrophages. These comprehensive lipidomic data could clarify the phenotypes of macrophages in the atherosclerotic aorta.

Left Ventricular Remodeling in Patients with Primary Aldosteronism: A Prospective Cardiac Magnetic Resonance Imaging Study

  • Tao Wu;Yan Ren;Wei Wang;Wei Cheng;Fangli Zhou;Shuai He;Xiumin Liu;Lei Li;Lu Tang;Qiao Deng;Xiaoyue Zhou;Yucheng Chen;Jiayu Sun
    • Korean Journal of Radiology
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    • v.22 no.10
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    • pp.1619-1627
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    • 2021
  • Objective: This study used cardiac magnetic resonance imaging (MRI) to compare the characteristics of left ventricular remodeling in patients with primary aldosteronism (PA) with those of patients with essential hypertension (EH) and healthy controls (HCs). Materials and Methods: This prospective study enrolled 35 patients with PA, in addition to 35 age- and sex-matched patients with EH, and 35 age- and sex-matched HCs, all of whom underwent comprehensive clinical and cardiac MRI examinations. The analysis of variance was used to detect the differences in the characteristics of left ventricular remodeling among the three groups. Univariable and multivariable linear regression analyses were used to determine the relationships between left ventricular remodeling and the physiological variables. Results: The left ventricular end-diastolic volume index (EDVi) (mean ± standard deviation [SD]: 85.1 ± 13.0 mL/m2 for PA, 75.9 ± 14.3 mL/m2 for EH, and 77.3 ± 12.8 mL/m2 for HC; p = 0.010), left ventricular end-systolic volume index (ESVi) (mean ± SD: 35.2 ± 9.8 mL/m2 for PA, 30.7 ± 8.1 mL/m2 for EH, and 29.5 ± 7.0 mL/m2 for HC; p = 0.013), left ventricular mass index (mean ± SD: 65.8 ± 16.5 g/m2 for PA, 56.9 ± 12.1 g/m2 for EH, and 44.1 ± 8.9 g/m2 for HC; p < 0.001), and native T1 (mean ± SD: 1224 ± 39 ms for PA, 1201 ± 47 ms for EH, and 1200 ± 44 ms for HC; p = 0.041) values were higher in the PA group compared to the EH and HC groups. Multivariable linear regression demonstrated that log (plasma aldosterone-to-renin ratio) was independently correlated with EDVi and ESVi. Plasma aldosterone was independently correlated with native T1. Conclusion: Patients with PA showed a greater degree of ventricular hypertrophy and enlargement, as well as myocardial fibrosis, compared to those with EH. Cardiac MRI T1 mapping can detect left ventricular myocardial fibrosis in patients with PA.

Comparative analysis of the transcriptomes and primary metabolite profiles of adventitious roots of five Panax ginseng cultivars

  • Lee, Yun Sun;Park, Hyun-Seung;Lee, Dong-Kyu;Jayakodi, Murukarthick;Kim, Nam-Hoon;Lee, Sang-Choon;Kundu, Atreyee;Lee, Dong-Yup;Kim, Young Chang;In, Jun Gyo;Kwon, Sung Won;Yang, Tae-Jin
    • Journal of Ginseng Research
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    • v.41 no.1
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    • pp.60-68
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    • 2017
  • Background: Various Panax ginseng cultivars exhibit a range of diversity for morphological and physiological traits. However, there are few studies on diversity of metabolic profiles and genetic background to understand the complex metabolic pathway in ginseng. Methods: To understand the complex metabolic pathway and related genes in ginseng, we tried to conduct integrated analysis of primary metabolite profiles and related gene expression using five ginseng cultivars showing different morphology. We investigated primary metabolite profiles via gas chromatography-mass spectrometry (GC-MS) and analyzed transcriptomes by Illumina sequencing using adventitious roots grown under the same conditions to elucidate the differences in metabolism underlying such genetic diversity. Results: GC-MS analysis revealed that primary metabolite profiling allowed us to classify the five cultivars into three independent groups and the grouping was also explained by eight major primary metabolites as biomarkers. We selected three cultivars (Chunpoong, Cheongsun, and Sunhyang) to represent each group and analyzed their transcriptomes. We inspected 100 unigenes involved in seven primary metabolite biosynthesis pathways and found that 21 unigenes encoding 15 enzymes were differentially expressed among the three cultivars. Integrated analysis of transcriptomes and metabolomes revealed that the ginseng cultivars differ in primary metabolites as well as in the putative genes involved in the complex process of primary metabolic pathways. Conclusion: Our data derived from this integrated analysis provide insights into the underlying complexity of genes and metabolites that co-regulate flux through these pathways in ginseng.

Effects of Aqueous Extract Isolated from Platycodon grandiflorum Against t-Buty lhydroperoxide-induced Oxidative Stress in Rat Primary Hepatocytes (일차배양 간세포에서 t-Buty lhydroperoxide에 의해 유발된 산화적 스트레스에 대한 길경 열수 추출물의 보호효과)

  • 최철웅;이경진;정혜광
    • YAKHAK HOEJI
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    • v.46 no.6
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    • pp.466-471
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    • 2002
  • Oxidative stress is considered to be associated with many diseases, such as inflammatory and cardiovascular diseases, aging and cancer. An important etiological mechanism of these diseases may be a causal relationship between the presence of oxidants and the generation of lipid hydroperoxides derived from enzymatic reactions or xenobiotic metabolism. The hydroperoxides can be decomposed to alkoxy- (ROㆍ) and peroxy- (ROOㆍ) free radicals that can oxidize other cell components, resulting in changes in enzyme activity or the generation of mediators, which can cause further cell damage. The aim of this study was to evaluate the ability of aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK), to affect cellular response in primary cultures of rat hepatocytes to t-butyl hydroperoxide (t-BHP) induced oxidative stress and hepatotoxicity. CK-treated cells showed an increased resistance to oxidative challenge, as revealed by a higher percent of survival capacity in respect to control cells. CK reduced t-BHP-enhanced lipid peroxidation measured as production of malondialdehyde and enhanced intracellular reduced glutathione depletion by t-BHP. Furthermore, CK protected from the t-BHP-induced intracellular generation of reactive oxygen species assessed by monitoring dichlorodihydrofluorescein fluorescence. It can be concluded that CK exerts an antioxidant action inside the cell, responsible for the observed modulation of the cellular response to oxidative challenge, and CK have a marked antioxidative and hepatoprotective potency.

Cloning and Characterization of S-Adenosyl-L-methionine synthetase gene from Saccharomyces cerevisiae

  • Ko, Kwon-Hye;Yoon, Gee-Sun;Choi, Gi-Sub;Suh, Joo-Won;Ryu, Yeon-Woo
    • 한국생물공학회:학술대회논문집
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    • 2005.10a
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    • pp.301-304
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    • 2005
  • S-Adenosyl-L-Methionine(SAM) has an important role for DNA methylation and cell signaling. SAM was synthesized from methionine and ATP by SAM synthetase and play an pivotal function in the primary and secondary metabolism of cells. Recent studies have revealed in the effect of SAM in case of morphological differentiation in both eukaryotes and prokaryotes. We isolated SAM gene from Saccharomyces cerevisiae and cloned it into expression vector for E. coli respectively. An 1.15 kb SAM-s gene fragment was isolated by Low-strigency PCR using ORF primer. By the analysed primary sequence deduced from DNA sequence, this gene included conserved domains similar with other well-known SAM synthetase. First of all, SAM synthetase gene cloned pGEM-T vector and subcloned into histidine tagging system to purify the expressed protein using metal chelating resin. Typical characteristic analysis of this enzyme is underway.

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Nutritional Regulation of GLUT Expression, Glucose Metabolism, and Intramuscular Fat Content in Porcine Muscle

  • Katsumata, M.;Kaji, Y.;Takada, R.;Dauncey, M.J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.8
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    • pp.1297-1304
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    • 2007
  • We conducted a series of investigations in order to elucidate role of nutritional status in regulating GLUT expression and energy metabolism in porcine muscle. Firstly, the role of mild undernutrition in regulating muscle GLUT gene expression and function was studied in growing pigs (3 wk of age) on a high (H) or low (L) food intake (H = 2L) at $35^{\circ}C$ or $26^{\circ}C$. Low food intake selectively upregulates GLUT1 and GLUT4 gene expression; mRNA levels were elevated in longissimus dorsi (L. dorsi) and rhomboideus muscles but not in diaphragm or cardiac muscles. Our next step was to determine whether dietary lysine, a major primary limiting amino acid in diets for pigs, affects muscle GLUT4 expression. Pigs of 6 wk of age were pair-fed a control or low lysine (LL) diet. The control diet contained optimal amounts of all essential amino acids, including 1.15% lysine. The LL diet was similar but contained only 0.70% lysine. GLUT4 mRNA expression was upregulated by the LL diet in L. dorsi and rhomboideus muscles, whereas that in cardiac muscle was unaffected. GLUT4 protein abundance was also higher in rhomboideus muscle of animals on the LL diet. We conducted another investigation in order to elucidate effects of the LL diet on post-GLUT4 glucose metabolism. Activity of hexokinase was unaffected by dietary lysine levels while that of citrate synthase was higher both in L. dorsi and rhomboideus muscles of pigs fed on the LL diet. Glucose 6-phosphate content was higher in L. dorsi msucle in the LL group. Glycogen content was higher both in L. dorsi and rhomboideus muscles in the LL group. Further, we determined the effects of dietary lysine levels on accumulation of intramuscular fat (IMF) in L. dorsi muscle of finishing pigs. A low lysine diet (lysine content was 0.40%) meeting approximately 70% of the requirement of lysine was given to finishing pigs for two months. IMF contents in L. dorsi of the pigs given the low lysine diet were twice higher than those of the pigs fed on a control diet (lysine content was 0.65%). Finally, we proved that a well known effect of breadcrumbs feeding to enhance IMF of finishing pigs could be attributed to shortage of amino acids in diets including breadcrumbs.

Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD

  • Zehong Yang;Yuanyuan Yu ;Nannan Sun;Limian Zhou;Dong Zhang;HaiXin Chen ;Wei Miao ;Weihang Gao ;Canyang Zhang ;Changhui Liu ;Xiaoying Yang ;Xiaojie Wu ;Yong Gao
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.376-384
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    • 2023
  • Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.