• Journal of Applied Biological Chemistry
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• 제55권1호
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• pp.19-25
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• 2012

Green tea leaves were fermented for 15 and 30 days with Monascus pilosus which is known to produce functional statins (TMs), and the content of various biochemical constituents such as total polyphenol (TP), total flavonoid (TF), theaflavin, and thearubigin were analyzed and compared with that of non-fermented green tea (GT) and Pu-erh Chinese post-fermented tea (PU). In addition to the electron donating ability (EDA), ferric iron reducing power (FIRP), xanthine oxidase (XO) inhibitory activity, superoxide dismutase (SOD)-like activity, iron chelating activity (ICA) and hydrogen peroxide contents were also measured and compared with that of GT and PU. Content of TP and TF in the water and ethanol extracts in TMs were lower than those in GT and PU. Theaflavin and thearubigin contents of water and ethanol extracts in TMs were higher than those of GT. And, these components were increased depending on the period of fermentation. While, EDA and FIRP of TMs were lower than those of GT, XO inhibitory activity of TMs was higher than non-fermented tea. While, ICA of TMs was slightly higher than GT and PU, the content of hydrogen peroxide in TMs was markedly lower than GT. This results suggested that the green tea fermented by M. pilosus was valuable for oxidative stress-induced diseases by decreasing hydrogen peroxide, and forming theaflavins and thearubigins with functionality of genus Monascus.

• 대한후두음성언어의학회지
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• 제26권1호
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• pp.58-62
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• 2015

Xanthoma disseminatum (XD) is a benign, non-Langerhans cell histiocytosis characterized by disseminated xanthomatous lesions with face, flexures, and mucosa. Most of XD develops in mucocutaneous lesions including skin, oral cavity and pharynx, however laryngeal involvement is uncommon. While the natural course of XD is usually benign and often self-limiting, but XD develop in critical anatomical locations may result in morbidity and mortality. Localized mucous lesions in oropharynx and larynx lead to dysphagia, dyspnea and air way obstruction. The diagnosis of XD was based on clinical, histological and immunohistochemical findings. The treatment is complex and non-consensual. Local treatment with cryotherapy, radiotherapy, surgery, and carbon dioxide lasers have been attempted with various results. Systemic medication with peroxisome proliferator-activated gamma receptors, statins, fenofibrate, chlorodeoxyadenosine, cyclophosphamide, doxycycline, and cyclosporine have also been reported, but none have proven particularly successful. A 59-year-old man presented with respiratory symptoms because of laryngeal involvement of XD. We had to remove the obstructive lesion for relieving the symptoms. We experienced XD in Larynx that was rare in otorhinolaryngology. So we report this case with review of literatures.

• 한국식품과학회지
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• 제47권3호
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• pp.409-412
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• 2015

Monascus pilosus KCCM 60084를 백태와 서리태에 각각 접종시켜 $30^{\circ}C$에서 발효한 후, 홍국발효 콩에 함유된 미량의 생리활성물질에 대한 영향을 측정하였다. 천연 스타틴 성분인 mevinolin은 발효 전의 미 검출에서 홍국 발효 20일 후에 건조시료 g당(${\mu}g/g$ DW) 최대 $568.18{\mu}g$ 생산하였고, CoQ10의 함량은 발효전의 농도에 비해 발효 20일 후에 백태와 서리태 모두 2배 이상 증가하여 각각 $65.59{\pm}9.53$과 $54.92{\pm}5.27{\mu}g$으로 나타났다. 토코페롤 함량은 홍국발효에 의해 뚜렷한 변화가 관찰되지 않았다. 발효 전의 백태에 함유된 총 토코페롤 함량은 $312.87{\mu}g$으로 서리태의 $256.76{\mu}g$ 보다 약 22% 더 높았으며(p<0.05), 가장 많이 함유된 토코페롤 종류는 ${\gamma}$-토코페롤로 전체 농도의 약 55%을 차지 하였다. 따라서 홍국발효는 콩의 메비놀린과 CoQ10 성분의 농도를 발효과정을 통해 변화시키는 것으로 나타났다.

• 약학회지
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• 제57권1호
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• pp.24-31
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• 2013

Although statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been shown to increase melanin synthesis, the exact mechanism of this action is not fully understood. In this study we investigated the possible involvement of intracellular $Ca^{2+}$ signal in the mechanism of stimulation of melanin synthesis induced by lovastatin in B16 cells. Lovastatin stimulated the production of melanin in a dose-dependent manner in the cells. Treatment with mevalonate, FPP and GGPP, precursors of cholesterol, did not significantly suppress the lovastatin-induced melanin production, suggesting that inhibition of cholesterol synthesis may not be involved in the mechanism of the action of lovastatin. In addition, lovastatin did not significantly alter the cAMP concentration and the stimulated production of melanin by lovastatin was not significantly changed by treatment with H89, a potent inhibitor of protein kinase A, which demonstrates that cAMP pathway may not be involved. However, lovastatin increased intracellular $Ca^{2+}$ concentration in a dose-related fashion. Treatment with EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the lovastatin-induced intracellular $Ca^{2+}$ increase and melanin synthesis, whereas intracellular $Ca^{2+}$ reduction with BAPTA/AM and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8) completely blunted these actions of lovastatin. Taken together, these results suggest that the intracellular $Ca^{2+}$ release may play an important role in the lovastatin-induced stimulation of melanin synthesis in B16 cells. These results further suggest that lovastatin may be useful for the treatment of hypopigmentation disorders, such as vitiligo.

• 한국임상약학회지
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• 제31권3호
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• pp.198-204
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• 2021

Background: Cardiovascular (CV) disease is known as one of the major causes of death from disease worldwide. Statin therapy plays a pivotal role in atherosclerotic cardiovascular disease (ASCVD) lowering the LDL-cholesterol level effectively. The purpose of this study was to evaluate the association of the intensity of statin therapy in adult patients of Korea and the risk of ASCVD of the patient group. Methods: We used data from sample of patients from the Health Insurance Review and Assessment Service (HIRA-NPS-2018). We analyzed the patterns of prescribing statins including types of statin, statin intensity, and number of patients with ASCVD or risk of ASCVD. Results: 155,512 patients were included in the analysis, and 27,950 patients (18.0%) was over 75 years. High-intensity statin usage was increased in ASCVD patients compared with the low-intensity statin use. The OR (odds ratio) of high-intensity statin were increased in myocardial infarction patients compared with low-intensity statin use showing the highest OR; 12.40 (95% CI; 9.48-16.22). At patient groups of angina, ischemic heart disease and carotid disease, high-intensity statin prescription rate was increased compared with low-intensity statin. However, there was no statistical significance between both statin prescription rates in patients of peripheral arterial disease, abdominal aneurysm, diabetic mellitus and atherosclerosis. Conclusion: The statin prescription rate showed intensity increasing tendency according to the risk of ASCVD. More aggressive statin therapy might be beneficial for the ASCVD patients based on the recent guidelines of dyslipidemia.

• 한국임상약학회지
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• 제28권4호
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• pp.320-332
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• 2018

Background: This study was performed to clarify the effect of SLCO1B1 T521C on statin-induced myotoxicity. Methods: The PubMed, Embase, Ovid, and Cochrane Library databases were searched for all published studies between database inception and April 2018. Using Review Manager 5, the pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were determined to assess the effect of SLCO1B1 T521C on statin-induced myotoxicity by using different genetic models. Results: Eleven observational studies and one randomized controlled trial were included in the meta-analysis. The pooled analysis showed that the incidence of statin-induced myotoxicity was significantly associated with the SLCO1B1 521C variant allele. Among patients using statins, the incidence of myotoxicity was higher in those carrying the 521TC or 521CC variant than in those carrying the 521TT variant in the dominant model (TC + CC vs TT, OR: 1.57; 95% CI: 1.20, 2.05; p = 0.001). The 521TC genotype was associated with a higher risk of myotoxicity than the 521TT genotype (OR: 1.42; 95% CI: 1.09, 1.86; p = 0.009). Furthermore, the incidence of myotoxicity was higher in 521CC carriers than in 521TC carriers (OR: 1.40; 95% CI: 1.06, 1.83; p = 0.02) and noticeably higher in 521CC carriers than in 521TT carriers (OR: 2.26; 95% CI: 1.23, 4.17; p = 0.009). Conclusion: The identification of individuals with the SLCO1B1 521C variant allele prior to the initiation of statin therapy might be useful to predict the risk of toxicity development, determine the individual dose, and prevent myotoxicity.

• 한국임상약학회지
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• 제33권3호
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• pp.168-177
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• 2023

Background & Objectives: Fixed-dose combinations (FDCs) offer advantages in adherence and cost-effectiveness compared to free combinations (FCs), but they can also complicate the prescribing process, potentially leading to therapeutic duplication (TD). This study aimed to identify the prescribing patterns of FDCs for dyslipidemia and investigate their associated risk of TD. Methods: This was a retrospective cohort study involving drugs that included statins, using Health Insurance Review & Assessment Service-National Patient Sample (HIRA-NPS) data from 2018. The unit of analysis was a prescription claim. The primary outcome was TD. The risk ratio of TD was calculated and adjusted for patient, prescriber, and the number of cardiovascular drugs prescribed using a multivariable Poisson model. Results: Our study included 252,797 FDC prescriptions and 515,666 FC prescriptions. Of the FDC group, 46.52% were male patients and 56.21% were aged 41 to 65. Ezetimibe was included in 71.61% of the FDC group, but only 0.25% of the FC group. TD occurred in 0.18% of the FDC group, and the adjusted risk ratio of TD in FDC prescriptions compared to FC was 6. 44 (95% CI 5. 30-7. 82). Conclusions: Prescribing FDCs for dyslipidemia was associated with a higher risk of TD compared to free combinations. Despite the relatively low absolute prevalence of TD, the findings underline the necessity for strategies to mitigate this risk when prescribing FDCs for dyslipidemia. Our study suggests the potential utility of Clinical Decision Support Systems and standardizing nomenclature in reducing medication errors, providing valuable insights for clinical practice and future research.

• Journal of Digestive Cancer Research
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• 제4권2호
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• pp.64-76
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• 2016

The step-wise process of colorectal carcinogenesis from aberrant crypt foci, adenoma to adenocarcinoma, is relatively suitable for chemopreventive intervention. Accumulated evidences have revealed that maintaining an undifferentiated state (stemness), inflammation, and oxidative stress play important roles in this colon carcinogenesis process. However, appropriate molecular targets that are applicable to chemopreventive intervention regarding those three factors are still unclear. In this review, we summarized appropriate molecular targets by identification and validation of the prospective targets from a comprehensive overview of data that showed colon cancer preventive effects in clinical trials, epidemiological studies and basic research. We first selected a study that used aspirin, statins and metformin from FDA approved drugs, and epigallocatechin-gallate and curcumin from natural compounds as potential chemopreventive agents against colon cancer because these agents are considered to be promising chemopreventive agents. Experimental and observational data revealed that there are common target molecules in these potential chemopreventive agents: T-cell factor/lymphoid enhancer factor (TCF/LEF), nuclear factor-&B (NF-κB) and nuclear factor-erythroid 2-related factor 2(NRF2). Moreover, these targets, TCF/LEF, NF-κB and NRF2, have been also indicated to suppress maintenance of the undifferentiated state, inflammation and oxidative stress, respectively. In the near future, novel promising candidate agents for colon cancer chemoprevention could be identified by integral evaluation of their effects on these three transcriptional activities.

• 생명과학회지
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• 제31권4호
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• pp.418-424
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• 2021

자외선과 병원미생물 감염 등으로 야기되는 다양한 피부조직의 손상은 피부염증을 일으킨다. 피부염 치료제로 염증을 완화시키는 항히스타민 또는 스테로이드 계열 약물이 처방되고 있다. 하지만 부적절한 스테로이드 복용은 피부 장벽 약화나 골다공증 등의 부작용을 초래할 수 있어, 부작용이 적은 피부염 치료 약물은 임상적으로 중요하다. 콜레스테롤 합성에 필요한 3-hydroxy-3-methylglutaryl-coenzyme A 환원효소를 억제하는 statin은 혈청 콜레스테롤 수준을 낮추는 약물로 고지혈증이나 심혈관질환에 널리 처방되고 있다. 이러한 콜레스테롤 생성 억제 기능에 더하여, 흥미롭게도, statin 약물은 골관절염과 관련된 여러 연구에서 항염증 효과가 있는 것으로 보고되고 있다. 본 연구에서는 피부 장벽의 주요 구성 세포인 각질형성세포(HaCaT 세포주)에서 atorvastatin 및 fluvastatin의 잠재적인 항염증 효과를 조사하였다. IL-1β 자극에 반응하여 HaCaT 세포에서 염증반응의 주요한 인자인 COX2 단백질의 발현이 증가하였다. 이러한 COX2 단백질의 발현 증가는 atorvastatin 또는 fluvastatin 약물 처리로 억제되었다. 비슷하게, IL-1β에 의해 발현이 증가된 다른 염증반응 유전자(iNOS 그리고MMP-1 등)의 발현양도 atorvastatin 또는 fluvastatin 약물 처리로 감소되었다. 종합하면, 본 연구결과는 HaCaT 세포에서 IL-1β 로 유도된 염증반응이 atorvastatin 및 fluvastatin 약물 처리로 하향 조절될 수 있음을 보여준다. 따라서, 본 연구결과는 atorvastatin 및 fluvastatin 약물이 피부염증을 완화시키는 조절제로 응용될 수 있다는 것을 제시한다.

• Journal of Medicine and Life Science
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• 제21권2호
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• pp.40-48
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• 2024

Understanding the effectiveness of statin treatment is essential for developing tailored stroke prevention strategies. We aimed to evaluate the efficacy of statin treatment in preventing recurrent stroke among patients with various ischemic stroke subtypes. Using data from the Clinical Research Collaboration for Stroke-Korea-National Institute for Health (CRCS-K-NIH) registry, we included patients with acute ischemic stroke admitted between January 2011 and July 2020. To evaluate the differential effects of statin treatment based on the ischemic stroke subtype, we analyzed patients with large artery atherosclerosis (LAA), cardio-embolism (CE), and small vessel occlusion (SVO). The primary outcomes were recurrent ischemic stroke and recurrent stroke events. The hazard ratio for outcomes between statin users and nonusers was compared using a Cox proportional hazards model adjusted for covariates. A total of 46,630 patients who met the inclusion criteria were analyzed. Statins were prescribed to 92%, 93%, and 78% of patients with LAA, SVO, and CE subtypes, respectively. The hazards of recurrent ischemic stroke and recurrent stroke in statin users were reduced to 0.79 (95% confidence interval [CI], 0.63-0.99) and 0.77 (95% CI, 0.62-0.95) in the LAA subtype and 0.63 (95% CI, 0.52-0.76) and 0.63 (95% CI, 0.53-0.75) in CE subtype compared to nonusers. However, the hazards of these outcomes did not significantly decrease in the SVO subtype. The effectiveness of statin treatment in reducing the risk of recurrent stroke in patients with LAA and CE subtypes has been suggested. Nonetheless, no significant effect was observed in the SVO subtype, suggesting a differential effect of statins on different stroke subtypes.