• Journal of Acupuncture Research
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• 제23권2호
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• pp.1-19
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• 2006

Objectives : The aim of this study was to investigate the hypoglycemic and hypolipidemic activities and mechanisms of Acanthopanax senticosus (AS) herbal acupuncture. Methods : Anti-diabetic and anti-steatotic activity of the AS herbal acupuncture was investigated on C57BL/6J ob/ob mice. After random grouping at the age of 9 weeks, the herbal acupuncture groups were injected subcutaneously at the left and right Gansu (BL18) corresponding acupuncture points alternately on exactly the same time every day with 0.1ml of either 400 mg/kg or 800 mg/kg of AS (AS400 and AS800) for 8-week period. As a positive control, metformin was administrated at a dose of 300 mg/kg (MT300). Body weights were measured weekly, and on every other week blood was collected for blood glucose analysis. At the end of study, blood was also collected for determination of plasma insulin and lipid levels, after which they were killed and periepidydimal fat, liver, muscle, and pancreas were immediately removed. The removed tissues were instantly soaked in liquid nitrogen and stored at $-70^{\circ}C$ for morphological examination and mRNA analysis. Results : The AS herbal acupuncture significantly prevented weight gain on C57BL/6J ob/ob mice. The AS herbal acupuncture lowered blood glucose and improved glucose tolerance in C57BL/6J ob/ob mice. The increase of insulin response during the OGTT was inhibited by the AS herbal acupuncture. Insulin sensitivity of skeletal tissue was enhanced. Plasma lipid levels were significantly improved in the AS herbal acupuncture groups. The AS herbal acupuncture decreased hepatic lipogenesis and hepatic triglyceride production, and increased fatty acid (FA) transporter that involves in FA uptake. The AS herbal acupuncture inhibited the increase of liver mass by prevention of the accumulation of TG but did not inhibit weight gain of fat tissue on C57BL/6J ob/ob mice. Conclusion : In summary, we have demonstrated several unique properties of the AS herbal acupuncture in decreasing body weight, and reversing insulin resistance and hepatic steatosis in ob/ob mice. This AS herbal acupuncture acts as an insulin sensitizer and specifically decreases circulating glucose and lipids, and suppresses hepatic lipogenesis.

• 약학회지
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• 제58권1호
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• pp.71-79
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• 2014

Although Korean patients with type 2 diabetes mellitus (T2DM) are generally treated by western medicine, many of them strongly believe in the traditional oriental Sasang constitutional classification and depend on it for food, health supplements, and oriental medicines decision making. Sasang constitutional classification is a part of traditional Korean medicine that divides people into four constitutional types (Tae-Yang: TY, Tae-Eum: TE, So-Yang: SY, and So-Eum: SE), which differ in inherited characteristics such as appearance, personality traits, susceptibility to diseases, and drug responses. It is recommended for T2DM patients to control their blood glucose very well from early stages with drugs and diet. However, many T2DM patients respond differently to their drugs, even though they receive the same medicine. Therefore, the present study investigated whether Sasang constitutional type can explain the therapeutic differences between oral hypoglycemic agents (OHAs) therapy (mono, dual and triple drug therapy). Patients of 618 with T2DM diagnosis and Sasang constitutional type known who received both western and oriental medicine treatment in a hospital between April 2006 and April 2013 retrospectively studied. HbA1c (%) and blood glucose (mg/dl) levels before OHAs therapy and 3 month after were collected for metformin (MET) or sulfonylurea (SU) monotherapy, MET+SU dual therapy, MET+except SU (where was either alpha-glucosidase inhibitor, dipeptidyl peptidase-4 inhibitor, meglitinide or thiazolidinedione) dual therapy, and triple therapy, according to Sasang constitutional type. For statistical analysis, ANOVA was used and paired t-test by SPSS 19.0 where P values less than 0.05 were considered statistically significant. Pattern was similar levels of HbA1c and blood glucose and which was decreased in order of mono, MET+SU dual, MET+except SU dual and triple therapy. In all patients comparison, for the So-yang (SY) constitutional type, either monotherapy was less effective; for Te-eum (TE) type, MET+SU dual therapy was less effective while MET+except SU dual therapy was more effective and the triple therapy was less effective; and for So-eum (SE) type, the triple therapy was more effective. For the management of TE type it is recommended to use drugs except SU when dual therapy is needed, restrict triple therapy and consider dual and insulin therapy; for SY type it is recommended to follow current guidelines; and for SE type it is advisable to skip dual therapy and start the triple therapy early. Finally, the therapeutic response to OHAs is different among Korean T2DM patients with different Sasang constitutional types. Taken together, the choice of effective OHAs therapy for each type is necessary in order to minimize the poor control of blood glucose level, the risk of complications, and the costs from a failure of therapy.

• 대한본초학회지
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• 제34권6호
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• pp.45-55
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• 2019

Objective : Diabetic gastroparesis is a complication that is defined as delayed gastric emptying and upper gastrointestinal symptoms and often occurs in long-standing diabetic patients. Bojungikgi-tang (BJT) is a traditional oriental herbal formula that has long been used for the treatment of digestive disorders. The purpose of this study was to investigate the effects of BJT on streptozotocin (STZ)-induced diabetic gastroparesis rat model. Methods : Sprague-Dawley (SD) male rats (250-270g) were divided into 13 groups including normal group, STZ-induced diabetic control group, BJT diet (7 various concentrations), and insulin-, glibenclamide-, metformin-treated group were used for the experiments for the comparison. Diabetic gastroparesis was induced by intraperitoneal injection of STZ. The water intake, food intake, body weights and fasting blood glucose levels were measured. After 4 weeks the animals were sacrificed and gastrin, leptin, insulin, hemoglobin A1C (HbA1c), lactate, lactate dehydrogenase (LDH), bilirubin, creatinine, albumin and lipid levels were evaluated. Results : Intraperitoneal injection of BJT for 4 weeks resulted in increased levels of gastrin in blood and decreased leptin and lactate concentration in STZ-induced diabetic gastroparesis rat model. BJT did not affect insulin, fasting glucose, HbA1c, and lipid levels in STZ-induced diabetic gastroparesis rat model. Conclusion : These results indicated that BJT would have protect effect on diabetic gastroparesis through the improvement effect of gastric motility and fatigue syndrome in STZ-induced diabetic rats. This study shows that BJT might be effective for treatment of diabetes and its complications such as gastroparesis.

• 상하수도학회지
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• 제36권2호
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• pp.107-119
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• 2022

The frequent detection and occurrence of micropollutants (MPs) in aquatic ecosystems has raised public health concerns worldwide. In this study, the behavior of 50 MPs was investigated in three different domestic wastewater treatment plants (WWTPs). Furthermore, the Kruskal-Wallis test was used to assess the geographical and seasonal variation of MPs in the WWTPs. The results showed that the concentrations of 43 MPs ranged from less than 0.1 to 237.6 ㎍ L^-1, while other seven MPs including 17-ethynylestradiol, 17-estradiol, sulfathiazole, sulfamethazine, clofibric acid, simvastatin, and lovastatin were not detected in all WWTPs. Among the detected MPs, the pharmaceuticals such as metformin, acetaminophen, naproxen, and caffeine were prominent with maximum concentrations of 133.4, 237.6, 71.5, and 107.7 ㎍ L^-1, respectively. Most perfluorinated compounds and nitrosamines were found at trace levels of 1.2 to 55.3 ng L^-1, while the concentration of corrosion inhibitors, preservatives (parabens), and endocrine disruptors ranged from less than 0.1 to 4310.8 ng L^-1. Regardless of the type of biological treatment process such as MLE, A2O, and MBR, the majority of pharmaceuticals (except lincomycin, diclofenac, iopromide, and carbamazepine), parabens (except Methyl paraben), and endocrine disruptors were removed by more than 80%. However, the removal efficiencies of certain MPs such as atrazine, DEET, perfluorinated compounds (except PFHxA), nitrosamines, and corrosion inhibitors were relatively low or their concentration even increased after treatment. The results of statistical analysis reveal that there is no significant geographical difference in the removal efficacy of MPs, but there are temporal seasonal variations in all WWTPs.

• 한방비만학회지
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• 제22권2호
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• pp.93-101
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• 2022

Objectives: This study aimed to observe the anti-diabetic effect and underlying mechanisms of Galgunhwanggumhwangryun-tang (GHH; Gegen-Qinlian-decoction) in the C2C12 myotubes. Methods: GHH (1.0 mg/ml) or metformin (0.75 mM) or insulin (100 nM) were treated in C2C12 myotubes after 4 days differentiation. The glucose uptake was assessed by 2-[N-(7-160 nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose uptake by C2C12 cells. The expression of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation AMPK (pAMPK) were measured by western blot. We also evaluated gene expression of glucose transporter type 4 (Slc2a4, formerly known as GLUT4), glucokinase (Gk), carnitine palmitoyltransferase IA (Cpt1a), nuclear respiratory factors 1 (Nrf1), mitochondrial transcription factor A (Tfam), and peroxisome proliferator-activated receptor γ coactivator 1α (Ppargc1a) by quantitative real-time polymerase chain reaction. Results: GHH promoted glucose uptake in C2C12 myotubes. The expression of AMPK protein, which plays an essential role in glucose metabolism, was increased by treatment with GHH. GHH treatment tended to increase gene expression of Slc2a4, Gk, and Nrf1 but was not statistically significant. However, GHH significantly improved Tfam and Ppargc1a gene expression in C2C12 myotubes. Conclusions: In summary, GHH treatment promoted glucose uptake in C2C12 myotubes. We suggest that these effects are associated with increased gene expression involved in mitochondrial biosynthesis and oxidative phosphorylation, such as Tfam and Ppargc1a, and increased expression of AMPK protein.

• 대한조현병학회지
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• 제22권2호
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• pp.21-33
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• 2019

Objectives: The current study covers a secondary revision of the guidelines for the pharmacotherapy of schizophrenia issued by the Korean Medication Algorithm for Schizophrenia (KMAP-SCZ) 2001, specifically for co-existing symptoms and antipsychotics-related side-effects in schizophrenia patients. Methods: An expert consensus regarding the strategies of pharmacotherapy for positive symptoms of schizophrenia, co-existing symptoms of schizophrenia, and side-effect of antipsychotics in patients with schizophrenia was retrieved by responses obtained using a 30-item questionnaire. Results: For the co-existing symptoms, agitation could be treated with oral or intramuscular injection of benzodiazepine or antipsychotics; depressive symptoms with atypical antipsychotics and adjunctive use of antidepressant; obsessive-compulsive symptoms with selective serotonin reuptake inhibitors and antipsychotics other than clozapine and olanzapine; negative symptoms with atypical antipsychotics or antidepressants; higher risk of suicide with clozapine; comorbid substance abuse with use of naltrexone or bupropion/varenicline, respectively. For the antipsychotics-related side effects, anticholinergics (extrapyramidal symptom), propranolol and benzodiazepine (akathisia), topiramate or metformin (weight gain), change of antipsychotics to aripiprazole (hyperprolactinemia and prolonged QTc) or clozapine (tardive dyskinesia) could be used. Conclusion: Updated pharmacotherapy strategies for co-existing symptoms and antipsychotics-related side effects in schizophrenia patients as presented in KMAP-SCZ 2019 could help effective clinical decision making of psychiatrists as a preferable option.

• Korean Circulation Journal
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• 제53권7호
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• pp.425-451
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• 2023

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, longterm anticoagulants are recommended according to the CHA₂DS₂-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.

• 한국식품영양과학회지
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• 제43권11호
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• pp.1658-1664
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• 2014

본 연구에서는 고지방식이와 streptozotocin으로 유도된 제2형 당뇨 마우스에서 새싹추출물의 항당뇨 효과를 살펴보았다. 제2형 당뇨 유도 후 4주 동안의 체중 변화를 관찰한 결과 새싹추출물군과 메트포민군에서 유의한 체중 감소 변화가 나타났으며, 식이섭취량에 따른 변화는 모든 실험군 간의 차이가 없었다. 공복혈당은 고지방식이군의 경우 실험종료일까지 지속적으로 상승하였고, 이와 대조적으로 새싹추출물과 메트포민군의 경우 실험 2주째부터 감소하여 실험 종료 4주째에서는 고지방식이군보다 유의적으로 감소하였다. 경구 내당능 검사는 포도당 섭취 후 60분, 90분, 120분에서 새싹추출물과 메트포민군이 고지방식이군보다 유의적으로 감소하였으며, 인슐린 내성 검사는 120분에서 새싹추출물과 메트포민군이 고지방식이군보다 유의성 있게 감소하였다. 혈중 지질 농도 변화에서 총콜레스테롤, 중성지방 그리고 LDL 콜레스테롤 농도는 고지방식이군에 비해 새싹추출물과 메트포민군에서 유의적으로 감소하였고, HDL 콜레스테롤 농도는 고지방식이군에 비해 새싹추출물과 메트포민군에서 증가하였다. 간독성의 지표인 glutamate oxaloacetate transaminase와 glutamate pyruvate transaminase 효소 활성도는 메트포민투여군과 고지방식이군을 제외한 실험군들 간에 유의성이 나타나지 않았다. 혈중 인슐린과 렙틴 농도는 고지방식이군에 비해 새싹추출물과 메트포민군에서 유의적으로 감소하였다. 이상의 결과를 바탕으로 새싹추출물은 제2형 당뇨 마우스에서 체중을 감소시키고 혈중지질 대사 이상을 조절하면서 인슐린 저항성을 감소시켜 혈당을 개선하므로 항당뇨 효과가 있는 우수한 식품 소재로서의 개발 가능성을 시사하고 있다.

• 생명과학회지
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• 제28권6호
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• pp.671-680
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• 2018

돼지감자 농축액(JA, 50%)에 명월초(12.5%), 여주(12.5%), 울금(12.5%) 추출물이 혼합된 돼지감자 복합물(JAP)을 streptozotocin (STZ)으로 당뇨 유발된 흰쥐에 4주간 급이하였을 때 혈당강하 및 지질개선에 미치는 영향을 분석하였다. 실험군은 정상군(Normal), 당뇨 대조군(Diabetic), 당뇨 유발된 흰쥐에 명월초 추출물 급이군(D-GPE), 돼지감자 복합물 급이군(0.5 g/kg, D-JAP1; 1.5 g/kg, D-JAP2), 돼지감자 농축액 급이군(D-JA) 및 메타포민 급이군(D-MET)으로 구분하였다. 실험사육 4주 동안 혈당 변화는 D-JAP2군 및 D-MET군에서 3주간 실험식이 급이 후 두드러진 감소현상을 보였다. 혈청 인슐린 함량은 실험식이의 급이에 따른 유의차가 없었으나, HOMA-IR값은 당뇨 대조군에 비해 실험식이 급이군에서 유의적으로 감소되었다. 혈청의 AST 및 ALT 활성은 D-JAP1군에서 가장 낮았다. 혈청의 총 지질 및 중성지방 함량은 당뇨 대조군에 비해 시료 급이군에서 유의적으로 감소되었으며, HDL-콜레스테롤 함량은 당뇨 대조군에 비해 D-GPE, D-JAP1 및 D-JAP2군에서 유의적으로 증가되었다. 간 조직 중 중성지방 함량은 당뇨 대조군에 비해 D-GPE, D-JAP1 및 D-JAP2군에서 유의적으로 감소되었으며, 지질과산화물의 함량은 당뇨 대조군에 비해 D-JAP1 및 D-JAP2군에서 유의적으로 감소되었다. 간 조직의 SOD 및 catalase 수준은 당뇨 대조군에 비해 D-GPE, D-JAP1 및 D-JAP2군에서, GSH-Px 수준은 모든 실험식이 급이군에서 유의적으로 증가되었다. 이상의 결과에서 돼지감자 복합물은 돼지감자 농축액에 비해 혈당강하 및 당뇨로 인한 지질개선에 효과적인 것으로 판단된다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2007년도 추계 학술대회
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• pp.57-58
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• 2007

Purpose: Ginseng is a well-known medical plant used in traditional Oriental medicine. Korean red ginseng (KRG) has been known to have potent biological activities such as radical scavenging, vasodilating, anti-tumor and anti-diabetic activities. However, the mechanism of the beneficial effects of KRG on diabetes is yet to be elucidated. The present study was designed to investigate the anti-diabetic effect and mechanism of KRG extract in C57BL/KsJ db/db mice. Methods: The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. During the experiment, body weight and blood glucose levels were measured once every week. At the end of treatment, we measured Hemoglobin A1c (HbA1c), blood glucose, insulin, triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). Morphological analyses of liver, pancreas and white adipose tissue were done by histological observation through hematoxylin-eosin staining. Pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. To elucidate an action of mechanism of KRG, DNA microarray analyses were performed, and western blot and RT-PCR were conducted for validation. Results: Compared to the DC group mice, body weight gain of PIO treated group mice showed 15.2% increase, but the other group mice did not showed significant differences. Compared to the DC group, fasting blood glucose levels were decreased by 19.8% in RGL, 18.3% in RGH, 67.7% in MET, 52.3% in GPZ, 56.9% in PIO-treated group. With decreased plasma glucose levels, the insulin resistance index of the RGL-treated group was reduced by 27.7% compared to the DC group. Insulin resistance values for positive drugs were all markedly decreased by 80.8%, 41.1% and 68.9%, compared to that of DC group. HbA1c levels in RGL, RGH, MET, GPZ and PIO-treated groups were also decreased by 11.0%, 6.4%, 18.9%, 16.1% and 27.9% compared to that of DC group, and these figure revealed a similar trend shown in plasma glucose levels. Plasma TG and NEFA levels were decreased by 18.8% and 16.8%, respectively, and plasma adiponectin and leptin levels were increased by 20.6% and 12.1%, respectively, in the RGL-treated group compared to those in DC group. Histological analysis of the liver of mice treated with KRG revealed a significantly decreased number of lipid droplets compared to the DC group. The control mice exhibited definitive loss and degeneration of islet, whereas mice treated with KRG preserved islet architecture. Compared to the DC group mice, KRG resulted in significant reduction of adipocytes. From the pancreatic islet double-immunofluorescence staining, we observed KRG has increased insulin production, but decreased glucagon production. KRG treatment resulted in stimulation of AMP-activated protein kinase (AMPK) phosphorylation in the db/db mice liver. To elucidate mechanism of action of KRG extract, microarray analysis was conducted in the liver tissue of mice treated with KRG extract, and results suggest that red ginseng affects on hepatic expression of genes responsible for glycolysis, gluconeogenesis and fatty acid oxidation. In summary, multiple administration of KRG showed the hypoglycemic activity and improved glucose tolerance. In addition, KRG increased glucose utilization and improved insulin sensitivity through inhibition of lipogenesis and activation of fatty acid $\beta$-oxidation in the liver tissue. In view of our present data, we may suggest that KRG could provide a solid basis for the development of new anti-diabetic drug.