• Journal of Ginseng Research
• /
• 제36권2호
• /
• pp.153-160
• /
• 2012

Panax ginseng has long been used as a traditional herbal medicine. More recently, it has received attention for its anti-diabetic and anti-obesity effects in humans and in animal models of type 2 diabetes. In the present study, we tested the hypoglycemic effects of ginseng berry extract in beta-cell-deficient mice and investigated the mechanisms involved. Red (ripe) and green (unripe) berry extracts were prepared and administered orally (100 or 200 mg/kg body weight) to streptozotocin-induced diabetic mice daily for 10 wk. The body weight was measured daily, and the nonfasting blood glucose levels were measured after 5 and 10 wk after administration. Glucose tolerance tests were performed, and the serum insulin levels were measured. The proliferation of beta-cells was measured in vitro. The administration of red or green ginseng berry extract significantly reduced the blood glucose levels and improved the glucose tolerance in beta-cell deficient mice, with the higher doses resulting in better effects. Glucose-stimulated insulin secretion was significantly increased in berry extract-treated mice compared with streptozotocin-induced diabetic control mice. Treatment with ginseng berry extract increased beta-cell proliferation in vitro. Both red berry and green berry extracts improved glycemic control in streptozotocin-induced diabetic mice and increased insulin secretion, possibly due to increased beta-cell proliferation. These results suggest that ginseng berry extracts might have beneficial effects on beta-cell regeneration.

• Molecular & Cellular Toxicology
• /
• 제3권4호
• /
• pp.292-298
• /
• 2007

Zinc plays indispensable roles in metabolism, including cell growth, apoptosis, proliferation and differentiation. Kidneys are target organs for various regulators of mineral metabolism, and play a key role in zinc balance. To investigate the zinc uptake efficiency, we examined the zinc uptake and accumulation level in vivo and in vitro study. Plasma zinc concentration was peaked out at 1 hr after oral zinc administration. The renal zinc level was peaked out at 12 hr after oral zinc administration, and it was the highest in 40 mg/kg Zn-Asp administrated group in comparison with other groups. In addition, the m-RNA expression level of zinc transporter-1 (ZnT-1), zinc transporter-2 (ZnT-2) and high-affinity L-aspartate transporter (EAAT-3) in Zn-Asp administered group were increased compared with control groups and $ZnSO_4$ group. In order to investigate the intracellular zinc uptake mechanism, we performed the in vitro study by using human embryonic kidney cell line, HEK 293. Intracellular zinc level was peaked out at 3 hr after zinc treatment. In the same way, the mRNA expression level of ZnT-1 and EAAT-3 were increased compared with control group. This study showed that Zn-Asp is effective the zinc uptake into the kidney by increasing the zinc transporter expression.

• Journal of Pharmaceutical Investigation
• /
• 제31권3호
• /
• pp.143-150
• /
• 2001

Butyrolactone ester of ceftezole (CFZ-BL) was synthesized by esterification of ceftezole (CFZ) with ${\alpha}-bromo-{\gamma}-butyrolactone$. The synthesis was confirmed by spectroscopic analysis. CFZ-BL was more lipophilic than CFZ when the lipophilicity was assessed by partition coefficients between n-octanol and water at various pH. CFZ-BL itself did not show any microbiological activity in vitro, but serums taken after oral administration of CFZ-BL showed substaintial microbiological activity indicating that CFZ-BL is converted to microbiologically active metabolite, probably CFZ, in the body. The conversion was confirmed by in vitro incubation study, in which CFZ-BL was incubated in some body tissues of rabbit. Liver homogenate showed fastest conversion of CFZ-BL among the tissues tested (blood and intestine). Thus, CFZ-BL appeares to be rapidly metabolized in the liver to CFZ following oral administration. The metabolism process appears to be hydrolysis of the ester to CFZ, the parent drug of CFZ-BL. In vivo metabolism of CFZ-BL to CFZ was confirmed by analying CFZ by HPLC. CFZ concentration in the serum samples taken after oral administration of CFZ-BL were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-BL, a prodrug of CFZ, was 1.45-fold higher than that of CFZ in rabbits possibly due to enhanced lipophility and absorption of the prodrug.

• 약학회지
• /
• 제42권4호
• /
• pp.414-421
• /
• 1998

In order to compare the suppressive effect of quercetin and its glycosides, such as quercitrin (quercetin-3-rhamnoside), isoquercitrin (quercetin-3-glucoside), hyperin (querceti n-3-galactoside)and rutin (quercetin-3-rhamnosyl glucoside), on the genotocicity by benzo(a)pyrene(B(a)P), in vitro sister chromatid exchange(SCE) test using mouse spleen lymphocytes and in vivo micronucleus test using mouse peripheral blood were performed. B(a)P-induced SCEs in vitro were slightly decreased by the simultaneous treatment of quercetin and its glycosides, although there was no significant decrease. On the other hand, MNU induced micronucleated reticulocytes(MNRL7s) in vivo were significantly decreased with a dose-dependent manner in all compounds tested. However, there were no differences between quercetin aglycone and glycosides in the suppressive effects under experimental condition of this study. To elucidate, the action mechanism of quercetin aglycone and its glycosides against B(a)P-induced genotoxicity, the assay of DNA binding with B(a)P was studied. Quercetin aglycone and its glycosides inhibited B(a)P metabolism in the presence of S-9 mix and decreased the B(a)P/DNA binding in the calf thymus DNA with S-9 mix. These results suggest that antigenotoxicity of quercetin antiglycosides on B(a)P-induced genotoxicity is due to decrease of DNA binding with B(a)P through the inhibition of metabolism with B(a)P in the calf thymus DNA. Therefore, quercetin and its glycosides may act as an antigenotoxicity agent and may be useful as a chemopreventive agent of polycyclic aromaic hydrocarbons like B(a)P.

• Journal of Microbiology and Biotechnology
• /
• 제34권2호
• /
• pp.249-261
• /
• 2024

New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.

• Asian-Australasian Journal of Animal Sciences
• /
• 제2권1호
• /
• pp.1-6
• /
• 1989

Nutritive values and fermentation rates of rice straw treated with 3% anhydrous and 3% aqueous ammonia were evaluated both in vitro and sheep metabolism trials. Daily gain, feed efficiency and feed cost per gain were also determined with growing Holstein bulls fed anhydrous and aqueous ammonia treated rice straw. Crude protein was increased 2.4 fold and NDF was decreased 6.5%, but ADF and cellulose were not different between untreated and ammonia treated rice straw. An average of 35.5% of total added ammonia-N retained in the rice straw and other 64.5% was not retained in the rice straw. Ammonia treatment increased in vitro DM, NDF, ADF and cellulose digestibilities by 44.8%, 43.3%, 49.4% and 42.4%, respectively, and fermentation rates by 63.3%, 132.4%, 49.4% and 42.4%, respectively. In sheep metabolism trials, DM digestibilities of rice straw treated with anhydrous and aqueous ammonia were increased 22% and 36%, respectively, and digestible DM intakes by 48% and 70%, respectively in sheep fed anhydrous and aqueous ammonia treated rice straw over untreated rice straw. Rumen ammonia and blood urea were considerably higher in sheep fed ammonia treated rice straw than sheep fed untreated rice straw. Daily gain of Holstein bulls was increased 20.8% and 29.9% and rice straw intakes were increased 28.4% and 44.3% in anhydrous and aqueous ammonia treated rice straw over untreated rice straw. Feed conversion was improved 9.5% and 10.3% and feed cost/gain was reduced 7.1% and 9.2% respectively in anhydrous and aqueous ammonia treated rice straw group as compared with untreated rice straw group.

• 한국동물학회지
• /
• 제17권3호
• /
• pp.107-116
• /
• 1974

생쥐 小腸의 deoxycytidine-2-$^14 C$ (CdR-2-$^14 C$)와 deoxyuridine-2-$^14 C$ (UdR-2-$^14 C$)의 代謝를 관계酵素의 熱處理에 대한 영향과 관련해서 in vitro에서 고찰하였다. CdR-2-$^14 C$는 CdR-aminohydrolase의 作用에 의해서 먼저 nucleoside level에 급속히 deamination된 후, nucleosidase의 作用에 의해 uracil로 分解된다. 생쥐 小腸에서는 nucleosidase 가 CdR과 CR에는 親和力이 없기 때문에 이들 cytosine nucleoside의 N-pentose 結合을 分解하지 못하는 것으로 보인다. CdR-aminohydrolase는 $80^\\circ C$ 높은 不活性化溫度를 나타냈으며, 이에 반해서 nucleosidase는 $60^\\circ C$에서 不活性化가 되었다. 品種이 다른 생쥐의 여러 組織에 있는 CdR-aminohydrolase는 모두 $80^\\circ C$에서 不活性化됨이 관찰되었으나, 토끼 組織에서는 $80^\\circ C$에서도 不活性化가 일어나지 않는 점으로 미루어 不活性化溫度에는 "屬"特異性이 있는 것으로 짐작된다. 哺乳類의 分化된 組織에서 CdR-aminohydrolase 가 出現하는 生物學的 意味는 주로 分解過程과 有關한 것으로 생각된다. 것으로 생각된다.

• Journal of Pharmaceutical Investigation
• /
• 제26권1호
• /
• pp.29-32
• /
• 1996

In vivo and in vitro skin permeation of $recombinant^{125}$ I-EGF through normal, stripped and the first degree burn skin were studied. The in vitro skin permeation rate through the first degree burn skin $(296\;cpm/cm^2/hr)$ and the stripped skin $(1131\;cpm/cm^2/hr)$ were 3.5 times and 13 times higher, respectively, as compared with the one through normal skin. In vivo absorption study with the first degree burn skin, the peak concentration of EGF in the skin was achieved at 1-3 hr and decreased afterward up to 8 hr with an elimination constant of $1.31{\times}10^{-3}\;g/ml/hr$. To investigate the higher elimination rate of EGF in burn skin, binding and metabolism studies were conducted. No significant metabolism of EGF in burn skin $(100^{\circ}C,\;5-second\;burning)$ was observed. With the presence or unlabelled-EGF $^{125}I-EGF$ permeation through the burn skin showed higher permeation rate than the one without unlabelled-EGF. The result nay indicate that EGF-receptor binding play a role in determining the skin permeation rate.

• Nutrition Research and Practice
• /
• 제18권4호
• /
• pp.479-497
• /
• 2024

BACKGROUND/OBJECTIVES: Activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can protect against obesity and obesity-related metabolic conditions. Cryptotanshinone (CT) regulates lipid metabolism and significantly ameliorates insulin resistance. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a receptor for cellular energy metabolism, is believed to regulate brown fat activity in humans. MATERIALS/METHODS: The in vivo study included high-fat-fed obese mice administered orally 200/400 mg/kg/d CT. They were evaluated through weight measurement, the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), cold stimulation test, serum lipid (total cholesterol, triglycerides, and low-density lipoprotein) measurement, hematoxylin and eosin staining, and immunohistochemistry. Furthermore, the in vitro study investigated primary adipose mesenchymal stem cells (MSCs) with incubation of CT and AMPK agonists (acadesine)/inhibitor (Compound C). Cells were evaluated using Oil Red O staining, Alizarin red staining, flow cytometry, and immunofluorescence staining to identify and observe the osteogenic versus adipogenic differentiation. Quantitative real-time polymerase chain reaction and the Western blot were used to observe related gene expression. RESULTS: In the diet-induced obesity mouse model mice CT suppressed body weight, food intake, glucose levels in the IPGTT and IPTT, serum lipids, the volume of adipose tissue, and increased thermogenesis, uncoupling protein 1, and the AMPK pathway expression. In the in vitro study, CT prevented the formation of lipid droplets from MSCs while activating brown genes and the AMPK pathway. AMPK activator enhanced CT's effects, while the AMPK inhibitor reversed the effects of CT. CONCLUSION: CT promotes adipose tissue browning to increase body thermogenesis and reduce obesity by activating the AMPK pathway. This study provides an experimental foundation for the use of CT in obesity treatment.

• Journal of Animal Science and Technology
• /
• 제44권6호
• /
• pp.757-768
• /
• 2002

본 연구는 반추가축에 있어 통옥수수를 주로 이용한 조사료 무급여사료의 발효특징을 알아 보기 위하여 실시하였다. 대조구는 steam- flaked corn으로 구성된 농후사료 (80%)와 볏짚(20%)을 혼합한 사료 SFCR)와 통옥수수와 면실피로 구성된 조사료 무급여사료(WC)를 사용하였다. 실험 1은 한우 반추위 미생물을 이용하여 in vitro 시험을 2처리 3반복 시험을 배양시간 48시간 동안 실시하였고, 실험 2는 한국재래산양을 이용한 반추위 내 발효 특성을 알아보기 위하여 in vivo 시험을 2처리 4반복 실험을 15일간 실시 하였으며, in sacco 시험은 2처리 3반복으로 시험을 3일간 실시하였다. 실험 1에서 SFCR구와 WC구 모두 반추위 적정 pH를 유지하였으며 처리간에 유의성은 없었으나 배양 4시간 대에 SFCR에서 다소 낮은 경향을 나타내었다. Gas 발생량은 SFCR구에서 유의적으로 높았으며(p<0.01), $NH_3$-N 농도는 WC구에서 다소 높은 경향을 나타내었다. Total VFA농도는 8시간대까지 WC구에서 유의성있게(p<0.01) 낮았고 이후 유의성은 없었으나 두 처리구 모두 점차적으로 증가하는 경향을 나타내었다. 전체 평균 Acetate 함량은 SFCR구에서 모두 유의적으로 높았으며(p<0.01), 전체배양시간에 동안 propionate 함량은 WC구에서 유의적으로 높았다(p<0.01). 건물소화율은 두 처리구 모두 유의적 차이가 없으나 SFCR구에서 다소 높은 경향을 보였다. 실험 2에서 두 처리구 모두 전체적으로 다소 낮은 pH를 보였으며 유의적 차이는 없었으나 SFCR구에서 다소 높은 경향을 보였다. 반추위 미생물단백질 함량은 SFCR구에서 유의하게 높았으나, $NH_3$-N 농도는 WC구에서 유의하여 높았다(p<0.01). Total VFA함량과 propionate 함량도 WC구에서 유의하게 높았으나(p<0.01), acetate 함량은 유의성은 없었고 WC구에서 다소 높았다. 전체적인 Lactate 함량은 두 처리구에서 유의적 차이를 보였으나(p<0.01) 산독증 발병 수준 이하의 함량을 나타내었다. Nylon bag에 의한 한국재래산양 반추위 내 in sacco 건물소실율은 SFCR에서 유의적으로 높은 경향을 나타내었다(p<0.01). 이상의 시험 결과에 의하면 농후사료 80%와 볏짚 20%로 구성된 SFCR 사료가 반추위 내 발효 특성에 있어서 통옥수수와 면실피로 구성된 조사료 무급여사료와 큰 차이가 없었으며, 반면 조사료 무급여사료는 사료 가공비용 감소에 의해 경제성이 증가할 것이다.