• Journal of Korean Neurosurgical Society
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• 제63권4호
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• pp.433-443
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• 2020

Objective : Osteoporosis is a disease of unbalanced bone metabolism that results in low bone mineral density with increased bone fragility and propensity for fractures. The increased rate of bone fracture due to osteoporosis places a significant burden on public health care expenditures. Therefore, numerous studies have been designed and performed to identify the drugs or health foods that can improve the bone quality or quantity. This study was designed to evaluate and analyze the therapeutic effects of rutin on histomorphometric values of the spine and femur in an osteoporotic mouse model induced by bilateral ovariectomy. Methods : Thirty female ICR mice (8 weeks old) underwent either a sham operation (only abdominal incision, sham group, n=10) or bilateral ovariectomy (n=20). The ovariectomized (OVX) animals were randomly divided into two groups : untreated OVX group (OVX-C, n=10), or rutin-administered group (OVX-R, n=10). The OVX-C group received weight-adjusted doses of saline vehicle and the OVX-R group received 50 mg/kg of rutin intraperitoneally, starting 1 day after surgery. At 4 and 8 weeks after surgery, serum estrogen, osteocalcin, alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX-1) were analyzed. Interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α were also analyzed. Bone histomorphometric parameters of the 4th lumbar vertebra and femur were determined by micro-computed tomography. Results : In OVX-C group, ALP, osteocalcin, CTX-1, IL-1β, IL-6, and TNF-α levels were significantly increased at 4 and 8 weeks compared to sham operation group. Rutin administration after OVX statistically significantly reduced ALP, CTX-1, IL-1β, IL-6, and TNF-α levels at 4 and 8 weeks. Rutin administration also improves bone histomorphometric parameters including trabecular bone volume fraction, trabecular thickness, and trabecular number. Trabecular separation was also decreased in OVX-R group compared to OVX-C group. Conclusion : The present study demonstrated that rutin has therapeutic effects on improving bone histomorphometric values in an OVX mouse model. The improvement in histomorphometric values may be associated with the reduction of osteoclastic activity via inhibition of IL-1β, IL-6, and TNF-α. In future studies, the mechanism for the effect of rutin on osteoporosis should be demonstrated more clearly to use rutin in human osteoporosis.

• 약학회지
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• 제40권4호
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• pp.428-437
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• 1996

The in vitro and in vivo antibacterial activities of a new fluoroquinolone, DWP20364(1-cyclopropyl-5-amino-6,8-difluoro-7-(2,7-diazabicyclo[3.3.0]oto-4-ene-7-yl)-1 ,4-di-hydro-4-oxoquinoline-3-carboxylic acid) were evaluated in comparison with those of ciprofloxacin(CPFX), sparfloxacin(SPFX) and ofloxacin(OFLX). DWP20364 was more potent than CPFX and OFLX against Staphylococcus spp., Streptococcus spp. and Enterococcus faecium MD8b and it was similarly or slightly less active than CPFX against Escherichia spp. and Pseudomonas spp.. For MRSA and OFLX resistant strains (Staphylococcus spp.(14),Enterococcus spp.(4), Acinetobacter spp.(2), Pseudomonas spp.(9), Klebsiella spp.(2) and Serratia spp.(6)),DWP20364(MICs for 90% of strains,0.025 and 12.5${\mu}$g/ml, respectively) was 4 to 32 folds more potent than SPFX and CPFX. The activity of DWP20364 decreased moderately in the presence of 5mM $Mg^{2+}$. However, various pHs and the concentrations of various serum had no effect on the activity of DWP20364. DWP20364 possessed a bacteriocidal effect at the 1MIC against gram positive and gram negative strains. The protective effect of DWP20364 against systemic infections in mice caused by S. aureus Smith or S. aureus L2379 was superior to that of CPFX and SPFX but it was less active than that of CPFX against infection by P. aeruginosa E-2.

• 약학회지
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• 제45권1호
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• pp.64-70
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• 2001

Protein-polysaccharide fractions, PJ-3 and PJ-4, were prepared from mycelial culture filtrate of an insect-born fungus, Paecilomyces japonica DGUM 32001, and subjected to a flow cytometrical analysis for their vivo antitumor and immunomodulating activity in ICR mice. When i.p. injected once daily for semen days at 100 mg/kg, PJ-4 exerted a strong antitumor activity showing the growth inhibition ratio of 85.1% against i.p. implanted sarcoma 180 cells, while PJ-3 showed only a weak activity. Moreover, PJ-4 signiscantly increased the expression level of CD25 (IL-2R $\alpha$-chain) as well as forward scatter (FSC) values of splenic CD8$^{8}$ T cells. It is also noteworthy that PJ-4 strongly induced the peritoneal exudate cells in the same experiment. In an in vitro study, PJ-4 slightly inhibited the growth of sarcoma 180 cells at the concentration of 50$\mu$g/ml or higher. These results strongly suggest that PJ-4 might exert its antitumor activity through immunostimulation as well as direct inhibitory activity on the tumor cells.

• 대한화장품학회지
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• 제30권2호
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• pp.263-278
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• 2004

Ursolic acid (UA)와 oleanolic acid (ONA)는 pentacyclic triterpenoid 성분으로 많은 식물들과 의학, 임상용 허브 등에 존재한다. 이런 UA나 ONA는 free acid 형태로 나타나거나, 1개 이상의 당이 연결된 aglycone으로 triterpenoid 배당체를 구성한다. UA와 ONA는 유사한 구조를 가지며 비슷한 약리효과를 나타내는 것으로 알려져 있다. 최근 연구에 의하면, 항종양, 간보호, 항염증, 함암 및 항균역할을 하는 것으로 보고되고 있다. 우리는 급성 장벽손상 및 정상 무모쥐 피부에 미치는 영항에 대한 연구를 했다. UA와 ONA의 피부장벽 회복에 대한 효과를 평가하기 위해서, 8-12주 된 무모쥐를 테이프 스트리핑 한 후, 한쪽 옆구리에 0.01 -0.1mg/mL 농도로 UA 또는 ONA를 국소도포하고 한쪽에는 vehicle만 처치하여 경표피 수분손실(TEWL)량을 측정하였다. UA (0.1mg/mL)와 ONA (0.5mg/mL)를 처리한 그룹의 회복률이 vehicle 처리군에 비해 테이프 스트리핑 후 6 h에서 20% 이상 증가했다.(p < 0.01). 또한 UA와 ONA의 급성장벽손상 회복과 함께 정상 피부장벽 기능에 미치는 영향을 확인하였다. 정상 피부장벽 기능에 대한 효과를 알아보기 위해, 보습력과 경표피 수분손실량을 UA와 ONA (각 2 mg/mL)를 처리한 1주째와 3주째에 측정하였고, 또한 표피와 진피의 상태를 확인하기 위해서 현미경 관찰을 실시하였다. 두 시료를 1주째부터 vehicle 도포군과 비교, 경표피 수분손실 없이 보습력을 증가시켰다(p < 0.005). 전자현미경 사진을 통해 UA와 ONA 도포에 따라 분비되는 층판소체의 증감(ONA$\geq$UA$\geq$vehicle)과 지질이중막 구조 이상 여부를 확인하였다 Light microscopy를 통해 각질층의 두께가 약간 증가함을 보였으며, 특히 표피두께 강화와 편평 현상이 나타났다(UA < ONA < Vehicle). 우리는 또한 UA와 ONA가 PPAR $\alpha$를 통해 표피 각질세포의 분화를 촉진함을 관찰하였다. Western blotting 실험을 통해, 표피 각질세포 분화와 관련된 involucrin, loricrin, filaggrin의 단백질 발현이 최소한 2-3배 이상 증가함을 HaCaT 세포에 UA와 ONA(각 10$\mu$M)를 24 h 처리 후 실험 결과로 확인할 수 있었다. 이런 결과를 토대로 UA와 ONA가 장벽기능 향상뿐 아니라 PPAR $\alpha$를 통한 표피 각질세포 분화를 유도함을 제시할 수 있었다. Masson-trichrome과 elastic fiber 염색법을 통해서, UA와 ONA 도포에 따른 콜라겐섬유의 비후(thickening)와 엘라스틴섬유의 신장(elongation)을 조직 사진으로 확인하였다. 시험관 시험을 통한 콜라겐 및 엘라스틴 합성실험과 엘라스틴 분해효소에 대한 저해능 평가를 통해 진피에 대한 UA와 ONA의 효과를 확인할 수 있었다. 이런 결과들을 토대로 UA와 ONA는 피부장벽기능 유지뿐 아니라, 진피 내 콜라겐섬유와 엘라스틴섬유 합성을 촉진하는 것을 관찰할 수 있었다. 이 결과로부터, UA와 ONA는 장벽기능 및 진피강화에 관여할 수 있는 기능성 화장품으로의 응용에 적절한 후보 물질로 제안할 수 있겠다.

• Biomolecules & Therapeutics
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• 제28권2호
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• pp.152-162
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• 2020

Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.

• 분석과학
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• 제34권5호
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• pp.193-201
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• 2021

We have demonstrated a sensitive analytical method of measuring oleracone D in mouse plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oleracone D and oleracone F (internal standard) in mouse plasma samples were processed using a liquid-liquid extraction method with methyl tertbutyl ether, resulting in high and reproducible extraction recovery (80.19-82.49 %). No interfering peaks around the peak elution time of oleracone D and oleracone F were observed. The standard calibration curves for oleracone D ranged from 0.5 to 100 ng/mL and were linear with r² of 0.992. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. The pharmacokinetics of oleracone D following intravenous and oral administration of oleracone D at doses of 5 mg/kg and 30 mg/kg, respectively, were investigated. When oleracone D was intravenously injected, it had first-order elimination kinetics with high clearance and volume of distribution values. The absolute oral bioavailability of this compound was calculated as 0.95 %, with multi-exponential kinetics. The low aqueous solubility and a high oral dose of oleracone D may explain the different elimination kinetics of oleracone D between intravenous and oral administration. Collectively, this newly developed sensitive LC-MS/MS method of oleracone D could be successfully utilized for investigating the pharmacokinetic properties of this compound and could be used in future studies for the lead optimization and biopharmaceutic investigation of oleracone D.

• Mass Spectrometry Letters
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• 제12권1호
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• pp.21-25
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• 2021

We aimed to develop and validate a sensitive analytical method of nannozinone A, active metabolite of Nannochelins A extracted from the Myxobacterium Nannocytis pusilla, in mouse plasma using a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Mouse plasma samples containing nannozinone A and 13C-caffeine (internal standard) were extracted using a liquid-liquid extraction (LLE) method with methyl tert-butyl ether. Standard calibration curves were linear in the concentration range of 1 - 1000 ng/mL (r2 > 0.998) with the inter- and intra-day accuracy and precision results less than 15%. LLE method gave results in the high and reproducible extraction recovery in the range of 78.00-81.08% with limited matrix effect in the range of 70.56-96.49%. The pharmacokinetics of nannozinone A after intravenous injection (5 mg/kg) and oral administration (30 mg/kg) of nannozinone A were investigated using the validated LC-MS/MS analysis of nannozinone A. The absolute oral bioavailability of nannozinone A was 8.82%. Plasma concentration of nannozinone A after the intravenous injection sharply decreased for 4 h but plasma concentration of orally administered nannozinone A showed fast distribution and slow elimination for 24 h. In conclusion, we successfully applied this newly developed sensitive LC-MS/MS analytical method of nannozinone A to the pharmacokinetic evaluation of this compound. This method can be useful for further studies on the pharmacokinetic optimization and evaluating the druggability of nannozinone A including its efficacy and toxicity.

• Nutrition Research and Practice
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• 제17권2호
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• pp.192-205
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• 2023

BACKGROUND/OBJECTIVES: It is known that the renin-angiotensin system (RAS) in the brain could regulate cognitive functions as well as blood pressure. Inhibition of RAS for the improvement of cognitive function may be a new strategy, but studies so far have mostly reported on the effects of RAS inhibition by drugs, and there is no research on cognitive improvement through RAS inhibition of food ingredients. Therefore, this study investigated the effect of curcumin on blood pressure and cognitive function and its related mechanism in spontaneously hypertensive rat/Izm (SHR/Izm). MATERIALS/METHODS: Six-week-old SHR/Izm rats were divided into 5 groups: control group (CON), scopolamine group (SCO, drug for inducing cognitive deficits), positive control (SCO and tacrine [TAC]), curcumin 100 group (CUR100, SCO + Cur 100 mg/kg), and curcumin 200 group (CUR200, SCO + Cur 200 mg/kg). Changes in blood pressure, RAS, cholinergic system, and cognitive function were compared before and after cognitive impairment. RESULTS: The SCO group showed increased blood pressure and significantly reduced cognitive function based on the y-maze and passive avoidance test. Curcumin treatments significantly improved blood pressure and cognitive function compared with the SCO group. In both the CUR100 and CUR200 groups, the mRNA expressions of angiotensin-converting enzyme (ACE) and angiotensin II receptor type1 (AT1), as well as the concentrations of angiotensin II (Ang II) in brain tissue were significantly decreased. The mRNA expression of the muscarinic acetylcholine receptors (mAChRs) and acetylcholine (ACh) content was significantly increased, compared with the SCO group. CONCLUSIONS: The administration of curcumin improved blood pressure and cognitive function in SCO-induced hypertensive mice, indicating that the cholinergic system was improved by suppressing RAS and AT1 receptor expression and increasing the mAChR expression.

• 한국식품위생안전성학회지
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• 제20권2호
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• pp.118-122
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• 2005

체내 면역 증강정을 관찰하기 위하여 체내 임파구의 활성 및 증가 여부를 3개월간 의뢰한 물질인 Immu-Forte EX, Immu-Forte 된장고추장, Immu-Forte A, Immu-Forte를 투여한 후, flowcyometry 및 sandwitch ELISA를 이용하여 측정하였다. 본 실험의 실험 기간 중에 동물의 질병이나 감염에 의한 면역학적인 변화가 있었는지를 확인하기 위하여 혈액학적인 검사를 실시하였으며, 혈액학적인 검사에서 Alkaline phosphatase, T protein, Albumin, Creatine, ALT, AST, Total bilirubin, Potasium을 검사해 본 결과 대조군과 비교 했을때 투여군 전군에서 정상적인 범위내 수치를 나타내는 것으로 나타났다. 이러한 결과로부터 본 실험에서 나온 결과는 질병이나 감염에 의한 것이 아닌 생체내에서의 면역성 증강에 의한 것으로 판단할수 있는 근거를 제공한다고 판단되어진다. 한편, 3개월간 장기 투여시 Immu-Forte EX, Immu-Forte 된장고추장, Immu-Forte A과 Immu-Forte 의 모든 물질은 전반적으로 면역 세포와 사이토카인의 수치를 유의적으로 증가시켰다 그러나, 3개월간 Immu-Forte EX를 투여 후 혈중콜레스테롤 수치를 검사해 본 결과 대조군$(118\pm24.4 mg/dL)$과 비교하였을때, 고용량$(126\pm7.7 mg/dL)$, 중간용량$(121\pm8.4 mg/dL)$, 저용량$(109\pm24.Smg/dL)$으로서 통계학적인 유의적 감소로는 보이지 않는다. 각각의 물질의 면역학적인 변화양상을 살펴보면 물질 동암 EX는 중간 농도군에서는 CD4 T 림파구, CD8 림파구, 대식세포, IL-12, IFN-r가 대조군에 비해서 유의적으로 증가했으며 떠농도에서는 전체 T 임파구, 전체 B 임파구, CD4 T 임파구, 대식세포, IL-2, IL4, IL-12가 대조군에 비해서 유의적으로 증가했다. 물질 Immu-Forte 된장고추장에서는 고농도에서는 CD4 T 임파구, IL-2, IL-4, IL-12가 유의적으로 증가했으며, 중간농도에서는 CD4 임파구, 대식세포, IL-2,IL-4,IL-12 가 유의적으로 증가했고, 저농도에서는 전체 T 임파구, CD4 T 임파구, IL-2, IL-4, IL-12가 유의적으로 증가했다. 물질 Immu-Forte A의 경우 고농도에서 대식세포,자연살해세포, IL-12가 중간농도에서는 전체 T임파구, CD4 T임파구, 대식세포, 자연살해세포, IL-2, IL-4, IL-12가 저농도에서는 자연살해세포가 유의적으로 증가했다. 물질 Immune-Forte f의 경우 고농도에서 전체 B 임파구, IL-4, IL-12가 중간농도에서 전체 T임파구, 전체 B임파구, CD4 T임파구, CD8 T 임파구, 대식세포, IL-2, IL-4, IL-12, IFN-r가 저농도에서는 자연살해세포, IL-12가 유의적으로 증가하였다. 이상과 같이 각각의 물질은 전반적으로 면역증강 효과가 있는 것으로 나타났으며 그 면역증강을 유도하는 세포나 사이토카인은 서로 정확히 일치하지 않는 것으로 보아 각각의 물질이 다른 기전을 통해서 면역증강을 유도하는 것으로 생각된다.

• Nutrition Research and Practice
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• 제12권3호
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• pp.199-207
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• 2018

BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.