• 대한한의학회지
• /
• 제26권3호
• /
• pp.188-203
• /
• 2005

Objectives : This study was designed to investigate the effects of Jayun-tang extract (JYT) on the change of cerebral hemodynamics [regional cerebral blood flow (rCBF), pial arterial diameter (PAD) and mean arterial blood pressure (MABP)] in normal and cerebral ischemic rats, na to determine the mechanisms of action of JYT. Methods : We investigated whether JYT inhibits lactate dehydrogenase activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. Results : 1. JYT significantly increased rCBF and PAD in a dose-dependent manner, but MABP was not changed by injecting JYT. These results suggested JYT significantly increased rCBF by dilating PAD. 2. The JYT-induced increase in rCBF was significantly inhibited from pretreatment with indomethacin (1mg/kg, i.p.), an inhibitor of cyclooxygenase and methylene blue $(10{\mu}g/kg, i.p.)$, an inhibitor of guanylate cyclase. 3. The JYT-induced dilation in PAD was significantly inhibited from pretreatment with indomethacin, but was increased by pretreatment with methylene blue. 4 The JYT-induced increase in MABP was reduced by pretreatment with indomethacin and methylene blue. 5. JYT significantly inhibited lactate dehydrogenase activity in neuronal cells. These results suggest that JYT prevented the neuronal death. 6. Both rCBF and PAD were significantly and stably increased by JYT $(10{\mu}g/kg,\;i.p.)$ during the Period or cerebral reperfusion, which contrasted with the findings of rapid and marked increase in the control group. 7. In cytokine production in the serum drawn from femoral artery 1hr after middle cerebral artery occlusion, the sample group showed significantly decreased production of $IL-1\beta$ and $TNF-\alpha$ as well as increased production of IL-10 and $TGF-\beta$ compared with rho control group. 8. In cytokine production in the serum drawn from femoral artery 1hr after reperfusion, the sample group showed significantly decreased production of $IL-1\beta$ and $TNF-\alpha$ as well as significantly increased production of IL-10 and $TGF-\beta$ compared with the control group. Conclusions : JYT mediated by cyclooxygenase had an inhibitive effect on brain damage by inhibiting lactate dehydrogenase activity, $IL-1\beta$ and $TNF-\alpha$ production, and by accelerating IL-10 and $TGF-\beta$ production. The author feels that JYT had anti-ischemic effects through the improvement of cerebral hemodynamics and inhibitive effects on brain damage.

• 생명과학회지
• /
• 제26권7호
• /
• pp.812-818
• /
• 2016

본 연구는 칼슘 배합 비율에 따른 초석잠이 scopolamine 치매유도 흰쥐의 기억손상 개선효과에 대하여 연구하였다. 칼슘 배합 비율별(S, 1CS, 5CS군)로 군을 나누어 Y자 미로와 수중미로를 통한 행동실험을 실시한 결과, Y자 미로 실험에서 5CS군이 N군과 비교하였을 때 유사한 수치를 보이며 공간 인지기능을 개선시켰고, 수중미로 실험 또한 CS군의 escape latency가 감소하여 N군과 유사한 수치를 보여 기억력 및 학습능력 개선에 효과적이라는 것을 알 수 있었다. 또한 아세틸콜린 함량과 아세틸콜린에스테라제의 활성을 측정한 결과, CS군은 아세틸콜린에스테라제의 활성을 저해함으로써 뇌 조직 내 신경전달물질인 아세틸콜린의 함량을 증가시켜 뇌 신경세포 활성화 효과를 통해 인지기능 개선 효과를 유도할 수 있을 것으로 사료된다. 해마를 병리조직학적으로 관찰한 결과, 앞선 결과와 유사하게 손상 정도가 심하여 많은 수의 응축된 신경세포가 관찰된 C군에 비하여 CS군은 응축된 신경세포 수가 현저하게 감소하여 신경세포 손상을 억제한 것으로 보인다. 따라서 칼슘 배합 비율에 따른 초석잠은 scopolamine 치매유도 흰쥐모델에서 기억력, 학습능력 및 인지능력 개선에 효과적으로 작용하는 천연물 유래 기능성 소재로 이용될 수 있을 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제17권5호
• /
• pp.393-403
• /
• 2013

Baicalein (BA), a plant-derived active flavonoid present in the root of Scutellaria baicalensis, has been widely used for the treatment of stress-related neuropsychiatric disorders including depression. Previous studies have demonstrated that repeated restraint stress disrupts the activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. The behavioral and neurochemical basis of the BA effect on depression remain unclear. The present study used the forced swimming test (FST) and changes in brain neurotransmitter levels to confirm the impact of BA on repeated restraint stress-induced behavioral and neurochemical changes in rats. Male rats received 10, 20, or 40 mg/kg BA (i.p.) 30 min prior to daily exposure to repeated restraint stress (2 h/day) for 14 days. Activation of the HPA axis in response to repeated restraint stress was confirmed by measuring serum corticosterone levels and the expression of corticotrophin-releasing factor in the hypothalamus. Daily BA administration significantly decreased the duration of immobility in the FST, increased sucrose consumption, and restored the stress-related decreases in dopamine concentrations in the hippocampus to near normal levels. BA significantly inhibited the stress-induced decrease in neuronal tyrosine hydroxylase immunoreactivity in the ventral tegmental area and the expression of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. Taken together, these findings indicate that administration of BA prior to the repeated restraint stress significantly improves helpless behaviors and depressive symptoms, possibly by preventing the decrease in dopamine and BDNF expression. Thus, BA may be a useful agent for the treatment or alleviation of the complex symptoms associated with depression.

• 대한핵의학회지
• /
• 제29권1호
• /
• pp.105-109
• /
• 1995

Tyrosine의 유도체인 [$^{123}I$]IMT를 각종 악성종양의 SPECT에 이용하기 위하여 표지시 반응조건과 뇌종양이식 백서에서의 체내 동태를 연구하여 다음과 같은 결과를 얻었다. AMT의 [$^{123}I$] 표지에 chloramine-T 보다 Iodobead를 이용하는 것이 훨씬 간편하고 수율이 높았으며, Iodobead 1개, AMT $200{\mu}g/100{\mu}L$ phosphate buffer, PH 5.5, 상온에서 7분간 반응시키는 것이 최적 반응조건이었다. 9L glioma 이식 백서 체내동태는 [$^{123}I$]IMT가 신장으로 배설됨과 체내에서 탈요오드 반응이 일어남이 추측되었고, 정상조직의 3배 방사능 섭취가 관찰되어, 각종 뇌종양의 진단 및 치료 후 경과 관찰에 이용 가능성이 보여 임상연구의 진행이 기대된다.

• 대한한의학방제학회지
• /
• 제14권1호
• /
• pp.105-119
• /
• 2006

Objectives & Methods : This present study was performed to investigate the effect of Hwadamtongrak-Tang extract (HTT) on the regulation of cerebral hemodynamics in terms of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP)] in normal and cerebral ischemic rats. Also the effects of HTT on changes in local blood flow, inhibition of LD H activity in neuronal cells, and levels of cytokine production in the serum were determined in the ischemic rat model. The major findings are summarized below. Results : 1. HTT significantly increased rCBF in a dose-dependent manner, but MABP was not changed by HTT treatment. These results suggest that HTT may increase rCBF by dilating cerebral arterial diameter. 2. HTT-induced increase in rCBF was blocked by pretreatment with cyclooxygenase inhibitor indomethacin (IDN, 1 mg/kg, i.p.) and MABP was significantly increased by ID N. 3. Pretreatment of methylene blue $(MTB,\;10\;{\mu}g/kg,\;i.p.)$, an inhibitor of guanylate cyclase, significantly decreased both rCBP and MABP in HTT-treated rats. 4. HTT treatment significantly increased rCBP to a stable level during the period of cerebral reperfusion. 5. HTT significantly inhibited LD H activity in neuronal cells, suggesting a neuroprotection by HTT. 6. Serum interleukin $(IL)-1{\beta}$ and tumor necrosis factor $(TNF)-{\alpha}$ levels were significantly decreased in the femoral artery 1 hr after middle cerebral arterial occlusion in HTT-treated rats. IL-10 levels in the serum were significantly increased by HTT treatment whereas transforming growth factor $(TGF)-{\beta}$ levels were similar between HTT-treated and control groups. 7. Serum interleukin $(IL)-1{\beta}$ and tumor necrosis factor $(TNF)-{\alpha}$ levels were significantly decreased in the femoral artery 1 hr after reperfusion in HTT-treated rats. Serum IL-10 levels were significantly decreased in HTT-treated rats compared with the control group, and no significant changes in $(TGF)-{\beta}$ in the serum were observed by HTT treatment. Conclusions: The present data suggest that HTT may have an anti-ischemic effect via the improvement of cerebral hemodynamics and thus protect the brain from ischemic damage.

• Journal of Nutrition and Health
• /
• 제14권3호
• /
• pp.129-135
• /
• 1981

체중(體重)이 $200{\sim}250g$되는 Sprague Dawley 암컷쥐 10마리를 두 그룹으로 나누어서 임신말기(姙娠末期)(third trimester)부터 분만후(分娩後) 11일까지 저(低) phenylalanine식이(食餌)(low phenylalanine diet)를 섭취(攝取)시켜서 새끼쥐의 체중증가(體重增加) 및 혈장(血裝)과 뇌조직(腦組織)의 phenylalanine과 tyrosine농도(濃度)를 측정(測定)하였다. 새끼쥐의 체중증가(體重增加)는 대조군(對照群)에 비해 실험군(實驗群)은 현저히 감소(減少)하였으며, 3일째부터는 두 군(群)사이에 유의적(有意的)인 차이(差異)(p<0.05)를 나타내었다. 뇌(腦)무게의 증가(增加)는 대조군(對照群)에 비해 실험군(實驗群)은 약간 증가(增加)되었으며, 실험(實驗) 전기간(全期間) 동안 매우 유의적(有意的)인 차이(差異)(p <0. 01)를 나타내었다. 혈장중(血漿中)의 phenylalanine농도(濃度)는 대조군(對照群)이 실험군(實驗群)에 비해 약간 높았고, 두 군(群) 모두 점차 감소(滅少)하다가 증가(增加)하는 경향을 보였으며, 5일째에만 유의적(有意約)인 차 (P<0.05)를 보였으나, 전반적으로 혈장중(血漿中)의 phenylalanine농도(濃度)는 식이(食餌)의 phenylalanine양과 상관관계(相關關係)가 없었다. 혈장중(血漿中)의 tyrosine농도(濃度)는 실험군(實驗郡)이 점차로 감소(減少)한 반면 대조군(對照群)은 점차로 증가(增加)했고, 5, 9, 11일에는 유의적(有意的)인 차(差)(P<0.05)를 나타냈다. 그러므로 혈장중(血漿中)의 tyrosine농도(濃度)는 식이(食餌)중의 phenylalanine양과 positive한 상관관계(相關關係)가 있었다. 뇌조직(腦組織)의 phenylalanine은 두 군(群) 모두 증가(增加)하는 경향(傾向)을 보였으며, 실험군(實驗群)이 대조군(對照群)에 비해 약간 낮았으며, 초기(初期)에는(1, 3, 5일) 유의적(有意的)인 차(差)(p<0.05)를 보였으나 후기(後期)에는 유의적(有意的)인 차(差)가 없었다. 뇌조직(腦組織)의 tyrosine은 두 군(群) 모두 증가(增加)하다가 감소(減少)하는 경향(傾向)을 보였으며, 실험군(實驗群)이 대조군(對照群)에 비해 약간 낮았고 2, 9, 11일에는 유의적(有意的)인 차(差)(p<0.05)가 있었다. 본(本) 연구(硏究)를 통하여 임신기(姙娠期)와 수유시(授乳時)의 어미쥐의 정상적(正常的)인 phenylalanine섭취(攝取)는 새끼쥐의 정상적(正常的)인 성장(成長)과 생존(生存)에 필수론(必須論)임을 알 수 있으며, 어미쥐의 endogenous phenylalanine에 의해서 보상(補償)되지 않았다.

• Toxicological Research
• /
• 제22권4호
• /
• pp.445-452
• /
• 2006

Aralia elata, a common medicinal and culinary herb, has beer consumed for centuries without any reported adverse effects. However, due to its limited safety information, we decided to investigate the repeated-dose toxicity of ethanolic extract of Aralia elata. The test was administered once daily by the gavage to male and female rats at doses of 0, 250, 500 and 1,000 mg/kg/day for four weeks. Throughout the study, no treatment-related deaths or clinical signs were observed. Also, no apparent changes were detected in ophthalmoscopy, urinalysis, serum biochemistry, hematology and gross necropsy. The test result showed a significant decrease in body and heart weight of males treated with 250 mg/kg of extract of Aralia elata compared to normal control, a significant increase in relative brain weight and adrenal weight in females treated with 250 mg/kg of extract compared to normal control. However, all these changes were not considered toxicologically important due to irrelevant dose-response relationship to gross and microscopic findings. Histopathologically, abnormal changes were not observed in any target organs. On the basis of these results, the NOAEL of extract of Aralia elata was estimated to be more than 1,000 mg/kg/day under the tested conditions.

• 대한본초학회지
• /
• 제33권4호
• /
• pp.77-85
• /
• 2018

Objective : This study was intended to examine the effects of water extract of Prunellae Spica (PS), which is a herb with 'cold' nature based on hot and cold theory of traditional Korean medicine. Methods : Hyperthyroidism was induced in SD rats by LT4 (0.5 mg/kg, i.p.) daily for four weeks. After 2 weeks of LT4 injection, rats were divided randomly into four groups; normal, LT4-induced hyperthyroid control, PS extract (500 mg/kg, p.o.)-treated group, and propylthiouracil (PTU, 10 mg/kg, s.c.)-treated positive group. After 2 weeks of drug treatment, all rats were sacrificed and harvested blood samples and thyroid tissues. The changes of body weight, food and water intake, and body temperature were measured weekly. Serological markers were analyzed in sera using an enzyme-based assay, and thyroid tissues were stained with Hematoxylin & Eosin (H&E). Brain and dorsal root ganglion (DRG) tissues were isolated and analyzed the expression of transient receptor potential (TRP) channels by Western blot. Results : PS extract administration attenuated the loss of body weight and the increase of body temperature in LT4-induced hyperthyroidism rats. PS extract increased the level of thyroid stimulating hormone (TSH) and decreased tiiodothyronine (T3) and tetraiodothyronine (T4). In action mechanism, PS extract regulated the expression of transient receptor potential channel subfamily V member 1 (TRPV1) and transient Receptor Potential channel subfamily M member 8 (TRPM8), the thermoregulators. Conclusion : To conclude, PS extract can improve the symptoms of hyperthyroidism through regulation of the thyroid hormones imbalance and thermoregulation via TRP channels.

• Reproductive and Developmental Biology
• /
• 제34권2호
• /
• pp.89-94
• /
• 2010

Melatonin is induced by light information through the retina and leads to growth factor activation. Thus, we investigated the effects of melatonin by controlling the photoperiod of growing young rats. Male Sprague-Dawley rats (n=6; 4 weeks old) were divided into two experimental groups: the L/D group (normal photoperiod; light/dark: 12/12 h; lights on at 9:00 a.m.) and the L/L group (light/light: 24 h). Rat body weight and food consumption were measured daily for 8 weeks. After 8 weeks, the rats were anesthetized with a mixture of ketamine (50 mg/kg) and xylazine (10 mg/kg) and sacrificed. Tissue was then collected for RNA isolation (from brain, heart, liver, kidney, adrenal gland, testis, tibia, hind limb muscles). Also, serum was isolated from blood using a centrifugal separation. The L/L group had significantly lower body weight than the L/D group from 4 to 6 weeks (p<0.05). The L/D group had increased tissue mass, compared with the L/L group, but the difference was not statistically significant. The L/D group had a significantly higher melatonin concentration than the L/L group between the hours of midnight and 2:00 a.m (p<0.01). These results indicate that photoperiod length may affect the secretion of melatonin from the pineal gland. Also, the reduction of nocturnal melatonin secretion may retard the development of growing young rats. In future studies, we plan to compare exogenous melatonin administration with endogenous melatonin concentration induced by photoperiod control. Moreover, we will confirm whether the effects seen in pathological animal models can be reversed by controlling the photoperiod.

• The Korean Journal of Physiology and Pharmacology
• /
• 제19권2호
• /
• pp.177-181
• /
• 2015

The subfornical organ (SFO) is one of circumventricular organs characterized by the lack of a normal blood brain barrier. The SFO neurons are exposed to circulating glutamate ($60{\sim}100{\mu}M$), which may cause excitotoxicity in the central nervous system. However, it remains unclear how SFO neurons are protected from excitotoxicity caused by circulating glutamate. In this study, we compared the glutamate-induced whole cell currents in SFO neurons to those in hippocampal CA1 neurons using the patch clamp technique in brain slice. Glutamate ($100{\mu}M$) induced an inward current in both SFO and hippocampal CA1 neurons. The density of glutamate-induced current in SFO neurons was significantly smaller than that in hippocampal CA1 neurons (0.55 vs. 2.07 pA/pF, p<0.05). To further identify the subtype of the glutamate receptors involved, the whole cell currents induced by selective agonists were then compared. The current densities induced by AMPA (0.45 pA/pF) and kainate (0.83 pA/pF), non-NMDA glutamate receptor agonists in SFO neurons were also smaller than those in hippocampal CA1 neurons (2.44 pA/pF for AMPA, p<0.05; 2.34 pA/pF for kainate, p< 0.05). However, the current density by NMDA in SFO neurons was not significantly different from that of hippocampal CA1 neurons (1.58 vs. 1.47 pA/pF, p>0.05). These results demonstrate that glutamate-mediated action through non-NMDA glutamate receptors in SFO neurons is smaller than that of hippocampal CA1 neurons, suggesting a possible protection mechanism from excitotoxicity by circulating glutamate in SFO neurons.