• Journal of Sasang Constitutional Medicine
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• v.22 no.4
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• pp.65-76
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• 2010

1. Objectives The present study was designed to investigate the effect of Soyangin Hyeongbangdojeok-san(HBDJS) on acute cocaine-induced behavior effect and gene expression in the rat brain. 2. Methods Experimental animals were composed of saline(SAL), cocaine(COC), HBDJS + COC, HBDJS + SAL group. Rats received HBDJS(100, 200 mg/kg, p.o.) 1 h prior to cocaine hydrochloride(20 mg/kg, i.p.) treatment respectively. After cocaine injection, locomotor activity and rearing were measured in a rectangular container equipped with a video camera above the center of the floor for 60 min. In addiction, c-Fos expression in the rat brain was detected using immunohistochemistry 2 h after cocaine injection. And the effect of HBDJS on acute cocaine-induced pERK, pElk, pCREB upstream of c-Fos expression was detected using western blotting and immunohistochemistry 15 min after cocaine challenge. 3. Results The present results show that HBDJS at dose of 200 mg/kg attenuated cocaine-induced both locomotor activity and rearing. Also HBDJS at dose of 200 mg/kg significantly decreased c-Fos expression in the rat brain(nucleus accumebns and striatum). However HBDJS at dose of 200 mg/kg have no effect on cocaine-induced pERK, pCREB, pElK-1 expression. HBDJS is c-Fos expression through ERK-independent pathway. 4. Conclusions. These results suggest that HBDJS may be effective in suppressing the reinforcing effects of cocaine.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.30 no.4
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• pp.37-48
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• 2017

Objectives : This Study was conducted to investigate the melanin synthesis effect of Eclipta prostrata and to determine the relationship between melanin synthesis effect of Eclipta prostrata and cAMP/PKA melanin synthesis pathway. Methods : We measured melanin contents, tyrosinase activity, expression of TRPs, p-CREB in B16F10 cells cultured with Eclipta prostrata ethanol extracts(EEP). And after treatment with H89 and dibutyryl cAMP, which inhibit or promote the activation of PKA, we observed changes in melanin synthesis and tyrosinase activity stimulated by EEP. Results : EEP increased melanin synthesis by promoting the expression of tyrosinase and TRP-1. It also promoted expression of p-CREB. H89 suppresses melanogenic effect and expression of tyrosinase, TRP-1 in B16F10 stimulated by EEP. Dibutyryl cAMP promotes melanogenic effect of EEP. Conclusions : The results of this study suggest that melanin synthesis effect of EEP is related to induction of tyrosinase and TRP-1 expression through the cAMP/PKA pathway.

• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.13-19
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• 2005

The study was undertaken to determine the antagonism of the AP1700 on the development of nalbuphine-induced tolerance and physical dependence. AP1700 is an oriental drug preparationcomposed of 5 natural products and is known to have antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of nalbuphine-induced physical dependence but does not the tolerance. Mitogen-activated protein kinase, which include extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) play critical roles in cell growth and survival and drug abuse. The level of pCREB was elevated in the hippocampus by the chronic treatment with nalbuphine, however, the elevation of pCREB was not inhibited by the AP1700 co-treatment. Interestingly, the level of pERK was decreased in the co-treatment with nalbuphine and AP1700 on the cortex and striatum. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or AP1700 on the cortex, hippocampus and striatum in the rat brain. These results suggest that the AP1700 could be used to ameliorate the nalbuphine withdrawal symptoms.

• Journal of the Korean Applied Science and Technology
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• v.38 no.3
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• pp.883-890
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• 2021

In this study, we investigated the melanogenesis inhibitory effects of Rubus crataefifolius Leaf Extract (RCLE) in B16F10 melanoma cells. We examined the effects of RCLE on the melanin contents and tyrosinase activity, as well as the protein expression levels of the melanogenic enzymes TRP-1, TRP-2, and MITF in α-MSH -stimulated B16F10 melanoma cells. RCLE effectively inhibited tyrosinase activity and melanogenesis, suppressed the phosphorylation of PKA and CREB, and expression of MIT involved in the melanogenesis pathway, and down-regulated expression of melanogenesis related proteins. These result suggest that RCLE inhibited α-MSH-stimulated melanin synthesis by suppressing MITF expression. Therefore, our study suggests that RCLE has potential as a safe treatment for excessive pigmentation or as a natural ingredient in cosmetics.

• Journal of Oriental Neuropsychiatry
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• v.28 no.3
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• pp.287-302
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• 2017

Objectives: To evaluate effects of Resina Dendropanacis Morbiferus (RDM) on stress and sleep hormones when administered to Chronic Mild Stressed (CMS) rats. Methods: Twenty-five healthy rats were randomly divided into 5 groups; Normal, CMS (Control), Resina Dendropanacis Mobiferus 50 mg/kg (RDM 50), 100 mg/kg (RDM 100), and 200 mg/kg (RDM 200). All rats except the normal group were exposed to unpredicted stress conditions such as water deprivation, empty bottles, forced thread mill, etc. according to timetable of CMS for 3 weeks. After a week starting experiments, rats in RDM 50, RDM 100, and RDM 200 groups were fed orally once a day for 2 weeks. Afterward, blood samples were taken from rats to analyze complete blood count, AST, ALT, and glucose. Noradrenalin, GABA and Melatonin were measured by ELISA kit. BDNF, CREB and TrkB were measured by RT-PCT. Results: 1. In Noradrenalin content, RDM 100 and RDM 200 groups revealed significant decrease compared to the control group. 2. In GABA content, RDM 50 and RDM 100 groups revealed significant decrease compared to the control group. 3. In Melatonin content, RDM 100 and 200 groups revealed significant decrease compared to the control group. 4. In Activity of BDNF, RDM 100 and 200 groups revealed significant increase compared to the control group. 5. In Activity of CREB and TrkB, RDM 100 group revealed significant increase compared to the control group. 6. In Erythrocyte and Thrombocyte changes, red blood cells and hematocrit significantly increased in RDM 50 and RDM 200 groups than the control group. Hemoglobin and platelet significantly increased in all experimental groups and the control group. 7. In Weight gain content, all RDM groups revealed insignificant increase compared to the control group. 8. In Glucose content, RDM 50, RDM 100, and RDM 200 groups revealed significant decrease compared to the control group. Conclusions: Results suggest that RDM have effects on stress and sleep hormones when administered to Chronic Mild Stressed (CMS) rats.

• Korean Journal of Medicinal Crop Science
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• v.28 no.2
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• pp.85-94
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• 2020

Background: Alzheimer's disease (AD) is caused by various factors, such as cholinergic dysfunction, regulation of neurotrophic factor expression, and accumulation of amyloid-beta. We investigated whether or not a combination of Carthamus tinctorius L. seed and Taraxacum coreanum (CT) has a protective effect on scopolamine-induced memory impairment in a mouse model. Methods and Results: Mice were orally pretreated with CT (50, 100 and 200 mg/kg/day) for 14 days, and scopolamine (1 mg/kg/day) was injected intraperitoneally before subjecting them to behavior tests. CT-administered mice showed better novel object recognition and working memory ability than scopolamine-treated control mice. In T-maze and Morris water maze tests, CT (100 and 200 mg/kg/day) significantly increased space perceptive ability and occupancy to the target quadrant, respectively. In addition, 100 and 200 mg/kg/day of CT attenuated cholinergic dysfunction through inhibition of butyryl cholinesterase in brain tissue. Furthermore, CT-administered mice showed higher cyclic adenosine monophosphate-response element-binding protein (CREB) levels and lower amyloid precursor protein (APP) levels compared to scopolamine-treated control mice. Conclusions: CT improved scopolamine-induced memory impairment through inhibition of cholinergic dysfunction, up-regulation of CREB, and down-regulation of APP. Therefore, CT could be a useful therapeutic agent for AD with protective effects on cognitive impairment.

• Nutrition Research and Practice
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• v.13 no.3
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• pp.205-213
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• 2019

BACKGROUND/OBJECTIVES: Myocardial infarction (MI) is caused by extensive myocardial damage attributed to the occlusion of coronary arteries. Our previous study in a rat model of ischemia/reperfusion (I/R) demonstrated that administration of arabinoxylan (AX), comprising arabinose and xylose, protects against myocardial injury. In this study, we undertook to investigate whether psyllium seed husk (PSH), a safe dietary fiber containing a high level of AX (> 50%), also imparts protection against myocardial injury in the same rat model. MATERIALS/METHODS: Rats were fed diets supplemented with PSH (1, 10, or 100 mg/kg/d) for 3 d. The rats were then subjected to 30 min ischemia through ligation of the left anterior descending coronary artery, followed by 3 h reperfusion through release of the ligation. The hearts were harvested and cut into four slices. To assess infarct size (IS), an index representing heart damage, the slices were stained with 2,3,5-triphenyltetrazolium chloride (TTC). To elucidate underlying mechanisms, Western blotting was performed for the slices. RESULTS: Supplementation with 10 or 100 mg/kg/d of PSH significantly reduces the IS. PSH supplementation (100 mg/kg/d) tends to reduce caspase-3 generation and increase BCL-2/BAX ratio. PSH supplementation also upregulates the expression of nuclear factor erythroid 2-related factor 2 (NRF2), and its target genes including antioxidant enzymes such as glutathione S-transferase mu 2 (GSTM2) and superoxide dismutase 2 (SOD2). PSH supplementation upregulates some sirtuins ($NAD^+$-dependent deacetylases) including SIRT5 (a mitochondrial sirtuin) and SIRT6 and SIRT7 (nuclear sirtuins). Finally, PSH supplementation upregulates the expression of protein kinase A (PKA), and increases phosphorylated cAMP response element-binding protein (CREB) (pCREB), a target protein of PKA. CONCLUSIONS: The results from this study indicate that PSH consumption reduces myocardial I/R injury in rats by inhibiting the apoptotic cascades through modulation of gene expression of several genes located upstream of apoptosis. Therefore, we believe that PSH can be developed as a functional food that would be beneficial in the prevention of MI.

• Journal of Ginseng Research
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• v.32 no.1
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• pp.1-7
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• 2008

Ginseng saponin has been shown to inhibit the development of dependence on morphine, cocaine, methamphetamine, but the antinarcotics effects of ginseng on nalbuphine remains still largely unknown. Ginseng administration attenuated the naloxone-induced jumping behavior on nalbuphine dependent mice. The development of morphine dependence was mediated through ${\mu}-opioid$ receptor, however, development of nalbuphine dependence was mediated through ${\kappa}-opioid$ receptor. However, it was found that the efficacy of analgesic antagonism of GTS was mediated through the serotonergic mechanism, not mediated through the opioid receptor. In addition, ginseng administration modulated cellular signal transduction in the brain. The increased NMDA receptor subunit (NR1, pNR1), phosphate extracellular signal regulated protein kinase (pERK), phosphate cAMP response element binding protein (pCREB) expression by nalbuphine was decreased by the administration of ginseng powder in cortex, hippocampus, striatum of rat brain. These results suggest that ginseng could be one of the targets of antinarcotic therapies to reduce the development of tolerance and dependence on nalbuphine as well as morphine.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.4
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• pp.309-316
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• 2003

연구목적: 스테로이드 계통의 에스트로겐 호르몬은 막 수용체와 결합하고 DNA에 부착되어, 자궁조직에서 발현되는 많은 유전자들의 발현 양상을 조절하는 것으로 알려져 있다. 본 연구에서는 난소를 제거한 생쥐 모델을 이용하여 에스트로겐에 의해 조절되는 전사 관련 유전자(transcription factor)들을 동정하고, early up-regulation gene으로 확인된 Fos related antigen (Fra1과 Fra2) 유전자의 발현 양상을 RT-PCR과 면역염색방법으로 살펴보았다. 연구재료 및 방법: 난소 절제술을 시행한 생쥐에 에스트로겐을 피하주사하고 2, 4, 6, 12시간 간격으로 자궁조직을 적출하였다. 대조군으로는 sesame oil만을 주사한 후 2시간째에 수획한 자궁조직을 사용하였으며, 시간대별로 채취한 자궁조직(n=4)에서 RT-PCR을 수행하였다. RT-PCR을 통해 early response gene으로 확인된 Fra1과 Fra2에 대한 에스트로겐의 영향을 살펴보기 위해 estrogen receptor antagonist인 ICI 182, 780을 주사하여 유전자 발현 양상의 변화를 살펴보았다. 또한, 자궁조직내에서의 단백질 발현 부위를 관찰하기 위해 면역조직화학염색을 실시하였다. 결 과: 생쥐 자궁조직에서 에스트로겐에 의해 발현 양상의 변화가 확인된 유전자는 early up-regulation genes (CREB2, Fra-1, 2, GATA5), late up-regulation gene (E2F1), no response genes (CREB1, ATF1, GLI3, E2F3), down-regulation genes (GLI2, E2F5, GATA-2, 3, 6) 등으로 구분할 수 있었다. 그 중 early up-regulation genes에 해당하는 Fra1과 Fra2 유전자는 ICI 182, 780에 의해 그 발현이 유의하게 감소되는 것을 확인하였다(p < 0.01). 이들 단백질은 생쥐 자궁조직의 상피세포층, 기질층, 근육층에서 고루 발현되었으며, 특히 근육층에서 강한 염색정도를 관찰할 수 있었다. 결 론: 이상의 결과를 통해 Fra1과 Fra2 유전자의 발현은 에스트로겐에 의해 조절됨을 알 수 있었으며, 이들의 강한 발현이 자궁조직의 근육층에서 관찰되어 이들의 기능에 대한 연구가 필요할 것으로 생각된다.

• Horticultural Science & Technology
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• v.31 no.6
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• pp.813-820
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• 2013

Monoterpenoids were recently found as main biologically active compounds which is responsible for various physiological effect in goat's beard (Aruncus dioicus). Ethyl acetate extract of A. dioicus (ADE) was treated to B16F10 melanoma cells for the examination of whitening activity. MTT assay was performed to evaluate cell toxicity and the result showed that slight cell toxicity (> 10%) by over $500{\mu}g{\cdot}mL^{-1}$. Thus, 0, 5, 10, or $50{\mu}g{\cdot}mL^{-1}$ ADE was used for further experiments. We found that tyrosinase activity was decreased according to ADE concentration, and the total melanin content was also dramatically reduced. Especially with $50{\mu}g{\cdot}mL^{-1}$ ADE treatment tyrosinase activity was reduced to 35.6%, and 58.8% of melanin content was lowered. In addition, whitening related proteins including tyrosinase, tyrosinase related protein 1 (TRP1), TRP2, microphthalmia associated transcription factor (MITF) and cAMP and protein kinase A (PKA) were reduced by ADE treatment. It caused decreased phosphorylation of cAMP response binding protein (CREB) but increased phosphorylation of extracellular signal related kinase (ERK). Therefore, in this paper we would like to suggest the potent usage of A. dioicus natively grown in Ulleungdo, Korea as materials of functional cosmetics by confirming whitening activity related with melanin content.