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α-Pinene Attenuates Methamphetamine-Induced Conditioned Place Preference in C57BL/6 Mice

  • Chan Lee;Jung-Hee Jang;Gyu Hwan Park
    • Biomolecules & Therapeutics
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    • v.31 no.4
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    • pp.411-416
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    • 2023
  • Methamphetamine (METH) is a powerful neurotoxic psychostimulant affecting dopamine transporter (DAT) activity and leading to continuous excess extracellular dopamine levels. Despite recent advances in the knowledge on neurobiological mechanisms underlying METH abuse, there are few effective pharmacotherapies to prevent METH abuse leading to brain damage and neuropsychiatric deficits. α-Pinene (APN) is one of the major monoterpenes derived from pine essential oils and has diverse biological properties including anti-nociceptive, anti-anxiolytic, antioxidant, and anti-inflammatory actions. In the present study, we investigated the therapeutic potential of APN in a METH abuse mice model. METH (1 mg/kg/day, i.p.) was injected into C57BL/6 mice for four alternative days, and a conditioned place preference (CPP) test was performed. The METH-administered group exhibited increased sensitivity to place preference and significantly decreased levels of dopamine-related markers such as dopamine 2 receptor (D2R) and tyrosine hydroxylase in the striatum of the mice. Moreover, METH caused apoptotic cell death by induction of inflammation and oxidative stress. Conversely, APN treatment (3 and 10 mg/kg, i.p.) significantly reduced METH-mediated place preference and restored the levels of D2R and tyrosine hydroxylase in the striatum. APN increased the anti-apoptotic Bcl-2 to pro-apoptotic Bax ratio and decreased the expression of inflammatory protein Iba-1. METH-induced lipid peroxidation was effectively mitigated by APN by up-regulation of antioxidant enzymes such as manganese-superoxide dismutase and glutamylcysteine synthase via activation of nuclear factor-erythroid 2-related factor 2. These results suggest that APN may have protective potential and be considered as a promising therapeutic agent for METH-induced drug addiction and neuronal damage.

Ginsenoside Rg5 promotes wound healing in diabetes by reducing the negative regulation of SLC7A11 on the efferocytosis of dendritic cells

  • Wei Xia;Zongdong Zhu;Song Xiang;Yi Yang
    • Journal of Ginseng Research
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    • v.47 no.6
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    • pp.784-794
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    • 2023
  • Background: ginsenoside Rg5 is a rare ginsenoside with known hypoglycemic effects in diabetic mice. This study aimed to explore the effects of ginsenoside Rg5 on skin wound-healing in the Leprdb/db mutant (db/db) mice (C57BL/KsJ background) model and the underlying mechanisms. Methods: Seven-week-old male C57BL/6J, SLC7A11-knockout (KO), the littermate wild-type (WT), and db/db mice were used for in vivo and ex vivo studies. Results: Ginsenoside Rg5 provided through oral gavage in db/db mice significantly alleviated the abundance of apoptotic cells in the wound areas and facilitated skin wound healing. 50 μM ginsenoside Rg5 treatment nearly doubled the efferocytotic capability of bone marrow-derived dendritic cells (BMDCs) from db/db mice. It also reduced NF-κB p65 and SLC7A11 expression in the wounded areas of db/db mice dose-dependently. Ginsenoside Rg5 physically interacted with SLC7A11 and suppressed the cystine uptake and glutamate secretion of BMDCs from db/db and SLC7A11-WT mice but not in BMDCs from SLC7A11-KO mice. In BMDCs and conventional type 1 dendritic cells (cDC1s), ginsenoside Rg5 reduced their glycose storage and enhanced anaerobic glycolysis. Glycogen phosphorylase inhibitor CP-91149 almost abolished the effect of ginsenoside Rg5 on promoting efferocytosis. Conclusion: ginsenoside Rg5 can suppress the expression of SLC7A11 and inhibit its activity via physical binding. These effects collectively alleviate the negative regulations of SLC7A11 on anaerobic glycolysis, which fuels the efferocytosis of dendritic cells. Therefore, ginsenoside Rg5 has a potential adjuvant therapeutic reagent to support patients with wound-healing problems, such as diabetic foot ulcers.

Pycnogenol, a Standardized Extract of French Maritime Pine Bark, Inhibited the Transcriptional Expression of Th2 Cytokines by Suppressing $NF-{\kappa}B$ Activation in Primary Splenocytes of C57BL/6 Mice with Murine AIDS (Murine AIDS 감염쥐 splenocytes에서 $NF-{\kappa}B$의 활성화 억제를 통한 pycnogenol의 Th2 cytokines의 mRNA 발현 조절 효과)

  • Lee, Jeong-Min
    • Korean Journal of Food Science and Technology
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    • v.38 no.6
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    • pp.829-834
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    • 2006
  • LP-BM5 murine leukemia retrovirus induces the immune dysfunction by imbalanced secretion of Th1 and Th2 cytokines in the murine AIDS model. In the present study, it was investigated whether pycnogenol (Pyc) administration could deactivate $NF-{\kappa}B$ to regulate the gene expression of Th1 and Th2 cytokines in C57BL/6 mice with murine AIDS. Treatment with Pyc for 12 weeks significantly inhibited the loss of body weight and enlargement of spleen and lymph node usually seen with AIDS. Moreover, Pyc increased the plasma level of Th1 cytokines, IL-2 and $IFN-{\gamma}$, while reducing the plasma level of Th2 cytokines, IL-6, IL-10, and $TNF-{\alpha}$. In primary culture of splenocytes, mRNA expression of Th2 cytokines was suppressed, but that of Th1 cytokines was not affected. The LP-BM5 retrovirus infection stimulated the cytoplasmic activation of $NF-{\kappa}B$ and nuclear translocation of $I-{\kappa}B$, whereas Pyc administration significantly reduced $NF-{\kappa}B$ activation and $I-{\kappa}B$ degradation. These results suggested that the inhibitory effect of Pyc on Th2 cytokines in mice with murine AIDS was dependent on suppression of the $NF-{\kappa}B$ signaling pathway and was not dependent on $INF-{\gamma}$ level, which regulates Th2 cytokines.

Cornu cervi pantotrichum Pharmacopuncture Solution Facilitate Hair Growth in C57BL/6 Mice

  • Lee, Seon-Yong;Lee, Dong-Jin;Kwon, Kang;Lee, Chang-Hyun;Shin, Hyun Jong;Kim, Jai Eun;Ha, Ki-Tae;Jeong, Han-Sol;Seo, Hyung-Sik
    • Journal of Pharmacopuncture
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    • v.19 no.2
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    • pp.122-128
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    • 2016
  • Objectives: Cornu cervi pantotrichum (CCP) has been widely used in Korean and China, as an anti-fatigue, anti-aging, and tonic agent to enhance the functions of the reproductive and the immune systems. Because CCP has various growth factors that play important roles in the development of hair follicles, we examined whether CCP pharmacopuncture solution (CCPPS) was capable of promoting hair growth in an animal model. Methods: One day after hair depilation, CCPPS were topically applied to the dorsal skin of C57BL/6 mice once a day for 15 days. Hair growth activity was evaluated by using macro- and microscopic observations. Dorsal skin tissues were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), and fibroblast growth factor (FGF)-7 were examined by using immunohistochemical staining. A reverse transcription polymerase chain reaction (RT-PCR) analysis was also conducted to measure the messenger RNA (mRNA) expression of FGF-7. Results: CCPPS induced more active hair growth than normal saline. Histologic analysis showed enlargement of the dermal papilla, elongation of the hair shaft, and expansion of hair thickness in CCPPS treated mice, indicating that CCPPS effectively induced the development of anagen. CCPPS treatment markedly increased the expressions of BrdU and PCNA in the hair follicles of C57BL/6 mice. In addition, CCPPS up regulated the expression of FGF-7, which plays an important role in the development of hair follicles. Conclusion: These results reveal that CCPPS facilitates hair re-growth by proliferation of hair follicular cells and up-regulation of FGF-7 and suggest that CCPPS can potentially be applied as an alternative treatment for patients with alopecia.

Effects of Phytoestrogens on Glucose Metabolism in C57BL/KsOlaHsd-db/db Mice (주요 Phytoestrogen들이 제2형 당뇨 마우스의 당질대사에 미치는 효과)

  • Seo, Bo-Hyeon;Kim, Kwang-Ok;Lee, Ji-Hye;Lee, Hye-Sung
    • Journal of Nutrition and Health
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    • v.44 no.4
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    • pp.275-283
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    • 2011
  • This study was conducted to evaluate the antihyperglycemic effects of three phytoestrogens, genistein, coumestrol, and enterolactone, in type 2 diabetic animals. Forty male C57BL/KsOlaHsd-db/db mice were used as a diabetic animal model. The animals were divided into four groups and fed a phytoestrogen-free AIN-76 diet (control), or one of three phytoestrogen-supplemented (3.75 mg/100 g diet) AIN-76 diets for six weeks. During the experimental period, fasting blood glucose levels were measured on week 0, 2, 5, and 6 of the experiment, and oral glucose tolerance tests were performed on the 5th week. After the experimental period, blood concentrations of HbA1c, insulin, and glucagon were measured, and hepatic glycogen content and glucose regulating enzyme activities were analyzed. Fasting blood glucose, HbA1c level, and the area under the blood glucose curve in the oral glucose tolerance test were significantly lower in all of the phytoestrogen-supplemented groups compared to the control group. Plasma glucagon levels were also significantly lower in all of the phytoestrogen-supplemented groups compared to the control group. Hepatic glycogen level was significantly higher in the coumestrol-supplemented group compared to the other groups. However, there were no significant differences in the activities of glucokinase and glucose-6-phosphatase between the groups. These results suggest that all of the three major phytoestrogens tested in the present study were effective in lowering blood glucose levels in type 2 diabetic animals. However, further studies need to be conducted to elucidate the exact mechanism for the hypoglycemic effects of phytoestrogens.

Induction of Micronuclei in Human and Mouse Lymphocytes Irradiated with Gamma Radiation and Effect of Panax ginseng C.A. Meyer (마우스와 사람 림프구에서 방사선에 의한 미소핵의 형성 및 고려인삼의 효과)

  • Kim, Sung-Ho;Oh, Heon;Lee, Song-Eun;Lee, Yun-Sil;Kim, Tae-Hwan;Jeong, Kyu-Sik;Ryu, Si-Yun
    • Journal of Radiation Protection and Research
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    • v.22 no.3
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    • pp.153-160
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    • 1997
  • The frequencies of ${\gamma}$-ray-induced micronuclei (MN) in cytokinesis-blocked (CB) lymphocytes at several doses were measured in three donors of human and C57BL/6 mice. Measurements performed after irradiation showed a dose-related increases in MN frequency in each of the donors studied. The relative sensitivity of mouse in spleen lymphocytes (SLs) compared with human peripheral blood lymphocytes (PBLs) was estimated by best fitting linear-quadratic model based on the radiation-induced MN data over the range from 0 cGy to 400 cGy. In the case of MN frequency with 0.2 per CB cell, the relative sensitivity of mouse SLs was 1.67. Compared with the radiation-induced MN formation in the PBLs of human, the SLs of mouse were more radiosensitive. Using this MN assay with human PBLs and mouse SLs, studies were performed to determine whether the water fraction of ginseng (Panax ginseng C.A.Meyer) against radiation-induced MN in human PBLs after in vitro irradiation (3Gy) and in SLs of C57BL/6 mice after in vivo irradiation (3Gy). The frequency of MN in human PBLs was reduced by water fraction of ginseng (0.5mg/ml of medium) both pre-and post treatment (p<0.0l) in vitro. In addition, the frequency of MN in mouse SLs was also reduced by pretreatment of ginseng (2mg/ml of drinking water for 7days) in vivo. The data suggested that the ginseng may reduce cell damage caused by ${\gamma}$-rays in vitro and in vivo. Further studies are needed to characterize better the protective nature of ginseng extract, its fractions and compounds.

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Effects of Cordyceps militaris Mycelia(CMM) herbal acupuncture at BL13, LU4 on airway smooth muscle, airway inflammation, IgE and Interleukin-4 in mouse model of allergic bronchial asthma (동충하초(冬蟲夏草) 약침(藥鍼)이 백서(白鼠)의 기관지평활근(氣管支平滑筋) 장력(張力)과 염증(炎症) 및 면역(免疫) 반응(反應)에 미치는 영향(影響))

  • Youn, Dae-Hwan;Choi, Gwan-Jun;Chae, Woo-Seok;Na, Chang-Su
    • Korean Journal of Acupuncture
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    • v.21 no.2
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    • pp.111-123
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    • 2004
  • Objectives : It has been reported that Cordyceps militaris Mycelia(CMM) has an effect on deficiency allergic asthma(虛喘) clinically. The aim of this study was to determine an appropriate oriental treatment and the doses of CMM to treat asthma. Methods : In order to study the effect of herbal acupuncture solution of the CMM on allergic asthma, the mouse were pretreated by CMM herbal acupuncture at BL13, LU4 before antigen sensitization. 2 days later Mice were actively sensitized with a subcutaneous injection of ovalbumin(OA) and 13 days later they were provoked with OA aerosols. IL-4, lymphocyte, macrophage in bronchoalveolar lavage fluid(BALF), IgE in serum, WBC, RBC, HGB in blood, and in vitro isometric contractile responses of the isolated tracheal smooth muscle(TSM) to acetylcholine$(ACh,\;0.1-1000\;{\mu}M)$, KCl were measured. Results : Contractile responses of TSM to ACh were significantly increased in CMM herbal acupuncture 1 group $(Ach\;1000\;{\mu}M)$, CMM herbal acupuncture 2 group $(ACh\;1,\;10\;{\mu}M)$, CMM herbal acupuncture 3 group $(Ach\;0.3,\;1,\;30,\;300\;{\mu}M)$. The sensitivity of TSM to ACh was significantly decreased in CMM herbal acupuncture 3 group. The maximal contractile response of TSM to ACh was significantly decreased in CMM herbal acupuncture 1, 3 group. The maximal contractile response of TSM to KCl was significantly decreased in CMM herbal acupuncture 1, 2, 3 group. The counts of lymphocytes in BALF was significantly increased in CMM herbal acupuncture 3 group. The counts of macrophages in BALF was significantly decreased in CMM herbal acupuncture 3 group. Interleukin-4 level in BALF was significantly increased in CMM herbal acupuncture 1,3 group. and it was increased in CMM herbal acupuncture 2 group, but there was no significance. Serum IgE level was significantly decreased in CMM herbal acupuncture 1, 2, 3 group. The counts of WBC in blood was significantly increased in CMM herbal acupuncture 1, 3 group Conclusion : Based on the above results it is assumed that CMM herbal acupuncture at BL13, LU4 can help the treatment of deficiency allergic Asthm.

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Hair Growth Promoting Effect of Black Soybean Extract In Vitro and In Vivo (In vitro 및 in vivo에서 검은콩 추출물의 육모 효과)

  • Jeon, Hee-Young;Kim, Seung-Hun;Kim, Chae-Wook;Shin, Hyun-Jeong;Seo, Dae-Bang;Lee, Sang-Jun
    • Korean Journal of Food Science and Technology
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    • v.43 no.6
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    • pp.747-753
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    • 2011
  • It is commonly believed that black soybean (Glycine max: BB) prevents and alleviates hair loss. However, few studies have directly assessed the effect of BB on hair growth. We presently evaluated the mitosis induction on dermal papillae cell and mitogenic effect on NIH3T3 cells in vitro. To elucidate the hair growth promoting effect in vivo, anagen induction and hair restoration were examined in a shaving model of C57BL/6 mice. We also conducted biochemical analysis of blood plasma. Significant stimulation of dermal papillae and NIH3T3 cell proliferation were observed by treatment of BB in a dose-dependent manner. BB markedly promoted hair growth and significantly improved blood total antioxidant capacity and reduced lipid peroxidation and triglyceride level. These results suggest that BB has hair growth promoting effect and it is a potent candidate for the prevention of hair loss.

INFLUENCE OF THE SHADE GUIDE DESIGN ON COLOR HATCHING (Shade guide의 형태가 색상 결정에 미치는 영향)

  • Park, Geol;Kim, Dong-Jun;Lee, Shee-Eun;Hwang, Yun-Chan;Oh, Won-Mann;Hwang, In-Nam
    • Restorative Dentistry and Endodontics
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    • v.30 no.3
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    • pp.170-177
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    • 2005
  • This study was conducted in order to assess whether the form of the shade guide affects in deciding the color of the teeth using the shade guide Eight shade light cured composite resins (Esthet-X, Dentsply, Milford, USA) were used in this study. Shade guides including the model of maxillary central incisors, teeth-form shade guide, doughnut form shade guide, and shade guide with perforated gray shield were prepared with eight shade composite resins and provided the codes randomly After arranging the models of teeth, 19 dentists working at the clinic of the Dentistry of Chonnam University Hospital and 65 students of college of dentistry, Chonnnam University selected the shade guides corresponding to the color of each tooth on the gray board under the D$_{65}$ standard illuminant. Bl shade showed highest accuracy of about 95% among all shade guides of 3 forms applied to the test and regardless of observer, tooth form shade guide showed the highest accuracy (p < 0.05) , and the doughnut form showed the lowest accuracy (p < 0.05). At the time of deciding on the color of the teeth using the shade guides as a result of above, the forms of the shade guides can affect the accuracy, and it suggests that the development of the diversified forms of shade guides, which may obtain more accurate results, is required.

Effect of the supplementation of Coconopsis lanceolata extract on lipid metabolism amelioration in type 2 diabetes mouse model induced by high fat diet (울릉도 섬더덕 추출물의 급여가 제2형 당뇨 동물의 지질대사 개선에 미치는 영향)

  • Yun, Won-Kap;Bae, Hyun-Ji;Kim, You-Jeong;Kwon, O Jun;Im, Moo Hyeog;Cho, Hyun Duk;Kim, Taewan
    • Food Science and Preservation
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    • v.21 no.1
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    • pp.107-113
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    • 2014
  • The present study was designed to investigate the antihyperlipidemic effect of Coconopsis lanceolata extract in C57BL/6J mice. The mice were divided into four groups: normal diet group (ND), high fat diet group (HFD), positive control group with 0.05% metformin (PC), Coconopsis lanceolata extract group (UCL). After 5 weeks of feeding, average body weight of the UCL group mice was slightly decreased, while that of the HFD group significantly increased) Also, liver and adipose tissue weights in the UCL group significantly increased. The levels of trigliceride (TG) and total in the plasma of UCL-supplemented group were significantly lower than those of high fat diet group. On the other hand, HDL-cholesterol level was increased. Expression level of proteins related with adipogenesis such as SREBP-1c, ACC, and FAS in the liver of the UCL group mice was much lower comparing with the HFD group mice. In conclusion, the results showed that the Coconopsis lanceolata extract possesses significant antihyperlipidemic effects in C57BL/6J mice.