• Biomolecules & Therapeutics
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• 제25권4호
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• pp.383-389
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• 2017

Dexmedetomidine is an ${\alpha}2$-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of $1{\mu}g/kg$ load dose, followed by $0.05{\mu}g/kg/min$ infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-$1{\beta}$, interleukin-6 and tumor nevrosis factor-${\alpha}$ as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-${\kappa}Bp65$, inhibitor of ${\kappa}B{\alpha}$ and phosphorylated of ${\kappa}B{\alpha}$ in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-${\kappa}B$ pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.

• Natural Product Sciences
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• 제9권4호
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• pp.249-255
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• 2003

Zizypus is one of the herbs widely used in Korea and China due to CNS calming effect. The present study aims to investigate the effect of the methanol extract of Zizyphi Jujube Semen (ZJS) on kainic acid (KA)-induced neurotoxicity in cultured rat cerebellar granule neuron. ZJS, over a concentration range of 0.05 to $5\;{\mu]g/ml$, inhibited KA $(500\;{\mu}M)-induced$ neuronal cell death, which was measured by a trypan blue exclusion test and a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. Pretreatment of ZJS $(0.5\;{\mu}g/ml)$ inhibited KA$(50\;{\mu}M)$-induced elevation of cytosolic calcium concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, Fura 2-AM, and generation of reactive oxygen species (ROS). ZJS $(0.5\;{\mu}g/ml)$ inhibited glutamate release into medium induced by KA $(500\;{\mu}M)$, which was measured by HPLC. These results suggest that ZJS prevents KA-induced neuronal cell damage in vitro.

• 한국약용작물학회지
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• 제11권4호
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• pp.298-305
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• 2003

Polygalae Radix (PR) from Polygala tenuifolia. (Polygalaceae) is traditionally used in China and Korea, since this herb has a sedative, antiinflammatory, and antibacterial agent. To extend pharmacological actions of PR in the CNS on the basis of its CNS inhibitory effect, the present study examined whether PR has the neuroprotective action against kainic acid (KA) -induced cell death in primarily cultured rat cerebellar granule neurons. PR, over a concentration range of 0.05 to $5{\mu}g/ml$ inhibited KA $(500\;{\mu}M)$-induced neuronal cell death, which was measured by a trypan blue exclusion test and a 3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyl-tetrazolium bromide (MTT) assay. PR $(0.5{\mu}g/ml)$ inhibited glutamate release into medium induced by KA $(500\;{\mu}M)$, which was measured by HPLC. Pretreatment of PR $(0.5{\mu}g/ml)$ inhibited KA $(500\;{\mu}M)$-induced elevation of cytosolic calcium concentration $([Ca^{2+}]_c)$ which was measured by a fluorescent dye, Fura 2-AM, and generation of reactive oxygen species (ROS). These results suggest that PR prevents KA-induced neuronal cell damage in vitro.

• 한국수산과학회지
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• 제39권5호
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• pp.419-426
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• 2006

This study investigated the ecology and growth of Monostroma nitidum Wittrock in both its natural habitat and the laboratory. The maximum length, width, and weight of M. nitidum in March were 9.0$\pm$4.7 cm, 9.6$\pm$3.6 cm, and 1.52$\pm$1.13 g, respectively. Yellowish-green or yellowish-brown reproductive thalli began to appear in January, and over 80% of the thalli matured by March. The male and female spores were ca. 6 $\mu$m long, and elongate and ovoid in shape. The spores had two flagella and one-eye spot, and tended to swim toward light. Maximum number of spores released from matured thalli was 236 cells/mL after 70 minutes at a light intensity of 100 $\mu$mol/m$^2$/s. The zygote diameter ranged from 3.4-6.0 $\mu$m (mean 4.2 $$m) and increased to 69.8 $\mu$m 14 weeks after culture. The mass release of zoospores was observed from thalli in the dark (3 to 12 days), after 30 min under dry conditions in the shade, at 25$^{\circ}C$, and a light intensity of 100 $\mu$mol/m$^2$/s. The maximum number of zoospores released was 109.8 cells/mL after 60 min of induction. M. nitidum fronds on the net increased to 6.8-7.2 cm in length, and 6.6-8.9 cm in width during the winter.

• 한국약용작물학회지
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• 제13권2호
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• pp.95-102
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• 2005

Caulis Bambusae in Taenia is widely used in Korea and China due to its various pharmacological activity. The present study aims to investigate the effect of the methanol extract of Caulis Bambusae in Taenia (CB) from Phyllostachys nigra Munro var. henonis Stapf (Gramineae) on amyloid ${\beta}$ protein (25-35) $(A{\beta}\;(25-35))$, a synthetic 25-35 amyloid peptide, -induced neurotoxicity using cultured rat cortical neurons. CB, over a concentration range of $10-50{\mu}g/{\mu}l$, inhibited the $A{\beta}\;(25-35)\;(10\;{\mu}M)$-induced neuronal cell death, as assessed by a 3-[4,5-dimethyIthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. CB $(50\;{\mu}g/{\mu}l)$ inhibited glutamate release into medium induced by $10\;{\mu}M\;A{\beta}$, (25-35) which was measured by HPLC. Pretreatment of CB $(50\;{\mu}g/{\mu}l)$ inhibited $10{\mu}M\;A{\beta}$ (25-35)-induced elevation of cytosolic calcium concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, fluo-4 AM, and generation of reactive oxygen species. These results suggest that CB prevents $A{\beta}$ (25-35)-induced neuronal ell damage in vitro.

• The Korean Journal of Physiology and Pharmacology
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• 제19권1호
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• pp.51-57
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• 2015

The etiology of periodontal disease is multifactorial. Exogenous stimuli such as bacterial pathogens can interact with toll-like receptors to activate intracellular calcium signaling in gingival epithelium and other tissues. The triggering of calcium signaling induces the secretion of pro-inflammatory cytokines such as interleukin-8 as part of the inflammatory response; however, the exact mechanism of calcium signaling induced by bacterial toxins when gingival epithelial cells are exposed to pathogens is unclear. Here, we investigate calcium signaling induced by bacteria and expression of inflammatory cytokines in human gingival epithelial cells. We found that peptidoglycan, a constituent of grampositive bacteria and an agonist of toll-like receptor 2, increases intracellular calcium in a concentration-dependent manner. Peptidoglycan-induced calcium signaling was abolished by treatment with blockers of phospholipase C (U73122), inositol 1,4,5-trisphosphate receptors, indicating the release of calcium from intracellular calcium stores. Peptidoglycan-mediated interleukin-8 expression was blocked by U73122 and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester). Moreover, interleukin-8 expression was induced by thapsigargin, a selective inhibitor of the sarco/endoplasmic reticulum calcium ATPase, when thapsigargin was treated alone or co-treated with peptidoglycan. These results suggest that the gram-positive bacterial toxin peptidoglycan induces calcium signaling via the phospholipase C/inositol 1,4,5-trisphosphate pathway, and that increased interleukin-8 expression is mediated by intracellular calcium levels in human gingival epithelial cells.

• 생명과학회지
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• 제25권1호
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• pp.1-7
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• 2015

칼슘 의존적으로 활성화되는 neutral protease calpain에 의한 단백질 분해는 세포의 성장을 조절하는데 중요한 단백질들의 역할에 매우 중요한 역할을 한다. Cyclin의 분해는 세포주기의 진행을 위한 필연적인 과정이다. D-type cyclins는 외부자극이나 신호에 의하여 세포주기의 G1 초기에 합성이 된 후 cyclin-dependent kinases (cdk4 및 cdk6)와의 결합하여 세포주기 S기 진입을 촉진하는 역할을 한다. 본 연구에서는 cyclin D3 단백질이 calpain protease에 의하여 번역 후 수준에서 조절 받고 있음을 제시하였다. 본 실험의 조건에서 lovastatin과 actinomycin D가 처리된 PC-3-M 전립선 암세포에서 cyclin D3 단백질의 발현이 완전히 사라졌지만, calpain inhibitor인 LLnL의 처리에 의하여 정상 수준으로 회복되었음을 알 수 있었다. 그러나 26S proteasome의 선택적 억제제인 lactacystin, lysosome 억제제인 ammonium chloride 및 chloroquine, serine protease 억제제인 PMSF는 동일 조건에서 lovastatin과 actinomycin D 처리에 의한 cyclin D3 단백질의 발현저하를 억제하지는 못하였다. In vitro 조건에서 순수 분리된 calpain은 cyclin D3 단백질을 칼슘 농도 의존적으로 분해하였으며, cyclin D3 단백질의 반감기는 LLnL 처리에 의하여 매우 유의적으로 증가되었다. 또한 calpain 저해인자인 calpastatin의 과발현은 PC-3-M 세포에서 뿐만 아니라 NIH 3T3 섬유아세포에서도 cyclin D3 단백질의 반감기 및 안전성을 증대시켰다. 이러한 결과는 cyclin D3 단백질이 칼슘에 의해 활성화 되는 protease calpain에 의해 조절됨을 보여주는 것이다.

• 한국약용작물학회지
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• 제13권5호
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• pp.219-226
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• 2005

Sanguisorbae radix (SR) from Sanguisorba officinalis L. (Losaceae) is widely used in Korea and China due to its various pharmacological activity. The present study aims to investigate the effect of the methanol extract of SR on amyloid ${\beta}$ Protein(25-35) $(A{\beta}\;(25-35))$, a synthetic 25-35 amyloid peptide, -induced neurotoxicity using cultured rat cortical neurons. SR, over a concentration range of $10-50\;{\mu}g/ml$, inhibited the $A{\beta}$ (25-35) $(10\;{\mu}M)-induced$ neuronal cell death, as assessed by a 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. Pretreatment of SR $(50\;{\mu}g/ml)$ inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced} elevation of cytosolic calcium concentration $([Ca^{2+}]c)$, which was measured by a fluorescent dye, fluo-4 AM. SR $(10\;and\;50\;{\mu}g/ml)$ inhibited glutamate release into medium induced by $10\;{\mu}M\;A{\beta}(25-35)$, which was measured by HPLC, and generation of reactive oxygen species. These results suggest that SR prevents $A{\beta}$ (25-35)-induced neuronal cell damage in vitro.

• Biomolecules & Therapeutics
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• 제5권3호
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• pp.239-245
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• 1997

Trimetoquinol (TMQ) and its analogs are known to have thromboxane $A_2$ antagonistic action. We also reported that GS389, chemically similar to TMQ, has competitive antagonistic action in rat aorta and human platelets. In the present study, we investigated the pharmacological characteristics of GS283 and GS 386, analogs of GS389, using vascular smooth muscle, human platelets and rat brain homogenates. In isolated pig coronary artery (PCA), both of GS283 and GS386 relaxed U46619-contracted rings in concentration dependent manner. Pretreatment with several concentrations of GS283 and GS386 shifted the dose-response curves to the right, and reduced of maximum contration dose-dependently. Furthermore, GS283 and GS386 strongly inhibited $Ca^{2+}$ -induced contraction in the PCA. In human platelets, U46619- and A23187-induced platelet aggregation was inhibited by GS283 and GS386, concentration-dependently. Anti-platelet aggregation was related to the compound\`s ability to inhibit ATP release at each stimulation. In rat brain homogenates, receptor-binding assay resulted that both GS283 and GS386 have a relative affinity to $\alpha$-adrenergic receptor. Taken together. we concluded that the mechamism of action of GS283 and GS86 is not related with in TXA$_2$ receptor but concerned with calcium antagonistic action and a-blocking action.n.

• Molecules and Cells
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• 제38권9호
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• pp.796-805
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• 2015

Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced $[Ca^{2+}]_i $ transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated $[Ca^{2+}]_i $ transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin-enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 1 2 weeks) also significantly attenuated amyloid-${\beta}$ protein ($A{\beta}$)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to $A{\beta}$ and could be utilized for AD prevention or therapy.