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Mechanism of the relaxant action of Trazodone in isolated rat aorta (흰쥐 대동맥에서 Trazodone의 혈관이완 작용기전)

  • Kim, Shang-jin;Kim, Jeong-gon;Kim, Jin-shang
    • Korean Journal of Veterinary Research
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    • v.43 no.4
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    • pp.587-595
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    • 2003
  • The aim of this study was to investigate trazodone's effect on vasorelaxation and blood pressure lowering and to examine its underlying mechanism of action in isolated thoracic aorta and anesthesized rats. Precontracted aortic rings with high KCl were relaxed with trazodone, at concentrations of $50{\mu}M$ or greater. However, precontracted rings with phenylephrine (PE) were relaxed with trazodone, at concentrations of $0.03{\mu}M$ or greater, in a concentration-dependent manner. These relaxant effects of trazodone on endothelium intact rat aortic rings were significantly greater than those on denuded rings. The trazodone-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA) and N(omega)-nitro-L-arginine methyl ester (L-NAME), guanylate cyclase inhibitors, methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a $Ca^{2+}$-activated $K^+$ channel blocker, tetrabutylammonium (TBA), a $Ca^{2+}$ channel blocker, nifedipine, $Na^+$ channel blockers, lidocaine and procaine, and removal of extracellular $Na^+$, but not by aminoguanidine, 2-nitro-4-carboxyphenyl-n, n-diphenylcarbamate (NCDC), indomethacin, glibenclamide and clotrimazole. In vivo, infusion of trazodone elicited significant decrease in arterial blood pressure. Trazodone-induced decrease in blood pressure was markedly inhibited by pretreatment of intravenous injection of saponin, L-NNA, methylene blue, TBA, lidocaine or nifedipine. These findings suggest that the endothelium-dependent relaxation and decrease in blood pressure induced by trazodone is mediated by release of NO from the endothelium, activation of TBA-sensitive $Ca^{2+}$-activated $K^+$ channels or inhibition of $Ca^{2+}$ entry through voltage-gated channel.

Phylogenetic Analysis of Schizonepeta Spike on the Basis of DNA Sequences (염기서열을 이용한 한약재 형개의 기원 및 유연관계 분석)

  • Jigden, Baigalmaa;Kim, Myung-Kyum;Noh, Jong-Hun;Sun, Hua;Yang, Deok-Chun
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.1
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    • pp.46-53
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    • 2009
  • Schizonepeta spike (Korean name "Hyung-Gae") has been used for oriental medicinal purposes in Korea, China and Japan. In this study, twenty six "Hyung-Gae" samples were collected including nine certified Schizonepeta tenuifolia plants, and seventeen commercially marketed "Hyung-Gae" products. Chloroplast trnL-F and rDNA ITS regions of the "Hyung-Gae" samples were sequenced and used to identify whether the samples were genuine S. tenuifolia or not. As the result, the trnL-F and ITS sequences of all the "Hyung-Gae" samples were shown to be identical and it was proven that commercially available medicinal products "Hyung-Gae" are genuine S. tenuifolia. Phylogenetic tree of S. tenuifolia using the trnL-F sequences was constructed and compared with phylogenetic tree using ITS of rDNA region sequences. In these tree, S. tenuifolia was affiliated in the family Lamiaceae. It is proven that trnL-F and ITS phylogenetic trees are useful to study taxonomic position of S. tenuifolia.

Possible Involvement of $Ca^{2+}$ Activated $K^+$ Channels, SK Channel, in the Quercetin-Induced Vasodilatation

  • Nishida, Seiichiro;Satoh, Hiroyasu
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.5
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    • pp.361-365
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    • 2009
  • Effects of quercetin, a kind of flavonoids, on the vasodilating actions were investigated. Among the mechanisms for quercetin-induced vasodilatation in rat aorta, the involvement with the $Ca^{2+}$ activated $K^+$ ($K_{Ca}$) channel was examined. Pretreatment with NE ($5\;{\mu}M$) or KCl (60 mM) was carried out and then, the modulation by quercetin of the constriction was examined using rat aorta ring strips (3 mm) at $36.5^{\circ}C$. Quercetin (0.1 to $100\;{\mu}M$) relaxed the NE-induced vasoconstrictions in a concentrationdependent manner. NO synthesis (NOS) inhibitor, NG-monomethyl-L-arginine acetate (L-NMMA), at $100\;{\mu}M$ reduced the quercetin ($100\;{\mu}M$)-induced vasodilatation from $97.8{\pm}3.7%$ (n=10) to $78.0{\pm}11.6%$ (n=5, p<0.05). Another NOS inhibitor, L-NG-nitro arginine methyl ester (L-NAME), at $10\;{\mu}M$ also had the similar effect. In the presence of both $100\;{\mu}M$ L-NMMA and $10\;{\mu}M$ indomethacin, the quercetin-induced vasodilatation was further attenuated by $100\;{\mu}M$ tetraethylammonium (TEA, a $K_{Ca}$ channel inhibitor). Also TEA decreased the quercetin-induced vasodilatation in endothelium-denuded rat aorta. Used other $K_{Ca}$ channel inhibitors, the quercetin-induced vasodilatation was attenuated by $0.3\;{\mu}M$ apamin (a SK channel inhibitor), but not by 30 nM charybdotoxin (a BK and IK channel inhibitor). Quercetin caused a concentration-dependent vasodilatation, due to the endotheliumdependent and -independent actions. Also quercetin contributes to the vasodilatation selectively with SK channel on smooth muscle.

A newly naturalized species in Korea: Amaranthus powellii S. Watson (Amaranthaceae) (한국 미기록 귀화식물: 민털비름(비름과))

  • Park, Yong-Ho;Park, Su-Hyun;Yoo, Ki-Oug
    • Korean Journal of Plant Taxonomy
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    • v.44 no.2
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    • pp.132-135
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    • 2014
  • A newly naturalized plant, Amaranthus powellii S. Watson was found Jail-dong, Uijeongbu-si, Gyeonggi-do, Korea. This species is native to Southwestern USA and Northern Mexico, and it is also naturalized in worldwide of temperate regions. This species was distinguished from the related species, A. patulus Bertol. and A. hybridus L., by leave blades broadly elliptic, rhombic or lanceolate, petals unequal, without conspicuous green mid-veins, and utricle gradually narrowed toward the stigma. Korean name was given as 'Min-teol-bi-reum' to A. powellii S. Watson, based on the character, it was hairy less than the three related species, A. patulus Bertol., A. hybridus L. and A. retroflexus L., conspicuously. Descriptions for mophological characters, photographs, illustrations and keys to allied taxa were provided.

In vivo Investigation of Anti-diabetic Properties of Ripe Onion Juice in Normal and Streptozotocin-induced Diabetic Rats

  • Lee, Chul-Won;Lee, Hyung-Seok;Cha, Yong-Jun;Joo, Woo-Hong;Kang, Dae-Ook;Moon, Ja-Young
    • Preventive Nutrition and Food Science
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    • v.18 no.3
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    • pp.169-174
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    • 2013
  • The acute and subacute hypoglycemic and antihyperglycemic effects of drinkable ripe onion juice (Commercial product name is "Black Onion Extract") were investigated in normal and streptozotocin-induced diabetic rats. For tests of acute and subacute hypoglycemic effects, ripe onion juice (5 and 15 mL/kg b.w.) was administered by oral gavage to normal Sprague Dawley rats and measurements of fasting glucose levels and oral glucose tolerance tests were performed. Tolbutamide was used as a reference drug at a single oral dose of 250 mg/kg b.w. To test anti-hyperglycemic activity, the ripe onion juice was administered to streptozotocin-induced diabetic rats by oral gavage at single dose of 15 mL/kg b.w. per day for 7 consecutive days. Oral administration of the ripe onion juice at either dosed level of 5 or 15 mL/kg b.w. showed no remarkable acute hypoglycemic effect in normal rats. The two dosed levels caused a relatively small reduction, only 18% and 12% (5 and 15 mL/kg b.w., respectively) decrease in glucose levels at 2 h after glucose loading in normal rats. However, at 3 h after glucose loading, blood glucose levels in the ripe onion juice-dosed rats were decreased to the corresponding blood glucose level in tolbutamide-dosed rats. Although showing weak hypoglycemic potential compared to that of tolbutamide, oral administration of ripe onion juice (15 mL/kg b.w.) for a short period (8 days) resulted in a slight reduction in the blood glucose levels that had elevated in Streptozotocin-induced diabetic rats. In conclusion, these results suggest that the commercial product "Black Onion Extract" may possess antihyperglycemic potential in diabetes.

Inhibitory Effects of Polyphenol-Rich Fraction Extracted from Rubus coreanum M on Thoracic Aortic Contractility of Spontaneously Hypertensive Rats

  • Lim, Hyo-Jeong;Min, Seon-Young;Woo, Eun-Ran;Lim, Dong-Yoon
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.477-486
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    • 2011
  • The purpose of the present study was to investigate whether polyphenol-rich fraction extracted from fruit wine of Rubus coreanum M (PCRC) can affect the contractility of the thoacic aortic strips isolated from spontaneously hypertensive rats (SHRs), and to clarify its mechanism of action. PCRC (200-800 ${\mu}g/mL$) concentration-depenedently blocked phenylephrine (10 ${\mu}M$)-induced contractile responses of the isolated aortic strips of SHRs. PCRC (400 ${\mu}g/mL$), added in to bath medium, also depressed the contractile active tension evoked by both phenylephrine (3 and 10 ${\mu}M$) and high potassium (25 and 56 mM). In the simultaneous presence of PCRC (400 ${\mu}g/mL$) and L-NAME (a selective inhibitor of NO synthase, 300 ${\mu}M$), the contractile responses evoked by phenylephrine and high $K^+$ were recovered to considerable level of the corresponding control contractility compared with those effects of PCRC-treatment alone. However, in the simultaneous presence of indomethacin (10 ${\mu}M$, a selective cyclooxygenase inhibitor) and PCRC (400 ${\mu}g/mL$), they were not affected. In the endothelium-denuded aortic strips by CHAPS-treatment, PCRC did not affect the contractile responses induced by phenylephrine or high potassium. Interestingly, PCRC (1.0, 3.0 and 10.0 mg/kg/30 min, i.v., respectively) dose-dependently suppressed norepiphrine-induced vasopressor responses in anesthetized SHRs. Collectively, we concluded that PCRC causes vasorelaxation in the thoracic aortic strips with intact endothelium of SHRs at least partly by the increased NO production through the activation of NO synthase of vascular endothelium, but not through the activation of cyclooxygenase. These results suggest that PCRC might be helpful to prevent or alleviate cardiovascular diseases, including hypertension.

Analysis on Antioxidant Activity and Agronomic Characteristics of Extract from Smilacis Chinae Radix

  • Hyeon Mi Jo;Sin Park;Eun Bi Choi;In-Ho Choi
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2022.10a
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    • pp.313-313
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    • 2022
  • The Smilacis chinae Radix refers to the root of Smilax chinae L distributed in mountain and filed of Korea, and it is a vine shrub in the Lilaceae family, called Berchemia berchemiaefolia, and is referred to as Smilacis chinae Radix in it's a natural medicine name. Antibacterial, inflammatory, and antioxidant activity were studied in Smilacis chinae Radix. In this study, biological activities such as antioxidant (DPPH, ABTs, TPC), cytotoxicity, wrinkle improvement, and whitening improvement to increase the utilization value of Smilacis chinae Radix and identify the botanical value. Therefore, we tried to explore the applicability of Smilacis chinae Radix as a functional cosmetic material. Smilacis chinae Radix (SCR) was dried and extracted with ethanol. In order to measure the biological activity of the SCR, antioxidant activity, inhibition activities of collagenase, tyrosinase and cell viability were measured. The DPPH (1,1-diphenyl-2-picryl hydrazyl) radical scavenging activity in the extract with a concentration of 400㎍/mL is 91.22% ± 0.41%%. ABTs (2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity in the extract with a concentration of 400㎍/mL is 99.60% ± 0.03%. Total polyphenol contents (TPC) are 0.203 ± 0.05 mg GAE/mg Ext when SCR was lmg/mL. And the Cell viability for HaCaT derived human keratinocyte and Raw264.7, a mouse-derived macrophage was determined using the MTT assay. When cell was treated with 100㎍/mL of SCR, HaCaT cell showed cell viability of 78.09 ± 0.1% and Raw264.7 cell showed cell viability of 91.88 ± 0.42%. From the above results, we have shown the possibility that the CSR have antioxidant ability, inhibition activity of collagenase and tyrosinase and cell safety ability which can be useful in a functional cosmetic material.

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$H_2$ Receptor-Mediated Relaxation of Circular Smooth Muscle in Human Gastric Corpus: the Role of Nitric Oxide (NO)

  • Lee, Sang Eok;Kim, Dae Hoon;Kim, Young Chul;Han, Joung-Ho;Choi, Woong;Kim, Chan Hyung;Jeong, Hye Won;Park, Seon-Mee;Yun, Sei Jin;Choi, Song-Yi;Sung, Rohyun;Kim, Young Ho;Yoo, Ra Young;Park, Hee Sun;Kim, Heon;Song, Young-Jin;Xu, Wen-Xie;Yun, Hyo-Yung;Lee, Sang Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.5
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    • pp.425-430
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    • 2014
  • This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, $K^+$ channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, $N^G$-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the $H_2$ receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through $H_2$ receptor and NO/sGC pathways.

Red Ginseng Saponin Fraction A Isolated from Korean Red Ginseng by Ultrafiltration on the Porcine Coronary Artery

  • Jung, Young-Hyun;Park, Kwang-Yeol;Jeon, Jin-Hong;Kwak, Yi-Seong;Song, Yong-Bum;Wee, Jae-Joon;Rhee, Man-Hee;Kim, Tae-Wan
    • Journal of Ginseng Research
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    • v.35 no.3
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    • pp.325-330
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    • 2011
  • Red ginseng saponin fraction-A (RGSF-A) contains a high percentage of panaxadiol saponins that were isolated from Korean red ginseng by ultrafiltration. The aim of this study was to elucidate the effects of RGSF-A on the porcine distal left anterior descending (LAD) coronary artery. The relaxant responses to RGSF-A were examined during contractions induced by 100 nM U46619 (9,11-dideoxy-9a,11a-methanoepoxy-prostaglandin F2a), a stable analogue of thromboxane A2. RGSF-A dose-dependently induced biphasic (fast- and slow-) relaxation in the distal LAD coronary artery in the presence of an intact endothelium. The fast-relaxation was quickly achieved in a minute, and then the slow-relaxation was slowly developed and sustained for more than thirty minutes after the administration of RGSF-A. The slow-relaxation had a tendency to be bigger than the fast-relaxation. Fast relaxation induced by RGSF-A was almost blocked by $N_{\omega}$-Nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase synthase inhibitor and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. However slow relaxation induced by RGSF-A was only partially inhibited by L-NAME and ODQ. In the endothelium-removed ring, RGSF-A evoked only slowrelaxation to a certain extent. These data suggest that RGSF-A induced both endothelium dependent fast- and slow-relaxation and endothelium independent slow-relaxation in the porcine distal LAD coronary artery. The endothelium dependent fast-relaxation is mediated by the nitric oxide (NO)-cGMP pathway, and the endothelium dependent slow-relaxation is at least partially mediated by the NO-cGMP pathway. However, the endothelium-independent slow-relaxation remains to be elucidated.

Ethanol Extract of Cynanchum wilfordii Produces Endothelium-Dependent Relaxation in Rat Aorta and Anti-inflammatory Activity in Human Aortic Smooth Muscle Cells

  • Choi, Deok-Ho;Lee, Yun-Jung;Kim, Eun-Joo;Li, Xiang;Kim, Hye-Yoom;Hwang, Sun-Mi;Yoon, Jung-Joo;Lee, So-Min;Min, Eun-Kyeong;Kang, Dae-Gill;Lee, Ho-Sub
    • The Journal of Korean Medicine
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    • v.31 no.6
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    • pp.47-57
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    • 2010
  • Objective: The present study investigated the effect of ethanol extract of Cynanchum wilfordii (ECW) on vascular relaxation and vascular inflammation in rat artery isolated from rats and anti-inflammatory activity in human aortic smooth muscle cells (HASMC). Methods: Vascular tone and guanosine 3',5'-cyclic monophosphate (cGMP) production were examined in rat artery isolated from Sprague Dawley rats, in the presence of ECW. HASMC were incubated with tumor necrosis factor-alpha (TNF-${\alpha}$) or Angiotensin II for 24 h. Matrix metalloproteinase (MMP)-2 and anti-oxidant activity of ECW was investigated by pretreatment with ECW in HASMC. Results: Cumulative treatment of ECW relaxed aortic smooth muscles of rats in a dose-dependent manner. ECW-induced vasorelaxation was significantly decreased by pretreatment of L-arginine methyl ester (L-NAME) or oxadiazolo-quinoxalinone (ODQ). Furthermore, ECW treatment of thoracic aorta significantly increased cGMP production. Incubation of ECW with ODQ or L-NAME markedly decreased ECW-induced cGMP production. ECW treatment dose-dependently suppressed TNF-${\alpha}$- or Angiotensin II-induced increase in matrix metalloproteinase-2 expression in HASMC. Also, ECW exhibited 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity in vitro and reduced TNF-${\alpha}$-induced increase in reactive oxygen species production in a dose-dependent manner. Conclusions: Taken together, the results suggest that ECW exerts vascular relaxation via NO/cGMP signaling pathway and decreases MMP-2 expression via anti-oxidant activity.