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Evidence for the Participation of ATP-sensitive Potassium Channels in the Antinociceptive Effect of Curcumin

  • Paz-Campos, Marco Antonio De;Chavez-Pina, Aracely Evangelina;Ortiz, Mario I;Castaneda-Hernandez, Gilberto
    • The Korean Journal of Pain
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    • 제25권4호
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    • pp.221-227
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    • 2012
  • Background: It has been reported that curcumin, the main active compound of Curcuma longa, also known as turmeric, exhibits antinociceptive properties. The aim of this study was to examine the participation of ATP-sensitive potassium channels ($K_{ATP}$ channels) and, in particular, that of the L-arginine-nitric oxide-cyclic GMP-$K_{ATP}$ channel pathway, in the antinociceptive effect of curcumin. Methods: Pain was induced by the intraplantar injection of 1% formalin in the right hind paw of Wistar rats. Formalin-induced flinching behavior was interpreted as an expression of nociception. The antinociceptive effect of oral curcumin was explored in the presence and absence of local pretreatment with L-NAME, an inhibitor of nitric oxide synthase, ODQ, an inhibitor of soluble guanylyl cyclase, and glibenclamide, a blocker of $K_{ATP}$ channels. Results: Oral curcumin produced a dose-dependent antinociceptive effect in the 1% formalin test. Curcumin-induced antinociception was not altered by local L-NAME or ODQ, but was significantly impaired by glibenclamide. Conclusions: Our results confirm that curcumin is an effective antinociceptive agent. Curcumin-induced antinociception appears to involve the participation of $K_{ATP}$ channels at the peripheral level, as local injection of glibenclamide prevented its effect. Activation of $K_{ATP}$ channels, however, does not occur by activation of the L-arginine-nitric oxide-cGMP-$K_{ATP}$ channel pathway.

Genetic Diversity and Population Structure of the Xanthomonas campestris pv. campestris Strains Affecting Cabbages in China Revealed by MLST and Rep-PCR Based Genotyping

  • Chen, Guo;Kong, Congcong;Yang, Limei;Zhuang, Mu;Zhang, Yangyong;Wang, Yong;Ji, Jialei;Fang, Zhiyuan;Lv, Honghao
    • The Plant Pathology Journal
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    • 제37권5호
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    • pp.476-488
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    • 2021
  • Xanthomonas campestris pv. campestris (Xcc) is the causal agent of black rot for cruciferous vegetables worldwide, especially for the cole crops such as cabbage and cauliflower. Due to the lack of resistant cabbage cultivars, black rot has brought about considerable yield losses in recent years in China. Understanding of the pathogen features is a key step for disease prevention, however, the pathogen diversity, population structure, and virulence are largely unknown. In this study, we studied 50 Xcc strains including 39 Xcc isolates collected from cabbage in 20 regions across China, using multilocus sequence genotyping (MLST), repetitive DNA sequence-based PCR (rep-PCR), and pathogenicity tests. For MLST analysis, a total of 12 allelic profiles (AP) were generated, among which the largest AP was AP1 containing 32 strains. Further cluster analysis of rep-PCR divided all strains into 14 DNA groups, with the largest group DNA I comprising of 34 strains, most of which also belonged to AP1. Inoculation tests showed that the representative Xcc strains collected from diverse regions performed differential virulence against three brassica hosts compared with races 1 and 4. Interestingly, these results indicated that AP1/DNA I was not only the main pathotype in China, but also a novel group that differed from the previously reported type races in both genotype and virulence. To our knowledge, this is the first extensive genetic diversity survey for Xcc strains in China, which provides evidence for cabbage resistance breeding and opens the gate for further cabbage-Xcc interaction studies.

Characterization of valacyclovir transport mechanism across the intestinal epithelium

  • Han, H.;Covitz, M.;Surendran, N.;Stewart, B.;Amidon, G.L.
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1997년도 춘계학술대회
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    • pp.119-119
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    • 1997
  • Valacyclovir is a L-valyl ester prodrug of acyclovir which is a highly effective and selective antiviral agent in the treatment of herpes virus diseases. Valacyclovir is rapidly and almost completely converted to acyclovir and increases the oral bioavailability of acyclovir three to five fold. However, the intestinal absorption mechanism of valacyclovir is not clear. If the improved absorption mechanism of valacyclovir is fully understood, it will provide a rationale of designing the amino acid ester prodrugs of polar drugs containing hydroxyl group. The main objective of our present study is to characterize the membrane transport mechanism of valacyclovir. Methods : Intestinal absorption of valacyclovir was investigated by using in-situ rat perfusion study and its wall permeability was estimated by modified boundary layer model. The membrane transport mechanism was also investigated through the uptake study in Caco-2 cells and in CHO-hPepTl cells. Results : In the rat perfusion study, the wall permeability of valacyclovir was ten times higher than acyclovir and showed concentration dependency, Valacyclovir also demonstrated a D,L stereo-selectivity with L-isomer having an approximately five-fold higher permeability than D-isomer. Mixed dipeptides and cephalexin, which are transported by dipeptide carriers, strongly competed with valacyclovir for the intestinal absorption, while L-valine did not show any competition with valacyclovir. This indicated that the intestinal absorption of valacyclovir could be dipeptide carrier-mediated. In addition, the competitive uptake study in Caco-2 cells presented that dipeptides reduced the valacyclovir uptake but valine did not. Also, in IC$\sub$50/ study, valacyclovir showed strong inhibition on the $^3$H-gly-sar uptake in CHO-hPepTl cells over-expressing a human intestinal peptide transporter. Taken together, the result from our present study indicated that valacyclovir utilized the peptide transporter for the intestinal absorption.

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고콜레스테롤 식이로 유발된 동맥경화병태흰쥐의 혈관조직내 지질과산화 및 산화스트레스에 대한 삼칠근의 영향 (Influence of Panax notoginseng on the Atherosclerosis Induced by High-cholesterol Feed in Rats)

  • 김종구;박선동;박원환
    • 동의생리병리학회지
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    • 제20권5호
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    • pp.1187-1195
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    • 2006
  • Panax notoginseng exhibit several beneficial effects including anti-oxidant effects. P. notoginseng is used as a therapeutic agent to stop haemorrhages and a tonic to promoted health in Korean and Chinese medicine. The pharmacokinetic profiles of the main P. notoginseng are still not accurately investigated. The exact mechanism of the anti-oxidant activitys of water extracts of P. notoginseng, however, has not been determined. in present study, I examined the effects of water extracts of P. notoginseng on high cholesterol diet atherosclerosis-induced rats in serum and abdominal aorta. A total of 3-week old 9 male rats of Sprague-Dawley were divided into 3 groups and fed with the basal diet (normal group), high cholesterol diet (atherosclerosis induced group) for 8 weeks, high cholesterol diet supplemented with water extracts of P. notoginseng (P. notoginseng group) for 4 weeks. And rats were sacrificed, serum lipid level, abodominal aortic anti-oxidant activities and lipid peroxide were measured. These results indicated that serum total cholesterl, LDL-cholesterol, triglycerides concentration significently lowered in P. notoginseng group than high cholesterol diet group. But HDL-cholesterol concentraion significently higher in P. notoginseng group than high cholesterol feed group. And abdominal aortic xanthine oxidase activity was significantly reduced by dietary water extracts of P. notoginseng supplementation (p<0.05) Also abdominal aortic superoxide dismutase, catalase, glutathione peroxidase activities were significantly increased by dietary water extracts of P. notoginseng supplementation (p<0.05) Especially, abdominal aortic level of lipid peroxide tended to increase in high cholesterol feed group, but water extract of P. notoginseng intake reduced the value (p<0.05).

Effect of Panax notoginseng on Hepatic Microvascular Dysfunction in Rats

  • Lee, Soo-Kyoung;Kim, Jun-Gi;Choi, Dall-Young;Park, Won-Hwan
    • 동의생리병리학회지
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    • 제20권6호
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    • pp.1658-1663
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    • 2006
  • Panax notoginseng (Buck) F.H chen. root (PNS) is used as a therapeutic agent to stop haemorrhages and a tonic to promote health in Korean and Chinses medicine. The pharmacokinetic profiles of the main PNS are still not accurately investigated. Our preliminary aim is to elucidate the pharmacokinetics features of the PNS in rats. Objective of this study is to determine whether PNS affects hepatic microvascular dysfunction elicited by gut ischemia and reperfusion (I/R), since gut I/R causes hepatic microvascular dysfunction, and to investigate the role of nitric oxide (NO). No has been found to be a modulator of the adhesive interactions between platelet and endothelial cells. Male Wistar rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Intravital microscopy was used to monitor the number of non-perfused sinusoids (NPS). In another set of experiments, PNS (1 g/kg pre day intragastrically) was administered to rats for 7 days. In some experiments, dexamethasone (ST) (2 mg/kg per day intravenously) was administered. In control rats, gut I/R elicited increases in the number of NPS, and plasma TNF-${\alpha}$ and ALT activities, and these changes were mitigated by the pretreatment with PNS. Pretreatment with an No synthase inhibitor diminished the protective effects of PNS on the increase in NPS and plasma TNF-${\alpha}$ levels, but not its effect on the increase in plasma ALT activities. Pretreatment with PNS increased plasma nitrite/nitrate levels. The responses caused by gut I/R were attenuated by the pretreatment with ST. Pretreatment with an NO synthase inhibitor did not affect the effect of ST. These results suggest that PNS attenuates the gut I/R-induced hepatic microvascular dysfunction and inflammatory responses such as TNF-${\alpha}$ production in the early phase via enhancement of NO production, and sequential hepatocellular damage via its anti-inflammatory effect like corticosteroid effect.

Hesa-A Down-Regulates erb/b2 Oncogene Expression and Improves Outcome of Oral Carcinoma in a Rat Model

  • Abbasi, Mehran Mesgari;Mehdipour, Masoumeh;Monfaredan, Amir;Jahanban-Esfahlan, Rana
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권16호
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    • pp.6947-6951
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    • 2015
  • Background: Oral carcinoma (OC) remains one of the most difficult malignancies to cure. Hesa-A is an Iranian herbal-marine compound that has shown promising anti-tumor properties against various human tumors. However, its mechanism of action remains to be addressed. The present study was conducted to evaluate the effect of two doses of Hesa-A on mRNA expression of erb$\backslash$b2 as a main prognosticator tumor marker for OC in an animal model. Materials and Methods: A total of 60 rats were randomly divided into 5 groups of 12 animals each. Rats in carcinoma groups received 0, 250 and 500mg/kg body weight doses of Hesa-A 3 times a day. The other two groups were considered as treated and untreated control groups. At the end of the experiment, animals were sacrificed and tongue tissues subjected to H and E staining and real time PCR. Results: Our results showed that compared to the control group, erb$\backslash$b2 was over-expressed ~ 30% in the carcinoma group. After treatment with 250mg/kg and 500mg/kg body weight of Hesa-A, erb$\backslash$b2 levels dropped by 24.1% and 3.4 % respectively compared to the control carcinoma group (p<0.01, p<0.0001). Moreover, there was a significant relation between erb$\backslash$b2 mRNA content and observed pathological changes in studied groups (p<0.05). Conclusions: These data provide insight into mechanism(s) by which Hesa-A may improve clinical outcome of oral carcinoma by affecting oncogene erb$\backslash$b2 expression and suggest Hesa-A as an effective chemotherapeutic agent in treatment of HER+tumors.

First Description of Coleosporium plectranthi Causing Perilla Rust in Korea

  • Yun, Hye-Young;Kim, Young-Ho;Hong, Soon-Gyu;Lee, Kyung-Joon
    • The Plant Pathology Journal
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    • 제23권1호
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    • pp.7-12
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    • 2007
  • Perilla rust is a damaging disease in perilla cultivation in Korea. Its causal agent was identified as Coleosporium plectranthi based on descriptions of morphological characteristics of spores and spore-producing fruiting structures(in uredinial and telial stages from perilla and in aecial stage from the alternate host pine) collected in 15 locations in Korea during the disease survey from 2004 to 2006. These characteristics were yellow or orange uredinium; globose or ellipsoid urediniospore of $20.8{\mu}m{\times}18{\mu}m$ in size; verruca of $0.3mm{\times}1.2mm$; orange telium; one-celled, oblong ellipsoid teliospore of $63.1{\mu}m{\times}19.7{\mu}m$ with one-layered crusts or four-celled(when mature), internal basidium of $64.2{\mu}m{\times}19.7{\mu}m$; ellipsoid to globoid basidiospore of $20.3{\mu}m{\times}12{\mu}m$; type 2 spermogonium; yellow, broadly ellipsoid peridial cell of $35.6{\mu}m{\times}23.1{\mu}m$; and broadly ellipsoidal or subglobose aeciospore of $25.9{\mu}m{\times}18.8{\mu}m$. Phylogenetic analysis of 28S rDNA sequences revealed the closest relatedness to those of the genus Coleosporium, a monophyletic group distinguished from other rust fungi and divided into two main lineages, one of which was C. plectranthi grouped with high bootstrap value(96%). In pathogenicity test, both aeciospores and urediniospores caused rust development on perilla leaves. This is the first description of C. plectranthi causing perilla rust with the first findings of its telial stage on perilla and the first rust disease on the aecial host in Pinus densiflora. These aspects would provide basic information for the development of control measures of the disease.

Gintonin-enriched fraction improves sarcopenia by maintaining immune homeostasis in 20- to 24-month-old C57BL/6J mice

  • Oh, Hyun-Ji;Jin, Heegu;Nah, Seung-Yeol;Lee, Boo-Yong
    • Journal of Ginseng Research
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    • 제45권6호
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    • pp.744-753
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    • 2021
  • Background: Gintonin-enriched fraction (GEF) is a new non-saponin component glycolipoprotein isolated from ginseng root. This study examined the effect of GEF on age-related sarcopenia in old C57BL/6J mice. Methods: Young (3-6 months) and old (20-24 months) C57BL/6J mice received oral GEF (50 mg/kg/day or 150 mg/kg/day) daily for 5 weeks. During the oral administration period, body weight and grip strength were measured weekly. After sacrifice, muscles from the hindlimb were excised and used for hematoxylin and eosin staining and western blotting to determine the effects of GEF on sarcopenia. The thymus was photographed to compare size, and flow cytometry was performed to examine the effect of GEF on immune homeostasis in the thymus and spleen. Blood samples were collected, and the concentrations of pro-inflammatory cytokines and IGF-1 were measured. Results: GEF caused a significant increase in muscle strength, mass, and fiber size in old mice. GEF restored age-related disruption of immune homeostasis by maintaining T cell compartments and regulating inflammatory biomarkers. Thus, GEF reduced common low-grade chronic inflammatory parameters, which are the main cause of muscle loss. Conclusion: GEF maintained immune homeostasis and inhibited markers of chronic inflammation, resulting in anti-sarcopenia effects in aged C57BL/6J mice. Thus, GEF is a potential therapeutic agent that slows sarcopenia in the elderly.

Ca(OH)2와 전구체의 화학 조성이 고속경화 지오폴리머의 물성에 미치는 영향 (Effects of Chemical Composition of Ca(OH)2 and Precursors on the Properties of Fast-Curing Geopolymers)

  • 고현석;노정영;임형미
    • 한국재료학회지
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    • 제29권11호
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    • pp.690-696
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    • 2019
  • Geopolymer is an alumina silicate-based ceramic material that has good heat-resistance and fire-resistance; it can be cured at room temperature, and thus its manufacturing process is simple. Geopolymer can be used as a reinforcement or floor finish for high-speed curing applications. In this manuscript, we investigate a high-speed curing geopolymer achieved by adding calcium to augment the curing rate. Metakaolin is used as the main raw material, and aqueous solutions of KOH and $K_2SiO_3$ are used as the activators. As a result of optimizing the high bending strength as a target factor for geopolymers with $SiO_2/Al_2O_3$ ratio of 4.1 ~ 4.8, the optimum ranges of the active agent are found to be $0.1{\leq}K_2O/SiO_2{\leq}0.4$ and $10{\leq}H_2O/K_2O{\leq}32.5$, and the optimum range of the curing accelerator is found to be $$0.82{\leq_-}Ca(OH)_2/Al_2O_3{\leq_-}2.87$$. The maximum flexural strength is found to be 1.35 MPa at $Ca(OH)_2/Al_2O_3=2.82$, $K_2O/SiO_2=0.3$, and $H_2O/K_2O=11.3$. The physical and thermal properties are analyzed to validate the applicability of these materials as industrial insulating parts or repairing finishing materials in construction.

Co-Doped Augite 보라색 유약의 발색기구 (Investigation of Color Mecchanism in Co-Doped Augite Purple for Color Glaze)

  • 권영주;이병하
    • 한국재료학회지
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    • 제23권5호
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    • pp.271-275
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    • 2013
  • Cobalt (Co) compounds have been used for centuries to impart rich blue color to glass, glazes and ceramics. Cobalt monoxide (CoO), an oxide of Co, is an inorganic compound that has long been used as a coloring agent in the ceramic industry. Unlike other coloring agents, CoO can be used to develop colors other than blue, and several factors such as its concentration in the glaze and firing condition have been suggested as possible mechanisms. For example, CoO produces a typical blue color called "cobalt blue" at very low concentrations such as 1 wt% in both oxidation and reduction firing conditions; a higher concentration of CoO (5 wt%) develops a darker blue color under the same firing conditions. Interestingly, CoO also develops a purple color at high concentrations above 10 wt%. In this study, we examined the applicability and mechanism of a novel purple glaze containing cobalt(II, III) oxide, one of the well characterized cobalt oxides. Experimental results show that an Augite crystal isoform (Augite-Fe/Co) in which Fe was replaced with Co is the main component contributing to the formation of the purple color. Based on these results, we developed a glaze using chemically synthesized Augite-Fe/Co crystal as a color pigment. Purple color glaze was successfully developed by the addition of 6~15 wt% of $Co_3O_4$ to magnesia lime.