히알루론산 함량에 따른 유분・수분 변화 및 만족도 조사

류혜란,이종헌 대한구강악안면병리학회 2018 대한구강악안면병리학회지 Vol.42 No.3

Hyaluronic acid is natural polysaccharide existing around skin or cartilage, and is known as a moisturizing factor. It is expected that hyaluronic acid cosmetics market will continue to grow in the future, as its use and demand increases, like medical supplies and health food besides cosmetics containing hyaluronic acid. However, There are few present studies on content in cosmetics containing hyaluronic acid. The purpose of this study was to evaluate satisfaction and examine what effect was produced on sebum and moisture in skin after applying to cosmetics the hyaluronic acid helpful in maintaining moisture in skin at 5%, 20% and 50% concentration. For 71 days, a clinical trial in a total 39 persons living in the national capital region was carried out. And sebum and moisture was measured through skin diagnosis system A-ONE TAB before trial and each day when clinical trial was conducted for hyaluronic acid content group. Besides, this study was to examine subjects' general characteristics, eating habits, and living habits, and satisfaction after the clinical trial. This study analyzed a difference according to the time to measure the skin condition among hyaluronic acid content groups by utilizing statistical package program SPSS v. 21.0 through data coding and data cleaning process. There was no statistically significant difference in hyaluronic acid content according to any of demographic characteristics, eating habits and living habits among groups (p>.05). With regard to hyaluronic acid content, there was no statistically significant difference in moisture and sebum prior to clinical trial in T zone and U zone among groups (p>.05). A change of moisture in T zone among groups according to hyaluronic acid content showed statistically significant difference in the 2nd week (F =3.636, p<.05). And the highest level was shown in 50%(44.15±2.672), being followed by 20%(43.15±2.340), and 5%(41.62±2.219). Accordingly, it was shown that, as hyaluronic acid content relatively increased, the moisture in T zone increased. In the results of analyzing the change of moisture in U zone, the change of sebum in T zone and U zone by group according to hyaluronic acid content, no statistically significant difference was shown in sebum level of T zone by group(p>.05). For analyzing the subjective satisfaction after clinical trial among groups according to hyaluronic acid content, satisfaction score was the highest in 'skin moistness' (4.38±0.650) for 5% group, 'skin moistness' (4.69±0.480) for 20% group and 'skin texture smoothness' (4.54±0.519) for 50% group. And no statistically significant difference was shown in each subjective satisfaction by group according to hyaluronic acid content(p>.05). It was thought that the results of skin condition and subjective satisfaction survey according to hyaluronic acid content would be baseline data for developing cosmetics containing the hyaluronic acid and marketing a skin moisturizer.

HOCl과 NH₂Cl에 의한 Hyaluronic Acid의 변성에 있어서 Taurine의 억제 효과

이정수(Chung-Soo Lee),이경용(Kyung-Yong Lee),이광수(Kwang-Soo Lee) 대한약리학회 1992 대한약리학잡지 Vol.28 No.2

외인성 taurine이 HOCl, NH₂Cl과 그밖의 산화성 물질에 의한 hyaluronic acid의 변성에 미치는 영향을 관찰하였다. HOCl, NH₂Cl과 그밖의 산화성 물질에 대한 taurine의 제거 작용을 조사하였다. Taurine의 항 산화 작용을 또한 치올 화합물의 작용과 비교 관찰하였다. Hyaluronic acid의 점성도는 HOCl과 NH₂Cl에 의하여 뚜렷하게 용량에 따라 감소하였다. Hyaluronic acid에 대한 HOCl의 변성 효과는 NH₂Cl에 의한 것보다 현저하였다. Taurine은 HOCl과 NH₂Cl에 의한 hyaluronic acid의 변성을 효과적으로 용량에 따라 억제하였다. HOCl의 변성 효과는 DMSO에 의하여 뚜렷하게 억제되었다. Fe²⁺과 H₂O₂에 의한 hyaluronic acid의 변성은 catalase와 DMSO에 의하여 억제되었으나 taurine의 영향은 받지 않았다. Xanthine과 xanthine oxidase의 변성 작용은 SOD와 catalase에 의하여 효과적으로 억제되었으나 taurine의 영향은 받지 않았다. HOCl은 taurine, DMSO, GSH와 MPG에 의하여 유의하게 분해되었다. 파장 250 nm에서의 HOCl의 흡광도와 파장 242 nm에서의 NH₂Cl의 흡광도는 taurine의 첨가로 유의하게 증가하였다. NH₂Cl과 GSH 또는 MPG의 상호 작용으로 초기에 최대의 흡광도가 관찰되었으나, 이러한 흡광도는 반응 시간에 따라 점차적으로 감소하였다. Fe²⁺와 H₂O₂의 존재하에서 OH 의 생성은 catalase와 DMSO에 의하여 억제되었으나 taurine의 영향은 받지 않았다. DABCO와 DABA에 반응하는 자외선 조사에 따른 ¹O₂의 생성은 taurine의 영향을 받지 않았다. GSH와 MPG는 HOCl의 변성 작용을 뚜렷하게 억제하였다. 이상의 결과로 부터 hyaluronic acid의 변성을 포함한 조직 구성성분의 산화성 손상에 있어서 taurine의 보호 작용은 산소 유리 라디칼에 대한 제거 작용과 관계없으며 HOCl과 NH₂Cl에 대한 제거 작용 그리고 taurine과 HOCl 또는 NH₂Cl의 복합체 형성에 기인할 것으로 시사된다. Taurine의 치올 기가 HOCl과 NH₂Cl에 의한 변성에 부분적으로 보호 작용을 나타 낼 것으로 추정된다. Effect of exogenous taurine on HOCl, NH₂Cl and other oxidants-induced degradation of hyaluronic acid was investigated. The scavenging action of taurine on HOCl, NH₂Cl and other oxidants was examined. The antioxidant action of taurine was also compared with that of thiol compounds. Viscosity of hyaluronic acid was markedly decreased by HOCl and NH₂Cl on a dose dependent fashion. The degradative effect of HOCl on hyaluronic acid was greater than that of NH₂Cl. Taurine effectively inhibited HOCl-and NH₂Cl-induced degradation of hyaluronic acid in a dose dependent fashion. The degradative effect of HOCl was markedly inhibited by DMSO. Fe²⁺ plus H₂O₂-induced degradation of hyaluronic acid was inhibited by catalase and DMSO but not affected by taurine. The desradative action of xanthine and xanthine oxidase was effectively inhibited by SOD and catalase but not affected by taurine. HOCl was significantly decomposed by taurine, DMSO, GSH and MPG. Both absorbance of HOCl at 250 nm and absorbance of NH₂Cl at 242 nm were significantly increased by the addition of taurine. Interaction of NH₂Cl with GSH or MPG showed an initial peak absorbance, but these absorbances were gradually decreased with time. OH production in the presence of Fe²⁺ and H₂O₂ was inhibited by catalase and DMSO but not affected by taurine. Taurine did not affect ¹O₂ production by U.V. irradiation which is responsible for DABCO and DABA. GSH and MPG markedly inhibited the degradative action of HOCl. These results suggest that the protective action of taurine on oxidants-induced damages of tissue components, including degradation of hyaluronic acid may be attributable to both its scavenging action on HOCl and NH₂Cl and the complex formation of taurine with HOCl or NH₂Cl without scavenging action on oxygen free radicals. Sulfhydryl group of taurine appears to show partially a protective action on HOCl-and NH₂Cl-induced degradation.

Inhibitory Effect of Taurine on HOCl-and $NH_2Cl-induced$ Degradation of Hyaluronic Acid

이정수,이경용,이광수,Lee, Chung-Soo,Lee, Kyung-Yong,Lee, Kwang-Soo The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.2

외인성 taurine이 HOCl, $NH_2Cl$과 그밖의 산화성 물질에 의한 hyaluronic acid의 변성에 미치는 영향을 관찰하였다. HOCl, $NH_2Cl$과 그밖의 산화성 물질에 대한 taurine의 제거 작용을 조사하였다. Taurine의 항 산화 작용을 또한 치올 화합물의 작용과 비교 관찰하였다. Hyaluronic acid의 점성도는 HOCl과 $NH_2Cl$에 의하여 뚜렷하게 용량에 따라 감소하였다. Hyaluronic acid에 대한 HOCl의 변성 효과는 $NH_2Cl$에 의한 것보다 현저하였다. Taurine은 HOCl과 $NH_2Cl$에 의한 hyaluronic acid의 변성을 효과적으로 용량에 따라 억제하였다. HOCl의 변성 효과는 DMSO에 의하여 뚜렷하게 억제되었다. $Fe^{2+}$과 $H_2O_2$에 의한 hyaluronic acid의 변성은 catalase와 DMSO에 의하여 억제되었으나 taurine의 영향은 받지 않았다. Xanthine과 xanthine oxidase의 변성 작용은 SOD와 catalase에 의하여 효과적으로 억제되었으나 taurine의 영향은 받지 않았다. HOCl은 taurine, DMSO, GSH와 MPG에 의하여 유의하게 분해되었다. 파장 250 nm에서의 HOCl의 흡광도와 파장 242 nm에서의 $NH_2Cl$의 흡광도는 taurine의 첨가로 유의하게 증가하였다. $NH_2Cl$과 GSH 또는 MPG의 상호 작용으로 초기에 최대의 흡광도가 관찰되었으나, 이러한 흡광도는 반응 시간에 따라 점차적으로 감소하였다. $Fe^{2+}$와 $H_2O_2$의 존재하에서 OH 의 생성은 catalase와 DMSO에 의하여 억제되었으나 taurine의 영향은 받지 않았다. DABCO와 DABA에 반응하는 자외선 조사에 따른 $^1O_2$의 생성은 taurine의 영향을 받지 않았다. GSH와 MPG는 HOCl의 변성 작용을 뚜렷하게 억제하였다. 이상의 결과로 부터 hyaluronic acid의 변성을 포함한 조직 구성성분의 산화성 손상에 있어서 taurine의 보호 작용은 산소 유리 라디칼에 대한 제거 작용과 관계없으며 HOCl과 $NH_2Cl$에 대한 제거 작용 그리고 taurine과 HOCl 또는 $NH_2Cl$의 복합체 형성에 기인할 것으로 시사된다. Taurine의 치올 기가 HOCl과 $NH_2Cl$에 의한 변성에 부분적으로 보호 작용을 나타 낼 것으로 추정된다. Effect of exogenous taurine on HOCl, $NH_2Cl$ and other oxidants-induced degradation of hyaluronic acid was investigated. The scavenging action of taurine on HOCl, $NH_2Cl$ and other oxidants was examined. The antioxidant action of taurine was also compared with that of thiol compounds. Viscosity of hyaluronic acid was markedly decreased by HOCl and $NH_2Cl$ on a dose dependent fashion. The degradative effect of HOCl on hyaluronic acid was greater than that of $NH_2Cl$. Taurine effectively inhibited HOCl-and $NH_2Cl-induced$ degradation of hyaluronic acid in a dose dependent fashion. The degradative effect of HOCl was markedly inhibited by DMSO. $Fe^{2+}$ plus $H_2O_2-induced$ degradation of hyaluronic acid was inhibited by catalase and DMSO but not affected by taurine. The desradative action of xanthine and xanthine oxidase was effectively inhibited by SOD and catalase but not affected by taurine. HOCl was significantly decomposed by taurine, DMSO, GSH and MPG. Both absorbance of HOCl at 250 nm and absorbance of $NH_2Cl$ at 242 nm were significantly increased by the addition of taurine. Interaction of $NH_2Cl$ with GSH or MPG showed an initial peak absorbance, but these absorbances were gradually decreased with time. OH production in the presence of $Fe^{2+}$ and $H_2O_2$ was inhibited by catalase and DMSO but not affected by taurine. Taurine did not affect $^1O_2$ production by U.V. irradiation which is responsible for DABCO and DABA. GSH and MPG markedly inhibited the degradative action of HOCl. These results suggest that the protective action of taurine on oxidants-induced damages of tissue components, including degradation of hyaluronic acid may be attributable to both its scavenging action on HOCl and $NH_2Cl$ and the complex formation of taurine with HOCl or $NH_2Cl$ without scavenging action on oxygen free radicals. Sulfhydryl group of taurine appears to show partially a protective action on HOCl-and $NH_2Cl-induced$ degradation.

Characterization of low-molecular-weight hyaluronic acid-based hydrogel and differential stem cell responses in the hydrogel microenvironments

Kim, Jungju,Park, Yongdoo,Tae, Giyoong,Lee, Kyu Back,Hwang, Chang Mo,Hwang, Soon Jung,Kim, In Sook,Noh, Insup,Sun, Kyung Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of biomedical materials research. Part A Vol.a88 No.4

<P>Hyaluronic acid is a natural glycosaminoglycan involved in biological processes. Low-molecular-weight hyaluronic acid (10 and 50 kDa)-based hydrogel was synthesized using derivatized hyaluronic acid. Hyaluronic acid was acrylated by two steps: (1) introduction of an amine group using adipic acid dihydrazide, and (2) acrylation by N-acryloxysuccinimide. Injectable hyaluronic acid-based hydrogel was prepared by using acrylated hyaluronic acid and poly(ethylene glycol) tetra-thiols via Michael-type addition reaction. Mechanical properties of the hydrogel were evaluated by varying the molecular weight of acrylated hyaluronic acid (10 and 50 kDa) and the weight percent of hydrogel. Hydrogel based on 50-kDa hyaluronic acid showed the shortest gelation time and the highest complex modulus. Next, human mesenchymal stem cells were cultured in cell-adhesive RGD peptide-immobilized hydrogels together with bone morphogenic protein-2 (BMP-2). Cells cultured in the RGD/BMP-2-incorporated hydrogels showed proliferation rates higher than that of control or RGD-immobilized hydrogels. Real-time RT-PCR showed that the expression of osteoblast marker genes such as CBFα1 and alkaline phosphatase was increased in hyaluronic acid-based hydrogel, and the expression level was dependent on the molecular weight of hyaluronic acid, RGD peptide, and BMP-2. This study indicates that low-molecular-weight hyaluronic acid-based hydrogel can be applied to tissue regeneration as differentiation guidance materials of stem cells. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009</P>

Physiochemical and Organoleptic Properties of Kefir Containing Different Concentrations of Hyaluronic Acid : A Preliminary Study

( Jung-whan Chon ),( Binn Kim ),( Kun-ho Seo ),( Dongryeoul Bae ),( Dongkwan Jeong ),( Kwang-young Song ) 한국낙농식품응용생물학회(구 한국유가공학회) 2020 Journal of Dairy Science and Biotechnology (JMSB) Vol.38 No.3

Recently, hyaluronic acid, which is the most popular among various biomaterials, has been used in osteoarthritis treatment, eye surgery, and wound healing. This study was carried out to determine the physicochemical and organoleptic properties of kefir containing various concentrations of hyaluronic acid. The pH value of hyaluronic-acid-containing kefir ranged from 3.58 to 3.46. Moreover, for hyaluronic-acid-containing kefir, the score of taste ranged from 4.75 to 4.0, the flavor ranged from 4.0 to 3.38, the color ranged from 4.38 to 4.0, the texture ranged from 4.38 to 3.75, and the overall acceptability ranged from 4.59 to 3.72. Overall, the organoleptic properties of hyaluronic-acid-containing kefir were better than those of the control. Because this is the first study involving hyaluronic acid and kefir, the results are valuable. The addition of hyaluronic acid did not significantly affect the physicochemical and organoleptic properties of kefir. Therefore, the commercial availability of various hyaluronic-acid-added dairy food products must be investigated.

Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration

Jeong, Jae Young,Hong, Eun-Hye,Lee, Song Yi,Lee, Jae-Young,Song, Jae-Hyoung,Ko, Seung-Hak,Shim, Jae-Seong,Choe, Sunghwa,Kim, Dae-Duk,Ko, Hyun-Jeong,Cho, Hyun-Jong Elsevier Science B.V. Amsterdam 2017 ACTA BIOMATERIALIA Vol. No.

<P><B>Abstract</B></P> <P>(3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid–ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) <I>via</I> amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, <I>in vitro</I> antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced <I>in vivo</I> tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs.</P> <P><B>Statement of Significance</B></P> <P>(3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies <I>via</I> the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface of HACE-AMPB/MB NPs (in the aqueous <I>milieu</I>) may react with the sialic acid over-expressed in cancer cells and intramolecular B‒O bond can be formed. This phenylboronic acid-sialic acid interaction may provide additional tumor targeting and penetration potentials together with an enhanced permeability and retention (EPR) effect (passive tumor targeting) and HA-CD44 receptor interaction (active tumor targeting). Developed HACE-AMPB NP may be one of promising nanocarriers for the imaging and therapy of CD44 receptor-expressed cancers.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

히알루론산의 세계시장 동향과 전망

이송희 ( Song Hee Lee ),권태훈 ( Tae Hoon Kwon ),이준우 ( Joon Woo Lee ) 한국키틴키토산학회 2016 한국키틴키토산학회지 Vol.21 No.1

This study deals with hyaluronic acid market analysis which composed of revenue and demand forecasting. The global market for hyaluronic acid was estimated at US$ 1.69 billions in 2012, and is expected to reach US$ 2.42 billions by 2016. In 2012, the Americas dominated market, where the major contribution was from the US, and this trend is expected to continue during the forecast period. The Americas was followed by the Asia-Pacific region. Nationally the US was the leading hyaluronic acid market with an estimated US$0.78 billion in 2012 and a projected US$1.20 billion by 2015. The Japan represented the second biggest market for hyaluronic acid. Most of hyaluronic acid substances were used as an additive to cosmetics, medical product, or cosmetic filler. The global hyaluronic acid market is driven by the steadily growing aging population and the increasing consumer awareness about hyaluronic acid. In spite of the several drivers, the intense pricing competition among the vendors will considerably lead to a reduction in the price of the hyaluronic acid products. However, because of the presence of several drivers and emerging trends, the future of the global hyaluronic acid market is expected to be promising during the forecast period.

$Fe^{++}$ 및 $H_2O_2$에 의한 hyaluronic acid 분해에 있어서 ascorbic acid의 역할

이정수,정명희,임정규,박찬웅,차인준,Lee, Jung-Soo,Chung, Myung-Hee,Lim, Jung-Kyoo,Park, Chan-Woong,Cha, In-Joon The Korean Society of Pharmacology 1985 대한약리학잡지 Vol.21 No.1

Hydroxyl raical$(OH{\cdot})$을 생성하는 것으로 알려진 iron-catalyzed Haber-Weiss rocation에서 superoxide anion $(O^{-}_{2}{\cdot})$은 주로 $Fe^{+++}$을 $Fe^{++}$로 환원시키는 데에 작용하는 것으로 추정하고 있다. 이러한 $OH{\cdot}$ 의 역할은 다른 환원제들에 의하여 대체가 가능할 것으로 추측되며 생물계의 환원제의 하나로써 ascorbate가 관심의 대상이 되고 있다. 이에 따라 본 연구에서는 $Fe^{++}$와 $H_2O_2$ 존재하에서 $OH{\cdot}$ 을 생성하는 ascorbate 의 역할을 hyaluronic acid의 변성과 methional로 부터 ethylene 생성에 대한 효과로써 관찰하였다. Ascorbate는 $Fe^{++}$와 $H_2O_2$에 의한 hyaluronic acid의 변성을 촉진하였으며, 이런 현상은 점성도 변화와 Sepharose 4B를 이용한 코로마토그라피에 의하여 확인할 수 있었다. 이때 관찰되는 변성은 catalase와 $OH{\cdot}$ scavenger에 의하여 거의 완전히 억제 되었다. 또한 ascorbate는 $Fe^{++}$와 $H_2O_2$에 의한 methional로 부터 ethylene생성을 항진시킴으로써 상기의 결과를 뒷받침 하였다. 다른 환원제들(cysteine, glutathione, NADH와 NADH와 NAKPH)도 ascorbate와 같이 hyaluronic acid의 변성과 methional로 부터 ethylene생성을 촉진하였으나, 그들의 산화형인 NAD와 NADP의 효과는 관찰 할 수 없었다. 그러므로 $OH{\cdot}$ 생성에 있어 철이온의 환원이 관여함을 시사하였다. 또한 metal ion가운데 $Fe^{++}$는 $OH{\cdot}$ 생성에 가장 강력한 촉매작용을 나타내었다. 이상의 결과는 ascorbate가 $(OH{\cdot})$ 을 생성하는 metal-catalyzed reaction에서 $Fe^{+++}$을 $Fe^{++}$로 환원하는 $O^{-}_{2}{\cdot}$의 작용을 대신할 수 있음을 증명하며 이와같은 ascorbate 의존적인 $OH{\cdot}$ 의 생성은 ascorbate가 조직손상에 관여할 가능성을 시사하였다. In tile Iron-catalyzed Haber-Weiss reaction to produce OH., the requirement for $O^{-}_{2}{\cdot}$ is only to reduce $Fe^{+++}$. Possibly, the role of $O^{-}_{2}{\cdot}$ can be replaced by other reducing agents. Ascorbate is one of them in biological system. In the present study, the ability of ascorbate to produce $OH{\cdot}$ in the presence of $Fe^{++}$ and $H_2O_2$ was investigated by observing the degradation of hyaluronic acid and ethylene production from methional. Ascorbate stimulated the degradation of hyaluronic by $Fe^{++}$ and $H_2O_2$. That was confirmed by both viscosity change and gel-permeation chromatographic analysis. The observed degradation was almost completely prevented by catalase and $OH{\cdot}$ scavengers. In support of the above results, ascorbate enhanced the prouction of ethylene from methional in the presence of $Fe^{++}$ and $H_2O_2$. Other reducing agents (cysteine, glutathione, NADH and NADPH) showed similar activities to ascorbate in the degradation of hyaluronic acid and ethylene production. But no stimulatory effects were observed with their oxidized forms such as NAD and NADP. Thus, it appears that reduction of the metal ion was needed for $OH{\cdot}$ production. Among the metal ions tested, $Fe^{++}$ showed most potent catalytic action in the production of $OH{\cdot}$ The results obtained support that ascorbate can substitute $O^{-}_{2}{\cdot}$ in the metal-catalyzed reactions, particularly with $Fe^{++}$ by which $OH{\cdot}$ is produced with $H_2O_2$. The significance of the ascorbate-dependent production of $OH{\cdot}$ was considered with respect to possible role of ascorbate in the damage of inflamed joints.

Fe⁺⁺및 H₂O₂에 의한 hyaluronic acid 분해에 있어서 ascorbic acid의 역할

이정수(Jung-Soo Lee),정명희(Myung-Hee Chung),임정규(Jung-Kyoo Lim),박찬웅(Chan-Woong Park),차인준(In-Joon Cha) 대한약리학회 1985 대한약리학잡지 Vol.21 No.1

Hydroxyl raical(OH⋅)을 생성하는 것으로 알려진 iron-catalyzed Haber-Weiss rocation에서 superoxide anion (O₂^-⋅)은 주로 Fe⁺⁺⁺을 Fe⁺⁺로 환원시키는 데에 작용하는 것으로 추정하고 있다. 이러한 OH⋅ 의 역할은 다른 환원제들에 의하여 대체가 가능할 것으로 추측되며 생물계의 환원제의 하나로써 ascorbate가 관심의 대상이 되고 있다. 이에 따라 본 연구에서는 Fe⁺⁺와 H₂O₂ 존재하에서 OH⋅ 을 생성하는 ascorbate 의 역할을 hyaluronic acid의 변성과 methional로 부터 ethylene 생성에 대한 효과로써 관찰하였다. Ascorbate는 Fe⁺⁺와 H₂O₂에 의한 hyaluronic acid의 변성을 촉진하였으며, 이런 현상은 점성도 변화와 Sepharose 4B를 이용한 코로마토그라피에 의하여 확인할 수 있었다. 이때 관찰되는 변성은 catalase와 OH⋅ scavenger에 의하여 거의 완전히 억제 되었다. 또한 ascorbate는 Fe⁺⁺와 H₂O₂에 의한 methional로 부터 ethylene생성을 항진시킴으로써 상기의 결과를 뒷받침 하였다. 다른 환원제들(cysteine, glutathione, NADH와 NADH와 NAKPH)도 ascorbate와 같이 hyaluronic acid의 변성과 methional로 부터 ethylene생성을 촉진하였으나, 그들의 산화형인 NAD와 NADP의 효과는 관찰 할 수 없었다. 그러므로 OH⋅ 생성에 있어 철이온의 환원이 관여함을 시사하였다. 또한 metal ion가운데 Fe⁺⁺는 OH⋅ 생성에 가장 강력한 촉매작용을 나타내었다. 이상의 결과는 ascorbate가 (OH⋅) 을 생성하는 metal-catalyzed reaction에서 Fe⁺⁺⁺을 Fe⁺⁺로 환원하는 O₂^-⋅의 작용을 대신할 수 있음을 증명하며 이와같은 ascorbate 의존적인 OH⋅ 의 생성은 ascorbate가 조직손상에 관여할 가능성을 시사하였다. In tile Iron-catalyzed Haber-Weiss reaction to produce OH., the requirement for O₂^-⋅ is only to reduce Fe⁺⁺⁺. Possibly, the role of O₂^-⋅ can be replaced by other reducing agents. Ascorbate is one of them in biological system. In the present study, the ability of ascorbate to produce OH⋅ in the presence of Fe⁺⁺ and H₂O₂ was investigated by observing the degradation of hyaluronic acid and ethylene production from methional. Ascorbate stimulated the degradation of hyaluronic by Fe⁺⁺ and H₂O₂. That was confirmed by both viscosity change and gel-permeation chromatographic analysis. The observed degradation was almost completely prevented by catalase and OH⋅ scavengers. In support of the above results, ascorbate enhanced the prouction of ethylene from methional in the presence of Fe⁺⁺ and H₂O₂. Other reducing agents (cysteine, glutathione, NADH and NADPH) showed similar activities to ascorbate in the degradation of hyaluronic acid and ethylene production. But no stimulatory effects were observed with their oxidized forms such as NAD and NADP. Thus, it appears that reduction of the metal ion was needed for OH⋅ production. Among the metal ions tested, Fe⁺⁺ showed most potent catalytic action in the production of OH⋅ The results obtained support that ascorbate can substitute O₂^-⋅ in the metal-catalyzed reactions, particularly with Fe⁺⁺ by which OH⋅ is produced with H₂O₂. The significance of the ascorbate-dependent production of OH⋅ was considered with respect to possible role of ascorbate in the damage of inflamed joints.

Effects of Quercetin and Rutin Fe^(2+) and H_2O_2-induced Degradation of Hyaluronic Acid

Kim, Hyun-Ho,Shin, Yong-Kyoo,Lee, Chung-Soo 중앙대학교 의과대학 의과학연구소 1993 中央醫大誌 Vol.18 No.2

Flavonoid는 주어진 조건에 따라 항산화 능력과 산화성 조직 손상을 자극하는 능력을 나타내는 것으로 보고하고 있다. 이와 함게 생체내에서 산화성 조직 손상에 대한 그들의 작용은 분명하지 않다. 본 연구에서는 Fe^2+와 H_2O_2에 의한 hyaluronic acid의 변성에 나타내는 quercetin과 rutin의 효과를 관찰하였다. Fe^+2와 H_2O_2의 상호 작용에 따른 OH 생성에 대한 quercetin과 rutin의 영향을 조사 하였다. Hyaluronic acid의 점성도는 Fe^2와 H^2O^2에 의하여 효과적으로 감소하였다. Fe^2+와 H_2O_2에 의한 hyaluronic acid의 변성은 SOD, catalase, DMSO, DABCO, DETAPAC과 EDTA에 의하여 억제되었다. Quercetin은 유의하게 Fe^2와 H_2O_2의 변성 작용을 용량에 따라 촉진시켰으나 이에 반하여 rutin은 억제하였다. KCN에 의한 quercetin과 rutin의 산화는 ferricytochrome c의 환원을 초래하였으며, 이는 SOD에 의하여 억제되었다. Fe^+2와 H_2O_2의 존재하에서 OH 생성은 quercetin에 의하여 촉진되었으나 rutin, DMSO와 sodium formate에 의하여 억제되었다. 이상의 결과로부터 quercetin과 rutin은 반응성 산소 대사물에 의하여 이루어지는 Fe^+2와 H^2O^2에 의한 hyaluronic acid의 변성에 서로 다른 효과를 나타낼 것으로 제시되었다. 이 반응에서 quercetin은 산화성 조직손상을 자극하는 물질로서 그리고 rutin은 항산화 물질로서 작용할 것으로 추정된다. Flavonoids are reported to have both antioxidant and pro-oxidant properties according to a given conditions. In addition, their actions on the oxidative tissue injuries in vivo are uncertain. In the present study, effects of flavonoids quercetin and rutin on Fe^2+ and H_2O_2-induced degradation of hyaluronic acid were investigated. Effects of quercetin and rutin on the production of hydroxyl radical from the interaction of Fe^2+ with H_2O_2 were examined. Viscosity of hyaluronic acid was effectively decreased by Fe^2+ and H_2O_2 Fe^2+ and H_2O_2 -induced degradation of hyaluronic acid was inhibited by SOD, catalase, DMSO, DABCO, DETAPAC and EDTA. Quercetin significantly promoted the dependent fashion, whereas rutin inhibited it. KCN-induced oxidations of quercetin and rutin caused the reduction of ferricytochrome c, which was inhibited by SOD. OH. production in the presence of Fe^2 and H_2O_2 was promoted by quercetin but inhibited by rutin, DMSO and sodium formate. These results suggest that quercetin and rutin show a different effect on the degradation of hyaluronic acid induced by Fe^2+ and H_2O_2, which is responsible for reactive oxygen species. In this reaction quercetin may act as the pro-oxidant, whereas rutin act as the anti oxidant.