PLGA/헤스페리딘 함량별 필름에서 염증 완화 효과: In vitro, In vivo 결과

송정은; 심초록; 이유정; 고현아; 윤현; 이동원; 강길선; Jeong Eun Song; Cho Rok Shim; Yujung Lee; Hyun Ah Ko; Hyeon Yoon; Dongwon Lee; Gilson Khang

Polymer(Korea), Vol.37, No.3, 323-331, May, 2013

Export Citation

PLGA/헤스페리딘 함량별 필름에서 염증 완화 효과: In vitro, In vivo 결과

Effect of Inflammatory Responses to PLGA Films Incorporated Hesperidin: In vitro and In vivo Results

송정은 , 심초록, 이유정, 고현아, 윤현, 이동원 , 강길선 ^†

전북대학교 BIN 융합공학과, 고분자나노공학과

Jeong Eun Song , Cho Rok Shim, Yujung Lee, Hyun Ah Ko, Hyeon Yoon, Dongwon Lee , and Gilson Khang^†

Dept. of BIN Fusion Tech, and Dept. of PolymerNano Sci. & Tech., Chonbuk National University, 567 Baekje-daero, Deokjin, Jeonju 561-756, Korea

E-mail:

초록

헤스페리딘은 혈관 순환계 보호 효과, 항암 효과, 항산화 효과, 항염증 효과 등의 작용이 있다고 알려져 있다. 본 연구에서는 헤스페리딘을 함유한 poly(lactic-co-glycolic acid)(PLGA) 필름을 조직공학적 세포담체로 이용하고 생체 내/외의 실험을 통하여 헤스페리딘과 염증 반응의 상관관계를 알아보고자 하였다. 세포담체에서의 세포의 증식과 부착을 확인하고자 PLGA/헤스페리딘 필름에 세포(RAW 264.7, NIH/3T3)를 파종하여 1, 3일 후에 MTT와 SEM을 통하여 분석하였다. 또한 항산화 효과와 염증 완화 효과를 알아보고자 ELISA, RT-PCR, FACS 등을 평가한 결과 PLGA 필름보다는 헤스페리딘이 첨가된 PLGA 필름에서 염증 반응이 감소하는 것을 확인하였다. In vivo 실험에서도 헤스페리딘이 PLGA에 의해 유도된 염증세포와 섬유피막 축적을 감소시켜 헤스페리딘의 항염증 효과를 볼 수 있었다. 이 실험 결과 PLGA 필름보다는 PLGA/헤스페리딘 필름에서 염증 반응이 감소함을 확인하였다.

Hesperidin (Hes) has known to having some functions like protection of blood circulatory system, anti-tumor effect, antioxidant effect and anti-inflammatory effect. The goal of this study is to demonstrate the relationship between Hes and inflammatory through in vitro and in vivo studies using poly(lactic-co-glycolic acid) (PLGA) film including Hes as a tissue engineered scaffold. To confirm the proliferation of cells on fabricated scaffold, cells (RAW 264.7 and NIH/3T3) were seeded on PLGA/Hes film then analyzed with MTT and SEM at 1 and 3 days after seeding. The results from ELISA, RT-PCR, and FACS for anti-oxident and anti-inflammatory effect showed that inflammatory response of PLGA/Hes film decreased more than that of PLGA film. Also, in vivo result confirmed that inflammatory response by implanted PLGA/Hes film decreased more comparing with PLGA film. This is because of anti-inflammatory effect of Hes reducing induced inflammatory cell and accumulation of fibrous capsule. The results showed that PLGA/Hes film’s capacity on reducing inflammatory is better than PLGA film because of Hes.

Keywords:poly(lactic-co-glycolic acid);hesperidin;inflammatory response.

[References]

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Khang G, Kim MS, Min BY, Tissue Eng. Regen. Med., 3, 376 (2004)
Khang G, Kim MS, Cho SH, Tissue Eng. Regen. Med., 1, 9 (2004)
Yoon SJ, Kim SH, Ha HJ, Ko YK, So JW, Kim MS, Yang YI, Khang G, Rhee JM, Lee HB, Tissue Eng. Part A., 14, 539 (2008)
Ko YK, Kim SH, Jeong JS, Ha HJ, Yoon SJ, Rhee JM, Kim MS, Lee HB, Khang G, Polym.(Korea), 31(1), 14 (2007)
Song Y, Kwon J, Kim B, Jeon Y, Khang G, Lee D, J.Biomed. Mater. Res., 98A, 517 (2011)
Oh SH, Kang SG, Lee JH, J. Mater. Sci. Mater. Med., 17, 131 (2006)
Chan JM, Zhang L, Yuet KP, Liao G, Rhee JW, Langer R, Farokhzad OC, Biomaterials., 30, 1627 (2009)
Bostman O, J. Bone Joint Surg. Am., 73, 148 (1991)
Taylor MS, J. Appl. Biomater., 5, 151 (1994)
Kim MS, Ahn HH, Shin YN, Cho MH, Khang G, Lee HB, Biomaterials., 28, 5137 (2007)
Jeon YP, Mohammad LM, Park CH, Hong JH, Lee GD, Song JC, Kim GS, J. Life Science., 19, 479 (2009)
Willoughby DA, Ann. Rheum. Dis., 34, 471 (1975)
Cho EJ, Li L, Yamabe N, Kim HY, CNU J. Agricultural Science., 38, 717 (2011)
Middleton E, Annal Aller., 61, 523 (1988)
Lee Y, Howard LR, Villalon B, J. Food Sci., 60, 473 (1995)
Marie HS, Joel L, Marin C, Toxicol. Appl. Pharmacol., 130, 73 (1995)
Hong HH, Kim SJ, Kim SH, Kim HL, Park JH, Lee D, Khang G, Tissue Eng. Regen. Med., 6, 711 (2009)
Sulaiman OAR, Gordon T, Glia., 32, 234 (2000)
Shim CR, Lee YJ, Ko HA, Kim MJ, Bae JW, Lee LH, Song JE, Khang G, Int. J. Tissue Regen., 3, 50 (2012)
Muschler GE, Nakamoto C, Griffith LG, J. Bone Joint Surg. Am., 86A, 1541 (2004)
Amens BN, Shigenoga MK, Hagen TM, Proc. Natl. Acad. Sci., 90, 7915 (1993)
Harman D, J. Gerontol., 2, 298 (1956)
Lee Y, Kwon J, Khang G, Lee D, Tissue Eng. Part A., 18, 1967 (2012)
Delgado AV, McManus AT, Chambers JP, Neuropeptides., 37, 355 (2003)
Aggarwal BB, Nat. Rev. Immunol., 3, 745 (2003)
Kim SJ, Hong HH, Kim SH, Kim HL, Kim SH, Khang G, Polymer(Korea)., 1, 63 (2010)
Meinel L, Hofmann S, Karageorgiou V, Kirker-Head C, McCool J, Gronowicz G, Zichner L, Langer R, Vunjak-Novakovica G, Kaplan DL, Biomaterials., 26, 147 (2005)
Sy JC, Seshadri G, Yang SC, Brown M, Oh T, Dikalov S, Murthy N, Davis ME, Nat. Mater., 7(11), 863 (2008)
Chen M, Gu H, Ye Y, Lin B, Sun L, Deng W, Zhang J, Liu J, Food Chem. Toxicol., 48, 2980 (2010)
Nandakumar N, Rengarajan T, Haribabu L, Perumal S, Balasubramanian P, Biomedicine & Preventive Nutrition., 1, 207 (2011)

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[2] Khang G, Kim MS, Min BY, Tissue Eng. Regen. Med., 3, 376 (2004)

[3] Khang G, Kim MS, Cho SH, Tissue Eng. Regen. Med., 1, 9 (2004)

[4] Yoon SJ, Kim SH, Ha HJ, Ko YK, So JW, Kim MS, Yang YI, Khang G, Rhee JM, Lee HB, Tissue Eng. Part A., 14, 539 (2008)

[5] Ko YK, Kim SH, Jeong JS, Ha HJ, Yoon SJ, Rhee JM, Kim MS, Lee HB, Khang G, Polym.(Korea), 31(1), 14 (2007)

[6] Song Y, Kwon J, Kim B, Jeon Y, Khang G, Lee D, J.Biomed. Mater. Res., 98A, 517 (2011)

[7] Oh SH, Kang SG, Lee JH, J. Mater. Sci. Mater. Med., 17, 131 (2006)

[8] Chan JM, Zhang L, Yuet KP, Liao G, Rhee JW, Langer R, Farokhzad OC, Biomaterials., 30, 1627 (2009)

[9] Bostman O, J. Bone Joint Surg. Am., 73, 148 (1991)

[10] Taylor MS, J. Appl. Biomater., 5, 151 (1994)

[11] Kim MS, Ahn HH, Shin YN, Cho MH, Khang G, Lee HB, Biomaterials., 28, 5137 (2007)

[12] Jeon YP, Mohammad LM, Park CH, Hong JH, Lee GD, Song JC, Kim GS, J. Life Science., 19, 479 (2009)

[13] Willoughby DA, Ann. Rheum. Dis., 34, 471 (1975)

[14] Cho EJ, Li L, Yamabe N, Kim HY, CNU J. Agricultural Science., 38, 717 (2011)

[15] Middleton E, Annal Aller., 61, 523 (1988)

[16] Lee Y, Howard LR, Villalon B, J. Food Sci., 60, 473 (1995)

[17] Marie HS, Joel L, Marin C, Toxicol. Appl. Pharmacol., 130, 73 (1995)

[18] Hong HH, Kim SJ, Kim SH, Kim HL, Park JH, Lee D, Khang G, Tissue Eng. Regen. Med., 6, 711 (2009)

[19] Sulaiman OAR, Gordon T, Glia., 32, 234 (2000)

[20] Shim CR, Lee YJ, Ko HA, Kim MJ, Bae JW, Lee LH, Song JE, Khang G, Int. J. Tissue Regen., 3, 50 (2012)

[21] Muschler GE, Nakamoto C, Griffith LG, J. Bone Joint Surg. Am., 86A, 1541 (2004)

[22] Amens BN, Shigenoga MK, Hagen TM, Proc. Natl. Acad. Sci., 90, 7915 (1993)

[23] Harman D, J. Gerontol., 2, 298 (1956)

[24] Lee Y, Kwon J, Khang G, Lee D, Tissue Eng. Part A., 18, 1967 (2012)

[25] Delgado AV, McManus AT, Chambers JP, Neuropeptides., 37, 355 (2003)

[26] Aggarwal BB, Nat. Rev. Immunol., 3, 745 (2003)

[27] Kim SJ, Hong HH, Kim SH, Kim HL, Kim SH, Khang G, Polymer(Korea)., 1, 63 (2010)

[28] Meinel L, Hofmann S, Karageorgiou V, Kirker-Head C, McCool J, Gronowicz G, Zichner L, Langer R, Vunjak-Novakovica G, Kaplan DL, Biomaterials., 26, 147 (2005)

[29] Sy JC, Seshadri G, Yang SC, Brown M, Oh T, Dikalov S, Murthy N, Davis ME, Nat. Mater., 7(11), 863 (2008)

[30] Chen M, Gu H, Ye Y, Lin B, Sun L, Deng W, Zhang J, Liu J, Food Chem. Toxicol., 48, 2980 (2010)

[31] Nandakumar N, Rengarajan T, Haribabu L, Perumal S, Balasubramanian P, Biomedicine & Preventive Nutrition., 1, 207 (2011)