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The Effect of Glycyrrhizic acid on Vascular Contractility

혈관수축에 대한 감초산 Glycyrrhizic acid의 효과

  • Hyun Dong Je (Dept. of Pharmacy, Daegu Catholic University) ;
  • Young Sil Min (Dept. of Pharmaceutical Science, Jungwon University)
  • 제현동 (대구가톨릭대학교 약학과) ;
  • 민영실 (중원대학교 식품제약학과)
  • Received : 2023.08.11
  • Accepted : 2023.10.20
  • Published : 2023.10.28

Abstract

This study aims to elucidate the effect of glycyrrhizic acid on smooth muscle contraction and to determine the detailed mechanism incorporated. We hypothesized that glycyrrhizic acid played a role in the agonist-sensitive management of smooth muscle contraction. Stripped smooth muscles of Sprague-Dawley rats were prepared in organ baths and isometric tensions were converted, stored and analyzed by using isometric transducers, a physiograph and one way ANOVA. Interestingly, glycyrrhizic acid attenuated the thick filament regulating agonist (fluoride or thromboxane mimetic)-sensitive contraction (p=0.113, 0.008, 0.004 (Student's t-test), p=0.113, 0.008, 0.004 (One way ANOVA) at 0.01, 0.03, 0.1 mM fluoride, and p=0.156, 0.004, 0.003 (Student's t-test), p=0.156, 0.004, 0.003 (One way ANOVA) at 0.01, 0.03, 0.1 mM thromboxane mimetic) and did not attenuate the thin filament regulating agonist (phorbol ester)-induced contraction (p=0.392, 0.086, 0.065 (Student's t-test), p=0.392, 0.086, 0.065 (One way ANOVA) at 0.01, 0.03, 0.1 mM phorbol ester). It is suggesting that endothelial EDRF (NO) synthesis and accessory pathways besides endothelial EDRF (NO) synthesis such as ROCK restriction might be incorporated in the glycyrrhizic acid-induced modulation of smooth muscle contraction inhibiting acto-myosin interaction.

평활근 수축에 대한 감초산(glycyrrhizic acid)의 효과를 연구하고자 하였고 관련 상세 기전을 결정하기 위해 glycyrrhizic acid가 agonist-sensitive하게 평활근 수축한다는 가설을 제시하였다. S/D rats의 평활근을 수조 내 준비하였고 신호 변환기에서 평활근에 의한 운동 신호가 전기적 신호로 변환되어 생리기록기에 표시되는 데이터는 일원배치 분산분석으로 분석하였다. 재미있게도, 감초산은 불화물, 트롬복산 유사체 등 굵은 미세섬유성 조절성 수축제에 의한 평활근 수축을 중등도로 억제하였고 (농도 0.01, 0.03, 0.1 mM 불화물에서 p=0.113, 0.008, 0.004 (Student's t-test), p=0.113, 0.008, 0.004 (One way ANOVA), 그리고 0.01, 0.03, 0.1 mM 트롬복산 유사체에서 p=0.156, 0.004, 0.003 (Student's t-test), p=0.156, 0.004, 0.003 (One way ANOVA)) 포볼 에스테르 등 가는 미세섬유성 조절성 수축제에 의한 평활근 수축에 대해 효과가 소실되었다 (0.01, 0.03, 0.1 mM 포볼 에스테르에서 p=0.392, 0.086, 0.065 (Student's t-test), p=0.392, 0.086, 0.065 (One way ANOVA)). 이러한 결과는 내피 기능이 억제된 평활근에서 감초산은 평활근 내피에서 EDRF (NO) 생성 효과 외에 주로 ROCK 활성 감소 등 평활근에 대한 직접적 효과를 통해 최종적으로 평활근에서 악틴-미오신 상호작용을 제한하여 평활근을 이완시키는 것으로 생각된다.

Keywords

References

  1. Appel, L. J., Champagne, C. M., Harsha, D. W., Cooper, L. S., Obarzanek, E., Elmer, P. J., Stevens, V. J. Vollmer, W. M., Lin, P. H., Svetkey, L. P., Stedman, S. W., & Young, D. R. (2003). Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA, 289(16), 2083-2093. DOI : 10.1001/jama.289.16.2083
  2. Wang, H., Ge, X., Qu, H., Wang, N., Zhou, J., Xu, W., Xie, J., Zhou, Y., Shi, L., Qin, Z., Jiang Z, Yin, W., & Xia, J. (2020). Glycyrrhizic acid inhibits proliferation of gastric cancer cells by inducing cell cycle arrest and apoptosis. Cancer Manag. Res., 12, 2853-2861. DOI : 10.2147/CMAR.S244481
  3. Cai, S., Bi, Z., Bai, Y., Zhang, H., Zhai, D., Xiao, C., Tang, Y., Yang, L., Zhang, X., Li, K., Yang, R., Liu, Y., Chen, S., Sun, T., Liu, H., & Yang, C. (2019). Glycyrrhizic acid-induced differentiation repressed stemness in hepatocellular carcinoma by targeting c-Jun N-terminal kinase 1. Front Oncol., 9, 1431. DOI : 10.3389/fonc.2019.01431
  4. Somlyo, A. P., & Somlyo, A. V. (1994). Signal transduction and regulation in smooth muscle. Nature, 372, 231-236. DOI : 10.1038/372231a0
  5. Zicha, J., Behuliak, M., Pinterova, M., Bencze, M., Kunes, J., & Vaneckova, I. (2014). The interaction of calcium entry and calcium sensitization in the control of vascular tone and blood pressure of normotensive and hypertensive rats. Physiol. Res., 63(Suppl 1), S19-S27. DOI : 10.33549/physiolres.932639
  6. Somlyo, A. P., & Somlyo, A. V. (1998). From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta Physiol Scand, 164(4), 437-448. DOI : 10.1046/j.1365-201X.1998.00454.x
  7. Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M., & Narumiya, S. (1997). Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature, 389, 990-994. DOI : 10.1038/40187
  8. Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y., & Takuwa, Y. (2003). Ca2+-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ Res, 93(6), 548-556. DOI : 10.1161/01.RES.0000090998.08629.60
  9. Kitazawa, T., Masuo, M., & Somlyo, A. P. (1991). G protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proc Natl Acad Sci USA, 88(20), 9307-9310. DOI : 10.1073/pnas.88.20.9307
  10. Gohla, A. Schultz, G., & Offermanns, S. (2000). Roles for G(12)/G(13) in agonist-induced vascular smooth muscle cell contraction. Circ Res, 87(3), 221-227. DOI : 10.1161/01.res.87.3.221
  11. Leung, T., Manser, E., Tan, L., & Lim, L. (1995). A novel serine/threonine kinase binding the Ras- related RhoA GTPase which translocates the kinase to peripheral membranes. J Biol Chem, 270(49), 29051-29054. DOI : 10.1074/jbc.270.49.29051
  12. Matsui, T., Amano, M., Yamamoto, T., Chihara, K., Nakafuku, M., Ito, M., Nakano, T., Okawa, K., Iwamatsu, A., & Kaibuchi, K. (1996). Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO J, 15(9), 2208-2216. https://doi.org/10.1002/j.1460-2075.1996.tb00574.x
  13. Wier, W. G., & Morgan, K. G. (2003). Alpha1-adrenergic signaling mechanisms in contraction of resistance arteries. Rev Physiol Biochem Pharmacol, 150, 91-139. DOI : 10.1007/s10254-003-0019-8
  14. Kordowska, J., Huang, R., & Wang, C. L. (2006). Phosphorylation of caldesmon during smooth muscle contraction and cell migration or proliferation. J Biomed Sci, 13(2), 159-172. DOI : 10.1007/s11373-005-9060-8
  15. Zhao, Z., Wang, J., Huo, Z., Wang, Z., & Mei, Q. (2017). FTY720 elevates smooth muscle contraction of aorta and blood pressure in rats via ERK activation. Pharmacol Res Perspect, 5(3), e00308. DOI : 10.1002/prp2.308
  16. Je, H. D., & Min, Y. (2022). The Effect of Silymarin and Ethanol Intake on Vascular Contractility. Journal of Industrial Convergence, 20(7), 131-137. DOI : 10.22678/JIC.2022.20.7.131
  17. Bang, J. S., Je, H. D., & Min, Y. (2020). The Convergence Effect of Phloretin Existent in Plants on Vascular Contractility. Journal of Convergence for Information Technology, 10 (10), 143-149. DOI : 10.22156/CS4SMB.2020.10.10.143
  18. Je, H. D., & Min, Y. (2022). The convergence effect of phenylephrine, isoprenaline and prazosin on vascular contractility. Journal of Convergence for Information Technology, 12 (4), 119-125. DOI : 10.22156/CS4SMB.2022.12.04.119
  19. Jeon, S. B., Jin, F., Kim, J. I., Kim, S. H., Suk, K., Chae, S. C., Jun, J. E., Park, W. H., & Kim, I. K. (2006). A role for Rho kinase in vascular contraction evoked by sodium fluoride. Biochem Biophys Res Commun, 343(1), 27-33. DOI : 10.1016/j.bbrc.2006.02.120