ACE Inhibitory and Antihypertensive Effect of Chitosan Oligosaccharides in SHR

Chitosan 올리고당의 안지오텐신 전환효소 활성 억제 및 SHR에서의 고혈압 억제 특성

Effect of chitosan oligosaccharides on the ACE (angiotensin I converting enzyme) inhibition and antihypertension in SHR (Spontaneously hypertensive rat) was examined. The ACE inhibition activity was observed in all the chitosan oligosaccharides used in this study, and chitosan trimer exhibited the highest inhibitory activity $(IC_{50}=0.9{\mu}M)$ compared with other chitosan oligosaccharides $(IC_{50}\;:\;2.4{\sim}100\;{\mu}M)$. The results suggested that chitosan trimer was a good inhibitor of ACE in molecular level. When the single oral dose (2.14 mg/kg, similar to dose level of Captopril, known as strong ACE inhibitor) of chitosan trimer was given to 8 or 21 week aged SHR, the blood pressure reduction of both SHRs in 4hrs were $27{\pm}4.8\;mmHg\;and\;36{\pm}4.3\;mmHg$, respectively. Therefore, it was suggested that chitosan trimer could be applicable as natural ACE inhibitor related to antihypertension.

키토산 올리고당이 ACE 저해활성과 SHR의 혈압에 미치는 영향을 검토하였다. 키토산 올리고당은 모두 ACE 저해활성을 나타내었다. ACE 저해활성$(IC_{50})$은 3량체가 $0.9\;{\mu}mole$로 가장 우수하였고 2량체의 경우에는 $2.4\;{\mu}mole$, 그 외의 올리고당은 모두 $>100\;{\mu}mole$였다. 강력한 ACE 저해제인 Captopril(2-D-mercaptopropanoyl-L-proline)의 인체 투여량을 기준으로 3량체 키토산 올리고당 2.14 mg/kg을 SHR에 강제 경구투여한 바, 4시간 경에 8주령 및 21주령 SHR모두 최저혈압을 보였고 이 때의 혈압 강하는 8주령 SHR $27{\pm}4.8\;mmHg$, 21주령 SHR $36{\pm}4.3\;mmHg$로 나타났다. 따라서 3량체 키토산 올리고당은 2량체 키토산 올리고당과 함께 향후 고혈압 치료제로서 응용가능함이 시사되었다.