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Original Article

Korean J Physiol Pharmacol 2022; 26(1): 15-24

Published online January 1, 2022

Copyright © Korean J Physiol Pharmacol.

Gallic acid-mitochondria targeting sequence-H3R9 induces mitochondria-targeted cytoprotection

Yoonhee Bae1,2, Goo-Young Kim3, Flores Jessa1, Kyung Soo Ko1,4, and Jin Han1,*

1Department of Physiology, Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, Inje University College of Medicine, Busan 47392, 2Division of Applied Medicine, Research Institute for Korea Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, 3Department of Biology and Clinical Pharmacology, R&D Center, Samyang Biopharmaceuticals Corporation, Seongnam 13488, 4Department of Internal Medicine, Sanggye Paik Hospital, Cardiovascular and Metabolic Disease Center, Inje University, Seoul 01757, Korea

Correspondence to:Jin Han

Received: April 1, 2021; Revised: October 13, 2021; Accepted: October 21, 2021

This is an Open Access journal distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


The development of selective targeting of drug molecules towards the mitochondria is an important issue related to therapy efficacy. In this study, we report that gallic acid (GA)-mitochondria targeting sequence (MTS)-H3R9 exhibits a dual role as a mitochondria-targeting vehicle with antioxidant activity for disease therapy. In viability assays, GA-MTS-H3R9 showed a better rescue action compared to that of MTS-H3R9. GA-MTS-H3R9 dramatically exhibited cell penetration and intercellular uptake compared to MTS and fit escape from lysosome release to the cytosol. We demonstrated the useful targeting of GA-MTS-H3R9 towards mitochondria in AC16 cells. Also, we observed that the antioxidant properties of mitochondrial-accrued GA-MTSH3R9 alleviated cell damage by reactive oxygen species production and disrupted mitochondrial membrane potential. GA-MTS-H3R9 showed a very increased cytoprotective effect against anticancer activity compared to that of MTS-H3R9. We showed that GA-MTS-H3R9 can act as a vehicle for mitochondria-targeting and as a reagent for therapeutic applications intended for cardiovascular disease treatment.

Keywords: Antioxidant activity, Gallic acid, Mitochondria