PMID- 29361719 OWN - NLM STAT- MEDLINE DCOM- 20190422 LR - 20190422 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 23 IP - 1 DP - 2018 Jan 20 TI - Antioxidant and Cytoprotective Effects of the Di-O-Caffeoylquinic Acid Family: The Mechanism, Structure-Activity Relationship, and Conformational Effect. LID - 10.3390/molecules23010222 [doi] LID - 222 AB - In this study, a series of di-O-caffeoylquinic acids (di-COQs) were systematically investigated for their antioxidant and cytoprotective effects towards *OH-damaged bone marrow-derived mesenchymal stem cells (bmMSCs). Five di-COQs were measured using a set of antioxidant assays. The results show that adjacent 4,5-Di-O-caffeoylquinic acid (4,5-COQ) and 3,4-di-O-caffeoylquinic acid (3,4-COQ) always gave lower IC(50) values than did non-adjacent di-COQs. In the Fe(2+)-chelating assay, 4,5-COQ and 3,4-COQ presented greater UV-Vis spectra and darker colors than did non-adjacent di-COQs. In the UPLC-ESI-MS/MS analysis, no corresponding radical adduct formation (RAF) peak was found in the reaction products of di-COQs with PTIO*. In the MTT assay, all di-COQs (especially 1,5-COQ, 1,3-COQ, and 4,5-COQ) dose-dependently increased the cellular viabilities of *OH-damaged bmMSCs. Based on this evidence, we conclude that the five antioxidant di-COQs can protect bmMSCs from *OH-induced damage. Their antioxidant mechanisms may include electron-transfer (ET), H(+)-transfer, and Fe(2+)-chelating, except for RAF. Two adjacent di-COQs (4,5-COQ and 3,4-COQ) always possessed a higher antioxidant ability than the non-adjacent di-COQs (1,3-COQ, 1,5-COQ, and 3,5-COQ) in chemical models. However, non-adjacent 1,3-COQ and 1,5-COQ exhibited a higher cytoprotective effect than did adjacent di-COQs. These differences can be attributed to the relative positions of two caffeoyl moieties and, ultimately, to the conformational effect from the cyclohexane skeleton. FAU - Li, Xican AU - Li X AUID- ORCID: 0000-0002-4358-3993 AD - School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. lixican@126.com. AD - Innovative Research & Development Laboratory of TCM, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. lixican@126.com. FAU - Li, Ke AU - Li K AD - School of Basic Medical Science, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. ys1090992678@163.com. AD - The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. ys1090992678@163.com. FAU - Xie, Hong AU - Xie H AD - School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. xiehongxh1@163.com. AD - Innovative Research & Development Laboratory of TCM, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. xiehongxh1@163.com. FAU - Xie, Yulu AU - Xie Y AD - School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. xieyulu1900@163.com. AD - Innovative Research & Development Laboratory of TCM, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. xieyulu1900@163.com. FAU - Li, Yueying AU - Li Y AD - School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. lln@gzucm.edu.cn. FAU - Zhao, Xiaojun AU - Zhao X AD - School of Chinese Herbal Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. zxj@gzucm.edu.cn. AD - Innovative Research & Development Laboratory of TCM, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. zxj@gzucm.edu.cn. FAU - Jiang, Xiaohua AU - Jiang X AD - School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong 999077, China. xjiang@cuhk.edu.hk. FAU - Chen, Dongfeng AU - Chen D AD - School of Basic Medical Science, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. chen888@gzucm.edu.cn. AD - The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Waihuan East Road No. 232, Guangzhou Higher Education Mega Center, Guangzhou 510006, China. chen888@gzucm.edu.cn. LA - eng PT - Journal Article DEP - 20180120 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Antioxidants) RN - 0 (Iron Chelating Agents) RN - 0 (caffeoylquinic acid) RN - 058C04BGYI (Quinic Acid) SB - IM MH - Animals MH - Antioxidants/*chemistry/pharmacology MH - Cell Survival/drug effects MH - Cytoprotection MH - Iron Chelating Agents/chemistry MH - Mesenchymal Stem Cells/cytology/drug effects MH - Molecular Conformation MH - Quinic Acid/*analogs & derivatives/chemistry/pharmacology MH - Rats MH - Structure-Activity Relationship PMC - PMC6017143 OTO - NOTNLM OT - antioxidant OT - caffeoylquinic acids OT - conformational effect OT - cytoprotective effect COIS- The authors declare that they have no competing interests. EDAT- 2018/01/25 06:00 MHDA- 2019/04/23 06:00 PMCR- 2018/01/20 CRDT- 2018/01/25 06:00 PHST- 2017/12/08 00:00 [received] PHST- 2018/01/06 00:00 [revised] PHST- 2018/01/18 00:00 [accepted] PHST- 2018/01/25 06:00 [entrez] PHST- 2018/01/25 06:00 [pubmed] PHST- 2019/04/23 06:00 [medline] PHST- 2018/01/20 00:00 [pmc-release] AID - molecules23010222 [pii] AID - molecules-23-00222 [pii] AID - 10.3390/molecules23010222 [doi] PST - epublish SO - Molecules. 2018 Jan 20;23(1):222. doi: 10.3390/molecules23010222.