Antioxidant and Cytoprotective Effects of the Di-O-Caffeoylquinic Acid Family: The Mechanism, Structure–Activity Relationship, and Conformational Effect

Abstract

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 IC50 values than did non-adjacent di-COQs. In the Fe2+-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 Fe2+-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.

2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide Radical (PTIO•) Trapping Activity and Mechanisms of 16 Phenolic Xanthones

“…Our findings regarding the role of ortho -di-OHs was further supported by a number of reports, which usually referred to ortho -di-OHs as the catechol moiety [ 22 , 23 , 24 , 25 , 26 ]. The reason why the ortho -di-OHs play a critical role in antioxidant xanthones may be the fact that ortho -di-OHs can be oxidized to ortho -benzo quinone by free radicals [ 27 , 28 ].…”

“…It must be emphasized that (1) the antioxidant role of para -di-OHs type in natural phenolics has not been mentioned previously [ 32 ]. This may be attributed to the fact that para -di-OHs are hardly found in flavonoids [ 13 , 14 , 26 , 33 ] and other phenolics [ 13 , 14 , 19 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 34 , 35 ]. For instance, among thousands of flavonoids, only 5 para -di-OHs flavonoids (i.e., 5,8-dihydroxy-flavonoids) have been documented: rhodionin [ 36 ], 5,8-dihydroxy-3,6,7-trimethoxyflavone [ 37 ], 5,8-dihydroxy-6,7-dimethoxyflavone [ 37 ], 5,8-dihydroxy-6,7,4′-trimethoxyflavone, and 5,8-dihydroxy-6,7,3′,4′,5′-pentamethoxyflavone [ 38 ].…”

pH Effect and Chemical Mechanisms of Antioxidant Higenamine

“…As seen in Figure 4 , from pH 4.5 to pH 7.4 and from pH 6.0 to pH 7.4, Trolox antioxidant levels increased by only 2.0 times and 1.2 times, respectively. Similar mild pH effect was observed in the 3,5-di- O -caffeoylquinic acid family, which even slightly decreased the antioxidant level 0.93 times (108.6/116.5) from pH 4.5 to pH 7.4 [ 38 ]. The difference suggests that N-containing antioxidant is more sensitive to lower pH values than O-containing antioxidant; and thus, the strong pH effect might be closely associated with the existence of N-atom.…”

Structure–Activity Relationship and Prediction of the Electron‐Transfer Potential of the Xanthones Series

“…Previously, several studies reported that the catechol moiety played a critical role in phenolic antioxidants . However, Woodman insisted on a minor role of the catechol moiety .…”

“…The isoprenyl moiety occasionally occurs in other phenolic antioxidants, such as flavonoids, [51] lignanoids,c oumarins, and stilbenes. [1,14,37,[51][52][53][54] However,u ntil now there have not been any systematic reviewsm entioning its role in antioxidant (especially ET) potential. [55] In the present study,t he isoprenyl group was shown to decrease slightly the ET potential.…”