Synthesis of Short-Chain-Fatty-Acid Resveratrol Esters and Their Antioxidant Properties

Abstract

To expand the applications and enhance the stability and bioactivity of resveratrol (RE), and to simultaneously include the potential health benefits of short chain fatty acids (SCFA) esters of RE were prepared by Steglich reactions with acetic, propionic, and butyric acids, respectively. RE and the esterified RE-SCFA products (including RAE, RPE, and RBE) were analyzed using nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), differential thermal analysis (DTA), and liquid chromatography–mass spectrometry (LC–MS). The FTIR and 13C NMR spectra of the esterified products included ester-characteristic peaks at 1751 cm−1 and 171 ppm, respectively. Moreover, the peaks in the range of 1700 to 1600 cm−1 in the FTIR spectra of the esterified products indicated that the esterification of RE-SCFA was successful. The TGA results revealed that the RE-SCFA esters decomposed at lower temperatures than RE. The peaks in the LC–MS profiles of the esterified products indicated the formation of mono- and diesters, and the calculated monoester synthesis rates ranged between 45.81 and 49.64%. The RE esters inhibited the Cu2+-induced low-density lipoprotein oxidation reaction, exhibited antioxidant activity in bulk oil, and effectively inhibited the hydroxyl radical-induced DNA scission. Moreover, the RE-SCFA esters had better hydrogen peroxide scavenging activity than RE. Our results are the first in the literature to successfully including short chain fatty acids in the esters of resveratrol, and the products could be used as a functional food ingredient in processed foods or can be used as dietary supplements to promote health.

Resveratrol Butyrate Esters Inhibit BPA-Induced Liver Damage in Male Offspring Rats by Modulating Antioxidant Capacity and Gut Microbiota

“…However, our previous study demonstrated that RBE does not cause cytotoxicity to HepG2, according to an MTT assay [ 39 ]. In addition, RBE can inhibit hydroxyl radical-induced DNA scission [ 40 ], which indirectly demonstrates the safety of RBE. For the sake of caution, the ADME of resveratrol and RBE (including resveratrol, resveratrol monoester 1, resveratrol monoester 2, and resveratrol diester) were evaluated using the SwissADME software, which is a free web tool for evaluating pharmacokinetics, drug-likeness, and medicinal chemistry friendliness, taking six physicochemical properties into account: lipophilicity, size, polarity, solubility, flexibility, and saturation [ 53 ].…”

“…Upon completion of the reaction, a copious amount of distilled water was added, and the reaction mixture was filtered to obtain the precipitated RBE, which was freeze-dried and stored at −20 °C. The novel RBE was produced by the esterification of RSV and butyric acid, including RSV (about 17.11%), RBE monoester (47.12%), and RBE diester (35.00%) [ 40 ].…”

“…Subsequently, N-ethyl-N -(3-dimethylaminopropyl) carbodiimide (EDC) (Sigma-Aldrich, Missouri, USA) and 4-dimethylaminopyridine (DMAP) (Sigma-Aldrich, Missouri, USA) were added, and the esterification reaction was carried out for 48 h in the absence of light. Upon completion of the reaction, a copious amount of distilled water was added, and the reaction mixture was filtered to obtain the precipitated RBE, which was freeze-dried and stored at −20 • C. The novel RBE was produced by the esterification of RSV and butyric acid, including RSV (about 17.11%), RBE monoester (47.12%), and RBE diester (35.00%) [40].…”

“…When the reaction was performed for the esterification of RSV and butyric acid to form resveratrol butyrate esters (RBEs), a 30% increase in the production of RBE was observed [ 39 ]. In addition, in the previous study, we reported novel resveratrol butyrate esters (RBE) and indicated that the esterification of RSV with butyrate produced RSV, RBE monoester, and RBE diester, which also showed better hydrogen peroxide-scavenging activity than RSV [ 40 ]. It was also found that RBE can effectively inhibit fatty acid-induced lipid accumulation in HepG2 cells, with effects similar to those of RSV achieved at a lower dose [ 39 ].…”

Resveratrol Butyrate Esters Inhibit Obesity Caused by Perinatal Exposure to Bisphenol A in Female Offspring Rats

“…The pharmacokinetic study reported by Huang et al (2019) showed that the blood concentration of RSV peaked within 0.5 to 2 h after oral administration, followed by a rapid decline [ 36 ], indicating that RSV is unable to induce adequate pharmacological responses in pregnant women; hence, it is not an ideal clinical drug. We reported novel resveratrol butyrate esters (RBEs) and indicated the esterification of RSV with butyrate that contained RSV (~17.1%), RBE monoester (~47.1%), and RBE diester (~35.0%), which also had better hydrogen peroxide scavenging activity than RSV [ 37 ] and could effectively inhibit fatty-acid-induced lipid accumulation in HepG2 cells, with effects similar to those of RSV, but achieved at a lower dose level [ 38 ]. Butyrate, one of the short-chain fatty acids (SCFAs), can selectively promote the growth of beneficial bacteria that improve the intestinal barrier’s function [ 39 ].…”