A galloylated dimeric proanthocyanidin from grape seed exhibits dentin biomodification potential

Abstract

Grape seeds are a rich source of polyphenols, especially proanthocyanidins (PACs), and are also known for the presence of galloylated oligomeric PACs (OPACs). The present study focuses on phytochemical methodology for grape seed (O)PACs and their potential role as dentin bio-modifiers to be used in restorative and reparative dentistry. A new method using centrifugal partition chromatography (CPC) was developed for the preparative separation of the grape seed (O)PACs. Orthogonal phytochemical profiling of the resulting CPC fractions was performed using C18 and diol HPLC, normal phase HPTLC, and IT-TOF MS analysis. A galloylated procyanidin dimer (1) was isolated from a CPC fraction in order to evaluate its potential to enhance dentin bio-mechanical properties. Moreover, it helped to evaluate the impact of the galloyl moiety on the observed bioactivity. Structure elucidation was performed using ESI-MS, 1D and 2D NMR analyses. For the first time, 1H iterative full spin analysis (HiFSA) was performed on this type of molecule, enabling a detailed proton chemical shift and coupling constant assignment. The CPC fractions as well as 1 showed promising results in the dentin stiffness bioassay and indicate that it may be used as dental intervention material.

Experimental primers containing synthetic and natural compounds reduce enzymatic activity at the dentin–adhesive interface under cyclic loading

“…Recently, the modification of the dentin matrix has been extensively studied with extracts rich in proanthocyanidins (PACs) [3, 20]. The effective interaction of PACs and the dentin matrix remarkably increases the dentin matrix’s resistance to enzymatic degradation [3, 7, 22, 33, 44] without interfering with the formation of the hybrid layer [6, 21, 35].…”

“…Three experimental primers were obtained as follow: (i) oligomeric proanthocyanidin enriched grape seed extract (e-GSE) prepared by a solvent partitioning protocol previously published [20] and prepared at 15% w/v concentration in buffer solution (20 mM HEPES pH 7.4); (ii) primer of Doxycycline Hydrochloride (DOXY - Fisher Scientific - New Jersey, NJ, USA) at 3% w/v in buffer solution; (iii) Chlorhexidine digluconate (CHX) primer prepared by dilution of stock solution (20% CHX, Sigma; St. Louis, MO, USA) to 0.2% CHX in distilled water. HEPES buffer solution was used as negative control primer.…”

“…Proanthocyanidins (PAC) are known antioxidant and collagen cross-linking agent with vast biological and functional activities [3]. Certain grape seed extracts (GSE) are main sources of PAC [19] shown to enhance the mechanical properties and reduce biodegradation rates of demineralized dentin [3, 20] by multi-interaction with dentin matrix components, including type I collagen [3], proteoglycans [3, 14] and endogenous proteases [3, 21, 22]. Isolation of highly bioactive compounds of GSE has recently shown promising results [20] for future design of a standardized clinical intervention material.…”

Preparative separation of grape skin polyphenols by high-speed counter-current chromatography

“…Because galloylated procyanidins were confirmed to have much higher antioxidant activities than the non-galloylated ones (Phansalkar et al, 2015;Zhang et al, 2015), the results obtained by this part of work were of utmost importance, providing a new method for preparation of these bioactive compounds. Fig.…”

Effect of Bioactive Primers on Bacterial-Induced Secondary Caries at the Tooth-Resin Interface

“…Using a previously published method, 19 the polymeric PACs were selectively depleted from the crude extract to yield an enriched oligomeric mixture (e-GSE). The refined e-GSE material was composed of phenolic acids and phenolic monomers (PACs) that are commonly known as catechins and the oligomeric PACs.…”