Oligomeric proanthocyanidins (OPACs) are potent and renewable natural bioactives possible to be refined into chemically standardized mixtures for biological applications. Herein, we found that multiscale interactions of OPACs with the dentin matrix create tight biointerfaces with hydrophobic methacrylate adhesives on wet surfaces. An enriched mixture of OPACs, with a known phytochemical profile, was produced from grape seed crude extract ( Vitis vinifera; enriched grape seed extract [e-GSE]) and applied to dentin matrices to determine changes to the mechanical properties and biodegradability of the dentin matrix and favorable resin adhesion mechanisms. Methods included a 3-point flexural test, quantification of hydroxyproline (collagen solubilization), static and dynamic nanomechanical analyses, resin-dentin microtensile bond strength, and micropermeability at the adhesive interface. The e-GSE-modified dentin matrix exhibited remarkably low collagen solubilization and sustained the bulk elastic properties over 12 mo. Tan δ findings reveal a more elastic-like behavior of the e-GSE-modified dentin matrix, which was not affected by H-bond destabilization by urea. Dentin-methacrylate biointerfaces with robust and stable adhesion were created on e-GSE-primed dentin surfaces, leading to a dramatic decrease of the interfacial permeability. Standardized OPAC mixtures provide a new mechanism of adhesion to type I collagen-rich tissues that does not rely on hydrophilic monomers. The bioadhesion mechanism involves physicochemical modifications to the dentin matrix, reduced tissue biodegradation, and bridging to methacrylate resins.

Daphne genkwa SIEB. et ZUCC. (Thymelaeaceae) is a traditional oriental medicine that is widely distributed in Korea and China.1) The flower of this plant (Genkwa flos) has been traditionally used for abortifacient, diuretic, antitussive, expectorant, and anticancer effects.1-3) Previous phytochemical investigations of Genkwa flos led to the isolation of various compounds such as flavonoids, coumarins, amides, and diterpenes.4-9) Daphnane-type diterpenoids are typical constituents of plants from the families Thymelaeaceae and Euphorbiaceace. There have been reported several biological activities of daphnanes including antileukemia, piscicidal, toxicity, anticancer, abortion, and neurotrophy. 8,10,11) As part of our ongoing study for discovery of plant-derived anticancer agents, two new daphnane diterpenoids, namely, yuanhuahine (1) and yuanhualine (2), were isolated from Genkwa flos. The present study describes the structural elucidation of the two new isolates 1 and 2, along with their antiproliferative activities against human lung cancer cells and normal lung epithelial cells. Results and DiscussionCompound 1 was obtained as a white amorphous powder. Its molecular formula was determined as C 33 H 44 O 10 by the pseudo molecular ion peak at m/z 601.3013 [MϩH] ϩ in positive HR-FAB-MS. The IR spectrum of 1 showed absorptions at 3456 cm Ϫ1 for the hydroxyl groups and at 1695 cm Ϫ1 for the conjugated carbonyl group. The 13 C-and distortionless enhancement by polarization transfer (DEPT) 135 spectra of 1 indicated the presence of five methyls, seven methylenes, twelve methines, and nine quaternary carbons. In particular, an unusual quaternary carbon (C-1Ј) at d 117.2 was attributable to an orthoester group, which is a structural feature of daphnane-type diterpenoids. The quaternary carbon signals at d 209.7 and 173.4 in the 13 C-NMR spectrum were assignable to an a,b-unsaturated cyclopentanone and an ester group, respectively. The resonances of d H 3.56 and d C 64.3 (C-7) for an oxygenated methine group and at d C 60.7 (C-6) for an oxygenated quaternary carbon were upfield shifted, suggesting the presence of an epoxy group between C-6 and C-7. C-NMR of 1 were similar to those of yuanhuadine (4), except for the ethyl signals (C-2Љ and C-3Љ) of 1 instead of the methyl signal for the acetyl group in 4. 8,[12][13][14] The methyl signal at d H 1.09 (3H, t, 7.5, H-3Љ) exhibited three-bond connectivity with the conjugated carbon at d C 173.4 (C-1Љ) in the heteronuclear multiple bond correlation (HMBC) spectrum of 1, indicating that the ethyl group was attached to the carbon at C-1Љ (Fig. 2).The relative stereochemistry was determined by analysis of the rotating frame Overhauser enhancement spectroscopy (ROESY) data of 1 as shown in Fig. 3. The ROE correlation between H-12 and CH 3 -18 indicated the trans configuration between the functional groups at C-11 and C-12. Additional correlations between H-7 and H 2 -20, and between H-8 and H-11 and H-14 confirmed their cis positions to each other. Continuous correlations of H-1...

Objectives: The interactivity of proanthocyanidins (PACs) with collagen modulates dentin matrix biomechanics and biostability. Herein, PAC extracts selected based on structural diversity were investigated to determine key PAC features driving sustained effects on dentin matrices over a period of 18 months. Methods: The chemical profiles of PAC-rich plant sources, Pinus massoniana (PM), Cinnamomum verum (CV), Hamamelis virginiana (HV) barks, and Vitis vinifera (VV) seeds, were obtained by diol UHPLC analysis after partitioning of the extracts between methyl acetate and water. Dentin matrices (n = 15) were prepared from human molars to determine the apparent modulus of elasticity over 18 months of aging. Susceptibility of the dentin matrix to degradation by endogenous and exogenous proteases was determined by presence of solubilized collagen in supernatant, and resistance to degradation by bacterial collagenase, respectively. Data were analyzed using ANOVA and Games-Howell post hoc tests (α=0.05). Results: After 18 months, dentin matrices modified by PM and CV extracts, containing only non-galloylated PACs, were highly stable mechanically (p<0.05). Dentin matrices treated with CV exhibited the lowest degradation by bacterial collagenase after 1 hr and 18 months of aging (p<0.05), while dentin matrices treated with PM showed the least mass loss and collagen solubilization by endogenous enzymes over time (p<0.05).

The roots of Angelica tenuissima have been commonly used for the treatment of cardiovascular diseases and menstrual discomfort in Asian countries, such as China and Korea. The primary volatile flavor components are essential oil ingredients, phthalide lactones. In this study, (Z)-ligustilide was tested for its anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We found that (Z)-ligustilide strongly inhibitis the induction of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at both the mRNA and protein levels in a dose-dependent manner. The transcriptional activity of nuclear factor kappa B (NF-B) was also down-regulated in a concentration-dependent manner. Further study revealed that (Z)-ligustilide inhibited the phosphorylation and subsequent degradation of IBα, an inhibitor protein of NF-B. In addition, (Z)-ligustilide inhibited the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK) and c-Jun NH(2)-terminal kinase (JNK) in a dose-dependent manner. Taken together, these data suggest that (Z)-ligustilide can exert its antiinflammatory effects by regulating the NF-B and MAPK signal pathways.

Aimed at exploring the dentin biomodification potential of proanthocyanidins (PACs) for the development of dental biomaterials, this study reports the phytochemical and dental evaluation of nine B-type PACs from grape seed extract (GSE). Out of seven isolated dimers (1−7), four new compounds (2, 3, 5, and 6) involved relatively rare entcatechin or ent-epicatechin monomeric flavan-3-ol units. Lowtemperature NMR analyses conducted along with phloroglucinolysis and electronic circular dichroism enabled unequivocal structural characterization and stereochemical assignment. Additionally, one known (8) and one new (9) B-type trimer were characterized. Differential 13 C NMR chemical shifts (Δδ) were used to determine the absolute configuration of 9, relative to the dimers 1 and 2 as the possible constituent subunits. Compared to the dimers, the trimers showed superior dentin biomodification properties. The dimers, 1−7, exhibited pronounced differences in their collagenase inhibitory activity, while enhancing dentin stiffness comparably. This suggests that PAC structural features such as the degree of polymerization, relative and absolute configuration have a differential influence on enhancement of dentin biomechanical and biostability. As mechanical enhancement to dentin and resistance to proteolytic biodegradation are both essential properties functional and stable dentin substrate, the structurally closely related PACs suggest a new metric, the dentin biomodification potential (DBMP) that may rationalize both properties.