To date, quantitative analysis of proanthocyanidin (PAC) containing materials including plant extracts and fractions depends on colorimetric assays or phloroglucinolysis/thiolysis combined with UV-HPLC analysis. Such assays are of limited accuracy, particularly lack specificity, require extensive sample preparation and degradation, and need appropriate physical reference standards. To address this analytical challenge and toward our broader goal of developing new plant-sourced biomaterials that chemically and mechanically modulate the properties of dental tissue for clinical interventions, we have characterized 12 different PAC DESIGNER (Depletion and Enrichment of Select Ingredients Generating Normalized Extract Resources) materials.
View Article and Find Full Text PDFObjective: Investigate the bioactivity and stability of Rhodiola rosea (RR) fractions as a natural source of prodelphinidin gallate (PDg) on dentin collagen via analysis of the viscoelastic and resin-dentin adhesive properties of the dentin matrix.
Methods: The biomimicry and stability of RR subfractions (F1, F2, F3 and F4) with collagen were determined by dynamic mechanical analysis (DMA). DMA used a strain sweep method to assess the dentin matrix viscoelastic properties [storage (E'), loss (E"), and complex (E*) moduli and tan δ] after treatment, 7-, 30- and 90-days of storage in simulated body fluids (SBF).
J Biomed Mater Res B Appl Biomater
January 2024
Flavan-3-ol monomers are the building blocks of proanthocyanidins (PACs), natural compounds from plants shown to mediate specific biologic activities on dentin. While the stereochemistry of the terminal flavan-3-ols, catechin (C) versus epicatechin (EC), impacts the biomechanical properties of the dentin matrix treated with oligomeric PACs, structure-activity relationships driving this bioactivity remain elusive. To gain insights into the modulatory role of the terminal monomers, two highly congruent trimeric PACs from Pinus massoniana only differing in the stereochemistry of the terminal unit (Trimer-C vs.
View Article and Find Full Text PDFProanthocyanidins (PACs) are complex flavan-3-ol polymers with stunning chemical complexity due to oxygenation patterns, oxidative phenolic ring linkages, and intricate stereochemistry of their heterocycles and inter-flavan linkages. Being promising candidates for dental restorative biomaterials, trace analysis of dentin bioactive cinnamon PACs now yielded novel trimeric ( and ) and tetrameric () PACs with unprecedented - and benzoquinone motifs (benzoquinonoid PACs). Challenges in structural characterization, especially their absolute configuration, prompted the development of a new synthetic-analytical approach involving comprehensive spectroscopy, including NMR with quantum mechanics-driven H iterative functionalized spin analysis (HifSA) plus experimental and computational electronic circular dichroism (ECD).
View Article and Find Full Text PDFIn botanical extracts, highly abundant constituents can mask or dilute the effects of other, and often, more relevant biologically active compounds. To facilitate the rational chemical and biological assessment of these natural products with wide usage in human health, we introduced the DESIGNER approach of Depleting and Enriching Selective Ingredients to Generate Normalized Extract Resources. The present study applied this concept to clinical Red Clover Extract (RCE) and combined phytochemical and biological methodology to help rationalize the utility of RCE supplements for symptom management in postmenopausal women.
View Article and Find Full Text PDFBreast cancer risk continues to increase post menopause. Anti-estrogen therapies are available to prevent postmenopausal breast cancer in high-risk women. However, their adverse effects have reduced acceptability and overall success in cancer prevention.
View Article and Find Full Text PDFMonoterpenoids are integral to the chemical composition of the widely used adaptogenic dietary supplement . The present study expands the chemical space and stereochemical information about these taxon-specific constituents from the isolation and characterization of five geraniol-derived glucosides, -. While and exhibited almost identical NMR spectra and shared the same 2D structure ascribed to the 4-hydroxygeraniolglucoside previously described as rosiridin, the NMR-based Mosher ester method revealed the enantiomeric nature of their aglycone moieties.
View Article and Find Full Text PDFInvestigation of a pine bark extract for bioactive proanthocyanidin oligomers resulted in the isolation of structurally related dimeric B-type procyanidin derivatives, -. This includes scalemic mixtures of gambiriin A1 () and A2 () and their newly described optical antipodes, -gambiriin A1 () and -gambiriin A2 (), respectively, as well as a racemic mixture of the newly described (-)gambiriin A5 (/). Furthermore, the study now fully characterizes the previously reported optically pure dimers gambiriin B1 () and gambirflavan D1 (), and characterized the novel B-type procyanidin trimer, (gambirifuran C1).
View Article and Find Full Text PDFLicorice, the roots and rhizomes of L., has been used as a medicinal herb, herbal adjuvant, and flavoring agent since ancient times. Recently, licorice extracts have become popular as dietary supplements used by females to alleviate menopausal symptoms.
View Article and Find Full Text PDFFour new rufomycins, compounds -, named rufomycins 56, 57, 58, and 61, respectively, exhibiting new skeletal features, were obtained from strain MJM3502 and were fully characterized. Compounds and possess a 4-imidazolidinone ring not previously encountered in this family of cyclopeptides, thereby resulting in a [5,17] bicyclic framework. The in vitro anti- potency of compounds and is remarkable, with minimum inhibitory concentration values of 8.
View Article and Find Full Text PDFTo enable translational studies, a scalable preparative isolation scheme was developed for underivatized cocoa () proanthocyanidins (PACs), affording six all-B-type oligomeric PACs, including a new tetramer . Their structures, including absolute configuration, were unambiguously established by comprehensive spectroscopic and chemical methods. Evaluation of the PACs' dentin biomodification properties employed dynamic mechanical and infrared spectroscopic analyses in dentin bioassay models.
View Article and Find Full Text PDFAim: Grape seed extract contains a complex mixture of proanthocyanidins (PACs), a plant biopolymer used as a biomaterial to improve reparative and preventive dental therapies. Co-polymerization of PACs with type I collagen mechanically reinforces the dentin extracellular matrix. This study assessed the biocompatibility of PACs from grape seed extract on dental pulp stem cells (DPSCs) in a model simulating leaching through dentin to the pulp cavity.
View Article and Find Full Text PDFThe ICH guidelines recommend reporting thresholds for regular impurities in drug substances at the level of 0.05% or 0.03% (w/w) depending on the maximum daily intake.
View Article and Find Full Text PDFTo enable the further exploration of structure-activity relationships (SARs) of proanthocyanidins (PACs) with dentin biomodification abilities, was selected for scaled-up purification of mixed A-/B-type, medium-size PAC oligomers. Sequential purification by centrifugal partition chromatography (CPC), Sephadex LH-20, and semiprep HPLC chromatography yielded four underivatized tetrameric (-) and two pentameric (-) PACs. Their unambiguous structural characterization involved extensive spectral and chemical degradation approaches to show that epicatechin units are connected by plant-specific combinations of doubly linked A- and singly linked B-type interflavanyl bonds.
View Article and Find Full Text PDFMuch confusion exists about the chemical composition of widely sold products that utilize the cannabidiol (CBD) acronym and related terms such as "CBD oil", "CBD plus hemp oil", "full spectrum CBD", "broad spectrum CBD", and "cannabinoids". Their rational chemical and subsequent biological assessment requires both knowledge of the chemical complexity and the characterization of significant individual constituents. Applicable to hemp preparations in general, this study demonstrates how the combination of liquid-liquid-based separation techniques, NMR analysis, and quantum mechanical-based NMR interpretation facilitates the process of natural product composition analysis by allowing specific structural characterization and absolute quantitation of cannabinoids present in such products with a large dynamic range.
View Article and Find Full Text PDFRufomycin and ilamycin are synonymous for the same class of cyclopeptides, currently encompassing 33 structurally characterized isolates and 9 semisynthetic derivatives. Elucidation of new structures prioritized the consolidation of the names and established the structures of four diastereoisomeric rufomycins with a 2-piperidinone, named rufomycins 4-7, including full H/C NMR assignments. The characteristic HSQC cross-peak for the CH-5, the hemiaminal carbon in amino acid #5, allows assignment of the stereocenters C-4 and C-5 within this ring.
View Article and Find Full Text PDFOff-line combination of countercurrent separation (CCS) and quantitative H NMR (qHNMR) methodologies enabled the systematic dissection and gravimetric quantification of a chemically complex crude extract (RCE). The loss-free nature and high selectivity of CCS achieved the quantitative discrimination of fatty acids (FAs), sugars, and proanthocyanidins (PACs) from ten other metabolite classes: phenylpropanoids, phenylethanoids, acyclic monoterpenoid glycosides, pinene derived glycosides, benzyl alcohol glycosides, cyanogenic glycosides, flavonoids, gallic acids, methylparabens, and cuminol glycosides. The ability of CCS to remove ("knockout") PACs completely resolved challenges with baselines that plague NMR and UHPLC analyses and produce inaccurate integral and AUC quantitation, respectively.
View Article and Find Full Text PDFNontuberculous mycobacterial pulmonary infection is often aggravated due to antibiotic resistance issues. There is a need for development of new drugs inducing both host immune responses and antimicrobial activities. This study shows that the rufomycins 4/5/6/7 (Rufomycin 4-7), which targets ClpC1 as a subunit of caseinolytic protein complex ClpC1/ClpP1/ClpP2 of mycobacteria, exhibits a dual effect in host innate defense and antimicrobial activities against a rough morphotype of (Mabs-R), a clinically severe morphotype that causes hyperinflammation.
View Article and Find Full Text PDFThe importance of Trifolium pratense L. as a dietary supplement and its use in traditional medicine prompted the preparation of a thorough metabolite profile. This included the identification and quantitation of principal constituents as well as low abundant metabolites that constitute the residual complexity (RC) of T.
View Article and Find Full Text PDFPlant-derived proanthocyanidins (PACs) mediate physicochemical modifications to the dentin extracellular matrix (ECM). The structure-activity relationships of PACs remain largely unknown, mostly due to the varied complex composition of crude extracts, as well as the challenges of purification and mechanistic assessment. To assess the role of galloylated PACs as significant contributors to high yet unstable biomodification activity to the dentin ECM, we removed the galloyl moieties (de-galloylation) via enzymatic hydrolysis from three galloyl-rich PAC-containing extracts (Camellia sinensis, Vitis vinifera, and Hamamelis virginiana).
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