Tao Yuan

Anti-Inflammatory Effects of Polyphenolic-Enriched Red Raspberry Extract in an Antigen Induced Arthritis Rat Model

The red raspberry ( Rubus idaeus ) fruit contains bioactive polyphenols including anthocyanins and ellagitannins with reported anti-inflammatory properties. This study sought to investigate the cartilage-protecting and anti-inflammatory effects of a polyphenolic-enriched red raspberry extract (RRE; standardized to total polyphenol, anthocyanin, and ellagitannin contents) using (1) an in vitro bovine nasal explant cell culture model and (2) an in vivo adjuvant-induced arthritis rat model. RRE contained 20% total polyphenols (as gallic acid equivalents), 5% anthocyanins (as cyanidin-3-glucoside equivalents), and 9.25% ellagitannins (as ellagic acid equivalents). In the in vitro studies, bovine nasal explants were stimulated with 10 ng/mL IL-1β to induce the release of proteoglycan and type II collagen. On treatment with RRE (50 μg/mL), there was a decrease in the rate of degradation of both proteoglycan and type II collagen. In the in vivo antigen-induced arthritis rat model, animals were gavaged daily with RRE (at doses of 30 and 120 mg/kg, respectively) for 30 days after adjuvant injection (750 μg of Mycobacterium tuberculosis suspension in squalene). At the higher dose, animals treated with RRE had a lower incidence and severity of arthritis compared to control animals. Also, histological analyses revealed significant inhibition of inflammation, pannus formation, cartilage damage, and bone resorption by RRE. This study suggests that red raspberry polyphenols may afford cartilage protection and/or modulate the onset and severity of arthritis.

Antioxidant and α-glucosidase inhibitory phenolics isolated from highbush blueberry flowers

Blueberries have been extensively researched, but there are limited studies on other parts of the plant. Here we report the first phytochemical examination of highbush blueberry (Vaccinium corymbosum) flowers, which yielded 21 phenolics. The compounds were identified from extensive NMR and mass spectral analyses and included five caffeic acid (1-5), three coumaric acid (6-8), and two cinnamyl alcohol (9-10) derivatives, eight flavonol glycosides (11-18), and three phenylpropanoid-substituted catechins (19-21). The isolates were evaluated for antioxidant and α-glucosidase inhibitory activities. Overall, the flavonol glycosides and phenylpropanoid-substituted catechins showed superior antioxidant activities compared to the positive controls, vitamin C (IC(50)=63μM) and butylated hydroxytoluene (IC(50)=1548μM). Similarly, these phenolic sub-classes were more potent α-glucosidase inhibitors than the clinical drug, acarbose (IC(50)=200μM). Thus, non-consumed parts of food plants may be exploited as sources of bioactive compounds beyond their edible parts alone for nutraceutical and functional food applications.

α-Glucosidase inhibitory hydrolyzable tannins from Eugenia jambolana seeds.

Three new hydrolyzable tannins including two gallotannins, jamutannins A (1) and B (2), and an ellagitannin, iso-oenothein C (3), along with eight known phenolic compounds were isolated from the seeds of Eugenia jambolana fruit. The structures were elucidated on the basis of spectroscopic data analysis. All compounds isolated were evaluated for α-glucosidase inhibitory effects compared to the clinical drug acarbose.

Maplexins, new α-glucosidase inhibitors from red maple (Acer rubrum) stems.

Thirteen gallic acid derivatives including five new gallotannins, named maplexins A-E, were isolated from red maple (Acer rubrum) stems. The compounds were identified by spectral analyses. The maplexins varied in number and location of galloyl groups attached to 1,5-anhydro-d-glucitol. The isolates were evaluated for α-glucosidase inhibitory and antioxidant activities. Maplexin E, the first compound identified with three galloyl groups linked to three different positions of 1,5-anhydro-d-glucitol, was 20 fold more potent than the α-glucosidase inhibitory drug, Acarbose (IC(50)=8 vs 160 μM). Structure-activity related studies suggested that both number and position of galloyls attached to 1,5-anhydro-d-glucitol were important for α-glucosidase inhibition.

Pomegranate’s Neuroprotective Effects against Alzheimer’s Disease Are Mediated by Urolithins, Its Ellagitannin-Gut Microbial Derived Metabolites

Pomegranate shows neuroprotective effects against Alzheimers disease (AD) in several reported animal studies. However, whether its constituent ellagitannins and/or their physiologically relevant gut microbiota-derived metabolites, namely, urolithins (6H-dibenzo[b,d]pyran-6-one derivatives), are the responsible bioactive constituents is unknown. Therefore, from a pomegranate extract (PE), previously reported by our group to have anti-AD effects in vivo, 21 constituents, which were primarily ellagitannins, were isolated and identified (by HPLC, NMR, and HRESIMS). In silico computational studies, used to predict blood-brain barrier permeability, revealed that none of the PE constituents, but the urolithins, fulfilled criteria required for penetration. Urolithins prevented β-amyloid fibrillation in vitro and methyl-urolithin B (3-methoxy-6H-dibenzo[b,d]pyran-6-one), but not PE or its predominant ellagitannins, had a protective effect in Caenorhabditis elegans post induction of amyloid β(1-42) induced neurotoxicity and paralysis. Therefore, urolithins are the possible brain absorbable compounds which contribute to pomegranates anti-AD effects warranting further in vivo studies on these compounds.

Phenolic glycosides from sugar maple (Acer saccharum) bark.

Four new phenolic glycosides, saccharumosides A-D (1-4), along with eight known phenolic glycosides, were isolated from the bark of sugar maple (Acer saccharum). The structures of 1-4 were elucidated on the basis of spectroscopic data analysis. All compounds isolated were evaluated for cytotoxicity effects against human colon tumorigenic (HCT-116 and Caco-2) and nontumorigenic (CCD-18Co) cell lines.

Chemical Compositional, Biological, and Safety Studies of a Novel Maple Syrup Derived Extract for Nutraceutical Applications

Maple syrup has nutraceutical potential given the macronutrients (carbohydrates, primarily sucrose), micronutrients (minerals and vitamins), and phytochemicals (primarily phenolics) found in this natural sweetener. We conducted compositional (ash, fiber, carbohydrates, minerals, amino acids, organic acids, vitamins, phytochemicals), in vitro biological, and in vivo safety (animal toxicity) studies on maple syrup extracts (MSX-1 and MSX-2) derived from two declassified maple syrup samples. Along with macronutrient and micronutrient quantification, thirty-three phytochemicals were identified (by HPLC-DAD), and nine phytochemicals, including two new compounds, were isolated and identified (by NMR) from MSX. At doses of up to 1000 mg/kg/day, MSX was well tolerated with no signs of overt toxicity in rats. MSX showed antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH) assay) and anti-inflammatory (in RAW 264.7 macrophages) effects and inhibited glucose consumption (by HepG2 cells) in vitro. Thus, MSX should be further investigated for potential nutraceutical applications given its similarity in chemical composition to pure maple syrup.

New phenolics from the flowers of Punica granatum and their in vitro α-glucosidase inhibitory activities.

Two new phenolics, a 3-substituted coumarin, 7,8-dihydroxy-3-carboxymethylcoumarin-5-carboxylic acid, and a hydrolyzable tannin, namely punicatannin C, together with 10 known phenolics, were isolated from the flowers of pomegranate (Punica granatum). Their structures were determined on the basis of extensive spectroscopic analyses including HRESIMS, 1D and 2D NMR data. All the isolates were evaluated for in vitro α-glucosidase inhibitory activities.

Indazole-Type Alkaloids from Nigella sativa Seeds Exhibit Antihyperglycemic Effects via AMPK Activation in Vitro

Six rare naturally occurring indazole-type alkaloids including two new compounds, 17-O-(β-d-glucopyranosyl)-4-O-methylnigellidine (1) and nigelanoid (2), and four known compounds (3–6) were isolated from a defatted extract of Nigella sativa (black cumin) seeds. 17-O-(β-d-Glucopyranosyl)-4-O-methylnigellidine (1) increased glucose consumption by liver hepatocytes (HepG2 cells) through activation of AMP-activated protein kinase (AMPK). Also, this is the first report of compounds 4 and 6 from a natural source.

Antidiabetic ellagitannins from pomegranate flowers: inhibition of α-glucosidase and lipogenic gene expression.

Two new ellagitannins containing a rare 3-oxo-1,3,3a,8b-tetrahydrofuro[3,4-b]benzofuran moiety, namely punicatannins A (1) and B (2), were isolated from pomegranate (Punica granatum) flowers. Their structures with absolute configuration were determined by detailed analysis of spectroscopic data, electronic circular dichroism (ECD) calculation, and chemical hydrolysis. A plausible biogenetic route involving a key enzymatic 1,4-Michael addition is proposed. Punicatannin A showed potent inhibition of α-glucosidase and lipogenic gene expression.