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Animal studies and clinical trials have shown that dietary polyphenols and polyphenol-rich foods can reduce the risk of type 2 diabetes (T2D) and its complications, but how diabetes regulates the metabolism of polyphenol has not been fully elucidated. This study investigated the effects of diabetes on litchi pericarp oligomeric procyanidin (LPOPC) dynamic metabolism and its major static metabolites in urine. First, a high-fat and streptozotocin (STZ)-induced diabetic Sprague Dawley (SD) rat model was established. In the diabetic rat model, elevated fasting blood glucose, severely impaired glucose tolerance test, and increased reactive oxygen species (ROS) levels in serum and the liver were observed. Subsequently, 200 mg per kg body weight of LPOPC was administrated to control and diabetic SD rats, and the gastrointestinal tract was collected at 0.5 h, 1 h, 3 h, and 6 h. The results showed that the retention time of LPOPC was not changed in our diabetic rat model. However, the gut microbiota were significantly altered, with elevated Proteobacteria and Verrucomicrobia abundance in diabetic rats and decreased short chain fatty acid (SCFA)-producing bacteria. Interestingly, after one dose of 300 mg per kg body weight LPOPC, the total antioxidant capacity of urine in diabetic rats significantly decreased. We then tested the static metabolites of LPOPC, demonstrating that epicatechin had not changed in urine in diabetic rats, but that shikimic acid was significantly reduced in urine in diabetic rats. The changes in shikimic acid may be due to the alteration of gut microbiota and elevated ROS levels in serum.

This study explored the effects of lotus seedpod oligomeric procyanidins (LSOPC) and their main monomer catechin (CC) on the formation of advanced glycation end products (AGEs) and Caco-2 cytotoxicity during gastrointestinal digestion. Studies have found that LSOPC and CC inhibited the AGEs formation effectively in simulated gastrointestinal digestion and protected Caco-2 cells from AGEs attack. The effect of CC on the inhibition of AGEs formation was significantly better than that of LSOPC. Further, they could effectively inhibit the digestive enzyme activity, reactive oxygen species, RAGE-p38MAPK-NF-κB signaling pathway, inflammatory factors (tumor necrosis factor alpha, interleukin 6), and adhesion factors (intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1) to protect Caco-2 cells.

Dietary polyphenols have shown hypolipidemic effects by reducing triglyceride absorption. The mechanisms may involve modifying fat emulsion during digestion in the gastrointestinal tract and suppressing lipase during hydrolysis in the small intestine. In an in vivo study, lotus seedpod oligomeric procyanidin (LSOPC) decreased total serum triglyceride and total cholesterol and elevated the high-density lipoprotein level in the hyperlipidemic rat model. In addition, LSOPC suppressed de novo lipogenesis-related gene expressions. In an in vitro study, the LSOPC-enriched emulsion decreased the mean droplet size from 0.36 to 0.33 μm and increased the viscosity of the emulsion. Moreover, the LSOPC-enriched emulsion improved the antioxidant properties. A digestion model was developed and showed that the particle size of the LSOPC-enriched emulsion increased in the oral cavity. However, an increase and then a significant drop of the particle size was measured in the stomach and small intestine. The free fatty acid release rate was decreased in the LSOPC-enriched emulsion partly ascribed to the inhibition of lipase by LSOPC.

It has been proven that A-type procyanidins, containing an additional ether bond, compared to B-type procyanidins are also bioavailable in vitro and in vivo. However, their bioavailability and absorption in the gastrointestinal tract remain uncertain. In this study, a model of the human adenocarcinoma stomach cell line (MKN-28) was established to explore the cellular transport of flavanolic monomers and procyanidin dimer A2, which were isolated from the litchi pericarp extract. After the integrity and permeability of the cell monolayer were ensured by measurement of the transepithelial electrical resistance and the apparent permeability coefficient for Lucifer yellow, the transportation of procyanidins A2 and B2, (-)-epicatechin (EC), and (+)-catechin (CC) was studied at pH 3.0, 5.0, or 7.0 in the apical side, with compound concentrations of 0.05 and 0.1 mg/mL based on the cytotoxicity test. High-performance liquid chromatography and liquid chromatography-mass spectrometry analyses indicated that EC, CC, and A2 were transported in the MKN-28 cell line from 30 to 180 min, while B2 showed no transport. The maximal transport efficiencies of EC, CC, and A2 were 23 ± 0.81, 13.16 ± 1.53, and 16.41 ± 1.36%, respectively, existing at 120, 180, and 120 min of transportation. Laser scanning confocal microscopy analysis presented the dynamic transmission of EC, in accordance with the result of concentration determination, suggesting that the A-type procyanidins are possibly absorbed through the stomach barrier, which is pH- and time-dependent.

Litchi pericarp procyanidins (LPP) are dietary supplements with high antioxidant activity, but poor oral bioavailability and efficacy. Lactobacillus casei (L. casei-01) can transform flavan-3-ols from litchi pericarp and increase their antioxidant ability; thus, L. casei-01 with LPP was administered to rats for four and eight weeks to study the effect of such a combination on metabolic parameters and on phase II metabolism and detoxification pathways in the liver as an indirect measure for phenolic bioavailability. Our data indicated that the T-AOC of the plasma, the liver GSH-Px and GSH-ST activity, and the expression of UGT and SULT isoforms in the liver of the rats were all enhanced after the eight-week administration compared with those of the control. However, at 1 h after administration the concentration of (-)-epicatechin in the combined system was lower than that obtained after the ingestion of LPP alone, suggesting that L. casei-01 enhances the bioavailability of phenolics from LPP by modulating the transformation to other compounds but not by increasing its absorption in the native form.

The bioavailability of A-type procyanidins in vivo has been rarely investigated; as such, this study discusses the effect of A-type linkage and degree of polymerization on the metabolism of procyanidins extracted from litchi pericarp (LPOPC). Sprague-Dawley rats were gavaged with (-)-epicatechin (EC) and LPOPC and sacrificed at different time points after ingestion. A-type linkage procyanidin oligomers inhibited the absorption of EC. Analysis of urinary contents from rats administered with EC, A-type procyanidin dimer (A-2), and A-type procyanidin trimer (A-3) showed distinct native and metabolite profiles for each rat. Rats fed with A-2 and A-3 presented significantly higher levels of shikimic acid and less amount of m(p)-coumaric acid metabolites in vivo and provide insight into the quantitative structure-activity relationship of procyanidin oligomers during metabolism, indicating that procyanidins with A-type linkage could induce an altered metabolic pathway of oligomers in the gastrointestinal system.

The main purpose of this study is to characterize and prepare A-type oligomeric procyanidins from litchi pericarp (Litchi chinensis Baila). The variety of oligomeric procyanidins was characterized by LC-ESI-MS analysis. There were (+)-catechin, (-)-epicatechin, twelve dimers and six trimers of procyanidins were found in litchi pericarp extracts, and A-type procyanidins were much more abundant than B-type procyanidins. The main flavan-3-ol monomer and oligomeric procyanidins in litchi pericarp were (-)-epicatechin, A-type dimers (A1 and A2) and trimer (epicatechin-(4β-8, 2β-O-7)-epicatechin- (4β-8)-epicatechin). Procyanidin A1 (epicatechin-(4β-8, 2β-O-7)-catechin) was identified by NMR in litchi pericarp for the first time. (-)-Epicatechin and oligomeric procyanidins were prepared by the combination of AB-8 column chromatography and Toyopearl HW-40S column chromatography. The results showed that each fraction predominantly owned a single compound and gave a high yield with (-)-epicatechin, A-type dimers (A1 and A2) and trimer, suggesting a useful method to obtain pure (-)-epicatechin and A-type oligomeric procyanidins., (Copyright © 2016. Published by Elsevier B.V.)

This study investigated the protective properties of lotus seedpod oligomeric procyanidins (LSOPC) against nonalcoholic fatty liver disease (NAFLD) and its underlying mechanism. Sprague-Dawley (SD) male rats were fed a basic diet, a high-fat diet (HFD), or HFD plus 0.2 or 0.5% (w/w) LSOPC for 12 weeks. Administration of LSOPC markedly reduced serum and hepatic biochemical parameters and protein expression of advanced glycation endproducts (AGEs). Additionally, 0.5% (w/w) LSOPC treatment remarkably reversed the increasing tendency of receptor of advanced glycation endproduct (RAGE) to normal level. Furthermore, dietary LSOPC significantly decreased the protein levels of mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) and down-regulated genes involved in pro-inflammatory cytokines and adhesion molecules. Taken together, these findings demonstrate that LSOPC may protect obese rats with long-term HFD-induced NAFLD against RAGE-MAPK-NF-κB signaling suppression.

Learning and memory abilities are associated with alterations in gut function. The two-way proanthocyanidins-microbiota interaction in vivo enhances the physiological activities of proanthocyanidins and promotes the regulation of gut function. Proanthocyanidins extracted from lotus seedpod (LSPC) have shown the memory-enhancing ability. However, there has been no literature about whether Lactobacillus casei-01 (LC) enhances the ameliorative effects of LSPC on learning and memory abilities. In this study, learning and memory abilities of scopolamine-induced amnesia mice were evaluated by Y-maze test after 20-day administration of LC (10(9) cfu/kg body weight (BW)), LSPC (low dose was 60 mg/kg BW (L-LSPC) and high dose was 90 mg/kg BW (H-LSPC)), or LSPC and LC combinations (L-LSPC+LC and H-LSPC+LC). Alterations in antioxidant defense ability and oxidative damage of brain, serum and colon, and brain cholinergic system were investigated as the possible mechanisms. As a result, the error times of H-LSPC+LC group were reduced by 41.59% and 68.75% relative to those of H-LSPC and LC groups respectively. LSPC and LC combinations ameliorated scopolamine-induced memory impairment by improving total antioxidant capacity (TAOC) level, glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities of brain, serum and colon, suppressing malondialdehyde (MDA) level of brain, serum and colon, and inhibiting brain acetylcholinesterase (AchE), myeloperoxidase, total nitric oxide synthase and neural nitric oxide synthase (nNOS) activities, and nNOS mRNA level. Moreover, LC facilitated the ameliorative effects of H-LSPC on GSH-Px activity of colon, TAOC level, GSH-Px activity and ratio of T-SOD to MDA of brain and serum, and the inhibitory effects of H-LSPC on serum MDA level, brain nNOS mRNA level and AchE activity. These results indicated that LC promoted the memory-enhancing effect of LSPC in scopolamine-induced amnesia mice.

Several lines of evidence suggested that B-type procyanidin oligomers from lotus seedpod (LSOPC) may effectively modulate the formation of advanced glycation end products (AGEs). In vivo, LSOPC is metabolized by intestinal flora to become various kinds of phenolic compounds that possess potent antioxidant activities. However, few reports of the absorption and metabolism of LSOPC have been revealed. In the present study, rats were orally administered with LSOPC at a dose of 300 mg/kg body weight. The metabolites of LSOPC in urine were elucidated by HPLC-MS/MS analysis 24 h post-administration. Eight major metabolites were significantly increased by the administration of 300 mg/kg of LSOPC (p < 0.01). The anti-glycative activity of LSOPC and its metabolites were investigated. The results showed that LSOPC and catechin had greater anti-glycative activities than other metabolites, which were positively correlated to their carbonyl scavenging activities and antioxidant capacities.

It has been reported that oligomeric procyanidins of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimer's disease and diabetes through its antioxidant and insulin-potentiating activities. This study investigated the anti-glycative activity of LSOPC in a bovine serum albumin (BSA)-glucose model. The level of glycation and conformational alterations were assessed by specific fluorescence, Congo red binding assay and circular dichroism. The results show that LSOPC has a significant anti-glycative activity in vitro and it can also effectively protect the secondary structure of BSA during glycation. LSOPC or catechin (a major constituent unit of LSOPC), were used to react with methylglyoxal. The structures of their carbonyl adducts were tentatively identified using HPLC-MS(2). Their capacity to scavenge methylglyoxal suggested carbonyl scavenging as a major mechanism of antiglycation. Therefore, LSOPC could be helpful to prevent AGEs-associated diseases, and with the potential to be used as functional food ingredients., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Intervention studies with A-type oligomeric procyanidins from litchi (Litchi chinensis) pericarp (LPOPC) suggested its protective effect against cardiovascular diseases. However, there is no consensus on the absorption and metabolism of LPOPC. It was demonstrated that the main components in LPOPC were (-)-epicatechin, A-type procyanidin dimers, trimers and tetramers. Rats were orally administered different levels of LPOPC (150 and 300 mg/kgbw), the procyanidins and their microbial metabolites in urine were identified by HPLC-MS/MS analysis 18 h post-administration. Data indicated that seven aromatic acid metabolites excreted were significantly increased by 300 mg/kgbw of LPOPC (P<0.01). However, only (-)-epicatechin and its methylated derivatives were detected in rat plasma 1h after 300 mg/kgbw of LPOPC administration. The total EC content absorbed in plasma was only 2.54 ± 0.53 μmol/L, indicating that the biological properties of LPOPC should be probably explained by its microbial degraded phenolic acids., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Litchi chinensis pericarp from litchi processing waste is an important plant source of A-type procyanidins, which were considered a natural dietary supplement because of their high biological activity in vivo. Litchi pericarp oligomeric procyanidins (LPOPCs) did not selectively modify the growth of Streptococcus thermophilus and Lactobacillus casei -01 at concentrations of 0.25 and 0.5 mg/mL, and it was demonstrated that the two strains could transform procyanidins during their log period of growth by two different pathways. S. thermophilus was able to metabolize procyanidin A2 to its isomer, and L. casei could decompose flavan-3-ols into 3,4-hydroxyphenylacetic acid, 4-hydroxyphenylpropionic acid, m-coumaric acid, and p-coumaric acid. The total antioxidant capability (T-AOC) of LPOPCs before and after microbial incubation was estimated, and the results suggested that probiotic bacteria bioconversion is a feasible and efficient method to convert litchi pericarp procyanidins to a more effective antioxidant agent.

Proanthocyanidins extracted from lotus seedpod (LSPC) have been shown to ameliorate cognitive deficits and oxidative damage. However, there is no scientific evidence of combined LSPC and l-cysteine in the treatment for Alzheimer's disease (AD) in animal models. The first aim of this study was to study whether LSPC and l-cysteine combination was more potent than LSPC on improving memory impairment in alcohol-induced mice. The results showed LSPC and l-cysteine combination was more effective than LSPC, as indicated by same behavioral performance in Y-maze, but significantly enhanced total antioxidant capacity and superoxide dismutase (SOD) activity. The second goal of this study was to investigate whether different combination ratio of LSPC to l-cysteine impacts the cognition-enhancing effect in scopolamine-induced memory-deficit mice. Alterations in oxidative stress parameters and cholinergic activity in brains were also determined as possible mechanisms. Both M-Dose and H-Dose of LSPC and l-cysteine combination significantly improved scopolamine-induced memory impairment in Y-maze and step-down avoidance test by improving brain glutathione peroxidase and SOD activities, inhibiting brain malondialdehyde and hippocampus nitric oxide levels, inducible nitric oxide synthase activity in hippocampus and serum, and brain acetylcholinesterase activity. These results indicate that chronic administration of LSPC and l-cysteine combination ameliorates memory impairment, which may be related to inhibition of oxidative stress and improvement of cholinergic activity. These findings suggest LSPC and l-cysteine combination may provide a viable therapy in the treatment for AD and other forms of cognitive impairment. [ABSTRACT FROM AUTHOR]