Zhida Sun

Oligomeric procyanidins of lotus seedpod inhibits the formation of advanced glycation end-products by scavenging reactive carbonyls.

It has been reported that oligomeric procyanidins of lotus seedpod (LSOPC) is effective in the alleviation of Alzheimers 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.

Increasing Antioxidant Activity of Procyanidin Extracts from the Pericarp of Litchi chinensis Processing Waste by Two Probiotic Bacteria Bioconversions

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.

Ameliorative effect of lotus seedpod proanthocyanidins on cognitive impairment and brain aging induced by D-galactose.

This study mainly investigated the ameliorative effect of lotus seedpod proanthocyanidins (LSPC) and the mechanism underlying such effect on cognitive impairment and brain aging induced by d-galactose. Aging mice induced by d-galactose (150 mg/kg, sc injection daily for 6 weeks) were chosen for the experiment. LSPCs (30, 60, and 90 mg/kg, ig) were provided after d-galactose injection. Learning and memory functions were detected by Y-maze and step-down avoidance tests. Then, some biochemical indexes related to cognitive ability and aging were measured. Histopathological feature and P53 protein expression in the hippocampus were observed. Results showed that the three different doses of LSPC could significantly ameliorate the learning and memory abilities impaired by d-galactose. LSPC significantly reduced the levels of malondialdehyde and nitric oxide (i.e. 90 mg/kg LSPC group vs. model group, P=0.008), reduced the content of β-amyloid peptide 1-42 (i.e. 90 mg/kg LSPC group vs. model group, P=0.009), decreased the activities of acetylcholinesterase, monoamine oxidase B, total nitric oxide synthase (i.e. 90 mg/kg LSPC group vs. model group, P=0.006), and neuronal nitric oxide synthase and synchronously increased the activities of superoxide dismutase and glutathione peroxidase in the brain. Furthermore, LSPC could prevent neuron damage and could lessen the expression of P53 protein in the hippocampus. These findings demonstrated that LSPC effectively attenuated cognitive damage and improved parameters related to brain aging in senescent mice induced by d-galactose, and may be used to treat Alzheimers disease.

Absorption and urinary excretion of A-type procyanidin oligomers from Litchi chinensis pericarp in rats by selected ion monitoring liquid chromatography-mass spectrometry.

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.

Inhibition of Advanced Glycation Endproduct Formation by Lotus Seedpod Oligomeric Procyanidins through RAGE-MAPK Signaling and NF-κB Activation in High-Fat-Diet Rats.

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.

Lactobacillus casei-01 Facilitates the Ameliorative Effects of Proanthocyanidins Extracted from Lotus Seedpod on Learning and Memory Impairment in Scopolamine-Induced Amnesia Mice

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 (109 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.

Characterization and preparation of oligomeric procyanidins from Litchi chinensis pericarp

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.

A Significant Inhibitory Effect on Advanced Glycation End Product Formation by Catechin as the Major Metabolite of Lotus Seedpod Oligomeric Procyanidins

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.

In vitro antioxidant activities of proanthocyanidins extracted from the lotus seedpod and ameliorative effects on learning and memory impairment in scopolamine-induced amnesia mice

The antioxidant activity of proanthocyanidins extracted from the lotus seedpods (LSPC) in vitro and ameliorative effects on memory impairment induced using scopolamine in mice were studied. 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, oxygen radical absorbance capacity, and cellular antioxidant activity assays revealed a potent LSPC antioxidant activity. Y-maze and step-down avoidance testing showed that LSPC administration at 30, 60, and 90 mg/kg ameliorated memory impairment. LSPC improved glutathione peroxidase and superoxide dismutase activities, inhibited activities of monoamine oxidase-B, total nitric oxide synthase, neuronal nitric oxide synthase, and acetylcholinesterase, and had no influence on inducible nitric oxide synthase and nitric oxide levels in the brain. LSPC ameliorated scopolamineinduced memory impairment based on improvement of the antioxidant system and cholinergic activity, which may be associated with potent antioxidant ability.

Combination of proanthocyanidins extracted from lotus seedpod and l-cysteine ameliorates memory impairment induced by alcohol and scopolamine in mice

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.