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Dipeptidyl peptidase-IV (DPP-IV) inhibiting peptides have attracted increased attention because of their possible beneficial effects on glycemic homeostasis. However, the structural basis underpinning their activities has not been well understood. This study combined computational and in vitro investigations to explore the structural basis of DPP-IV inhibitory peptides. We first superimposed the Xaa–Pro-type peptide-like structures from several crystal structures of DPP-IV ligand–protein complexes to analyze the recognition interactions of DPP-IV to peptides. Thereafter, a small set of Xaa–Pro-type peptides was designed to explore the effect of key interactions on inhibitory activity. The intramolecular interaction of Xaa–Pro-type peptides at the first and third positions from the N-terminus was pivotal to their inhibitory activities. Residue interactions between DPP-IV and residues of the peptides at the fourth and fifth positions of the N-terminus contributed significantly to the inhibitory effect of Xaa–Pro-type tetrapeptides and pentapeptides. Based on the interaction descriptors, quantitative structure–activity relationship (QSAR) studies with the DPP-IV inhibitory peptides resulted in valid models with high R2values (0.90 for tripeptides; 0.91 for tetrapeptides and pentapeptides) and Q2values (0.33 for tripeptides; 0.68 for tetrapeptides and pentapeptides). Taken together, the structural information on DPP-IV and peptides in this study facilitated the development of novel DPP-IV inhibitory peptides.

This study focused on the enzymatic characteristics, with regard to primary specificity, secondary specificity, and hydrolysis ability of five proteases (Alcalase, Protamex, papain, Flavourzyme, and ProtexA), towards the release of dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides from bovine casein. The secondary specificity of the five proteases, especially the release capability for Xaa-Pro-type peptide played a determining role in the release of DPP-IV inhibitory peptides from bovine casein. Moreover, protease combinations, chosen based on their Xaa-Pro-type peptide release abilities, resulted in superior DPP-IV inhibitory activity compared to other combinations. Particularly, the hydrolysate with the highest DPP-IV inhibitory activity (IC50value of 0.45 ± 0.07 mg/mL) was obtained by the combination hydrolysis of ProtexA and papain, achieving a 74.63% ± 1.62% (peak area) release of Xaa-Pro-type peptide, and a significant improving glucose tolerance in mice (33.42% ± 1.68% reduction of blood glucose AUC compared with control mice). The mechanistic insights revealed that papain efficiently released long Xaa-Pro-type peptides in the early hydrolysis stage, and subsequently, the synergistic effect of papain and ProtexA led to an accelerated and extensive release of short Xaa-Pro-type peptides. These findings provide valuable insight into enzymatic processes for generating DPP-IV inhibiting peptides from casein.

Probiotic fermentation is attractive for beverage processing. However, its regulatory role in quality of coix seed-chrysanthemum beverage (CCB) rich in phenolics and polysaccharides was unknown. Results showed that co-fermentation with Bifidobacterium animalissubsp. lactisBLa80 (BLa80), Lactobacillus delbrueckiisubsp. bulgariaLB42 (LB42), Streptococcus salivariussubsp. thermophilusST81 (ST81), and Lactobacillus plantarumLP90 (LP90) for 12 h combined their respective advantages to prepare fermented CCB with viable counts of 8.78 lg CFU/mL, high phenolics bioaccessibility (>60 %), good sensory quality, and strong antioxidant activity. LP90 greatly contributed to the aroma. BLa80 and LP90 hydrolyzed resistant starch/polymer dextrin. BLa80 showed the strongest deglycosidic ability, decreasing bitterness. The compound probiotic fermentation led to the biotransformation of endogenous polysaccharides/phenolics and introduction of exogenous viable probiotics resistant to gastrointestinal digestion, facilitating the proliferation of beneficial gut microbiota and accumulation of their metabolites. These findings provided a useful strategy for dual regulation of high quality of plant-based beverage.

Our previous study has suggested that the crude polysaccharide obtained from Laminaria japonicaby acid assisted extraction (LP-A) have significant bile acid-binding capacity, which probably ascribed to its specific structure characterization. The relationship between structure characterization and bile acid-binding capacity of the purified LP-A fractions are still unknown. This paper conducted a comparison study on the structure characterization and bile acid-binding capacity of three LP-A fractions (LP-A4, LP-A6, and LP-A8). The results indicated that LP-A4, LP-A6, and LP-A8, characterized as mannoglucan, fucomannoglucan, and fucogalactan, had significantly different structure characterization. Furthermore, the bile acid-binding capacity of LP-A8 was obviously higher than the other fractions, which may be attributed to its highly branched structure, abundant sulfate, fucose, and galactose in chemical composition and denser interconnected macromolecule network in molecular morphology. This study provides scientific evidence for the potential utilization of LP-A8 as an attractive functional food supplement candidate for the hyperlipidemia population.

Lotus leaf is an optimal raw material for the preparation of foods with the function of regulating glycolipid metabolism. However, further investigation is required to elucidate the synergistic regulatory effects of lotus leaf polysaccharides (LLP), flavonoids, and alkaloids, which act as the main active components in lotus leaves. This study optimally prepared LLP and whole functional components (LLE) containing LLP, flavonoids and alkaloids by high-pressure homogenization-assisted dual enzyme extraction with and without pre-/post treatment. LLP and LLE exerted regulatory roles in glycolipid metabolism and alleviated liver, kidney, and pancreas damages of db/dbmice. LLP was utilized by gut bacteria, promoting the production of beneficial metabolites i.e. lithodeoxycholic and butyric acids, which reached the liver through blood circulation, activating insulin signaling, and regulating glycolipid metabolism. The combination of polysaccharide, flavonoids and alkaloids promoted the production of butyric acid but different secondary bile acids i.e. deoxycholic and ursodeoxycholic acids, acted in the intestine and liver, and intervened in more metabolic pathways, showing a synergistic effect on glycolipid metabolism. This study provided insights into the rational processing of lotus leaf for hypoglycaemic foods.

Due to the difficulty in obtaining highly branched rhamnogalacturonan-I (RG-I) type pectin, the relationship between the extent of RG-I branching (EB) of pectin and prebiotic/immunomodulatory activity has not been systematically investigated. Moreover, it is only possible to establish a structure–activity relationship using pectin that is highly purified and accurately characterized. In this study, a homogeneous highly branched RG-I type pectin (LBP-P4, a final product) with dual proliferative effects on Bifidobacteriumand macrophage was effectively purified for the first time using enzyme hydrolysis combined with ultrafiltration. The RG-I content and EB of LBP-P4 reached 97.32 and 77.12, respectively. Its two branches were composed of arabinan and arabinogalactan-II, containing → 5)-Araf-(1→, →3)-Araf-(1→, →3,6)-Galp-(1→ and →6)-Galp-(1→ residues). The structure–activity relationship analysis indicated that strong prebiotic/immunomodulatory activity of LBP-P4 was depended on its high EB, which was further confirmed by the molecular docking simulation between low/high branched pectin with β-1,6-galactosidase, α-l-arabinanase, and Toll-like receptor 4 (TLR4).

The aim of this study was to investigate the dipeptidyl peptidase-IV (DPP-IV) inhibition and metabolic stability of a casein-derived peptide Val-Pro-Tyr-Pro-Gln (VPYPQ) and its fragments as well as their release from casein following hydrolysis. Results showed that VPYPQ was the most potent DPP-IV inhibitory peptide among them with an IC50value of 41.45 μM. This might be due to its two internal Pro residues at positions 2 and 4. Moreover, VPYPQ was resistant to hydrolysis by gastrointestinal enzymes and was relatively more stable to hydrolysis by DPP-IV and peptidases in plasma compared with its fragments. Additionally, oral administration of VPYPQ at a dose of 90 μmol/kg body weight could reduce the postprandial blood glucose levels in mice. More importantly, VPYPQ could be released efficiently from casein following hydrolysis by a combination of papain and in vitro digestion, reaching up to 3211.15 μg/g. Therefore, VPYPQ was a promising casein-derived DPP-IV inhibitor.

Our previous study has proved that the three polysaccharide fractions from L. japonica(LP-A4, LP-A6, and LP-A8) had significantly different structure characterization. Herein, we conducted in vitro simulated digestion and fermentation to study the digestive mechanism of LP-As. The results of gastrointestinal digestion indicated that LP-A6 and LP-A8 would be easier to trap the enzyme molecules for their denser interconnected macromolecule network compared with LP-A4. Fermentation of LP-As by human gut microbiota, especially for LP-A8, generated a large amount of short-chain fatty acids (SCFAs), which could upregulate the abundance of Firmicutes(Lachnoclostridiumand Eubacterium). The high content of sulfate and highly branched sugar residue of LP-A8 might help it be easily used by Firmicutesin gut microbiota of hyperlipidemic patients. Functional analysis revealed that the increased metabolic activities of glycerophospholipid metabolism, ether lipid metabolism, and fatty acid metabolism induced by LP-A8 treatment were closely associated with metabolic syndromes and hyperlipidemia.

Yin-deficiency-heat (YDH) syndrome characterized by inflammatory lesions is a common sub-health state in human body. Chrysanthemum and coix seed are commonly used to improve YDH syndrome. The chemical, volatile, and phenolic profiles and sensory and functional properties of five plant-based solid beverages (PSB) prepared by hydrothermal treatment coupling with enzymatic hydrolysis by amylase and protease using chrysanthemum and coix seed as materials were determined. Chrysanthemum-coix seed beverage had wonderful water solubility, reduced bitter and sour taste, sweet taste, and harmonious aroma. Chrysanthemum phenolics extracted by enzymatic hydrolysis might impact multiple metabolic pathways and biological processes to intervene in inflammation and most of them had high bioaccessibility. PSB promoted the production of beneficial gut microbiota metabolites. Chrysanthemum-coix seed beverages exerted more positive effects on YDH syndrome due to anti-inflammatory phenolics from chrysanthemum and resistant starch/dextrin from coix seed facilitating short-chain fatty acids production. This study provided new sight for developing plant-based beverages with anti-YDH syndrome potential.

Lotus leaf is effective in regulating glycolipid absorption and metabolism, but the roles of small-molecule compounds and polysaccharides are unknown. In this study, the small-molecule compounds including flavonoids, alkaloids, and polysaccharides were gradually isolated from lotus leaf infusion by multi-column chromatography and applied to in vitro activity verification and structural characterization. Although flavonoids and alkaloids were effective in inhibiting pancrelipase and α-glucosidase, polysaccharides more effectively bounded bile acids, inhibited cholesterol micelle solubility, and stimulated the growth of Bifidobacteriumthan lotus leaf infusion. Polysaccharides, presented as spherical conformation in water, were identified as rhamnogalacturonan I-enriched (93%) low-ester pectin with multiple branches mainly composed of arabinan, arabinogalactan-type II, and galactan formed by →3)-Galp-(1→, →5)-Araf-(1→ and →4)-Galp-(1→ residues. Polysaccharides, which were a key constituent of lotus leaf infusion in regulating glycolipid absorption and metabolism, should be paid more attention and developed as a functional food ingredient.

Chrysanthemum tea infusions are famous and nutritious beverages worldwide. The results showed that numerous negatively charged spherical particles of 60–1000 nm in diameter generally existed in all chrysanthemum tea infusions prepared from 9 kinds of chrysanthemums for tea use. Taking Chrysanthemum morifolium‘Hangbaiju’ tea infusion as an example, crushing, heating and increasing flower-to-water ratio were three strategies to prepare optimal submicroparticles with the smallest mean hydrodynamic diameter as 288.40 nm and polydispersity index as 0.25. The submicroparticles were stable when temperature change, dialysis, centrifugation, storage, pH change (2–9) and ionic strength change were applied but unstable when freeze-thaw, lyophilization, ultrafiltration, concentration and pH change (10) were applied. Polysaccharides and phenolics were dominant components of submicroparticles which were maintained by hydrogen bonds and hydrophobic interactions among polysaccharides and phenolics. This study provided a novel perspective to decipher and control supramolecular aggregation in chrysanthemum tea infusions for rational manufacturing.

The application of Isodon species in Chinese folk medicine has a long histroy, especially the ones called ‘Xihuangcao’ in Chinese. ‘Xihuangcao’ has been successfully applied to treat acute hepatitis, cholecystitis, enteritis, dysentery and trauma. The original species of ‘Xihuangcao’ is Isodon lophanthoides (Buch.-Ham.ex D.Don). However, there are five sources of Chinese medicinal herb ‘Xihuangcao’ due to their similar morphology and close pharmaceutical activity. Each source belongs to Isodon. However, their chemical composition and bioactivities are significantly different. In order to differentiate these sources of ‘Xihuangcao’ and to know their pharmaceutical effects, this review summarizes the chemical constituents, bioactive properties of ‘Xihuangcao’ and their available application.

In the present study, various lotus leaf extracts were prepared by multiple methods, characterized by 12 alkaloids, 14 flavonoids, and superoxide anion radical scavenging (OS) and xanthine oxidase inhibitory (XOI) activities, and divided into 3/4 groups with different characteristics. Both alkaloids and flavonoids contributed to XOI activity of representative lotus leaf extract. Norcoclaurine, O-nornuciferine, N-nornuciferine, nuciferine, luteolin, diosmetin, quercetin, and quercetin-3-O-glucuronide were defined as quality control standards for lotus leaf extracts with dual OS and XOI activities. Enzymatic hydrolysis coupled with ultrasound-assisted extraction method using 50% (v/v) ethanol was the most favorable approach for preparing food-grade lotus leaf extract with dual functions. Network pharmacology revealed that this extract having abundant alkaloids and flavonoids (especially flavonoid aglycones) could improve hyperuricemia by multiple actions on uric acid synthesis and transport, inflammation response, oxidative stress and lipid metabolism. Our study provided crucial data about clear quality control standards for plant-based functional food with potential hypouricemic effect.