Uncovering the Role of Hydroxycinnamoyl Transferase in Boosting Chlorogenic Acid Accumulation in Carthamus tinctorius Cells under Methyl Jasmonate Elicitation.

Chlorogenic acids (CGAs) are bioactive compounds widely used in the food, pharmaceutical, and cosmetic industries. Carthamus tinctorius is an important economic crop, and its suspension cells are rich in CGAs. However, little is known about the biosynthesis and regulation of CGAs in Carthamus tinctorius cells. This study first elucidated the regulatory mechanism of CGA biosynthesis in methyl jasmonate (MeJA)-treated Carthamus tinctorius cells and the role of the MeJA-responsive hydroxycinnamoyl transferase (HCT) gene in enhancing their CGA accumulation. Firstly, temporal changes in intracellular metabolites showed that MeJA increased the intracellular CGA content up to 1.61-fold to 100.23 mg·g-1. Meanwhile, 31 primary metabolites showed significant differences, with 6 precursors related to increasing CGA biosynthesis. Secondly, the transcriptome data revealed 3637 new genes previously unannotated in the Carthamus tinctorius genome and 3653 differentially expressed genes. The genes involved in the plant signaling pathway and the biosynthesis of CGAs and their precursors showed a general up-regulation, especially the HCT gene family, which ultimately promoted CGA biosynthesis. Thirdly, the expression of a newly annotated and MeJA-responsive HCT gene (CtHCT, CtNewGene_3476) was demonstrated to be positively correlated with CGA accumulation in the cells, and transient overexpression of CtHCT enhanced CGA accumulation in tobacco. Finally, in vitro catalysis kinetics and molecular docking simulations revealed the ability and mechanism of the CtHCT protein to bind to various substrates and catalyze the formation of four hydroxycinnamic esters, including CGAs. These findings strengthened our understanding of the regulatory mechanism of CGA biosynthesis, thereby providing theoretical support for the efficient production of CGAs.

Mechanistic insights into gel formation of egg-based yoghurt: The dynamic changes in physicochemical properties, microstructure, and intermolecular interactions during fermentation.

This study aimed to elucidate the mechanism of acid-induced gelation in egg-based yoghurt by investigating the dynamic changes in physicochemical properties, texture, rheology, and microstructure of the gel during fermentation, combined with the role of intermolecular forces in gel formation. Results showed that protein aggregation and cross-linking increased as pH decreased during fermentation. Gel hardness increased with fermentation, eventually reaching 11.36 g, while maintaining low fracturability. Water holding capacity (WHC) decreased from 91.77% to 73.13% during fermentation. Rheological testing demonstrated a significant increase in viscosity and dynamic moduli (G' and G''), consistent with the observation of a more compact microstructure by scanning electron microscopy (SEM) and particle size analysis. Furthermore, dynamic changes of surface hydrophobicity, sulfhydryl content, and intermolecular forces suggested that hydrophobic interactions were likely the main driving force for gel formation, as well as that hydrophobic interactions and disulfide bonds played an important role in the maintenance and construction of the gel network structure. Although ionic bonds and hydrogen bonds also had an effect on the gel formation of egg-based yoghurt, their contributions were not significant. The study provided new insights for the development of novel egg-based fermentation foods and the research of acid-induced protein gels, and also contributed to the deep exploitation and utilization of poultry eggs.

Ovotransferrin Inhibits TNF-α Induced Inflammatory Response in Gastric Epithelial Cells via MAPK and NF-κB Pathway.

Ovotransferrin (OVT) has been confirmed to have anti-inflammatory activity. However, its effect and mechanism on gastric inflammation are unclear. In this study, the effect and mechanism of the OVT on the tumor necrosis factor-α (TNF-α) induced inflammatory response in gastric epithelial cells (GES-1) were investigated. The enzyme linked immunosorbent assay (ELISA) was used to determine the levels of inflammation cytokines, followed by RNA sequencing to explore the potential pathways of its anti-inflammatory effect, and then it was validated by Western blotting and pathways inhibitors. Results showed that the OVT at concentrations of 50-400 µg/mL displayed nontoxicity against GES-1 cells. Additionally, 100 µg/mL of OVT obviously reduced the secretion of interleukin (IL)-8, IL-6, and TNF-α by 63.02% (630.09/1703.98), 35.53% (935.81/1451.43), and 36.19% (964.60/1511.63), respectively. The results of RNA sequencing exhibited that the OVT significantly influences the activation of mitogen-activated protein kinase (MAPK) and the nuclear factor kappa-light-chain enhancer of activated B cell (NF-κB) pathways, which was verified by the levels of p-IKK, p-IκB, p-P65, p-ERK, p-JNK, and p-P38 protein. IL-8 contents released by GES-1 cells after incubation with inhibitors of NF-κB and MAPK pathways further confirmed that OVT hindered activation of these two pathways. Collectively, these results suggested that OVT was a natural protein with the potential to treat gastric inflammation.

Investigating the induction of polyphenol biosynthesis in the cultured Cycolocarya paliurus cells and the stimulatory mechanism of co-induction with 5-aminolevulinic acid and salicylic acid.

Background: Plant cell culture technology is a potential way to produce polyphenols, however, this way is still trapped in the dilemma of low content and yield. Elicitation is regarded as one of the most effective ways to improve the output of the secondary metabolites, and therefore has attracted extensive attention. Methods: Five elicitors including 5-aminolevulinic acid (5-ALA), salicylic acid (SA), methyl jasmonate (MeJA), sodium nitroprusside (SNP) and Rhizopus Oryzae Elicitor (ROE) were used to improve the content and yield of polyphenols in the cultured Cyclocarya paliurus (C. paliurus) cells, and a co-induction technology of 5-ALA and SA was developed as a result. Meanwhile, the integrated analysis of transcriptome and metabolome was adopted to interpret the stimulation mechanism of co-induction with 5-ALA and SA. Results: Under the co-induction of 50 µM 5-ALA and SA, the content and yield of total polyphenols of the cultured cells reached 8.0 mg/g and 147.12 mg/L, respectively. The yields of cyanidin-3-O-galactoside, procyanidin B1 and catechin reached 28.83, 4.33 and 2.88 times that of the control group, respectively. It was found that expressions of TFs such as CpERF105, CpMYB10 and CpWRKY28 increased significantly, while CpMYB44 and CpTGA2 decreased. These great changes might further make the expression of CpF3'H (flavonoid 3'-monooxygenase), CpFLS (flavonol synthase), CpLAR (leucoanthocyanidin reductase), CpANS (anthocyanidin synthase) and Cp4CL (4-coumarate coenzyme A ligase) increase while CpANR (anthocyanidin reductase) and CpF3'5'H (flavonoid 3', 5'-hydroxylase) reduce, ultimately enhancing the polyphenols accumulation Conclusion: The co-induction of 5-ALA and SA can significantly promote polyphenol biosynthesis in the cultured C. paliurus cells by regulating the expression of key transcription factors and structural genes associated with polyphenol synthesis, and thus has a promising application.

Extraction, identification, and starch-digestion inhibition of phenolics from Euryale ferox seed coat.

BACKGROUND: Euryale ferox is an important cash crop and valuable tonic in traditional medicine. The seeds of E. ferox are rich in starch, which is hard to digest, and the digestion speed is significantly slower than that of rice starch. The goal of this study was to evaluate the effects of E. ferox seed-coat phenolics (EFCPs) on the digestion of E. ferox seed starch. RESULTS: EFCPs were extracted and identified by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. We optimized the extraction parameters, and the final extraction yield was about 1.49%. We identified seven phenolics from the E. ferox seed-coat extracts: gallic acid, digalloylhexoside, catechin, procyanidin B2, epicatechin, ellagic acid, and epicatechin gallate. Quantitative analysis results showed that the E. ferox seed phenolics mainly distributed in the seed coat and the gallic acid, digalloylhexoside, and epicatechin gallate were three main phenolic compounds. The phenolics displayed strong inhibitory activities on α-glucosidase and α-amylase with an IC50 of 3.25 µg mL-1 and 1.36 mg mL-1 respectively. Furthermore, these phenolics could interact with starch by hydrogen bonds, which might make its starch more difficult to digest. CONCLUSION: Our investigation suggests that the EFCPs can strongly inhibit the digestion of E. ferox seed starch by inhibiting the α-amylase and α-glucosidase activities and interacting with starch by hydrogen bonds; therefore, E. ferox seeds have a promising application prospect in foods for hypoglycemia. © 2023 Society of Chemical Industry.

Combating Escherichia coli O157:H7 with Functionalized Chickpea-Derived Antimicrobial Peptides.

The rapid dissemination of antibiotic resistance accelerates the desire for new antibacterial agents. Here, a class of antimicrobial peptides (AMPs) is designed by modifying the structural parameters of a natural chickpea-derived AMP-Leg2, termed "functionalized chickpea-derived Leg2 antimicrobial peptides" (FCLAPs). Among the FCLAPs, KTA and KTR show superior antibacterial efficacy against the foodborne pathogen Escherichia coli (E. coli) O157:H7 (with MICs in the range of 2.5-4.7 µmol L-1 ) and demonstrate satisfactory feasibility in alleviating E. coli O157:H7-induced intestinal infection. Additionally, the low cytotoxicity along with insusceptibility to antimicrobial resistance increases the potential of FCLAPs as appealing antimicrobials. Combining the multi-omics profiling andpeptide-membrane interaction assays, a unique dual-targeting mode of action is characterized. To specify the antibacterial mechanism, microscopical observations, membrane-related physicochemical properties studies, and mass spectrometry assays are further performed. Data indicate that KTA and KTR induce membrane damage by initially targeting the lipopolysaccharide (LPS), thus promoting the peptides to traverse the outer membrane. Subsequently, the peptides intercalate into the peptidoglycan (PGN) layer, blocking its synthesis, and causing a collapse of membrane structure. These findings altogether imply the great potential of KTA and KTR as promising antibacterial candidates in combating the growing threat of E. coli O157:H7.

Effects of citric acid crosslinking on the structure and properties of ovotransferrin and chitosan composite films.

In this study, ovotransferrin/chitosan (OVT/CS) composite films cross-linked by citric acid (CA) were prepared and the effects of CA cross-linking on the structure and physicochemical properties of the composite films were investigated. The cross-linking degree measured by 2,4,6-trinitrobenzenesulfonic acid (TNBS) method confirmed that CA was cross-linked with the matrix, and Fourier transform infrared spectroscopy confirmed that more hydrogen bonds and electrostatic interactions were formed between CA and the matrix. Differential scanning calorimetry, X-ray diffraction and Scanning electron microscope images revealed the compatibility between substances. The synergistic inhibition between the matrix results in a significantly higher antibacterial activity of the composite film than the pure film. Compared with uncross-linked films, the mechanical properties, barrier properties and water resistance of the cross-linked films were significantly improved. When the concentration of CA was 5 wt% (W/W, on a dry basis of the weight of OVT and CS), the most significant improvement in film performance was obtained. The tensile strength of the film increased from 32.05 MPa without cross-linking to 61.99 MPa and the swelling degree decreased from 51.5 % to 24.23 %. The observed phenomena suggest that cross-linking OVT and CS with CA can obtain functional edible films with improved properties.

Chalcone-1-Deoxynojirimycin Heterozygote Reduced the Blood Glucose Concentration and Alleviated the Adverse Symptoms and Intestinal Flora Disorder of Diabetes Mellitus Rats.

Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.

Anti-inflammatory effects of tripeptide WLS on TNF-α-induced HT-29 cells and DSS-induced colitis in mice.

Inflammatory bowel disease is a chronic disease of the intestinal tract, which is related to increased levels of various inflammatory mediators. This study aims to explore the anti-inflammatory mechanism of small molecular peptide WLS and its alleviating effect on inflammatory bowel disease (IBD). In TNF-α-induced HT-29 cells, WLS inhibited IL-8 secretion, decreased gene expression of pro-inflammatory cytokines IL-8, IL-6, IL-1ß, and TNF-α, and inhibited the activation of MAPK/NF-κB signaling pathways. In the dextran sulfate sodium salt (DSS) induced colitis mouse model, WLS inhibited weight loss and disease activity index scores, increased colon length, improved colon histopathology, inhibited secretion of IL-6 and TNF-α in the colon, and down-regulated gene expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1ß, IFN-γ, IL-17A). This study revealed that WLS was a novel small molecule peptide with anti-inflammatory activity and may be a potential candidate for the treatment of inflammatory bowel disease.

Design, Synthesis and Bioactivity Evaluation of Coumarin-BMT Hybrids as New Acetylcholinesterase Inhibitors.

Coumarin possesses the aromatic group and showed plentiful activities, such as antioxidant, preventing asthma and antisepsis. In addition, coumarin derivatives usually possess good solubility, low cytotoxicity and excellent cell permeability. In our study, we synthesized the compound bridge methylene tacrine (BMT), which has the classical pharmacophore structure of Tacrine (THA). Based on the principle of active substructure splicing, BMT was used as a lead compound and synthesized coumarin-BMT hybrids by introducing coumarin to BMT. In this work, 21 novel hybrids of BMT and coumarin were synthesized and evaluated for their inhibitory activity on AChE. All obtained compounds present preferable inhibition. Compound 8b was the most active compound, with the value of Ki as 49.2 nM, which was higher than Galantamine (GAL) and lower than THA. The result of molecular docking showed that the highest binding free energy was -40.43 kcal/mol for compound 8b, which was an identical trend with the calculated Ki.

Metabolism, tissue distribution and excretion of taxifolin in rat.

The metabolism, tissue distribution and excretion of taxifolin in rat after oral administration of taxifolin encapsulated zein-caseinate Nanoparticles (TZP) were studied. The isomerization of taxifolin in rat small intestine and colon was found. Besides isomers, 16 metabolites of taxifolin were identified in rat feces, plasma and urine by UPLC-QTOF-MS. In colon, taxifolin underwent the metabolism of hydration, dehydration and ring-fission through the gut microflora. The main metabolites of taxifolin found in plasma and urine were its sulfated, glucuronidated, and/or methylated products. The dynamic variation of taxifolin and its metabolites in tissues and urine were quantified by UPLC-QqQ-MS/MS. Taxifolin and its metabolites could be quickly absorbed and distributed in the tissues, and relatively low concentrations were found in the heart and brain. The feces excretion of taxifolin was determined by HPLC. The total excretion during 24 h was 2.83 ± 0.80% to its given does, and the maximum excretion was found during 8-10 h post administration. Compared with feces, the excretion of taxifolin and its metabolites in urine was much faster, and the total excretion was 1.96 ± 0.23% during 12 h.

Processing, digestion property and structure characterization of slowly digestible gorgon nut starch.

Slowly digestible gorgon nut starch (GN-SDS) was prepared by heating-cooling treatment (HCT), meanwhile its morphological and structural features were characterized in detail by SEM, DSC, XRD and IR detection. The optimized parameters of GN-SDS processing were as following: starch milk (20%) was heated at 100 °C for 20 min, and then cooled under 4 °C for 24 h. Under the optimized parameters, the SDS content increased from 20.49 to 61.74%. GN-SDS showed typical SDS characteristics in in vivo digestion with a low postprandial blood glucose. SEM images suggested that GN-S particles changed from uniform regular polyhedron with smooth surface to irregular gravel-like particles with coarse surface and obvious layered structure inside after HCT. The results of SEM, DSC, XRD and IR determination indicated that HCT changed the granule morphology, interior structure, gelatinization temperature and crystal type (A to B-type) of GN-S, and therefore made it hard to be digested accordingly. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-01007-6.

Dihydromyricetin Improves Cognitive Impairments in d-Galactose-Induced Aging Mice through Regulating Oxidative Stress and Inhibition of Acetylcholinesterase.

SCOPE: Alzheimer's disease (AD) is a neurodegenerative disease with phenomena of cognitive impairments. Oxidative stress and cholinergic system dysfunction are two widely studied pathogenesis of AD. Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactivities. In this study, it is aimed to investigate the effects of DMY on cognitive impairment in d-galactose (d-gal) induced aging mice. METHODS AND RESULTS: Mice are intraperitoneally injected with d-gal for 16 weeks, and DMY is supplemented in drinking water. The results show that DMY significantly improves d-gal-induced cognitive impairments in novel object recognition and Y-maze studies. H&E and TUNEL staining show that DMY could improve histopathological changes and cell apoptosis in mice brain. DMY effectively induces the activities of catalase, superoxide dismutase and glutathione peroxidase, and reduces malondialdehyde level in mice brain and liver. Furthermore, DMY reduces cholinergic injury by inhibiting the activity of Acetylcholinesterase (AChE) in mice brain. In vitro studies show that DMY is a non-competitive inhibitor of AChE with IC50 value of 161.2 µg mL-1 . CONCLUSION: DMY alleviates the cognitive impairments in d-gal-induced aging mice partly through regulating oxidative stress and inhibition of acetylcholinesterase.

The anti-obesity and gut microbiota modulating effects of taxifolin in C57BL/6J mice fed with a high-fat diet.

BACKGROUND: Taxifolin is a natural dihydroflavonol found in many plants and health products. In the present study, its anti-obesity and gut microbiota modulating effects were studied. C57BL/6J mice were fed with a high-fat diet (HFD) supplemented with taxifolin (0, 0.5 and 1 mg mL-1 , respectively) in drinking water for 15 weeks. RESULTS: Taxifolin supplementation showed no influence on food and water intake. However, it decreased body weight gain, inhibited fat accumulation, and decreased total cholesterol and triacylglycerol level in mice liver. Taxifolin enhanced superoxide dismutase (SOD) activity in mice liver, which in turn protected the liver from lipid peroxidation damage. It also improved insulin resistance in obese mice. Metagenomic analysis of bacterial 16S rRNA demonstrated that HFD decreased gut microbiota diversity and caused dysbiosis. However, taxifolin improved the gut microbiota diversity and decreased the Firmicutes/Bacteroidetes ratio. In particular, it inhibited Proteobacteria from blooming, this being a signature of dysbiosis in gut microbiota. CONCLUSION: Taxifolin ameliorated the symptoms of obesity, hepatic steatosis, lipid peroxidation, insulin resistance, and gut microbiota dysbiosis in HFD fed C57BL/6J mice. © 2021 Society of Chemical Industry.

In vivo and in vitro comparison of three astilbin encapsulated zein nanoparticles with different outer shells.

Three shell materials, lecithin (ZNP-L), chitosan (ZNP-CH) and sodium caseinate (ZNP-SC), were used to prepare core-shell zein nanoparticles. Astilbin was encapsulated as a model flavonoid to compare the influence of the shell materials on zein nanoparticles both in vitro and in vivo. The particle size was moderately increased by lecithin and sodium caseinate, but notably increased by chitosan. All the shell materials provided good redispersibility for the nanoparticles and significantly improved the colloidal stability. Chitosan and sodium caseinate significantly delayed and decreased the feces excretion of astilbin in rats, while lecithin exhibited a very weak effect. The results may be attributed to the difference in mucoadhesive properties between the shell materials. As a consequence, the bioavailability values of astilbin in rats were 18.2, 9.3 and 1.89 times increased through ZNP-CH, ZNP-SC and ZNP-L compared with that of free astilbin, respectively.

Efficacy and Safety of Regorafenib Monotherapy among Patients with Previously Treated Metastatic Colorectal Cancer in a Chinese Population: A Real-World Exploratory Study.

BACKGROUND: Present study was condeucted to investigate the efficacy and safety of regorafenib for patients with previously treated metastatic colorectal cancer (mCRC) in a Chinese population and the prognostic implications of adverse reactions. METHODS: This retrospective study a total of 96 consecutive patients with mCRC who had failed standard chemotherapy regimens from June 2017 to December 2020. Patients received regorafenib at an initial dosage of 160 mg or 120 mg. The primary end point was progression-free survival (PFS), and secondary end points objective response rate (ORR), disease-control rate (DCR), overall survival (OS), safety, and associations between prognosis and adverse-reaction status. RESULTS: There were three patients with partial response, 49 with stable disease, and 44 with progressive disease. Consequently, the ORR and DCR of the 96 patients were 3.1% (95% CI 0.6%-8.9%) and 54.2% (95% CI 43.7-64.4%), respectively. Prognosis results showed that median PFS of the 96 patients was 2.5 (95% CI 1.98-3.02) months and median OS 9.8 (95% CI 7.02-12.59) months. Additionally, the most frequent adverse reactions during regorafenib treatment were hand-foot syndrome (HFS; 52.1%), hypertension (38.5%), and fatigue (33.3%). Interestingly, the relevance of prognosis to adverse-reaction status exhibited that median PFS of patients with HFS and patients without HFS was 3.3 months and 2.0 months, respectively (P=0.013). Similarly, median PFS of patients with hypertension and without hypertension was 3.6 months and 2.2 months, respectively (P=0.023). CONCLUSION: Potential clinical benefit of regorafenib monotherapy was observed for patients with mCRC who had failed standard chemotherapy regimens. Hypertension and HFS induced by regorafenib therapy could be used as valuable biomarkers to predict the prognosis of regorafenib.

Inhibitory Effect of Fisetin on α-Glucosidase Activity: Kinetic and Molecular Docking Studies.

The inhibition of α-glucosidase is a clinical strategy for the treatment of type 2 diabetes mellitus (T2DM), and many natural plant ingredients have been reported to be effective in alleviating hyperglycemia by inhibiting α-glucosidase. In this study, the α-glucosidase inhibitory activity of fisetin extracted from Cotinus coggygria Scop. was evaluated in vitro. The results showed that fisetin exhibited strong inhibitory activity with an IC50 value of 4.099 × 10-4 mM. Enzyme kinetic analysis revealed that fisetin is a non-competitive inhibitor of α-glucosidase, with an inhibition constant value of 0.01065 ± 0.003255 mM. Moreover, fluorescence spectrometric measurements indicated the presence of only one binding site between fisetin and α-glucosidase, with a binding constant (lgKa) of 5.896 L·mol-1. Further molecular docking studies were performed to evaluate the interaction of fisetin with several residues close to the inactive site of α-glucosidase. These studies showed that the structure of the complex was maintained by Pi-Sigma and Pi-Pi stacked interactions. These findings illustrate that fisetin extracted from Cotinus coggygria Scop. is a promising therapeutic agent for the treatment of T2DM.

Physicochemical properties of dihydromyricetin and the effects of ascorbic acid on its stability and bioavailability.

BACKGROUND: Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactive effects. However, the physicochemical properties of DMY related to its bioavailability, especially its stability, are unclear. RESULTS: The effects of pH, temperature, metal ions and ascorbic acid (AA) on the stability of DMY were studied using high-performance liquid chromatography (HPLC). The bioavailability of DMY in the presence and absence of AA was compared. Dihydromyricetin was unstable in weak alkaline solutions, and the degradation was significantly accelerated in the presence of Cu2+ and Fe3+ . The degradation process followed the first-order kinetic model. The degradation rate constant (k) increased with increasing pH and temperature. The remaining DMY was only 49% of its initial concnentration after 4 h in simulated intestinal fluid (SIF) at 37 °C. However, by supplementing with AA, the degradation of DMY was rarely occured within 6 h. The solubility of DMY at pH 3-5 was about 750 µg mL-1 , slightly increasing to 853 µg mL-1 at pH 6. Pharmacokinetic studies showed that the bioavailability of DMY increased from 0.122% to 0.341% by supplementing with AA (10% of DMY). CONCLUSION: The degradation of DMY is one reason for its poor bioavailability. The presence of AA could significantly improve the stability of DMY, and further improve its bioavailability in rats. © 2020 Society of Chemical Industry.

A Comparison of Solubility, Stability, and Bioavailability between Astilbin and Neoastilbin Isolated from Smilax glabra Rhizoma.

Astilbin and neoastilbin are two flavonoid stereoisomers. In the present study, their solubility, stability, and bioavailability were compared in a rat. The results revealed that the water solubility of astilbin and neoastilbin was 132.72 µg/mL and 217.16 µg/mL, respectively. The oil-water distribution coefficient (log P) of astilbin and neoastilbin in simulated gastric fluid (SGF) was 1.57 and 1.39, and in simulated intestinal fluid (SIF) was 1.09 and 0.98, respectively. In SIF, about 78.6% astilbin remained after 4 h of incubation at 37 °C, while this value was 88.3% for neoastilbin. Most of the degraded astilbin and neoastilbin were isomerized into their cis-trans-isomer, namely neoisoastilbin and isoastilbin, respectively, and the decomposed parts were rare. For bioavailability comparison in a rat, an HPLC method for trace amounts of astilbin and neoastilbin determination in plasma was developed, and the pretreatment of plasma was optimized. A pharmacokinetic study showed that the absolute bioavailability of astilbin and neoastilbin in a rat showed no significant difference with values of 0.30% and 0.28%, respectively.

Synthesis, in vitro inhibitory activity, kinetic study and molecular docking of novel N-alkyl-deoxynojirimycin derivatives as potential α-glucosidase inhibitors.

A series of novel N-alkyl-1-deoxynojirimycin derivatives 25 ∼ 44 were synthesised and evaluated for their in vitro α-glucosidase inhibitory activity to develop α-glucosidase inhibitors with high activity. All twenty compounds exhibited α-glucosidase inhibitory activity with IC50 values ranging from 30.0 ± 0.6 µM to 2000 µM as compared to standard acarbose (IC50 = 822.0 ± 1.5 µM). The most active compound 43 was ∼27-fold more active than acarbose. Kinetic study revealed that compounds 43, 40, and 34 were all competitive inhibitors on α-glucosidase with Ki of 10 µM, 52 µM, and 150 µM, respectively. Molecular docking demonstrated that the high active inhibitors interacted with α-glucosidase by four types of interactions, including hydrogen bonds, π-π stacking interactions, hydrophobic interactions, and electrostatic interaction. Among all the interactions, the π-π stacking interaction and hydrogen bond played a significant role in a various range of activities of the compounds.