Synthesis and evaluation of pentacyclic triterpenoids conjugates as novel HBV entry inhibitors targeting NTCP receptor.

Chronic liver diseases caused by hepatitis B virus (HBV) are the accepted main cause leading to liver cirrhosis, hepatic fibrosis, and hepatic carcinoma. Sodium taurocholate cotransporting polypeptide (NTCP), a specific membrane receptor of hepatocytes for triggering HBV infection, is a promising target against HBV entry. In this study, pentacyclic triterpenoids (PTs) including glycyrrhetinic acid (GA), oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA) were modified via molecular hybridization with podophyllotoxin respectively, and resulted in thirty-two novel conjugates. The anti-HBV activities of conjugates were evaluated in HepG2.2.15 cells. The results showed that 66% of the conjugates exhibited lower toxicity to the host cells and had significant inhibitory effects on the two HBV antigens, especially HBsAg. Notably, the compounds BA-PPT1, BA-PPT3, BA-PPT4, and UA-PPT3 not only inhibited the secretion of HBsAg but also suppressed HBV DNA replication. A significant difference in the binding of active conjugates to NTCP compared to the HBV PreS1 antigen was observed by SPR assays. The mechanism of action was found to be the competitive binding of these compounds to the NTCP 157-165 epitopes, blocking HBV entry into host cells. Molecular docking results indicated that BA-PPT3 interacted with the amino acid residues of the target protein mainly through π-cation, hydrogen bond and hydrophobic interaction, suggesting its potential as a promising HBV entry inhibitor targeting the NTCP receptor.

The metabolism of pyrene by a novel Altererythrobacter sp. with in-situ co-substrates: A mechanistic analysis based on pathway, genomics, and enzyme activity.

Using co-substrates to enhance the metabolic activity of microbes is an effective way for high-molecular-weight polycyclic aromatic hydrocarbons removal in petroleum-contaminated environments. However, the long degradation period and exhausting substrates limit the enhancement of metabolic activity. In this study, Altererythrobacter sp. N1 was screened from petroleum-contaminated soil in Shengli Oilfield, China, which could utilize pyrene as the sole carbon source and energy source. Saturated aromatic fractions and crude oils were used as in-situ co-substrates to enhance pyrene degradation. Enzyme activity was influenced by the different co-substrates. The highest degradation rate (75.98%) was achieved when crude oil was used as the substrate because strain N1 could utilize saturated and aromatic hydrocarbons from crude oil simultaneously to enhance the degrading enzyme activity. Moreover, the phthalate pathway was dominant, while the salicylate pathway was secondary. Furthermore, the Rieske-type aromatic cyclo-dioxygenase gene was annotated in the Altererythrobacter sp. N1 genome for the first time. Therefore, the co-metabolism of pyrene was sustained to achieve a long degradation period without the addition of exogenous substrates. This study is valuable as a potential method for the biodegradation of high-molecular-weight polycyclic aromatic hydrocarbons.

Aromatic Acids and Leucine Derivatives Produced from the Deep-Sea Actinomycetes Streptomyceschumphonensis SCSIO15079 with Antihyperlipidemic Activities.

Six new aromatic acids (1-6) and three new leucine derivatives containing an unusual oxime moiety (7-9) were isolated and identified from the deep-sea-derived actinomycetes strain Streptomyces chumphonensis SCSIO15079, together with two known compounds (10-11). The structures of 1-9 including absolute configurations were determined by detailed NMR, MS, and experimental and calculated electronic circular dichroism spectroscopic analyses. Compounds 1-9 were evaluated for their antimicrobial and cytotoxicity activities, as well as their effects on intracellular lipid accumulation in HepG2 cells. Compounds 3 and 4, with the most potent inhibitory activity on intracellular lipid accumulation at 10 µM, were revealed with potential antihyperlipidemic effects, although the mechanism needs to be further studied.

Synthesis and antitumor activity of new tetrahydrocurcumin derivatives via click reaction.

Three new derivatives of tetrahydrocurcumin 6, 7 and 9 have been prepared as potent antitumor agents using copper(II)-catalyzed 'click chemistry'. Their structures were identified using 1H-NMR, 13C-NMR and HRMS techniques. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay has been carried out to investigate the in vitro cytotoxicity against human cervical carcinoma (HeLa), human lung adenocarcinoma (A549), human hepatoma carcinoma (HepG2) and human colon carcinoma (HCT-116). Compound 6 has showed significant inhibitory activity against HCT-116 cell line with an IC50 value of 17.86 µM compared to tetrahydrocurcumin (50.96 µM) and positive control etoposide (19.48 µM) while showed no inhibitory activity against NCM460 cell line. Compounds 7 showed moderate inhibitory activity compared to tetrahydrocurcumin and etoposide while compound 9 showed no obvious inhibitory activity. The results suggested further structure modifications of tetrahydrocurcumin to improve its anticancer activity.[Formula: see text].

Engineered polymer nanoparticles incorporating l-amino acid groups as affinity reagents for fibrinogen.

Synthetic polymer hydrogel nanoparticles (NPs) were developed to function as abiotic affinity reagents for fibrinogen. These NPs were made using both temperature-sensitive N-isopropyl acrylamide (NIPAm) and l-amino acid monomers. Five kinds of l-amino acids were acryloylated to obtain functional monomers: l-phenylalanine (Phe) and l-leucine (Leu) with hydrophobic side chains, l-glutamic acid (Glu) with negative charges, and l-lysine (Lys) and l-arginine (Arg) with positive charges. After incubating the NPs with fibrinogen, γ-globulin, and human serum albumin (HSA) respectively, the NPs that incorporated N-acryloyl-Arg monomers (AArg@NPs) showed the strongest and most specific binding affinity to fibrinogen, when compared with γ-globulin and HSA. Additionally, the fibrinogen-AArg binding model had the best docking scores, and this may be due to the interaction of positively charged AArg@NPs and the negatively charged fibrinogen D domain and the hydrophobic interaction between them. The specific adsorption of AArg@NPs to fibrinogen was also confirmed by the immunoprecipitation assay, as the AArg@NPs selectively trapped the fibrinogen from a human plasma protein mixture. AArg@NPs had a strong selectivity for, and specificity to, fibrinogen and may be developed as a potential human fibrinogen-specific affinity reagent.

Cinnamaldehyde Improves Metabolic Functions in Streptozotocin-Induced Diabetic Mice by Regulating Gut Microbiota.

PURPOSE: The aim of the present study was to examine the protective effects of cinnamaldehyde (CA) on type 1 diabetes mellitus (T1DM) and explore the underlying molecular mechanisms by using multiple omics technology. METHODS: T1DM was induced by streptozotocin in the mice. Immunostaining was performed to evaluate glycogen synthesis in the liver and morphological changes in the heart. Gut microbiota was analyzed using 16S rRNA gene amplification sequencing. The serum metabolomics were determined by liquid chromatography-mass spectrometry. The relevant gene expression levels were determined by quantitative real-time PCR. RESULTS: CA treatment significantly improved the glucose metabolism and insulin sensitivity in T1DM mice. CA increased glycogen synthesis in the liver and protected myocardial injury in T1DM mice. CA affected the gut microbiota particularly by increasing the relative abundance of Lactobacillus johnsonii and decreasing the relative abundance of Lactobacillus murinus in T1DM mice. The glucose level was positively correlated with 88 functional pathways of gut microbiota and negatively correlated with 2 functional pathways of gut microbiota. Insulin resistance was positively correlated with 11 functional pathways. The analysis of serum metabolomics showed that CA treatment significantly increased the levels of taurochenodeoxycholic acid, tauroursodeoxycholic acid, tauro-α-muricholic acid and tauro-ß-muricholic acid, taurodeoxycholic acid, taurocholic acid and taurohyodeoxycholic acid in T1DM mice. Taurohyodeoxycholic acid level was highly correlated with the blood glucose levels. Furthermore, the abundance of Faecalibacterium prausnitzii was positively correlated with AKT2, insulin like growth factor 1 receptor, E2F1 and insulin receptor substrate 1 mRNA expression levels, while taurohyodeoxycholic acid level was negatively correlated with IRS1 mRNA expression level. CONCLUSION: Our results indicated that CA may interfere with gut microbiota to affect host metabolomics, especially the bile acids, so as to directly or indirectly modulate the expression levels of glucose metabolism-related genes, thus subsequently reducing the blood glucose level in the T1DM mice.

Metal-Free Polymer-Based Affinity Medium for Selective Purification of His6-Tagged Proteins.

We report a metal free synthetic hydrogel copolymer with affinity and selectivity for His6-tagged peptides and proteins. Small libraries of copolymers incorporating charged and hydrophobic functional groups were screened by an iterative process for His6 peptide affinity. The monomer selection was guided by interactions found in the crystal structure of an anti-His tag antibody-His6 peptide antigen complex. Synthetic copolymers incorporating a phenylalanine-derived monomer were found to exhibit strong affinity for both His6-containing peptides and proteins. The proximity of both aromatic and negatively charged functional groups were important factors for the His6 affinity of hydrogel copolymers. His6 affinity was not compromised by the presence of enzyme cleavage sequences. The His6-copolymer interactions are pH sensitive: the copolymer selectively captured His6 peptides at pH 7.8 while the interactions were substantially weakened at pH 8.6. This provided mild conditions for releasing His6-tagged proteins from the copolymer. Finally, a synthetic copolymer coated chromatographic medium was prepared and applied to the purification of a His6-tagged protein from an E. coli expression system. The results establish that a synthetic copolymer-based affinity medium can function as an effective alternative to immobilized metal ion columns for the purification of His6-tagged proteins.

Recent progress in chemical approaches for the development of novel neuraminidase inhibitors.

Influenza virus is the main cause of an infectious disease called influenza affecting the respiratory system including the throat, nose and lungs. Neuraminidase inhibitors are reagents used to block the enzyme called neuraminidase to prevent the influenza infection from spreading. Neuraminidase inhibitors are widely used in the treatment of influenza infection, but still there is a need to develop more potent agents for the more effective treatment of influenza. Complications of the influenza disease lead to death, and one of these complications is drug resistance; hence, there is an urgent need to develop more effective agents. This review focuses on the recent advances in chemical synthesis pathways used for the development of new neuraminidase agents along with the medicinal aspects of chemically modified molecules, including the structure-activity relationship, which provides further rational designs of more active small molecules.

Engineered polymer nanoparticles incorporating L-amino acid groups as affinity reagents for fibrinogen / 药物分析学报

Synthetic polymer hydrogel nanoparticles(NPs)were developed to function as abiotic affinity reagents for fibrinogen.These NPs were made using both temperature-sensitive N-isopropyl acrylamide(NIPAm)and L-amino acid monomers.Five kinds of L-amino acids were acryloylated to obtain functional mono-mers:L-phenylalanine(Phe)and L-leucine(Leu)with hydrophobic side chains,L-glutamic acid(Glu)with negative charges,and L-lysine(Lys)and L-arginine(Arg)with positive charges.After incubating the NPs with fibrinogen,y-globulin,and human serum albumin(HSA)respectively,the NPs that incorporated N-acryloyl-Arg monomers(AArg@NPs)showed the strongest and most specific binding affinity to fibrin-ogen,when compared with y-globulin and HSA.Additionally,the fibrinogen-AArg binding model had the best docking scores,and this may be due to the interaction of positively charged AArg@NPs and the negatively charged fibrinogen D domain and the hydrophobic interaction between them.The specific adsorption of AArg@NPs to fibrinogen was also confirmed by the immunoprecipitation assay,as the AArg@NPs selectively trapped the fibrinogen from a human plasma protein mixture.AArg@NPs had a strong selectivity for,and specificity to,fibrinogen and may be developed as a potential human fibrinogen-specific affinity reagent.

Vinblastine-Loaded Nanoparticles with Enhanced Tumor-Targeting Efficiency and Decreasing Toxicity: Developed by One-Step Molecular Imprinting Process.

Molecularly imprinted polymers have exhibited good performance as carriers on drug loading and sustained release. In this paper, vinblastine (VBL)-loaded polymeric nanoparticles (VBL-NPs) were prepared by a one-step molecular imprinting process, avoiding the waste and incomplete removal of the template, and evaluated as targeting carriers for VBL delivery after modification. Using acryloyl amino acid comonomers and disulfide cross-linkers, VBL-NPs were synthesized and then conjugated with poly(ethylene glycol)-folate. The dynamic size of the obtained VBL-NPs-PEG-FA was 258.3 nm (PDI = 0.250), and the encapsulation efficiency was 45.82 ± 1.45%. The nanoparticles of VBL-NPs-PEG-FA were able to completely release VBL during 48 h under a mimic tumor intracellular condition (pH 4.5, 10 mM glutathione (GSH)), displaying significant redox responsiveness, whereas the release rates were much slower in the mimic body liquid (pH 7.4, 2 µM GSH) and tumor extracellular environment (pH 6.5, 2 µM GSH). Furthermore, the carriers NPs-PEG-FA, prepared without VBL, showed satisfactory intrinsic hemocompatibility, cellular compatibility, and tumor-targeting properties: they could rapidly and efficiently accumulate to folate receptor positive Hela cells and then internalized via receptor-mediated endocytosis, and the retention in tumor tissues could last for over 48 h. Interestingly, VBL-NPs-PEG-FA could evidently increase the accumulation of VBL in tumor tissues while decreasing the distribution of VBL in organs, exert similar anticancer efficacy against Hela tumors in the xenograft model of nude mice to VBL injection, and significantly improve the abnormality of liver and spleen observed in VBL injection. VBL-NPs-PEG-FA has the potential to be the delivery carrier for VBL by enhancing the tumor-targeting efficacy of VBL and decreasing toxicity to normal tissues.

Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors.

A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion with IC50 values of 0.14 µM and 0.86 µM respectively, and the inhibitory activities were also confirmed by detecting the fluorescence intensity of FITC-labeled monoclonal mouse HBeAg antibody via flow cytometry. Compounds D7 and D10 as well as B4, ring-A cleaved 3,30-dioic acid, also displayed remarkable inhibition on both HBV DNA replication at the concentration of 25 µM and HBV cccDNA (covalently closed circularDNA) replication with IC50 values of 33.5 µM, 32.7 µM and 12.3 µM respectively.

Molecularly imprinted nanoparticles and their releasing properties, bio-distribution as drug carriers.

Molecular imprinted nanoparticles (MINPs) can memorize the shape and functional group positions complementary to template, which account for the large drug loading capacity and slow drug release behavior as drug carriers. We synthesized MINPs via precipitation polymerization with vinblastine (VBL) as a model drug, and investigated the drug loading, releasing property in vitro and bio-distribution in vivo. The obtained MINPs, from 300 to 450 nm, had smooth surface and favorable dispersibility. The entrapment efficacy and drug loading capacity of VBL loaded MINPs (MINPs-VBL) were 83.25% and 8.72% respectively. In PBS (pH7.4), MINPs-VBL showed sustained release behavior. The cumulative release percentage reached about 70% during 216 h and no burst release was observed. The releasing behavior of MINPs-VBL in vitro conformed to the first-order kinetics model. MINPs-VBL and commercially available vinblastine sulfate injection (VBL injection) were injected via tail vein of SD rats respectively to investigate the bio-distribution. MINPs-VBL group showed higher concentration of VBL in tissues and serum than VBL injection group after 60 min, and the drug level in liver was the highest. MINPs-VBL exhibited liver targeting trend to some extent, which was based on the evaluation of drug targeting index (DTI) and drug selecting index (DSI).

Anti-hepatitis B virus activities of friedelolactones from Viola diffusa Ging.

BACKGROUND: Hepatitis B virus (HBV) infection is the major factor of causing hepatitis B, cirrhosis and liver cancer. Interferon and nucleoside drugs, the main drugs to treat HBV infection, have disadvantages of scavenge difficulty and drug resistance respectively. Viola diffusa Ging is used as a traditional Chinese herbal medicine for the treatment of hepatitis. PURPOSE: The aim of the study is to investigate the chemical constituents of Viola diffusa Ging and their anti-HBV activity. METHODS: Chemical constituents were extracted and purified by ethanol reflux extraction and chromatographic separation technology including D-101 Macroporous resin, silica gel, Sephadex LH-20 and preparative thin-layer chromatography. Their structures were elucidated on the basis of extensive NMR and MS data. Cytotoxicity and inhibiting effects on HBsAg and HBeAg secretion of HepG2.2.15 of all compounds except 10 were studied by MTT method and ELISA method. RESULTS: Three friedelolactones with naturally occurring seco-ring-A friedelane triterpenoids, 2ß-hydroxy-3, 4-seco-friedelolactone-27-oic acid (1), 2ß, 28ß-dihydroxy-3,4-seco-friedelolactone-27-oic acid (2) and 2ß, 30ß-dihydroxy-3,4-seco-friedelolactone-27-lactone (3), and a stigmastane, stigmast-25-ene-3ß,5α,6ß-triol (11) together with nine known compounds were isolated from the whole plant of Viola diffusa G. (Violaceae). Compounds 1-3, 9, 11, 12 exhibited significant activities of blocking both HBsAg and HBeAg secretion, and compound 4, 6, 7, 8 selectively inhibited HBeAg secretion while compound 13 selectively inhibited HBsAg secretion. IC50 values of compounds 1 and 2, 26.2 µM and 33.7 µM for HBsAg, 8.0 µM and 15.2 µM for HBeAg, was significantly lower than that of positive control lamivudine. CONCLUSION: Compounds 1-3, 11 are new compounds never reported before and the promising results demonstrate the potential of compound 1-3, 9, 11, 12 for the treatment of HBV infection.

Molecularly imprinted polymers on a silica surface for the adsorption of tobacco-specific nitrosamines in mainstream cigarette smoke.

Tobacco-specific nitrosamines are one of the most important groups of carcinogens in tobacco products. Using adsorbents as filter additives is an effective way to reduce tobacco-specific nitrosamines in cigarette smoke. Molecularly imprinted polymers (MIPs) using nicotinamide as template were grafted on the silica gel surface to obtain MIP@SiO2 and employed as filter additives to absorb tobacco-specific nitrosamines in mainstream cigarette smoke. Four milligrams of MIP@SiO2 per cigarette was added to the interface between filter and tobacco rod to prepare a binary filter system. The mainstream smoke was collected on an industry-standard Cambridge filter pad and extracted with ammonium acetate aqueous solution before analysis. Compared to the cigarette smoke of the control group, the levels of tobacco-specific nitrosamines with silica gel and with MIP@SiO2 were both reduced, and the adsorption rates of N-nitrosonornicotine, N-nitrosoanabasine, N-nitrosoanatabine, and 4-(methylnitrosamino)-1-(3-pyridine)-1-butanone with silica gel and with MIP@SiO2 were 20.76, 15.32, 18.79, and 18.01%, and 41.33, 34.04, 37.86, and 35.53%, respectively. Furthermore the content of total particle materials in cigarette smoke with silica gel was decreased evidently but showed no observable change with MIP@SiO2 . It indicated MIP@SiO2 could selectively reduce tobacco-specific nitrosamines in the mainstream cigarette smoke with no change to the cigarette flavor.

Effects of cinnamene enhancers on transdermal delivery of ligustrazine hydrochloride.

Cinnamene compounds, cinnamic acid, cinnamaldehyde and cinnamic alcohol, were employed as enhancers. The effects and mechanisms of penetration promoters on the in vitro percutaneous absorption of ligustrazine hydrochloride across hairless porcine dorsal skin were investigated. Transdermal fluxes of ligustrazine hydrochloride through porcine skin were determined in vitro by Franz-type diffusion cells. The results indicated that the penetration flux of ligustrazine hydrochloride by cinnamic acid was the greatest. Significant statistical differences (P<0.05) were found between cinnamic acid and other promoters. Fourier transform-infrared (FT-IR) were carried out to analyze the effects of enhancers on the biophysical properties of the stratum corneum and the permeation enhancement mechanisms. FT-IR results revealed that the changes of peak shift and peak area due to C-H stretching vibrations in the stratum corneum lipids were associated with the selected enhancers. All of them could perturb and extract the stratum corneum lipids to different extent. Morphological changes of the skin treated with enhancers were monitored by a scanning electron microscope. It was demonstrated that the extraction of the stratum corneum lipids by the enhancers led to the disruption of stratum corneum and the desquamation of stratum corneum flake. Apparent density was newly proposed to estimate the desquamated extent of stratum corneum flake. Correlation analysis revealed that there was a linear relationship between apparent density and decrease in peak area. The results showed that the permeation enhancement mechanisms of cinnamene were pleiotropic ones, including disordering the lipids, extracting the lipids and competitive hydrogen bonding between cinnamene enhancers and amides of ceramide head groups in stratum corneum.

[Removal of the template molecules from vinblastine-imprinted polymer].

OBJECTIVE: To investigate the optimal condition for complete removal of the template molecules from vinblastine (VLB)-imprinted polymer. METHOD: The prepared polymers were packed into the cartridges of solid-phase extraction column and washed by methanol-glacial acetic acid mixture with different proportions. The contents and recoveries of VLB in the effluents were determined. RESULTS: Polymer extraction with methanol-glacial acetic acid (9:1, V/V) resulted in VLB recovery of 91.73%, but template bleeding was observed because of incomplete VLB removal. Using methanol-glacial acetic acid (6:4, V/V) as the extraction solvent, the recovery of VLB reached 98.03% with less solvents and extract times. The polymers could selectively adsorb VLB through non-covalent interactions and still exhibited strong affinity for the template molecule but not for the structural analogue vincristine after extraction with methanol-glacial acetic acid (6:4, V/V). CONCLUSION: Methanol-glacial acetic acid (6:4, V/V) is an ideal extract solvent for complete template molecule removal from the polymers, and the processed polymers possess stable capacity of specific recognition and selectivity to the template.

Investigation of imprinting parameters and their recognition nature for quinine-molecularly imprinted polymers.

A series of molecularly imprinted polymers (MIPs) was prepared using quinine as the template molecules by bulk polymerization. The presence of monomer-template solution complexes in non-covalent MIPs systems has been verified by both fluorescence and UV-vis spectrometric detection. The influence of different synthetic conditions (porogen, functional monomer, cross-linkers, initiation methods, monomer-template ratio, etc.) on recognition properties of the polymers was investigated. Scatchard analysis revealed that two classes of binding sites were formed in the imprinted polymer. The corresponding dissociation constants were estimated to be 45.00 micromol l(-1) and 1.42 mmol l(-1), respectively, by utilizing a multi-site recognition model. The binding characteristics of the imprinted polymers were explored in various solvents using equilibrium binding experiments. In the organic media, results suggested that polar interactions (hydrogen bonding, ionic interactions, etc.) between acidic monomer/polymer and template molecules were mainly responsible for the recognition, whereas in aqueous media, hydrophobic interactions had a remarkable non-specific contribution to the overall binding. The specificity of MIP was evaluated by rebinding the other structurally similar compounds. The results indicated that the imprinted polymers exhibited an excellent stereo-selectivity toward quinine.

[Optimization of the polymerization conditions of vinblastine imprinted polymer by uniform design].

OBJECTIVE: To optimize the polymerization conditions of vinblastine (VLB) imprinted polymer. METHODS: The conditions were optimized by the method of uniform design. The major factors investigated included the amount of functional monomer (MAA) and the cross-linker (EDMA) and the progenic solvent (toluene or acetonitril). The adsorption rate of VLB on the solid-phase extraction (SPE) column packed with MIP was adopted as the response value. RESULTS: The optimal conditions were MAA 0.4 mmol, EDMA 1.6 mmol and using acetonitrile as the solvent. Under the conditions,the VLB imprinted polymer was synthesized and the absorption rate of VLB was 88.20%. The characterizations of the optimal MIP were determined by IR spectrometry and scanning electron microscope (SEM) analysis. CONCLUSION: It is possible to furtherly improve the nature of the polymer by optimizing the polymerization parameters with uniform design. The polymer synthesized under the optimal conditions exhibited high affinity to the target molecule VLB.

[Mechanism of quercetin as an antidiarrheal agent].

OBJECTIVE: To investigate the antidiarrheal mechanism of quercetin extracted from Psidium guajava L. METHODS: The effects of quercetin on the contractility of guinea pig ileum in vitro and on the peristaltic motion of mouse small intestine in vivo were observed, and the peak value of contractility and peristaltic distance recorded. The inhibitory effect of quercetin on the permeability of the abdominal capillaries was also observed. RESULTS: Quercetin inhibited the contraction of guinea pig ileum in vitro and the peristaltic motion of mouse small intestine, and reduced the permeability of abdominal capillaries. CONCLUSION: Quercetin can inhibit the intestinal movement and reduce capillary permeability in the abdominal cavity, which may be the antidiarrheal mechanism of Psidium guajava L extract.