Lignans are the main active components of Schisandrae Chinensis Fructus for liver disease treatment:a review

As a traditional Chinese herbal medicine,Schisandrae Chinensis Fructus(SC)has been used in medicine and food industry due to its health care and therapeutic effects.Over the past 20 years,the use of SC and its active ingredient lignans in the prevention and treatment of liver diseases has been increasing,and their hepatoprotective effects has increased the interest of the public and academia.Therefore,in the present work,we first determined the effectiveness of SC in the treatment of liver diseases such as metabolic associated fatty liver disease,alcoholic liver disease,cholestatic liver disease and acute liver injury.Subsequently,the pharmacological effects and molecular mechanisms of lignans,the active components of SC,for liver disease treatment were comprehensively summarized for the first time.The results showed that the lignans in SC could achieve hepatoprotective effects by regulating lipid metabolism,anti-fibrosis,anti-inflammation,anti-oxidation,anti-tumor and regulating bile acid metabolism.The mechanism mainly involved adenosine 5’-monophosphate-activated protein kinase,endoplasmic reticulum stress,sterol regulatory element binding protein 1c,autophagy,transforming growth factor-β,mitogen-activated protein kinase,microRNA,nuclear factor kappa-B,nuclear factor erythroid-2-related factor 2,heat shock proteins and pregnane X receptor signaling pathways.These results can lay a scientific foundation for the development of hepatoprotective drugs or functional foods from SC/lignans.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.Methods A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii.Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.Results Six potential active components,namely quercetin,β-sitosterol,stigmasterol,7-Omethylluteolin-6-C-beta-glucoside_qt,atropine,and glycitein,were identified to have potency in improving exercise fatigue via multiple pathways,such as the PI3K-Akt,neuroactive ligand-receptor interaction,IL-17,TNF,and MAPK signaling pathways.The immunofluorescence results indicated that quercetin,a significant active component in Fructus lycii,increased the mean staining area of 2-NBDG,TMRM,and MitoTracker,and decreased the area of CellRox compared to the control.Furthermore,the protein expression levels of p-38 MAPK,p-MAPK,p-JNK,p-PI3K,and p-AKT markedly increased after quercetin treatment.Conclusion Fructus lycii might alleviate exercise fatigue through multiple components and pathways.Among these,quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress.The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Determination of Benzoylaconitine Compounds in the Decoctions of Aconiti Lateralis Radix Praeparata(Heishun Pieces),Trichosanthis Fructus and Their Combination

[Objectives]This study was conducted to determine the contents of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the decoctions of Heishun pieces,Trichosanthis Fructus and their combination.[Methods]Heishun pieces,Trichosanthis Fructus and their combination were extracted for different time periods,and then grouped.HPLC was performed using an Agilent ZORBAX SB-C 18 chromatographic column(4.6 mm×250 mm,5μm)and acetonitrile-0.02 mol/L sodium dihydrogen phosphate as the mobile phase at a flow rate of 1 mL/min and a column temperature of 30℃,and the sample volume was 20μL.The detection wavelength was 230 nm.[Results]The total amounts of benzoylmesaconine,benzoylaconitine and benzoylhypacoitine in the single decoction group of Heishun pieces were all significantly different from those in the combined decoction group at corresponding time.[Conclusions]The total content of the benzoylaconitine type increased significantly after the combined decoction of Heishun pieces and Fructus Trichosanthis,which proves the scientificity of"eighteen incompatible medicaments,19 counteraction"in traditional Chinese medicine to some extent.

Insight into the Efficacy and Potential Mechanism of Fructus Aurantii on Skin Based on Network Pharmacology

[Objectives]This study was conducted to explore the mechanism and pharmacological activity of Fructus Aurantii on human skin through network pharmacology.[Methods]The active components and targets of Fructus Aurantii were screened byTCMSPand SymMap data-bases,and the targets were humanized after de-duplication by UniProt database.Relevant therapeutic targets were searched in Gencards data-base with"skin"as the key word,and those with higher weights were retained.An effective component-human skin action target network of Fructus Aurantii was established by Cytoscape software.Then,the topological analysis of protein-protein interaction(PPI)network was made by using String database and Cytoscape software.Gene Ontology(GO)funetional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were carried out by david database,and the analysis results were visualized by Hiplot soft-ware.[Results]Thirteen active compounds of Fructus Aurantii were obtained by screening,and 99 gene targets of Fructus Aurantii which might have pharmacological activity on human skin were obtained by intersection analysis.PTGS2,PTGS1,HSP90AB1,HSP90AAI,NCOA2 and PIK3CG might be core action targets of Fructus Aurantii on human skin according to the topological analysis of the active component-target network.The analysis of PPI network showed that IL-1β,INS,TNF,TP53 and ESR1 might be core action proteins of Fructus Auranti.GO enrichment analysis showed that Fructus Aurantii might balance the imbalance of skin microenvironment caused by various in-vitro stimuli by participating in biological processes such as response to xenobiotic stimulus and regulation of small molecule metabolic process.KEGG pathway enrichment analysis showed that the targets of Fructus Aurantii acting on human skin were enriched in pathways in cancer,Kaposi sarcoma-associated herpesvirus infection,pathways in measles,AGE-RAGE signaling pathway in diabetic complications,IL.-17 signaling pathway,etc.[Conclusions]Fructus Aurantii may act on human skin targets through a variety of active components,and play a regulatory role in skin-related diseases.

Study on the mechanism of Euphorbia fischeriana Steud.- Jujubae Fructus in the treatment of hepatocirrhosis based on network pharmacology

The active components,targets,and pathways of Euphorbia fischeriana Steud.-Jujubae Fructus in treating hepatocirrhosis and the mechanism of action were explored by means of network pharmacology.Firstly,the active components and related targets of Jujubae Fructus were screened by TCMSP database and standardized by Uniprot database.The compounds of Euphorbia fischeriana Steud.were obtained by searching the literature and finally screened by PubChem database,Swiss ADME,and SwissTargetPrediction.Hepatocirrhosis targets were obtained through Genecards database,PPI network analysis was conducted on common targets of Euphorbia fischeriana Steud.-Jujubae Fructus and hepatocirrhosis by using String database,GO enrichment analysis and KEGG pathway enrichment analysis was conducted through Metascape database by using intersection targets of Euphorbia fischeriana Steud.-Jujubae Fructus and hepatocirrhosis,and the results were drawn by using Weishengxin online drawing platform.Then,the network of drug-compound-target-pathway was constructed by the software of Cytoscape3.8.0.Finally,the above results were verified by molecular docking.47 active compounds from Euphorbia fischeriana Steud.-Jujubae Fructus were screened out,which had 38 common targets,162 intersection targets,and 340 signal pathways with hepatocirrhosis,mainly involving hepatitis C,JAK-STAT signal pathway and AGE-RAGE signal pathway.Targets,such as MAPK1,AKT1,TNF,JUN,IL6 and PTGS2,play important roles in the treatment.The findings suggested that the main active ingredients of Euphorbia fischeriana Steud.-Jujubae Fructus in treating hepatocirrhosis are quercetin,scopolamine,physcion,7-deoxyrangduin,17-Hydroxyjolkinolide A,etc.Molecular docking results showed that the main active components and core targets might have a good binding capacity.This study preliminarily explored the potential mechanism of Euphorbia fischeriana Steud.-Jujubae Fructus in treating hepatocirrhosis and provided a theoretical basis for the clinical application of Euphorbia fischeriana Steud.-Jujubae Fructus.

How Schisandrae Fructus Benefits the Body: Mechanisms in Traditional Chinese Medicine and Modern Medicine

Schisandrae chinensis Fructus (SF) is a commonly used herb in Traditional Chinese Medicine (TCM). According to TCM theory, SF can invigorate Qi in the liver and other visceral organs through the meridian system. Furthermore, the liver’s pivotal role in regulating the functions of various visceral organs helps explain how SF can promote holistic health benefits. The main active ingredient of SF, schisandrin B (Sch B), has been found to improve mitochondrial ATP production and enhance glutathione redox status in multiple organs. This could account for the overall protective effects of Sch B on organs. Due to its stronger impact on liver function, the positive influence of Sch B on different organs may be facilitated by signal molecules originating from the liver.

Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons

AIM: To examine the effect of aqueous fructus aurantii immaturus(FAI) extracts on the intestinal plexus of cathartic colons.METHODS: Cathartic colons were induced in rats with dahuang,a laxative used in traditional Chinese medicine. Once the model was established(after approximately 12 wk),rats were administered mosapride(1.54 mg/kg) or various doses of aqueous FAI extracts(1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed,and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4(5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR,Western blot,and immunohistochemistry.RESULTS: Mosapride and high dose(4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate(70.06 ± 7.25 and 72.02 ± 8.74,respectively,vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls,the ultramicrostructure of cathartic colons showed signsof neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls(P < 0.05 for both). Treatment with aqueous FAI extracts(≥ 2 g/kg) increased 5-HTR4 m RNA levels(P < 0.05),but no change in protein level was observed by Western blot or immunohistochemistry. The m RNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls(P < 0.05 for all).CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.

Orthogonal Test Design for Optimization of the Extraction of Flavonid from the Fructus Gardeniae

Objective It is imperative to provide some consistent experimental results for the extraction of flavonid from Fructus Gardeniae. Methods The key extraction parameters that influenced the yield of flavonid from Fructus Gardeniae were optimized by employing an orthogonal experiment [L9（3）4], including the ratio of buffer solution （Na2B4O7· 10H2O） to raw material, concentration of Fructus Gardeniae in extracting solution, extraction time and pH of buffer solution. An UV/Vis detector was used to perform the qualitative and quantitative analyses of the extracted flavonid with the using of the standard sample. Results The maximum extraction yield of the crude extract was 5.0533 （mg/g） after 20 min when the mass ratio of Na2B4O7 · 10H2O to raw material was 0.4%, the concentration of Fructus Gardeniae in the extraction solution was 1/12 （g/mL）, and pH of buffer solution was 4.5. The positive reactions to the Molish and HCI-Mg tests suggested that the extracted compound was flavonoid, and FTIR measurements also identified the presence of flavonoid in the extracts. Conclusion This work is expected to provide a basis for further research, development, and utilization of Fructus gardenia in flavonid extraction.

LC-MS determination and pharmacokinetic study of salidroside in rat plasma after oral administration of suspensions of traditional Chinese medicine Erzhi Wan and Fructus Ligustri lucidi

A simple,rapid and sensitive liquid chromatography-mass spectrometry（LC-MS）method was developed for the determination of salidroside in rat plasma and study of its pharmacokinetics after oral administration of suspension of Erzhi Wan and Fructus Ligustri lucidi into Wistar rats.Plasma sample of 200 μL was extracted with acetic ether-isopropanol（2∶1）and the extraction was performed on a Kromasil C18 column（150 mm×4.6 mm,5 μm）with the mobile phase of methanol-water（41∶59,v/v）within a run time of 6.0 min.The analyte was monitored with positive electrospray ionization（ESI）by selected ion monitoring（SIM）mode.The target ions were m/z 323.05 for salidroside and m/z 411.05 for internal standard（IS）geniposide.A good linear relationship was obtained over the range of 5.0-500.0 ng/mL and the lower limit of quantification was 5.0 ng/mL.The validated method was successfully applied to the pharmacokinetic study of salidroside in rat plasma after oral administration of suspension of Erzhi Wan and Fructus Ligustri lucidi.

Fructus Broussonetae extract improves cognitive function and endoplasmic reticulum stress in Alzheimer's disease models

This study investigated the effects and possible targets of Fructus Broussonetiae extract, a traditional Chinese medicinal herb, on a model of Alzheimer＇s disease induced by beta-amyloid peptide 25 35 and D-galactose. The results revealed that intragastric administration of Fructus Broussonetiae significantly increased the expression of immunoglobulin-binding protein, a key factor in the endoplasmic reticulum stress-signaling pathway in rat hippocampus. In contrast, the treatment significantly decreased expression levels of PKR-like endoplasmic reticulum kinase and C/EBP homologous protein, and substantially improved learning, memory and spatial recognition dysfunction in rats. This evidence indicates that Fructus Broussonetiae extract improves spatial learning and memory abilities in rats by affecting the regulation of hippocampal endoplasmic reticulum stress and activation of the apoptosis pathway.

Separation,identification,and quantification of active constituents in Fructus Psoraleae by high-performance liquid chromatography with UV,ion trap mass spectrometry,and electrochemical detection

The qualitative and quantitative analysis of active constituents in Fructus Psoraleae is presented by high-performance liquid chromatography (HPLC) coupled with different detections.Extracts of Fructus Psoraleae were examined by HPLC with ion trap mass spectrometry (IT-MS) and 18 major compounds of coumarins,benzofuran glycosides,flavonoids,and meroterpene were identified.The determination of four major constituents including bavachin,isobavachalcone,bavachinin,and bakuchiol was accomplished by HPLC with UV,MS,and electrochemical detection (ECD).These methods were evaluated for a number of validation characteristics (repeatability,LOD,calibration range,and recovery).ECD obtained a high sensitivity for analysis of the four components;MS provided a high selectivity and sensitivity for determination of bavachin,isobavachalcone,and bavachinin in negative-ion mode.After optimization of the methods,separation,identification.and quantification of the four components in Fructus Psoraleae were comprehensively tested by HPLC with UV,MS,and ECD.

Mori fructus aqueous extracts attenuates liver injury by inhibiting ferroptosis via the Nrf2 pathway

Background Liver fibrosis and hepatocellular carcinogenesis secondary to liver fibrosis are serious liver diseases with no effective treatments.Mori fructus aqueous extracts(MFAEs)have served as successful treatments for many types of liver injury including fibrosis although the molecular mechanisms are unknown at present.Purpose To investigate the effect of MFAEs in alleviating acute and chronic liver injury and tried to decipher the underlying mechanism.Methods and results Mice were divided into 5 groups(n ps:contro=8)for acute(groups:control,0.3%CCl_(4),bifendate(BD),100 and 200 mg/kg MFAEs,7 d)and chronic(groul,10%CCl_(4),BD,100 and 200 mg/kg MFAEs,4 weeks)liver injury study.Each mouse was injected intraperitoneally with 10μL/g corn oil containing CCl_(4)expect the control group.HepG2 cells were used in vitro study.Eighteen communal components were identified by UPLC-LTQOrbitrap-MS.We utilized a mouse model for acute and chronic liver injury using CCl_(4)and MFAEs administration effectively blocked fibrosis and significantly inhibited inflammation in the liver.MFAEs activated the nuclear factor erythroid derived 2 like 2/heme oxygenase 1(Nrf2/HO-1)pathway and promoted the synthesis of the antioxidants glutathione(GSH),superoxidedismutase(SOD)and glutathione peroxidase(GSH-Px)that resulted in reduced levels of CCl_(4)-induced oxidative stress molecules including reactive oxygen species.These extracts administered to mice also inhibited ferroptosis in the liver by regulating the expression of Acyl-CoA synthetase long chain family member 4(ACSL4),solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),thus reducing the occurrence of liver fibrosis.Both in vivo and in vitro tests indicated that the mechanism of MFAEs protection against liver fibrosis was linked to activation of Nrf2 signaling.These effects were blocked in vitro by the addition of a specific Nrf2 inhibitor.Conclusion MFAEs inhibited oxidative stress,ferroptosis and inflammation of the liver by activating Nrf2 signal pathway and provided a significant protective effect against CCl_(4)-induced liver fibrosis.

Chromatographic fingerprint analysis of Fructus Aurantii Immaturus by HPLC-DAD and chemometric methods

An efficient method for quality control of Fructus Aurantii Immaturus (FAI),a famous traditional Chinese medicine (TCM) was established. A simple and reliable high-performance liquid chromatography-photodiode array detector (HPLC-DAD) procedure coupled with chemometric methods was developed for fingerprint analysis,qualitative analysis and quantitative determination of this herb. In qualitative and quantitative analyses,heuristic evolving latent projection (HELP) method was employed to resolve the overlapping peaks of the tested samples. Two bioactive components,namely hesperidin and naringin,are confirmed and determined,together with four flavonoids compounds tentatively identified including two new ones. From fingerprint analysis,the fingerprint data were processed with correlation coefficients for quantitative expression of their similarity and dissimilarity. The developed method based on an integration of chromatographic fingerprint and quantitative analysis is scientific,and the obtained results can be applied to the quality control of herb medicine.

Isoflavones’effects on pharmacokinetic profiles of main iridoids from Gardeniae Fructus in rats

Gardeniae Fructus(GF)and Semen Sojae Praeparatum(SSP)are both medicine food homologies and widely used in Chinese clinical prescriptions together.The research investigated the pharmacokinetics of four iridoids in normal rats and isolfavones-fed rats,which were administered with isolfavones from SSP for 7,14,21 and 28 consecutive days.A validated LC-MS/MS method was developed for determining shanzhiside,genipin-1-gentiobioside,geniposide and their metabolite genipin in rat plasma.Plasma samples were pretreated by solid-phase extraction using paeoniflorin as the internal standard.The chromatographic separation was performed on a Waters Atlantis T3(4.6 mm×150 mm,3 mm)column using a gradient mobile phase consisting of acetonitril and water(containing 0.06%acetic acid).The mass detection was under the multiple reaction monitoring(MRM)mode via polarity switching between negative and positive ionization modes.The calibration curves exhibited good linearity(r>0.997)for all components.The lower limit of quantitation was in the range of 1 e10 ng/m L.The intra-day and inter-day precisions(RSD)at three different levels were both less than 12.2%and the accuracies(RE)ranged fromà10.1%to 16.4%.The extraction recovery of them ranged from 53.8%to 99.7%.Pharmacokinetic results indicated the bioavailability of three iridoid glycosides and the metabolite,genipin in normal rats was higher than that in rats exposed to isoflavones.With the longer time of administration of isoflavones,plasma concentrations of iridoids decreased,while genipin sulfate,the phase II metabolite of genposide and genipin-1-gentiobioside,appeared the rising exposure.The pharmacokinetic profiles of main iridoids from GF were altered by isoflavones.

The Inhibitory Effect of Extracts From Fructus lycii and Rhizoma polygonati on in vitro DNA Breakage by Alternariol

Alternariol caused DNA single-strand breakage. Conversion of the closed circular double-stranded supercoiled DNA (pBR 322) to the nicked circular form and linear form was used to investigate the effect of extracts of some Chinese medical herbs on DNA nicking induced by alternariol. Some substances in the extracts of Rhizoma polygonati (RP) and Fructus lycii (FL) were shown to protect DNA from the attack by alternariol.Some substance in the RP may bind to plasmid DNA, and this binding reduces the electrophoretic mobility of DNA. These results indicate that substances from FL and RP may be used as DNA protectors. It is possible that they play an important role in preventing cancer.

Study on Alkaloids in Fructus Hordei Germinatus

[Objectives]To isolate and analyze alkaloids in Fructus Hordei Germinatus.[Methods]The alkaloids in the Fructus Hordei Germinatus were extracted by ultrasonic technology,and analyzed by the ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) technique.[Results] According to the mass spectrometry information,compared with the literature reports,the possible structures of seven alkaloids in the Fructus Hordei Germinatus could be inferred.Compounds 1,2 and 3 were organic amine alkaloids,respectively tyramine and N-methyltyramine,hordenine,compounds 4,5,6 and 7 were indole alkaloids,respectively,tryptamine,gramine,harmine,and bufotenidine.The alkaloids in the Fructus Hordei Germinatus were separated by preparative high performance liquid chromatography(p HPLC) technique,a compound was obtained and identified by UPLC-MS/MS and nuclear magnetic resonance(NMR) technique as hordenine.[Conclusions]This experiment is expected to lay a foundation for the development of alkaloids in the Fructus Hordei Germinatus.

Effects of Chinese Fructus Mume Formula and Its Separated Prescription Extract on Insulin Resistance in Type 2 Diabetic Rats

The effect of Fructus Mume formula and its separated prescription extract on insulin resis- tance in type 2 diabetic rats was investigated. The rat model of type 2 diabetes was established by feed- ing on a high-fat diet for 8 weeks and by subsequently intravenous injection of small doses of strepto- zotocin. Rats in treatment groups, including the Fructus Mume formula treatment group （FM）, the cold property herbs of Fructus Mume formula treatment group （CFM）, the warm property herbs of Fructus Mume formula treatment group （WFM）, were administrated with Fructus Mume formula and its sepa- rated prescription extract by gavage, while the rats in diabetic model group （DM） and metformin group （MET） were given by gavage with normal saline and metformin correspondingly. The body weight be- fore and after treatment was measured, and the oral glucose tolerance test （OGTT） and the insulin re- lease test （IRT） were performed. The homeostasis model assessment-insulin resistance index （HOMA-IR） was calculated. The protein and mRNA expression levels of Insr, β-arrestin-2, Its-1 and Glut-4 in the liver, skeletal muscle and fat tissues were detected by using Western blotting and RT-PCR respectively. The results demonstrated that, as compared with DM group, OGTT, IRT （0 h, 1 h） levels and HOMR-IR in treatment groups were all reduced, meanwhile their protein and mRNA expression levels of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues were obviously increased, and their protein and mRNA expression levels of β-arrestin-2 in the liver and skeletal muscle tissues were also markedly increased. It was suggested that the Fructus Mume formula and its separated prescription extracts could effectively improve insulin resistance in type 2 diabetic rats, which might be related to the up-regulated expression of Insr, Irs-1 and Glut-4 in the liver, skeletal muscle and fat tissues, and β-arrestin-2 in the liver and skeletal muscle tissues.

Studies on the Components of Crude and Processed Fructus Corni by ESI-MS^n

The components of crude and processed Fructus Corni were investigated by means of electrospray ionization-tandem mass spectrometry（ESI-MSn） technique in the negative ion mode. Compared with those of crude Fructus Corni, the chemical components of the processed Fructus Corni were changed both in quality and in quantity. From the ESI-MS spectra of the crude and processed Fructus Corni, six peaks were selected to establish the characte-ristic ESI-MS peaks. Several factors in the processing procedure were examined. The experimental results demonstrate that the chemical reactions that occurred in the processing procedure can be used for the elucidation of the processed mechanism of Fructus Corni, which is regularly affected by the processing conditions. The present article provides both the chemistry evidence for the understanding of the processing procedure of Fructus Corni and the specific methodology for the research of the processing procedure and quality identification of traditional Chinese medicine.

Preparative separation and purification of deoxyschizandrin from Schisandrae Sphenantherae Fructus by high-speed counter-current chromatography

A high-speed counter-current chromatography （HSCCC） method was successfully developed for the preparative separation and purification of deoxyschizandrin from Schisandrae Sphenantherae Fructus in one step. The purity of deoxyschizandrin was 98.5%, and the structure was identified by MS, UV and NMR. This method was simple, fast, convenient and appropriate to prepare pure compound as reference substances for related research on Schisandrae Sphenantherae Fmctus.

5-Hydroxymethylfurfural from wine-processed Fructus corni inhibits hippocampal neuron apoptosis

Previous studies have shown that 5-hydroxymethylfurfural, a compound extracted from wine- processed Fructus corni, has a protective effect on hippocampal neurons. The present study was designed to explore the related mechanisms. Our study revealed that high and medium doses （10, 1 μmol/L） of 5-hydroxymethylfurfural could improve the morphology of H2O2-treated rat hippocampal neurons as revealed by inverted phase-contrast microscopy and transmission electron microscopy. MTT results showed that incubation with high and medium doses of 5-hydroxymethylfurfural caused a significant increase in the viability of neuronal cells injured by H2O2. Flow cytometry assays con- firmed that H2O2 could induce cell apoptosis, while high and medium doses of 5-hydroxymethylfurfural had a visible protective effect on apoptotic rat hippocampal neurons. Real-time PCR and western blot analysis showed that high and medium doses of 5-hydroxymethylfurfural prevented H2O2-induced up-regulation of p53, Bax and caspase-3 and an- tagonized the down-regulation of Bcl-2 induced by H2O2 treatment. These results suggested that 5-hydroxymethylfurfural could inhibit apoptosis of cultured rat hippocampal neurons injured by H2O2 via increase in Bcl-2 levels and decrease in p53, Bax and caspase-3 protein expression levels.