OBJECTIVE: To investigate the protective effect against intestinal mucosal injury in rats following traumatic brain injury (TBI) and explore the underlying mechanism. METHODS: SD rat models of TBI were established by fluid percussion injury (FPI), and the specimens were collected at 12, 24, 48, and 72 h after TBI. Another 15 rats were randomly divided into shamoperated group (n=5), TBI with saline treatment (TBI+NS) group (n=5), and TBI with PD treatment (TBI+PD) group (treated with 30 mg/kg PD after TBI; n=5). Body weight gain and fecal water content of the rats were recorded, and after the treatments, the histopathology of the jejunum was observed, and the levels of D-lactic acid (D-LAC), diamine oxidase (DAO), ZO-1, claudin-5, and reactive oxygen species (ROS) were detected. Lipid peroxide (LPO) and superoxide dismutase (SOD) 2 content, jejunal pro-inflammatory factors (IL-6, IL-1β, and TNF- α), Sirt1 activity, SOD2 and HMGB1 acetylation level were also determined after the treatments. RESULTS: The rats showed significantly decreased body weight and fecal water content and progressively increased serum levels of D-LAC and DAO after TBI (P < 0.05) with obvious jejunal injury, significantly decreased expression levels of ZO-1 and claudin-5, lowered SOD2 and Sirt1 activity (P < 0.05), increased expression levels of LPO, ROS, and pro-inflammatory cytokines, and enhanced SOD2 and HMGB1 acetylation levels (P < 0.05). Compared with TBI+NS group, the rats in TBI+PD group showed obvious body weight regain, increased fecal water content, reduced jejunal pathologies, decreased D-LAC and DAO levels (P < 0.05), increased ZO-1, claudin-5, SOD2 expression levels and Sirt1 activity, and significantly decreased ROS, LPO, pro-inflammatory cytokines, and acetylation levels of SOD2 and HMGB1 (P < 0.05). CONCLUSION PD alleviates oxidative stress and inflammatory response by activating Sirt1-mediated deacetylation of SOD2 and HMGB1 to improve intestinal mucosal injury in TBI rats.
Animals ; Brain Injuries, Traumatic ; Glucosides/pharmacology* ; HMGB1 Protein/metabolism* ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Stilbenes/pharmacology* ; Superoxide Dismutase/metabolism*

OBJECTIVES: To explore the effect of polydatin on the proliferation and apoptosis of acute monocytic leukemia cell line THP-1 and the possible mechanism. METHODS: After THP-1 cells were treated with polydatin at gradient concentrations for 24 hours and 48 hours, their proliferation was determined by CCK-8 assay, and half maximal inhibitory concentration (IC50) was calculated. Logarithmically growing THP-1 cells were divided into two groups, a polydatin treatment group (treated with IC50 of polydatin) and a blank control group (treated without polydatin solution), and incubated for 48 hours. Cell apoptosis and cell cycle were measured by flow cytometry. The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins were measured by Western blotting. RESULTS: After treatment with polydatin, the proliferation of THP-1 cells was strongly inhibited, and the IC50 at 48 hours was 1 800 μmol/L. After treatment with 1 800 μmol/L polydatin solution for 48 hours, the apoptosis rate of THP-1 cells increased significantly compared with the blank control group (P<0.05). The cell cycle was arrested in the G₀/G₁ and S phases, with a significantly increased proportion of cells in the G₀/G₁ phase and a significantly decreased proportion of cells in the S phase, as compared with the blank control group (P<0.05). The expression levels of PI3K, AKT, p-AKT, mTOR, p-mTOR, p70 S6K, and p-p70 S6K proteins decreased significantly compared with the blank control group (P<0.05). CONCLUSIONS Polydatin can effectively inhibit the proliferation, block the cell cycle, and induce the apoptosis of THP-1 cells, which may be related to inhibition of the PI3K/AKT/mTOR signaling pathway.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Glucosides/pharmacology* ; Humans ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Signal Transduction ; Stilbenes/pharmacology* ; THP-1 Cells ; TOR Serine-Threonine Kinases

A novel β-glucosidase BglD2 with glucose and ethanol tolerant properties was screened and cloned from the deep-sea bacterium Bacillus sp. D1. The application potential of BglD2 toward polydatin-hydrolyzing was also evaluated. BglD2 exhibited the maximal β-glucosidase activity at 45 °C and pH 6.5. BglD2 maintained approximately 50% of its origin activity after incubation at 30 °C and pH 6.5 for 20 h. BglD2 could hydrolyze a variety of substrates containing β (1→3), β (1→4), and β (1→6) bonds. The activity of β-glucosidase was enhanced to 2.0 fold and 2.3 fold by 100 mmol/L glucose and 150 mmol/L xylose, respectively. BglD2 possessed ethanol-stimulated and -tolerant properties. At 30 °C, the activity of BglD2 enhanced to 1.2 fold in the presence of 10% ethanol and even remained 60% in 25% ethanol. BglD2 could hydrolyze polydatin to produce resveratrol. At 35 °C, BglD2 hydrolyzed 86% polydatin after incubation for 2 h. Thus, BglD2 possessed glucose and ethanol tolerant properties and can be used as the potential candidate of catalyst for the production of resveratrol from polydatin.
Enzyme Stability ; Glucose ; Glucosides/pharmacology* ; Hydrogen-Ion Concentration ; Stilbenes/pharmacology* ; Substrate Specificity ; Temperature ; Xylose ; beta-Glucosidase/genetics*

OBJECTIVES: To study the antitumor effect of piceatannol (PIC) on malignant melanoma METHODS: B16F10 cells were cultured RESULTS: The cell viability of B16F10 decreased with increasing PIC concentration. The results of the Transwell assay showed that invasion ability decreased with increasing PIC concentration, and healing time was prolonged at increased PIC concentration in the wound healing assay. Western blot results showed that PIC mainly inhibited the phosphorylation of Syk and inhibited the expression of MMP-2, MMP-9, and VEGF. RNA interference pointed out that blocking the expression of Syk can reveal the same inhibition effect on B16F10 cells as PIC. CONCLUSIONS PIC might block the progression of malignant melanoma by inhibiting spleen tyrosine kinase.
Animals ; Cell Line, Tumor ; Cell Movement ; Matrix Metalloproteinase 2 ; Matrix Metalloproteinase 9 ; Melanoma/drug therapy* ; Mice ; Neoplasm Invasiveness ; Stilbenes/pharmacology* ; Syk Kinase ; Vascular Endothelial Growth Factor A

Animals ; Diabetes Mellitus, Experimental/drug therapy* ; Fibrosis/prevention & control* ; Hyperglycemia/prevention & control* ; Hypoglycemic Agents/pharmacology* ; Inflammation/prevention & control* ; Male ; Rats ; Rats, Sprague-Dawley ; Stilbenes/pharmacology*

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Dyslipidemias ; drug therapy ; Glycemic Load ; drug effects ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Specific Pathogen-Free Organisms ; Stilbenes ; pharmacology

Antifungal drug resistance is a significant clinical problem, and antifungal agents that can evade resistance are urgently needed. In infective niches, resistant organisms often co-existed with sensitive ones, or a subpopulation of antibiotic-susceptible organisms may evolve into resistant ones during antibiotic treatment and eventually dominate the whole population. In this study, we established a co-culture assay in which an azole-resistant Candida albicans strain was mixed with a susceptible strain labeled with green fluorescent protein to mimic in vivo conditions and screen for antifungal drugs. Fluconazole was used as a positive control to verify the validity of this co-culture assay. Five natural molecules exhibited antifungal activity against both susceptible and resistant C. albicans. Two of these compounds, retigeric acid B (RAB) and riccardin D (RD), preferentially inhibited C. albicans strains in which the efflux pump MDR1 was activated. This selectivity was attributed to greater intracellular accumulation of the drugs in the resistant strains. Changes in sterol and lipid compositions were observed in the resistant strains compared to the susceptible strain, and might increase cell permeability to RAB and RD. In addition, RAB and RD interfered with the sterol pathway, further aggregating the decrease in ergosterol in the sterol synthesis pathway in the MDR1-activated strains. Our findings here provide an alternative for combating resistant pathogenic fungi.
ATP-Binding Cassette Transporters ; genetics ; metabolism ; Antifungal Agents ; chemistry ; metabolism ; pharmacology ; Azoles ; pharmacology ; Biosynthetic Pathways ; drug effects ; genetics ; Candida albicans ; chemistry ; drug effects ; metabolism ; Cell Membrane ; chemistry ; metabolism ; Coculture Techniques ; Drug Resistance, Fungal ; drug effects ; Ergosterol ; metabolism ; Fungal Proteins ; genetics ; metabolism ; Lipids ; chemistry ; Molecular Structure ; Permeability ; Phenyl Ethers ; chemistry ; metabolism ; pharmacology ; Sterols ; chemistry ; metabolism ; Stilbenes ; chemistry ; metabolism ; pharmacology ; Triterpenes ; chemistry ; metabolism ; pharmacology

Pterostilbene (3,5-dimethoxy-4'-hydroxystilbene) is a polyphenolic compound primarily found in blueberries, grapes, and a tree wood, pterocarpus marsupium. Studies demonstrate that pterostilbene inhibits a variety of cancers, such as lung, breast, stomach, colon, etc. The anti-cancer activities are related to the regulation of several hallmarks of cancer. Moreover, pterostilbene exhibits much greater bioavailability and bioactivity than resveratrol which warrants further investigation in the anti-cancer functions and mechanisms.
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Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; Humans ; Neoplasms ; drug therapy ; Plant Extracts ; chemistry ; pharmacology ; Stilbenes ; chemistry ; pharmacology

OBJECTIVETo investigate the host-defense role of short palate, lung, and nasal epithelium clone 1 (SPLUNC1) in Streptococcus pneumoniae (SP) infection and the effect of resveratrol (Res) on SPLUNC1 expression, and to provide new thoughts for the treatment of diseases caused by SP infection.

METHODSAccording to the multiplicity of infection (MOI), BEAS-2B cells with SP infection were divided into control group, MOI20 SP group, and MOI50 SP group. According to the different concentrations of Res, the BEAS-2B cells with MOI20 SP infection pretreated by Res were divided into 12.5Res+SP group, 25Res+SP group, and 50Res+SP group (the final concentrations of Res were 12.5, 25, and 50 μmol/L, respectively). Cell Counting Kit-8 was used to measure cell activity and determine the optimal concentration and action time of SP and Res. In the formal experiment, the cells were divided into control group, Res group, SP group, and Res+SP group. Real-time PCR and ELISA were used to measure the mRNA and protein expression of SPLUNC1.

RESULTSOver the time of SP infection, cell activity tended to decrease. Compared with the control group and the MOI20 SP group, the MOI50 SP group had a reduction in cell activity. Compared with the MOI20 SP group, the 25Res+SP group had increased cell activity and the 50Res+SP group had reduced cell activity (P<0.05). MOI20 SP bacterial suspension and 25 μmol/L Res were used for the formal experiment. Over the time of SP infection, the mRNA expression of SPLUNC1 in BEAS-2B cells firstly increased and then decreased in the SP group and the Res+SP group (P<0.05). Compared with the SP group, the Res+SP group had significant increases in the mRNA and protein expression of SPLUNC1 at all time points (P<0.05). Compared with the control group, the Res group had no significant changes in the mRNA and protein expression of SPLUNC1 (P>0.05).

CONCLUSIONSSP infection can induce SPLUNC1 expression and the host-defense role of SPLUNC1. Res can upregulate SPLUNC1 expression during the development of infection and enhance cell protection in a concentration- and time-dependent manner.

Bronchi ; metabolism ; Cells, Cultured ; Cytoprotection ; Epithelial Cells ; metabolism ; Glycoproteins ; analysis ; genetics ; physiology ; Humans ; Phosphoproteins ; analysis ; genetics ; physiology ; RNA, Messenger ; analysis ; Stilbenes ; pharmacology ; Streptococcus pneumoniae ; pathogenicity

The present study aimed to study lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system. Zebrafish were fed with high fat diet to establish a hyperlipemia model, then fasted and bathed with seven traditional Chinese medicine monomers stigmasterol, triacontanol, chrysophanol, vanillic acid, shikimic acid, polydatin and oleanolic acid respectively. The oil red O staining was used to detect the blood lipids of zebrafish. Serum total cholesterol and triglyceride levels were detected to validate the lipid-lowering effect. The result showed that a zebrafish model of hyperlipemia could be established by feeding larvae zebrafish with high fat diet. Among the seven traditional Chinese medicine monomers, chrysophanol had lipid-lowering effect. Chrysophanol significantly reduced serum total cholesterol and triglyceride levels in adult zebrafish fed with high fat diet. Chrysophanol accelerated peristalsis frequency of zebrafish intestine and the excretion of high fat food. It is concluded that chrysophanol has lipid- lowering effect in zebrafish, and the mechanism of the effect may be due to the roles of chrysophanol in reducing lipid absorption from gastrointestinal tract and accelerating the excretion of food.
Animals ; Anthraquinones ; pharmacology ; Diet, High-Fat ; Fatty Alcohols ; pharmacology ; Glucosides ; pharmacology ; Hyperlipidemias ; drug therapy ; Hypolipidemic Agents ; pharmacology ; Larva ; Lipids ; blood ; Medicine, Chinese Traditional ; Oleanolic Acid ; pharmacology ; Shikimic Acid ; pharmacology ; Stigmasterol ; pharmacology ; Stilbenes ; pharmacology ; Vanillic Acid ; pharmacology ; Zebrafish