Effect of Quzhi Ruangan prescription on the farnesoid X receptor-fibroblast growth factor 19 pathway in rats with nonalcoholic steatohepatitis / 临床肝胆病杂志

Objective To investigate the effect of Quzhi Ruangan prescription on the farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) pathway in rats with nonalcoholic steatohepatitis (NASH). Methods Male Sprague-Dawley rats were randomly divided into normal group (Control group with 8 rats), model group (HFD group with 12 rats), simvastatin group with 8 rats, high-dose Quzhi Ruangan prescription group (QH group with 8 rats), and low-dose Quzhi Ruangan prescription group (QL group with 8 rats). The rats in the Control group were fed with a normal diet and those in the other groups were fed with a high-fat diet. Related samples were collected at the end of week 10 to observe liver pathological changes and measure the serum levels of liver function parameters, the level of FGF19 in the liver and the small intestine, and the level of bile acid (BA) in the liver. The expression levels of FXR in the small intestine and cholesterol 7α-hydroxylase (CYP7A1) in the liver were also measured. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison bewteen two groups. Results Compared with the Control group, the HFD group showed the pathological manifestations of marked inflammatory lesions and steatosis. Compared with the HFD group, all administration groups had a significant increase in high-density lipoprotein cholesterol and significant reductions in alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, and low-density lipoprotein cholesterol (all P < 0.05). Compared with the Control group, the HFD group had a significant reduction in FGF19 in the small intestine and a significant increase in BA in the liver (both P < 0.05). Compared with the HFD group, all administration groups had a significant increase in FGF19 in the small intestine and a significant reduction in BA in the liver (all P < 0.05). Compared with the Control group, the HFD group had a significant reduction in the mRNA expression of FXR in the small intestine and a significant increase in the mRNA expression of CYP7A1 in the liver (both P < 0.05). Compared with the HFD group, the QH group had a significant increase in the mRNA expression of FXR in the small intestine, while the QL group had a significant reduction (both P < 0.05), and the QH group had a significant reduction in the mRNA expression of CYP7A1 in the liver ( P < 0.05). Compared with the Control group, the HFD group had a significant reduction in the positive rate of FXR in the small intestine and a significant increase in the positive rate of CYP7A1 in the liver (both P < 0.05). Compared with the HFD group, the simvastatin group and the QH group had a significant increase in the positive rate of FXR in the small intestine (both P < 0.05), and the simvastatin group, the QH group, and the QL group had a significant reduction in the positive rate of CYP7A1 in the liver (all P < 0.05). Conclusion Quzhi Ruangan prescription can activate the FXR-FGF19 pathway in NASH rats and may exert a preventive and therapeutic effect on NASH through this pathway.

Effect of Shuangyu Tiaozhi Decoction on SRB1/CYP7A1/FXR Signaling Pathway in Liver of Hypercholesterolemic Rats / 中国实验方剂学杂志

Objective:To observe the effect of Shuangyu Tiaozhi decoction on B-type scavenger receptor （SRB1）/cholesterol 7<italic>α</italic>-hydroxylase protein （CYP7A1）/farnesol X receptor （FXR） signaling pathway in liver of hypercholesterolemic rats， and its mechanism in reducing blood lipid. Method:Among 40 SD rats， 8 were randomly selected as normal group， and the remaining 32 were successfully established as hypercholesterolemic model， and randomly divided into 4 groups： model group， low and high-dose Shuangyu Tiaozhi decoction groups （7.8， 15.6 g·kg^-1）， and simvastatin group （4 mg·kg^-1）， with 8 rats in each group. The drugs were continuously given for 8 weeks. Serum total cholesterol （TC）， triglyceride （TG） and liver TC，free cholesterol （FC） and total bile acid （TBA） were measured. The pathomorphological changes in liver were observed by Hematoxylin and eosin （HE） Staining. The mRNA and protein expressions of SRB1， CYP7A1 and FXR were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. The immunohistochemistry was used to detect CYP7A1 and FXR expressions in liver. Result:Compared with the normal group， TC， TG， FC levels in the model group were significantly increased， while the TBA level was markedly decreased， the morphology showed obvious liver steatosis， and significant declines in expressions of SRB1， CYP7A1， FXR were observed by Real-time PCR， Western blot and immunohistochemistry assays （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the levels of TC，TG，FC in each treatment group were reduced significantly， and the TBA level was increased markedly， the liver steatosis decreased significantly， the results of Real-time PCR， Western blot and immunohistochemistry assays showed significant increase in the expressions of SRB1， CYP7A1， FXR （<italic>P</italic><0.05， <italic>P</italic><0.01）. The therapeutic effect of high-dose Shuangyu Tiaozhi decoction group was more remarkable than that in low-dose Shuangyu Tiaozhi Decoction group （<italic>P</italic><0.05）， with no obvious difference compared with simvastatin group. Conclusion:Shuangyu Tiaozhi decoction can promote hepatic RCT and synthesize bile acid by up-regulating SRB1/CYP7A1/FXR signaling pathway， so as to reduce the blood lipid levels and improve hepatic lipid metabolism of hypercholesterolemic rats.

Mechanism of action of bile acid-farnesoid X receptor-intestinal microecological axis in the development of liver failure and liver regeneration / 临床肝胆病杂志

Liver failure is a common critical medical disease, and extensive liver cell necrosis within a short period of time exceeds the regeneration capacity of liver cells and thus results in an extremely high fatality rate. Promotion of effective liver regeneration is the key to antagonizing liver failure. Recent studies have shown that bile acid, farnesoid X receptor (FXR), and intestinal microecology play an important role in liver failure and liver regeneration. This article reviews the association between bile acid, FXR, and intestinal microecology and their role in liver failure and liver regeneration, so as to provide new ideas for the treatment of liver failure in clinical practice.

Reinforcement of Rhodobacter sphaeroides cofactor NADPH to increase the production of farnesol / 生物工程学报

Farnesol (FOH) is produced by dephosphorylation of farnesyl diphosphate (FPP) derived from two universal building blocks, dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP). In Rhodobacter sphaeroides these building blocks are generated by MEP pathway, however, many of the biosynthetic reactions and biotransformations in the MEP pathway are limited by low availability of NADPH. Improvement of the amount of intracellular NADPH may enhance the synthesis of FOH. In this study, we utilized the strategies of increasing the production of NADPH and decreasing the consumption of NADPH. The expression of glucose 6-phosphate isomerase (pgi) and glutamate dehydrogenase (gdhA) were inhibited by RNA interference, respectively, and overexpression of 6-glucose phosphate dehydrogenase (zwf) and 6-glucose phosphate dehydrogenase (gnd) in the pentose phosphate pathway were carried out. The results showed that the content of NADPH in the recombinant strains increased significantly, the highest FOH production of RSpgii in the RNA interfered strain was 3.91 mg/g, and the FOH production increased to 3.43 mg/g after zwf gene and gnd gene has been overexpressed. In order to obtain strains with higher FOH production, we used RSpgii as the starting strain, and zwf, gnd and co-overexpressed zwf + gnd gene were overexpressed in RSpgii, respectively. The highest FOH production of the strain RSzgpi reached to 4.48 mg/g which was 2.24 times that of the starting strain RS-GY2.

Mechanism of action of intestinal farnesoid X receptor in nonalcoholic fatty liver disease and related targeted drugs / 临床肝胆病杂志

The incidence rate of nonalcoholic fatty liver disease (NAFLD) is gradually increasing in recent years, and the treatment of NAFLD is unsatisfactory due to the failure in lifestyle adjustment and a lack of effective drugs. Farnesoid X receptor (FXR), as the main bile acid receptor, may affect NAFLD by participating in glucose and fat metabolism, and intestinal FXR (iFXR) acts on the intestinal tract alone and may thus avoid the side effects of systemic release. Therefore, it may have potential value in the treatment of NAFLD, but there are also certain controversies. This article reviews the research advances in the role of iFXR in NAFLD.

Role of farnesol X receptor in glycolipid metabolism regulation / 上海交通大学学报（医学版）

Farnesol X receptor (FXR), also known as bile acid nuclear receptor, is a ligand-dependent nuclear transcription factor distributed in multiple tissues and organs such as liver and intestinal tract. And bile acid is its endogenous natural ligand. Recent studies have shown that intestinal FXR plays an indispensable role in glycolipid metabolism regulation, and intestinal specific FXR agonists or antagonists can participate in glucose and lipid metabolism regulation in vivo. In this paper, the role of intestinal FXR in glycolipid metabolism reported in recent years is systematically reviewed.

Systematic analysis of protein expression in Candida albicans exposed to farnesol / 中华医学杂志(英文版)

Background@#The phenotypic switching of Candida spp. plays an important role in the development of vulvovaginal candidiasis (VVC). Farnesol, as a quorum-sensing molecule in Candida albicans, has the ability to prevent yeast-to-hyphal conversion in vitro. However, the mechanism underlying this ability is unclear. This study aimed to investigate changes in protein levels to better understand how farnesol impacts processes contributing to VVC.@*Methods@#The isobaric tag for relative and absolute quantitation technique was used to detect protein expression in C. albicans strain SC5314 (ATCC MYA-2876) with or without farnesol exposure. Proteins with a threshold fold change greater than 1.5 were screened and considered differentially expressed proteins. All the altered proteins were analyzed using Gene Ontology annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, and metabolic pathway annotation.@*Results@#Between the farnesol-exposed group and the farnesol-unexposd group, we detected 297 altered proteins among all 2047 tested proteins based on a threshold fold change of more than 1.5 (P < 0.05). Eighty-seven of the 297 altered proteins exhibited metabolic enzyme activity and participated in 85 metabolic pathways according to KEGG pathway analysis. Most of these metabolic pathways were associated with central carbon metabolism processes. In the sterol synthesis pathway, which involves the synthesis of farnesol, ERG25 (methylsterol monooxygenase) and ERG4 (delta 24(24(1))-sterol reductase) were both down-regulated in the farnesol-exposed group. All six altered proteases associated with the oxidative phosphorylation process were down-regulated in the farnesol-exposed group relative to the farnesol-unexposed group.@*Conclusions@#The mechanisms underlying farnesol-induced phenotype switching involves the adjustment of metabolic activities and epigenetic modification. Exogenous farnesol had an evident, but non-deterministic effect on the synthesis of ergosterol. The potential drug activity of farnesol warrants further investigation.

Production of farnesol in Candida albicans biofilms of resistant and standard strains in different media / 中华皮肤科杂志

Objective To compare the production of farnesol between Candida albicans (C.albicans) biofilms formed by resistant and standard strains in different media,and to investigate the changing trend of farnesol production in different phases of biofilm formation and the features of farnesol production by resistant C.albicans.Methods Fluconazole-resistant C.albicans strains were induced in vitro.Standard strains and fluconazole-resistant strains of C.albicans were separately inoculated onto different media,including RPMI 1640 medium,yeast extract peptone dextrose (YPD) medium,yeast nitrogen base (YNB) + 0.5％ glucose medium,RPMI 1640 + 10％ fetal calf serum (FCS),so as to form C.albicans biofilms.Morphological changes of C.albicans biofilms at 24 hours were observed under an inverted microscope,and gas chromatography-mass spectrometry (GC/MS)was performed to detect the level of farnesol at 1.5,3,6,12,24,36 and 48 hours.Results There were no obvious differences in the morphology of C.albicans biofilms between the resistant and standard strains when they were cultured in the same medium,while the morphology of C.albicans biofilms markedly differed between the 2 kinds of strains in the different media.Three-factor analysis of variance showed that the production of farnesol in the C.albicans biofilms changed over time (F =70.628,P ＜ 0.001).Concretely speaking,during the formation of resistant and standard C.albicans biofilms,the production of farnesol gradually increased in the RPMI 1640,YPD and YNB + 0.5％ glucose media until the biofilms matured,then showed a decreasing trend.However,the time to peak levels of farnesol was different between the 2 kinds of strains in these media.Moreover,the levels of farnesol in the 2 kinds of strains both slowly increased in the RPMI 1640 + 10％ FCS medium within 12-48 hours.Culture media also significantly affected the production of farnesol (F =176.665,P ＜ 0.001),and the levels of farnesol in the resistant and standard C.albicans biofilms were both higher in the YNB + 0.5％ glucose medium.When resistant and standard strains were separately cultured in the RPMI 1640 media and the YPD media,the level of farnesol was significantly higher in the resistant strains than in the standard stains (RPMI 1640 media at 36 hours:1.157 ± 0.064 vs.0.250 ± 0.075,P ＜ 0.05;YPD media at 6 hours:0.262 ± 0.036 vs.0.055 ± 0.062,P ＜ 0.05;YPD media at 12 hours:0.730 ± 0.030 vs.0.482 ± 0.024,P ＜ 0.05).However,when they were separately cultured in the YNB + 0.5％ glucose media,the farnesol level was significantly higher in the standard stains than in the resistant strains (36 hours:2.950 ± 0.677 vs.0.523 ± 0.266,P =0.020).Conclusion The media markedly affect the production of farnesol in the C.albicans biofilms,and there is a certain difference in the production of farnesol between resistant and standard C.albicans strains.

GC fingerprint of volatile components in Qishen Yiqi Dropping Pills / 中草药

Objective :To establish the GC fingerprint of Qishen Yiqi Dropping Pills(QYDP)and Dalbergiaodorifera oiland identify the common chromatographic peaks by GC-MS. Methods: The GC analysis was performed on an Agilent HP-INNOWaxcapillary gas chromatography column (30 m × 0.25 mm, 0.25 μm). The temperature program was as follows: 100 ℃ for 2 min, 160 ℃ at 3 ℃/min, 190 ℃ at 1 ℃/min, 220 ℃ at 5 ℃/min, then 250 ℃ at 10 ℃/min; Nitrogen was used as the carrier gas with its flow rate 0.5 mL/min; The sample injection temperature was 250 ℃ and the split ratio was 5:1; The detector was FID with its temperature of 300 ℃. MS parameters: MS electron energy of 70 eV, ion source temperature of 230 ℃, full-ion scan mass rangem/z 35-600, solvent delay for 8 min. Results: Thirty-three common peaks were found from QYDP and 25 common peaks were found from D.odorifera oil in their GC fingerprints. Twenty-three common peaks in the fingerprint ofD.odorifera oil,such as trans-nerolidol,3,7,11-trimethyl-3,6-epoxy-1,10-dodecadien-7-ol isomers, farnesol isomers, α-santalene, norbornane, andβ-bisabolene were identified. The similarity of all batches of QYDP and D.odorifera oil were both over 0.979. Conclusion: This method is simple and reliable and can be used to evaluate the quality of QYDP and D.odorifera oil.

Efeito inibitório in vitro do composto farnesol frente ao biofilme de Burkholderia pseudomallei

A intrínseca resistência apresentada pela bactéria Burkholderia pseudomallei é um grave empecilho para o tratamento da melioidose. Muitas pesquisas focam na busca de adjuvantes que aumentem a sensibilidade desta bactéria aos antimicrobianos. Nesse contexto, a açãoinibitória do farnesol frente às cepas de B. pseudomallei, na forma planctônica, já foi relatadaem estudo prévio. Diante disso, esse estudo objetivou analisar a atividade in vitro do farnesol contra cepas de B. pseudomallei na forma de biofilme. Aliado à análise da ação do farnesolisoladamente, foi investigada a combinação desse composto com os antimicrobianosamoxicilina, ceftazidima, doxiciclina, imipenem e sulfametoxazol/trimetoprim frente a obiofilme. A sensibilidade foi avaliada por meio do teste de microdiluição em caldo e a leiturada viabilidade celular feita com a resazurina. A concentração inibitória mínima em biofilme(CEMB) para o farnesol foi de 75 a 2400 mM. Ademais, o farnesol reduziu em até 256, 16, 4e 4 vezes os valores de CEMB para ceftazidima, amoxicilina, doxiciclina esulfametoxazol/trimetoprim, respectivamente (P<0.05). Por meio de técnicas de microscopia,tais como óptica, confocal e eletrônica, observou-se que o farnesol foi capaz de causar danosna matriz do biofilme, facilitando assim, a penetração dos antibióticos. Deste modo, opresente estudo mostrou a eficácia do farnesol contra biofilmes de B. pseudomallei e seuefeito potenciador, em especial com ceftazidima, amoxicilina, doxiciclina esulfametoxazol/trimetoprim.

The intrinsic antimicrobial resistance of Burkholderia pseudomallei is a serious challenge tothe treatment of melioidosis. Many studies have searched for adjuvants that increasesusceptibility bacteria to antimicrobials. In this context, the antimicrobial activity of farnesolagainst B. pseudomallei in planktonic growth has been reported. Thus, the aim of this studywas to analyze the in vitro activity of farnesol alone against Burkholderia pseudomalleibiofilms, as well as its combination with the antibacterials amoxicillin, doxycycline,ceftazidime and sulfamethoxazole-trimethoprim. Susceptibility was assessed by the brothmicrodilution test and cell viability was read with the oxidation-reduction indicator dyeresazurin. The interaction between farnesol and antibacterial drugs against B. pseudomalleibiofilms was evaluated through the calculation of the fractional inhibitory concentrationindex. The minimum biofilm erradication concentration (MBEC) for farnesol was 75 to 2400mM. In addition, farnesol significantly reduced the MBEC values for ceftazidime,amoxicillin, doxycycline and sulfamethoxazole-trimethoprim by 256, 16, 4 and 4 timesrespectively (P<0.05). Optical, confocal and electronic microscopic analyses of farnesoltreatedB. pseudomallei biofilms demonstrated that this compound damages biofilm matrix,facilitating antimicrobial penetration in the biofilm structure. This study demonstrated theeffectiveness of farnesol against B. pseudomallei biofilms and its potentiating effect on theactivity of antibacterial drugs, in particular ceftazidime, amoxicillin, doxycycline andsulfamethoxazole-trimethoprim.

The function of Farnesol in formation of Staphylococcus epidermidis-Candida albicans mixed species biofilms / 西安交通大学学报(医学版)

(P < 0.05 ).Scanning electron microscopy showed that the three-dimensional structure of mix-biofilm in control group was more complex.As real-time PCR showed,after 6-hour culture,the expressions of icaA,fbe,aap,hwp1, als3 and efg1 genes in Farnesol group were down-regulated compared to those in control group and after 24-hour culture the expressions of aap,hwp1,als3 and efg1 genes in Farnesol group were down-regulated compared to those in control group.Conclusion With the intervention by fungal quorum sensing molecules Farnesol,the structure in control group became denser and more complex than that in Farnesol group.This change may have a closer correlation with the down-regulated expressions of als3,hwp1 and efg1 genes,which are related to the formation of Candida albicans biofilms.

Farnesol Sensitivity of Serum Induced Yeast to Hyphae Morphogenesis: A Study on Fifty Clinical Isolates of Candida albicans.

Aim: Objective of this study was to examine farnesol sensitivity of yeast to hyphae dimorphism in clinical isolates of Candida albicans. Study Design: Variations in virulence attributes contribute to variations in pathogenicity of C. albicans. Ability to switch from yeast to hyphae morphology is an important virulence factor. Farnesol, a quorum sensing molecule is known to play an important role in the regulation of C. albicans morphogenesis. Analysis of farnesol susceptibility of yeast to hyphae conversion may reveal a factor responsible for variation in pathogenicity among clinical isolates of C. albicans. Place and Duration of Study: SCG Medical College & SGGS Memorial Hospital, and School of Life Sciences, SRTM University, Nanded, India. Duration of this study was, December 2008 to December 2010. Methodology: Fifty clinical isolates of C. albicans were recovered from body fluids (such as, sputum, blood, urine, vaginal swab, tracheal swab, throat swab, feces, pus and cerebrospinal fluid, etc.) of patients with different clinical manifestations, in the tertiary care center hospital. Presumptive identification of C. albicans was done on HiCHROM agar- Candida, while confirmation was done by Germ tube formation assay, Carbohydrate assimilation and Corn meal agar test. Serum induced yeast to hyphae morphogenesis in C. albicans was performed in 96 well plates. Recent methodology of micro broth dilution was used for farnesol susceptibility testing in fifty clinical isolates. Results: Farnesol prevented hyphae formation in a concentration dependent manner, in the range 25 to 400 μM. Inhibition of ≥ 50% hyphae was considered as significant reduction in morphogenesis. MIC70 for farnesol mediated inhibition of morphogenesis in C. albicans was at 200 μM. Mean values for percentage inhibition of morphogenesis in fifty strains was compared by analysis of variance (ANOVA). P = 0.05 was considered significant. Conclusion: Susceptibility of yeast to hyphae morphogenesis to the quorum sensing molecule farnesol, varied significantly among clinical isolates of C. albicans. We hypothesize that variation in farnesol sensitivity may be a factor responsible for variable dissemination and infection ability of C. albicans.

Biofilm biomass disruption by natural substances with potential for endodontic use

This study evaluated the in vitro effects of four natural substances on the biomass of bacterial biofilms to assess their potential use as root canal irrigants. The following substances and their combinations were tested: 0.2% farnesol; 5% xylitol; 20% xylitol; 0.2% farnesol and 5% xylitol; 0.2% farnesol, 5% xylitol, and 0.1% lactoferrin; 5% xylitol and 0.1% lactoferrin; and 20 mM salicylic acid. The crystal violet assay was used to evaluate the effects of these substances on the biomass of biofilms formed by Enterococcus faecalis and Staphylococcus epidermidis. All substances except for 20 mM salicylic acid and 20% xylitol reduced biofilm mass when compared to controls. The combination of farnesol and xylitol was the most effective agent against E. faecalis ATCC 29212 (p < 0.05). Farnesol combined with xylitol and lactoferrin was the most effective against biofilms of the endodontic strain of E. faecalis MB35 (p < 0.05). Similarly, combinations involving farnesol, xylitol, and lactoferrin reduced the biomass of S. epidermidis biofilms. In general, farnesol, xylitol, and lactoferrin or farnesol and xylitol reduced biofilm biomass most effectively. Therefore, it was concluded that combinations of antibiofilm substances have potential use in endodontic treatment to combat biofilms.

Study on the transcription profiling of biofilm formation by Candida albicans at different phases exposed to tyrosol and farnesol / 中华微生物学和免疫学杂志

Objective To investigate the effects of tyrosol and farnesol on the transcription profiling of C.albicans biofilm by microarray analysis.Methods The standard strain of C.albicans,SC5314 were cultured into four groups (tyrosol treated,farnesol treated,tyrosol and farnesol co-treated,and untreated control).The cell suspensions of SC5314 were prepared and dispensed into polystyrene flasks to form biofilm.Then,the biofilms were collected at 6 h and 24 h respectively after culturing.RNA samples were extracted and synthesized into cDNA through reverse transcription.The genome arrays were scanned with a confocal LuxScanTM scanner and the images were then analyzed by using LuxScanTM 3.0 software (both from CapitalBio).Bioinformatics analysis of the data was carried out by comparatively analyzing S.cerevisiae gene in KEGG gene database.Results The cDNA microarray data showed that tyrosol and farnesol regulated biofilm formation by regulating the genes associated with biofilm formation such as hypha genes and yeast genes.Tyrosol positively regulated gene expression of C.albicans biofilm,while farnesol played negative role.There were striking differences in gene expression patterns between tyrosol or farnesol treated groups and the control.Tyrosol had no antagonistic effect to farnesol.Bioinformatics analysis showed that the differential gene expression was involved in biological process,molecular function process and cell component formation.These genes regulated the C.albicans biofilm formation by encoding proteins involved in the biological metabolism.Conclusion Tyrosol and farnesol influenced the formation of C.albicans biofilm through regulating gene expression which showed differences at different phases of biofilm formation.

Farnesol in combination with N-acetylcysteine against Staphylococcus epidermidis planktonic and biofilm cells

Staphylococcus epidermidis is the most frequent cause of nosocomial sepsis and catheter-related infections, in which biofilm formation is considered to be the main virulence mechanism. In biofilm environment, microbes exhibit enhanced resistance to antimicrobial agents. This fact boosted the search of possible alternatives to antibiotics. Farnesol and N-acetylcysteine (NAC) are non-antibiotic drugs that have demonstrated antibacterial properties. In this study, the effect of farnesol and NAC isolated or in combination (farnesol+NAC) was evaluated. NAC at 10 × MIC caused a total cell death in planktonic cells. On the other hand, S. epidermidis biofilms exhibited 4 log reduction in viable cell number after a 24h treatment with NAC at the former concentration. Our results demonstrated that there was a higher CFU log reduction of S. epidermidis planktonic cells when farnesol was combined with NAC at 1 × MIC relatively to each agent alone. However, these results were not relevant because NAC alone at 10 × MIC was always the condition which gave the best results, having a very high killing effect on planktonic cells and a significant bactericidal effect on biofilm cells. This study demonstrated that no synergy was observed between farnesol and NAC. However, the pronounced antibacterial effect of NAC against S. epidermidis, on both lifestyles, indicates the use of NAC as a potential therapeutic agent in alternative to antibiotics.

Farnesol inhibits cell proliferation and induces apoptosis after partial hepatectomy in rats / Farnesol inibe a proliferação celular e induz a apoptose após a hepatectomia parcial em ratos

PURPOSE: To study farnesol (FOH) effects on liver regeneration after 70 percent partial hepatectomy (PH) in rats. METHODS: Animals received FOH (25 mg/100 g body weight/day) or corn oil (CO, 0.25 mL/100 g body weight/day, controls). After a 2 week-treatment, all animals were subjected to PH and euthanized at different time points (0 h, 0.5 h, 4 h, 8 h, 18 h and 24 h) after surgery. Hepatic cell proliferation (PCNA positive nuclei) and apoptosis (fluorescence microscopy) were evaluated. RESULTS: Compared to CO treatment, FOH treatment inhibited (p<0.05) cell proliferation at 24h (S phase of the cell cycle) after PH. This was preceded by an induction of apoptosis 0.5 h (p<0.05; G0/G1 transition phase) after surgery. CONCLUSION: The results of the present study suggest that apoptosis induction could be associated with the reduced number of cells at the S phase observed in FOH group. These novel in vivo data reinforce FOH as a promising chemopreventive and therapeutic agent against cancer.

OBJETIVO: Estudar o efeito do farnesol (FOH) durante a regeneração hepática em ratos submetidos à Hepatectomia Parcial (HP) a 70 por cento. MÉTODOS: Os animais foram tratados com FOH (25 mg/100g de peso corpórel/dia) ou óleo de milho (OM, 0,25 mL/100g de peso corpóreo/dia, grupo controle). Depois de 2 semanas de tratamento, todos os animais foram submetidos à HP e eutanaziados em diferentes momentos (0h, 30min., 4h, 8h, 18h, 24h.) após o procedimento cirúrgico. Foi avaliada a proliferação celular (imunohistoquímica para PCNA) e a apoptose (microscopia de fluorescência). RESULTADOS: Em comparação aos animais controles, animais tratados com FOH apresentaram menor (p<0,05) proliferação celular 24h. (fase S do ciclo celular) após a HP. Tal efeito foi precedido de uma indução de apoptose 30min. (p<0,05; transição entre as fases G0/G1 do ciclo celular) após a cirurgia. CONCLUSÃO: Os resultados do presente estudo sugerem que a indução da apoptose pode estar associada com o menor número de células na fase S observadas nos animais tratados com FOH. Essa nova evidência in vivo reforça o farnesol como um promissor agente preventivo e terapêutico contra o câncer.

Preliminary study on the effect of tyrosol and farnesol on biofilm formation of Candida albicans / 中华微生物学和免疫学杂志

Objective To study the regulation of quorum sensing molecule tyrosol and farnesol on biofilm formation of Candida albicans. Methods Candida albicans biofilms of clinic isolates and standard strain SC5314 were built when quorum sensing molecule existed. And inverted microscope was used to observe the morphology of C. albicans cells. RT-PCR and MTT assay were carried out to investigate the effect of quorum sensing molecule on expression of the two genes (HTA1 and EFG1) and cytoactive. Results Tyrosol could not promote hyphae development and cytoactive of C. albicans biofilms. The expression of HTA1 of C. albicans in biofilms was up-regulated by tyrosol but EFG1 was not. The inhibitory effect of farnesol on hyphae development, cytoactive and gene expression were not changed by addition of tyrosol. Conclusion Tyrosol can make C. albicans biofilms active in early stage. But when tyrosol and farnesol were simultaneously added, the effect of tyrosol were masked by farnesol. And C. albicans cells were more sensitive to farnesol than to tyrosol.

Flower scent analysis of Encyclia Vespa (vell.) Dressler & G. E. Pollard and E. Fragrans (Sw.) Lemée

The volatile constituents obtained from the pentane extract, using simultaneous distillation-extraction of the flowers of Encyclia vespa and E. fragrans were analysed by GC/ MS. The main volatile components identified in the flowers of E. vespa were terpinen-4-ol (20.3%), verbenone (14.8%), trans-verbenol (13.6%) and x-pinene (11.8%). The major volatiles of the flowers of E. fragrans were terpinen-4-ol (18.3%), (2Z,6E)-farnesol (15.4%) and trans-verbenol (10.2%).

Os constituintes voláteis obtidos dos extratos pentânicos das flores de Encyclia vespa e E. fragrans através de destilação-extração simultânea foram analisados por CG/EM. Os principais componentes voláteis identificados nas flores de E. vespa foram terpinen-4-ol (20,3%), verbenona (14,8%), trans-verbenol (13,6%) e a-pineno (11,8%). Os principais voláteis das flores de E. fragrans foram terpinen-4-ol (18,3%), (2Z,6E)-farnesol (15,4%) e trans-verbenol (10,2%).