Bioactivities,Mechanisms,Production,and Potential Application of Bile Acids in Preventing and Treating Infectious Diseases

Infectious diseases are a global public health problem,with emerging and re-emerging infectious diseases on the rise worldwide.Therefore,their prevention and treatment are still major challenges.Bile acids are common metabolites in both hosts and microorganisms that play a significant role in controlling the metabolism of lipids,glucose,and energy.Bile acids have historically been utilized as first-line,valuable therapeutic agents for related metabolic and hepatobiliary diseases.Notably,bile acids are the major active ingredients of cow bezoar and bear bile,which are commonly used traditional Chinese medicines(TCMs)with the therapeutic effects of clearing heat,detoxification,and relieving wind and spasm.In recent years,the promising performance of bile acids against infectious diseases has attracted attention from the scientific community.This paper reviews for the first time the biological activities,possible mechanisms,production routes,and potential applications of bile acids in the treatment and prevention of infectious diseases.Compared with previous reviews,we comprehensively summarize existing studies on the use of bile acids against infectious diseases caused by pathogenic microorganisms that are leading causes of global morbidity and mortality.In addition,to ensure a stable supply of bile acids at affordable prices,it is necessary to clarify the biosynthesis of bile acids in vivo,which will assist scientists in elucidating the accumulation of bile acids and discovering how to engineer various bile acids by means of chemosynthesis,biosynthesis,and chemoenzymatic synthesis.Finally,we explore the current challenges in the field and recommend a development strategy for bile-acid-based drugs and the sustainable production of bile acids.The presented studies suggest that bile acids are potential novel therapeutic agents for managing infectious diseases and can be artificially synthesized in a sustainable way.

Low eradication rate of Helicobacterpyloriwith triple 7-14 days and quadriple therapy in Turkey

AIM:The eradication rate of Helicobacter pylori (H pylori) shows variation among countries and regimens of treatment. We aimed to study the eradication rates of different regimens in our region and some factors affecting the rate of eradication. METHODS:One hundred and sixty-four H pylori positive patients (68 males,96 females;mean age:48±12 years) with duodenal or gastric ulcer without a smoking history were included in the study.The patients were divided into three groups according to the treatment regimens.Omeprazole 20mg,clarithromycin 500mg,amoxicillin 1g were given twice daily for 1 week (Group Ⅰ) and 2 weeks (Group Ⅱ). Patients in Group Ⅲ received bismuth subsitrate 300mg, tetracyline 500mg and metronidazole 500mg four times daily in addition to Omeprazole 20mg twice daily.Two biopsies each before and after treatment were obtained from antrum and corpus,and histopathologically evaluated. Eradication was assumed to be successful if no H pylorus was detected from four biopsy specimens taken after treatment.The effects of factors like age,sex,H pylori density on antrum and corpus before treatment,the total H pylori density,and the inflammation scores on the rate of H pylori eradication were evaluated. RESULTS:The overall eradication rate was 42%.The rates in groups Ⅱ and Ⅲ were statistically higher than that in group Ⅰ (P<0.05).The rates of eradication were 24.5%, 40.7% and 61.5% in groups Ⅰ,Ⅱ and Ⅲ,respectively.The eradication rate was negatively related to either corpus H pylori density or total H pylori density (P<0.05).The median age was older in the group in which the eradication failed in comparison to that with successful eradication (55 yr vs 39 yr,P<0.001).No correlation between sex and H pylori eradication was found. CONCLUSION:Our rates of eradication were significantly lower when compared to those reported in literature.We believe that advanced age and high H pylori density are negative predictive factors for the rate of H pylori eradication.

Biosynthesis of titanium dioxide nanoparticles using Hypericum perforatum and Origanum vulgare extracts and their main components,hypericin and carvacrol as promising antibacterial agents

OBJECTIVE:To evaluate the anti-bacterial activities of titanium dioxide(Ti O;)nanoparticles of Origanum(O.)vulgare and Hypericum(H.)perforatum extracts,carvacrol and hypericin against Staphylococcus(S.)aureus.METHODS:In this study,Ti O;nanoparticles of O.vulgare and H.perforatum extracts,carvacrol and hypericin,were prepared and their antibacterial effects were evaluated against Staphylococcus(S.)aureus.In this study,scanning electron microscope,fourier transform infrared spectrometer,atomic force microscopy,dynamic light scattering and zeta potential were used to investigate the structure of synthesized drugs.RESULTS:Anti-bacterial activity of synthesized NPs was tested by minimum inhibitory concentration(MIC),minimum bactericidal concentration and disc diffusion method.MICs of Ti O;-NPs synthesized using O.vulgare,H.perforatum,carvacrol and hypericin and Ti O;were obtained 250,62.5,250,and 250,and 500μg/m L,respectively.The MBCs for all of these were obtained 1000μg/m L.CONCLUSION:Green-synthesized of Ti O;nanoparticles provides a promising approach to the use of O.vulgare and H.perforatum,carvacrol and hypericin as novel agents and safer antibacterial compounds,especially anti-S.aureus compounds.

Screening strategies for quorum sensing inhibitors in combating bacterial infections

Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.

Methanolic extract from Lespedeza bicolor： potential candidates for natural antioxidant and anticancer agent

OBJECTIVE: To evaluate the anticancer, antioxidant and antimicrobial activities along with total phenolic and flavonoids contents extracted from Lespedeza bicolor indigenous to Khyber Pukhtoonkhwa Pakistan.METHODS: Anticancer activity against human lung carcinoma(LU-1) and human prostate carcinoma(Ln Cap), antimicrobial against Aspergillus fumigates, Aspergillus niger, Fusarium solani, Mucor sp Klebsiella pneumonia and Enterococcus and antioxidant activity on 1,1-Diphenyl-2-picryl-hydrazy(DPPH) and Hydrogen peroxide radicals scavenging activity were assessed in methanol extract o Lespedeza bicolor.RESULTS: Lespedeza bicolor aerial parts and root extract showed IC_(50)value of 12.5 and 50 μg/m L against LU-1 whereas, ≤ 12.5 and 12 μg/m L were calculated against Ln Cap cell line. Minimum inhibition concentration(MIC) value of 20-35 μg/m L has been observed against Aspergillus fumigates, Aspergillus niger, Fusarium solani and Mucor sp in comparision with 1-2.5 μg/m L of Terbinafine used as a standard fungicide. MIC value of 20 and 35 μg/m L of Lespedeza bicolor aerial parts and root extract against bacterial pathogen Klebsiella pneumonia and 20-50 μg/m L against Enterococcus has been measured. DPPH radical scavenging activity of Lespedeza bicolor with IC_(50)values of ≤ 50 μg/m L and ≤ 200 μg/m L was observed whereas, hydrogen peroxide scavenging activity with IC_(50)values of ≤25 μg/m L for aerial parts and ≤ 50 μg/m L for the root extract of Lespedeza bicolor has been shown.CONCLUSION: These data suggested that the methanolic extract of Lespedeza bicolor could be potential candidates for natural antioxidants and anticancer.

Study of isolation of fluoroquinolone-resistant Ureaplasma urealyticum and identification of mutant sites

OBJECTIVE: To study the resistance mechanism of clinical isolates of Ureaplasma urealyticum resistant to fluoroquinolones. METHODS: Thirteen isolates of Ureaplasma urealyticum resistant to six fluoroquinolones were selected out of 184 clinical isolates and their QRDRs (quinolone resistance-determining region) gyrA, gyrB, parC and parE were amplified by PCR. Sequencing results were compared to those susceptible reference strains and a comparison of deduced amino acid sequences were performed. RESULTS: Sequence comparison revealed a C to A change at 87nt of gyrA QRDR leading to the substitution of Asp95 with glutamic acid and a C to T change at 50nt of parC QRDR leading to the substitution of Ser80 with leucine. CONCLUSION: These results suggest that a C to A change at 87nt of gyrA QRDR and a C to T change at 50nt of parC QRDR are associated with fluoroquinolone resistance of Ureaplasma urealyticum.

眼部体外培养细菌对常用氟喹诺酮类药物敏感性的研究

目的 研究眼部体外培养细菌对常用氟喹诺酮类药物的敏感性。方法 对 1999年 1月至 2 0 0 0年 12月间北京市眼科研究所微生物室收集的 132 8份眼部标本行体外细菌培养 ,采用纸片扩散法观察体外培养阳性细菌对氧氟沙星、环丙沙星和诺氟沙星等药物的敏感性。结果 体外培养阳性细菌共 347株 ,其中革兰阳性球菌 192株 ( 5 5 3 %) ,革兰阴性球菌 16株 ( 4 6 %) ;革兰阳性杆菌 44株( 12 7%) ,革兰阴性杆菌 89株 ( 2 5 7%) ;放线菌 6株 ( 1 7%)。氧氟沙星、环丙沙星和诺氟沙星的总耐药性分别为 2 8 5 %、2 5 9%和 34 9%。链球菌属对环丙沙星和氧氟沙星的耐药性明显低于庆大霉素和妥布霉素 ,诺氟沙星明显低于妥布霉素 ,两者比较差异有非常显著意义 (P <0 0 1) ;假单胞菌属对环丙沙星耐药性明显低于庆大霉素 ,两者比较差异有非常显著意义 (P <0 0 1) ,而对氧氟沙星和诺氟沙星的耐药性低于庆大霉素 ,差异有显著意义 (P <0 0 5 )。常见葡萄球菌对庆大霉素和妥布霉素的耐药性明显低于诺氟沙星 ,差异有显著意义 (P <0 0 1) ;革兰阳性杆菌对 3种氟喹诺酮类药物的耐药性比较 ,差异无显著意义 (P >0 0 5 )。结论 多数眼部常见细菌对环丙沙星和氧氟沙星的敏感性较高 。

Synergistic antibacterial effect of honey and Herba Ocimi Basilici against some bacterial pathogens

OBJECTIVE： To evaluate the antibacterial activity of the combination of different honey brands and methanolic fraction of Herba Ocimi Basilici using agar well diffusion assay. METHODS： The antibacterial activity was deter- mined against thirteen pathogenic bacterial clini- cal isolates including six gram negative （Klebsiella pneumonia, Pseudomonas aeroginosa, Escherichia coli, Salmonella typhi, Salmonella typhimirium, Xanthomonas campestris） and six gram positive strains （Enterococcus faecalis faecalis, Bacillus subti- lis, Staphylococcus aureus, Clostridium perfringens type C, Clostridium perfringens type D, CIostridium chauvoei）. Agar well diffusion method was used while zones of inhibition were measured with verni- er scale. RESULTS： At higher concentration, all the honey brands showed good to significant activity. Thehighest activity was observed for Hamdard brand honey （27.60±0.40） against Enterococcus faecalis. CONCLUSION： These results revealed that combi- nations of plant extracts of Herba Ocimi Basilici with honey can be used for the development of potent and novel antibacterial agents.

Rumex dentatus could be a potent alternative to treatment of microbial infections and of breast cancer

OBJECTIVE:To investigate the phytochemicals and in vitro antioxidant,antimicrobial and cytotoxic potential of Rumex dentatus(R.dentatus)leaf extracts.METHODS:The total phenolics and flavonoids content of R.dentatus extracts were evaluated by the Folin-Ciocalteu and aluminum chloride colorimetric methods respectively.Antioxidant potential of studied plant extracts was assessed through 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity,total reducing power and total antioxidant methods.Moreover,antibacterial and antifungal capacity was also evaluated by disc diffusion method against six clinically isolated multi-drug resistant bacterial strains as well as six fungal isolates.Further,cell cytotoxicity was also evaluated through3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay.RESULTS:Ethanol extract showed highest total phenolic[(38.9±1.5)μg gallic acid equivalent/mg]and total flavonoids[(17.2±1.9)μg quercetin equivalent/mg]contents.Antioxidant assays indicated that ethanol and methanol extracts possess potent antioxidant potential.Moreover,it was observed that ethanol and hexane extracts have the potential to inhibit most of the tested multi-drug resistant bacterial strains while methanol,chloroform and hexane extracts could inhibit the growth of pathogenic fungal strains successfully.Among all the studied extracts,ethanolic extract showed highest cytotoxicity against MCF-7 cell line then Hep-2 and DU-145 cell lines by MTT assay with lowest IC50 of 47.3μg/m L.CONCLUSION:These results suggest that R.dentatus could be a potent alternative candidate for treatment of microbial infections and for breast cancer treatment.

Microbiostatic, antioxidative and cytotoxic potentiation of some grasses of Bahawalpur, Pakistan

OBJECTIVE: To evaluate biological potential of methanol and n-hexane extracts of aerial parts in seven species of family Poaceae.METHODS: Qualitative phytochemical tests were done by using standard protocols. In vitro antioxidant activity was performed via different assays and antimicrobial potential was observed via disc diffusion method. Cytotoxic activity was carried out using brine shrimps’ assay.RESULTS: Phytochemical studies revealed the presence of alkaloids, flavonoids, glycosides, phenols,steroids, saponins, tannins, anthocyanins and coumarins in most of the plant extracts. Maximum antioxidant and antimicrobial potential were observed in Cymbopogon citratus methanol extract and Cymbopogon citratus n-hexane extract along with significant number of total flavonoids and phenols contents. However, Polypogon monspeliensis methanol extract and Polypogon monspeliensis n-hexane extract showed minimum antioxidant as well as antimicrobial potential. Moreover, methanol extracts showed a cytotoxic effect with their effectiveness ranked Polypogon monspeliensis methanol extract > Cymbopogon citratus methanol extract > Phalaris minor n-hexane extract > Aristida funiculata methanol extract > Stipagrostis plumosa methanol extract > Cenchrus ciliaris methanol extract > Panicum antidotale methanol extract. Similarly, n-hexane plant extracts revealed cytotoxic activity in decreasing order Cenchrus ciliaris n-hexane extract > Stipagrostis plumosa n-hexane extract > Phalaris minor n-hexane extract > Aristida funiculata n-hexane extract > Polypogon monspeliensis n-hexane extract > Panicum antidotale n-hexane extract > Cymbopogon citratus n-hexane extract respectively.CONCLUSION: Methanol extracts exhibit significant antioxidant and antimicrobial potential which can be correlated to their medicinal values. The observed brine shrimp’s lethality of the plant extracts revealed the presence of potent cytotoxic components in these plants.