Study of the Effectiveness of Papaver Sp. Alkaloids as Future Therapeutic Alternatives against Enterococcus Sp. Causing Hospital-Acquired Septicemic Infections

Background and Objective: In recent years, control of Enterococcus sp. It has been proven in the local medical environment to be a cause of acquired septicemia in various age groups, and medical instruments are considered an effective means of transmitting enterococcal septicemia, and catheters are at the forefront in terms of danger. Based on this risk, this study aimed to monitor the spread of Enterococcus sp., which causes blood poisoning acquired from catheters, and to compare its response to antibiotics with that of those isolated from clinical samples in children, as a first study locally. The effectiveness of alkaloids of different types of Papaver sp. In Syrian plants, they were tested against infection with this bacteria. Materials and Methods: The study dealt with two parts: The first part included collecting clinical samples from the University Children’s Hospital in Damascus/bacterial diagnostic laboratories/then isolating and diagnosing the bacteria by following a set of tests to identify the most prevalent genera and species and comparing their prevalence rate with Enterococcus. The second part;It included collecting plant samples, confirming the species taxonomically, then extracting alkaloids from plant parts (fruit, stem, Flowers), then comparing the extent of resistance of bacterial strains to antibiotics compared to the Enterococcus sp., and then confirming the antibacterial activity of the Papaver sp. alkaloids against Enterococcus sp. Result:In its first part, the study confirmed the significant contribution of the Enterococcus sp. to infections acquired from various sources, largely in catheter tip infections (9.09%) and to a lesser extent in other sources (3.7%), The second part was to confirm the effective-ness of the alkaloid extract of the Papaver sp., especially the two species Papaver syriacum, and Papaver dubium, against Enterococcus sp. with areole diameters that ranged between (15 - 26 mm) for the fruit extract and at a minimum inhibitory concentration (3.12 - 6.25 mml) and then the stem (5 - 20 mm). And the effectiveness of the Flowers extract is very weak to almost non-existent. Conclusions: The catheter and medical sources surrounding the patient constitute a dangerous source of multi-resistant Enterococcus sp., which poses a real threat to the lives of children, with new mechanisms represented by colonization of the skin and the ability to form biofilms Surfaces of medical instruments, with are resistant to a wide range of antibiotics. As an alternative and effective modern source to limit its spread in the future, the alkaloid extract of the fruits and stems of the wild Papaver sp. has proven a strong antibiotic effect, especially the two types: Papaver syriacum and Papaver dubium.

Anti-inflammatory maistemonine-class alkaloids of Stemona japonica

Three hitherto undescribed Stemona alkaloids,named stemajapines A-C(1-3),along with six known alkaloids(4-9),were isolated and identified from the roots of Stemona japonica(Blume)Miq.(Stemonaceae).Their structures were established by the analysis of the mass data,NMR spectra,and computational chemistry.Stemjapines A and B were degraded maistemonines without spiro-lactone ring and skeletal methyl from maistemonine.Concurrence of alkaloids 1 and 2 revealed an undescribed way to form diverse Stemona alkaloids.Bioassay results disclosed the anti-inflammatory natural constituents stemjapines A and C with IC_(50) values of 19.7 and 13.8μM,respectively,compared to positive control dexamethasone with 11.7μM.The findings may point out a new direction of Stemona alkaloids inaddition to its traditional antitussive and insecticide activities.

Uncarialines A-E,new alkaloids from Uncaria rhynchophylla and their anticoagulant activity

Uncarialines A-E(1-5),five undescribed monoterpene indole alkaloids,together with five known analogues were obtained from the stems of Uncaria rhynchophylla.Alkaloids 1-3 were unique 3,4-seco-tricyclic alkaloids with a 6/5/10 ring system,while 4 and 5 possessed a rare rearranged scaffold originated from corynantheine-type alkaloids with C-2/C-7 oxidation.Their structures were characterized by a comprehensive analysis of MS,NMR,and ECD.Their effects on blood clotting times of human plasma were evaluated and alkaloid 5 had a slight prolongation effect on both thrombin time and activated partial thromboplastin time(p<0.001).

Effects of Different Alkaloids in Coptis chinensis on Inhibiting TGEV Proliferation

[Objectives]To study the effects of different alkaloids in Coptis chinensis on inhibiting the proliferation of Transmissible gastroenteritis virus(TGEV).[Methods]The components and content of the main alkaloids in the extract of C.chinensis were analyzed.The main alkaloids were selected as drugs to inhibit the proliferation of TGEV.The maximum non-toxic concentration of Columbamine,Jatrorrhizine,Epiberberine,Coptisine,Palmatine,and Berberine was screened.The protective rate of each drug on TGEV-infected ST cells was determined,and the transcriptional inhibitory effect of the drug on TGEV N gene was detected by fluorescent quantitative PCR.[Results]The extract of C.chinensis mainly contains 6 alkaloids:Columbamine,Jatrorrhizine,Epiberberine,Coptisine,Palmatine,and Berberine,accounting for 2.03%,8.88%,9.21%,15.07%,14.63%,and 50.18%,respectively.In the range of the safe concentration,Jatrorrhizine,Palmatine,and Coptisine had better protective effects on ST cells infected with TGEV;compared with the Columbamine group,the cell protection rate was significantly different(P<0.05);compared with the Berberine group,the difference was extremely significant(P<0.01).The Coptisine and Palmatine groups had significant inhibitory effects on the transcription of TGEV N gene,and the difference was extremely significant compared with the virus group(P<0.05).[Conclusions]Jatrorrhizine and Palmatine in C.chinensis are the main components to inhibit the proliferation of TGEV.

Synergistic effect of pinellia total alkaloids and uncaria total alkaloids on anticonvulsant action in mice and rats

Aim To investigate the synergistic effect of the combination of pinellia total alkaloid （PTA） and uncaria total alkaloid （UTA）, and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1：4, 1 ：1, 4：1, were evaluated in maximal electroshock （MES）-induced seizures and acute toxicity test in mice. Respective ED50 and LD50 were calculated with Bliss＇s method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices （BI） for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high performance liquid chromatography （HPLC）. Results Combinations of PTA and UTA at the ratio of 4：1 were synergistic in MES test and antagonistic in acute toxicity test, showing the best profile for combinations of PTA with UTA. In contrast, the ratios of 1 ：4 and 1 ： 1, despite synergistic in MES test, were additive in acute toxicity test. The 4：1 combination and two drugs alone significantly decreased Glu level and increased GABA level in the hippocampus, but the GABA level in the 4：1 combination group was higher than that in the two drugs alone groups. They did not have significant influence on the levels of ASp and Gly. Conclusion Combinations of PTA and UTA at 4：1 ratio demonstrated synergistic effect in anticonvulsant action and antagonistic effect in toxicity. The anticonvulsant mechanism might be related to decreasing the excitability of Glutamatergic neurons and increasing the inhibition of GABAergic neurons.

Alkaloids as potential antivirals.A comprehensive review

Alkaloids are a diverse group of natural phytochemicals.These phytochemicals in plants provide them protection against pests,and herbivorous organisms and also control their development.Numerous of these alkaloids have a variety of biological effects,and some have even been developed into medications with different medicinal properties.This review aims to provide a broad overview of the numerous naturally occurring alkaloids(isolated from both terrestrial and aquatic species)along with synthetically produced alkaloid compounds having prominent antiviral properties.Previous reviews on this subject have focused on the biological actions of both natural and synthetic alkaloids,but they have not gone into comprehensive detail about their antiviral properties.We reviewed here several antiviral alkaloids that have been described in the literature in different investigational environments i.e.(in-vivo,in-ovo,in-vitro,and in-silico),and found that these alkaloid compounds have significant antiviral properties against several infectious viruses.These alkaloids repressed and targeted various important stages of viral infection at non-toxic doses while some of the alkaloids reported here also exhibited comparable inhibitory activities to commercially used drugs.Overall,these anti-viral effects of alkaloids point to a high degree of specificity,implying that they could serve as effective and safe antiviral medicines if further pursued in medicinal and pharmacological investigations.

New Neuraminidase Inhibitory Alkaloids from the Mangrove Soil-Derived Fungus Arthrinium sp.SCSIO 41305

New alkaloid,(E)-2-(hydroxyimino)-4-methylpentanamide(1)and a new cyclopentano[b]pyridine,4-hydroxy-7-methyl-6,7-dihydro-5H-cyclopenta[c]pyridin-5-one(2),together with ten known compounds(3–12)were isolated from the mangrove soil-derived fungus Arthrinium sp.SCSIO 41305.Extensive spectroscopic analysis and X-Ray crystallographic analysis were used to elucidate the structure of(E)-2-(hydroxyimino)-4-methylpentanamide(1),including its absolute configuration.All the isolated compounds(1–12)were evaluated for their antimicrobial and enzyme inhibitory activities against acetylcholinesterase(ACh E),neuraminidase(NAs),and phosphatidylinositol 3-kinase(PI3K).Among them,compounds 1 and 3 exhibited strong neuraminidase inhibitory activity with IC_(50)values of 12.04,1.92μmol L^(-1)(IC_(50)20μmol L^(-1)for oseltamivir acid),while compounds 5,6,8,and 10showed moderate neuraminidase inhibitory activity,and compounds 6–10 displayed weak enzyme inhibitory activities against PI3K.

Two Novel Hydroperoxylated Lycopodium Alkaloids from Huperzia serrata

Two novel hydroperoxylated Lycopodium alkaloids, 11alpha-hydroperoxyphlegmariurine B (1) and 7-hydroperoxyphlegmariurine B (2), along with a known compound, phlegmanurine B (3), were isolated from the total alkaloid fraction of the Chinese medicinal herb Huperzia serrata (Thunb.) Trev. Their structures and relative configurations were elucidated on the basis of spectroscopic analyses.

Isolation and Identification of Eleven Tertiary Alkaloidsin Corydalis decumbens

Eleven tertiarv alkaloids were isolated from Corvdalis decumbens rhizome Their structures were identified as protopine(Ⅶ),allocryptopine(Ⅷ),cryptopine (Ⅸ),muramine(ⅩⅦ);(+)-tetrahydropalmatine(Ⅲ),(+)-kikemanine (Ⅳ),(一)-scoulerine (ⅩⅧ),(十)-bulbo- capnine (ⅩⅨ),and(一)一capnoidine(Ⅰ),(一)一bicuculline(Ⅴ),(+) coriumidine(ⅩⅣ), respecti vely。 Among these,cryptopine,muramine,(+)-kikemanine,(-)-scoulerine,(一)capnoidine,(一)一bicuculline were isolated for the first time from this plant

The Alkaloids from Leaves of Croton hemiargyerius var. gymnodiscus

Aim Investigation of alkaloids from the leaves of Brazilian medicinal plantCroton hemiargyerius var. gymnodiscus. Methods Silica gel column chromatography was used repeatedlyfor the isolation and purification, and their structures were identified by extensive spectroscopyand comparison of the chemical and physical data with those of authentic samples reported inliterature. Results Twelve alkaloids were isolated and their structures were identified. ConclusionFour new alkaloids named hemiargines A (1), B (5), C (6) and D (7), together with eight knownalkaloids namely isoc-orydine (2), corydine (3), norcorydine (4), salutaridine (8), glaucine (9),tetrahydropalmatrubine (10), xylopinoine (11), and norlaudanosine (12) were isolated.

Norditerpenoid Alkaloids from Delphinium orthocentrum (Ranunculaceae)

Two new norditerpenoid alkaloids, orthocentrine (1) and deacetylswinanine A (2), together with a known alkaloid, swinanine A (3), were isolated from the whole plants of Delphinium orthocentrum Franch. The structures of the new alkaloids (1 and 2) were elucidated as 7,10_dihydroxy_8,14,16_trimethoxy_19,20_didehydro_aconitane (7β,8β,14α,16β) (1) and 20_ethyl_2,3_didehydro_6,10_dihydroxy_7,8_methylenedioxy_1,14,16_trimethoxy_aconitane (1α,6β,14α,16β) (2) by spectroscopic evidence and chemical transformation.

Abnormal Secondary Growth and Histochemical Localization of Alkaloids in Root System of Aconitum flavum Hand.-Mazz.

[Objective] The purpose of this study was to clarify the structure,growth pattern and histochemical localization of alkaloids in root system of Aconitum flavum Hand.-Mazz.[Method] Paraffin sectioning and histochemistry were employed for performing the analysis in this study.[Result] The root system of Aconitum flavum Hand.-Mazz.consists of taproot,lateral root and adventitious root.The primary structure of root system is normal,but secondary structure shows abnormal.The cambium and the extra cambium of taproot form a ＂U＂-shaped secondary vascular bundle and tertiary bundle in abnormal secondary structure.The sieve tube group is made of little sieve tube group which is differentiated from primary phloem and cambium.Meanwhile,the secondary xylem in tuberous root also appears to be a ＂U＂ shape.Parenchyma cells of secondary phloem occupy most of the tuberous root.The sieve tube group of tuberous root is mainly differentiated from parenchyma cell of secondary phloem.[Conclusion] The difference in abnormal secondary structure of taproot and tuberous root are attributed to their varied cambium compose and activity pattern.Alkaloids are mainly accumulated in parenchyma cell of the inside cortex and between bundle in taproot,while parenchyma of secondary phloem and pith in tuberous root.

Rapid analysis and identification for the alkaloids from Ranunculus japonicus by UPLC /Q-TOF-MS

To establish a rapid and effective method for analysis and identification of the alkaloids from Ranunculus japoni- cus Thunb by ultra-performance liquid chromatogaraphy with quadruple-time-of-flight mass spectrometry （UPLC/Q-TOF- MS） and discuss their fragmentation regularity, the UPLC/Q-TOF-MS was used to identify the alkaloids from Ranunculus japonicus Thunb by their MS data, tandem characteristic fragment ions and standards. In the end, 12 alkaloids were identi- fied from Ranunculus japonicus for the first time, and their fragmentation regularity was discussed. Thus, a rapid and effec- tive analysis and identification method for the alkaloids from Ranunculus japonicus by UPLC/Q-TOF-MS is established.

Determination of the Content of Total Alkaloids in Different Solvent Extracts from Climbing Groundsel Herb Produced in Guizhou Province and Their Antibacterial Activity

[Objective] This study aimed to compare the contents of total alkaloids in different solvent extracts from climbing groundsel herb produced in Guizhou Province and their antibacterial activity. [Method] The content of total alkaloids was measured by UV spectrophotometry, and Oxford cups were used to investigate the antibacterial activity of each solvent extract. [Result] There was a good linear correlation between the absorbance measured by the UV spectrophotometer and the content of total al- kaloids within the concentration of 0.011 0-0.054 8 mg/ml at 207 nm, and the re- gression equation was Y=23.654X＋0.021, R=0. 999 7 and the average recovery rate was 99.2%. The contents of total alkaloids in 60% ethanol extract, 95% ethanol and water ethanol were 38.71, 52.25 and 60.50 mg/g, respectively. The 60% ethanol ex- tract had strong antibacterial activity against Streptococcus pneumoniae, Staphylo- coccus aureus and Escherichia coil; the water extractive had stronger antibacterial activity against Escherichia colr, 95% ethanol extract had weak antibacterial activity, with no inhibition of Pseudomonas aeruginosa. [Conclusion] This method is accurate, simple, with good repeatability, which can be used for the determination of alkaloids content of the climbing groundsel herb; there is no positive correlation between the content of total alkaloids in different solvent extracts of climbing groundsel herb and their antibacterial activity.

Pyrrolizidine alkaloids-induced hepatic sinusoidal obstruction syndrome: Pathogenesis, clinical manifestations, diagnosis,treatment, and outcomes

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by the intake of pyrrolizidine alkaloids (PAs). To date, PAs-induced HSOS has not been extensively studied. In view of the difference in etiology of HSOS between the West and China, clinical profiles, imaging findings, treatment, and outcomes of HSOS associated with hematopoietic stem cell transplantation or oxaliplatin might be hardly extrapolated to PAs-induced HSOS. Reactive metabolites derived from PAs form pyrrole-protein adducts that result in toxic destruction of hepatic sinusoidal endothelial cells. PAs-induced HSOS typically manifests as painful hepatomegaly, ascites, and jaundice. Laboratory tests revealed abnormal liver function tests were observed in most of the patients with PAs-induced HSOS. In addition, contrast computed tomography and magnetic resonance imaging scan show that patients with PAs-induced HSOS have distinct imaging features, which reveal that radiological imaging provides an effective noninvasive method for the diagnosis of PAs-induced HSOS. Liver biopsy and histological examination showed that PAs-induced HSOS displayed distinct features in acute and chronic stages. Therapeutic strategies for PAs-induced HSOS include rigorous fluid management, anticoagulant therapy, glucocorticoids, transjugular intrahepatic portosystemic shunt, liver transplantation, etc. The aim of this review is to describe the pathogenesis, clinical profiles, diagnostic criteria, treatment, and outcomes of PAs-induced HSOS.

Effect of processing on the alkaloids in Aconitum tubers by HPLC-TOF/MS

According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry(HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids,monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine,and aconine in SD rats were used to validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diesterditerpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids.Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoesterditerpenoid alkaloids and amine-diterpenoid alkaloids.

Protective effects of Dendrobium nobile Lindl. alkaloids on amyloid beta(25–35)-induced neuronal injury

Dendrobium nobile Lindl.alkaloids（DNLA）,the active ingredients of a traditional Chinese medicine Dendrobium,have been shown to have anti-oxidative effects,anti-inflammatory action,and protective effect on neurons against oxygen-glucose deprivation.However,it is not clear whether DNLA reduces amyloid-beta（Aβ）-induced neuronal injury.In this study,cortical neurons were treated with DNLA at different concentrations（0.025,0.25,and 2.5 mg/L）for 24 hours,followed by administration of Aβ（25-35）（10μM）.Aβ（25-35） treatments increased cell injury as determined by the leakage of lactate dehydrogenase,which was accompanied by chromatin condensation and mitochondrial tumefaction.The damage caused by Aβ（25-35） on these cellular properties was markedly attenuated when cells were pretreated with DNLA.Treatment with Aβ（25-35）down-regulated the expressions of postsynaptic density-95 mRNA and decreased the protein expression of synaptophysin and postsynaptic density-95,all changes were significantly reduced by pretreatment of cells with DNLA.These findings suggest that DNLA reduces the cytotoxicity induced by Aβ（25-35） in rat primary cultured neurons.The protective mechanism that DNLA confers on the synaptic integrity of cultured neurons might be mediated,at least in part,through the upregulation of neurogenesis related proteins synaptophysin and postsynaptic density-95.

Two New Indole Alkaloids from Evodia rutaecarpa

Two new indole alkaloids. wuchuyuamide I and II were isolated from the fruits of Evodia rutaecarpa (Juss.) Benth and their structures were elucidated on the basis of spectral data.

Structural characterization of monoterpene indole alkaloids in ethanolic extracts of Rauwolfia species by liquid chromatography with quadrupole time-of-flight mass spectrometry

Rauwolfia species(Apocynaceae) are medicinal plants well known worldwide due to its potent bioactive monoterpene indole alkaloids(MIAs) such as reserpine,ajmalicine,ajmaline,serpentine and yohimbine.Reserpine,ajmalicine and ajmaline are powerful antihypertensive,tranquilizing agents used in hypertension.Yohimbine is an aphrodisiac used in dietary supplements.As there is no report on the comparative and comprehensive phytochemical investigation of the roots of Rauwolfia species,we have developed an efficient and reliable liquid chromatography-tandem mass spectrometry(LC–MS/MS) method for ethanolic root extract of Rauwolfia species to elucidate the fragmentation pathways for dereplication of bioactive MIAs using highperformance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(HPLC–ESI–QTOF–MS/MS) in positive ion mode.We identified and established diagnostic fragment ions and fragmentation pathways using reserpine,ajmalicine,ajmaline,serpentine and yohimbine.The MS/MS spectra of reserpine,ajmalicine,and ajmaline showed C-ring-cleavage whereas E-ring cleavage was observed in serpentine via Retro Diels Alder(RDA).A total of 47 bioactive MIAs were identified and characterized on the basis of their molecular formula,exact mass measurements and MS/MS analysis.Reserpine,ajmalicine,ajmaline,serpentine and yohimbine were unambiguously identified by comparison with their authentic standards and other 42 MIAs were tentatively identified and characterized from the roots of Rauwolfia hookeri,Rauwolfia micrantha,Rauwolfia serpentina,Rauwolfia verticillata,Rauwolfia tetraphylla and Rauwolfia vomitoria.Application of LC–MS followed by principal component analysis(PCA) has been successfully used to discriminate among six Rauwolfia species.

Two New Norditerpenoid Alkaloids from Aconitum spicatum Stapf

Two new norditerpenoid alkaloids, spicatine A (1) and spicatine B (2) were isolated from the root of Aconitum spicatum. The new compounds were deduced on the basis of their spectral data (IR, HREIMS, EIMS, 1D, 2D-NMR). This is the first whole report on the isolation of diterpenoid alkaloids from the A.spicatum Stapf.