Aim To find the original active compounds from three medicinal plants of Menispermaceae family in Qinling Montain,Shaanxi,China.Method Several kinds of isolation techniques such as liquid-liquid partition,column chrom...Aim To find the original active compounds from three medicinal plants of Menispermaceae family in Qinling Montain,Shaanxi,China.Method Several kinds of isolation techniques such as liquid-liquid partition,column chromatography,thin layer chromatography and sephadex LH-20 gel chromatography are used to separate the compounds and all kinds of identification techniques such as mass,high resolution mass,1H-NMR,13C-NMR,all kinds of 2D-NMR,CD spectra and X-ray diffraction analysis are used to determine the structure of the isolated compounds;several enzymes linked immunosorbent assay are used to test the biological activities of some isolated compounds.Results 30 alkaloids were isolated and identified from Sinomenium acutum of which 8 are new compounds;nine alkaloids were isolated and identified from Menispermum dauricum of which 6 are new compounds;six alkaloids were isolated and identified from Stephania epigaea.Among all the identified alkaloids,six compounds show protective effects against hydrogen peroxide induced cell injury;eight compounds show weak or strong cytotoxicity activity;one compound shows neuroprotective effect against hydrogen peroxide and.β-amyloid25-35-induced oxidative injury.Conclusion These three plants of Menispermaceae family may be considered as the potential drugs for Alzheimer's disease therapy and anticancer agents.展开更多
Melodinus henryi is a good source of terpenoid indole alkaloids,and traditionally used as a folk medicine in the treatment of meningitis and fracture.In order to further exploit their potential uses,its anti-inflammat...Melodinus henryi is a good source of terpenoid indole alkaloids,and traditionally used as a folk medicine in the treatment of meningitis and fracture.In order to further exploit their potential uses,its anti-inflammatory and immunosuppressive activi-ties,safety evaluations and chemical profiles have been illustrated.Compared to the crude methanol extract from M.henryi and its non-alkaloidal fraction,the total alkaloidal fraction(MHTA)had the strongest anti-inflammatory and immunosup-pressive activities.In the acute oral toxicity assay,the half lethal dose(LD50)of MHTA was more than 2000 mg/kg.The sub-acute toxicity assay for consecutive 28 days exhibited MHTA at a lower concentrations of less than 500 mg/kg might be regarded as safe,and might damage spleen,liver,kidney,and heart when the dose is higher than 1000 mg/kg.In addition,a phytochemical investigation on MHTA led to the isolation of 15 monoterpenoid indole alkaloids.Thus,in regard with the potent side effects of MHTA,it should be used with caution in the development of phytomedicine.展开更多
Acalypha gaumeri(Euphorbiaceae)is the only endemic species of the genus in the Yucatan Peninsula.It is dioecious and has antifungal properties against various phytopathogens.In the present study,molecular identificati...Acalypha gaumeri(Euphorbiaceae)is the only endemic species of the genus in the Yucatan Peninsula.It is dioecious and has antifungal properties against various phytopathogens.In the present study,molecular identification of A.gaumeri was performed using the rbcL region,confirming its belonging to the Acalypha genus.Its genetic diversity was evaluated using 10 SPAR markers(ISSR and DAMD)from 60 individuals collected from female and male plants of the Kiuic,Tinum and Yaxcaba ex-situ populations.The results showed a high level of genetic polymorphism(PIC=0.980)and significant differences among the populations.Ethanol and aqueous extracts from leaves,stems,and roots of both genders and three populations were evaluated against three phytopathogenic fungi.Only the ethanol extracts of the roots showed inhibitory antifungal activity,whereas Kiuic and Tinum,both male and female individuals,showed inhibitory effects at 1000μg/mL against the three pathogens.The ethanol extract of the female flowering plant of Kiuic showed activity at minimum inhibitory concentrations of 250μg/mL against Alternaria chrysanthemi CICY004 and 500μg/mL against Colletotrichum gloeosporioides CICY002 and Penicillium oxalicum ITC25.Chromatographic profile of the ethanol extracts confirmed the presence of alkaloidal components in the ex-situ cultivated plants,which were analyzed by HPLC.The results revealed that the peaks at T_(R) of 7.60,7.88,and 8.49 min were the most abundant components(9.95%-21.93%),with differences between female and male plants of the three populations.This research confirms that A.gaumeri cultivated and genetically characterized is a potential raw material to develop an eco-friendly product for the control of fungal diseases in crops.展开更多
As its tuberous alkaloids induce valuable pharmacological effects,Pinellia ternata has considerable clinical value.However,its production currently fails to meet its demand.In vitro microtuber culture,combined with sa...As its tuberous alkaloids induce valuable pharmacological effects,Pinellia ternata has considerable clinical value.However,its production currently fails to meet its demand.In vitro microtuber culture,combined with salicylic acid(SA)elicitation,may provide an effective alternative to traditional field production.In this study,an in vitro P.ternata microtuber induction system was developed and used to evaluate SA-induced elicitation of alkaloid accumulation.The quality of in vitro microtubers was assessed by total alkaloid measurement,a cytotoxicity assay,and transcriptomic analysis.With or without SA treatment,P.ternata microtuber induction was achieved within 60 d using petiole-derived explants,with a microtuber proliferation rate of approximately 17 microtubers per explant.The total alkaloid content of in vitro microtubers elicited with 100μM SA was equivalent to that of field-grown tubers,while those not treated with SA contained lower alkaloid content.The cytotoxicity assay showed preliminary cytotoxic effects of SA-treated microtubers against the breast cancer cell line SUM159,comparable to field-grown tubers.Transcriptomic analysis revealed many differentially expressed genes(DEGs)in SA-treated in vitro microtubers.Six and twelve DEGs were annotated to the tropane,piperidine,and pyridine alkaloid pathway and the isoquinoline alkaloid pathway,respectively.RT-qPCR confirmed that the genes encoding spermidine synthase(c64642_g1),hyoscyamine(6S)-dioxygenase(c62620_g1),catechol oxidase(c61704_g3),monoamine oxidase(c65996_g3),and aspartate transaminase(c71069_g1)were significantly induced by SA.This study advances the production of P.ternata microtubers without field cultivation and provides considerable genetic information regarding SA-promoted alkaloid accumulation in P.ternata.展开更多
Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products socia...Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.展开更多
Pyrrolizidine alkaloids(PAs)and their N-oxides(PANOs)are phytotoxins produced by various plant species and have been emerged as environmental pollutants.The sorption/desorption behaviors of PAs/PANOs in soil are cruci...Pyrrolizidine alkaloids(PAs)and their N-oxides(PANOs)are phytotoxins produced by various plant species and have been emerged as environmental pollutants.The sorption/desorption behaviors of PAs/PANOs in soil are crucial due to the horizontal transfer of these natural products from PA-producing plants to soil and subsequently absorbed by plant roots.This study firstly investigated the sorption/desorption behaviors of PAs/PANOs in tea plantation soils with distinct characteristics.Sorption amounts for seneciphylline(Sp)and seneciphylline-N-oxide(SpNO)in three acidic soils ranged from 2.9 to 5.9μg/g and 1.7 to 2.8μg/g,respectively.Desorption percentages for Sp and SpNO were from 22.2%to 30.5%and 36.1%to 43.9%.In the mixed PAs/PANOs systems,stronger sorption of PAs over PANOs was occurred in tested soils.Additionally,the Freundlich models more precisely described the sorption/desorption isotherms.Cation exchange capacity,sand content and total nitrogen were identified as major influencing factors by linear regression models.Overall,the soils exhibiting higher sorption capacities for compounds with greater hydrophobicity.PANOs were more likely to migrate within soils and be absorbed by tea plants.It contributes to the understanding of environmental fate of PAs/PANOs in tea plantations and provides basic data and clues for the development of PAs/PANOs reduction technology.展开更多
Aconitum(Ranunculaceae)has a long-standing history in traditional Chinese medicine(TCM),where it has been widely used to treat conditions such as rheumatoid arthritis(RA),myocardial infarction,and heart failure.Howeve...Aconitum(Ranunculaceae)has a long-standing history in traditional Chinese medicine(TCM),where it has been widely used to treat conditions such as rheumatoid arthritis(RA),myocardial infarction,and heart failure.However,the potency of Aconitum alkaloids,the primary active components of Aconitum,also confers substantial toxicity.Therefore,assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety.Metabolomics,a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways,provides a comprehensive view of the metabolic state across multiple systems in vivo.This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity,identifying potential sensitive biomarkers,and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM.This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing,aiming to identify more viable methods for characterizing toxic medicinal plants.展开更多
From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganu...From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganumium C(3)were ionic alkaloid salts and peganumium B was a hexacycliccondensed alkaloid.The biosynthetic pathways of the three compounds above were also speculated.A preliminary cytotoxicity assay revealed that peganumium B had strong in vitro antiproliferative ability against a variety of cancer cells.The analysis of^(1)H nuclear magnetic resonance(NMR)metabolomics suggested that the antiproliferative mechanism of peganumium B could be associated with the biosynthesis of phenylalanine,tyrosine and tryptophan,the metabolism of glycine,serine,and threonine,the metabolism of taurine and hypotaurine,and the metabolism of nicotinate and nicotinamide.In addition,peganumium B could reduce the mitochondrial content of body-wall muscle cells of a Caenorhabditis elegans(C.elegans)strain in vivo.展开更多
Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect ...Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus(T2DM)and its underlying mechanism remain unclear.The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1,exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes.This combination demonstrated significant synergistic effects in improving glucose tolerance,reducing fasting blood glucose(FBG),the weight ratio of epididymal white adipose tissue(eWAT),and the homeostasis model assessment of insulin resistance(HOMA-IR)in leptin receptor-deficient(db/db)mice.Subsequently,a T2DM liver-specific network was constructed based on RNA sequencing(RNA-seq)experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions(PPIs).The network recovery index(NRI)score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components.The research identified that activated adenosine 5'-monophosphate-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)signaling in the liver played a crucial role in the synergistic treatment of T2DM,as verified by western blot experiment in db/db mice.These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice,surpassing the efficacy of individual treatments.The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.展开更多
Aposematism is an antipredator strategy in which conspicuous coloration acts as a warning of chemical defenses to potential predators.Evidence suggests that aposematism largely functions under positive frequency-depen...Aposematism is an antipredator strategy in which conspicuous coloration acts as a warning of chemical defenses to potential predators.Evidence suggests that aposematism largely functions under positive frequency-dependent selection,which is thought to maintain uniformity of aposematic signals.Many studies of aposematic organisms have found evidence that color signals and defenses are positively correlated,indicating a quantitatively honest aposematic signal.Dendrobatid poison frogs represent a well-studied group of aposematic organisms that in addition to exhibiting a diversity of color signals also display unique defensive behaviors.Few studies have examined if both behavior and coloration act as quantitative honest signals of alkaloid defenses in poison frogs.We aimed to determine if coloration and behavior are quantitatively honest signals in the green and black poison frog(Dendrobates auratus)among 6 populations from Costa Rica.We(1)evaluated antipredator displays by using behavioral assays in the field,(2)assessed frog conspicuousness and pattern using digital images,and(3)quantified alkaloid profiles from frog skin secretions.We found that Pacific populations are less conspicuous in coloration,had greater quantities of alkaloids,and more frequently performed body-raising defensive behaviors when compared with Caribbean populations.Our results do not support the hypothesis that aposematic traits in D.auratus are quantitatively honest.Rather,our results suggest that phenotypic differences among populations may represent different phenotypic optima for advertising unprofitability to predators based on local environmental conditions,leading to the diversification of aposematic signals in this species.展开更多
[Objectives]To analyze the main chemical components in Cocculus laurifolius DC.by ultra-high performance liquid chromatography-quaternary rod/electrostatic field orbital hydrazine high resolution mass spectrometry.[Me...[Objectives]To analyze the main chemical components in Cocculus laurifolius DC.by ultra-high performance liquid chromatography-quaternary rod/electrostatic field orbital hydrazine high resolution mass spectrometry.[Methods]Using Welch AQ-C 18 chromatographic column(150 mm×2.1 mm,1.8μm),gradient elution was performed with 0.1%formic acid aqueous solution(A)-methanol(B)as the mobile phase,and electrospray ESI ionization source and simultaneous mass spectrometry scanning mode of positive and negative ions were used.[Results]26 kinds of chemical component were identified or inferred,including 3 organic acids,5 flavonoids,4 alkaloids,1 coumarin and 13 others.[Conclusions]The UPLC-Q-Exactive HRMS technique is simple,which lays a foundation for the drug-efficacy material basis and medicinal quality evaluation of C.laurifolius DC.展开更多
Alduronic acid lactones and glyconolactones are highly functionalized and versatile chiral building blocks.Herein,we describe a novel approach to these compounds via decarboxylative oxygenation of uronic acids.The tra...Alduronic acid lactones and glyconolactones are highly functionalized and versatile chiral building blocks.Herein,we describe a novel approach to these compounds via decarboxylative oxygenation of uronic acids.The transformations proceed using Selectfluor and TEMPO as oxidants,either in the presence of catalytic amounts of Ag_(2)CO_(3)or in the absence of this catalyst.The methodology provides structurally diverse alduronic acid lactones and enables the preparation of rare sugar glyconolactones from easily available D-C-glycosides.Based on the^(18)O-labeling experiments,control experiments,and isolation of the key intermediates,a radical-polar crossover reaction mechanism is proposed.The utility of this method is demonstrated through efficient conversions of alduronic acid lactones into polyhydroxylated cyclic alkaloids and castanospermine-type architectures.展开更多
Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believ...Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believed to exert various toxicological effects,including survival inhibition and induction of apoptosis of hepatocytes.However,the effects of echimidine on development remain unclear.We selected three concentrations of 0.02,0.2,and 2 mg/L to investigate the developmental toxicity of echimidine on zebrafish embryos.After a 7-day exposure,we observed hyperactivity and anxiety-like behavior in zebrafish larvae.Furthermore,we found that echimidine exposure significantly promoted embryonic motor neurodevelopment in geneticallymodified zebrafish.Next,we detected that echimidine exposure significantly increased the content of the excitatory neurotransmitter acetylcholine(ACh),accompanied by a significant decrease in acetylcholinesterase(AChE)activity.Conversely,echimidine led to a significant reduction in the content of the sedative neurotransmitterγ-aminobutyric acid(GABA),accompanied by abnormal gene expression of enzymes related to GABA synthesis.Moreover,we elucidated the strong direct binding of echimidine to zebrafish and human AChE protein through molecular docking.In summary,our study found that echimidine induced ACh accumulation possibly by inhibiting AChE activity,leading to motor neurodevelopmental abnormalities and hyperactivity in zebrafish larvae.This work provides important scientific knowledge on the effects and mechanisms of PAs on neural development,which is helpful for controlling the risk of PAs in food and protecting public health.展开更多
1 Plant SecondaryMetabolism and Functional Biology Progress Plants have long been recognized as biochemical powerhouses,producing a vast array of compounds through their secondary metabolic pathways[1].Although histor...1 Plant SecondaryMetabolism and Functional Biology Progress Plants have long been recognized as biochemical powerhouses,producing a vast array of compounds through their secondary metabolic pathways[1].Although historically referred to as‘secondary’due to their perceived non-essential role in basic plant survival,it is now understood that these metabolites are integral to plant growth,development and adaptation to environmental challenges.Secondary metabolites,such as alkaloids,terpenoids,phenolics and flavonoids,serve as critical mediators of plant-environment interactions,conferring resistance to biotic and abiotic stressors[2].Beyond their ecological functions,these compounds are invaluable to humans,supporting industries ranging from pharmaceuticals and nutrition to agrochemicals and chemical additives.展开更多
Inflammation plays a pivotal role in the etiology and progression of various diseases.In traditional Chinese medicine,the whole plants of Thesium chinense Turcz.and its preparations(e.g.Bairui Granules)have been emplo...Inflammation plays a pivotal role in the etiology and progression of various diseases.In traditional Chinese medicine,the whole plants of Thesium chinense Turcz.and its preparations(e.g.Bairui Granules)have been employed to manage inflammatory conditions.While flavonoids were previously considered the primary anti-inflammatory components,other potentially active constituents have been largely overlooked and not thoroughly investigated.This study presents a novel finding that the total alkaloids of T.chinense(BC-Alk)are potent active substances underlying the traditional and clinical applications of T.chinense and Bairui Granules as anti-inflammatory agents.UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids.The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide(LPS)-induced lung inflammation model in mice.Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation,attenuated the overproduction of IL-1β and the overproduction of inflammatory factors(TNF-α),and ameliorated lung tissue hyperplasia in mice in vivo.Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit(GCLM),inhibited NF-κB phosphorylation,and suppressed NLRP3 activation.Collectively,these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2,NF-κB,and NLRP3 pathways.This study provides new insights into the anti-inflammatory constituents of T.chinense and Bairui Granules.展开更多
A promising solution to combat harmful cyanobacterial blooms(CyanoHABs)is the use of naturally-derived cyanocidal compound.This study found that the crude extracts of the herbaceous plant Macleaya cordata can inhibit ...A promising solution to combat harmful cyanobacterial blooms(CyanoHABs)is the use of naturally-derived cyanocidal compound.This study found that the crude extracts of the herbaceous plant Macleaya cordata can inhibit the growth of the bloom-forming cyanobacterium Microcystis aeruginosa.Growth inhibition test suggested that the inhibitory effect was significant at a concentration as low as 5μg/L of the crude extracts.To comprehensively elucidate inhibitory mechanisms,we examined the responses in anti-oxidative systems,changes in triggering signals in cells,and hallmarks of programmed cell death(PCD)under the two levels of exposure to the crude extracts of M.cordata.A notable observation across all treatment groups was the significant increase in the superoxide dismutase activity of M.aeruginosa at 72 h.However,distinct patterns were observed in malondialdehyde(MDA),with no significant difference observed between the low concentration treatment group(5μg/L)and the control group.In contrast,Microcystis cells subjected to high concentration(10μg/L)exhibited a significant difference in MDA content at both 24 and 72 h.Furthermore,we observed that the levels of potential signaling molecules,e.g.,intracellular reactive oxygen species,nitric oxide,and Ca^(2+)were altered in the Microcystis cells after exposure to the crude extracts.This results in alterations to the levels of signaling molecules,which in turn stimulate the upregulation of orthocaspase,leading to PCD and population collapse eventually.This study examines the mechanisms of Microcystis suppression through naturally-derived substances,providing theoretical and technical foundations for the sustainable management of CyanoHABs.展开更多
The rapid screening of bioactive constituents within traditional Chinese medicine(TCM)presents a significant challenge to researchers.Prevailing strategies for the screening of active components in TCM often overlook ...The rapid screening of bioactive constituents within traditional Chinese medicine(TCM)presents a significant challenge to researchers.Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents.To address this limitation,a fishing strategy based on offline two-dimensional liquid chromatography(2D-LC)combined with surface plasmon resonance(SPR)was utilized to screen bioactive trace components targeting peroxiredoxin 3(PRDX3),using Uncaria alkaloids(UAs)as a case study.Initially,an orthogonal preparative offline 2D-LC system combining a positively charged C_(18)column and a conventional C_(18)column under disparate mobile phase conditions was constructed.To fully reveal the trace alkaloids,132D fractions of UAs were prepared,and their components were characterized using mass spectrometry(MS).Subsequently,employing PRDX3 as the targeting protein,a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether(GSM)serving as a positive control for binding.Employing this refined strategy,29 candidate binding alkaloids were fished from the 132D fractions.Notably,combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone.Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids,with isovallesiachotamine(IV),corynoxeine N-oxide(CO-N),and cadambine(CAD)demonstrating the highest affinity for PRDX3.Their interactions were further validated through molecular docking analysis.Subsequent intracellular H_(2)O_(2)measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H_(2)O_(2)clearance.In conclusion,this study introduced an innovative strategy for the identification of active trace components in TCM.This approach holds promise for accelerating research on medicinal components within this field.展开更多
Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce th...Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.展开更多
Peganum harmala L.(P.harmala)is a significant economic and medicinal plant.The seeds of P.harmala have been extensively utilized in traditional Chinese medicine,Uighur medicine,and Mongolian medicine,as documented in ...Peganum harmala L.(P.harmala)is a significant economic and medicinal plant.The seeds of P.harmala have been extensively utilized in traditional Chinese medicine,Uighur medicine,and Mongolian medicine,as documented in the Drug Standard of the Ministry of Health of China.Twelve novel tryptamine-derived alkaloids(1−12)and eight known compounds(13−20)were isolated from P.harmala seeds.Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers,comprising tryptamine and aniline fragments with previously undocumented C-3−N-1′linkage and C-3−C-4′connection,respectively.Compounds 3−5 were identified as indole-quinazoline heteromers,exhibiting a novel C-3 and NH-1′linkage between indole and quinazoline-derived fragments.Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer.Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton,featuring an unusual spiro-tricyclic ring(7)and conventional bicyclic tryptamine.Compounds 9−11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine.Compounds 1−3 and 6−11 were identified as racemates.Compounds 2,7,9,10,and 12 were confirmed via X-ray crystallographic analysis.All isolated compounds(1−20)exhibited varying degrees of antiviral efficacy against respiratory syncytial virus(RSV).Notably,the anti-RSV activity of compound 12(IC505.01±0.14μmol·L^(−1))surpassed that of the positive control(ribavirin,IC506.23±0.95μmol·L^(−1)),as validated through plaque reduction and immunofluorescence assays.The identification of anti-RSV compounds from P.harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.展开更多
Anisodus tanguticus (Maxim.) Pascher, a medicinal plant in the Solanaceae family, is widely distributed across the Qinghai-Tibet Plateau. Its medicinal properties, particularly the tropane alkaloids, are influenced by...Anisodus tanguticus (Maxim.) Pascher, a medicinal plant in the Solanaceae family, is widely distributed across the Qinghai-Tibet Plateau. Its medicinal properties, particularly the tropane alkaloids, are influenced by various ecological factors, but the underlying ecological mechanisms remain poorly understood. This study aimed to investigate how key environmental variables influence both the morphological traits and tropane alkaloid contents of A. tanguticus, with the goal of providing data to support the sustainable cultivation and management of this species. We collected samples from 71 sites across its natural habitat, analyzing the effects of factors such as soil nutrients, altitude, and climate variables on plant traits and alkaloid composition. Statistical methods including Pearson correlation analysis, multiple regression, random forest analysis, and structural equation modeling were used to identify key environmental drivers. Our results indicate that available phosphorus significantly affects aboveground traits, while Cu concentration is most influential for root development. Altitude and longitude were found to be the main determinants of biomass accumulation. Regarding alkaloid content, Mg concentration in the soil was closely linked to anisodine levels, while altitude and latitude were the primary factors influencing anisodamine and atropine content, respectively. These findings provide essential insights into the ecological factors that govern the growth and medicinal compound production in A. tanguticus. Our research not only contributes to understanding the plant’s ecological requirements but also offers practical guidelines for selecting optimal cultivation conditions to enhance both yield and alkaloid quality, supporting sustainable use and conservation of this valuable medicinal resource.展开更多
文摘Aim To find the original active compounds from three medicinal plants of Menispermaceae family in Qinling Montain,Shaanxi,China.Method Several kinds of isolation techniques such as liquid-liquid partition,column chromatography,thin layer chromatography and sephadex LH-20 gel chromatography are used to separate the compounds and all kinds of identification techniques such as mass,high resolution mass,1H-NMR,13C-NMR,all kinds of 2D-NMR,CD spectra and X-ray diffraction analysis are used to determine the structure of the isolated compounds;several enzymes linked immunosorbent assay are used to test the biological activities of some isolated compounds.Results 30 alkaloids were isolated and identified from Sinomenium acutum of which 8 are new compounds;nine alkaloids were isolated and identified from Menispermum dauricum of which 6 are new compounds;six alkaloids were isolated and identified from Stephania epigaea.Among all the identified alkaloids,six compounds show protective effects against hydrogen peroxide induced cell injury;eight compounds show weak or strong cytotoxicity activity;one compound shows neuroprotective effect against hydrogen peroxide and.β-amyloid25-35-induced oxidative injury.Conclusion These three plants of Menispermaceae family may be considered as the potential drugs for Alzheimer's disease therapy and anticancer agents.
基金supported by the open program of State Key of Phytochemistry and Plant Resources in West China(P2018-KF08)the Applied Basic Research Project of Yunnan Province(Grant numbers No.2018FB036 and 2017FD121)the National Natural Science Foundation of China(Grant Numbers 31600274).
文摘Melodinus henryi is a good source of terpenoid indole alkaloids,and traditionally used as a folk medicine in the treatment of meningitis and fracture.In order to further exploit their potential uses,its anti-inflammatory and immunosuppressive activi-ties,safety evaluations and chemical profiles have been illustrated.Compared to the crude methanol extract from M.henryi and its non-alkaloidal fraction,the total alkaloidal fraction(MHTA)had the strongest anti-inflammatory and immunosup-pressive activities.In the acute oral toxicity assay,the half lethal dose(LD50)of MHTA was more than 2000 mg/kg.The sub-acute toxicity assay for consecutive 28 days exhibited MHTA at a lower concentrations of less than 500 mg/kg might be regarded as safe,and might damage spleen,liver,kidney,and heart when the dose is higher than 1000 mg/kg.In addition,a phytochemical investigation on MHTA led to the isolation of 15 monoterpenoid indole alkaloids.Thus,in regard with the potent side effects of MHTA,it should be used with caution in the development of phytomedicine.
基金supported by the SECIHTI project PDCPN-2015-266,México.
文摘Acalypha gaumeri(Euphorbiaceae)is the only endemic species of the genus in the Yucatan Peninsula.It is dioecious and has antifungal properties against various phytopathogens.In the present study,molecular identification of A.gaumeri was performed using the rbcL region,confirming its belonging to the Acalypha genus.Its genetic diversity was evaluated using 10 SPAR markers(ISSR and DAMD)from 60 individuals collected from female and male plants of the Kiuic,Tinum and Yaxcaba ex-situ populations.The results showed a high level of genetic polymorphism(PIC=0.980)and significant differences among the populations.Ethanol and aqueous extracts from leaves,stems,and roots of both genders and three populations were evaluated against three phytopathogenic fungi.Only the ethanol extracts of the roots showed inhibitory antifungal activity,whereas Kiuic and Tinum,both male and female individuals,showed inhibitory effects at 1000μg/mL against the three pathogens.The ethanol extract of the female flowering plant of Kiuic showed activity at minimum inhibitory concentrations of 250μg/mL against Alternaria chrysanthemi CICY004 and 500μg/mL against Colletotrichum gloeosporioides CICY002 and Penicillium oxalicum ITC25.Chromatographic profile of the ethanol extracts confirmed the presence of alkaloidal components in the ex-situ cultivated plants,which were analyzed by HPLC.The results revealed that the peaks at T_(R) of 7.60,7.88,and 8.49 min were the most abundant components(9.95%-21.93%),with differences between female and male plants of the three populations.This research confirms that A.gaumeri cultivated and genetically characterized is a potential raw material to develop an eco-friendly product for the control of fungal diseases in crops.
基金supported by the Key Project of Natural Science Research for Colleges and Universities in Anhui Province(2024AH051661,2023AH050345)Excellent Scientific Research and Innovation Team of University in Anhui Province(2022AH010029).
文摘As its tuberous alkaloids induce valuable pharmacological effects,Pinellia ternata has considerable clinical value.However,its production currently fails to meet its demand.In vitro microtuber culture,combined with salicylic acid(SA)elicitation,may provide an effective alternative to traditional field production.In this study,an in vitro P.ternata microtuber induction system was developed and used to evaluate SA-induced elicitation of alkaloid accumulation.The quality of in vitro microtubers was assessed by total alkaloid measurement,a cytotoxicity assay,and transcriptomic analysis.With or without SA treatment,P.ternata microtuber induction was achieved within 60 d using petiole-derived explants,with a microtuber proliferation rate of approximately 17 microtubers per explant.The total alkaloid content of in vitro microtubers elicited with 100μM SA was equivalent to that of field-grown tubers,while those not treated with SA contained lower alkaloid content.The cytotoxicity assay showed preliminary cytotoxic effects of SA-treated microtubers against the breast cancer cell line SUM159,comparable to field-grown tubers.Transcriptomic analysis revealed many differentially expressed genes(DEGs)in SA-treated in vitro microtubers.Six and twelve DEGs were annotated to the tropane,piperidine,and pyridine alkaloid pathway and the isoquinoline alkaloid pathway,respectively.RT-qPCR confirmed that the genes encoding spermidine synthase(c64642_g1),hyoscyamine(6S)-dioxygenase(c62620_g1),catechol oxidase(c61704_g3),monoamine oxidase(c65996_g3),and aspartate transaminase(c71069_g1)were significantly induced by SA.This study advances the production of P.ternata microtubers without field cultivation and provides considerable genetic information regarding SA-promoted alkaloid accumulation in P.ternata.
基金supported by the National Natural Science Foundation of China(Nos.82273845,82304331,and 82360695)Guangxi Natural Science Foundation project(No.2023GXNSFBA026305).
文摘Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.
基金supported by the earmarked fund for the Modern Agro-Industry Technology Research System (No.CARS-19)the Innovative Research Team in Chinese Academy of Agricultural Sciences (No.CAAS ASTIP-2014-TRICAAS).
文摘Pyrrolizidine alkaloids(PAs)and their N-oxides(PANOs)are phytotoxins produced by various plant species and have been emerged as environmental pollutants.The sorption/desorption behaviors of PAs/PANOs in soil are crucial due to the horizontal transfer of these natural products from PA-producing plants to soil and subsequently absorbed by plant roots.This study firstly investigated the sorption/desorption behaviors of PAs/PANOs in tea plantation soils with distinct characteristics.Sorption amounts for seneciphylline(Sp)and seneciphylline-N-oxide(SpNO)in three acidic soils ranged from 2.9 to 5.9μg/g and 1.7 to 2.8μg/g,respectively.Desorption percentages for Sp and SpNO were from 22.2%to 30.5%and 36.1%to 43.9%.In the mixed PAs/PANOs systems,stronger sorption of PAs over PANOs was occurred in tested soils.Additionally,the Freundlich models more precisely described the sorption/desorption isotherms.Cation exchange capacity,sand content and total nitrogen were identified as major influencing factors by linear regression models.Overall,the soils exhibiting higher sorption capacities for compounds with greater hydrophobicity.PANOs were more likely to migrate within soils and be absorbed by tea plants.It contributes to the understanding of environmental fate of PAs/PANOs in tea plantations and provides basic data and clues for the development of PAs/PANOs reduction technology.
基金supported by the National Natural Science Foundation of China (No.82274223)。
文摘Aconitum(Ranunculaceae)has a long-standing history in traditional Chinese medicine(TCM),where it has been widely used to treat conditions such as rheumatoid arthritis(RA),myocardial infarction,and heart failure.However,the potency of Aconitum alkaloids,the primary active components of Aconitum,also confers substantial toxicity.Therefore,assessing the efficacy and toxicity of these Aconitum alkaloids is crucial for ensuring clinical effectiveness and safety.Metabolomics,a quantitative method for analyzing low-molecular-weight metabolites involved in metabolic pathways,provides a comprehensive view of the metabolic state across multiple systems in vivo.This approach has become a vital investigative tool for facilitating the evaluation of their efficacy and toxicity,identifying potential sensitive biomarkers,and offering a promising avenue for elucidating the pharmacological and toxicological mechanisms underlying TCM.This review focuses on the applications of metabolomics in pharmacological and toxicological studies of Aconitum alkaloids in recent years and highlights the significant role of metabolomics in exploring compatibility detoxification and the mechanisms of TCM processing,aiming to identify more viable methods for characterizing toxic medicinal plants.
基金Financial support from Beijing Natural Science Foundation(No.7232283)。
文摘From the seeds of Peganum harmala L.,three new alkaloids ofβ-carboline were isolated.Among them,peganumiums A(1)and B(2)were dimers with specific new scaffolds,all with long conjugated systems.Peganumium A and peganumium C(3)were ionic alkaloid salts and peganumium B was a hexacycliccondensed alkaloid.The biosynthetic pathways of the three compounds above were also speculated.A preliminary cytotoxicity assay revealed that peganumium B had strong in vitro antiproliferative ability against a variety of cancer cells.The analysis of^(1)H nuclear magnetic resonance(NMR)metabolomics suggested that the antiproliferative mechanism of peganumium B could be associated with the biosynthesis of phenylalanine,tyrosine and tryptophan,the metabolism of glycine,serine,and threonine,the metabolism of taurine and hypotaurine,and the metabolism of nicotinate and nicotinamide.In addition,peganumium B could reduce the mitochondrial content of body-wall muscle cells of a Caenorhabditis elegans(C.elegans)strain in vivo.
基金supported by the Pioneer and Leading Goose R&D Program of Zhejiang Province(No.2024C03106)the National Natural Science Foundation of China(No.U23A20513)+1 种基金Ningbo Top Medical and Health Research Program(No.2022030309)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202002).
文摘Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus(T2DM)and its underlying mechanism remain unclear.The research demonstrated that the optimal ratio of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1,exhibiting maximal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepatocytes.This combination demonstrated significant synergistic effects in improving glucose tolerance,reducing fasting blood glucose(FBG),the weight ratio of epididymal white adipose tissue(eWAT),and the homeostasis model assessment of insulin resistance(HOMA-IR)in leptin receptor-deficient(db/db)mice.Subsequently,a T2DM liver-specific network was constructed based on RNA sequencing(RNA-seq)experiments and public databases by integrating transcriptional properties of disease-associated proteins and protein-protein interactions(PPIs).The network recovery index(NRI)score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components.The research identified that activated adenosine 5'-monophosphate-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)signaling in the liver played a crucial role in the synergistic treatment of T2DM,as verified by western blot experiment in db/db mice.These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice,surpassing the efficacy of individual treatments.The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.
基金funded by 2 grants awarded to KPB(Animal Behavior Society,Student Research Grant and Sigma Xi,Grants-in-Aid of Research)funding from John Carroll University.
文摘Aposematism is an antipredator strategy in which conspicuous coloration acts as a warning of chemical defenses to potential predators.Evidence suggests that aposematism largely functions under positive frequency-dependent selection,which is thought to maintain uniformity of aposematic signals.Many studies of aposematic organisms have found evidence that color signals and defenses are positively correlated,indicating a quantitatively honest aposematic signal.Dendrobatid poison frogs represent a well-studied group of aposematic organisms that in addition to exhibiting a diversity of color signals also display unique defensive behaviors.Few studies have examined if both behavior and coloration act as quantitative honest signals of alkaloid defenses in poison frogs.We aimed to determine if coloration and behavior are quantitatively honest signals in the green and black poison frog(Dendrobates auratus)among 6 populations from Costa Rica.We(1)evaluated antipredator displays by using behavioral assays in the field,(2)assessed frog conspicuousness and pattern using digital images,and(3)quantified alkaloid profiles from frog skin secretions.We found that Pacific populations are less conspicuous in coloration,had greater quantities of alkaloids,and more frequently performed body-raising defensive behaviors when compared with Caribbean populations.Our results do not support the hypothesis that aposematic traits in D.auratus are quantitatively honest.Rather,our results suggest that phenotypic differences among populations may represent different phenotypic optima for advertising unprofitability to predators based on local environmental conditions,leading to the diversification of aposematic signals in this species.
基金Supported by Scientific Research Project of China Medical Association of Minorities(2022M2038-310401)Guangxi First-class Discipline Project for Traditional Chinese Medicine(GuiJiaoKeYan 202201)+3 种基金Scientific Research and Training Project for College Students of Guangxi University of Chinese Medicine(2023DXS14)Funding Project for High-level Innovation Team and Outstanding Scholars in Guangxi Universities(GuiJiaoRen 201407)NATCM s Project of High-level Construction of Key TCM Disciplines/Medicine for Ethnic Minorities(Zhuang Medicine)(ZYYZDXK-2023164)Guangxi Higher Education Key Laboratory for the Research of Toxic Diseases in Zhuang Medicine(GuiJiaoKeYan 202210).
文摘[Objectives]To analyze the main chemical components in Cocculus laurifolius DC.by ultra-high performance liquid chromatography-quaternary rod/electrostatic field orbital hydrazine high resolution mass spectrometry.[Methods]Using Welch AQ-C 18 chromatographic column(150 mm×2.1 mm,1.8μm),gradient elution was performed with 0.1%formic acid aqueous solution(A)-methanol(B)as the mobile phase,and electrospray ESI ionization source and simultaneous mass spectrometry scanning mode of positive and negative ions were used.[Results]26 kinds of chemical component were identified or inferred,including 3 organic acids,5 flavonoids,4 alkaloids,1 coumarin and 13 others.[Conclusions]The UPLC-Q-Exactive HRMS technique is simple,which lays a foundation for the drug-efficacy material basis and medicinal quality evaluation of C.laurifolius DC.
基金financial support from the Marine S&T Fund of Shandong Province for Qingdao Marine Science and Technology Center(No.2022QNLM030003-2)the National Key Research&Development Program of China(No.2022YFA2104902)the National Natural Science Foundation of China(Nos.21977088 and22377114)。
文摘Alduronic acid lactones and glyconolactones are highly functionalized and versatile chiral building blocks.Herein,we describe a novel approach to these compounds via decarboxylative oxygenation of uronic acids.The transformations proceed using Selectfluor and TEMPO as oxidants,either in the presence of catalytic amounts of Ag_(2)CO_(3)or in the absence of this catalyst.The methodology provides structurally diverse alduronic acid lactones and enables the preparation of rare sugar glyconolactones from easily available D-C-glycosides.Based on the^(18)O-labeling experiments,control experiments,and isolation of the key intermediates,a radical-polar crossover reaction mechanism is proposed.The utility of this method is demonstrated through efficient conversions of alduronic acid lactones into polyhydroxylated cyclic alkaloids and castanospermine-type architectures.
基金supported by the Key Project at the Central Government Level:the ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302)the National Natural Science Foundation of China(No.82104389)+2 种基金the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2023E002)the High-level Key Discipline Program of National Administration of Traditional Chinese Medicine(No.ZYYZDXK-2023244)China Agricultural Research System of MOF and MARA(No.CARS-21).
文摘Pyrrolizidine alkaloids(PAs)are natural toxins generated as secondarymetabolites in plants,predominantly consisting of unsaturated PAs with diverse toxicities,such as hepatotoxicity.Echimidine,a prominent PA,is believed to exert various toxicological effects,including survival inhibition and induction of apoptosis of hepatocytes.However,the effects of echimidine on development remain unclear.We selected three concentrations of 0.02,0.2,and 2 mg/L to investigate the developmental toxicity of echimidine on zebrafish embryos.After a 7-day exposure,we observed hyperactivity and anxiety-like behavior in zebrafish larvae.Furthermore,we found that echimidine exposure significantly promoted embryonic motor neurodevelopment in geneticallymodified zebrafish.Next,we detected that echimidine exposure significantly increased the content of the excitatory neurotransmitter acetylcholine(ACh),accompanied by a significant decrease in acetylcholinesterase(AChE)activity.Conversely,echimidine led to a significant reduction in the content of the sedative neurotransmitterγ-aminobutyric acid(GABA),accompanied by abnormal gene expression of enzymes related to GABA synthesis.Moreover,we elucidated the strong direct binding of echimidine to zebrafish and human AChE protein through molecular docking.In summary,our study found that echimidine induced ACh accumulation possibly by inhibiting AChE activity,leading to motor neurodevelopmental abnormalities and hyperactivity in zebrafish larvae.This work provides important scientific knowledge on the effects and mechanisms of PAs on neural development,which is helpful for controlling the risk of PAs in food and protecting public health.
基金supported by High Level Talents Research Initiation Fund of West Anhui University(WGKQ2022025)Quality Engineering Project of Anhui Province(2024zybj032)+1 种基金Quality Engineering Project of West Anhui University(wxxy2024011)Development of Big Data Integration and Analysis Platform for Traditional Chinese Medicine Genomics(0045025050).
文摘1 Plant SecondaryMetabolism and Functional Biology Progress Plants have long been recognized as biochemical powerhouses,producing a vast array of compounds through their secondary metabolic pathways[1].Although historically referred to as‘secondary’due to their perceived non-essential role in basic plant survival,it is now understood that these metabolites are integral to plant growth,development and adaptation to environmental challenges.Secondary metabolites,such as alkaloids,terpenoids,phenolics and flavonoids,serve as critical mediators of plant-environment interactions,conferring resistance to biotic and abiotic stressors[2].Beyond their ecological functions,these compounds are invaluable to humans,supporting industries ranging from pharmaceuticals and nutrition to agrochemicals and chemical additives.
基金supported by the National Natural Science Foundation of China(No.82274065)Toxicology of Traditional Chinese Medicines,a High-Level Priority Subject in Chinese Medicine in National Administration of Traditional Chinese Medicine(No.ZYYZDXK-2023296)Cutting Edge Development Fund of Advanced Medical Research Institute(No.GYY2023QY01)。
文摘Inflammation plays a pivotal role in the etiology and progression of various diseases.In traditional Chinese medicine,the whole plants of Thesium chinense Turcz.and its preparations(e.g.Bairui Granules)have been employed to manage inflammatory conditions.While flavonoids were previously considered the primary anti-inflammatory components,other potentially active constituents have been largely overlooked and not thoroughly investigated.This study presents a novel finding that the total alkaloids of T.chinense(BC-Alk)are potent active substances underlying the traditional and clinical applications of T.chinense and Bairui Granules as anti-inflammatory agents.UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids.The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide(LPS)-induced lung inflammation model in mice.Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation,attenuated the overproduction of IL-1β and the overproduction of inflammatory factors(TNF-α),and ameliorated lung tissue hyperplasia in mice in vivo.Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit(GCLM),inhibited NF-κB phosphorylation,and suppressed NLRP3 activation.Collectively,these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2,NF-κB,and NLRP3 pathways.This study provides new insights into the anti-inflammatory constituents of T.chinense and Bairui Granules.
基金supported by Technology Innovation Guidance Program of Jiangxi Province“Science and Technology&Water Conservancy”Joint Plan(No.2022KSG01004)the National Natural Science Foundation of China(Nos.42107150,32061143029,and 42307100)Kunming Dianchi and Plateau Lakes Institute(No.KMZC2023-C3–01268-YNYG-0015)。
文摘A promising solution to combat harmful cyanobacterial blooms(CyanoHABs)is the use of naturally-derived cyanocidal compound.This study found that the crude extracts of the herbaceous plant Macleaya cordata can inhibit the growth of the bloom-forming cyanobacterium Microcystis aeruginosa.Growth inhibition test suggested that the inhibitory effect was significant at a concentration as low as 5μg/L of the crude extracts.To comprehensively elucidate inhibitory mechanisms,we examined the responses in anti-oxidative systems,changes in triggering signals in cells,and hallmarks of programmed cell death(PCD)under the two levels of exposure to the crude extracts of M.cordata.A notable observation across all treatment groups was the significant increase in the superoxide dismutase activity of M.aeruginosa at 72 h.However,distinct patterns were observed in malondialdehyde(MDA),with no significant difference observed between the low concentration treatment group(5μg/L)and the control group.In contrast,Microcystis cells subjected to high concentration(10μg/L)exhibited a significant difference in MDA content at both 24 and 72 h.Furthermore,we observed that the levels of potential signaling molecules,e.g.,intracellular reactive oxygen species,nitric oxide,and Ca^(2+)were altered in the Microcystis cells after exposure to the crude extracts.This results in alterations to the levels of signaling molecules,which in turn stimulate the upregulation of orthocaspase,leading to PCD and population collapse eventually.This study examines the mechanisms of Microcystis suppression through naturally-derived substances,providing theoretical and technical foundations for the sustainable management of CyanoHABs.
基金supported by Shanghai Institute of Materia Medica-Shanghai University of Traditional Chinese Medicine(SIMM-SHUTCM)Traditional Chinese Medicine Innovation Joint Research Program,China(Grant No.:2022,E2G808H096)the National Key Research and Development Program of China(Grant Nos.:2022YFC3501704 and 2023YFC3504205)Sanming Project of Medicine in Shenzhen,China(Grant No.:ZZYSM202106004).
文摘The rapid screening of bioactive constituents within traditional Chinese medicine(TCM)presents a significant challenge to researchers.Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents.To address this limitation,a fishing strategy based on offline two-dimensional liquid chromatography(2D-LC)combined with surface plasmon resonance(SPR)was utilized to screen bioactive trace components targeting peroxiredoxin 3(PRDX3),using Uncaria alkaloids(UAs)as a case study.Initially,an orthogonal preparative offline 2D-LC system combining a positively charged C_(18)column and a conventional C_(18)column under disparate mobile phase conditions was constructed.To fully reveal the trace alkaloids,132D fractions of UAs were prepared,and their components were characterized using mass spectrometry(MS).Subsequently,employing PRDX3 as the targeting protein,a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether(GSM)serving as a positive control for binding.Employing this refined strategy,29 candidate binding alkaloids were fished from the 132D fractions.Notably,combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone.Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids,with isovallesiachotamine(IV),corynoxeine N-oxide(CO-N),and cadambine(CAD)demonstrating the highest affinity for PRDX3.Their interactions were further validated through molecular docking analysis.Subsequent intracellular H_(2)O_(2)measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H_(2)O_(2)clearance.In conclusion,this study introduced an innovative strategy for the identification of active trace components in TCM.This approach holds promise for accelerating research on medicinal components within this field.
基金supported by the Qi-Huang Chief Scientist Program of the National Administration of Traditional Chinese Medicine(2020)the National Key Research and Development Program of China(No.2022YFC3501705)+1 种基金Shanghai Sailing Program(No.23YF1447500)the China Postdoctoral Science Foundation(No.2023M732335).
文摘Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.
基金supported by the National Natural Science Foundation of China(Nos.82104015,82003609,and 81973190)the Guangdong Basic and Applied Basic Research Foundation(Nos.2020A1515110415,2020A1515110453,and 2020B1515020033)+1 种基金the Characteristic Innovation Project of General Universities in Guangdong Province(No.2024KTSCX167)the Science and Technology Planning Project of Guangzhou City(No.202201010485).
文摘Peganum harmala L.(P.harmala)is a significant economic and medicinal plant.The seeds of P.harmala have been extensively utilized in traditional Chinese medicine,Uighur medicine,and Mongolian medicine,as documented in the Drug Standard of the Ministry of Health of China.Twelve novel tryptamine-derived alkaloids(1−12)and eight known compounds(13−20)were isolated from P.harmala seeds.Compounds 1 and 2 represent the first reported instances of tryptamine-derived heteromers,comprising tryptamine and aniline fragments with previously undocumented C-3−N-1′linkage and C-3−C-4′connection,respectively.Compounds 3−5 were identified as indole-quinazoline heteromers,exhibiting a novel C-3 and NH-1′linkage between indole and quinazoline-derived fragments.Compound 6 demonstrates the dimerization pattern of C-C linked tryptamine-quinazoline dimer.Compound 8 represents a tryptamine-derived heterodimer with a distinctive carbon skeleton,featuring an unusual spiro-tricyclic ring(7)and conventional bicyclic tryptamine.Compounds 9−11 constitute novel 6/5/5/5 spiro-tetracyclic tryptamine-derived alkaloids presenting a unique ring system of tryptamine-spiro-pyrrolizine.Compounds 1−3 and 6−11 were identified as racemates.Compounds 2,7,9,10,and 12 were confirmed via X-ray crystallographic analysis.All isolated compounds(1−20)exhibited varying degrees of antiviral efficacy against respiratory syncytial virus(RSV).Notably,the anti-RSV activity of compound 12(IC505.01±0.14μmol·L^(−1))surpassed that of the positive control(ribavirin,IC506.23±0.95μmol·L^(−1)),as validated through plaque reduction and immunofluorescence assays.The identification of anti-RSV compounds from P.harmala seeds may enhance the development and application of this plant in antiviral therapeutic products.
基金supported by Qinghai Science and Technology Achievement Transformation Project(2021-SF-149)Natural Science Fund of Education Department of Anhui Province(2024AH051669)+2 种基金Innovation and Entrepreneurship Training Program for College Students(S202410373040)Anhui Provincial College Student Innovation and Entrepreneurship Project(20221502032)School-Level Quality Engineering Project of Huaibei Normal University(2024xjsxyj003).
文摘Anisodus tanguticus (Maxim.) Pascher, a medicinal plant in the Solanaceae family, is widely distributed across the Qinghai-Tibet Plateau. Its medicinal properties, particularly the tropane alkaloids, are influenced by various ecological factors, but the underlying ecological mechanisms remain poorly understood. This study aimed to investigate how key environmental variables influence both the morphological traits and tropane alkaloid contents of A. tanguticus, with the goal of providing data to support the sustainable cultivation and management of this species. We collected samples from 71 sites across its natural habitat, analyzing the effects of factors such as soil nutrients, altitude, and climate variables on plant traits and alkaloid composition. Statistical methods including Pearson correlation analysis, multiple regression, random forest analysis, and structural equation modeling were used to identify key environmental drivers. Our results indicate that available phosphorus significantly affects aboveground traits, while Cu concentration is most influential for root development. Altitude and longitude were found to be the main determinants of biomass accumulation. Regarding alkaloid content, Mg concentration in the soil was closely linked to anisodine levels, while altitude and latitude were the primary factors influencing anisodamine and atropine content, respectively. These findings provide essential insights into the ecological factors that govern the growth and medicinal compound production in A. tanguticus. Our research not only contributes to understanding the plant’s ecological requirements but also offers practical guidelines for selecting optimal cultivation conditions to enhance both yield and alkaloid quality, supporting sustainable use and conservation of this valuable medicinal resource.
