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
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
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
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
Benzylisoquinoline alkaloids(BIAs)are a structurally diverse group of plant metabolites renowned for their pharmacological properties.However,sustainable sources for these compounds remain limited.Consequently,researc...Benzylisoquinoline alkaloids(BIAs)are a structurally diverse group of plant metabolites renowned for their pharmacological properties.However,sustainable sources for these compounds remain limited.Consequently,researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches.CYP80B,a family of cytochrome P450(CYP450)enzymes,plays a crucial role in BIA biosynthesis.Previously reported CYP80Bs are known to catalyze the 3′-hydroxylation of(S)-Nmethylcoclaurine,with the N-methyl group essential for catalytic activity.In this study,we successfully cloned a full-length CYP80B gene(St CYP80B)from Stephania tetrandra(S.tetrandra)and identified its function using a yeast heterologous expression system.Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that St CYP80B could catalyze Nmethylcoclaurine and coclaurine into their respective 3'-hydroxylated products.Notably,St CYP80B exhibited an expanded substrate selectivity compared to previously reported wildtype CYP80Bs,as it did not require an N-methyl group for hydroxylase activity.Furthermore,St CYP80B displayed a clear preference for the(S)-configuration.Co-expression of St CYP80B with the CYP450 reductases(CPRs,StCPR1,and StCPR2),also cloned from S.tetrandra,significantly enhanced the catalytic activity towards(S)-coclaurine.Site-directed mutagenesis of St CYP80B revealed that the residue H205 is crucial for coclaurine catalysis.Additionally,St CYP80B exhibited tissue-specific expression in plants.This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.展开更多
One of the largest subfamilies within the famous Daphniphyllum alkaloid family is made up of the yuzurimine-type(or macrodaphniphyllamine-type) alkaloids. Their complex aza-polycyclic caged structures, several contigu...One of the largest subfamilies within the famous Daphniphyllum alkaloid family is made up of the yuzurimine-type(or macrodaphniphyllamine-type) alkaloids. Their complex aza-polycyclic caged structures, several contiguous stereogenic centers, and vicinal all-carbon quaternary centers make these alkaloids formidable challenge for synthetic chemists. Recently, synthesis of these alkaloids has received extensive attention from our community. Herein, we wish to report the total synthesis of C_(14)–epideoxycalyciphylline H, a putative member of yuzurimine-type alkaloid subfamily. Key transformations employed in our approach include an intramolecular Prins reaction and a Pd-catalyzed enyne cycloisomerization. In addition, synthesis of a daphnezomine L-type alkaloid, paxdaphnidine A, was also studied.展开更多
Three novel matrine-type alkaloids(1-3)and two unprecedented aloperine-type alkaloids(4 and 5)were isolated from the root of Sophora tonkinensis and the seeds of Sophora alopecuroides respectively.Notably,compound 1 p...Three novel matrine-type alkaloids(1-3)and two unprecedented aloperine-type alkaloids(4 and 5)were isolated from the root of Sophora tonkinensis and the seeds of Sophora alopecuroides respectively.Notably,compound 1 possessed an unprecedented 6/5/6 tricyclic skeleton,while compounds 2 and 3 characterized by rare 6/6/5/6 tetracyclic system and 6/6/6/6/6 pentacyclic system respectively.Moreover,compound 4 possessed an unprecedented 6/7/6/6 tetracyclic core,and compound 5 characterized by rare 6/6/6/6tetracyclic skeleton.Their structures were elucidated by comprehensive spectroscopic data analysis and electronic circular dichroism(ECD)calculations.Biological tests indicated that compound 5 displayed significant anti-tobacco mosaic virus(TMV)activity compared with the positive control ningnanmycin.展开更多
OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins,flavones, and alkaloids on experimental animals with autoimmune diseases(AIDs).METHODS: The protocol for this syst...OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins,flavones, and alkaloids on experimental animals with autoimmune diseases(AIDs).METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO(CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, Pub Med,Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases;consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines.RESULTS: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin(IL)-1β[standardized mean difference(SMD) =-1.94, 95%confidence interval(CI)(-2.99,-0.90), P = 0.0003], IL-6 [SMD =-1.65, 95% CI(-2.33,-0.97,) P < 0.000 01],IL-17 [SMD =-2.41, 95% CI(-3.61,-1.20), P <0.0001], tumor necrosis factor(TNF)-α [SMD =-1.84, 95%CI(-2.61,-1.06), P < 0.0001], and interferon(IFN)-γ[SMD =-1.54, 95% CI(-2.43,-0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI(0.15,2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI(1.39,2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD =-0.63, 95% CI(-1.82, 0.57), P = 0.30].CONCLUTIONS: Substances containing saponins,flavones, and alkaloids regulated the changes of immunerelated cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.展开更多
This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala L.Among these compounds,1 and 2 were characterized as rareβ-carbol...This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala L.Among these compounds,1 and 2 were characterized as rareβ-carboline-quinazoline dimers exhibiting axial chirality.Compound 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring,and compound 4 was a novel annomontineβ-carboline.The structures of these compounds were elucidated by spectroscopic data and quantum mechanical calculations.The biosynthetic pathways of 1−3 were proposed.Additionally,the cytotoxicity of some isolates against four cancer cell lines(HL-60,A549,MDA-MB-231,and DU145)was evaluated.Notably,compound 4 exhibited significant cytotoxicity against HL-60,A549,and DU145 cells with IC_(50) values of 12.39,12.80,and 30.65μmol·L^(−1),respectively.Furthermore,compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC_(50) value of 17.32μmol·L^(−1).展开更多
Wampee(Clausena lansium)is an important evergreen fruit tree native to southern China that has a long history of use for medicinal purposes.Here,a chromosome-level genome of C.lansium was constructed with a genome siz...Wampee(Clausena lansium)is an important evergreen fruit tree native to southern China that has a long history of use for medicinal purposes.Here,a chromosome-level genome of C.lansium was constructed with a genome size of 282.9 Mb and scaffold N50 of 30.75 Mb.The assembled genome contains 48.70%repetitive elements and 24,381 protein-coding genes.Comparative genomic analysis showed that C.lansium diverged from Aurantioideae 15.91-24.95 million years ago.Additionally,some expansive and specific gene families related to methyltransferase activity and S-adenosylmethionine-dependent methyltransferase activity were also identified.Further analysis indicated that N-methyltransferase(NMT)is mainly involved in alkaloid biosynthesis and O-methyltransferase(OMT)participates in the regulation of coumarin accumulation in wampee.This suggested that wampee's richness in alkaloids and coumarins might be due to the gene expansions of NMT and OMT.The tandem repeat event was one of the major reasons for the NMT expansion.Hence,the reference genome of C.lansium will facilitate the identification of some useful medicinal compounds from wampee resources and reveal their biosynthetic pathways.展开更多
Plant alkaloids,renowned for their structural diversity and bioactivity,are prominent in both modern and traditional medicine[1].Unraveling the intricacies of plant alkaloid biosynthesis could pave the way for the dis...Plant alkaloids,renowned for their structural diversity and bioactivity,are prominent in both modern and traditional medicine[1].Unraveling the intricacies of plant alkaloid biosynthesis could pave the way for the discovery of new natural products and pathways.It may also shed light on the roles of existing pathways in host biology and provide valuable tools for metabolic engineering in plants and microbes[2].Unlike other major classes of plant natural products,such as terpenoids and polyketides,the formation of alkaloid scaffolds does not conform to a uniform chemical theme or depend on a singular enzyme class[3].A case in point is the Lycopodium alkaloids in the Lycopodiaceae family,where the enzymes responsible for their core scaffold construction remain unidentified[4].展开更多
As one of the main active components of Dendrobium catenatum, alkaloids have high medicinal value. The physicochemicalproperties, conserved domains and motifs, phylogenetic analysis, and cis-acting elements of the gen...As one of the main active components of Dendrobium catenatum, alkaloids have high medicinal value. The physicochemicalproperties, conserved domains and motifs, phylogenetic analysis, and cis-acting elements of the genefamily members in the alkaloid biosynthesis pathway of D. catenatum were analyzed by bioinformatics, and theexpression of the genes in different years and tissues was analyzed by qRT-PCR. There are 16 gene families,including 25 genes, in the D. catenatum alkaloid biosynthesis pathway. The analysis of conserved domains andmotifs showed that the types, quantities, and orders of domains and motifs were similar among members ofthe same family, but there were significant differences among families. Phylogenetic analysis indicated that thegene family members showed some evolutionary conservation. Cis-acting element analysis revealed that therewere a large number of light-responsive elements and MYB (v-myb avian myeloblastosis viral oncogene homolog)-related elements in these genes. qRT-PCR showed that expressions of gene family members involved in alkaloidsynthesis were different in different years and tissues of D. catenatum. This study provides a theoretical basisfor further exploration of the regulatory mechanisms of these genes in the alkaloid biosynthesis of D. catenatum.展开更多
Flaviviruses,such as dengue virus(DENV),Zika virus(ZIKV),and Japanese encephalitis virus(JEV),represent a substantial public health challenge as there are currently no approved treatments available.Here,we investigate...Flaviviruses,such as dengue virus(DENV),Zika virus(ZIKV),and Japanese encephalitis virus(JEV),represent a substantial public health challenge as there are currently no approved treatments available.Here,we investigated the antiviral effects of bis-benzylisoquinoline alkaloids(BBAs)on flavivirus infections.We evaluated five specific BBAs—berbamine,tetrandrine,iso-tetrandrine,fangchinoline,and cepharanthine—and found that they effectively inhibited infections by ZIKV,DENV,or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle.Furthermore,we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes,causing lysosomal pH alkalization.Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels,leading to lysosomal dysfunction and reducing the expression of NCAM1,a key receptor for the entry of ZIKV into cells,thereby decreasing cells susceptibility to ZIKV infection.Additionally,BBAs inhibited the fusion of autophagosomes and lysosomes,significantly reducing viral RNA replication.Collectively,our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy,respectively,underscoring the potential of BBAs as therapeutic agents against flavivirus infections.展开更多
Four new isoquinoline alkaloids,hypecotumines A-D(1-4),were isolated and identified from the whole herbs of Hypecoum erectum L.Their structures were determined by a combination of HRESIMS,NMR,and X-ray diffraction ana...Four new isoquinoline alkaloids,hypecotumines A-D(1-4),were isolated and identified from the whole herbs of Hypecoum erectum L.Their structures were determined by a combination of HRESIMS,NMR,and X-ray diffraction analysis methods.Compounds 1-4 were characterized by a terminal double bond at C-9 and their plausible biosynthetic pathway was hypothesized.Since PCSK9 plays a key role in the development of cardiovascular disease(CVD),exploration of PCSK inhibitors from natural products are beneficial for drug discovery of CVD treatment.SPR and Western blot assays showed compound 4 had PCSK9 inhibition activity with KD value of 59.9μM and thus elevated the LDLR level.Further molecular docking studies demonstrated that 4 and PCSK9 could form stable interactions via key hydrogen bonds.展开更多
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 consid...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.展开更多
Alkaloids,a diverse group of naturally occurring organic compounds have demonstrated significant potential in the management of allergic responses.These bioactive compounds are commonly found in plants and possess var...Alkaloids,a diverse group of naturally occurring organic compounds have demonstrated significant potential in the management of allergic responses.These bioactive compounds are commonly found in plants and possess various pharmacological properties including immunomodulatory,anti-inflammatory and antihistaminic effects.Recent studies highlight their ability to inhibit the release of histamines and other proinflammatory mediators such as interleukins,NF-κB,TNF-α,CD4+regulatory T cells and T helper 2(Th2)cells etc.,thereby reducing the severity of allergic reactions.Alkaloids such as berberine,ephedrine and quinine have shown particular promises in preclinical models.Additionally,the modulation of immune cells activity by alkaloids suggests their role in preventing the onset of allergic symptoms.Despite these promising findings,further research is needed to fully elucidate the molecular mechanism and to explore the therapeutic potential of many alkaloids in clinical settings.This review discusses the source and potential of alkaloids as therapeutic agents in treating allergic conditions and examines the mechanism through which they exert their anti-allergy effects.展开更多
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 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 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.
文摘Benzylisoquinoline alkaloids(BIAs)are a structurally diverse group of plant metabolites renowned for their pharmacological properties.However,sustainable sources for these compounds remain limited.Consequently,researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches.CYP80B,a family of cytochrome P450(CYP450)enzymes,plays a crucial role in BIA biosynthesis.Previously reported CYP80Bs are known to catalyze the 3′-hydroxylation of(S)-Nmethylcoclaurine,with the N-methyl group essential for catalytic activity.In this study,we successfully cloned a full-length CYP80B gene(St CYP80B)from Stephania tetrandra(S.tetrandra)and identified its function using a yeast heterologous expression system.Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that St CYP80B could catalyze Nmethylcoclaurine and coclaurine into their respective 3'-hydroxylated products.Notably,St CYP80B exhibited an expanded substrate selectivity compared to previously reported wildtype CYP80Bs,as it did not require an N-methyl group for hydroxylase activity.Furthermore,St CYP80B displayed a clear preference for the(S)-configuration.Co-expression of St CYP80B with the CYP450 reductases(CPRs,StCPR1,and StCPR2),also cloned from S.tetrandra,significantly enhanced the catalytic activity towards(S)-coclaurine.Site-directed mutagenesis of St CYP80B revealed that the residue H205 is crucial for coclaurine catalysis.Additionally,St CYP80B exhibited tissue-specific expression in plants.This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
基金the National Natural Science Foundation of China (Nos.21971104 and 22271136)Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis (No.ZDSYS20190902093215877)+4 种基金Guangdong Provincial Key Laboratory of Catalysis (No.2020B121201002)Guangdong Innovative Program (No.2019BT02Y335)Education Department of Guangdong Province, Key research projects in colleges and universities in Guangdong Province (No.2021ZDZX2035)Shenzhen Nobel Prize Scientists Laboratory Project (No.C17783101)Innovative Team of Universities in Guangdong Province (No.2020KCXTD016)。
文摘One of the largest subfamilies within the famous Daphniphyllum alkaloid family is made up of the yuzurimine-type(or macrodaphniphyllamine-type) alkaloids. Their complex aza-polycyclic caged structures, several contiguous stereogenic centers, and vicinal all-carbon quaternary centers make these alkaloids formidable challenge for synthetic chemists. Recently, synthesis of these alkaloids has received extensive attention from our community. Herein, we wish to report the total synthesis of C_(14)–epideoxycalyciphylline H, a putative member of yuzurimine-type alkaloid subfamily. Key transformations employed in our approach include an intramolecular Prins reaction and a Pd-catalyzed enyne cycloisomerization. In addition, synthesis of a daphnezomine L-type alkaloid, paxdaphnidine A, was also studied.
基金financially supported by the National Natural Science Foundation of China(Nos.32160103 and U1812403)the Science and Technology Department of Guizhou Province(Nos.QKH ZC-[2021]-YB181,QKH CXTD-[2022]-007 and QKH ZYD-[2022]-4015)Guizhou Provincial Engineering Research Center for Natural Drugs。
文摘Three novel matrine-type alkaloids(1-3)and two unprecedented aloperine-type alkaloids(4 and 5)were isolated from the root of Sophora tonkinensis and the seeds of Sophora alopecuroides respectively.Notably,compound 1 possessed an unprecedented 6/5/6 tricyclic skeleton,while compounds 2 and 3 characterized by rare 6/6/5/6 tetracyclic system and 6/6/6/6/6 pentacyclic system respectively.Moreover,compound 4 possessed an unprecedented 6/7/6/6 tetracyclic core,and compound 5 characterized by rare 6/6/6/6tetracyclic skeleton.Their structures were elucidated by comprehensive spectroscopic data analysis and electronic circular dichroism(ECD)calculations.Biological tests indicated that compound 5 displayed significant anti-tobacco mosaic virus(TMV)activity compared with the positive control ningnanmycin.
基金Fundamental Research Program of Shanxi Province:to Explore the Material Basis and Mechanism of Codonopsis Pilosula for Preventing and Treating Immune Thrombocytopenia based on Network Pharmacology and Molecular Docking (202203021221251)the Doctor Starting Foundation of First Hospital of Shanxi Medical University:Material Basis and Mechanism of Codonopsis Pilosula for Preventing and Treating Immune Thrombocytopenia (YB2203)。
文摘OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins,flavones, and alkaloids on experimental animals with autoimmune diseases(AIDs).METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO(CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, Pub Med,Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases;consequently, corresponding data extraction tables were prepared. Systematic Review Centre for Laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum cytokines.RESULTS: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin(IL)-1β[standardized mean difference(SMD) =-1.94, 95%confidence interval(CI)(-2.99,-0.90), P = 0.0003], IL-6 [SMD =-1.65, 95% CI(-2.33,-0.97,) P < 0.000 01],IL-17 [SMD =-2.41, 95% CI(-3.61,-1.20), P <0.0001], tumor necrosis factor(TNF)-α [SMD =-1.84, 95%CI(-2.61,-1.06), P < 0.0001], and interferon(IFN)-γ[SMD =-1.54, 95% CI(-2.43,-0.65), P = 0.0007], but increased serum levels of IL-4 [SMD = 1.30, 95% CI(0.15,2.44), P = 0.03) and IL-10 [SMD = 2.05, 95% CI(1.39,2.70), P < 0.000 01) in animal models. However, no significant regulatory effect of these three active components was observed on serum levels of IL-2 [SMD =-0.63, 95% CI(-1.82, 0.57), P = 0.30].CONCLUTIONS: Substances containing saponins,flavones, and alkaloids regulated the changes of immunerelated cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.
基金supported by the National Natural Science Foundation of China(No.81773604)the National Science and Technology Major Project of the Ministry of Science and Technology of China(No.2018ZX09735005)+1 种基金the Doctoral Scientific Research Fund Project of Nanyang Institute of Technology(No.510197)the Interdisciplinary Sciences Project,Nanyang Institute of Technology(No.520097).
文摘This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala L.Among these compounds,1 and 2 were characterized as rareβ-carboline-quinazoline dimers exhibiting axial chirality.Compound 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring,and compound 4 was a novel annomontineβ-carboline.The structures of these compounds were elucidated by spectroscopic data and quantum mechanical calculations.The biosynthetic pathways of 1−3 were proposed.Additionally,the cytotoxicity of some isolates against four cancer cell lines(HL-60,A549,MDA-MB-231,and DU145)was evaluated.Notably,compound 4 exhibited significant cytotoxicity against HL-60,A549,and DU145 cells with IC_(50) values of 12.39,12.80,and 30.65μmol·L^(−1),respectively.Furthermore,compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC_(50) value of 17.32μmol·L^(−1).
基金supported by the Central Public-interest Scientific Institution Basal Research Fund for the Chinese Academy of Tropical Agricultural Sciences(1630062019010 and 1630062020010)the Fund of Protection of Species Resources for the Ministry of Agriculture and Rural Affairs of China(125A0605)。
文摘Wampee(Clausena lansium)is an important evergreen fruit tree native to southern China that has a long history of use for medicinal purposes.Here,a chromosome-level genome of C.lansium was constructed with a genome size of 282.9 Mb and scaffold N50 of 30.75 Mb.The assembled genome contains 48.70%repetitive elements and 24,381 protein-coding genes.Comparative genomic analysis showed that C.lansium diverged from Aurantioideae 15.91-24.95 million years ago.Additionally,some expansive and specific gene families related to methyltransferase activity and S-adenosylmethionine-dependent methyltransferase activity were also identified.Further analysis indicated that N-methyltransferase(NMT)is mainly involved in alkaloid biosynthesis and O-methyltransferase(OMT)participates in the regulation of coumarin accumulation in wampee.This suggested that wampee's richness in alkaloids and coumarins might be due to the gene expansions of NMT and OMT.The tandem repeat event was one of the major reasons for the NMT expansion.Hence,the reference genome of C.lansium will facilitate the identification of some useful medicinal compounds from wampee resources and reveal their biosynthetic pathways.
文摘Plant alkaloids,renowned for their structural diversity and bioactivity,are prominent in both modern and traditional medicine[1].Unraveling the intricacies of plant alkaloid biosynthesis could pave the way for the discovery of new natural products and pathways.It may also shed light on the roles of existing pathways in host biology and provide valuable tools for metabolic engineering in plants and microbes[2].Unlike other major classes of plant natural products,such as terpenoids and polyketides,the formation of alkaloid scaffolds does not conform to a uniform chemical theme or depend on a singular enzyme class[3].A case in point is the Lycopodium alkaloids in the Lycopodiaceae family,where the enzymes responsible for their core scaffold construction remain unidentified[4].
基金the Forestry Science and Technology Innovation and promotion Project of Jiangsu Province‘Long-Term Research Base of Forest and Wetland Positioning Monitoring in Jiangsu Province’(Grant No.LYKJ[2020]21)Natural Science Foundation of Jiangsu Province,China(Grant No.BK20210800)+1 种基金the National Natural Science Foundation of China(Grant Nos.32001341 and 32202523)Jiangsu Agriculture Science and Technology Innovation Fund(Grant No.CX(21)3047).
文摘As one of the main active components of Dendrobium catenatum, alkaloids have high medicinal value. The physicochemicalproperties, conserved domains and motifs, phylogenetic analysis, and cis-acting elements of the genefamily members in the alkaloid biosynthesis pathway of D. catenatum were analyzed by bioinformatics, and theexpression of the genes in different years and tissues was analyzed by qRT-PCR. There are 16 gene families,including 25 genes, in the D. catenatum alkaloid biosynthesis pathway. The analysis of conserved domains andmotifs showed that the types, quantities, and orders of domains and motifs were similar among members ofthe same family, but there were significant differences among families. Phylogenetic analysis indicated that thegene family members showed some evolutionary conservation. Cis-acting element analysis revealed that therewere a large number of light-responsive elements and MYB (v-myb avian myeloblastosis viral oncogene homolog)-related elements in these genes. qRT-PCR showed that expressions of gene family members involved in alkaloidsynthesis were different in different years and tissues of D. catenatum. This study provides a theoretical basisfor further exploration of the regulatory mechanisms of these genes in the alkaloid biosynthesis of D. catenatum.
基金supported by the National Key Research and Development Program of China(2022YFD1800100)the National Natural Science Foundation of China(32302843,32070702,and 82161128014)+5 种基金GuangDong Basic and Applied Basic Research Foundation(2023A1515010748)Innovation and Technology Fund of Hong Kong(MRP/064/21,GHP/097/20GD,and MHP/072/21)Hong Kong Research Grant Council(RGC)grant(11103620 and 11104422)research grants from Shenzhen Science and Technology Innovation Committee(SGDX20201103093201010 and JCYJ20210324134007020)Kunshan Shuang Chuang Grant(kssc202302073)the Kunshan Municipal Government research funding。
文摘Flaviviruses,such as dengue virus(DENV),Zika virus(ZIKV),and Japanese encephalitis virus(JEV),represent a substantial public health challenge as there are currently no approved treatments available.Here,we investigated the antiviral effects of bis-benzylisoquinoline alkaloids(BBAs)on flavivirus infections.We evaluated five specific BBAs—berbamine,tetrandrine,iso-tetrandrine,fangchinoline,and cepharanthine—and found that they effectively inhibited infections by ZIKV,DENV,or JEV by blocking virus entry and genome replication stages in the flavivirus life cycle.Furthermore,we synthesized a fluorophore-conjugated BBA and showed that BBAs targeted endolysosomes,causing lysosomal pH alkalization.Mechanistic studies on inhibiting ZIKV infection by BBAs revealed that these compounds blocked TRPML channels,leading to lysosomal dysfunction and reducing the expression of NCAM1,a key receptor for the entry of ZIKV into cells,thereby decreasing cells susceptibility to ZIKV infection.Additionally,BBAs inhibited the fusion of autophagosomes and lysosomes,significantly reducing viral RNA replication.Collectively,our results suggest that BBAs inhibit flavivirus entry and replication by compromising endolysosomal trafficking and autophagy,respectively,underscoring the potential of BBAs as therapeutic agents against flavivirus infections.
基金supported by National Key R&D Program of China(2022YFF1100301)Major Science and Technology Project of Henan Province(231100310200)+1 种基金Yunnan Applied Basic Research Projects(202301AS070057)Yunnan Science and Technology Department(202305AH340005),DR PLANT.
文摘Four new isoquinoline alkaloids,hypecotumines A-D(1-4),were isolated and identified from the whole herbs of Hypecoum erectum L.Their structures were determined by a combination of HRESIMS,NMR,and X-ray diffraction analysis methods.Compounds 1-4 were characterized by a terminal double bond at C-9 and their plausible biosynthetic pathway was hypothesized.Since PCSK9 plays a key role in the development of cardiovascular disease(CVD),exploration of PCSK inhibitors from natural products are beneficial for drug discovery of CVD treatment.SPR and Western blot assays showed compound 4 had PCSK9 inhibition activity with KD value of 59.9μM and thus elevated the LDLR level.Further molecular docking studies demonstrated that 4 and PCSK9 could form stable interactions via key hydrogen bonds.
文摘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.
基金supported by Postdoctoral research startup funding from Zhejiang Sci-Tech University(22042342-Y).
文摘Alkaloids,a diverse group of naturally occurring organic compounds have demonstrated significant potential in the management of allergic responses.These bioactive compounds are commonly found in plants and possess various pharmacological properties including immunomodulatory,anti-inflammatory and antihistaminic effects.Recent studies highlight their ability to inhibit the release of histamines and other proinflammatory mediators such as interleukins,NF-κB,TNF-α,CD4+regulatory T cells and T helper 2(Th2)cells etc.,thereby reducing the severity of allergic reactions.Alkaloids such as berberine,ephedrine and quinine have shown particular promises in preclinical models.Additionally,the modulation of immune cells activity by alkaloids suggests their role in preventing the onset of allergic symptoms.Despite these promising findings,further research is needed to fully elucidate the molecular mechanism and to explore the therapeutic potential of many alkaloids in clinical settings.This review discusses the source and potential of alkaloids as therapeutic agents in treating allergic conditions and examines the mechanism through which they exert their anti-allergy effects.
