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1.
J Agric Food Chem ; 72(19): 10897-10908, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691522

RESUMO

Gramine (GRM), which occurs in Gramineae plants, has been developed to be a biological insecticide. Exposure to GRM was reported to induce elevations of serum ALT and AST in rats, but the mechanisms of the observed hepatotoxicity have not been elucidated. The present study aimed to identify reactive metabolites that potentially participate in the toxicity. In rat liver microsomal incubations fortified with glutathione or N-acetylcysteine, one oxidative metabolite (M1), one glutathione conjugate (M2), and one N-acetylcysteine conjugate (M3) were detected after exposure to GRM. The corresponding conjugates were detected in the bile and urine of rats after GRM administration. CYP3A was the main enzyme mediating the metabolic activation of GRM. The detected GSH and NAC conjugates suggest that GRM was metabolized to a quinone imine intermediate. Both GRM and M1 showed significant toxicity to rat primary hepatocytes.


Assuntos
Ativação Metabólica , Citocromo P-450 CYP3A , Hepatócitos , Ratos Sprague-Dawley , Animais , Ratos , Masculino , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP3A/genética , Microssomos Hepáticos/metabolismo , Glutationa/metabolismo , Inseticidas/toxicidade , Inseticidas/metabolismo , Alcaloides/metabolismo
2.
Sci Total Environ ; 929: 172590, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38642746

RESUMO

Harmful cyanobacterial blooms have increased globally, releasing hazardous cyanotoxins that threaten the safety of water resources. Constructed wetlands (CWs) are a nature-based and low-cost solution to purify and remove cyanotoxins from water. However, bio-mechanistic understanding of the biotransformation processes expected to drive cyanotoxin removal in such systems is poor, and primarily focused on bacteria. Thus, the present study aimed at exploring the fungal contribution to microcystin-LR and cylindrospermopsin biodegradation in CWs. Based on CW mesocosms, two experimental approaches were taken: a) amplicon sequencing studies were conducted to investigate the involvement of the fungal community; and b) CW fungal isolates were tested for their microcystin-LR and cylindrospermopsin degradation capabilities. The data uncovered effects of seasonality (spring or summer), cyanotoxin exposure, vegetation (unplanted, Juncus effusus or Phragmites australis) and substratum (sand or gravel) on the fungal community structure. Additionally, the arbuscular mycorrhizal fungus Rhizophagus and the endophyte Myrmecridium showed positive correlations with cyanotoxin removal. Fungal isolates revealed microcystin-LR-removal potentials of approximately 25 % in in vitro biodegradation experiments, while the extracellular chemical fingerprint of the cultures suggested a potential intracellular metabolization. The results from this study may help us understand the fungal contribution to cyanotoxin removal, as well as their ecology in CWs.


Assuntos
Biodegradação Ambiental , Fungos , Microcistinas , Áreas Alagadas , Microcistinas/metabolismo , Fungos/metabolismo , Toxinas Bacterianas/metabolismo , Alcaloides/metabolismo , Toxinas de Cianobactérias , Toxinas Marinhas/metabolismo , Poluentes Químicos da Água/metabolismo , Eliminação de Resíduos Líquidos/métodos , Uracila/análogos & derivados , Uracila/metabolismo
3.
BMC Plant Biol ; 24(1): 276, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605285

RESUMO

BACKGROUND: Stephania kwangsiensis Lo (Menispermaceae) is a well-known Chinese herbal medicine, and its bulbous stems are used medicinally. The storage stem of S. kwangsiensis originated from the hypocotyls. To date, there are no reports on the growth and development of S. kwangsiensis storage stems. RESULTS: The bulbous stem of S. kwangsiensis, the starch diameter was larger at the stable expanding stage (S3T) than at the unexpanded stage (S1T) or the rapidly expanding stage (S2T) at the three different time points. We used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and Illumina sequencing to identify key genes involved in bulbous stem development. A large number of differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) were identified. Based on the differential expression profiles of the metabolites, alkaloids, lipids, and phenolic acids were the top three differentially expressed classes. Compared with S2T, significant changes in plant signal transduction and isoquinoline alkaloid biosynthesis pathways occurred at both the transcriptional and metabolic levels in S1T. In S2T compared with S3T, several metabolites involved in tyrosine metabolism were decreased. Temporal analysis of S1T to S3T indicated the downregulation of phenylpropanoid biosynthesis, including lignin biosynthesis. The annotation of key pathways showed an up-down trend for genes and metabolites involved in isoquinoline alkaloid biosynthesis, whereas phenylpropanoid biosynthesis was not completely consistent. CONCLUSIONS: Downregulation of the phenylpropanoid biosynthesis pathway may be the result of carbon flow into alkaloid synthesis and storage of lipids and starch during the development of S. kwangsiensis bulbous stems. A decrease in the number of metabolites involved in tyrosine metabolism may also lead to a decrease in the upstream substrates of phenylpropane biosynthesis. Downregulation of lignin synthesis during phenylpropanoid biosynthesis may loosen restrictions on bulbous stem expansion. This study provides the first comprehensive analysis of the metabolome and transcriptome profiles of S. kwangsiensis bulbous stems. These data provide guidance for the cultivation, breeding, and harvesting of S. kwangsiensis.


Assuntos
Alcaloides , Plantas Medicinais , Stephania , Stephania/química , Stephania/metabolismo , Plantas Medicinais/metabolismo , Cromatografia Líquida/métodos , Lignina/metabolismo , Espectrometria de Massas em Tandem , Melhoramento Vegetal , Perfilação da Expressão Gênica , Transcriptoma , Alcaloides/metabolismo , Amido/metabolismo , Isoquinolinas/metabolismo , Tirosina/metabolismo , Lipídeos , Regulação da Expressão Gênica de Plantas
4.
BMC Genomics ; 25(1): 418, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38679745

RESUMO

BACKGROUND: Plant specialized (or secondary) metabolites (PSM), also known as phytochemicals, natural products, or plant constituents, play essential roles in interactions between plants and environment. Although many research efforts have focused on discovering novel metabolites and their biosynthetic genes, the resolution of metabolic pathways and identified biosynthetic genes was limited by rudimentary analysis approaches and enormous number of candidate genes. RESULTS: Here we integrated state-of-the-art automated machine learning (ML) frame AutoGluon-Tabular and multi-omics data from Arabidopsis to predict genes encoding enzymes involved in biosynthesis of plant specialized metabolite (PSM), focusing on the three main PSM categories: terpenoids, alkaloids, and phenolics. We found that the related features of genomics and proteomics were the top two crucial categories of features contributing to the model performance. Using only these key features, we built a new model in Arabidopsis, which performed better than models built with more features including those related with transcriptomics and epigenomics. Finally, the built models were validated in maize and tomato, and models tested for maize and trained with data from two other species exhibited either equivalent or superior performance to intraspecies predictions. CONCLUSIONS: Our external validation results in grape and poppy on the one hand implied the applicability of our model to the other species, and on the other hand showed enormous potential to improve the prediction of enzymes synthesizing PSM with the inclusion of valid data from a wider range of species.


Assuntos
Arabidopsis , Genômica , Aprendizado de Máquina , Arabidopsis/genética , Arabidopsis/metabolismo , Genômica/métodos , Alcaloides/biossíntese , Alcaloides/metabolismo , Terpenos/metabolismo , Proteômica/métodos , Metabolômica/métodos , Genes de Plantas , Plantas/genética , Plantas/metabolismo , Fenóis/metabolismo , Multiômica
5.
Sci Rep ; 14(1): 6000, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472367

RESUMO

Oriental poppy (Papaver orientale L.) belonging to the Papaveraceae family, has the capacity to synthesize a wide range of benzylisoquinoline alkaloids (BIAs). This experiment was conducted to investigate the effects of green and chemical copper oxide nanoparticles (CuO NPs) elicitors on oxidative stress and the BIAs biosynthesis pathway in the cell suspension culture of P. orientale. This research shows that both green and chemical CuO NPs at concentrations of 20 mg/L and 40 mg/L, induce oxidative stress in the cell suspension of P. orientale by increasing the production of H2O2 and the activity of antioxidant enzymes. The comparison of treatments revealed that utilizing a lower concentration of CuO NPs (20 mg/L) and extending the duration of cell suspension incubation (up to 48 h) play a more influential role in inducing the expression of the BIAs biosynthesis pathway genes (PsWRKY, TYDC, SalSyn, SalR, SalAT, T6ODM, COR and CODM) and increasing the production of morphinan alkaloids (thebaine, codeine, and morphine). The overarching results indicate that the concentration of CuO NPs and the duration of cell treatment have a more significant impact than the nature of CuO NPs in inducing oxidative stress and stimulating the expression of the BIAs pathway genes.


Assuntos
Alcaloides , Benzilisoquinolinas , Nanopartículas Metálicas , Nanopartículas , Papaver , Papaver/genética , Cobre/metabolismo , Peróxido de Hidrogênio/metabolismo , Morfina/metabolismo , Alcaloides/metabolismo , Benzilisoquinolinas/metabolismo , Expressão Gênica
6.
Biomed Pharmacother ; 173: 116406, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460366

RESUMO

Sanguinarine is a quaternary ammonium benzophenanthine alkaloid found in traditional herbs such as Chelidonium, Corydalis, Sanguinarum, and Borovula. It has been proven to possess broad-spectrum biological activities, such as antitumor, anti-inflammatory, antiosteoporosis, neuroprotective, and antipathogenic microorganism activities. In this paper, recent progress on the biological activity and mechanism of action of sanguinarine and its derivatives over the past ten years is reviewed. The results showed that the biological activities of hematarginine and its derivatives are related mainly to the JAK/STAT, PI3K/Akt/mTOR, NF-κB, TGF-ß, MAPK and Wnt/ß-catenin signaling pathways. The limitations of using sanguinarine in clinical application are also discussed, and the research prospects of this subject are outlined. In general, sanguinarine, a natural medicine, has many pharmacological effects, but its toxicity and safety in clinical application still need to be further studied. This review provides useful information for the development of sanguinarine-based bioactive agents.


Assuntos
Alcaloides , Fosfatidilinositol 3-Quinases , Fosfatidilinositol 3-Quinases/metabolismo , Benzofenantridinas/farmacologia , Alcaloides/metabolismo , Isoquinolinas/farmacologia
7.
Nat Metab ; 6(3): 433-447, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38504132

RESUMO

Mitochondrial dysfunction and low nicotinamide adenine dinucleotide (NAD+) levels are hallmarks of skeletal muscle ageing and sarcopenia1-3, but it is unclear whether these defects result from local changes or can be mediated by systemic or dietary cues. Here we report a functional link between circulating levels of the natural alkaloid trigonelline, which is structurally related to nicotinic acid4, NAD+ levels and muscle health in multiple species. In humans, serum trigonelline levels are reduced with sarcopenia and correlate positively with muscle strength and mitochondrial oxidative phosphorylation in skeletal muscle. Using naturally occurring and isotopically labelled trigonelline, we demonstrate that trigonelline incorporates into the NAD+ pool and increases NAD+ levels in Caenorhabditis elegans, mice and primary myotubes from healthy individuals and individuals with sarcopenia. Mechanistically, trigonelline does not activate GPR109A but is metabolized via the nicotinate phosphoribosyltransferase/Preiss-Handler pathway5,6 across models. In C. elegans, trigonelline improves mitochondrial respiration and biogenesis, reduces age-related muscle wasting and increases lifespan and mobility through an NAD+-dependent mechanism requiring sirtuin. Dietary trigonelline supplementation in male mice enhances muscle strength and prevents fatigue during ageing. Collectively, we identify nutritional supplementation of trigonelline as an NAD+-boosting strategy with therapeutic potential for age-associated muscle decline.


Assuntos
Alcaloides , Sarcopenia , Humanos , Masculino , Camundongos , Animais , Sarcopenia/tratamento farmacológico , Sarcopenia/prevenção & controle , Sarcopenia/metabolismo , NAD/metabolismo , Caenorhabditis elegans , Envelhecimento , Músculo Esquelético/metabolismo , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Alcaloides/metabolismo
8.
J Integr Plant Biol ; 66(3): 510-531, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38441295

RESUMO

The basis of modern pharmacology is the human ability to exploit the production of specialized metabolites from medical plants, for example, terpenoids, alkaloids, and phenolic acids. However, in most cases, the availability of these valuable compounds is limited by cellular or organelle barriers or spatio-temporal accumulation patterns within different plant tissues. Transcription factors (TFs) regulate biosynthesis of these specialized metabolites by tightly controlling the expression of biosynthetic genes. Cutting-edge technologies and/or combining multiple strategies and approaches have been applied to elucidate the role of TFs. In this review, we focus on recent progress in the transcription regulation mechanism of representative high-value products and describe the transcriptional regulatory network, and future perspectives are discussed, which will help develop high-yield plant resources.


Assuntos
Alcaloides , Plantas Medicinais , Humanos , Plantas Medicinais/genética , Plantas Medicinais/metabolismo , Alcaloides/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas , Terpenos/metabolismo
9.
Z Naturforsch C J Biosci ; 79(3-4): 73-79, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38516999

RESUMO

The Sceletium-type alkaloids, known for their anxiolytic and antidepressant activities, have been recently found to be biosynthesized in Narcissus cv. Hawera, which is largely used as an ornamental plant. An alkaloid fraction enriched with Sceletium-type alkaloids from the plant has shown promising antidepressant and anxiolytic activities. In the present study, qualitative and quantitative analyses of the alkaloids in the plant organs were performed during one vegetation season by GC-MS. The alkaloid pattern and total alkaloid content was found to depend strongly on the stage of development and plant organ. The alkaloid content of bulbs was found to be highest during the dormancy period and lowest in sprouting bulbs. The leaves showed the highest alkaloid content during the intensive vegetative growth and lowest during flowering. In total, 13 alkaloids were detected in the methanol extracts of Narcissus cv. Hawera, six Sceletium-type and seven typical Amaryllidaceae alkaloids. Major alkaloids in the alkaloid pattern were lycorine, 6-epi-mesembrenol, mesembrenone, sanguinine, and galanthamine. The leaves of flowering plants were found to have the highest amount of 6-epi-mesembrenol. Mesembrenone was found to be dominant alkaloid in the leaves of sprouting bulbs and in the flowers. Considering the biomass of the plant, the dormant bulbs are the best source of alkaloid fractions enriched with 6-epi-mesembrenol. The flowers and the young leaves can be used for preparation of alkaloid fractions enriched with mesembrenone. The results indicates that Narcissus cv. Hawera is an emerging source of valuable bioactive compounds and its utilization can be extended as a medicinal plant.


Assuntos
Alcaloides , Alcaloides Indólicos , Narcissus , Fenantridinas , Folhas de Planta , Narcissus/química , Narcissus/metabolismo , Narcissus/crescimento & desenvolvimento , Alcaloides/metabolismo , Alcaloides/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Flores/química , Flores/metabolismo , Flores/crescimento & desenvolvimento , Extratos Vegetais/química , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Alcaloides de Amaryllidaceae/metabolismo , Alcaloides de Amaryllidaceae/química
10.
Plant Mol Biol ; 114(2): 23, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453737

RESUMO

Benzylisoquinoline alkaloids (BIAs) represent a significant class of secondary metabolites with crucial roles in plant physiology and substantial potential for clinical applications. CYP82 genes are involved in the formation and modification of various BIA skeletons, contributing to the structural diversity of compounds. In this study, Corydalis yanhusuo, a traditional Chinese medicine rich in BIAs, was investigated to identify the catalytic function of CYP82s during BIA formation. Specifically, 20 CyCYP82-encoding genes were cloned, and their functions were identified in vitro. Ten of these CyCYP82s were observed to catalyze hydroxylation, leading to the formation of protopine and benzophenanthridine scaffolds. Furthermore, the correlation between BIA accumulation and the expression of CyCYP82s in different tissues of C. yanhusuo was assessed their. The identification and characterization of CyCYP82s provide novel genetic elements that can advance the synthetic biology of BIA compounds such as protopine and benzophenanthridine, and offer insights into the biosynthesis of BIAs with diverse structures in C. yanhusuo.


Assuntos
Alcaloides , Benzilisoquinolinas , Corydalis , Benzofenantridinas , Corydalis/genética , Corydalis/química , Corydalis/metabolismo , Alcaloides/metabolismo , Extratos Vegetais/química
11.
J Orthop Surg Res ; 19(1): 178, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468339

RESUMO

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease characterized by persistent articular cartilage degeneration and synovitis. Oxymatrine (OMT) is a quinzolazine alkaloid extracted from the traditional Chinese medicine, matrine, and possesses anti-inflammatory properties that may help regulate the pathogenesis of OA; however, its mechanism has not been elucidated. This study aimed to investigate the effects of OMT on interleukin-1ß (IL-1ß)-induced damage and the potential mechanisms of action. METHODS: Chondrocytes were isolated from Sprague-Dawley rats. Toluidine blue and Collagen II immunofluorescence staining were used to determine the purity of the chondrocytes. Thereafter, the chondrocytes were subjected to IL-1ß stimulation, both in the presence and absence of OMT, or the autophagy inhibitor 3-methyladenine (3-MA). Cell viability was assessed using the MTT assay and SYTOX Green staining. Additionally, flow cytometry was used to determine cell apoptosis rate and reactive oxygen species (ROS) levels. The protein levels of AKT, mTOR, LC3, P62, matrix metalloproteinase-13, and collagen II were quantitatively analyzed using western blotting. Immunofluorescence was used to assess LC3 expression. RESULTS: OMT alleviated IL-1ß-induced damage in chondrocytes, by increasing the survival rate, reducing the apoptosis rates of chondrocytes, and preventing the degradation of the cartilage matrix. In addition, OMT decreased the ROS levels and inhibited the AKT/mTOR signaling pathway while promoting autophagy in IL-1ß treated chondrocytes. However, the effectiveness of OMT in improving chondrocyte viability under IL-1ß treatment was limited when autophagy was inhibited by 3-MA. CONCLUSIONS: OMT decreases oxidative stress and inhibits the AKT/mTOR signaling pathway to enhance autophagy, thus inhibiting IL-1ß-induced damage. Therefore, OMT may be a novel and effective therapeutic agent for the clinical treatment of OA.


Assuntos
Alcaloides , Cartilagem Articular , Matrinas , Osteoartrite , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Condrócitos/metabolismo , Interleucina-1beta/toxicidade , Interleucina-1beta/metabolismo , Osteoartrite/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Cartilagem Articular/metabolismo , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Alcaloides/metabolismo , Autofagia , Colágeno/metabolismo , Apoptose
12.
Angew Chem Int Ed Engl ; 63(20): e202401324, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38499463

RESUMO

We report the discovery and biosynthesis of new piperazine alkaloids-arizonamides, and their derived compounds-arizolidines, featuring heterobicyclic and spirocyclic isoquinolone skeletons, respectively. Their biosynthetic pathway involves two crucial non-heme iron enzymes, ParF and ParG, for core skeleton construction. ParF has a dual function facilitating 2,3-alkene formation of helvamide, as a substrate for ParG, and oxidative cleavage of piperazine. Notably, ParG exhibits catalytic versatility in multiple oxidative reactions, including cyclization and ring reconstruction. A key amino acid residue Phe67 was characterized to control the formation of the constrained arizonamide B backbone by ParG.


Assuntos
Alcaloides , Alcaloides/química , Alcaloides/metabolismo , Alcaloides/biossíntese , Piperazinas/química , Piperazinas/metabolismo , Ferro/química , Ferro/metabolismo , Ciclização , Biocatálise , Estrutura Molecular , Compostos de Espiro/química , Compostos de Espiro/metabolismo , Oxirredução , Piperazina/química , Piperazina/metabolismo
13.
Toxicon ; 240: 107651, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364982

RESUMO

Death Camas (Zigadenus spp.) are common poisonous plants distributed throughout North America. The toxic alkaloids in foothill death camas are zygadenine and a series of zygadenine esters, with zygacine, the 3-acetyl ester of zygadenine, being the most abundant. Both cattle and sheep can be poisoned by grazing death camas, however, sheep consume death camas more readily and are most often poisoned. We hypothesized that the presence of enzymes, including esterases present in the rumen, liver, and blood of livestock would metabolize zygacine. The objective of this study was to investigate the metabolism of zygacine in sheep and cattle using in-vitro and in-vivo systems. Results from experiments where zygacine was incubated in rumen culture, plasma, liver S9 fractions, and liver microsomes and from the analysis of rumen and sera from sheep and cattle dosed death camas plant material demonstrated that zygacine is metabolized to zygadenine in the rumen, liver and blood of sheep and cattle. The results from this study indicate that diagnosticians should analyze for zygadenine, and not zygacine, in the rumen and sera for the diagnosis of livestock suspected to have been poisoned by foothill death camas.


Assuntos
Alcaloides , Antineoplásicos , Melanthiaceae , Intoxicação por Plantas , Animais , Bovinos , Ovinos , Intoxicação por Plantas/veterinária , Intoxicação por Plantas/diagnóstico , Alcaloides/metabolismo , Plantas Tóxicas , Gado/metabolismo , Rúmen , Ruminantes
15.
J Pharm Biomed Anal ; 242: 116014, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38367517

RESUMO

This study aimed to investigate the absorption of alkaloids from Phellodendri chinensis Cortex (PC) by human renal tubular epithelial cells (HK-2). Cellular uptake and affinity ultrafiltration assays were employed to determine the alkaloid uptake pathway in HK-2 cells. Stemming from the hypothesis that salt-water processed PC introduces these alkaloids into the kidney at a cellular level, this research focused on different processed products of PC that are tailored for renal targeting. Utilizing the UPLC-QqQ-MS method, we quantified variations in the uptake capacity of phellodendrine, magnoflorine, jatrorrhizine, berberrubine, and berberine from raw Phellodendri chinensis Cortex (RPC), salt-water processed Phellodendri chinensis Cortex (SPC), and wine processed Phellodendri chinensis Cortex (WPC) in HK-2 cells. This study also tracked the concentration changes of these five alkaloids in HK-2 cells during the administration phase. Further, we evaluated the influence of two inhibitors on the absorption of these five alkaloids from PC and its processed products into HK-2 cells: the organic anion transporters (OATs) inhibitor-probenecid (PRO), and the organic cationic transporters (OCTs) inhibitor-tetraethylammonium chloride (TEAC). A pivotal component of this research was an investigation into the effects of PC and its processed products on the expression levels of OCT2, OAT1, and OAT3 proteins in HK-2 cells, facilitated by Western blot analysis. Finally, we appraised the binding affinity of PC's alkaloids to OCT2, OAT1, and OAT3 proteins using an ultrafiltration centrifugation technique. The uptake of different processed products of PC by HK-2 cells showed the following trend: SPC group > RPC group > WPC group. When considering inhibitor uptake in HK-2 cells, the group treated with PRO (an OATs inhibitor) demonstrated a higher uptake than the group treated with TEAC (an OCTs inhibitor). It was observed that different processed products of PC elevated the expression of OCT2 and OAT1 proteins in HK-2 cells. Specifically, both the SPC and berberrubine groups displayed enhanced expression of these proteins, with a marked increase noted for OCT2. Through affinity ultrafiltration assays, it was determined that the binding affinity of alkaloids from different processed products of PC to OCT2 and OAT1 significantly exceeded that to OAT3. These results indicate that PC-derived alkaloids are absorbed by HK-2 cells, predominantly through transport mechanisms mediated by OCT2 and OAT1, with OCT2 serving as the dominant transporter. The higher intake of alkaloids in SPC group can likely be linked to the amplified activity of kidney uptake transporters.


Assuntos
Alcaloides , Humanos , Alcaloides/metabolismo , Transporte Biológico , Rim/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Células Epiteliais/metabolismo , Água
16.
Ann Bot ; 133(4): 509-520, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38320313

RESUMO

BACKGROUND AND AIMS: In the subfamily Poöideae (Poaceae), certain grass species possess anti-herbivore alkaloids synthesized by fungal endophytes that belong to the genus Epichloë (Clavicipitaceae). The protective role of these symbiotic endophytes can vary, depending on alkaloid concentrations within specific plant-endophyte associations and plant parts. METHODS: We conducted a literature review to identify articles containing alkaloid concentration data for various plant parts in six important pasture species, Lolium arundinaceum, Lolium perenne, Lolium pratense, Lolium multiflorum|Lolium rigidum and Festuca rubra, associated with their common endophytes. We considered the alkaloids lolines (1-aminopyrrolizidines), peramine (pyrrolopyrazines), ergovaline (ergot alkaloids) and lolitrem B (indole-diterpenes). While all these alkaloids have shown bioactivity against insect herbivores, ergovaline and lolitrem B are harmful for mammals. KEY RESULTS: Loline alkaloid levels were higher in the perennial grasses L. pratense and L. arundinaceum compared to the annual species L. multiflorum and L. rigidum, and higher in reproductive tissues than in vegetative structures. This is probably due to the greater biomass accumulation in perennial species that can result in higher endophyte mycelial biomass. Peramine concentrations were higher in L. perenne than in L. arundinaceum and not affected by plant part. This can be attributed to the high within-plant mobility of peramine. Ergovaline and lolitrem B, both hydrophobic compounds, were associated with plant parts where fungal mycelium is usually present, and their concentrations were higher in plant reproductive tissues. Only loline alkaloid data were sufficient for below-ground tissue analyses and concentrations were lower than in above-ground parts. CONCLUSIONS: Our study provides a comprehensive synthesis of fungal alkaloid variation across host grasses and plant parts, essential for understanding the endophyte-conferred defence extent. The patterns can be understood by considering endophyte growth within the plant and alkaloid mobility. Our study identifies research gaps, including the limited documentation of alkaloid presence in roots and the need to investigate the influence of different environmental conditions.


Assuntos
Alcaloides , Endófitos , Epichloe , Festuca , Lolium , Poliaminas , Alcaloides/metabolismo , Alcaloides/análise , Endófitos/química , Endófitos/fisiologia , Epichloe/química , Epichloe/fisiologia , Ergotaminas/metabolismo , Festuca/microbiologia , Festuca/fisiologia , Herbivoria , Compostos Heterocíclicos com 2 Anéis , Alcaloides Indólicos/metabolismo , Lolium/microbiologia , Lolium/fisiologia , Micotoxinas , Defesa das Plantas contra Herbivoria , Poaceae/microbiologia , Poaceae/metabolismo , Simbiose
17.
Sci Rep ; 14(1): 2799, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38307917

RESUMO

Tinospora cordifolia (Willd.) Hook.f. & Thomson, also known as Giloy, is among the most important medicinal plants that have numerous therapeutic applications in human health due to the production of a diverse array of secondary metabolites. To gain genomic insights into the medicinal properties of T. cordifolia, the genome sequencing was carried out using 10× Genomics linked read and Nanopore long-read technologies. The draft genome assembly of T. cordifolia was comprised of 1.01 Gbp, which is the genome sequenced from the plant family Menispermaceae. We also performed the genome size estimation for T. cordifolia, which was found to be 1.13 Gbp. The deep sequencing of transcriptome from the leaf tissue was also performed. The genome and transcriptome assemblies were used to construct the gene set, resulting in 17,245 coding gene sequences. Further, the phylogenetic position of T. cordifolia was also positioned as basal eudicot by constructing a genome-wide phylogenetic tree using multiple species. Further, a comprehensive comparative evolutionary analysis of gene families contraction/expansion and multiple signatures of adaptive evolution was performed. The genes involved in benzyl iso-quinoline alkaloid, terpenoid, lignin and flavonoid biosynthesis pathways were found with signatures of adaptive evolution. These evolutionary adaptations in genes provide genomic insights into the presence of diverse medicinal properties of this plant. The genes involved in the common symbiosis signalling pathway associated with endosymbiosis (Arbuscular Mycorrhiza) were found to be adaptively evolved. The genes involved in adventitious root formation, peroxisome biogenesis, biosynthesis of phytohormones, and tolerance against abiotic and biotic stresses were also found to be adaptively evolved in T. cordifolia.


Assuntos
Alcaloides , Plantas Medicinais , Tinospora , Humanos , Plantas Medicinais/genética , Tinospora/genética , Tinospora/metabolismo , Filogenia , Extratos Vegetais/metabolismo , Alcaloides/metabolismo
18.
Food Funct ; 15(4): 2154-2169, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38311970

RESUMO

Postmenopausal osteoporosis (PMOP) is a metabolic bone disease that results from overproduction and hyperactivation of osteoclasts caused by insufficient estrogen in women after menopause. Current therapeutic strategies are mainly focused on treating PMOP patients who have already developed severe bone loss or even osteoporotic fractures. Obviously, a better strategy is to prevent PMOP from occurring in the first place. However, such reagents are largely lacking. Piperlongumine (PLM), an amide alkaloid extracted from long pepper Piper longum, exhibits the anti-osteoclastogenic effect in normal bone marrow macrophages (BMMs) and the protective effect against osteolysis induced by titanium particles in mice. This study examined the preventive effect of PLM on PMOP and explored the potential mechanism of this effect using both ovariectomized mice and their primary cells. The result showed that PLM (5 and 10 mg kg-1) administered daily for 6 weeks ameliorated ovariectomy-induced bone loss and osteoclast formation in mice. Further cell experiments showed that PLM directly suppressed osteoclast formation, F-actin ring formation, and osteoclastic resorption pit formation in BMMs derived from osteoporotic mice, but did not obviously affect osteogenic differentiation of bone marrow stromal cells (BMSCs) from these mice. Western blot analysis revealed that PLM attenuated maximal activation of p38 and JNK pathways by RANKL stimulation without affecting acute activation of NF-κB, AKT, and ERK signaling. Furthermore, PLM inhibited expression of key osteoclastogenic transcription factors NFATc1/c-Fos and their target genes (Dcstamp, Atp6v0d2, Acp5, and Oscar). Taken together, our findings suggest that PLM inhibits osteoclast formation and function by suppressing RANKL-induced activation of the p38/JNK-cFos/NFATc1 signaling cascade, thereby preventing ovariectomy-induced osteoporosis in mice. Thus, PLM can potentially be used as an anti-resorption drug or dietary supplement for the prevention of PMOP.


Assuntos
Alcaloides , Benzodioxóis , Reabsorção Óssea , Osteoporose Pós-Menopausa , Osteoporose , Humanos , Feminino , Animais , Camundongos , Osteogênese , Sistema de Sinalização das MAP Quinases , Osteoclastos , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/prevenção & controle , Osteoporose/etiologia , Osteoporose/genética , Diferenciação Celular , NF-kappa B/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Ovariectomia/efeitos adversos , Alcaloides/metabolismo , Ligante RANK/metabolismo
19.
J Ethnopharmacol ; 323: 117693, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38176669

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii is widely used in traditional Chinese medicine clinics as a bulk medicinal material. It has been used in China for more than two thousand years. Nevertheless, the stems and leaves of this plant are usually discarded as non-medicinal parts, even though they have a large biomass and exhibit therapeutic properties. Thus, it is crucial to investigate metabolites of different parts of Aconitum carmichaelii and explore the relationship between metabolites and toxicity to unleash the utilization potential of the stems and leaves. AIM OF THE STUDY: Using plant metabolomics, we aim to correlate different metabolites in various parts of Aconitum carmichaelii with toxicity, thereby screening for toxicity markers. This endeavor seeks to offer valuable insights for the development of Aconitum carmichaelii stem and leaf-based applications. MATERIALS AND METHODS: UHPLC-Q-Orbitrap MS/MS-based plant metabolomics was employed to analyze metabolites of the different parts of Aconitum carmichaelii. The cardiotoxicity and hepatotoxicity of the extracts from different parts of Aconitum carmichaelii were also investigated using zebrafish as animal model. Toxicity markers were subsequently identified by correlating toxicity with metabolites. RESULTS: A total of 113 alkaloids were identified from the extracts of various parts of Aconitum carmichaelii, with 64 different metabolites in stems and leaves compared to daughter root (Fuzi), and 21 different metabolites in stems and leaves compared to mother root (Wutou). The content of aporphine alkaloids in the stems and leaves of Aconitum carmichaelii is higher than that in the medicinal parts, while the content of the diester-diterpenoid alkaloids is lower. Additionally, the medicinal parts of Aconitum carmichaelii exhibited cardiotoxicity and hepatotoxicity, while the stems and leaves have no obvious toxicity. Finally, through correlation analysis and animal experimental verification, mesaconitine, deoxyaconitine, and hypaconitine were used as toxicity markers. CONCLUSION: Given the low toxicity of the stems and leaves and the potential efficacy of aporphine alkaloids, the stems and leaves of Aconitum carmichaelii hold promise as a valuable medicinal resource warranting further development.


Assuntos
Aconitum , Medicamentos de Ervas Chinesas , Animais , Aconitum/toxicidade , Alcaloides/metabolismo , Aporfinas/metabolismo , Cardiotoxicidade , Doença Hepática Induzida por Substâncias e Drogas , Diterpenos/metabolismo , Medicamentos de Ervas Chinesas/toxicidade , Medicamentos de Ervas Chinesas/metabolismo , Folhas de Planta , Raízes de Plantas , Espectrometria de Massas em Tandem , Peixe-Zebra
20.
Genes Genomics ; 46(3): 367-378, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38095842

RESUMO

BACKGROUND: Secondary metabolites such as benzylisoquinoline alkaloids (BIA) have attracted considerable attention because of their pharmacological properties and potential therapeutic applications. Methyltransferases (MTs) can add methyl groups to alkaloid molecules, altering their physicochemical properties and bioactivity, stability, solubility, and recognition by other cellular components. Five types of O-methyltransferases and two types of N-methyltransferases are involved in BIA biosynthesis. OBJECTIVE: Since MTs may be the source for the discovery and development of novel biomedical, agricultural, and industrial compounds, we performed extensive molecular and phylogenetic analyses of O- and N-methyltransferases in BIA-producing plants. METHODS: MTs involved in BIA biosynthesis were isolated from transcriptomes of Berberis koreana and Caulophyllum robustum. We also mined the methyltransferases of Coptis japonica, Papaver somniferum, and Nelumbo nucifera from the National Center for Biotechnology Information protein database. Then, we analyzed the functional motifs and phylogenetic analysis. RESULT: We mined 42 O-methyltransferases and 8 N-methyltransferases from the five BIA-producing plants. Functional motifs for S-adenosyl-L-methionine-dependent methyltransferases were retained in most methyltransferases, except for the three O-methyltransferases from N. nucifera. Phylogenetic analysis revealed that the methyltransferases were grouped into four clades, I, II, III and IV. The clustering patterns in the phylogenetic analysis suggested a monophyletic origin of methyltransferases and gene duplication within species. The coexistence of different O-methyltransferases in the deep branch subclade might support some cases of substrate promiscuity. CONCLUSIONS: Methyltransferases may be a source for the discovery and development of novel biomedical, agricultural, and industrial compounds. Our results contribute to further understanding of their structure and reaction mechanisms, which will require future functional studies.


Assuntos
Alcaloides , Benzilisoquinolinas , Metiltransferases/genética , Metiltransferases/metabolismo , Filogenia , Alcaloides/metabolismo , Plantas/metabolismo
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