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1.
Planta Med ; 90(5): 388-396, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490239

RESUMO

Diabetes mellitus, linked with insulin resistance and hyperglycaemia, is a leading cause of mortality. Glucose uptake through glucose transporter type 4, especially in skeletal muscle, is crucial for maintaining euglycaemia and is a key pathway targeted by antidiabetic medication. Abrus precatorius is a medicinal plant with demonstrated antihyperglycaemic activity in animal models, but its mechanisms are unclear.This study evaluated the effect of a 50% ethanolic (v/v) A. precatorius leaf extract on (1) insulin-stimulated glucose uptake and (2) related gene expression in differentiated C2C12 myotubes using rosiglitazone as a positive control, and (3) generated a comprehensive phytochemical profile of A. precatorius leaf extract using liquid chromatography-high resolution mass spectrometry to elucidate its antidiabetic compounds. A. precatorius leaf extract significantly increased insulin-stimulated glucose uptake, and insulin receptor substrate 1 and Akt substrate of 160 kDa gene expression; however, it had no effect on glucose transporter type 4 gene expression. At 250 µg/mL A. precatorius leaf extract, the increase in glucose uptake was significantly higher than 1 µM rosiglitazone. Fifty-five phytochemicals (primarily polyphenols, triterpenoids, saponins, and alkaloids) were putatively identified, including 24 that have not previously been reported from A. precatorius leaves. Abrusin, precatorin I, glycyrrhizin, hemiphloin, isohemiphloin, hispidulin 4'-O-ß-D-glucopyranoside, homoplantaginin, and cirsimaritin were putatively identified as known major compounds previously reported from A. precatorius leaf extract. A. precatorius leaves contain antidiabetic phytochemicals and enhance insulin-stimulated glucose uptake in myotubes via the protein kinase B/phosphoinositide 3-kinase pathway by regulating insulin receptor substrate 1 and Akt substrate of 160 kDa gene expression. Therefore, A. precatorius leaves may improve skeletal muscle insulin sensitivity and hyperglycaemia. Additionally, it is a valuable source of bioactive phytochemicals with potential therapeutic use for diabetes.


Assuntos
Abrus , Diabetes Mellitus , Hiperglicemia , Resistência à Insulina , Animais , Insulina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Abrus/química , Proteínas Substratos do Receptor de Insulina/metabolismo , Rosiglitazona/metabolismo , Rosiglitazona/farmacologia , Transportador de Glucose Tipo 4 , Fosfatidilinositol 3-Quinases , Músculo Esquelético/metabolismo , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/química , Glucose/farmacologia
2.
J Ethnopharmacol ; 324: 117740, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38219885

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Abrus cantoniensis Hance (AC), an abrus cantoniensis herb, is a Chinese medicinal herb used for the treatment of hepatitis. Total saponins extracted from AC (ACS) are a compound of triterpenoid saponins, which have protective properties against both chemical and immunological liver injuries. Nevertheless, ACS has not been proven to have an influence on drug-induced liver injury (DILI). AIM OF THE STUDY: This study used network pharmacology and experiments to investigate the effects of ACS on acetaminophen (APAP)-induced liver injury. MATERIALS AND METHODS: The targets associated with ACS and DILI were obtained from online databases. Cytoscape software was utilized to construct a "compound-target" network. In addition, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to analyze the related signaling pathways impacted by ACS. AutoDock Vina was utilized to evaluate the binding affinity between bioactive compounds and the key targets. To validate the findings of network pharmacology, in vitro and in vivo experiments were conducted. Cell viability assay, transaminase activity detection, immunofluorescence assay, immunohistochemistry staining, RT-qPCR, and western blotting were utilized to explore the effects of ACS. RESULTS: 25 active compounds and 217 targets of ACS were screened, of which 94 common targets were considered as potential targets for ACS treating APAP-induced liver injury. GO and KEGG analyses showed that the effects of ACS exert their effects on liver injury through suppressing inflammatory response, oxidative stress, and apoptosis. Molecular docking results demonstrated that core active compounds of ACS were successfully docked to core targets such as CASP3, BCL2L1, MAPK8, MAPK14, PTGS2, and NOS2. In vitro experiments showed that ACS effectively attenuated APAP-induced damage through suppressing transaminase activity and attenuating apoptosis. Furthermore, in vivo studies demonstrated that ACS alleviated pathological changes in APAP-treated mice and attenuated inflammatory response. Additionally, ACS downregulated the expression of iNOS, COX2, and Caspase-3, and upregulated the expression of Bcl-2. ACS also suppressed the MAPK signaling pathway. CONCLUSIONS: This study demonstrated that ACS is a hepatoprotective drug through the combination of network pharmacology and in vitro and in vivo experiments. The findings reveal that ACS effectively attenuate APAP-induced oxidative stress, apoptosis, and inflammation through inhibiting the MAPK signaling pathway. Consequently, this research offers novel evidence supporting the potential preventive efficacy of ACS.


Assuntos
Abrus , Doença Hepática Crônica Induzida por Substâncias e Drogas , Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Animais , Camundongos , Acetaminofen/toxicidade , Farmacologia em Rede , Simulação de Acoplamento Molecular , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Transaminases
3.
Int J Biol Macromol ; 261(Pt 1): 129590, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266859

RESUMO

As a Chinese folk health product, Abrus cantoniensis exhibits good immunomodulatory activity because of its polysaccharide components (ACP), and carboxymethylation of polysaccharides can often further improve the biological activity of polysaccharides. In this study, we explored the impact of prophylactic administration of carboxymethylated Abrus cantoniensis polysaccharide (CM-ACP) on immunosuppression and intestinal damage induced by cyclophosphamide (CTX) in mice. Our findings demonstrated that CM-ACP exhibited a more potent immunomodulatory activity compared to ACP. Additionally, CM-ACP effectively enhanced the abundance of short-chain fatty acid (SCFA)-producing bacteria in immunosuppressed mice and regulated the gene expression of STAT6 and STAT3 mediated pathway signals. In order to further explore the relationship among polysaccharides, intestinal immunity and intestinal flora, we performed a pseudo-sterile mouse validation experiment and fecal microbiota transplantation (FMT) experiment. The findings suggest that CM-FMT and butyrate attenuate CTX-induced immunosuppression and intestinal injury. CM-FMT and butyrate show superior immunomodulatory ability, and may effectively regulate intestinal cell metabolism and repair the damaged intestine by activating STAT6 and STAT3-mediated pathways. These findings offer new insights into the mechanisms by which CM-ACP functions as functional food or drug, facilitating immune response regulation and maintaining intestinal health.


Assuntos
Abrus , Microbioma Gastrointestinal , Camundongos , Animais , Ácido Butírico , Terapia de Imunossupressão , Intestinos , Polissacarídeos/farmacologia
4.
BMC Genomics ; 24(1): 714, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012556

RESUMO

BACKGROUND: The phylogenetic position and classification of Athysanini are poorly defined, as it includes a large group of polyphyletic genera that have historically been assigned to it mainly because they still exhibit the most typical deltocephaline genitalic and external body characters but lack the distinctive characteristics that other tribes possess. The bamboo-feeding leafhopper genus Abrus belong to the tribe Athysanini of subfamily Deltocephalinae, which currently comprises 19 valid described species, and are limited to the Oriental and Palaearctic regions in China. Although the taxonomy of Abrus are well updated, the references on comparative mitogenomic analyses of Abrus species are only known for a single species. In this study, we sequenced and analyzed the complete mitochondrial genomes (mitogenomes) of Abrus daozhenensis Chen, Yang & Li, 2012 (16,391bp) and A. yunshanensis Chen, Yang & Li, 2012 (15,768bp) (Athysanini), and compared with published mitogenome sequence of A. expansivus Xing & Li, 2014 (15,904bp). RESULTS: These Abrus species shared highly conserved mitogenomes with similar gene order to that of the putative ancestral insect with 37 typical genes and a non-coding A + T-rich region. The nucleotide composition of these genomes is highly biased toward A + T nucleotides (76.2%, 76.3%, and 74.7%), AT-skews (0.091 to 0.095, and 0.095), negative GC-skews (- 0.138, - 0.161, and - 0.138), and codon usage. All 22 tRNA genes had typical cloverleaf secondary structures, except for trnS1 (AGN) which lacks the dihydrouridine arm, and distinctively trnG in the mitogenome of A. expansivus lacks the TψC arm. Phylogenetic analyses based on 13 PCGs, 2 rRNA genes, and 22 tRNA genes consistently recovered the monophyletic Opsiini, Penthimiini, Selenocephalini, Scaphoideini, and Athysanini (except Watanabella graminea, previously sequenced species as Chlorotettix nigromaculatus) based on limited available mitogenome sequence data of 37 species. CONCLUSION: At present, Abrus belongs to the tribe Athysanini based on both morphological and molecular datasets, which is strongly supported in present phylogenetic analyses in both BI and ML methods using the six concatenated datasets: amino acid sequences and nucleotides from different combinations of protein-coding genes (PCGs), ribosomal RNA (rRNAs), and transfer RNA (tRNAs). Phylogenetic trees reconstructed herein based on the BI and ML analyses consistently recovered monophylitic Athysanini, except Watanabella graminea (Athysanini) in Opsiini with high support values.


Assuntos
Abrus , Genoma Mitocondrial , Hemípteros , Animais , Hemípteros/genética , Filogenia , Abrus/genética , RNA de Transferência/genética , RNA de Transferência/química , RNA Ribossômico/genética , Nucleotídeos/genética
5.
J Agric Food Chem ; 71(41): 15145-15155, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37800321

RESUMO

Abrus mollis Hance is a characteristic medicinal herb which is used in Guangdong and Guangxi provinces of China for making soup, medicinal meals, and herbal tea to treat dampheat jaundice and rib discomfort. Current phytochemical study on A. mollis led to the isolation of four new flavones, mollisone A-D (1-4), and thirty two known compounds (5-36). Their structures were characterized by an extensive analysis of spectroscopic data including IR, UV, HR-ESI-MS, and 1D and 2D NMR, as well as electronic circular dichroism calculation. In addition, in order to initially understand their biological activities for traditional applications, in vitro antioxidant and hepatoprotective tests were carried out, whose results illustrated that 25 compounds had significant free radical scavenging ability, and compounds 13 and 16 exhibited protective activities on D-GalN-induced LO2 cell damage than the positive control. Moreover, network pharmacological analysis revealed that the hepatoprotective activity of A. mollis involved multitargets and multipathways such as PI3K/Akt, MAPK, and JAK-STAT pathways and various biological processes such as positive regulation of phosphorylation and regulation of kinase activity. These results suggested that this species could serve as a potential hepatoprotective agent for functional food or medicinal use.


Assuntos
Abrus , Abrus/química , Extratos Vegetais/química , Fosfatidilinositol 3-Quinases/metabolismo , China , Fígado/metabolismo , Chá/metabolismo
6.
Ecotoxicol Environ Saf ; 266: 115560, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37827094

RESUMO

The liver is a well-known organ contributing to digestion, hemostasis and detoxification, while liver injury is a world-widely distributed health problem with limited treatment choices. We detected the protective effect of Abrus cantoniensis Hance (ACH) on Carbon tetrachloride-induced (CCl4) liver injury in mice. Fifty ICR (Institute of Cancer Research) animals were grouped into five groups of control (a), CCl4 (d), ACH (25 mg/kg) treated group (c), ACH (50 mg/kg) treated group (b), and ACH (100 mg/kg) treated group (e). Mice in groups d, c, b, and e were given CCl4 every four days, and treated animals received daily ACH supplementation. The results showed that the daily body weights in CCl4-induced animals were slightly lower; however, the weight of ACH-treated mice increased, particularly in the higher dose group. Treatment with CCl4 led to increased liver weight and liver indices in mice, whereas supplementation with ACH reduced both liver weights and liver indices in animals. Histo-pathological analysis indicated that CCl4 led to inflammatory cell infiltration and hepatocellular degeneration, with collagenous fibers proliferation in ICR animals. In contrast, supplementation with ACH prominently decreased inflammatory cells and degeneration of hepatocytes and inhibited collagen fiber hyperplasia. Furthermore, the levels or concentrations of AST (p < 0.0001), ALT (p < 0.0001), MDA (p < 0.0001), IL-1ß (p < 0.01), TNF-α (p < 0.01) and IL-6 (p < 0.01) were significantly higher in CCl4 induced ICR animals in group d. However, mice treated with ACH showed lower levels or concentrations of those indices in dose dependent manner. The levels of GSH-px (p < 0.0001), CAT (p < 0.0001) and SOD (p < 0.0001) were significantly reduced in CCl4 group; however, all these three enzymes exhibited significant (p < 0.05) increase in animals supplemented with ACH in dose dependent manner. The microbiome sequencing generated 1,168,327 filtered reads in the mice samples. A notable difference was observed in the composition of 6 phyla and 37 genera among the five ICR animal groups. Supplementation with ACH increased the abundance of beneficial genera of Coprococcus, Blautia and Clostridium, while concurrently decreased the presence of pathogenic genera of Mycoplasma and Helicobacter. In conclusion, we revealed that Abrus cantoniensis Hance has the potential to relieve liver damage induced by CCl4, through the reduction of inflammation, enhancement of antioxidant capacity, and regulation of intestinal microbiota.


Assuntos
Abrus , Doença Hepática Induzida por Substâncias e Drogas , Hepatopatias , Camundongos , Animais , Camundongos Endogâmicos ICR , Fígado , Inflamação/induzido quimicamente , Doença Hepática Induzida por Substâncias e Drogas/patologia
7.
Sci Rep ; 13(1): 13514, 2023 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-37598190

RESUMO

Biogenic silver nanoconjugates (AgNCs), derived from medicinal plants, have been widely explored in the field of biomedicines. AgNCs for the first-time were synthesized using ethyl acetate seed extracts of Abrus precatorius and their antiproliferative and antiangiogenic efficacies were evaluated against cervical and oral carcinoma. Ultraviolet-Visible spectrophotometry, dynamic light Scattering (DLS), and scanning electron microscopy (SEM) were used for characterization of AgNCs. Antiproliferative activity was investigated using MTT, DNA fragmentation and in-vitro antioxidant enzyme activity assays. In-vivo chick chorioallantoic membrane (CAM) model was used to evaluate antiangiogenic activity. A total of 11 compounds were identified in both the extracts in GCMS analysis. The synthesized AgNCs were spherical shaped with an average size of 97.4 nm for AgAPE (Sox) and 64.3 nm for AgAPE (Mac). AgNCs possessed effective inhibition against Hep2C and KB cells. In Hep2C cells, AgAPE (Mac) revealed the highest SOD, catalase, GST activity and lower MDA content, whereas AgAPE (Sox) showed the highest GSH content. On the other hand, in KB cells, AgAPE (Sox) exhibited the higher SOD, GST activity, GSH content, and least MDA content, while AgAPE (Mac) displayed the highest levels of catalase activity. Docking analysis revealed maximum binding affinity of safrole and linoleic acid with selected targets. AgAPE (Sox), AgAPE (Mac) treatment profoundly reduced the thickness, branching, and sprouting of blood vessels in the chick embryos. This study indicates that A. precatorius-derived AgNCs have enhanced efficacies against cervical and oral carcinoma as well as against angiogenesis, potentially limiting tumour growth.


Assuntos
Abrus , Carcinoma , Neoplasias Bucais , Embrião de Galinha , Animais , Humanos , Catalase , Nanoconjugados , Prata/farmacologia , Extratos Vegetais/farmacologia , Superóxido Dismutase
8.
BMC Plant Biol ; 23(1): 375, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37525109

RESUMO

BACKGROUND: Abrus cantoniensis Hance. (Ac) and Abrus mollis (Am), two edible and medicinal plants with economic value in southern China, belong to the Abrus genus. Due to its growth characteristics, Am often replaces Ac in folk medicine. However, the latest National Pharmacopeia of China only recommends Ac. The differences in the metabolite composition of the plants are directly related to the differences in their clinical efficacy. RESULTS: The difference in metabolites were analyzed using an untargeted metabolomic approach based on ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC‒ESI‒MS/MS). The roots (R), stems (S) and leaves (L) of the two varieties were examined, and 635 metabolites belonging to 8 classes were detected. A comparative study revealed clear variations in the metabolic profiles of the two plants, and the AmR group had more active ingredients (flavonoids and terpenoids) than the AcR group. The metabolites classified as flavonoids and triterpene saponins showed considerable variations among the various samples. Both Ac and Am had unique metabolites. Two metabolites (isovitexin-2''-xyloside and soyasaponin V) specifically belong to Ac, and nine metabolites (vitexin-2"-O-galactoside, ethyl salicylate, 6-acetamidohexanoic acid, rhein-8-O-glucoside, hederagenin-3-O-glucuronide-28-O-glucosyl(1,2)-glucoside, methyl dioxindole-3-acetate, veratric acid, isorhamnetin-3-O-sophoroside-7-O-rhamnoside, and isorhamnetin-3-O-sophoroside) specifically belong to Am. CONCLUSIONS: The metabolite differences between Ac and Am cause the differences in their clinical efficacy. Our findings serve as a foundation for further investigation of biosynthesis pathways and associated bioactivities and provide guidance for the clinical application of traditional Chinese medicine.


Assuntos
Abrus , Abrus/química , Espectrometria de Massas em Tandem , Flavonoides/química , Glucosídeos , Metabolômica
9.
Chem Biodivers ; 20(7): e202300696, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37269051

RESUMO

Through a phytochemical investigation of Abrus mollis Hance, a folk medicinal plant in China, we isolated and identified three undescribed compounds, including two flavonoids and one amides alkaloid, along with nine known from this plant. Their structures were elucidated by analyses of 1D, 2D NMR, HR-ESI-MS, ECD, and DP4+ analysis. Furthermore, we evaluated the hepatoprotective effects of all twelve compounds on D-GalN-induced Brl-3 A cells. According to the results, at a concentration of 25 µM, the cell survival rates were observed to be 71.92±0.34 %, 70.03±1.29 %, and 69.11±1.90 % for compound 2, 4, and 11, respectively. Further experimental studies showed that compound 2 (EC50 5.76±0.37 µM) showed more significant protective activity than the bicyclol.


Assuntos
Abrus , Alcaloides , Flavonoides/química , Extratos Vegetais/química , Abrus/química , Amidas/farmacologia , Alcaloides/farmacologia
10.
Biomed Chromatogr ; 37(10): e5696, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37357379

RESUMO

A simple and sensitive liquid chromatography tandem mass spectrometry method was established and validated for the quantitative determination of abrine, hypaphorine, schaftoside and soyasaponin Bb in rat plasma. After preparation by protein precipitation with acetonitrile, the analytes and internal standard were separated on a Waters CORTECS T3 column using acetonitrile containing 0.1% formic acid and 0.1% formic acid in water as mobile phase by gradient elution in 2 min. The method showed excellent linearity over the range of 5-500 ng/ml with acceptable intra- and inter-day precision, accuracy, matrix effect and recovery. The stability assay indicated that the four analytes were stable during the analysis process. The method was applied to a pharmacokinetic study of Abrus cantoniensis Hance in rats. The result suggested that after oral administration, the four analytes were quickly absorbed into the plasma. The dose-normalized exposure of hypaphorine was the highest with a long elimination half-life (t1/2 9.83 h), followed by abrine and schaftoside with t1/2 values of 1.07 and 1.15 h. The dose normalized exposure of soyasaponin Bb was the lowest, which is possibily due to the high polarity and poor permeability. This study provides a basis for elucidating the material foundation of A. cantoniensis Hance.


Assuntos
Abrus , Espectrometria de Massas em Tandem , Ratos , Animais , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Alcaloides Indólicos , Administração Oral , Reprodutibilidade dos Testes
11.
Chem Biodivers ; 20(6): e202300204, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37243962

RESUMO

Abrus mollis (MJGC) has been used as a substitute herb for Abrus cantoniensis (JGC) in China. However, an in-depth comparison on their key metabolites and the mechanism of anti-inflammation between these two is not available. In this report, high pressure liquid chromatography equipped with mass spectrometry was applied to capture their flavonoid profiles; transcriptomics was adopted to analyze their anti-inflammatory mechanisms. The results showed that the main flavonoids in MJGC were vicenin-2, schaftoside and isoschaftoside, while those in JGC were vicenin-1 isomer and schaftoside isomer. The anti-inflammatory activity of JGC was slightly stronger than that of MJGC. The number of differential expression genes regulated by JGC was significantly higher than MJGC. JGC regulated 151 (42 up and 109 down) of inflammation related genes, while MJGC regulated 58 (8 up and 50 down) of inflammation related genes. The results of this study provided scientific evidence and guidance for the substitution of MJGC and JGC.


Assuntos
Abrus , Flavonoides , Flavonoides/química , Extratos Vegetais , Abrus/química , Transcriptoma , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta Pressão/métodos
12.
Anticancer Agents Med Chem ; 23(12): 1376-1387, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36959155

RESUMO

OBJECTIVE: The present study aimed to investigate the cytotoxic effect of various extracts derived from Abrus precatorius Linn. leaves on rat L6 and human SK-N-MC neuroblastoma cell lines and determine the secondary metabolites responsible for the cytotoxicity of Abrus precatorius. METHODS: Successive solvent extraction of A. precatorius leaves was carried out using the Soxhlet apparatus with solvents such as petroleum ether, chloroform, ethyl acetate, and ethanol. HPTLC fingerprinting and LC-MS studies were performed to assess the presence of secondary metabolites, such as flavonoids and phenols, in the ethyl acetate extract. Furthermore, the cytotoxic effect of extracts was tested on rat skeletal muscle cell line L6 and human neuroblastoma cell line SK-N-MC using MTT assay. RESULTS: The total phenolic content of ethyl acetate and ethanol extracts of A. precatorius were 72.67 and 60.73 mg, respectively, of GAE/g dry weight of the extract. The total flavonoid content of ethyl acetate and ethanol extract of A. precatorius were 107.33 and 40.66 mg of Quercetin equivalents/g dry weight of the extract. LCMS analysis demonstrated that the flavonoids in specific Naringenin, Diosmetin, Glycitin, and Genistein might play a prominent role in the cytotoxicity of A. precatorius. The cytotoxicity study revealed that the extracts of A. precatorius were non-toxic to rat L6 myotubes, and the IC50 values of the various extracts, such as APPE, APCH, APEA, and APET, were >100 µg/ml. The extracts exhibited cytotoxic activity against human neuroblastoma SK-N-MC cells, and the IC50 values of APPE, APCH, APEA, APET, and the standard drug "Cisplatin" were >100, >100, 64.88, >100, and 3.72 µg/ml, respectively. CONCLUSION: It was concluded from the study that the extracts of Abrus precatorius were cytotoxic to neuroblastoma cell lines but non-toxic to normal cell lines. HPTLC and LC-MS studies confirmed that flavonoids in the ethyl acetate extract could be responsible for the biological activity.


Assuntos
Abrus , Neuroblastoma , Ratos , Humanos , Animais , Extratos Vegetais/farmacologia , Flavonoides/farmacologia , Linhagem Celular , Fenóis/farmacologia , Antioxidantes/análise , Solventes , Etanol , Neuroblastoma/tratamento farmacológico
13.
J Biomol Struct Dyn ; 41(12): 5568-5582, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35773777

RESUMO

Type 2 diabetes mellitus remains global health challenge with involvement of both insulin resistance and dysfunctional insulin secretion from the pancreatic ß-cell. Currently, peroxisome proliferator-activated receptor gamma (PPARγ) has been established to play a significant role in glucose homeostasis and insulin sensitization contributing to the pathogenesis of type 2 diabetes mellitus. Hence, this study used in-silico analysis to predict PPARγ antagonists from the natural compounds. ADMET screening, structure-based virtual screening and MM/GBSA calculations of phytochemicals from HPLC analysis of A. precatorius seeds were performed against PPARγ using Maestro Schrodinger suite, followed by the MD simulation of top hit compounds and reference ligand using GROMACS. The quantum chemical calculations of the compounds were performed using Spartan 14 computational chemistry software. The five compounds showed varying degree of binding affinity against PPARγ, the post-docking analysis confirmed strong interaction against the amino acid residues of the binding site of the target. Chlorogenic acid showed the highest docking score (-10.719 kcal/mol) among the compounds comparable to the reference ligand (acarbose = -10.634 kcal/mol). Additionally, MM/GBSA binding free energy (ΔGbind) calculations support the modulatory potential for the docked compounds, which exclusively revealed the highest binding energy for the compounds than the reference ligand (acarbose). The MD simulations suggested the stability of Chlorogenic acid and Quercetin in complex with PPARγ at least in the time period of 90 ns after initial equilibration state with more H-bond observed between the target-hit compounds complex compared to the Acarbose-PPARγ complex. ADMET profile revealed that the five compounds were favorably druggable and promising drug candidates. The quantum chemical calculations showed that the compounds possess better bioactivity and chemical reactivity with favorable intra-molecular charge transfer as electron-donor and electron-acceptor. This study revealed that bioactive compounds especially chlorogenic acid and quercetin identified from A. precatorius seeds demonstrated good modulatory potential against PPARγ compared to acarbose. Therefore, these compounds require further experimental validation for the discovery of new antagonist of PPARγ for developing new anti-diabetes therapy.Communicated by Ramaswamy H. Sarma.


Assuntos
Abrus , Diabetes Mellitus Tipo 2 , PPAR gama/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Simulação de Acoplamento Molecular , Acarbose , Ácido Clorogênico/farmacologia , Ligantes , Quercetina/farmacologia , Compostos Fitoquímicos/farmacologia , Simulação de Dinâmica Molecular
14.
J Sep Sci ; 46(2): e2200311, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36349515

RESUMO

Abrus mollis Hance is a traditional Chinese medicine that is widely used to treat acute and chronic hepatitis, steatosis, and fibrosis. Its therapeutic qualities of it have long been acknowledged, although the active ingredients responsible for its efficacy and the mechanisms of its action are unknown. In this study, the chemical constituents absorbed into the blood from Abrus mollis Hance were assessed by using liquid chromatography-quadrupole-time-of-flight mass spectrometry and the data was analyzed with the UNIFI screening platform. The results obtained were compared to existing chromatographic-mass spectrometry information, including retention times and molecular weights as well as known reference compounds. 41 chemical constituents were found in Abrus mollis Hance, and these included 16 flavonoids, 13 triterpenoids, five organic acids, and two alkaloids. Experimentally it was found that Abrus mollis Hance had a therapeutic benefit when treating α-naphthalene isothiocyanate-induced acute liver injury in rats. In addition, 11 blood prototypical constituents, including six flavonoids, three triterpenoids, and two alkaloids, were found in serum samples following intragastric administration of Abrus mollis Hance extracts to rats. This novel study can be used for the quality control and pharmacodynamic assessment of Abrus mollis Hance in order to assess its efficacy in the therapeutic treatment of patients.


Assuntos
Abrus , Alcaloides , Medicamentos de Ervas Chinesas , Triterpenos , Ratos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Abrus/química , Espectrometria de Massas , Medicamentos de Ervas Chinesas/análise , Flavonoides/análise , Triterpenos/análise
15.
Plant Signal Behav ; 17(1): 2149113, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36448597

RESUMO

The seeds of Abrus cantoniensis (A. cantonensis) have dormancy characteristics with very low germination under natural conditions. In general, its seed dormancy could be broken by friction or soaking with exogenous gibberellins (GA3). To date, the molecular mechanism underlying the effects of GA3 and friction on its seed germination is unclear. In this study, we tested the effects of different treatments, including soaking in sterile water (G1), friction (G2), soaking in GA3 (G3), combined treatment of friction, and GA3 (G4)) on seed germination. Then, we have investigated the seed transcriptome profiles corresponding to the different treatments by RNA sequencing. The results showed that seed germination was significantly increased by combined treatment with friction and GA3. RNA-Seq analysis generated 84.80 gigabases (Gb) of sequences. 82,996 out of 121,776 unigenes were annotated. Comparative transcriptome analysis observed that 1,130, 1,097, and 708 unigenes were deferentially expressed in G1 vs. G2, G1 vs. G3, and G1 vs. G4 groups, respectively. Additionally, 20 putatively candidate genes related to seed germination, including CYP78A5, Bg7s, GA-20-ox, rd22, MYB4, LEA, CHS, and STH-2, and other potential candidates with abundant expression were identified. Our findings provide first insights into gene expression profiles and physiological response for friction combined with GA3 on A. cantoniensis seed germination.


Assuntos
Abrus , Transcriptoma , Transcriptoma/genética , Giberelinas/farmacologia , Germinação/genética , Fricção , Perfilação da Expressão Gênica
16.
Toxins (Basel) ; 14(9)2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36136552

RESUMO

Abrin is a highly toxic protein obtained from the seeds of the rosary pea plant Abrus precatorius, and it is closely related to ricin in terms of its structure and chemical properties. Both toxins inhibit ribosomal function, halt protein synthesis and lead to cellular death. The major clinical manifestations following pulmonary exposure to these toxins consist of severe lung inflammation and consequent respiratory insufficiency. Despite the high similarity between abrin and ricin in terms of disease progression, the ability to protect mice against these toxins by postexposure antibody-mediated treatment differs significantly, with a markedly higher level of protection achieved against abrin intoxication. In this study, we conducted an in-depth comparison between the kinetics of in vivo abrin and ricin intoxication in a murine model. The data demonstrated differential binding of abrin and ricin to the parenchymal cells of the lungs. Accordingly, toxin-mediated injury to the nonhematopoietic compartment was shown to be markedly lower in the case of abrin intoxication. Thus, profiling of alveolar epithelial cells demonstrated that although toxin-induced damage was restricted to alveolar epithelial type II cells following abrin intoxication, as previously reported for ricin, it was less pronounced. Furthermore, unlike following ricin intoxication, no direct damage was detected in the lung endothelial cell population following abrin exposure. Reduced impairment of intercellular junction molecules following abrin intoxication was detected as well. In contrast, similar damage to the endothelial surface glycocalyx layer was observed for the two toxins. We assume that the reduced damage to the lung stroma, which maintains a higher level of tissue integrity following pulmonary exposure to abrin compared to ricin, contributes to the high efficiency of the anti-abrin antibody treatment at late time points after exposure.


Assuntos
Abrina , Abrus , Doenças Transmitidas por Alimentos , Lesão Pulmonar , Intoxicação por Plantas , Ricina , Toxinas Biológicas , Abrina/toxicidade , Animais , Pulmão/metabolismo , Lesão Pulmonar/induzido quimicamente , Camundongos , Ricina/metabolismo , Ricina/toxicidade
17.
Plant Genome ; 15(3): e20236, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35748235

RESUMO

Abrus cantoniensis Hance, a native medicinal plant in southern China, is officially recorded in the Chinese Pharmacopoeia. Here, we presented the first high-quality genome in Abrus genus, A. cantoniensis genome, as well as the detailed genomic information. The assembled genome size was 381.27 Mb with a scaffold N50 of 18.95 Mb, and 98.97% of the assembled sequences were anchored on 11 pseudochromosomes. The A. cantoniensis genome comprised 25,058 protein-coding genes and 45.12% of the assemblies were repetitive sequences. Comparative genome analysis suggested that chromosome translocation and inversion played an important role in the differentiation of Abrus. In addition, 24 toxin-related genes were identified, which formed two tandem gene clusters on chromosomes 2 and 3. The chromosome-level genome of A. cantoniensis obtained in this work provides a valuable resource for understanding the evolution, active ingredient biosynthesis, and genetic improvement for A. cantoniensis and Abrus species.


Assuntos
Abrus , Plantas Medicinais , Genoma , Genômica , Filogenia , Plantas Medicinais/genética
18.
J Ethnopharmacol ; 296: 115463, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-35714881

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Abrus precatorius L. (AP) is a folk medicine with a long-term medicinal history worldwide, which is extensively applied to various ailments, such as bronchitis, jaundice, hepatitis, contraception, tumor, abortion, malaria, etc. Meanwhile, its leaves are also served as tea in China, and its roots are employed as a substitute for Glycyrrhiza uralensis or as a raw material for the extraction of glycyrrhizin in India. Thus, AP is considered to be a plant with dual values of medicine and economy as well as its chemical composition and biological activity, which are of growing interest to the scientific community. AIM OF REVIEW: In the review, the traditional application, botany, chemical constituents, pharmacological activities, and toxicity are comprehensively and systematically summarized. MATERIALS AND METHODS: An extensive database retrieval was conducted to gather the specific information about AP from 1871 to 2022 using online bibliographic databases Web of Science, PubMed, SciFinder, Google Scholar, CNKI, and Baidu Scholar. The search terms comprise the keywords "Abrus precatorius", "phytochemistry", "pharmacological activity", "toxicity" and "traditional application" as a combination. RESULTS: To date, AP is traditionally used to treat various diseases, including sore throat, cough, bronchitis, jaundice, hepatitis, abdominal pain, contraception, tumor, abortion, malaria, and so on. More than 166 chemical compounds have been identified from AP, which primarily cover flavonoids, phenolics, terpenoids, steroids, alkaloids, organic acids, esters, proteins, polysaccharides, and so on. A wide range of in vitro and in vivo pharmacological functions of AP have been reported, such as antitumor, antimicrobial, insecticidal, antiprotozoal, antiparasitic, anti-inflammatory, antioxidant, immunomodulatory, antifertility, antidiabetic, other pharmacological activities. The crushed seeds in powder or paste form were comparatively toxic to humans and animals by oral administration. Interestingly, the methanolic extracts were non-toxic to adult Wistar albino rats at various doses (200 and 400 mg/kg) daily. CONCLUSIONS: The review focuses on the traditional application, botany, phytochemistry, pharmacological activities, and toxicity of AP, which offers a valuable context for researchers on the current research status and a reference for further research and applications of this medicinal plant.


Assuntos
Abrus , Compostos Fitoquímicos , Extratos Vegetais , Animais , Humanos , Bronquite/tratamento farmacológico , Medicina Tradicional , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Ratos
19.
Sci Rep ; 12(1): 10226, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715430

RESUMO

Abrus precatorius is a tropical medicinal plant with multiple medicinal benefits whose seeds have not yet been studied against cervical cancer. Herein, we have assessed the antioxidant and antiproliferative properties of seed extracts (ethyl acetate and 70% ethanol) prepared from Soxhlet and Maceration extraction methods against Hep2C and HeLa Cells. We observed that the APE (Sox) extract had a significantly higher total flavonoid content, APA (Mac) extract had a high total phenolic content, and APA (Sox) extract had a high total tannin content. Further, HPLC analysis of extracts revealed the presence of tannic acid and rutin. Moreover, APA (Sox) exhibited the highest free radical scavenging activity. APE (Mac) had the best antiproliferative activity against Hep2C cells, while APA (Sox) had the best antiproliferative activity against HeLa cells. In Hep2C cells, APE (Mac) extract revealed the highest SOD, catalase activity, GSH content, and the lowest MDA content, whereas APA (Mac) extract demonstrated the highest GST activity. In HeLa cells, APA (Sox) extract showed the highest SOD, GST activity, GSH content, and the least MDA content, whereas APA (Mac) extract showed the highest catalase activity. Lastly, docking results suggested maximum binding affinity of tannic acid with HER2 and GCR receptors. This study provides evidence that A. precatorius seed extracts possess promising bioactive compounds with probable anticancer and antioxidant properties against cervical cancer for restricting tumor growth.


Assuntos
Abrus , Neoplasias do Colo do Útero , Abrus/química , Antioxidantes/análise , Antioxidantes/farmacologia , Catalase , Feminino , Flavonoides/análise , Flavonoides/farmacologia , Células HeLa , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Superóxido Dismutase , Taninos/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico
20.
Molecules ; 27(7)2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35408435

RESUMO

Abrus cantoniensis is a Chinese herbal medicine with efficacy in clearing heat and detoxification, as well as relieving liver pain. The whole plant, except the seeds, can be used and consumed. Flavonoids have been found in modern pharmacological studies to have important biological activities, such as anti-inflammatory, antibacterial and antioxidant properties. The antibacterial and antioxidant bioactivities of the total flavonoids of Abrus cantoniensis (ATF) have been widely reported in national and international journals, but there are fewer studies on their anti-inflammatory effects. The present study focused on the optimization of the ultrasonic extraction process of ATF by response surface methodology and the study of its anti-inflammatory effects in vitro and in vivo. The results showed that the factors that had a great impact on the ATF extraction were the material-to-liquid ratio, ultrasonic extraction cycles and ethanol concentration. The best extraction process used a material-to-liquid ratio of 1:47, ultrasonic extraction cycles of 4 times, an ethanol concentration of 50%, an ultrasonic extraction time of 40 min and an ultrasonic power of 125 W. Under these conditions, the actual extraction rate of total flavonoids was 3.68%, which was not significantly different from the predicted value of 3.71%. In an in vitro anti-inflammatory assay, ATF was found to be effective in alleviating LPS (lipopolysaccharide)-induced inflammation in mouse peritoneal macrophages. In an in vivo anti-inflammatory assay, ATF was found to have a significant inhibitory effect on xylene-induced ear swelling in mice and cotton ball granuloma in mice, and the inhibitory effect was close to that of the positive control drug dexamethasone. This may provide a theoretical basis for the further development of the medicinal value of Abrus cantoniensis.


Assuntos
Abrus , Animais , Antibacterianos , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Etanol , Flavonoides/farmacologia , Camundongos , Extratos Vegetais/farmacologia , Ultrassom
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