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1.
Chem Biodivers ; 19(10): e202200562, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35965252

RESUMO

Leaves of Combretum quadrangulare Kurz showed potent α-glucosidase inhibition. Two new cycloartane-type triterpenes, combretic acids D and E were isolated from the bioactive fraction. The chemical structures were determined using NMR and MS methods. Combretic acid D represents for the first cycloartane having a dihydrofuran ring in the side chain. Combretic acids D and E showed significant α-glucosidase inhibition, with IC50 values of 13.9 and 30.7 µM, respectively. Combretic acid D was determined to be a non-competitive type in the kinetic study. The docking study in combination with dynamic simulations of this compound provided the molecular understanding of α-glucosidase inhibition.


Assuntos
Combretum , Triterpenos , Humanos , Combretum/química , alfa-Glucosidases , Estrutura Molecular , Triterpenos/química , Asiáticos , Simulação de Acoplamento Molecular , Inibidores de Glicosídeo Hidrolases/farmacologia
2.
Fundam Clin Pharmacol ; 36(5): 818-826, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35261066

RESUMO

Drugs used to manage type 2 diabetes mellitus cause adverse effects. Therefore, the search for new drugs as an alternative for the treatment of diabetes increases. The effect of triterpene 3ß-6ß-16ß-trihydroxylup-20(29)-ene isolated from the leaves of C. leprosum (CLF-1) on sucrose-induced hyperglycemia in adult zebrafish (Danio rerio) was evaluated. Initially, adult zebrafish (n = 6/group) underwent hyperglycemia induction by sucrose at 83.25 mM/L for 7 days by immersion. The hyperglycemic groups were treated with CLF-1 (4, 20, and 40 mg/kg), metformin (200 mg/kg), and acarbose (300 mg/kg) for 4 days. The in silico interaction of CLF-1, metformin, and acarbose with the enzyme maltase-glucoamylase (CtMGAM) was investigated. CLF-1 reduced sucrose-induced hyperglycemia after 4 days of treatment, in addition to having better affinity energy with CtMGAM than metformin and acarbose. Thus, CLF-1 may be a new pharmacological alternative as a hypoglycemic agent for the treatment of diabetes.


Assuntos
Combretum , Diabetes Mellitus Tipo 2 , Hiperglicemia , Metformina , Triterpenos , Acarbose/farmacologia , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta , Sacarose , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Peixe-Zebra
3.
Molecules ; 27(3)2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35164024

RESUMO

Tomato brown rugose fruit virus (ToBRFV) is a new damaging plant virus of great interest from both an economical and research point of view. ToBRFV is transmitted by contact, remains infective for months, and to-date, no resistant cultivars have been developed. Due to the relevance of this virus, new effective, sustainable, and operator-safe antiviral agents are needed. Thus, 4-hydroxybenzoic acid was identified as the main product of the alkaline autoxidation at high temperature of the methanolic extract of the leaves of C. micranthum, known for antiviral activity. The autoxidized extract and 4-hydroxybenzoic acid were assayed in in vitro experiments, in combination with a mechanical inoculation test of tomato plants. Catechinic acid, a common product of rearrangement of catechins in hot alkaline solution, was also tested. Degradation of the viral particles, evidenced by the absence of detectable ToBRFV RNA and the loss of virus infectivity, as a possible consequence of disassembly of the virus coat protein (CP), were shown. Homology modeling was then applied to prepare the protein model of ToBRFV CP, and its structure was optimized. Molecular docking simulation showed the interactions of the two compounds, with the amino acid residues responsible for CP-CP interactions. Catechinic acid showed the best binding energy value in comparison with ribavirin, an anti-tobamovirus agent.


Assuntos
Antivirais/farmacologia , Combretum/química , Lycopersicon esculentum/efeitos dos fármacos , Doenças das Plantas/prevenção & controle , Tobamovirus/efeitos dos fármacos , Antivirais/química , Homeostase , Lycopersicon esculentum/virologia , Metanol/química , Testes de Sensibilidade Microbiana , Modelos Moleculares , Simulação de Acoplamento Molecular , Oxirredução , Doenças das Plantas/virologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Vírus de Plantas/química , Vírus de Plantas/efeitos dos fármacos , Vírus de Plantas/patogenicidade , Tobamovirus/química , Tobamovirus/patogenicidade
4.
Chem Biodivers ; 19(2): e202100646, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34982514

RESUMO

Multidrug resistance is a significant drawback in malaria treatment, and mutations in the active sites of the many critical antimalarial drug targets have remained challenging. Therefore, this has necessitated the global search for new drugs with new mechanisms of action. Plasmodium falciparum lactate dehydrogenase (pfLHD), a glycolytic enzyme, has emerged as a potential target for developing new drugs due to the parasite reliance on glycolysis for energy. Strong substrate-binding is required in pfLDH enzymatic catalysis; however, there is a lack of information on small molecules' inhibitory mechanism bound to the substrate-binding pocket. Therefore, this study investigated a potential allosteric inhibition of pfLDH by targeting the substrate-binding site. The structural and functional behaviour of madecassic acid (MA), the most promising among the six triterpenes bound to pfLDH, were unravelled using molecular dynamic simulations at 300 ns to gain insights into its mechanism of binding and inhibition and chloroquine as a standard drug. The docking studies identified that the substrate site has the preferred position for the compounds even in the absence of a co-factor. The bound ligands showed comparably higher binding affinity at the substrate site than at the co-factor site. Mechanistically, a characteristic loop implicated in the enzyme catalytic activity was identified at the substrate site. This loop accommodates key interacting residues (LYS174, MET175, LEU177 and LYS179) pivotal in the MA binding and inhibitory action. The MA-bound pfLHD average RMSD (1.60 Å) relative to chloroquine-bound pfLHD RMSD (2.00 Å) showed higher stability for the substrate pocket, explaining the higher binding affinity (-33.40 kcal/mol) observed in the energy calculations, indicating that MA exhibited profound inhibitory activity. The significant pfLDH loop conformational changes and the allostery substrate-binding landscape suggested inhibiting the enzyme function, which provides an avenue for designing antimalarial compounds in the future studies of pfLDH protein as a target.


Assuntos
Antimaláricos , Combretum , Triterpenos , Antimaláricos/química , Antimaláricos/farmacologia , Combretum/metabolismo , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Plasmodium falciparum , Triterpenos/farmacologia
5.
Fundam Clin Pharmacol ; 36(3): 486-493, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34989452

RESUMO

Globally, plant-derived medicines have been playing an increasing and relevant role in the treatment of several diseases, thus fostering the search for new bioactive substances. Among the various families of plants studied, those of the Combretum genus can be highlighted since they are widely used in folk medicine for the treatment of hepatitis, malaria, respiratory infections, cancer, skin hemorrhage, and anxiety. Phytochemical studies carried out on species of the Combretum genus demonstrated the presence of several classes of bioactive chemical compounds, including the triterpene 3ß,6ß,16ß-trihydroxilup-20(29)-ene (CLF-1). In this perspective, the objective of this review was to gather all pharmacological activities attributed to the CLF-1 triterpene, highlighting its importance for the pharmaceutical industry. The research was performed in scientific databases such as PubMed, SciELO, LILACS, SciFinder and Science Direct. The literature indicates a great pharmacological potential of CLF-1, evidencing its antioxidant, anti-inflammatory, antiviral, antiparasitic, antinociceptive, healing, and antibacterial action, antinociceptive and antitumor effect. Therefore, based on the different research above, it is plausible to consider CLF-1, obtained from different parts of the C. leprosum plant, as a molecule with biotechnological potential that may contribute to the development of new drugs and, consequently, in the treatment of various human pathologies.


Assuntos
Combretum , Triterpenos , Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Combretum/química , Etnofarmacologia , Humanos , Extratos Vegetais/farmacologia , Triterpenos/farmacologia
6.
J Asian Nat Prod Res ; 24(7): 691-696, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34319176

RESUMO

Phytochemical investigation on the leaves of Combretum quadrangulare growing in Vietnam afforded a new trinorcycloartane triterpenoid, norquandrangularic acid D (1), along with three known compounds, betulinic acid (2), luteolin (3), and apigenin (4). Their structures were elucidated using spectroscopic methods and comparison was made with reports in the literature. Compounds 1 and 3 were evaluated for α-glucosidase inhibition. Compound 3 showed significant activity, with an IC50 value of 11.39 µM, (acarbose, used as a positive control, had an IC50 of 367 µM).


Assuntos
Combretum , Triterpenos , Combretum/química , Estrutura Molecular , Extratos Vegetais/química , Folhas de Planta/química , Triterpenos/química , alfa-Glucosidases
7.
J Toxicol Environ Health A ; 85(9): 364-375, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-34933666

RESUMO

The beneficial pharmacological actions including antioxidant effects as an antileishmanial, antibacterial, antifungal, antidiabetic, anti-inflammatory, antitumor, antiviral, and analgesic of compounds isolated from Combretum mellifluum Eichler (Combretaceae) are well established. The aim of the present study was to determine the phytochemistry as well as assess the antioxidant and antileishmanial activities of the leaves from Combretum mellifluum Eichler (Combretaceae). Analysis of ethanolic extract resulted in isolation and identification of two epimeric mixtures of four previously unknown cycloartane-type triterpenoids, methyl quadrangularate M and methyl 24-epiquadrangularate M, and 2α,3ß,24ß-trihydroxy-cycloart-25-ene and 2α, 3ß, 24α-trihydroxy-cycloart-25-ene, and eight known compounds. Their structures were using one-dimensional nuclear magnetic resonance (1D NMR), 2D NMR and high-resolution electrospray ionization mass spectroscopy (HRESIMS) analysis. Further, the extract and fractions were tested for antioxidant potential. The ethyl acetate and aqueous fractions demonstrated the highest antioxidant activity against 2,2-dipheny-1-picrylhydrazl (DPPH) free radicals, which correlated directly with total flavonoid content. All extracts and fractions from C. mellifluum Eichler were assessed for antileishmanial activity. The supernatant fraction exhibited highest potential, inhibiting the growth of Leishmania amazonensis with IC50 value 31.29 µg/ml. Our findings provide information on the chemical composition of C. mellifluum and the potential beneficial therapeutic usefulness as an antioxidant agent in various diseases.


Assuntos
Combretum , Triterpenos , Antioxidantes/análise , Antioxidantes/farmacologia , Combretum/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Triterpenos/análise , Triterpenos/química , Triterpenos/farmacologia
8.
Biomed Pharmacother ; 144: 112264, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34624680

RESUMO

In Sudanese traditional medicine, decoctions, macerations, and tonics of the stem and root of Combretum hartmannianum are used for the treatment of persistent cough, a symptom that could be related to tuberculosis (TB). To verify these traditional uses, extracts from the stem wood, stem bark, and roots of C. hartmannianum were screened for their growth inhibitory effects against Mycobacterium smegmatis ATCC 14468. Methanol Soxhlet and ethyl acetate extracts of the root gave the strongest effects (MIC 312.5 and 625 µg/ml, respectively). HPLC-UV/DAD and UHPLC/QTOF-MS analysis of the ethyl acetate extract of the root led to the detection of 54 compounds, of which most were polyphenols and many characterized for the first time in C. hartmannianum. Among the major compounds were terflavin B and its two isomers, castalagin, corilagin, tellimagrandin I and its derivative, (S)-flavogallonic acid dilactone, punicalagin, and methyl-ellagic acid xylopyranoside. In addition, di-, tri- and tetra-galloyl glucose, combregenin, terminolic acid, cordifoliside D, luteolin, and quercetin-3-O-galactoside-7-O-rhamnoside-(2→1)-O-ß-D-arabinopyranoside were characterized. Luteolin gave better growth inhibition against M. smegmatis (MIC 250 µg/ml) than corilagin, ellagic acid, and gallic acid (MIC 500-1000 µg/ml). Our study justifies the use of C. hartmannianum in Sudanese folk medicine against prolonged cough that could be related to TB infection. This study demonstrates that C. hartmannianum should be explored further for new anti-TB drug scaffolds and antibiotic adjuvants.


Assuntos
Antibacterianos/farmacologia , Combretum , Flavonoides/farmacologia , Glicosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Mycobacterium smegmatis/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Antibacterianos/isolamento & purificação , Combretum/química , Etnofarmacologia , Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Humanos , Taninos Hidrolisáveis/isolamento & purificação , Testes de Sensibilidade Microbiana , Mycobacterium smegmatis/crescimento & desenvolvimento , Triterpenos Pentacíclicos/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Sudão
9.
Acta Crystallogr C Struct Chem ; 77(Pt 9): 505-512, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482293

RESUMO

A chemical study of the hydro-ethanol extract of the leaves of Combretum glutinosum resulted in the isolation of nine compounds, including 5-demethylsinensetin (1), umuhengerin (2), (20S,24R)-ocotillone (3), lupeol (4), ß-sitosterol (5), oleanolic acid (6), betulinic acid (7), corymbosin (8) and ß-sitosterol glucoside (9). Four compounds have been isolated for the first time from the genus Combretum [viz. (1), (2), (3) and (8)]. The crystal structures of flavonoid (2), C20H20O8, Z' = 2, and triterpene (3), C30H50O3, Z' = 1, have been determined for the first time; the latter confirmed the absolute configuration of native (20S,24R)-ocotillone previously derived from the crystal structures of related derivatives. The molecules of (3) are linked into supramolecular chains by intermolecular O-H...O hydrogen bonds. The crude extracts obtained by aqueous decoction and hydro-ethanolic maceration, as well as the nine isolated compounds, were tested for their anthelmintic activity on the larvae and adult worms of Haemonchus contortus, a hematophage that causes parasitic disorders in small ruminants. The evaluated anthelmintic activity showed that the extracts at different doses, as well as all the compounds tested at 150 µg ml-1, inhibited the migration of the larvae and the motility of the adult worms of the parasite compared with the phosphate buffer solution negative reference control. The best activity was obtained with flavonoids (1), (2) and (8) on both stages of the parasite. The flavones that showed good activity can be used for the further development of other derivatives, which could increase the anthelmintic efficacy.


Assuntos
Anti-Helmínticos/farmacologia , Anti-Infecciosos/farmacologia , Combretaceae/efeitos dos fármacos , Combretum/química , Flavonas/farmacologia , Flavonoides/química , Haemonchus/efeitos dos fármacos , Larva/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Animais , Anti-Helmínticos/química , Anti-Helmínticos/uso terapêutico , Anti-Infecciosos/química , Cristalografia por Raios X , Flavonas/química , Flavonoides/farmacologia , Haemonchus/crescimento & desenvolvimento , Ligação de Hidrogênio , Folhas de Planta/química
10.
Molecules ; 26(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34361788

RESUMO

This research investigated a UPLC-QTOF/ESI-MS-based phytochemical profiling of Combretum indicum leaf extract (CILEx), and explored its in vitro antioxidant and in vivo antidiabetic effects in a Long-Evans rat model. After a one-week intervention, the animals' blood glucose, lipid profile, and pancreatic architectures were evaluated. UPLC-QTOF/ESI-MS fragmentation of CILEx and its eight docking-guided compounds were further dissected to evaluate their roles using bioinformatics-based network pharmacological tools. Results showed a very promising antioxidative effect of CILEx. Both doses of CILEx were found to significantly (p < 0.05) reduce blood glucose, low-density lipoprotein (LDL), and total cholesterol (TC), and increase high-density lipoprotein (HDL). Pancreatic tissue architectures were much improved compared to the diabetic control group. A computational approach revealed that schizonepetoside E, melianol, leucodelphinidin, and arbutin were highly suitable for further therapeutic assessment. Arbutin, in a Gene Ontology and PPI network study, evolved as the most prospective constituent for 203 target proteins of 48 KEGG pathways regulating immune modulation and insulin secretion to control diabetes. The fragmentation mechanisms of the compounds are consistent with the obtained effects for CILEx. Results show that the natural compounds from CILEx could exert potential antidiabetic effects through in vivo and computational study.


Assuntos
Antioxidantes/farmacologia , Combretum/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Arbutina/química , Arbutina/isolamento & purificação , Sítios de Ligação , Glicemia/efeitos dos fármacos , HDL-Colesterol/agonistas , HDL-Colesterol/sangue , LDL-Colesterol/antagonistas & inibidores , LDL-Colesterol/sangue , Biologia Computacional/métodos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Flavonoides/química , Flavonoides/isolamento & purificação , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Insulina/agonistas , Insulina/metabolismo , Masculino , Modelos Moleculares , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Extratos Vegetais/química , Folhas de Planta/química , Ligação Proteica , Conformação Proteica , Ratos , Ratos Long-Evans , Triterpenos/química , Triterpenos/isolamento & purificação
11.
Molecules ; 26(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34443320

RESUMO

Crop diseases caused by Fusarium pathogens, among other microorganisms, threaten crop production in both commercial and smallholder farming. There are increasing concerns about the use of conventional synthetic fungicides due to fungal resistance and the associated negative effects of these chemicals on human health, livestock and the environment. This leads to the search for alternative fungicides from nature, especially from plants. The objectives of this study were to characterize isolated compounds from Combretum erythrophyllum (Burch.) Sond. and Withania somnifera (L.) Dunal leaf extracts, evaluate their antifungal activity against Fusarium pathogens, their phytotoxicity on maize seed germination and their cytotoxicity effect on Raw 264.7 macrophage cells. The investigation led to the isolation of antifungal compounds characterized as 5-hydroxy-7,4'-dimethoxyflavone, maslinic acid (21-hydroxy-3-oxo-olean-12-en-28-oic acid) and withaferin A (4ß,27-dihydroxy-1-oxo-5ß,6ß-epoxywitha-2-24-dienolide). The structural elucidation of the isolated compounds was established using nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS) and, in comparison, with the available published data. These compounds showed good antifungal activity with minimum inhibitory concentrations (MIC) less than 1.0 mg/mL against one or more of the tested Fusarium pathogens (F. oxysporum, F. verticilloides, F. subglutinans, F. proliferatum, F. solani, F. graminearum, F. chlamydosporum and F. semitectum). The findings from this study indicate that medicinal plants are a good source of natural antifungals. Furthermore, the isolated antifungal compounds did not show any phytotoxic effects on maize seed germination. The toxicity of the compounds A (5-hydroxy-7,4'-dimethoxyflavone) and AI (4ß,27-dihydroxy-1-oxo-5ß,6ß-epoxywitha-2-24-dienolide) was dose-dependent, while compound B (21-hydroxy-3-oxo-olean-12-en-28-oic acid) showed no toxicity effect against Raw 264.7 macrophage cells.


Assuntos
Antifúngicos/farmacologia , Combretum/química , Fusarium/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Withania/química , Animais , Camundongos , Testes de Sensibilidade Microbiana , Células RAW 264.7
12.
Chem Biodivers ; 18(10): e2100350, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34399029

RESUMO

Endophytic fungi are an important class of microorganisms, able to interact with a host plant via a mutualistic mechanism without visible symptoms of the fungal colonization. The synergy between endophytic fungi and their host plant can promote morphological, physiological and biochemical changes through the expression of bioactive metabolites. This work aims to correlate metabolic changes in the Combretum lanceolatum plant metabolome with its endophytic fungi Diaporthe phaseolorum (Dp) and Trichoderma spirale (Ts), and to discover corresponding metabolite-biomarkers, with the principal focus being on its primary metabolism. The 1 H-NMR metabolomic analysis of qualitative and quantitative changes was performed through multivariate statistical analysis and the identification of primary metabolites was achieved on the Madison Metabolomics Consortium Database. The presence of Dp significantly impacted the plant's metabolic pathways, improving the biosynthesis of primary metabolites such as threonine, malic acid and N-acetyl-mannosamine, which are precursors of special metabolites involved in plant self-defence. This work represents a valuable contribution to advanced studies on the metabolic profiles of the interaction of plants with endophytes.


Assuntos
Ascomicetos/metabolismo , Combretum/metabolismo , Metabolômica , Trichoderma/metabolismo , Ascomicetos/química , Combretum/química , Espectroscopia de Prótons por Ressonância Magnética , Trichoderma/química
13.
Asian Pac J Cancer Prev ; 22(4): 1087-1093, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33906300

RESUMO

BACKGROUND: Cancer incidence has been growing in an alarming rate worldwide and new therapeutics are needed, particularly for intractable and chemoresistant cases. We evaluated the cytotoxic effects of Combretum fragrans F. Hoffm (Combretaceae) on glioblastoma (U87MG and C6) and prostate (PC-3) cancer cell lines. METHODS: The cytotoxic effect of the methanolic extract of the stem bark of Combretum fragrans was assessed using XTT (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) test. Expressions of Akt and ERK1/2 were determined using Western blot technique, while Caspase-3/7 kits were used to evaluate caspase-3/7 activity. RESULTS: C. fragrans extract inhibited the proliferation of U87 (IC50 = 20.13 µg/mL), C6 (IC50 = 12.17 µg/mL), and PC-3 (IC50 = 11.50 µg/mL) cells. Treatment with the extract resulted in lower levels (p < 0.001) of phospho-ERK1/2 and phospho-Akt in U87 cells, and instead, higher levels of phospho-ERK1/2 (p < 0.001) in C6 and PC-3 cells. An increase in caspase-3/7 activity was observed, mainly after 24 hours of treatment, indicating the activation of apoptotic processes. CONCLUSION: Altogether, these results suggest that C. fragrans have potent anticancer properties. This plant should be further investigated for developing new anticancer drugs.
.


Assuntos
Combretum , Glioblastoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/análise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Caules de Planta
14.
Molecules ; 26(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926133

RESUMO

Combretum quadrangulare Kurz is widely used in folk medicine in Eastern Asia and is associated with various ethnopharmacological properties including hepatoprotective, antipyretic, analgesic, antidysenteric, and anthelmintic activities. Previous phytochemical investigations reported the presence of numerous triterpenes (mostly cycloartanes, ursanes, lupanes, and oleananes) along with dozens of flavonoids. However, the extracts of C. quadrangulare and isolated flavonoids have not been evaluated for their alpha-glucosidase inhibition. In the frame of our efforts dedicated to the chemical investigation of Vietnamese medicinal plants and their biological activities, a phytochemical study of the MeOH extract of the leaves of C. quadrangulare using bioactive guided isolation was undertaken. In this paper, the isolation and structure elucidation of twelve known compounds, 5-hydroxy-3,7,4'-trimethoxyflavone (1), ayanin (2), kumatakenin (3), rhamnocitrin (4), ombuin (5), myricetin-3,7,3',5'-tetramethyl ether (6), gardenin D (7), luteolin (12), apigenin (13), mearnsetin (14), isoorientin (15), and vitexin (16) were reported. Bromination was applied to compounds 2 and 3 to provide four new synthetic analogues 8-11. All isolated and synthesized compounds were evaluated for alpha-glucosidase inhibition and antibacterial activity. Compounds 4 and 5 showed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus while others were inactive. All compounds failed to reveal any activity toward extended spectrum beta-lactamase-producing Escherichia coli. Compounds 2, 4, 6-9, and 11-14 showed good alpha-glucosidase inhibition with IC50 values in the range of 30.5-282.0 µM. The kinetic of enzyme inhibition showed that 8 and 11 were noncompetitive type inhibition against alpha-glucosidase. In silico molecular docking model indicated that compounds 8 and 11 were potential inhibitors against enzyme α-glucosidase.


Assuntos
Combretum/química , Flavonas/química , Flavonas/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Dose-Resposta a Droga , Flavonas/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Compostos Fitoquímicos/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade
15.
J Ethnopharmacol ; 273: 113981, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-33647425

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Combretum species are used traditionally for the treatment of diarrhoea, hookworm, fever, inflammation, pain and infectious diseases. Infections are commonly caused by the intake of food contaminated with foodborne pathogens. These are a significant concern in the food industry owing to their ability to form biofilms and cause food spoilage, despite the availability of modern food preservation techniques. Combretum elaeagnoides Klotzsch (Combretaceae) is used in southern African traditional medicine against infections and diarrhoea. AIM OF THE STUDY: This study evaluated the antimicrobial ability of C. elaeagnoides leaf fractions and the isolated compound quercetin-3-O-rhamnoside against a panel of foodborne pathogens, and biofilms formed by them. The samples were also assessed for their antioxidant activity and cytotoxicity. MATERIALS AND METHODS: Fractions prepared from the methanol extract of the leaves, and a bioactive compound (quercetin-3-O-rhamnoside) isolated from the ethyl acetate fraction were investigated for activity against nine reference and clinical strains of foodborne pathogens. The microdilution method was used to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the fractions and compound. The inhibition of biofilm formation and the crystal violet staining assays were used to determine the antibiofilm efficacy. The DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay and the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) electron reduction assay were used to determine the antioxidant potential of the fractions and compound. The cytotoxicity was assessed using the 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay against Vero African monkey kidney cells. RESULTS: The fractions were active against all tested organisms, with MIC values ranging from 0.03 to 1.25 mg/mL. The best MBC was 0.63 mg/mL. All the fractions and the purified compound inhibited biofilm formation of Staphylococcus aureus and Salmonella Typhimurium, with percentage inhibition values greater than 50% at 1 mg/mL. The compound had very promising antibiofilm activity against Escherichia coli 1 (ATCC 25922) with percentage inhibition of >150%. The compound and fractions had good radical scavenging potential against the DPPH and ABTS radicals. Quercetin-3-O-rhamnoside and the fractions were relatively non-cytotoxic. CONCLUSION: The ability of the fractions and compound to reduce and inhibit biofilm biomass and their promising antioxidant potential provide motivation to further investigate the use of plants to protect food products from contamination, as well as to treat infections characterized by bacterial biofilms.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Combretum/química , Microbiologia de Alimentos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antibacterianos/química , Extratos Vegetais/química
16.
J Ethnopharmacol ; 273: 113992, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-33677007

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Evaluation of plants such as Combretum racemosum with claimed traditional use in the management of sickle cell anaemia in Nigeria and other parts of West Africa could serve as a useful research strategy in the search for potential anti-sickling drugs and templates. AIM OF THE STUDY: This study aimed at evaluating the antisickling potential of C. racemosum by activity-guided purification and isolation of its active constituents. MATERIALS AND METHODS: Crude methanol extract of the root of C. racemosum and the fractions obtained by partitioning with chloroform, ethyl acetate, and aqueous were investigated for anti-sickling activity against sodium metabisulphite induced sickling of sickle cell haemoglobin (HbSS). Repeated chromatographic separations were conducted on the most active chloroform fraction to purify and isolate bioactive compounds for further tests for anti-sickling activity. The characterization of the isolated compounds was done by mass spectrometry (FD+MS) and nuclear magnetic resonance (1HNMR) spectroscopy. RESULTS: The chloroform fraction (FA) (% sickled erythrocyte ranged from 3.0 to 34.1) exhibited better anti-sickling activity than aqueous (% sickled erythrocyte ranged from 38.9 to 51.5) as well as the crude methanol (% sickled erythrocyte ranged from 19.1 to 30.4). Hence, the phytochemical investigation was focused on the chloroform fraction, which led to the identification of two ellagic acid derivatives (3,3',4'-tri-O-methyl ellagic acid (A) and 3,3'-di-O- methyl ellagic acid (B). The two isolated compounds possessed good, comparable anti-sickling activities with compound A exhibiting a slightly better in vitro activity. CONCLUSION: This paper reports for the first time anti-sickling principles from C. racemosum and therefore, provided some justification for the ethnomedicinal use of the plant in the management of sickle cell disease.


Assuntos
Anemia Falciforme/sangue , Combretum/química , Eritrócitos Anormais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Medicina Tradicional Africana , Compostos Fitoquímicos , Extratos Vegetais/química , Adulto Jovem
17.
Biomed Res Int ; 2021: 6049728, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33623782

RESUMO

Combretum zeyheri and Combretum platypetalum have been shown to have anticancer, antibacterial, antituberculosis, and antifungal effects in both in vivo and in vitro studies. This study sought to evaluate the antiproliferative effects of compounds isolated from C. zeyheri and C. platypetalum on Jurkat T and HL-60 cancer cell lines in combination with doxorubicin and/or chlorambucil. At their GI50 concentrations, the isolated compounds were combined with the corresponding GI50 of chlorambucil and doxorubicin. The cytotoxic effects of the combined compounds were determined on BALB/c mouse peritoneal cells. All the 4 isolated compounds had significant cytotoxic effects on Jurkat T cells. Compounds CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) had GI50s on Jurkat T cells of 3.98, 19.33, 6.82, and 20.28 µg/ml, respectively. CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) showed GI50s of 14.18, 28.69, 29.87, and 16.46 µg/ml on HL-60 cancer cell lines, respectively. The most potent combination against Jurkat T cells was found to be CP 404 (1) and chlorambucil. This combination showed no cytotoxic effects when tested on BALB/c mouse peritoneal cells. It was concluded that the compounds extracted from C. zeyheri and C. platypetalum inhibit the growth of Jurkat T cells in vitro. The combination of the compounds with anticancer drugs enhanced their anticancer effects. The combination of CP 404 (1) and chlorambucil was found not to be toxic to normal mammalian cells. Therefore, CP 404 (1), 3-O-ß-L-rrhamnopyranosyl-5,7,3'4',5'-pentahydroxyflavone, has the potential to be a source of lead compounds that can be developed for anticancer therapy. Further structure-activity relationship studies on this compound are warranted.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Combretum/química , Extratos Vegetais/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células HL-60 , Humanos , Células Jurkat , Camundongos , Camundongos Endogâmicos BALB C , Cavidade Peritoneal/citologia
18.
J Toxicol Environ Health A ; 84(10): 399-417, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-33494643

RESUMO

Combretum leprosum Mart. (Combretaceae), a shrub popularly known as mofumbo, is used in folk medicine for treatment of uterine bleeding, pertussis, gastric pain, and as a sedative. The aim of this study was to (1) determine the phytochemical profile,(2) identify chemical constituents and (3) examine antioxidant and cytogenotoxic activity of ethanolic extracts and fractions of stem bark and leaves. The plant material (leaf and stem bark) was submitted to extraction with ethanol, followed by partition using hexane, chloroform, and ethyl acetate. It was possible to identify and quantify the epicatechin in the ethanolic stem bark extract (0.065 mg/g extract) and rutin in the leaf extract (3.33 mg/g extract). Based upon in vitro tests a significant relationship was noted between findings from antioxidant tests and levels of total phenolic and flavonoid. Comparing all samples (extracts and fractions), the ethyl acetate fractions of stem bark (411.40 ± 15.38 GAE/g) and leaves (225.49 ± 9.47 GAE/g) exhibited higher phenolic content, whereas hexanic fraction of stem bark (124.28 ± 56 mg/g sample) and ethyl acetate fraction of leaves (238.91 ± 1.73 mg/g sample) demonstrated a higher content of flavonoids. Among the antioxidant tests, the intermediate fraction of stem bark (28.5 ± 0.60 µg/ml) and ethyl acetate fraction of leaves (40 ± 0.56 µg/ml) displayed a higher % inhibition of free radical DPPH activity, whereas intermediate fraction of stem bark (27.5 ± 0.9 µg/ml) and hydromethanol fraction of leaves (81 ± 1.4 µg/ml) demonstrated inhibition of the free radical ABTS. In biological tests (Allium cepa and micronucleus in peripheral blood), data showed that none of the tested concentrations of ethanolic extracts of leaves and stem bark produced significant cytotoxicity, genotoxicity, and mutagenic activity.Abbreviations AA%: percentage of antioxidant activity; ABTS: 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid); CEUA: Ethics Committee in the Use of Animals; TLC: Thin Layer Chromatography; DNA: deoxyribonucleic acid; DPPH: 1,1-diphenyl-2-picrylhydrazyl; ROS: Reactive oxygen species; EEB: ethanol extract of the stem bark; HFB: Hexanic fraction of stem bark; IFB: Intermediate fraction of stem bark; CFB: Chloroform fraction of stem bark; EAFB: Ethyl acetate fraction of stem bark; HMFB: Hydromethanol fraction of the stem bark; EEL: Ethanol extract from leaves; HFL: Hexane fraction of leaves; CFL: Chloroform fraction of leaves; EAFL: Ethyl acetate fraction of leaves; HMFL: Hydromethanol fraction of leaves; GAE: Gallic Acid Equivalent; IC50: 50% inhibition concentration; HCOOH: Formic acid; HCl: hydrochloric acid; HPLC: High-performance liquid chromatography; MN: micronucleus; WHO: World Health Organization; UFLC: Ultra-Fast Liquid Chromatography; UESPI: State University of Piauí.


Assuntos
Antioxidantes , Combretum/química , Flavonoides , Fenóis , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Antioxidantes/farmacologia , Citotoxinas/toxicidade , Flavonoides/farmacologia , Flavonoides/toxicidade , Testes para Micronúcleos , Mutagênicos/toxicidade , Cebolas/efeitos dos fármacos , Fenóis/farmacologia , Fenóis/toxicidade , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/toxicidade , Casca de Planta/química , Extratos Vegetais/química , Folhas de Planta/química , Caules de Planta/química
19.
Artigo em Inglês | MEDLINE | ID: mdl-33498657

RESUMO

Combretum erythrophyllum is an indigenous southern African tree species, a metal hyperaccumulator that has been used as a phytoextraction option for tailing dams in Johannesburg, South Africa. In hyperaccumulators, metal detoxification has also been linked or attributed to the activities of endophytes, and, in this regard, metal detoxification can be considered a form of endophytic behavior. Therefore, we report herein on the identification of proteins that confer heavy metal resistance, the in vitro characterization of heavy metal resistance, and the production of plant growth-promoting (PGP) volatiles by Methylobacterium radiotolerans MAMP 4754. Multigenome comparative analyses of M. radiotolerans MAMP 4754 against eight other endophytic strains led to the identification of zinc, copper, and nickel resistance proteins in the genome of this endophyte. The maximum tolerance concentration (MTC) of this strain towards these metals was also investigated. The metal-exposed cells were analyzed by transmission electron microscopy (TEM). The ethyl acetate and chloroform extracts (1:1 v/v) of heavy metal untreated M. radiotolerans MAMP 4754 were also screened for the production of PGP compounds by Gas Chromatography-Mass Spectroscopy (GC/MS). The MTC was recorded at 15 mM, 4 mM, and 12 mM for zinc, copper, and nickel, respectively. The TEM analysis showed the accumulation of metals in the intracellular environment of M. radiotolerans MAMP 4754, while the GC/MS analysis revealed several plant growth-promoting compounds, including alcohols, phthalate esters, alkenes, ketones, sulfide derivatives, phenols, and thiazoles. Our findings suggest that the genetic makeup of M. radiotolerans MAMP 4754 encodes heavy metal resistant proteins that indicate hyperaccumulator-specific endophytic behavior and the potential for application in bioremediation. The production of plant growth-promoting volatiles in pure culture by M. raditotolerans MAMP 4754 is a characteristic feature for plant growth-promoting bacteria.


Assuntos
Combretum , Metais Pesados , Poluentes do Solo , Genômica , Metais Pesados/análise , Methylobacterium , Poluentes do Solo/análise , África do Sul
20.
J Hum Hypertens ; 35(9): 800-808, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32948827

RESUMO

Hibiscus sabdariffa L. (local names: bissap, karkade) and Combretum micranthum (kinkeliba) are widely known in traditional medicines and popular beliefs for their antihypertensive effect. This study assessed the clinical effectiveness of these two plants in the galenic forms of tablet and brew (decoction) in noncomplicated hypertensive patients. In total, 219 hypertensive patients with systolic blood pressure (SBP) between 140 and 180 mmHg and/or diastolic blood pressure (DBP) between 90 and 110 mmHg, without cardiovascular or renal complications, were involved in a multicentric randomized clinical trial in Senegal comparing five treatment regimens: bissap tablets (2 × 375 mg/day), bissap brew (10 g of calyx/day), kinkeliba tablets (2 × 200 mg/day), kinkeliba brew (10 g of leaves/day), and captopril (2 × 50 mg/day) as control. During the 6 months' follow-up, a significant and equivalent decrease of SBP was observed with the herbal drug approach (-19.5 ± 16.1 mmHg, p < 0.001) and control group (-19.7 ± 16.7, p < 0.001). Regarding the galenic forms, the brews tended to be slightly more effective than tablets (reduction of SBP: -20.7 ± 15.1 mmHg vs -18.7 ± 16.7). The rates of clinically significant effectiveness (decrease in SBP ≥ 10 mmHg) were 75%, 67%, and 65% with bissap, kinkeliba, and captopril, respectively. After 6 months, target blood pressure of <140/90 mmHg was attained by 49% of patients with bissap, 51% with kinkeliba and 40% with captopril. Bissap and kinkeliba appeared, at doses utilized, to be as effective as captopril over the 6 months' follow-up. In subsequent studies, brews might be started with a lower dosage.


Assuntos
Combretum , Hibiscus , Hipertensão , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Humanos , Hipertensão/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Comprimidos/farmacologia
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