RESUMO
In this study, the extract from Artabotrys hexapetalus showed strong antifungal activity against phytopathogenic fungi in vitro. Four unreported aporphine alkaloids, hexapetalusine A-D (1-4), were isolated from stems and roots of Artabotrys hexapetalus (L.f.) Bhandari, along with six known aporphine alkaloids (5-10). Their chemical structures were elucidated by extensive spectroscopic analysis. The absolute configurations of 1-3 were determined using single-crystal X-ray diffractions and ECD calculations. Hexapetalusine A-C (1-3) were special amidic isomers. Additionally, all isolated compounds were evaluated for their antifungal activity against four phytopathogenic fungi in vitro. Hexapetalusine D (4) exhibited weak antifungal activity against Curvularia lunata. Liriodenine (5) displayed significant antifungal activity against Fusarium proliferatum and Fusarium oxysporum f. sp. vasinfectum, which is obviously better than positive control nystatin, suggesting that it had great potential to be developed into an effective and eco-friendly fungicide.
Assuntos
Annonaceae , Aporfinas , Antifúngicos/farmacologia , Antifúngicos/química , Estrutura Molecular , Fungos , Aporfinas/farmacologia , Annonaceae/químicaRESUMO
Three new compounds, 4,5,6,7-tetramethoxy-3-benzoylbenzofuran (1), 4-hydroxy-3,5,6-trimethoxydihydrochalcone-2-O-ß-D-glucopyranoside (2) and 2-hydroxy-3,4,5,6-tetramethoxyphenylethyl benzoate (3) along with five known flavonoids were isolated from the dichloromethane fraction of the stems of Fissistigma acuminatissimum Merr.'s ethanol extracts. The compounds were obtained by chromatographic methods and the structure elucidation was completed primarily on the basis of spectroscopic analyses, all of these compounds were isolated from F. acuminatissimum for the first time. All the fractions and compounds were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated tumor necrosis factor α (TNF-α) production in RAW264.7 cells in vitro. The dichloromethane fraction showed the most potent inhibition(38.2%) at 60 µg/mL, compound 1 (70.2%) and 3 (65.2%) showed significant inhibition at 10 µM.
Assuntos
Annonaceae , Annonaceae/química , Cloreto de Metileno , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Flavonoides/farmacologia , Flavonoides/químicaRESUMO
The Annonaceae are an old family of flowering plants belonging to the order Magnoliales, distributed mainly in tropical regions. Numerous Annonaceae species find ethnobotanical use for curing a broad range of diseases, among them cancer and infections by diverse pathogens. Hence, bioactive natural products from Annonaceae have received considerable interest in drug development. Beyond cytotoxic acetogenins, unique aporphine-derived polycyclic aromatic alkaloids are characteristic constituents of Annonaceae. Among them are unique tri- and tetracyclic aromatic alkaloids like azafluorenones, diazafluoranthenes, azaanthracenes, and azaoxoaporphines. The complex substitution pattern of these alkaloids represents a major challenge in structure elucidation of isolated natural products. Based on a broad spectrum of alkaloids available from our previous work, we present a GC-MS protocol for the identification of over 20 polycyclic aromatic alkaloids from Annonaceae. This collection of data will contribute to the future identification of the metabolite patterns of extracts from Annonaceae as an important source of novel bioactive secondary metabolites.
Assuntos
Alcaloides , Annonaceae , Produtos Biológicos , Annonaceae/química , Cromatografia Gasosa-Espectrometria de Massas , Alcaloides/química , AcetogeninasRESUMO
The medicinal plant Artabotrys hexapetalus (synonyms: A.uncinatus and A. odoratissimus) is known as yingzhao in Chinese. Extracts of the plant have long been used in Asian folk medicine to treat various symptoms and diseases, including fevers, microbial infections, ulcers, hepatic disorders and other health problems. In particular, extracts from the roots and fruits of the plant are used for treating malaria. Numerous bioactive natural products have been isolated from the plant, mainly aporphine (artabonatines, artacinatine) and benzylisoquinoline (hexapetalines) alkaloids, terpenoids (artaboterpenoids), flavonoids (artabotrysides), butanolides (uncinine, artapetalins) and a small series of endoperoxides known as yingzhaosu A-to-D. These natural products confer antioxidant, anti-inflammatory and antiproliferative properties to the plant extracts. The lead compound yingzhaosu A displays marked activities against the malaria parasites Plasmodium falciparum and P. berghei. Total syntheses have been developed to access yingzhaosu compounds and analogues, such as the potent compound C14-epi-yingzhaosu A and simpler molecules with a dioxane unit. The mechanism of action of yingzhaosu A points to an iron(II)-induced degradation leading to the formation of two alkylating species, an unsaturated ketone and a cyclohexyl radical, which can then react with vital parasitic proteins. A bioreductive activation of yingzhaosu A endoperoxide can also occur with the heme iron complex. The mechanism of action of yingzhaosu endoperoxides is discussed, to promote further chemical and pharmacological studies of these neglected, but highly interesting bioactive compounds. Yingzhaosu A/C represent useful templates for designing novel antimalarial drugs.
Assuntos
Annonaceae , Antimaláricos , Aporfinas , Benzilisoquinolinas , Antagonistas do Ácido Fólico , Malária , Plantas Medicinais , Sesquiterpenos , Annonaceae/química , Antimaláricos/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aporfinas/uso terapêutico , Benzilisoquinolinas/uso terapêutico , Dioxanos , Compostos Ferrosos , Flavonoides/uso terapêutico , Antagonistas do Ácido Fólico/uso terapêutico , Heme , Humanos , Ferro/uso terapêutico , Cetonas/uso terapêutico , Malária/tratamento farmacológico , Malária/parasitologia , Peróxidos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plasmodium falciparum , Sesquiterpenos/farmacologiaRESUMO
Duguetia A. St. Hill (Annonaceae) is recognized as one of the major genera with approximately 100 species, 67 of which are found in Brazil (29 of those are endemic). They are arboreal species with edible fruits known as "pindaíba", "pindaíva" "pinha", and "envira" in Brazil. Many Duguetia species, in particular, have been used in traditional medicine to treat renal colic, stomachache, rheumatism, cough, toothache, muscle pain, fever, gastrointestinal pain, and breathing difficulties. In this study, we reviewed the chemical constituents and pharmacological properties of essential oils (EOs) from Duguetia species. A total of 12 species were found, along with their EO chemical constituents and bioactivities. Bicyclogermacrene, humulene epoxide II, spathulenol, germacrene D, caryophyllene oxide, viridiflorene, α-pinene, ß-caryophyllene, and ß-pinene were the main chemical constituents reported. The pharmacological effects of Duguetia species EOs included anti-inflammatory, antinociceptive, antibacterial, antifungal, antioxidant, anti-trypanosoma, cytotoxic and antitumor properties. This information adds to our understanding of the potential of the EOs of Duguetia species.
Assuntos
Annonaceae , Óleos Voláteis , Annonaceae/química , Antibacterianos/farmacologia , Antifúngicos , Brasil , Óleos Voláteis/química , Óleos Voláteis/farmacologiaRESUMO
Repeated column chromatography resulted in the isolation of two new glycosides, miliusides A-B (1 and 7), along with six known metabolites (2-6, and 8) from the leaves of Miliusa sinensis Finet and Gagnep. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (NMR, HRMS), as well as comparison with the previous literature. The biological evaluation of acetylcholinesterase (AChE) inhibitory effects and anti-inflammatory activity by measuring nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophage cells, were also conducted. Among them, compounds 5 and 7 exhibited significant AChE inhibitory activities (IC50 = 53.36 ± 4.20 and 88.50 ± 8.79 µM, respectively), compared with the positive control (Galanthamine, IC50 = 1.65 ± 0.15 µM). Only the MeOH extract showed suppression effects on NO production in LPS-induced RAW264.7 cells (IC50 = 38.18 ± 3.25 µg/mL) comparable to that of the positive control, l-NMMA (IC50 = 2.21 ± 0.56 µg/mL).
Assuntos
Annonaceae , Glicosídeos Cardíacos , Camundongos , Animais , Glicosídeos/farmacologia , Glicosídeos/química , Lipopolissacarídeos/farmacologia , Acetilcolina , Acetilcolinesterase , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Annonaceae/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Óxido Nítrico , Células RAW 264.7RESUMO
Specialized pro-resolving mediators (SPMs) comprise lipid mediators (LMs) produced from polyunsaturated fatty acids (PUFAs) via stereoselective oxygenation particularly involving 12/15-lipoxygenases (LOXs). In contrast to pro-inflammatory LMs such as leukotrienes formed by 5-LOX and prostaglandins formed by cyclooxygenases, the SPMs have anti-inflammatory and inflammation-resolving properties. Although glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) that block prostaglandin production are still prime therapeutics for inflammation-related diseases despite severe side effects, novel concepts focus on SPMs as immunoresolvents for anti-inflammatory pharmacotherapy. Here, we studied the natural chalcone MF-14 and the corresponding dihydrochalcone MF-15 from Melodorum fruticosum, for modulating the biosynthesis of LM including leukotrienes, prostaglandins, SPM and their 12/15-LOX-derived precursors in human monocyte-derived macrophage (MDM) M1- and M2-like phenotypes. In MDM challenged with Staphylococcus aureus-derived exotoxins both compounds (10 µM) significantly suppressed 5-LOX product formation but increased the biosynthesis of 12/15-LOX products, especially in M2-MDM. Intriguingly, in resting M2-MDM, MF-14 and MF-15 strikingly evoked generation of 12/15-LOX products and of SPMs from liberated PUFAs, along with translocation of 15-LOX-1 to membranous compartments. Enhanced 12/15-LOX product formation by the chalcones was evident also when exogenous PUFAs were supplied, excluding increased substrate supply as sole underlying mechanism. Rather, MF-14 and MF-15 stimulate the activity of 15-LOX-1, supported by experiments with HEK293 cells transfected with either 5-LOX, 15-LOX-1 or 15-LOX-2. Together, the natural chalcone MF-14 and the dihydrochalcone MF-15 favorably modulate LM biosynthesis in human macrophages by suppressing pro-inflammatory leukotrienes but stimulating formation of SPMs by differential interference with 5-LOX and 15-LOX-1.
Assuntos
Araquidonato 12-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/metabolismo , Chalcona/farmacologia , Leucotrienos/metabolismo , Macrófagos/efeitos dos fármacos , Prostaglandinas/metabolismo , Adulto , Annonaceae/química , Araquidonato 12-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/genética , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Chalcona/química , Chalconas/química , Chalconas/farmacologia , Células HEK293 , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/classificação , Macrófagos/metabolismo , Estrutura Molecular , Extratos Vegetais/farmacologiaRESUMO
The chemical study of the acidic extract of Phaeanthus vietnamensis leaves led to the isolation of one new alkaloid, vietnamine A (1) and eight known alkaloids (R,S)-2N-norberbamunine (2), grisabine (3), 1S,1'R,O,O'-dimethylgrisabine (4), dauricine (5), neothalibrine (6), vietnamine (7), xylopine (8), and argentinine (9) by NMR and MS and comparing with the data reported in the literature. Compounds 1-9 were evaluated for inhibitory NO production in RAW 264.7 macrophages, LPS-stimulated. Compounds 1-3 significantly inhibited on NO production with the IC50 values of 6.8 ± 0.9, 9.8 ± 1.0, and 7.1 ± 0.4 µg/ml, respectively.
Assuntos
Alcaloides , Annonaceae , Alcaloides/química , Alcaloides/farmacologia , Annonaceae/química , Lipopolissacarídeos/farmacologia , Macrófagos , Estrutura Molecular , Óxido Nítrico , Óxido Nítrico Sintase Tipo II , Extratos Vegetais/químicaRESUMO
The root and stem bark essential oils from Isolona dewevrei (Annonaceae), growing wild in Côte d'Ivoire, were investigated for the first time, using a combination of chromatographic [CC, GC(RI)] and spectroscopic [MS, 13C-NMR] techniques. A new natural germacrone was isolated by repetitive column chromatography carried out on a stem bark oil sample. Its structure was elucidated as germacra-1(10),4(15),5-trien-8-one by 1 D, 2 D-NMR and QTOF-MS. Ninety-six components accounting for 95.5 ± 0.8% and 95.8 ± 1.0%, respectively, for the root and stem bark essential oil samples were identified. The major compounds of root oil were cyperene (19.7 ± 1.6%) and camphene (10.1 ± 2.1%), followed by 5-isopentenylindole (6.4 ± 2.4%), ß-elemene (3.9 ± 0.3%), (Z)-α-bisabolene (3.2 ± 1.2%) and γ-gurjunene (3.2 ± 0.3%). The stem bark oil was also dominated by cyperene (29.2 ± 4.1%), followed by ß-elemene (6.2 ± 1.1%), (Z)-α-bisabolene (3.8 ± 1.0%), (E)-ß-caryophyllene (3.3 ± 0.7%) and α-copaene (2.8 ± 1.1%).
Assuntos
Annonaceae , Óleos Voláteis , Annonaceae/química , Côte d'Ivoire , Óleos Voláteis/química , Casca de Planta/química , Folhas de Planta/química , Óleos de Plantas/química , Sesquiterpenos de GermacranoRESUMO
The present work involves a systematic review of the chemical composition and biological effects of essential oils from the Annonaceae species collected in Brazil from 2011 to 2021. Annonaceae is one of the most important botanical families in Brazil, as some species have economic value in the market as local and international fruit. In addition, the species have useful applications in several areas-for instance, as raw materials for use in cosmetics and perfumery and as medicinal plants. In folk medicine, species such as Annona glabra L. and Xylopia sericea A. St.-Hil. are used to treat diseases such as rheumatism and malaria. The species of Annonaceae are an important source of essential oils and are rich in compounds belonging to the classes of mono and sesquiterpenes; of these compounds, α-pinene, ß-pinene, limonene, (E)-caryophyllene, bicyclogermacrene, caryophyllene oxide, germacrene D, spathulenol, and ß-elemene are the most abundant. The antimicrobial, anti-inflammatory, antileishmania, antioxidant, antiproliferative, cytotoxic, larvicidal, trypanocidal, and antimalarial activities of essential oils from the Annonaceae species in Brazil have been described in previous research, with the most studies on this topic being related to their antiproliferative or cytotoxic activities. In some studies, it was observed that the biological activity reported for these essential oils was superior to that of drugs available on the market, as is the case of the essential oil of the species Guatteria punctata (Aubl.) R. A. Howard., which showed a trypanocidal effect that was 34 times stronger than that of the reference drug benznidazol.
Assuntos
Annonaceae/química , Óleos Voláteis/química , Compostos Fitoquímicos/química , Antibacterianos/química , Antibacterianos/uso terapêutico , Brasil , Humanos , Óleos Voláteis/uso terapêutico , Folhas de Planta/química , Sesquiterpenos Policíclicos/química , Sesquiterpenos/química , Sesquiterpenos de Germacrano/químicaRESUMO
The chemical variability and the in vitro anti-inflammatory activity of the leaf essential oil from Ivorian Isolona dewevrei were investigated for the first time. Forty-seven oil samples were analyzed using a combination of CC, GC(RI), GC-MS and 13C-NMR, thus leading to the identification of 113 constituents (90.8-98.9%). As the main components varied drastically from sample to sample, the 47 oil compositions were submitted to hierarchical cluster and principal components analyses. Three distinct groups, each divided into two subgroups, were evidenced. Subgroup I-A was dominated by (Z)-ß-ocimene, ß-eudesmol, germacrene D and (E)-ß-ocimene, while (10ßH)-1ß,8ß-oxido-cadina-4-ene, santalenone, trans-α-bergamotene and trans-ß-bergamotene were the main compounds of Subgroup I-B. The prevalent constituents of Subgroup II-A were germacrene B, (E)-ß-caryophyllene, (5αH,10ßMe)-6,12-oxido-elema-1,3,6,11(12)-tetraene and γ-elemene. Subgroup II-B displayed germacrene B, germacrene D and (Z)-ß-ocimene as the majority compounds. Germacrene D was the most abundant constituent of Group III, followed in Subgroup III-A by (E)-ß-caryophyllene, (10ßH)-1ß,8ß-oxido-cadina-4-ene, germacrene D-8-one, and then in Subgroup III-B by (Z)-ß-ocimene and (E)-ß-ocimene. The observed qualitative and quantitative chemical variability was probably due to combined factors, mostly phenology and season, then harvest site to a lesser extent. The lipoxygenase inhibition by a leaf oil sample was also evaluated. The oil IC50 (0.020 ± 0.005 mg/mL) was slightly higher than the non-competitive lipoxygenase inhibitor NDGA IC50 (0.013 ± 0.003 mg/mL), suggesting a significant in vitro anti-inflammatory potential.
Assuntos
Annonaceae/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Anti-Inflamatórios/isolamento & purificação , Côte d'Ivoire , Avaliação Pré-Clínica de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas , Técnicas In Vitro , Lipoxigenase/efeitos dos fármacos , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/isolamento & purificação , Inibidores de Lipoxigenase/farmacologia , Espectroscopia de Ressonância Magnética , Óleos Voláteis/classificação , Folhas de Planta/química , Óleos de Plantas/classificação , Plantas Medicinais/química , Glycine max/enzimologiaRESUMO
Two novel aporphine-derived alkaloids, aporaloids A and B (1 and 2), together with eight known biogenetically related alkaloids (3-10), two known isoquinoline alkaloids (3 and 4), and six known aporphinoid alkaloids (5-10) were isolated from the stems of Fissistigma glaucescens. Their structures were elucidated using comprehensive spectroscopic methods. Compounds 1 and 2 represent the rare example of a six-membered lactone ring aporphine-derived alkaloids from natural products. The inhibitory activities of all compounds against four cancer cell lines were evaluated. Aporaloids A and B (1 and 2) showed broad spectrum cytotoxic activities.
Assuntos
Annonaceae/química , Antineoplásicos Fitogênicos/farmacologia , Aporfinas/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Aporfinas/isolamento & purificação , Linhagem Celular Tumoral , China , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/químicaRESUMO
Diclinanona calycina R. E. Fries popularly known as "envira", is a species of the Annonaceae family endemic to Brazil. In our ongoing search for bioactive compounds from Annonaceae Amazon plants, the bark of D. calycina was investigated by classical chromatography techniques that yielded thirteen compounds (alkaloids and flavonoids) described for the first time in D. calycina as well as in the genus Diclinanona. The structure of these isolated compounds were established by extensive analysis using 1D/2D-NMR spectroscopy in combination with MS. The isolated alkaloids were identified as belonging to the subclasses: simple isoquinoline, thalifoline (1); aporphine, anonaine (2); oxoaporphine, liriodenine (3); benzyltetrahydroisoquinolines, (S)-(+)-reticuline (4); dehydro-oxonorreticuline (3,4-dihydro-7-hydroxy-6-methoxy-1-isoquinolinyl)(3-hydroxy-4-methoxyphenyl)-methanone) (5); (+)-1S,2R-reticuline Nß-oxide (6); and (+)-1S,2S-reticuline Nα-oxide (7); tetrahydroprotoberberine, coreximine (8); and pavine, bisnorargemonine (9). While the flavonoids belong to the benzylated dihydroflavones, isochamanetin (10), dichamanetin (11), and a mixture of uvarinol (12) and isouvarinol (13). Compound 5 is described for the first time in the literature as a natural product. The cytotoxic activity of the main isolated compounds was evaluated against cancer and non-cancerous cell lines. Among the tested compounds, the most promising results were found for the benzylated dihydroflavones dichamanetin (10), and the mixture of uvarinol (12) and isouvarinol (13), which presented moderate cytotoxic activity against the tested cancer cell lines (<20.0 µg·mL-1) and low cytotoxicity against the non-cancerous cell line MRC-5 (>25.0 µg·mL-1). Dichamanetin (11) showed cytotoxic activity against HL-60 and HCT116 with IC50 values of 15.78 µg·mL-1 (33.70 µmol·L-1) and 18.99 µg·mL-1 (40.56 µmol·L-1), respectively while the mixture of uvarinol (12) and isouvarinol (13) demonstrated cytotoxic activity against HL-60, with an IC50 value of 9.74 µg·mL-1, and HCT116, with an IC50 value of 17.31 µg·mL-1. These cytotoxic activities can be attributed to the presence of one or more hydroxybenzyl groups present in these molecules as well as the position in which these groups are linked. The cytotoxic activities of reticuline, anonaine and liriodenine have been previously established, with liriodenine being the most potent compound.
Assuntos
Alcaloides/química , Annonaceae/química , Flavonas/química , Isoquinolinas/química , Casca de Planta/química , Alcaloides/farmacologia , Aporfinas/química , Aporfinas/farmacologia , Brasil , Linhagem Celular Tumoral , Dioxóis/química , Dioxóis/farmacologia , Flavanonas/farmacologia , Flavonas/farmacologia , Células HCT116 , Células HL-60 , Células Hep G2 , Humanos , Isoquinolinas/farmacologia , Células MCF-7 , Extratos Vegetais , Folhas de Planta/químicaRESUMO
This study validates the antidiabetic efficacy of Enantia chlorantha stem bark and the possible therapeutic implications of the co-administration of lisinopril and E. chlorantha in type 2 diabetic rats. E. chlorantha stem bark was extracted by cold maceration. The inhibitory effect of the plant on carbohydrate metabolizing enzymes and its antioxidative potentials were assessed in vitro. The extract exhibited α-amylase and α-glucosidase inhibitory activities and also showed antioxidative properties in vitro. Administration of the extract normalized fasting hyperglycemia in vivo by showing 47.24 % reduction in blood glucose levels relative to untreated diabetic rats. Co-administration of E. chlorantha and lisinopril restored serum glucose and serum lipid profile levels. E. chlorantha stem bark displayed antidiabetic potentials as compared with a standard antidiabetic drug (metformin). The study also showed that the plant contained some bioactive compounds which we hypothesize might be responsible for the observed activities. Co-administration of the plant with lisinopril conferred no significant therapeutic advantage on the serum glucose level and lipid profile.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Lisinopril/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Annonaceae/química , Glicemia/análise , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Combinação de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Masculino , Casca de Planta/química , Caules de Planta/química , Ratos WistarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Breast cancer is a serious threat in low-income as well as developed countries. To face this, many herbal preparations are prescribed by traditional healers in Cameroon, among which is Anonidium mannii commonly called "wild soursop". AIM: This study was undertaken to assess the anti-tumor effect of A. mannii ethanolic extract on cancer cell growth and against DMBA-induced mammary tumors in rats. MATERIALS AND METHODS: The well characterized MTT bioassay was used to assess the cytotoxic potential of A. mannii ethanolic extract in liver (HepG2), prostate (DU145 & PC3) and breast (MCF-7) cancer cell lines. Considering the fact that breast cells were the most sensitive to the extract, a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast tumor rat model was used to assess the possible anticancer effect of A. mannii extract. Indeed, rats were treated with either tamoxifen (3.3 mg/kg BW) or A. mannii extract (16.5, 50 and 150 mg/kg BW) or vehicle (2% ethanol) for 20 weeks. Tumor incidence, tumor mass and volume, oxidative stress status in tumor as well as tumor histoarchitecture were evaluated. RESULTS: A 24 h incubation of tested cells with the A. mannii extract significantly slowed cell growth in a concentration-dependent manner with an interesting effect in breast cells (IC50 ~61.5 µg/mL). As compared to the DMBA rats, those treated with A. mannii extract (50 and 150 mg/kg) showed reduced breast tumor incidence (28%), tumor burden (95.34% at 50 mg/kg and 99.14% at 150 mg/kg) and tumor volume (~92%). A. mannii extract counteracted the high proliferation of terminal mammary ducts induced by DMBA, mainly at 50 mg/kg. Furthermore, the extract decreased MDA and nitrite levels but increased SOD activity in the mammary gland. High Performance Liquid Chromatography coupled with Mass Spectrometry (HPLC-MS) analysis detected potential anticancer and antioxidant alkaloids in A. manni extract, which are close to those found in Annona muricata. CONCLUSION: These results provide evidence on the in vitro and in vivo anticancer effects of A. mannii, and therefore support its use in traditional medicine system to fight against cancer.
Assuntos
Alcaloides/farmacologia , Annonaceae/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Neoplasias Mamárias Experimentais/prevenção & controle , Extratos Vegetais/farmacologia , Alcaloides/uso terapêutico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos Fitogênicos/toxicidade , Antioxidantes/química , Antioxidantes/uso terapêutico , Antioxidantes/toxicidade , Camarões , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Etanol/química , Feminino , Humanos , Neoplasias Mamárias Experimentais/sangue , Neoplasias Mamárias Experimentais/patologia , Medicina Tradicional , Minerais/análise , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Tamoxifeno/uso terapêutico , Carga Tumoral/efeitos dos fármacosRESUMO
Two new aporphine alkaloids, (R)-1,2-methylenedioxy-3,9-dimethoxy-11-hydroxy-N- carbamoyl-noraporphine (1) and 3,10,11-trimethoxy-1,2-methylenedioxy-7-oxoaporphine(2), and one new dihydrochalcone, 4',5'-dimethoxy-2'-hydroxy-3',6'-quinodihydrochalcone (3), along with five known alkaloids were isolated from the ethanol extracts of the stems of Fissistigma oldhamii var. longistipitatum. The compounds were obtained by various classical column chromatographic methods, and the structure elucidation was completed primarily on the basis of spectroscopic analysis, such as UV, NMR and HR-ESI-MS. The isolated compounds were subjected to evaluate cytotoxic activities in vitro, compound 1 had activity against HL-60 and HELA (IC50 value of 8.4 µM and 5.2 µM, respectively), compound 2 against MCF-7 (IC50 value of 3.7 µM), compound 3 against HEPG2 (IC50 value of 10.8 µM), respectively.
Assuntos
Annonaceae/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , China , Células HL-60 , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/químicaRESUMO
The roots of Fissistigma oldhamii (FO) are widely used as medicine with the effect of dispelling wind and dampness, promoting blood circulation and relieving pains, and its fruits are considered delicious. However, Hakka people always utilize its above-ground parts as a famous folk medicine, Xiangteng, with significant differences from literatures. Studies of chemical composition showed there were multiple aristolactams that possessed high nephrotoxicity, pending evaluation research about their distribution in FO. In this study, a sensitive, selective, rapid and reliable method was established to comparatively perform qualitative and semi-quantitative analysis of the constituents in roots, stems, leaves, fruits and insect galls, using an Ultra-High-Performance Liquid Chromatography coupled with Hybrid Quadrupole Orbitrap Mass Spectrometry (UPLC-Q-Exactive Orbitrap MS, or Q-Exactive for short). To make more accurate identification and comparison of FO chemicals, all MS data were aligned and screened by XCMS, then their structures were elucidated according to MSn ion fragments between the detected and standards, published ones or these generated by MS fragmenter. A total of 79 compounds were identified, including 33 alkaloids, 29 flavonoids, 11 phenylpropanoids, etc. There were 54 common components in all five parts, while another 25 components were just detected in some parts. Six toxic aristolactams were detected in this experiment, including aristolactam AII, AIIIa, BII, BIII, FI and FII, of which the relative contents in above-ground stems were much higher than roots. Meanwhile, multivariate statistical analysis was performed and showed significant differences both in type and content of the ingredients within all FO parts. The results implied that above-ground FO parts should be carefully valued for oral administration and eating fruits. This study demonstrated that the high-resolution mass spectrometry coupled with multivariate statistical methods was a powerful tool in compound analysis of complicated herbal extracts, and the results provide the basis for its further application, scientific development of quality standard and utilization.
Assuntos
Annonaceae/química , Medicamentos de Ervas Chinesas/química , Folhas de Planta/química , Raízes de Plantas/química , Alcaloides/química , Alcaloides/uso terapêutico , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Espectrometria de Massas em TandemRESUMO
BACKGROUND: P-glycoprotein (P-gp) over-expression plays a vital role in not only systemic drug bioavailability but also cancer multi-drug resistance (MDR). Develop functional inhibitors of P-gp can conquer both problems. PURPOSE AND STUDY DESIGN: The aim of the present study was to research the P-gp modulating effects and MDR reversing ability of a novel flavonoid from Fissistigma cupreonitens, the underlying inhibitory mechanisms were further elucidated as well. METHODS: Calcein-AM, rhodamine 123, and doxorubicin were fluorescent substrates for the evaluation of P-gp inhibitory function and detailed drug binding modes. Docking simulation was performed to reveal the in silico molecular bonding. ATPase assay and MDR1 shift assay were adopted to reveal the ATP consumption and conformational change of P-gp. The MDR reversing effects were demonstrated through cytotoxicity, cell cycle, and apoptosis analyses. RESULTS: 5hydroxy7,8dimethoxyflavanone inhibited the efflux of rhodamine 123 and doxorubicin in a competitive manner, and increased the intracellular fluorescence of calcein at a concentration as low as 2.5⯵g/ml. 5hydroxy7,8dimethoxyflavanone slightly changed P-gp's conformation and only stimulated ATPase at very high concentration (100⯵g/ml). The docking results showed that 5hydroxy7,8dimethoxyflavanone and verapamil exhibited similar binding affinity to P-gp. The MDR reversing effects were prominent in the vincristine group, the reversal folds were 23.01 and 13.03 when combined with 10⯵g/ml 5hydroxy7,8dimethoxyflavanone in the P-gp over-expressing cell line (ABCB1/Flp-In™-293) and MDR cancer cell line (KB/VIN), respectively. CONCLUSION: The present study demonstrated that 5hydroxy7,8dimethoxyflavanone was a novel effective flavonoid in the P-gp efflux inhibition and in vitro cancer MDR reversion.
Assuntos
Annonaceae/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Flavonoides/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/metabolismo , Fluoresceínas/metabolismo , Humanos , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Rodamina 123/metabolismo , Verapamil/farmacologiaRESUMO
Annona coriacea Mart., popularly known as "marolo", "araticum" and "araticum-liso" is a species distributed in Paraguay and Brazil, and easily found in Caatinga, Cerrado, and Pantanal biomes. The araticum has been used in folk medicine to treat stomatitis, neuralgia, rheumatism, headaches, furuncle, ulcers, and dermatitis. This systematic review aimed to provide a comprehensive overview of the ethnomedicinal use, phytochemistry, and pharmacological activity of A. coriacea. A search for scientific articles of electronic databases (Science Direct, PubMed, Lilacs, Scopus, Google Scholar, Scielo, and Web of Science) was performed identifying studies published until November 2020. All papers considering traditional medicinal uses, phytochemistry, and pharmacological properties were included. Forty-six articles (nâ¯=â¯212 subjects) met the inclusion criteria set for this review. Of the 46 articles reviewed, 34 were focused on biological activity investigations, while 12 were limited to phytochemical studies. These studies showed the presence of a diversity of secondary metabolites such as acetogenins, sesquiterpenes, alkaloids, flavonoids, and diterpenes. To date, pharmacological tests have demonstrated significant biological activities of this plant, being the most promising anticancer, anti-inflammatory, antiulcer, and insecticide activities. Additionally, the medicinal utilization of A. coriacea appears to be promising, supporting its possible uses for human health with antioxidant, anxiolytic, antiulcer, insecticide, and antiparasitic activities. Ultimately, comprehensive studies involving clinical trials are required to validate the existing traditional practices and their related health benefits scientifically.
Assuntos
Annonaceae/química , Anti-Inflamatórios/farmacologia , Antiulcerosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Inseticidas/farmacologia , Compostos Fitoquímicos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antiulcerosos/química , Antiulcerosos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Humanos , Inseticidas/química , Inseticidas/isolamento & purificação , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a global public health burden due to large number of annual infections and casualties caused by its hematological complications. The bark of Annickia polycarpa is an effective anti-malaria agent in African traditional medicine. However, there is no standardization parameters for A. polycarpa. The anti-malaria properties of its leaf are also not known. AIM OF THE STUDY: To standardize the ethanol leaf extract of A. polycarpa (APLE) and investigate its anti-malaria properties and the effect of its treatment on hematological indices in Plasmodium berghei infected mice in the Rane's test. MATERIALS AND METHODS: Malaria was induced by inoculating female ICR mice with 1.0 × 107P. berghei-infected RBCs in 0.2 mL (i.p.) of blood. Treatment was commenced 3 days later with APLE 50, 200, 400 mg/kg p.o., Quinine 30 mg/kg i.m. (Standard drug) or sterile water (Negative control) once daily per group for 4 successive days. Anti-malarial activity and gross malaria indices such as hyperparasitemia, mean change in body weight and mean survival time (MST) were determined for each group. Changes in white blood cells (WBCs), red blood cells (RBCs), platelets (PLT) counts, hemoglobin (HGB) concentration, hematocrit (HCT) and mean corpuscular volume (MCV) were also measured in the healthy mice before infection as baseline and on day 3 and 8 after inoculation using complete blood count. Standardization was achieved by UHPLC-MS chemical fingerprint analysis and quantitative phytochemical tests. RESULTS: APLE, standardized to its total alkaloids, phenolics and saponin contents, produced significant (P < 0.05) dose-dependent clearance of mean hyperparasitemia of 22.78 ± 0.93% with the minimum parasitemia level of 2.01 ± 0.25% achieved at 400 mg/kg p.o. on day 8. Quinine 30 mg/kg i.m. achieved a minimum parasitemia level of 6.15 ± 0.92%. Moreover, APLE (50-400 mg/kg p.o.) evoked very significant anti-malaria activity of 89.22-95.50%. Anti-malaria activity of Quinine 30 mg/kg i.m. was 86.22%. APLE also inverse dose-dependently promotes weight gain with the effect being significant (P < 0.05) at 50 mg/kg p.o. Moreover, APLE dose-dependently increased the MST of malaria infested mice with 100% survival at 400 mg/kg p.o. Quinine 30 mg/kg i.m. also produce 100% survival rate but did not promote (P > 0.05) weight gain. Hematological studies revealed the development of leukocytopenia, erythrocytosis, microcytic anemia and thrombocytopenia in the malaria infected mice which were reverted with the treatment of APLE 50-400 mg/kg p.o. or Quinine 30 mg/kg i.m. but persisted in the negative control. The UHPLC-MS fingerprint analysis of APLE led to identification of one oxoaporphine and two aporphine alkaloids (1-3). Alkaloids 1 and 3 are being reported in this plant for the first time. CONCLUSION: These results indicate that APLE possessed significant anti-malaria, immunomodulatory, erythropoietic and hematinic actions against malaria infection. APLE also has the ability to revoke deleterious physiological alteration produced by malaria and hence, promote clinical cure. These properties of APLE are due to its constituents especially, aporphine and oxoaporphine alkaloids.