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1.
Molecules ; 27(3)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35164324

RESUMO

Ardisiacrispin D-F (1-3), three new 13,28 epoxy bridged oleanane-type triterpenoid saponins, together with four known analogues (4-7) were isolated from the roots of Ardisia crispa. The structures of 1-7 were elucidated based on 1D and 2D-NMR experiments and by comparing their spectroscopic data with values from the published literatures. Ardisiacrispin D-F (1-3) are first examples that the monosaccharide directly linked to aglycone C-3 of triterpenoid saponins in genus Ardisia are non-arabinopyranose. In the present paper, all compounds are evaluated for the cytotoxicity against three cancer cell lines (HeLa, HepG2 and U87 MG) in vitro. The results show that compounds 1, 4 and 6 exhibited significant cytotoxicity against Hela and U87 MG cells with IC50 values in the range of 2.2 ± 0.6 to 9.5 ± 1.8 µM. The present investigation suggests that roots of A. crispa could be a potential source of natural anti-tumor agents and their triterpenoid saponins might be responsible for cytotoxicity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ardisia/química , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Saponinas/química , Triterpenos/química , Compostos de Epóxi/química , Humanos , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Células Tumorais Cultivadas
2.
Chem Biodivers ; 19(2): e202100796, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34850548

RESUMO

Ardisia elliptica Thunb. (AE) has been used as food and in traditional medicine to prevent and treat fever, diarrhea, chest pain, liver poisoning, and parturition complications in Southeast Asian countries. This study focused on phytochemical constituents of AE extracts and their antioxidant and anti-inflammatory activity in vitro by evaluating nitric oxide production, and DPPH and FRAP radical scavenging activity. The bioactive compounds from different plant parts, including old leaves, young leaves, flowers, roots, and fruits, were identified. The results showed the highest phenolic and flavonoid content in the root extract among all extracts, which resulted in the most potent free radical scavenging activity revealed by the DPPH and FRAP assay. The roots and flowers showed the highest bergenin (3.36±0.22 mg/g dry weight) and quercetin (2.99±0.10 mg/g dry weight) content, respectively. In contrast, embelin was found only in the fruits. Interestingly, AE extracts significantly suppressed the mRNA expression of inducible nitric oxide synthase, leading to inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. Conclusively, the results suggest the natural products of AE extracts as effective antioxidant and anti-inflammatory agents that can be utilized for food and pharmaceutical applications.


Assuntos
Ardisia , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Ardisia/química , Flavonoides/química , Extratos Vegetais/química , Folhas de Planta/química
3.
Sci Rep ; 11(1): 22239, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782652

RESUMO

Ardisia Sw. (Primulaceae) is naturally distributed in tropical and subtropical areas. Most of them possess edible and medicinal values and are popular in clinical and daily use in China. However, ambiguous species delineation and genetic information limit the development and utilization of this genus. In this study, the chloroplast genomes of four Ardisia species, namely A. gigantifolia Stapf, A. crenata Sims, A. villosa Roxb. and A. mamillata Hance, were sequenced, annotated, and analyzed comparatively. All the four chloroplast genomes possess a typical quadripartite structure, and each of the genomes is about 156 Kb in size. The structure and gene content of the Ardisia plastomes were conservative and showed low sequence divergence. Furthermore, we identified five mutation hotspots as candidate DNA barcodes for Ardisia, namely, trnT-psbD, ndhF-rpl32, rpl32-ccsA, ccsA-ndhD and ycf1. Phylogenetic analysis based on the whole-chloroplast genomes data showed that Ardisia was sister to Tapeinosperma Hook. f. In addition, the results revealed a great topological profile of Ardisia's with strong support values, which matches their geographical distribution patterns. Summarily, our results provide useful information for investigations on taxonomic differences, molecular identification, and phylogenetic relationships of Ardisia plants.


Assuntos
Ardisia/classificação , Ardisia/genética , Genoma de Cloroplastos , Genômica , China , Biologia Computacional/métodos , Genômica/métodos , Filogenia , Polimorfismo Genético , Análise de Sequência de DNA , Sequenciamento Completo do Exoma
4.
J Nat Prod ; 84(7): 1941-1953, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34197116

RESUMO

Both the soil bacterium Chromobacterium vaccinii and the bacterial endosymbiont Candidatus Burkholderia crenata of the plant Ardisia crenata are producers of FR900359 (FR). This cyclic depsipeptide is a potent and selective Gq protein inhibitor used extensively to investigate the intracellular signaling of G protein coupled receptors (GPCRs). In this study, the metabolomes of both FR producers were investigated and compared using feature-based molecular networking (FBMN). As a result, 30 previously unknown FR derivatives were identified, one-third being unique to C. vaccinii. Guided by MS, a novel FR derivative, FR-6 (compound 1), was isolated, and its structure unambiguously established. In a whole-cell biosensing assay based on detection of dynamic mass redistribution (DMR) as readout for Gq inhibition, FR-6 suppressed Gq signaling with micromolar potency (pIC50 = 5.56). This functional activity was confirmed in radioligand binding assays (pKi = 7.50). This work demonstrates the power of molecular networking, guiding the way to a novel Gq-inhibiting FR derivative and underlining the potency of FR as a Gq inhibitor.


Assuntos
Depsipeptídeos/farmacologia , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Ardisia/química , Chromobacterium/química , Células HEK293 , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Folhas de Planta/química
5.
Inflammopharmacology ; 29(3): 771-788, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34091811

RESUMO

Rheumatoid arthritis (RA) is a chronic joint disorder, of which, excessive angiogenesis is the well-established factor contributing to synovitis and joint destruction. Ardisia crispa (Primulaceae) is a medicinal herb with evidenced anti-angiogenic properties, attributed to 2-methoxy-6-undecyl-1,4-benzoquinone (BQ) found in its roots. However, it is still unclear how BQ is able to inhibit angiogenesis in RA. Hence, we investigated the anti-arthritic potential of quinone-rich fraction (QRF) separated from Ardisia crispa roots hexane extract (ACRH) by targeting angiogenesis on collagen-induced arthritis (CIA) in rats. The QRF was priorly identified by quantifying the BQ content in the fraction using GC-MS. Male Sprague-Dawley rats (n = 6) were initially immunised with type II collagen (150 µg) subcutaneously at the base of the tail on day 0. QRF (3, 10, and 30 mg/kg/day) and celecoxib (5 mg/kg/day) were orally administered for 13 consecutive days starting from day 14 post-induction, except for the vehicle and arthritic controls. QRF at all dosages moderately ameliorated the arthritic scores, ankle swelling, and hind paw oedema with no significant (p > 0.05) modulation on the bodyweights and organ weights (i.e., liver, kidney, and spleen). Treatment with QRF at 3, 10, and 30 mg/kg, significantly (p < 0.05) attenuated VEGF-A, PI3K, AKT, NF-κB, p38, STAT3, and STAT5 proteins and markedly restored the increased synovial microvessel densities (MVD) to the normal level in arthritic rats in a dose-independent manner. In conclusion, QRF conferred the anti-arthritic effect via angiogenesis inhibition in vivo, credited to the BQ content and synergism, at least in part, by other phytoconstituents.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Ardisia , Artrite Experimental/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Quinonas/uso terapêutico , Inibidores da Angiogênese/isolamento & purificação , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/patologia , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas/métodos , Masculino , Extratos Vegetais/isolamento & purificação , Quinonas/isolamento & purificação , Ratos , Ratos Sprague-Dawley
6.
Chem Biodivers ; 18(7): e2100335, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34089236

RESUMO

Ardisia crenata Sims (Primulaceae) occurs in natural habitats in two varieties, bearing red or white fruits. While roots of the red-berried ardisia are valued as a medicinal product, the pharmacological activity of which is attributed to triterpene saponins, including ardisiacrispin A, data on the white-berried variety are scarce. A TLC-densitometric method was developed and validated to estimate the levels of saponins, calculated as ardisiacrispin A, in different plant parts in both varieties. Their content amounted to 22.17±4.75 and 25.72±1.46 mg/g d.w. in roots, and 2.64±0.74 and 3.43±0.70 mg/g d.w. in fruits of red-berried and white-berried ardisia, respectively. Assessment of cytotoxicity of ardisiacrispin A and A. crenata extracts on a panel of human cancer cell lines revealed a similar effect of root extracts from both varieties, with the highest potency against melanoma WM793 and colon cancer Caco2. Thus, roots of the white-berried variety may be treated as a substitute for red-berried ardisia and serve as an alternative source for the acquisition of plant material rich in bioactive saponins.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ardisia/química , Ácido Oleanólico/análogos & derivados , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Antineoplásicos Fitogênicos/análise , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ácido Oleanólico/análise , Ácido Oleanólico/farmacologia , Extratos Vegetais/análise , Raízes de Plantas/química , Saponinas/análise
7.
BMC Complement Med Ther ; 21(1): 176, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172047

RESUMO

BACKGROUND: Ardisia crispa (Thunb.) A.DC (Primulaceae), is a medicinal herb traditionally used by Asian people as remedies to cure inflammatory related diseases, including rheumatism. The plant roots possess various pharmacological activities including antipyretic, anti-inflammation and antitumor. Previous phytochemical studies of the plant roots have identified long chain alkyl-1,4-benzoquinones as major constituents, together with other phytochemicals. Hexane fraction of the plant roots (ACRH), was previously reported with anti-angiogenic and anti-arthritic properties, while its effect on their anti-arthritic in vitro, is yet unrevealed. Considering the significance of angiogenesis inhibition in developing new anti-arthritic agent, thus we investigated the anti-arthritic potential of Ardisia crispa roots by suppressing angiogenesis, in vitro. METHODS: Ardisia crispa roots hexane extract (ACRH) was prepared from the plant roots using absolute n-hexane. ACRH was fractionated into quinone-rich fraction (QRF) and further isolated to yield benzoquinonoid compound (BQ), respectively. In vitro experiments using VEGF-induced human umbilical vein endothelial cells (HUVECs) and IL-1ß-induced human fibroblast-like synoviocytes for rheumatoid arthritis (HFLS-RA) were performed to evaluate the effects of these samples on VEGF-induced HUVECs proliferation and tube formation, and towards IL-1ß-induced HFLS-RA proliferation, invasion, and apoptosis, respectively. Therapeutic concentrations (0.05, 0.5, and 5 µg/mL) tested in this study were predetermined based on the IC50 values obtained from the MTT assay. RESULTS: ACRH, QRF, and BQ exerted concentration-independent antiproliferative effects on VEGF-induced HUVECs and IL-1ß-induced HFLS-RA, with IC50 values at 1.09 ± 0.18, 3.85 ± 0.26, and 1.34 ± 0.16 µg/mL in HUVECs; and 3.60 ± 1.38, 4.47 ± 0.34, and 1.09 ± 0.09 µg/mL in HFLS-RA, respectively. Anti-angiogenic properties of these samples were verified via significant inhibition on VEGF-induced HUVECs tube formation, in a concentration-independent manner. The invasiveness of IL-1ß-induced HFLS-RA was also significantly inhibited in a concentration-independent manner by all samples. ACRH and BQ, but not QRF, significantly enhanced the apoptosis of IL-1ß-induced HFLS-RA elicited at their highest concentration (5 µg/mL) (P < 0.05). CONCLUSIONS: These findings highlight the bioactive fractions and compound from Ardisia crispa roots as potential anti-arthritic agents by inhibiting both HUVECs and HFLS-RA's cellular functions in vitro, possibly mediated via their anti-angiogenic effects.


Assuntos
Inibidores da Angiogênese/farmacologia , Ardisia , Artrite Reumatoide/patologia , Extratos Vegetais/farmacologia , Raízes de Plantas , Apoptose/efeitos dos fármacos , Fibroblastos/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Membrana Sinovial/citologia
8.
Nat Prod Rep ; 38(12): 2276-2292, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33998635

RESUMO

Covering: up to April 2021The bacterial cyclic depsipeptides FR900359 (FR) and YM-254890 (YM) were shown to selectively inhibit Gαq proteins with high potency and selectivity and have recently emerged as valuable pharmacological tools due to their effective mechanism of action. Here, we summarize important aspects of this small and specialized natural product family, for which we propose the name chromodepsins, starting from their discovery, producing organisms and structural variety. We then review biosynthesis, structure-activity relationships and ecological and evolutionary aspects of the chromodepsins. Lastly, we discuss their mechanism of action, potential medicinal applications and future opportunities and challenges for further use and development of these complex inhibitor molecules from nature.


Assuntos
Produtos Biológicos/química , Depsipeptídeos/química , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/antagonistas & inibidores , Ardisia/química , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Chromobacterium/química , Depsipeptídeos/metabolismo , Depsipeptídeos/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade
9.
J Nat Med ; 75(3): 643-654, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33905079

RESUMO

From the leaves of Ardisia quinquegona, two alkylated tetronic acid derivatives, named ardisiatetrons A and B (1, 2), and four triterpenoids (3-6) were isolated together with one known compound (7) by a combination of various kinds of chromatography. The structure of new methyl migrated triterpene (3) was confirmed by X-ray crystallographic analysis. Compounds 2, 3, and 7 showed moderate anti-Leishmania activity and cytotoxicity towards A549 cells.


Assuntos
Ardisia/química , Furanos/química , Triterpenos/química , Células A549 , Antiprotozoários/química , Humanos , Japão , Leishmania major/efeitos dos fármacos , Estrutura Molecular , Compostos Fitoquímicos/química , Folhas de Planta/química
10.
Biomed Chromatogr ; 35(7): e5099, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33625742

RESUMO

Isolation and screening of different compounds from plant extracts are always the key for natural drug research, and the absorbed prototype components have been considered as potential active ingredients. UHPLC combined with quadrupole time-of-flight mass spectrometry (Q-TOF-LC/MS) has been widely used in the research of natural drugs; however, we still need a more effective tool to compare and treat from a raw data. In this study, we provided a fast analytical method to measure the absorbed prototype components and their metabolites both qualitatively and quantitatively based on molecular networking (MN). For example, in Ardisia japonica (Thunb.) Blume, a total of eight absorbed prototype components in rat plasma were identified. Furthermore, pharmacokinetic study was also successfully performed on the eight absorbed prototype components in rat plasma. Our findings have provided important information on the investigation of A. japonica in vivo. More importantly, the MS network analysis pattern serves as an integral solution for qualitative and quantitative determination of phytochemical compounds in natural drugs.


Assuntos
Ardisia/química , Cromatografia Líquida de Alta Pressão/métodos , Compostos Fitoquímicos/sangue , Extratos Vegetais/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Biologia Computacional , Modelos Lineares , Masculino , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacocinética , Extratos Vegetais/química , Extratos Vegetais/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
11.
Chin J Nat Med ; 19(1): 63-69, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33516453

RESUMO

Two new triterpenoid saponins, ardisicrenoside R and S (1 and 2), and one new phenylpropanoid glycoside, ardicrephenin (3), along with five known compounds (4-8), were isolated from roots of Ardisia crenata. Their structures were elucidated on the basis of NMR spectroscopic data and chemical methods. Compounds 2-7 were evaluated for their cytotoxic activities against A549, MCF-7, HepG2 and MDA-MB-231 cell lines by MTT assay. Ardicrenin (6) showed significant cytotoxicity, with IC50 values of 1.17 ± 0.01, 1.19 ± 0.06, 3.52 ± 0.23, and 16.61 ± 1.02 µmol·L-1, respectively.


Assuntos
Antineoplásicos Fitogênicos , Ardisia , Glicosídeos , Saponinas , Triterpenos , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Ardisia/química , Linhagem Celular Tumoral , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Humanos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
12.
Nat Prod Res ; 35(1): 157-161, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31135229

RESUMO

Ardisia crenata Sims (Myrsinaceae) occurs in two varieties differing in the fruit color, the red berries being common while the white ones are rare. The roots of red-berried A. crenata are a valued TCM product which contains bioactive benzoquinones such as embelin and rapanone. In this study we compared their profiles in different organs of the plant to provide an insight in the pattern of their accumulation within the two varieties. Moreover, cytotoxic activity against human melanoma and prostate cancer cells was evaluated. Quantitative HPLC revealed that the white-berried variety differs profoundly in the content of rapanone, with its total level of 606.5 mg/100 g d.w., as compared to 16.2 mg/100 g d.w. in A. crenata 'red'. Embelin was less distributed and found in minor amounts in both varieties. This is the first report on rapanone content in various parts of Ardisia crenata and on benzoquinones in the white-berried variety.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Ardisia/química , Benzoquinonas/farmacologia , Antineoplásicos Fitogênicos/análise , Ardisia/fisiologia , Benzoquinonas/análise , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Frutas/química , Humanos , Masculino , Melanoma/tratamento farmacológico , Melanoma/patologia , Pigmentação , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Plantas Medicinais/química , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia
13.
Phytochem Anal ; 32(5): 685-697, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33295100

RESUMO

INTRODUCTION: Ardisia elliptica Thunb. (Primulaceae) is a medicinal herb that is traditionally used for the treatment of fever, diarrhoea, measles and herpes. However, there is limited information regarding the correlation of its phytoconstituents with the bioactivity. Optimisation of solvent extraction is vital for maximising retention of bioactive molecules. OBJECTIVE: This study investigated the metabolite variations in A. elliptica leaves and the correlation with antioxidant activities. METHODOLOGY: Total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radicals scavenging assays were performed on A. elliptica leaves extracted with four different ethanol ratios (0%, 50%, 70% and absolute ethanol). The correlation of metabolites with antioxidant activities was evaluated using a nuclear magnetic resonance (NMR)-based metabolomics approach. RESULTS: The results showed that the 50% and 70% ethanolic extracts retained the highest TPC, and the 70% ethanolic extract was the most active, exhibiting half maximal inhibitory concentration (IC50 ) values of 10.18 ± 0.83 and 43.05 ± 1.69 µg/mL, respectively, in both radical scavenging assays. A total of 46 metabolites were tentatively identified, including flavonoids, benzoquinones, triterpenes and phenolic derivatives. The 50% and 70% ethanolic extracts showed similarities in metabolites content and were well discriminated from water and absolute ethanol extracts in a principal component analysis (PCA) model. Moreover, 31 metabolites were found to contribute significantly to the differentiation and antioxidant activity. CONCLUSION: This study provides information on bioactive compounds in A. elliptica leaves, which is promising as a functional ingredient for food production or for the development of phytomedicinal products.


Assuntos
Ardisia , Antioxidantes , Flavonoides , Metabolômica , Fenóis , Extratos Vegetais
14.
Oxid Med Cell Longev ; 2020: 7963212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123316

RESUMO

Triple-negative breast cancers (TNBCs) are associated with poor patient survival because of the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expressions. Our previous studies have shown that the triterpenoid saponin AG8 from Ardisia gigantifolia stapf. inhibits the proliferation of MDA-MB-231 cells. In this study, the effects of AG8 were further analyzed in different TNBC cell types: MDA-MB-231, BT-549, and MDA-MB-157 cells. AG8 inhibited the viability of MDA-MB-231, BT-549, and MDA-MB-157 cells in a dose-dependent manner and showed stronger cytotoxicity to African American (AA) and mesenchymal (M) subtypes than Caucasian (CA) and mesenchymal stem-like (MSL) subtypes, respectively. AG8 impaired the uptake of MitoTracker Red CMXRos by the mitochondria of TNBC cells in a dose-dependent manner, and this was recovered by N-acetyl-l-cysteine (NAC). AG8 affected GSH, SOD, and MDA levels of TNBC cells, but different TNBC subtypes had different sensitivities to AG8 and NAC. In addition, we found that AG8 increased the Bax/Bcl-2 ratio and the levels of cytoplasmic cytochrome c and significantly decreased phosphorylation of ERK and AKT in BT549 and MDA-MB-157 cells. AG8 elicited its anticancer effects through ROS generation, ERK and AKT activation, and by triggering mitochondrial apoptotic pathways in TNBC cells. AG8 had selective cytotoxic effects against the AA and M TNBC subtypes and markedly induced MDA-MB-157 (AA subtype) cell apoptosis through pathways that were not associated with ROS, which was different from the other two subtypes. The underlying mechanisms should be further investigated.


Assuntos
Apoptose/efeitos dos fármacos , Ardisia/química , Estresse Oxidativo/efeitos dos fármacos , Saponinas/farmacologia , Acetilcisteína/farmacologia , Ardisia/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Glutationa/metabolismo , Humanos , Malondialdeído/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteína Oncogênica v-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Triterpenos/farmacologia , Proteína X Associada a bcl-2/metabolismo
15.
J Nat Med ; 74(4): 732-740, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32643027

RESUMO

AG36 is a triterpenoid saponin from Ardisia gigantifolia stapf. Our recent studies proved that AG36 displayed prominent cytotoxicity against breast cancer cells both in vitro and in vivo. However, whether AG36 has antiangiogenic properties is unknown. Therefore, in the present study, we evaluated the antiangiogenic effect of AG36 and the underlying mechanism. The results indicated that AG36 could significantly inhibit the proliferation, migration and invasion of human umbilical vein endothelial cells (HUVEC). Further antiangiogenic molecular mechanism investigation showed that AG36 significantly suppressed phosphorylated FAK and AKT, and downregulated the expressions of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) in HUVECs. PI3K inhibitor (LY294002) and FAK inhibitor (PF562271) pretreatment could markedly enhance AG36-induced inhibition of HUVEC proliferation and p-FAK suppression, respectively. In addition, AG36 inhibited the tumor growth in xenograft model and expressions of p-VEGFR2 and p-Akt in vivo. Molecular docking simulation indicated that AG36 formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic potency and related underlying molecular of AG36, demonstrating that AG36 maybe a potential antiangiogenic cancer therapy agent or lead candidate.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Ardisia/química , Medicina Tradicional Chinesa/métodos , Saponinas/química , Inibidores da Angiogênese/farmacologia , Animais , Humanos
16.
Molecules ; 25(13)2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32640504

RESUMO

Plants and plant-based products have been used for a long time for medicinal purposes. This study aimed to determine the antioxidant and anti-α-glucosidase activities of eight selected underutilized plants in Malaysia: Leucaena leucocephala, Muntingia calabura, Spondias dulcis, Annona squamosa, Ardisia elliptica, Cynometra cauliflora, Ficus auriculata, and Averrhoa bilimbi. This study showed that the 70% ethanolic extract of all plants exhibited total phenolic content (TPC) ranging from 51 to 344 mg gallic acid equivalent (GAE)/g dry weight. A. elliptica showed strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging activities, with half maximal inhibitory concentration (IC50) values of 2.17 and 49.43 µg/mL, respectively. Most of the tested plant extracts showed higher inhibition of α-glucosidase enzyme activity than the standard, quercetin, particularly A. elliptica, F. auriculata, and M. calabura extracts with IC50 values of 0.29, 0.36, and 0.51 µg/mL, respectively. A total of 62 metabolites including flavonoids, triterpenoids, benzoquinones, and fatty acids were tentatively identified in the most active plant, i.e., A. elliptica leaf extract, by using ultra-high-performance liquid chromatography (UHPLC)-electrospray ionization (ESI) Orbitrap MS. This study suggests a potential natural source of antioxidant and α-glucosidase inhibitors from A. elliptica.


Assuntos
Ardisia/química , Inibidores de Glicosídeo Hidrolases/análise , Fenóis/análise , Extratos Vegetais/química , Plantas Medicinais/química , Antioxidantes/química , Ardisia/enzimologia , Benzoquinonas/química , Compostos de Bifenilo/metabolismo , Cromatografia Líquida de Alta Pressão , Fabaceae/química , Fabaceae/enzimologia , Ácidos Graxos/análise , Flavonoides/análise , Inibidores de Glicosídeo Hidrolases/química , Concentração Inibidora 50 , Malásia , Espectrometria de Massas , Óxido Nítrico/metabolismo , Picratos/metabolismo , Extratos Vegetais/análise , Caramujos/química , Triterpenos/análise
17.
J Biotechnol ; 311: 12-18, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32084416

RESUMO

To develop an alternative medicine related with taxol/camptothecin, a hairy roots induction system for measuring triterpenoid saponin ardicrenin was established. In the current study, mature and healthy seeds of Ardisia crenata plants were selected for obtaining aseptic seedlings. Two Agrobacterium rhizogenes strains ATCC 15834 and A4 were used to infect aseptic euphylla for inducing hairy roots of A. crenata plants. For the best combination of seeds germination, a Murashige-Skoog medium containing 1.0 mg L-1 6-benzylaminopurine and 1.0 mg L-1 naphthalene acetic acid was made, which reached a rate of 92.4 %. Results showed that ATCC 15834 and A4 both induced hairy roots of A. crenata for improving ardicrenin production. The PCR analysis demonstrated that ATCC 15834 and A4 Ri plasmid T-DNA had been successfully transferred and integrated into the genome of leaf cell nuclei, however the Vir region was not. Further, ardicrenin content in hairy roots ACHR 15834 8.2 %) induced by ATCC 15834 was quantified by the RP-HPLC, which was also 1.8-, 2.7-, 9.4- and 2.6-fold greater than those of ACHR 4 induced by A4 (4.5 %), ACR C formed by tissue culture (3.1 %), euphylla (0.8 %) and NR C formed nature (3.2 %), respectively. Taken together, hairy root lines of A. crenata obtained were able to express naturally more ardicrenin than natural plants.


Assuntos
Ardisia/metabolismo , Ácido Oleanólico/análogos & derivados , Raízes de Plantas/metabolismo , Saponinas/metabolismo , Agrobacterium/metabolismo , Ardisia/microbiologia , Cromatografia Líquida de Alta Pressão , Ácido Oleanólico/metabolismo , Raízes de Plantas/microbiologia
18.
Molecules ; 25(5)2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32106546

RESUMO

The present study is intended to carry out the chemical standardization and evaluation of the anti-proliferative activity of A. elliptica fruit extract. A. elliptica fruit powder was extracted with ethanol. The obtained extract was assessed for total phenolic content using the Folin-Ciocalteu method. Moreover, a simple, accurate, and precise reversed phase high-performance liquid chromatographic method was developed and validated to determine the embelin content of A. elliptica fruit extract. Then, the extract and embelin were investigated for their anti-proliferative effect against HCT-116 cells. Finally, the mechanisms of inhibition of the extract and embelin on the mRNA expression of pro-apoptotic genes Bad, Bax, and Caspase-8 and anti-apoptotic genes c-IAP1, Mcl-1, and XIAP were determined by real-time qRT-PCR. The phenolic content and embelin content of the extract were 5.20 ± 0.01 g of gallic acid equivalent per 100 g of dried fruit (g% GAE) and 5.57 ± 0.56 mg/g of extract, respectively. The extract and embelin showed strong anti-proliferative effects on HCT-116 cells with 50% inhibition concentration (IC50) values of 19.16 ± 1.09 µg/mL and 25.93 ± 1.75 µg/mL, respectively. The A. elliptica extract exhibited a significant increase in the mRNA level of Bad, Bax, and Caspase-8 and a significant decrease in c-IAP1, Mcl-1, and XIAP. Embelin showed a significant decrease in Mcl-1 and XIAP.


Assuntos
Apoptose/efeitos dos fármacos , Ardisia/química , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Antioxidantes/química , Antioxidantes/farmacologia , Caspase 8/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Frutas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Proteínas de Neoplasias/genética , Fenóis/química , Fenóis/farmacologia , Proteína X Associada a bcl-2/genética , Proteína de Morte Celular Associada a bcl/genética
19.
Biomed Pharmacother ; 118: 109221, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545225

RESUMO

Ardisia crispa Thunb. A. DC. (Primulaceae) has been used extensively as folk-lore medicine in South East Asia including China and Japan to treat various inflammatory related diseases. Ardisia crispa root hexane fraction (ACRH) has been thoroughly studied by our group and it has been shown to exhibit anti-inflammatory, anti-hyperalgesic, anti-arthritic, anti-ulcer, chemoprevention and suppression against inflammation-induced angiogenesis in various animal model. Nevertheless, its effect against human endothelial cells in vitro has not been reported yet. Hence, the aim of the study is to investigate the potential antiangiogenic property of ACRH in human umbilical vein endothelial cells (HUVECs) and zebrafish embryo model. ACRH was separated from the crude ethanolic extract of the plant's root in prior to experimental studies. MTT assay revealed that ACRH exerted a concentration-dependent antiproliferative effect on HUVEC with the IC50 of 2.49 ±â€¯0.04 µg/mL. At higher concentration (10 µg/mL), apoptosis was induced without affecting the cell cycle distribution. Angiogenic properties including migration, invasion and differentiation of HUVECs, evaluated via wound healing, trans-well invasion and tube formation assay respectively, were significantly suppressed by ACRH in a concentration-dependent manner. Noteworthily, significant antiangiogenic effects were observed even at the lowest concentration used (0.1 µg/mL). Expression of proMMP-2, vascular endothelial growth factor (VEGF)-C, VEGF-D, Angiopoietin-2, fibroblast growth factor (FGF)-1, FGF-2, Follistatin, and hepatocyte growth factor (HGF) were significantly reduced in various degrees by ACRH. The ISV formation in zebrafish embryo was significantly suppressed by ACRH at the concentration of 5 µg/mL. These findings revealed the potential of ACRH as antiangiogenic agent by suppressing multiple proangiogenic proteins. Thus, it can be further verified via the transcription of these proteins from their respective DNA, in elucidating their exact pathways.


Assuntos
Ardisia/química , Embrião não Mamífero/metabolismo , Hexanos/química , Células Endoteliais da Veia Umbilical Humana/metabolismo , Neovascularização Patológica/tratamento farmacológico , Raízes de Plantas/química , Peixe-Zebra/embriologia , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Movimento Celular , Proliferação de Células , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Metaloproteinases da Matriz/metabolismo , Modelos Animais , Neovascularização Patológica/patologia
20.
Z Naturforsch C J Biosci ; 74(11-12): 303-311, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31437126

RESUMO

Medicinal plants belonging to the genus Ardisia are traditionally used to cure various human diseases including inflammation and cancer. This study aimed to purify and characterize cytotoxic and anti-inflammatory compounds from Ardisia sieboldii leaves. Bioassay-guided chromatographic analyses yielded three compounds, 2-methyl-5-(8Z-heptadecenyl) resorcinol (1), 5-(8Z-heptadecenyl) resorcinol (2), and ardisiaquinone A (3), whereas liquid chromatography-electrospray ionisation-mass spectrometry chemical profiling revealed the presence of diverse resorcinol and alkylbenzoquinone derivatives in cytotoxic 70% methanol extracts. Chemical structures of 1-3 were confirmed by spectroscopic methods including 1H NMR (nuclear magnetic resonance), 13C NMR, and electrospray ionisation-mass spectrometry. Compounds 1 and 2 were purified from A. sieboldii for the first time, and all three compounds showed cytotoxicity against a panel of cancer cell lines and brine shrimps in a dose-response manner. Among them, compound 2 exhibited the highest cytotoxicity on cancer cells (IC50 values of 8.8-25.7 µM) as well as on brine shrimps (IC50 value of 5.1 µM). Compounds 1-3 exhibited anti-inflammatory effects through inhibiting protein denaturation (IC50 values of 5.8-9.6 µM), cyclooxygenase-2 activity (IC50 values of 34.5-60.1 µM), and nitrite formation in RAW 264.7 cells. Cytotoxic and anti-inflammatory activities of 1-3 demonstrated in this study deserve further investigation for considering their suitability as candidates or leads to develop anticancer and anti-inflammatory drugs.


Assuntos
Anti-Inflamatórios/farmacologia , Ardisia/química , Folhas de Planta/química , Resorcinóis/farmacologia , Albuminas/metabolismo , Animais , Anti-Inflamatórios/química , Artemia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Humanos , Concentração Inibidora 50 , Camundongos , Nitritos/metabolismo , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Desnaturação Proteica/efeitos dos fármacos , Células RAW 264.7
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