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1.
Pharmacogn Mag ; 13(52): 702-706, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29200736

RESUMO

BACKGROUND: Traditional Chinese herb Tithonia diversifolia, belonging to the Compositae family, has long been applied for the treatment of liver diseases. In recent years, many reports also indicated that it possesses hepato-protective, anti-inflammatory, and anti-cancer activities. OBJECTIVE: In this study, we evaluated whether T. diversifolia is an effective therapy for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Dry leaves of T. Diversifolia were first extracted in ethyl acetate, then further fractionated by different ratio of n-hexane-ethyl acetate (8:2→0:1) or methanol as fractions 1-6 (Td-F1 to Td-F6), respectively. We first showed that the ethyl acetate extracts of T. diversifolia leaves (Td-L-EA) exhibits growth inhibition on human hepatoma HepG2 cells. To further check the extracts-induced apoptosis, microscopic observation, fragmented chromosomal DNA electrophoresis, apoptotic DNA-detection ELISA assay, flow cytometry, and Western blot analysis were performed. RESULTS: After isolating the effective fractions from Td-L-EA, we found strong cytotoxic effects of fraction-2 (Td-F2). By further analyzing the mechanisms of cytotoxic activities using microscopic observation, fragmented chromosomal DNA electrophoresis, apoptotic DNA-detection ELISA assay, and flow cytometry, we found that induction of apoptosis such as DNA fragmentation increased the apoptosis rate and the apoptosis sub-G1 populations in Td-F2-treated HepG2 cells. In addition, we also confirmed Td-F2-induced degradation of caspase-8, caspase-9, caspase-3, and caspase-3 substrate PARP. Besides, Td-F2 also increased the Bcl-2 proapoptotic family protein Bax expression. CONCLUSION: In short, our results clearly showed the induction of apoptosis by ethyl acetate extracts of T. diversifolia leaves in human hepatoma HepG2 cells, suggesting its potential application as an antitumor agent. SUMMARY: T. Diversifolia leaves were first extracted in ethyl acetate, then further fractionated by different ratio of n-hexane/ethyl acetate (8:2→0:1) or methanol.These extracts exhibit growth inhibition on human hepatoma (HCC) HepG2 cells.n-Hexane/ethyl acetate (6:4) extract (Td-F2) induces apoptosis of HCC. Abbreviations used:T. diversifolia, Tithonia diversifolia; HCC, Hepatocellular carcinoma DMEM, Dulbecco's modified Eagle's medium; DMSO, dimethyl sulfoxide; HRP, horseradish peroxidase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; OD, optical density; SDS-PAGE, sodium dodecylsulfate-polyacrylamide gel electrophoresis; PARP, Poly (ADP-ribose) polymerase; PBS, phosphate buffered saline; PI, propidium iodide.

2.
Bioorg Med Chem Lett ; 26(8): 1905-9, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26988300

RESUMO

Atractylodes macrocephula Koidz (A. macrocephula, also known as Baizhu) is an important ingredient in several traditional Chinese herb complexes for the treatment of abdominal pain and gastroenterology diseases for thousands of years. We previously demonstrated the induction of ROS-mediated apoptosis by methanol extract of A. macrocephula in human leukemia cells. After purification and assessment of those active compounds from A. macrocephula ethanol extracts, in this study, we focused on the major active compound, atractylenolide I (ATL-I). Through MTT assay and morphology observation, we found cytotoxic effect of ATL-I in human K562 chronic myeloblastic leukemia (CML), U937 acute myeloblastic leukemia (AML) and Jurkat T lymphoma cells. In addition, ATL-I-induced apoptosis was demonstrated by sub G1 and fragmented chromosomal DNA detection using flow cytometry, enzyme-linked immunosorbent assay (ELISA) and agarose electrophoresis. Finally, we found ATL-I also induced caspase-3 and caspase-9 activation through the detection of procaspase-3, procaspase-9 and caspase-3 substrate poly(ADP-ribose) polymerase (PARP) by immunoblotting. Interestingly, we found that ATL-I induced not only apoptosis but also differentiation, as upregulation of CD14 and CD68 surface markers and increase of phagocytosis ability were discovered in ATL-I-treated K562 CML and U937 AML cells. Our study thus suggests the potential of developing new leukemia therapies by using ATL-I for leukemia treatment in the future.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Atractylodes/química , Diferenciação Celular/efeitos dos fármacos , Lactonas/farmacologia , Leucemia/patologia , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade
3.
Planta Med ; 81(10): 830-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26158522

RESUMO

Lindera megaphylla has been traditionally used as an antineoplastic and wound healing remedy. We previously demonstrated the antitumor effects of D-dicentrine, a natural aporphine alkaloid from the root of L. megaphylla. To generate analogues, series of phenanthrene alkaloids from D-dicentrine were synthesized by degradation with ethyl chloroformate in pyridine, base hydrolysis, and N-alkylation. In this study, we demonstrated that one of the synthesized D-dicentrine analogues (here after designated as analogue 1) exhibited more potent cytotoxic effects than D-dicentrine in colon adenocarcinoma, hepatoma, leukemia, and epidermoid carcinoma cells. We performed cell cycle and apoptotic analysis by flow cytometry, an apoptotic DNA detection ELISA assay, and topoisomerase II activity by the kinetoplast DNA concatenation assay for studying their cytotoxic mechanisms. We found that both D-dicentrine and analogue 1 induced apoptosis and G2/M arrest in HL-60 leukemia cells. The percentage of apoptotic cells induced by analogue 1 was 4.5-fold higher than that induced by D-dicentrine as evident from measuring the amount of histone-bound DNA fragments. Moreover, we found that analogue 1 was 28-fold more potent than D-dicentrine for inhibition of topoisomerase II activity by the kinetoplast DNA concatenation assay. Our findings indicate that D-dicentrine analogue 1 is very promising as a potential antitumor agent for future study.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Aporfinas/química , Inibidores da Topoisomerase II/farmacologia , Animais , Aporfinas/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Fibroblastos/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Camundongos , Estrutura Molecular , Inibidores da Topoisomerase II/química
4.
Bioorg Med Chem ; 18(3): 1213-26, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20061158

RESUMO

We have previously shown that helioxanthin can suppress human hepatitis B virus gene expression. A series of helioxanthin analogues were synthesized and evaluated for their anti-hepatitis B virus activity. Modifications at the lactone rings and methylenedioxy unit of helioxanthin can modulate the antiviral activity. Among them, compound 32 is the most effective anti-HBV agent. Compound 32 can suppress the secretion of viral surface antigen and e antigen in HepA2 cells with EC(50) values of 0.06 and 0.14 microM, respectively. Compound 32 not only inhibited HBV DNA with wild-type and lamivudine-resistant strain but also suppressed HBV mRNA, core protein and viral promoters. In this study, a full account of the preparation, structure-activity relationships of helioxanthin analogues, and the possible mechanism of anti-HBV activity of this class of compounds are presented. This type of compounds possesses unique mode of action differing from existing therapeutic drugs. They are potentially new anti-HBV agents.


Assuntos
Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Lignanas/química , Lignanas/farmacologia , Linhagem Celular Tumoral , Antígenos de Superfície da Hepatite B/genética , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Humanos , Regiões Promotoras Genéticas/efeitos dos fármacos , Relação Estrutura-Atividade , Proteínas do Core Viral/metabolismo , Replicação Viral/efeitos dos fármacos
5.
Planta Med ; 71(7): 646-53, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16041651

RESUMO

Bioassay-directed fractionation of the EtOAc extract of Kadsura japonica has led to the isolation of six new C18 dibenzocyclooctadiene lignans, schizanrins I, J, K, L, M, N, along with four known C19 homolignans, taiwanschirins A, B, C, and heteroclitin F. The elucidations of the new structures were based on spectral analysis. Bioassay evaluation against human type B hepatitis revealed that taiwanschirins A and B showed strong activity for anti-HBsAg and a medium effect for anti-HBeAg at 25 microg/mL (12.9 and 11.9 microM for taiwanschirins A and B, respectively).


Assuntos
Antivirais/farmacologia , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Antígenos E da Hepatite B/efeitos dos fármacos , Kadsura , Fitoterapia , Extratos Vegetais/farmacologia , Antivirais/química , Linhagem Celular , Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Hepatite B/prevenção & controle , Humanos , Lignanas/química , Lignanas/farmacologia , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Relação Estrutura-Atividade
6.
J Agric Food Chem ; 53(5): 1776-81, 2005 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-15740073

RESUMO

In this study, we examined the antitumor effect of marine algae extracts on human hepatoma and leukemia cells. Ethyl acetate extracts from Colpomenia sinuosa (Cs-EA), Halimeda discoidae (Hd-EA), and Galaxaura oblongata (Go-EA) directly inhibited the growth of human hepatoma HuH-7 cells and leukemia U937 and HL-60 cells in a time- and dose-dependent manner. Specifically, these algae extracts induced apoptosis of U937 and HL-60 cells as evaluated by detection of hypodiploid cells using flow cytometry and observation of condensed and fragmented nuclei in algae extract-treated cells. Intracellular reactive oxygen species (ROS), especially hydrogen peroxide and superoxide anion, were increased about 2-3-fold in U937 cells treated with Cs-EA for 3-5 h. Interestingly, antioxidant N-acetylcysteine effectively blocked Cs-EA-, Hd-EA-, and Go-EA-induced apoptosis, suggesting that ROS is a key mediator in the apoptotic signaling pathway. In conclusion, our results show that algae extracts induce apoptosis in human leukemia cells through generation of ROS.


Assuntos
Apoptose/efeitos dos fármacos , Eucariotos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/farmacologia , Carcinoma Hepatocelular , Clorófitas/metabolismo , Células HL-60 , Humanos , Leucemia Mieloide , Neoplasias Hepáticas , Phaeophyceae/metabolismo , Rodófitas/metabolismo , Células Tumorais Cultivadas
7.
Bioorg Med Chem ; 13(5): 1555-61, 2005 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-15698772

RESUMO

(+)-Gomisin K(3) (1) and kadsurarin (2) were isolated from Schizandra arisanensis and Kadsura matsudai, respectively, and a series of C(18) dibenzocyclooctadiene lignan analogues (5-20) derived from 1 and 2 were synthesized. Esterified derivatives of 1 and 2 were evaluated for inhibitory activity against human type B hepatitis with surface antigen (HBsAg) and e antigen (HBeAg). Most of the analogues (5-8, 10, 12-13) derived from 1 exhibited higher anti-HBsAg effects and lower toxicity, and 6, 7, 8 and 12 also showed higher anti-HBeAg activity. Among these active C(18) dibenzocyclooctadiene lignan analogues, the lignan with a but-3-enoyl group (6) exhibited the most active inhibition.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Antígenos E da Hepatite B/efeitos dos fármacos , Lignanas/síntese química , Lignanas/farmacologia , Antivirais/química , Linhagem Celular , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho
8.
J Ethnopharmacol ; 97(1): 21-9, 2005 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-15652270

RESUMO

Baizhu (Atractylodes macrocephala Koidz) has traditionally been used as an important ingredient of several Chinese herbal medicines, which have been used for abdominal pain and gastroenterology diseases for thousands of years. Despite its popularity in herbal therapies, little is known about the anticancer effect of Baizhu. In this study, the anticancer potential of Baizhu on human hepatoma and leukemia cell lines was evaluated. Baizhu methanol extract induced apoptosis in human lymphoma Jurkat T cells, leukemia U937, and HL-60 cells. This was confirmed by several methods, including hypodiploid cells detection using flow cytometry, the examination of apoptotic bodies containing cells using confocal laser scanning microscopy, and hypodiploid cell population inhibition using the broad spectrum caspase inhibitor z-VAD. Finally, the intracellular reactive oxygen species (ROS), especially hydrogen peroxide (H(2)O(2)) and superoxide anion (O(2)(-)), were found to be elevated after treatment of these cells with Baizhu extracts. Antioxidant N-acetyl cysteine (NAC) pretreatment almost completely inhibited Baizhu-induced apoptosis, suggesting that ROS are the key mediators for Baizhu-induced apoptosis. All these data indicate that Baizhu is a possible anti-tumor agent that induces apoptosis of human leukemia cells through ROS generation.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Atractylodes , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/isolamento & purificação , Apoptose/fisiologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Células HL-60 , Humanos , Células Jurkat , Células U937
9.
J Nat Prod ; 67(11): 1947-9, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15568798

RESUMO

Four new furanolabdane diterpenes, hypopurin A (1), hypopurin B (2), hypopurin C (3), and hypopurin D (4), together with eight lignans, alpha-O-methylcubebin, beta-O-methylcubebin, hinoquinin, helioxanthin, 7-hydroxyhinokinin, dehydroxycubebin, justicidine E, and (-)-hibalactone, as well as two triterpenes, lupeol and betulin, were isolated from the dried aerial part of Hypoestes purpurea. The structures of 1-4 were elucidated mainly on the basis of NMR and MS. Compound 1 was found to be moderately cytotoxic toward the KB cell line with an IC(50) value of 9.4 microM.


Assuntos
Acanthaceae/química , Diterpenos/isolamento & purificação , Plantas Medicinais/química , China , Diterpenos/química , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Células KB , Espectrometria de Massas , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Triterpenos Pentacíclicos , Triterpenos/química , Triterpenos/isolamento & purificação , Células Tumorais Cultivadas
10.
Chem Pharm Bull (Tokyo) ; 52(7): 866-9, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15256712

RESUMO

Using the anti-hepatitis B virus (HBV)-producing cell line MS-G2 in vitro cultural system-guided screening was performed, and two new benzophenones, 2,6-dihydroxy-4-[(E)-5-hydroxy-3,7-dimethylocta-2,7-dienyloxy]benzophenone (1) and 2,6-dihydroxy-4-[(E)-7-hydroxy-3,7-dimethylocta-2-enyloxy]benzophenone (2), a new xanthone, hyperxanthone (3), a new bisanthraquinone glycoside, R-(-)-skyrin-6-O-beta-D-xylopyranoside (4), and 2-caffeoyloxy-3-hydroxy-3-(3,4-dihydroxyphenyl)propyl alcohol (5), and 16 known compounds were isolated from the anti-HBV active fraction of the whole herbs of Hypericum sampsonii. Their structures were elucidated using spectroscopic methods, mainly 2D NMR and MS spectrometry. Circular dichroism was used to determine the stereochemistry of bisanthraquinone glycosides.


Assuntos
Hypericum , Fenóis/química , Preparações de Plantas/química , Fenóis/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Preparações de Plantas/isolamento & purificação
11.
J Nat Prod ; 67(6): 1014-7, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15217285

RESUMO

Imperatorin (1) was metabolized by Aspergillus flavus, in growth media, to give five metabolites. On the basis of their physical data, the structures of the five metabolites were elucidated as xanthotoxol (2), E-trichoclin (3), Z-trichoclin (4), E-imperatorin acid (5), and Z-imperatorin acid (6); among these, 4, 5, and 6 were characterized as new coumarins. The five metabolites 2-6 were tested for anti-hepatitis B virus activity in vitro and found to be less active than the parent compound 1.


Assuntos
Antivirais/metabolismo , Aspergillus flavus/metabolismo , Furocumarinas/metabolismo , Antivirais/farmacologia , Biotransformação , Cumarínicos/química , Furocumarinas/farmacologia , Vírus da Hepatite B/metabolismo , Estrutura Molecular , Estereoisomerismo , Taiwan
12.
Chem Pharm Bull (Tokyo) ; 51(11): 1233-6, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14600364

RESUMO

The C(18) dibenzocyclooctadiene lignans including three novel schizanrin F (1), G (2), H (3), along with the known kadsurarin (4), were isolated from Kadsura matsudai. A new C(19) homolignan named schiarisanrin E (5), together with the known C(18) lignans, gomisin B (6), G (7) and (+)-gomisin K(3) (8) were obtained from Schizandra arisanensis. Gomisin B, G and (+)-gomisin K(3) showed moderate to strong activity for antihepatitis in anti-HBsAg (human type B hepatitis, surface antigen) and/or anti-HBeAg (human type B hepatitis, e antigen) tests. The structural elucidations of new compounds 1-3 and 5 were based on two-dimensional (2D) NMR techniques including COSY, HMQC, HMBC, NOESY and CD spectra. Preliminary structure-activity relationship studies for these isolated lignans are also discussed.


Assuntos
Ciclo-Octanos/farmacologia , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Antígenos E da Hepatite B/efeitos dos fármacos , Kadsura/química , Lignanas/farmacologia , Schisandra/química , Aspartato Aminotransferases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Octanos/química , Frutas/química , Humanos , Lignanas/química , Espectroscopia de Ressonância Magnética , Caules de Planta/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho
13.
Phytother Res ; 17(5): 449-53, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12748977

RESUMO

Using an HBV-producing cell line and inhibition of the expression of the HBsAg and HBeAg as antiviral indicators, a study was conducted on 25 compounds isolated from four Phyllanthus (Euphorbiaceae) plants, including P. amarus Schum. & Thonn., P. multi florus Willd., P. tenellus Roxb. and P. virgatus Forst. f. It was found that niranthin (1), nirtetralin (3), hinokinin (5) and geraniin (13) at the non-cytotoxic concentration of 50 micro m, suppressed effectively both HBsAg and HBeAg expression, with the highest inhibition at 74.3%, 45.3%; 69.6%, 33.9%; 68.1%, 52.3%; 32.1%, 46.6%, respectively. Of these, niranthin (1) showed the best anti-HBsAg activity, while the most potent anti-HBeAg activity was observed with hinokinin (5).


Assuntos
4-Butirolactona/farmacologia , Anisóis/farmacologia , Dioxóis/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Taninos Hidrolisáveis , Lignanas , Phyllanthus , Extratos Vegetais/farmacologia , 4-Butirolactona/análogos & derivados , 4-Butirolactona/isolamento & purificação , Anisóis/isolamento & purificação , Benzodioxóis , Técnicas de Cultura , Dioxóis/isolamento & purificação , Ensaio de Imunoadsorção Enzimática , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Antígenos de Superfície da Hepatite B/biossíntese , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Antígenos E da Hepatite B/biossíntese , Antígenos E da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/crescimento & desenvolvimento , Vírus da Hepatite B/metabolismo , Humanos , Estrutura Molecular , Fitoterapia , Extratos Vegetais/química , Taninos/isolamento & purificação , Taninos/farmacologia
14.
FEMS Microbiol Lett ; 209(1): 63-7, 2002 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-12007655

RESUMO

Polysaccharides were extracted from fruiting bodies and cultured mycelia from five Antrodia camphorata strains. Polysaccharide profiles of the five strains, as determined by high-performance anion-exchange chromatography, showed varying yields and composition of neutral sugars. A. camphorata fruiting bodies also had different polysaccharide patterns compared to the cultured mycelium. Analysis of 26-day-old mycelia showed that the neutral sugars galactose, glucose, mannose, and galactosamine were predominant. All mycelia polysaccharide preparations exhibited anti-hepatitis B virus activity. Polysaccharides from strain B86 at a concentration of 50 microg ml(-1) showed the highest level of anti-hepatitis B surface antigen effect, which was higher than alpha-interferon at a dosage of 1000 U ml(-1). Only strains B86 and 35398 had substantial anti-hepatitis B e antigen activities. None of the polysaccharides exhibited cytotoxic effects.


Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Polyporales/química , Polissacarídeos/farmacologia , Antivirais/isolamento & purificação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos , Antígenos de Superfície da Hepatite B/análise , Humanos , Interferon alfa-2 , Interferon-alfa/farmacologia , Polissacarídeos/isolamento & purificação , Proteínas Recombinantes
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