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1.
Braz. arch. biol. technol ; 64: e21200163, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153296

ABSTRACT

HIGHLIGHTS Isolate, fractionate and characterize extracts obtained from soursop leaves. Use of emerging green technologies such as microwave-ultrasound hybridization. The extracts contain kaempferol, procyanidins, catechin, and quercetin. The total ethanolic extract demonstrates cytotoxic effect on HeLa cells.


Abstract Cervical cancer is classified as the fourth most common malignancy in women. Natural compounds are a therapeutic alternative in cancer therapy. The aim of the study is to isolate, fractionate, and characterize extracts obtained from soursop leaves (Annona muricata L.) and determine their cytotoxic effect against HeLa cervical cancer cells and non-carcinogenic fibroblast 3T3 cells. The phytochemicals of soursop leaves were extracted through emerging green technologies such as the novel use of microwave-ultrasound hybridization and the use of environmentally friendly solvents (water and ethanol), in addition to the purification of extracts enriched in polyphenols by liquid chromatography with Amberlite XAD-16. Total aqueous and ethanolic extract were purified, as well as the fraction one of each extract. The extracts recovered from soursop leaves contained kaempferol and its isomers, procyanidins, catechin, and quercetin. The viability of the cells was determined with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. HeLa and 3T3 cells were exposed to concentrations of 25, 50, 75, 100, 150, 200, and 250 ppm of a solution of soursop leaf extract powder. The MTT assay showed that soursop leaf extracts were toxic to both cell lines in general, however, the ethanolic extract at 25 and 50 ppm demonstrated inhibition in cell viability against the HeLa cancer line and low cytotoxicity for 3T3 fibroblast cells. In conclusion, the novel microwave-ultrasound hybridization technology allows the extraction of polyphenols that may have a potential cytotoxic effect on cancer cells.


Subject(s)
Humans , Female , HeLa Cells , Annona/chemistry , Polyphenols/isolation & purification , Phytochemicals/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Plant Extracts/pharmacology , Catechin/chemistry , Chromatography, Liquid/methods , Ethanol , Antineoplastic Agents, Phytogenic/pharmacology
2.
Biol. Res ; 52: 1, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011405

ABSTRACT

BACKGROUND: Ethnomedicinally, the family Polygonaceae is famous for the management of cancer. Various species of this family have been reported with anticancer potentials. This study was designed to isolate anticancer compounds from ethnomedicinally important species Polygonum barbatum. METHODS: The column chromatography was used for the isolation of compounds from the solvent fraction of P. barbatum. The characterization of isolated compounds was performed by various spectroscopic techniques like UV, IR, mass spectrometry and 1D-2D NMR spectroscopy. Keeping in view the ethnomedicinal importance of the family, genus and species of P barbatum, the isolated compounds (1-3) were screened for anticancer potentials against oral cancer (CAL-27) and lungs cancer (NCI H460) cell lines using MTT assay. Active compound was further investigated for apoptosis by using morphological changes and flow cytometry analysis. In vivo anti-angiogenic study of the isolated compounds was also carried using chorioallantoic membrane assay. Docking studies were carried out to explore the mechanism of anticancer activity. RESULTS: Three dihydrobenzofuran derivatives (1-3) have been isolated from the ethyl acetate fraction of P. barbatum. The structures of isolated compounds were elucidated as methyl (2S,3S)-2-(3,4-dimethoxyphenyl)-4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-7-methoxy-2,3-dihydrobenzo-furan-3-carboxylate (1), (E)-3-((2S,3S)-2-(3,4-dimethoxyphenyl)-7-methoxy-3-(methoxy carbonyl)-2,3-dihydrobenzofuran-4-yl)acrylic acid (2) and (2S,3 S)-4-((E)-2-carboxyvinyl)-2-(3,4-dimethoxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carboxylic acid (3). The compound 1 was found to be more potent with IC50 of 48.52 ± 0.95 and 53.24 ± 1.49 against oral cancer cells as compared to standard drug (IC50 = 97.76 ± 3.44 µM). Both compound also inhibited lung cancer cells but at higher concentrations. Morphological and flow cytometry analysis further confirms that compound 1 induces apoptosis after 24 to 48 h treatment. In antiangiogenesis assay, compounds 1, 2 and 3 exhibited IC50 values of 8.2 ± 1.1,13.4 ± 1.1 and 57.7 ± 0.3 µM respectively. The docking studies revealed that the compounds under study have the potential to target the DNA and thymidylate synthase (TS). CONCLUSION: Based on its overwhelming potency against the tested cell lines and in angiogenesis assay, compound 1 can be further evaluated mechanistically and can be developed as anticancer drug candidate.


Subject(s)
Humans , Benzofurans/pharmacology , Carcinoma, Squamous Cell/drug therapy , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Polygonum/chemistry , Cell Proliferation/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Benzofurans/isolation & purification , Benzofurans/chemistry , Carcinoma, Squamous Cell/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Polygonum/classification , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/isolation & purification
3.
Braz. j. med. biol. res ; 51(4): e6069, 2018. tab, graf
Article in English | LILACS | ID: biblio-889062

ABSTRACT

Melon (Cucumis melo L.) has high economic value and in recent years, its production has increased; however, part of the fruit is wasted. Usually, inedible parts such as peel and seeds are discarded during processing and consumption. Extracts of melon residues were prepared and their phenolic compounds, antioxidants and antiproliferative activities were evaluated. Total phenolic compounds were found in hydroethanolic, hydromethanolic, and aqueous extracts, especially for melon peel (1.016 mg gallic acid equivalent/100 g). Flavonoids total content found for melon peel aqueous extract was 262 µg of catechin equivalent (CA)/100 g. In all extracts of melon peel significant amounts of gallic acid, catechin, and eugenol were found. For total antioxidant capacity, reported as ascorbic acid equivalent, the hydroethanolic and hydromethanolic extracts in peels and hydromethanolic in seeds were 89, 74, and 83 mg/g, respectively. Different extracts of melon showed iron and copper ions chelating activity at different concentrations, especially melon peel aqueous extract, reaching values of 61% for iron and 84% for copper. The hydroethanolic extract of melon peel presented a significant ability for hydroxyl radicals scavenging (68%). To assess the antiproliferative potential in human cancer cell lines, such as kidney carcinoma, colorectal carcinoma, cervical adenocarcinoma and cervical carcinoma, MTT assay was performed. The proliferation was inhibited by 20-85% at extracts concentrations of 0.1-1.0 mg/mL in all cancer cell lines. The results suggest that melon residues extracts display a high antioxidant activity in in vitro assays and have effective biological activity against the growth of human tumor cells.


Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Cell Proliferation/drug effects , Cucurbitaceae/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/isolation & purification , Cell Line, Tumor , Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Flavonoids/isolation & purification , Flavonoids/pharmacology , Phenols/isolation & purification , Phenols/pharmacology , Seeds/chemistry , Tannins/isolation & purification , Tannins/pharmacology
4.
Braz. j. med. biol. res ; 51(4): e6891, 2018. graf
Article in English | LILACS | ID: biblio-889070

ABSTRACT

Gallbladder cancer (GBC) is the most common malignancy in the biliary tract. Without effective treatment, its prognosis is notoriously poor. Tea polyphenols (TPs) have many pharmacological and health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-thrombotic, antibacterial, and vasodilatory properties. However, the anti-cancer effect of TPs in human gallbladder cancer has not yet been determined. Cell viability and colony formation assay were used to investigate the cell growth. Cell cycle and apoptosis were evaluated by flow cytometry analysis. Western blot assay was used to detect the expression of proteins related to cell cycle and apoptosis. Human tumor xenografts were used to examine the effect of TPs on gallbladder cancer cells in vivo. TPs significantly inhibited cell growth of gallbladder cancer cell lines in a dose- and time-dependent manner. Cell cycle progression in GBC cells was blocked at the S phase by TPs. TPs also induced mitochondrial-related apoptosis in GBC cells by upregulating Bax, cleaved caspase-3, and cleaved PARP expressions and downregulating Bcl-2, cyclin A, and Cdk2 expressions. The effects of TPs on GBC were further proven in vivo in a mouse xenograft model. Our study is the first to report that TPs inhibit GBC cell growth and these compounds may have potential as novel therapeutic agents for treating gallbladder cancer.


Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Camellia sinensis/chemistry , Gallbladder Neoplasms/pathology , Polyphenols/pharmacology , S Phase/drug effects , Tea/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Gallbladder Neoplasms/drug therapy , Heterografts , Polyphenols/isolation & purification
5.
Braz. j. biol ; 75(1): 69-76, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-744335

ABSTRACT

The aim of this study was to evaluate the phenolic and flavonoids contents and the antioxidant and antitumoral activity of leaf and calyx methanolic extracts from Hibiscus sabdariffa (roselle) cultivated with poultry litter and organosuper® under three modes of application. The total phenolic content in the each extract was determined using the Folin-Ciocalteu reagent and for aluminium chloride flavonoids. The antioxidant parameters were analyzed using a 2, 2-diphenyl-1-picrylhydrazyl (DPPH.) free radical scavenging assay. An antitumor colorimetric assay using sulforhodamine B. The highest contents of phenolic and flavonoids were observed in leaf extracts (389.98 and 104.52 mg g–1, respectively) and calyx extracts (474.09 and 148.35 mg g–1, respectively) from plants cultivated with organosuper®, although these values did not differ significantly from those observed for the other treatments. The average IC50 of leaves (43.48 μg mL–1) and calyces (37.15 μg mL–1) demonstrated that both have substances that may contribute to free radical scavenging action. The methanol extract from calyces showed significant selective activity against a leukemia line (K-562), with IC50 values of 0.12 mg mL–1 (organosuper®) and 1.16 mg mL–1 (poultry litter), with concentration-dependent, cytotoxic and cytocidal effects.


O objetivo deste estudo foi avaliar a atividade antioxidante, antitumoral e o conteúdo de fenólicos e flavonoides do extrato metanólico das folhas e cálices de Hibiscus sabdariffa (rosela) cultivada com cama de frango e organosuper ® em três modos de aplicação. O conteúdo fenólico total de cada extrato foi determinado utilizando o reagente de Folin-Ciocalteu e cloreto de alumínio para flavonoides. Os parâmetros antioxidantes foram avaliados pelo ensaio de seqüestro de radical livre 2, 2-difenil-1-picrilhidrazil (DPPH.). Na avaliação antitumoral utilizou-se o ensaio colorimétrico com sulforrodamina B. Observou-se o maior conteúdo de fenólicos e flavonoides em extratos de folhas (389.98 e 104.52 mg g–1, respectivamente) e extratos de cálice (474.09 e 148.35 mg g–1, respectivamente) de plantas cultivadas com organosuper ®, embora esses valores não diferiram significativamente daqueles observados para os outros tratamentos. O IC50 de folhas (43.48 µg mL–1) e cálices (37.15 µg mL–1) demonstrou que ambos têm substâncias que podem contribuir para a ação seqüestradora de radicais livres. O extrato metanólico dos cálices mostrou seletividade na linhagem de leucemia (K-562), com valores de IC50 de 0,12 mg mL–1 (organosuper®) e 1,16 mg mL–1 (cama-de-frango) com concentração-dependente e efeito citotóxico e citocida.


Subject(s)
Humans , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Cell Proliferation/drug effects , Hibiscus/chemistry , Phenols/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Plant Leaves/chemistry
6.
Rev. paul. pediatr ; 33(1): 82-87, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-744697

ABSTRACT

OBJECTIVE: Investigate the relationship of the tumor volume after preoperative chemotherapy (TVAPQ) and before preoperative chemotherapy (TVBPQ) with overall survival at two and at five years, and lifetime. METHODS: Our sample consisted of consecutive patients evaluated in the period from 1989 to 2009 in an Onco-Hematology Service. Clinical, histological and volumetric data were collected from the medical records. For analysis, chi-square, Kaplan-Meier, log-rank and Cox regression tests were used. RESULTS: The sample consisted of 32 patients, 53.1% were male with a median age at diagnosis of 43 months. There was a significant association between TVAPQ>500mL and the difference between the TVBPQ and TVAPQ (p=0.015) and histologic types of risk (p=0.008). It was also verified an association between the difference between the TVBPQ and TVAPQ and the predominant stromal tumor (p=0.037). When assessing the TVAPQ of all patients, without a cutoff, there was an association of the variable with lifetime (p=0.013), i.e., for each increase of 10mL in TVAPQ there was an average increase of 2% in the risk of death. CONCLUSIONS: Although our results indicate that the TVAPQ could be considered alone as a predictor of poor prognosis regardless of the cutoff suggested in the literature, more studies are needed to replace the histology and staging by tumor size as best prognostic variable. .


OBJETIVO: Investigar a relação entre o volume do tumor após a quimioterapia pré-operatória (VTPOS) e antes da quimioterapia pré-operatória (VTPRE) com sobrevida geral aos dois e cinco anos e tempo de vida. MÉTODOS: A amostra foi composta por pacientes consecutivos avaliados de 1989 a 2009, em um serviço de onco-hematologia. Os dados clínicos, histológicos e volumétricos foram coletados a partir dos registros médicos. Para análise, usaram-se os testes qui-quadrado, Kaplan-Meier, log-rank e regressão de Cox. RESULTADOS: A amostra foi composta de 32 pacientes, 53,1% do sexo masculino, com mediana de idade ao diagnóstico de 43 meses. Houve associação significativa entre VTPOS >500 mL e a diferença entre o VTPRE e VTPOS (p=0,015) e os tipos histológicos de risco (p=0,008). Verificou-se também uma associação entre a diferença entre o VTPRE e VTPOS e o tumor de predomínio estromal (p=0,037). Quando se avaliou o VTPOS de todos os pacientes, sem um ponto de corte definido, observou-se associação dessa variável com o tempo de vida (p=0,013), isto é, para cada aumento de 10 mL no VTPOS houve um aumento médio de 2% no risco de morte. CONCLUSÕES: Embora os resultados indiquem que o VTPOS poderia ser considerado um preditor isolado de mau prognóstico, independentemente do ponto de corte sugerido na literatura, mais estudos são necessários para substituir a histologia e estadiamento pelo tamanho do tumor como melhor variável prognóstica. .


Subject(s)
Animals , Humans , Mice , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Macrocyclic Compounds/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Diterpenes/chemistry , Diterpenes/isolation & purification , Euphorbia/chemistry , Molecular Conformation , Macrocyclic Compounds/chemistry , Macrocyclic Compounds/isolation & purification , Phenotype , Structure-Activity Relationship , Tumor Cells, Cultured
7.
Mem. Inst. Oswaldo Cruz ; 110(1): 1-22, 03/02/2015. tab, graf
Article in English | LILACS | ID: lil-741625

ABSTRACT

An increasingly asked question is 'can we confidently link bats with emerging viruses?'. No, or not yet, is the qualified answer based on the evidence available. Although more than 200 viruses - some of them deadly zoonotic viruses - have been isolated from or otherwise detected in bats, the supposed connections between bats, bat viruses and human diseases have been raised more on speculation than on evidence supporting their direct or indirect roles in the epidemiology of diseases (except for rabies). However, we are convinced that the evidence points in that direction and that at some point it will be proved that bats are competent hosts for at least a few zoonotic viruses. In this review, we cover aspects of bat biology, ecology and evolution that might be relevant in medical investigations and we provide a historical synthesis of some disease outbreaks causally linked to bats. We provide evolutionary-based hypotheses to tentatively explain the viral transmission route through mammalian intermediate hosts and to explain the geographic concentration of most outbreaks, but both are no more than speculations that still require formal assessment.


Subject(s)
Animals , Humans , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/isolation & purification , Fatty Acids/analysis , Industrial Waste/analysis , Malus/chemistry , Plant Oils/isolation & purification , Seeds/chemistry , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/economics , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/adverse effects , Antioxidants/economics , Antioxidants/pharmacology , Cell Line, Tumor , Chemical Phenomena , CHO Cells , Cricetulus , Cell Proliferation/drug effects , Dietary Supplements/adverse effects , Dietary Supplements/economics , Fatty Acids, Nonesterified/adverse effects , Fatty Acids, Nonesterified/analysis , Fatty Acids, Nonesterified/economics , Fatty Acids/adverse effects , Fatty Acids/economics , Food Preservatives/adverse effects , Food Preservatives/economics , Food Preservatives/isolation & purification , Food Preservatives/pharmacology , Food-Processing Industry/economics , Fruit/chemistry , Fruit/economics , India , Industrial Waste/economics , Linoleic Acid/adverse effects , Linoleic Acid/analysis , Linoleic Acid/economics , Oleic Acid/adverse effects , Oleic Acid/analysis , Oleic Acid/economics , Plant Oils/chemistry , Plant Oils/economics , Plant Oils/pharmacology
8.
Biol. Res ; 48: 1-9, 2015. ilus, graf
Article in English | LILACS | ID: lil-734614

ABSTRACT

BACKGROUND: Curcuma longa Linnaeus and Zingiber officinale Roscoe are two main representatives ofZingiberaceae family studied for a wide range of therapeutic properties, including: antioxidant, anti-inflammatory, anti-angiogenic, antibacterial, analgesic, immunomodulatory, proapoptotic, anti-human immunodeficiency virus properties and anticancer effects. This study was aimed to analyse the ethanolic extracts of Curcuma rhizome (Curcuma longa Linnaeus) and Zingiber rhizome (Zingiber officinale Roscoe) in terms of polyphenols, antioxidant activity and anti-melanoma potential employing the B164A5 murine melanoma cell line. RESULTS: In order to evaluate the total content of polyphenols we used Folin-Ciocâlteu method. The antioxidant activity of the two ethanolic extracts was determined by DPPH assay, and for the control of antiproliferative effect it was used MTT proliferation assay, DAPI staining and Annexin-FITC-7AAD double staining test. Results showed increased polyphenols amount and antioxidant activity forCurcuma rhizome ethanolic extract. Moreover, 100 μg/ml of ethanolic plant extract from both vegetal products presented in a different manner an antiproliferative, respectively a proapoptotic effect on the selected cell line. CONCLUSIONS: The study concludes that Curcuma rhizome may be a promising natural source for active compounds against malignant melanoma.


Subject(s)
Animals , Antineoplastic Agents, Phytogenic/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Melanoma, Experimental/drug therapy , Plant Extracts/pharmacology , Polyphenols/analysis , Zingiberaceae/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antioxidants/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Curcuma/chemistry , Curcuma/classification , Ginger/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Polyphenols/classification , Rhizome/chemistry
9.
Biol. Res ; 47: 1-5, 2014. ilus, graf, tab
Article in English | LILACS | ID: biblio-950716

ABSTRACT

BACKGROUND: This study evaluated the cytotoxic activity of extracts from Caesalpinia sappan heartwood against multiple cancer cell lines using an MTT cell viability assay. The cell death though induction of apoptosis was as indicated by DNA fragmentation and caspase-3 enzyme activation. RESULTS: A methanol extract from C. sappan (MECS) showed cytotoxic activity against several of the cancer cell lines. The most potent activity exhibited by the MECS was against HeLa cells with an IC50 value of 26.5 ± 3.2 µg/mL. Treatment of HeLa cells with various MECS concentrations resulted in growth inhibition and induction of apoptosis, as indicated by DNA fragmentation and caspase-3 enzyme activation. CONCLUSION: This study is the first report of the anticancer properties of the heartwood of C. sappan native to Vietnam. Our findings demonstrate that C. sappan heartwood may have beneficial applications in the field of anticancer drug discovery.


Subject(s)
Humans , Animals , Female , Mice , Plant Extracts/pharmacology , Apoptosis , Caesalpinia/chemistry , Plant Vascular Bundle/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Tetrazolium Salts , Vietnam , Drug Screening Assays, Antitumor/methods , HeLa Cells , Cell Survival , Inhibitory Concentration 50 , Cytotoxins/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Methanol , Enzyme Activation/drug effects , Caspase 3/metabolism , DNA Fragmentation , Formazans , Growth Inhibitors/pharmacology , Indicators and Reagents , Mice, Inbred C57BL , Antineoplastic Agents, Phytogenic/isolation & purification
10.
Acta cir. bras ; 29(supl.2): 21-28, 2014. graf
Article in English | LILACS | ID: lil-721376

ABSTRACT

PURPOSE: To characterize the anatomy of the fruit and leaf and the presence of phytocompounds. To evaluate the antitumor and antimicrobial activity of ethanolic extract of Garcinia mangostana L. (mangosteen) cultivated in southeastern Brazil. METHODS: Anatomical characterization and histochemical reactions were performed for structural identification and the presence of phytocompounds. Preparation of ethanolic extract of the fruit, leaf and resin of mangosteen. Culture B16-F10 melanoma cells for treatment with mangosteen ethanolic extract to determine cell viability by MTT and genotoxic effect by comet assay. Evaluation by antimicrobial activity against Staphylococcus aureus and Escherichia coli by agar diffusion test and by determination of Minimum Inhibitory Concentration (MIC). RESULTS: Our results showed many secretory canals in resin fruit and leaf; identifying lipids, starch, lignin and phenolic compounds. The leaf extract induced genotoxicity and apoptosis in B16-F10 cells, since the fragmentation of DNA in the comet assay. The ethanolic extract of mangosteen obtained in the resin, leaf and fruit showed antimicrobial activity against Staphylococcus aureus and Escherichia coli with a MIC at 0.1 mg/mL. CONCLUSION: In conclusion, we have demonstrated both antimicrobial and antitumor activity of ethanol extract of mangosteen emphasizing its therapeutic potential in infectious diseases and in cancer, such as melanoma. .


Subject(s)
Animals , Mice , Anti-Infective Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Garcinia mangostana/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Brazil , Cell Line, Tumor , Comet Assay , Cell Survival/drug effects , Enzyme-Linked Immunosorbent Assay , Fruit/chemistry , Microbial Sensitivity Tests , Melanoma/drug therapy , Reproducibility of Results , Staphylococcus aureus/drug effects , Time Factors
11.
Acta cir. bras ; 29(supl.2): 10-14, 2014. graf
Article in English | LILACS | ID: lil-721384

ABSTRACT

PURPOSE: To evaluate the antitumor and antimicrobial activity of ethanolic extract of Morinda citrifolia L. fruit cultivated in southeastern Brazil. METHODS: Preparation ethanolic extract of the fruit of Morinda citrifolia L. Culture of melanoma cells B16-F10 for treatment with ethanolic extract of Morinda citrifolia L. fruit to determine cell viability by MTT and determination temporal effect of ethanolic extract fruit on the cell growth B16-F10 for 8 days. Evaluation of antimicrobial activity of ethanolic extract fruit against Staphylococcus aureus and Escherichia coli by determination of Minimum Inhibitory Concentration (MIC). RESULTS: The ethanolic extract of Morinda citrifolia L. fruit (10mg/mL) decreased cellular activity and inhibited 45% the rate of cell proliferation of B16-F10 melanoma treated during period studied. The ethanolic extract of Morinda citrifolia L. fruit demonstrated antimicrobial activity inhibiting the growth of both microorganisms studied. Staphylococcus aureus was less resistant to ethanolic extract of Morinda citrifolia L. fruit than Escherichia coli, 1 mg/mL and 10 mg/mL, respectively. CONCLUSION: What these results indicate that the ethanolic extract of the fruit of Morinda citrifolia L. showed antitumor activity with inhibition of viability and growth of B16-F10 cells and also showed antibacterial activity as induced inhibition of growth of Staphylococcus aureus and Escherichia coli. .


Subject(s)
Animals , Mice , Anti-Infective Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Morinda/chemistry , Plant Extracts/pharmacology , Analysis of Variance , Anti-Infective Agents/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Brazil , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor/methods , Enzyme-Linked Immunosorbent Assay , Ethanol , Escherichia coli/drug effects , Fruit/chemistry , Microbial Sensitivity Tests , Melanoma/drug therapy , Reproducibility of Results , Staphylococcus aureus/drug effects , Time Factors
12.
Rev. méd. Chile ; 141(9): 1150-1157, set. 2013. ilus, graf, tab
Article in Spanish | LILACS | ID: lil-699682

ABSTRACT

Background: The rainforest is an important source of natural compounds with therapeutic properties. Although there are many anti-inflammatory and antineoplastic drugs available to the clinician, there is an ongoing need for new therapeutic drugs with fewer serious adverse effects. Aim: To evaluate the in vitro cytotoxic effects of lupeol and casearin G on tumor cells, on phagocytic activity and nitric oxide (NO) production by blood mononuclear cells. Material and Methods: The cytotoxic effect of these compounds on cell lines MCF-7 (human breast adenocarcinoma) and PC-3 (human prostate cancer) was measured by a colorimetric assay (MTS/PMS) and the sulphorhodamine B assay. Peripheral blood mononuclear cells were obtained from eight healthy volunteers. The effect of these compounds on nitric oxide (NO) production was measured using the Griess reaction. Their effect on phagocytic activity of PBMC was also evaluated. Results: Lupeol (≥ 2 mM) resulted in a reduction of both the phagocytic index and the percentage of phagocytic monocytes and macrophages. Treatment of monocytes/macrophages with lupeol (72 µM) and casearin G (4 µM) reduced the production of NO. Neither lupeol (< 969 µM) nor casearin G (< 55 µM) had cytotoxic effects on PBMC. Casearin G showed both cytotoxic (IC50, LC50) and cytostatic (GI50) effects against tumor cells, PC-3 (IC50 = 12.5 µM; GI50 = 13.3 µM; LC50 = 51.9 µM) and MCF-7 (IC50 = 112.8 µM; GI50 = 11.8 µM; LC50 = 49.4 µM), as well as a hemolytic effect (≥ 182 µM). Conclusions: These observations indicate that lupeol and casearin G might be useful compounds in the preparation of anti-inflammatory drugs, whereas casearin G might be useful in the elaboration of antitumor drugs.


Subject(s)
Humans , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Leukocytes, Mononuclear/drug effects , Nitric Oxide/biosynthesis , Pentacyclic Triterpenes/pharmacology , Phagocytosis/drug effects , Antineoplastic Agents, Phytogenic/isolation & purification , Casearia/chemistry , Cell Line, Tumor/drug effects , Drug Screening Assays, Antitumor , Diterpenes/isolation & purification , Pentacyclic Triterpenes/isolation & purification , Zanthoxylum/chemistry
13.
An. acad. bras. ciênc ; 83(4): 1373-1384, Dec. 2011. ilus, tab
Article in English | LILACS | ID: lil-607443

ABSTRACT

Folk uses and scientific investigations have highlighted the importance of Casearia sylvestris extracts and their relevant bioactive potential. The aim of this work was to review the pharmacological properties of C. sylvestris, emphasizing its anti-ulcer, anti-inflammatory, anti-ophidian and antitumor potentialities. Ethanolic extracts and essential oil of their leaves have antiulcerogenic activity and reduce gastric volume without altering the stomach pH, which corroborates their consumption on gastrointestinal disorders. Leaf water extracts show phospholipase A2 inhibitory activity that prevents damage effects on the muscular tissue after toxin inoculation. This antiphospholipasic action is probably related to the use as an anti-inflammatory, proposing a pharmacological blockage similar to that obtained with non-steroidal anti-inflammatory drugs on arachidonic acid and cyclooxygenase pathways. Bioguided-assay fractionations lead to the identification of secondary metabolites, especially the clerodane diterpenes casearins (A-X) and casearvestrins (A-C), compounds with a remarkable cytotoxic and antitumor action. Therefore, the C. sylvestris shrub holds a known worldwide pharmacological arsenal by its extensive folk utilization, exciting searches for new molecules and a better comprehension about biological properties.


Usos populares e pesquisas científicas têm destacado a importância dos extratos da planta Casearia sylvestris e seu grande potencial bioativo. Neste trabalho, objetiva-se revisar as propriedades farmacológicas de C. sylvestris, enfatizando sua potencialidade antiulcerogênica, antiinflamatória, antiofídica e antitumoral. O extrato etanólico e o óleo essencial das folhas possuem atividade antiulcerogênica promissora, diminuindo o volume gástrico sem alterar o pH estomacal, corroborando sua aplicação contra dores gastrointestinais. Já os extratos aquosos das folhas têm atividade inibitória contra fosfolipase A2 presente em venenos de cobras, atenuando os efeitos lesivos sobre a musculatura esquelética resultantes da inoculação das toxinas. Essa ação antifosfolipásica provavelmente está relacionada ao seu uso como antiinflamatório, sugerindo um bloqueio análogo ao dos fármacos antiinflamatórios não-esteroidais na formação de mediadores oriundos do ácido araquidônico e na ativação da ciclooxigenase. Ensaios de fracionamento bioguiado dos extratos culminaram no isolamento e identificação de inúmeros metabólitos secundários, especialmente os diterpenos clerodânicos casearinas (A-X) e casearvestrinas (AC), compostos que têm surpreendido por sua ação citotóxica e antitumoral. Assim, a planta C. sylvestris apresenta um enorme arsenal farmacológico já mundialmente comprovado por seu vasto uso popular, estimulando pesquisas por novas moléculas e a busca pela compreensão de suas propriedades biológicas.


Subject(s)
Animals , Humans , Anti-Inflammatory Agents/pharmacology , Anti-Ulcer Agents/pharmacology , Antidotes/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Casearia/chemistry , Plant Extracts/pharmacology , Plant Oils/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Ulcer Agents/chemistry , Anti-Ulcer Agents/isolation & purification , Antidotes/chemistry , Antidotes/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Medicine, Traditional , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Oils/chemistry
14.
Biocell ; 34(3): 139-143, Dec. 2010. graf
Article in English | LILACS | ID: lil-595009

ABSTRACT

Camptothecin and its derivatives are monoterpenoid indole alkaloids exhibiting significant anti-tumor actions. With the aim of improving the production of these pharmaceuticals, the contents of camptothecin and 10-hydroxycamptothecin in different tissues including roots, stems, leaves, young flower buds, opening flowers, fading flowers and seeds from Camptotheca acuminata, were investigated. The young flower buds had the highest alkaloid concentrations (camptothecin, 2.46 mg/g of dry weight; 10-hydroxycamptothecin, 1.41 mg/g of dry weight). Callus showed lower concentrations but it should also be considered as a potential source of these pharmaceuticals. In the present study, the growth rate of Camptotheca acuminata cells in culture did not correlate with contents of camptothecin and 10-hydroxycamptothecin. Alkalo id accumulation by cells under various treatments (heavy metal ions, UV-B), methyl-jasmonate, abscisic acid, salicylic acid and hydrogen peroxide was examined, and the most notable effects appeared in the cells induced by UV-B light (which showed an 11-fold increase in camptothecin concentration) and by salicylic acid (which showed a 25-fold increase in 10-hydroxycamptothecin concentration). These results are significant in the context of the production of both pharmaceuticals.


Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Alkaloids/isolation & purification , Camptothecin/analogs & derivatives , Camptothecin/isolation & purification , Camptotheca/cytology , Camptotheca/growth & development , Camptotheca/chemistry , Culture Media , Drugs, Chinese Herbal/isolation & purification , Cell Culture Techniques/methods
15.
An. acad. bras. ciênc ; 80(3): 467-476, Sept. 2008. ilus, tab
Article in English | LILACS | ID: lil-491827

ABSTRACT

Plant-derived substances have been considered as important sources of drugs, including antineoplasic agents. Babassu mesocarp is popularly used in Brazil as a food additive, and in popular medicine against several conditions, such as inflammations, menstrual pains and leukaemia. From babassu Orbignya speciosa (Mart.) Barb. Rodr. [Arecaceae (Palmae)] epicarp/mesocarp, an ethanol extract was prepared and named OSEME, which was tested on the viability,morphology and metabolism of several cell lines, such as the leukaemic cell lines, HL-60, K562 and the latter multidrug resistant counterpart K562-Lucena 1, the human breast cancer cell line MCF-7, the mouse fibroblast cell line 3T3-L1 and fresh human lymphocytes. OSEME promoted a dose-dependent decrease on the viability of all cells. This effect was much more pronounced on the tumoral cell lines than on non-tumoral cells, a phenomenon revealed by the dose of OSEME which promotes half of maximal effect (ID50). The decrease on viability was followed by shrinkage of cells, alteration on their morphology, and a markedly nuclear condensation. Curiously, stimulation of 6-phosphofructokinase activity (6.6-times) was observed on HL-60 cells, treated with OSEME, when compared to control treated with ethanol (vehicle). These results support evidences to suggest OSEME as a promising source of novel antineoplasic agents.


Substâncias derivadas de plantas têm sido usadas como importante fonte de agentes antineoplásicos. O mesocarpo do babaçu é popularmente usado no Brasil como suplemento alimentar e na medicina popular para o tratamento de várias afecções, tais como: inflamações, cólicas menstruais e leucemia. A partir do epicarpo/mesocarpo do babaçu Orbignya speciosa (Mart.) Barb. Rodr. [Arecaceae (Palmae)] foi preparado um extrato etanólico, denominado OSEME, o qual foi incubado com as seguintes linhagens humanas leucêmicas: HL-60, K562 e a sua derivada resistente a múltiplas drogas, K562-Lucena 1; além destas, foram testadas a linhagem humana de câncer de mama, MCF-7; a linhagem de fibroblastos de camundongo, 3T3-L1 e linfócitos humanos de sangue periférico. OSEME promoveu diminuição da viabilidade em todas as linhagens celulares testadas de maneira dose-dependente. Este efeito foi mais pronunciado sobre as linhagens celulares tumorais quando comparado às não tumorais, o que foi revelado pela dose de OSEME capaz de promover metade do efeito máximo (ID50). A diminuição da viabilidade foi acompanhada por danos sobre a morfologia celular com pronunciada condensação citoplasmática e nuclear. Curiosamente, quando a linhagem HL-60 foi tratada com OSEME, foi detectado um aumento de 6,6 vezes da atividade da enzima 6-fosfofrutoquinase, quando comparado ao grupo controle (células tratadas com o veículo etanol). Esses resultados sugerem que OSEME pode ser uma promissora fonte de novos agentes antineoplásicos.


Subject(s)
Adult , Animals , Humans , Mice , Young Adult , Antineoplastic Agents, Phytogenic/pharmacology , Arecaceae/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor/drug effects , Cell Line/drug effects , Drug Screening Assays, Antitumor , Ethanol/pharmacology , Time Factors , Young Adult
16.
Braz. j. med. biol. res ; 40(11): 1537-1544, Nov. 2007. graf, tab
Article in English | LILACS | ID: lil-464308

ABSTRACT

The anti-tumor effect of the Moroccan endemic thyme (Thymus broussonettii) essential oil (EOT) was investigated in vitro using the human ovarian adenocarcinoma IGR-OV1 parental cell line OV1/P and its chemoresistant counterparts OV1/adriamycin (OV1/ADR), OV1/vincristine (OV1/VCR), and OV1/cisplatin (OV1/CDDP). All of these cell lines elicited various degrees of sensitivity to the cytotoxic effect of EOT. The IC50 values (mean ± SEM, v/v) were 0.40 ± 0.02, 0.39 ± 0.02, 0.94 ± 0.05, and 0.65 ± 0.03 percent for OV1/P, OV1/ADR, OV1/VCR, and OV1/CDDP, respectively. Using the DBA-2/P815 (H2d) mouse model, tumors were developed by subcutaneous grafting of tumor fragments of similar size obtained from P815 (murin mastocytoma cell line) injected in donor mouse. Interestingly, intra-tumoral injection of EOT significantly reduced solid tumor development. Indeed, by the 30th day of repeated EOT treatment, the tumor volumes of the animals were 2.00 ± 0.27, 1.35 ± 0.20, and 0.85 ± 0.18 cm³ after injection with 10, 30, or 50 æL per 72 h (six times), respectively, as opposed to 3.88 ± 0.50 cm³ for the control animals. This tumoricidal effect was associated with a marked decrease of mouse mortality. In fact, in these groups of mice, the recorded mortality by the 30th day of treatment was 30 ± 4, 18 ± 4, and 8 ± 3 percent, respectively, while the control animals showed 75 ± 10 percent of mortality. These data indicate that the EOT which contains carvacrol as the major component has an important in vitro cytotoxic activity against tumor cells resistant to chemotherapy as well as a significant antitumor effect in mice. However, our data do not distinguish between carvacrol and the other components of EOT as the active factor.


Subject(s)
Animals , Female , Humans , Mice , Adenocarcinoma/drug therapy , Antineoplastic Agents, Phytogenic/pharmacology , Ovarian Neoplasms/drug therapy , Plant Oils/pharmacology , Thymus Plant/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor/drug effects , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Plant Oils/isolation & purification
17.
Braz. j. med. biol. res ; 40(6): 839-847, June 2007. graf, tab
Article in English | LILACS | ID: lil-452676

ABSTRACT

The objective of the present study was to evaluate the in vitro and in vivo anti-cancer effect of Nigella sativa L. seed extracts. The essential oil (IC50 = 0.6 percent, v/v) and ethyl acetate (IC50 = 0.75 percent) extracts were more cytotoxic against the P815 cell line than the butanol extract (IC50 = 2 percent). Similar results were obtained with the Vero cell line. Although all extracts had a comparable cytotoxic effect against the ICO1 cell line, with IC50 values ranging from 0.2 to 0.26 percent (v/v), tests on the BSR cell line revealed a high cytotoxic effect of the ethyl acetate extract (IC50 = 0.2 percent) compared to the essential oil (IC50 = 1.2 percent). These data show that the cytotoxicity of each extract depends on the tumor cell type. In vivo, using the DBA2/P815 (H2d) mouse model, our results clearly showed that the injection of the essential oil into the tumor site significantly inhibited solid tumor development. Indeed, on the 30th day of treatment, the tumor volume of the control animals was 2.5 ± 0.6 cm³, whereas the tumor volumes of the essential oil-treated animals were 0.22 ± 0.1 and 0.16 ± 0.1 cm³ when the animals were injected with 30 µL (28.5 mg)/mouse and 50 µL (47.5 mg)/mouse per 48 h (six times), respectively. Interestingly, the administration of the essential oil into the tumor site inhibited the incidence of liver metastasis development and improved mouse survival.


Subject(s)
Animals , Mice , Antineoplastic Agents, Phytogenic/pharmacology , Neoplasms, Experimental/drug therapy , Nigella sativa/chemistry , Oils, Volatile/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Chlorocebus aethiops , Cell Line, Tumor/drug effects , Drug Screening Assays, Antitumor , Mice, Inbred DBA , Neoplasm Transplantation , Oils, Volatile/isolation & purification , Plant Extracts/pharmacology , Vero Cells
18.
Braz. j. med. biol. res ; 39(11): 1483-1491, Nov. 2006. ilus, graf
Article in English | LILACS | ID: lil-437834

ABSTRACT

Vernonia scorpioides has been widely used in Brazil to treat skin problems and chronic wounds, such as ulcers of the lower limbs and diabetic lesions. In the present study, we investigated the effect of a dichloromethane (DCM) fraction of V. scorpioides leaf extract on Ehrlich ascitic and solid tumor-bearing mice. The animals were treated once a day with the DCM fraction at a concentration of 5 mg/kg, administered ip during and after the development of the tumor. The lifespan, weight, number and type of leukocytes, number of tumor cells, volume of solid and ascitic tumors were measured. The development of the tumor with pre-treated tumor cells in vitro with the DCM fraction (5 mg/kg) was analyzed and the animals were sacrificed after 7 days. The DCM fraction (5 mg/kg) totally inhibited tumor development when in direct contact with tumor cells, and also ascitic tumor development with in vitro treatment or when administered ip, in loco (after 7 days). Animals treated with the DCM fraction increased their lifespan ca. 2 weeks and maintained their body weight for 30 days. When applied immediately after the inoculation of the tumor cells in vivo, it totally abolished tumor development, with tumor development only decreasing when treatment was started 3 days after the tumor challenge. These data suggest an antineoplastic activity of the fraction. Oral or ip administration of DCM fraction (5 mg/kg) for 7 days did not reduce the solid tumor volume. The cytotoxic activity described here differs from the conventional immune suppressing profile of standard chemotherapy because it increases neutrophil influx to the peritoneal cavity. These results show that, besides exhibiting a tumoricidal activity, the DCM fraction also exhibits inflammatory activity.


Subject(s)
Animals , Male , Mice , Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Ehrlich Tumor/drug therapy , Methylene Chloride/pharmacology , Plant Leaves/chemistry , Vernonia/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Drug Screening Assays, Antitumor , Injections, Intraperitoneal , Methylene Chloride/isolation & purification , Plant Extracts/pharmacology
19.
Braz. j. med. biol. res ; 39(6): 731-738, June 2006. ilus, tab
Article in English | LILACS | ID: lil-428280

ABSTRACT

The cytotoxicity of three extracts (petroleum ether, ethyl acetate and n-butanol) from a plant used in folk medicine, Marchantia convoluta, to human non-small cell lung carcinoma (H1299) and liver carcinoma (HepG2) cell lines was tested. After 72-h incubation of lung and liver cancer cell cultures with varying concentrations of extracts (15 to 200 æg/mL), cytotoxicity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and reported in terms of cell viability. The extracts that showed a significant cytotoxicity were subjected to gas chromatography-mass spectrometry analysis to identify the components. The ethyl acetate, but not the petroleum ether or n-butanol extract, had a significant cytotoxicity against lung and liver carcinoma cells with IC50 values of 100 and 30 æg/mL, respectively. A high concentration of ethyl acetate extract (100 æg/mL) rapidly reduced the number of H1299 cells. At lower concentrations of ethyl acetate extract (15, 30, and 40 æg/mL), the numbers of HepG2 cells started to decrease markedly. Gas chromatography-mass spectrometry analysis of the ethyl acetate extract revealed the presence of several compounds such as phytol (23.42 percent), 1,2,4-tripropylbenzene (13.09 percent), 9-cedranone (12.75 percent), ledene oxide (7.22 percent), caryophyllene (1.82 percent), and caryophyllene oxide (1.15 percent). HPLC analysis result showed that there were no flavonoids in ethyl acetate extract, but flavonoids are abundant in n-butanol extract. Further studies are needed regarding the identification, toxicity, and mechanism of action of active compounds.


Subject(s)
Humans , Antineoplastic Agents, Phytogenic/therapeutic use , Liver Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Marchantia/chemistry , Plant Leaves/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Chromatography, High Pressure Liquid , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Gas Chromatography-Mass Spectrometry , Liver Neoplasms/pathology , Lung Neoplasms/pathology , Plant Extracts/therapeutic use , Tumor Cells, Cultured
20.
Braz. j. med. biol. res ; 39(6): 801-807, June 2006. ilus, tab
Article in English | LILACS | ID: lil-428281

ABSTRACT

Piplartine {5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-2(1H)pyridinone} and piperine {1-5-(1,3)-benzodioxol-5-yl)-1-oxo-2,4-pentadienyl]piperidine} are alkaloid amides isolated from Piper. Both have been reported to show cytotoxic activity towards several tumor cell lines. In the present study, the in vivo antitumor activity of these compounds was evaluated in 60 female Swiss mice (N = 10 per group) transplanted with Sarcoma 180. Histopathological and morphological analyses of the tumor and the organs, including liver, spleen, and kidney, were performed in order to evaluate the toxicological aspects of the treatment with these amides. Administration of piplartine or piperine (50 or 100 mg kg-1 day-1 intraperitoneally for 7 days starting 1 day after inoculation) inhibited solid tumor development in mice transplanted with Sarcoma 180 cells. The inhibition rates were 28.7 and 52.3 percent for piplartine and 55.1 and 56.8 percent for piperine, after 7 days of treatment, at the lower and higher doses, respectively. The antitumor activity of piplartine was related to inhibition of the tumor proliferation rate, as observed by reduction of Ki67 staining, a nuclear antigen associated with G1, S, G2, and M cell cycle phases, in tumors from treated animals. However, piperine did not inhibit cell proliferation as observed in Ki67 immunohistochemical analysis. Histopathological analysis of liver and kidney showed that both organs were reversibly affected by piplartine and piperine treatment, but in a different way. Piperine was more toxic to the liver, leading to ballooning degeneration of hepatocytes, accompanied by microvesicular steatosis in some areas, than piplartine which, in turn, was more toxic to the kidney, leading to discrete hydropic changes of the proximal tubular and glomerular epithelium and tubular hemorrhage in treated animals.


Subject(s)
Animals , Female , Mice , Alkaloids/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Benzodioxoles/therapeutic use , Piper/chemistry , Piperidines/therapeutic use , Piperidones/therapeutic use , Polyunsaturated Alkamides/therapeutic use , /drug therapy , Alkaloids/isolation & purification , Alkaloids/toxicity , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/toxicity , Benzodioxoles/isolation & purification , Benzodioxoles/toxicity , Cell Proliferation/drug effects , Disease Models, Animal , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Neoplasm Transplantation , Piperidines/isolation & purification , Piperidines/toxicity , Piperidones/isolation & purification , Piperidones/toxicity , Plant Extracts/isolation & purification , Plant Extracts/therapeutic use , Plant Extracts/toxicity , Plant Roots/chemistry , Polyunsaturated Alkamides/isolation & purification , Polyunsaturated Alkamides/toxicity , /pathology , Spleen/drug effects , Spleen/pathology
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