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1.
Pharm Biol ; 54(9): 1564-74, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26878464

RESUMO

Context Considering the role of cellular oxidative stress in mutations and subsequent transformation, phytochemicals with antioxidant potential has become a primary choice as chemopreventives. Apodytes dimidiata E. Mey. Ex. Arn (Icacinaceae), a widely used plant in Zulu traditional medicine, is reported to possess antioxidant activity. Objective To investigate the chemopreventive efficacy of methanol extract of A. dimidiata leaf (AMF). Materials and methods Antimutagenic potential of AMF (25, 50 and 75 µg/plate) was evaluated by the Ames test. The ability of AMF (100 and 250 mg/kg orally) on restoration of depleted antioxidant status by sodium fluoride (NaF) was analysed on BALB/c mice. 7,12-Dimethylbenz[a]anthracene/croton oil induced mouse skin papilloma model was studied up to 20 weeks to analyse the anticarcinogenic effect of AMF (1%, 3% and 5% topically, twice weekly for 6 weeks). Phytochemicals of AMF were characterized by GC-MS. Results AMF (75 µg/plate) reverted 4-nitro-o-phenylenediamine (NPDA) induced mutations in Salmonella typhimurium strains, TA 98, 100 and 102 by 74.8%, 72.5% and 69.3%, respectively. Against sodium azide, the percentage reversion was 80.4, 71.3 and 71.3. In mice, AMF (250 mg/kg for 4 days) increased the serum superoxide dismutase (SOD) and catalase activities by 48.71% and 30.3% against the NaF-induced drop. GSH level was improved by 48.59% with a concomitant decrease in TBARS (57.67%). The skin papilloma reduction was 79.32% for 5% AMF. Squalene, dodecanoic, tetradecanoic and hexadecanoic acids are the known antioxidant and chemopreventive molecules identified by GC-MS. Discussion and conclusion Antioxidant and antimutagenic activities of AMF might have contributed to its anticarcinogenic potential.


Assuntos
9,10-Dimetil-1,2-benzantraceno , Antimutagênicos/farmacologia , Antioxidantes/farmacologia , Transformação Celular Neoplásica/efeitos dos fármacos , Óleo de Cróton , Magnoliopsida , Papiloma/prevenção & controle , Extratos Vegetais/farmacologia , Neoplasias Cutâneas/prevenção & controle , Animais , Anticarcinógenos/isolamento & purificação , Anticarcinógenos/farmacologia , Antimutagênicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Catalase/metabolismo , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas , Glutationa/metabolismo , Magnoliopsida/química , Masculino , Metanol/química , Camundongos Endogâmicos BALB C , Mutação/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Papiloma/induzido quimicamente , Papiloma/genética , Papiloma/metabolismo , Fitoterapia , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Plantas Medicinais , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Fluoreto de Sódio/farmacologia , Solventes/química , Superóxido Dismutase/metabolismo , Fatores de Tempo
2.
Planta Med ; 81(18): 1705-11, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26218335

RESUMO

Apodytes dimidiata, belonging to the family Icacinaceae, is used for treating inflammation and various gastrointestinal ailments in Zulu traditional medicine. In the present study, significant cytotoxicity was exhibited by the methanolic extract of the A. dimidiata leaf against various cancer cell lines. The extract was purified partially through silica gel column by successive elution using various solvents of increasing polarity. Among these, the active methanolic fraction was found to be the most cytotoxic with IC50 values ranging from 0.92 to 3.95 µg/mL for Ehrlich's ascites carcinoma (a carcinoma cell line), Jurkat (human T lymphocyte cell line), and SK-BR-3 (mammary tumour cell line). The treated cells showed morphological alterations characteristic of apoptosis. Upon oral administration of active methanolic fraction at a dose of 250 mg/kg body weight, the solid tumour volume in mice was significantly reduced to 55.14% and the life span of the ascites tumour-bearing mice increased to 44.65% compared to untreated control. The active fraction with Rf value 0.56 was purified from the methanolic fraction by preparative thin-layer chromatography and was subjected to high-performance thin-layer chromatography, high-performance liquid chromatography, liquid chromatography-mass spectrometry, and nuclear magnetic resonance analysis. The iridoid glycoside genipin was identified as the active component.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Magnoliopsida/química , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Índia , Masculino , Camundongos , Folhas de Planta/química , Plantas Medicinais
3.
J Biosci ; 43(2): 407-416, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29872027

RESUMO

Parasporins, a class of non-insecticidal crystal proteins of Bacillus thuringiensis (Bt) are being explored as promising anticancer agents due to their specific toxicity to cancer cells. The present study has identified 25 Bt isolates harbouring parasporin genes from Western Ghats region, the hotspot of biodiversity in India. Among these, the isolate, KAU 41 (Kerala Agricultural University isolate 41) contained non-hemolytic homogenous crystals showing specific cytotoxicity towards cancer cells. SDS-PAGE analysis of this crystal, isolated by aqueous biphasic separation, revealed a 31 kDa sized peptide. The N-terminal sequence deciphered in BLAST analysis showed homology to a hypothetical Bt protein. Upon proteolysis, a 29 kDa active peptide was generated which exhibited heterogenic cytotoxic spectrum on various cancer cells. HeLa cells were highly susceptible to this peptide with IC 50 1 lg/mL and showed characteristics of apoptosis. RT-qPCR analysis revealed the overexpression of APAF1, caspase 3 and 9 by 14.9, 8 and 7.4 fold, respectively which indicates the activation of intrinsic pathway of apoptosis. However, at higher concentrations of peptide (greater than 3 lg/mL), necrotic death was prominent. The results suggest that the 31 kDa protein from Bt isolate, KAU 41 is a parasporin that may have high therapeutic potential.


Assuntos
Apoptose/efeitos dos fármacos , Endotoxinas/genética , Endotoxinas/isolamento & purificação , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Bacillus thuringiensis/química , Endotoxinas/química , Endotoxinas/uso terapêutico , Células HeLa , Humanos , Índia/epidemiologia , Neoplasias/genética , Neoplasias/patologia
4.
J Tradit Complement Med ; 8(1): 244-250, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29322015

RESUMO

Saraca asoca (Fabaceae) is a prime ingredient in Asokarishta, a well-known Ayurvedic preparation for gynecological ailments. Due to scarcity, adulteration or substitution of related raw drugs is a common practice in its preparation. The bark of Kingiodendron pinnatum (Roxb. ex DC.) Harms, morphologically similar to S. asoca (Asoka) is a widely used substitute. The present study aimed to evaluate the pharmacological effectiveness of K. pinnatum as an alternative for S. asoca in Asokarishta by determining the inhibitory effect of estrogen induced uterus endometrial thickening in immature female rats. Arishta was prepared using S. asoca and with the substitute, K. pinnatum as per Ayurvedic Pharmacopeia. Uterus endometrial thickening was induced by the administration of estradiol (20 µg/kg b. wt, i.p) to 8-day-old rats for 5 alternate days. On day 16, following estradiol administration, the serum estrogen level was found elevated to 156.5 ± 8 pg/ml from the normal value 32.4 ± 5 pg/ml and consequently increased the thickness of uterus endometrium from 16.7 ± 1.4 to 75.2 ± 15.3 µm. Upon oral administration of 400 µl/kg b. wt Asokarishta (ASA) and Arishta made with K. pinnatum (AKP), the thickening was reduced to 42.5 ± 12.7 and 47.1 ± 10.5 µm and the estrogen level diminished to 102.6 ± 10 and 97.3 ± 8 pg/ml, respectively. Arishta also reduced the chronic/acute inflammations in mice and improved the antioxidant status of rats. No toxic symptom was observed in the animals by the treatment of Arishta. The study supports the use of K. pinnatum as an alternative to S. asoca in Asokarishta and gives a scientific validation for Asokarishta in gynecological ailments.

5.
J Basic Clin Physiol Pharmacol ; 27(4): 403-9, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26669246

RESUMO

BACKGROUND: Scutellaria baicalensis is a well-known plant in traditional Chinese medicine. Recently, several Scutellaria species with therapeutic potential have been recognized worldwide. Scutellaria colebrookiana and Scutellaria violacea, native to the Western Ghats of India, are reported to possess free radical scavenging efficacy. At present, the protective effect of these Scutellaria spp. against 2,2' azobis (2-amidinopropane) hydrochloride (AAPH)-induced oxidative damage in human erythrocytes has been analyzed. METHODS: Oxidative stress in erythrocyte was induced by AAPH. The inhibition of hemolysis, membrane lipid peroxidation, and protein damage by chloroform extracts of Scutellaria spp. was assessed biochemically. Phytochemicals of the extracts were analyzed by Fourier transform infrared spectrophotometer (FTIR). RESULTS: Approximately 95% of erythrocytes were lysed by AAPH over 3 h of incubation. Significant reduction in hemolysis was observed by the extracts, and the IC50 values were 18.3 and 23.5 µg/mL for S. colebrookiana and S. violacea, respectively. Both the extracts were found to inhibit AAPH-induced lipid peroxidation in ghost membrane with IC50 92±2.8 and 70±5.6 µg/mL. In the analysis of the membrane proteins using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the AAPH-induced degradation of actin was found reduced by both the extracts. The FTIR spectrum revealed the presence of polyphenols, carboxylic acids, alkanes, and aromatic compounds in extracts. In quantitative analysis, the total polyphenolic content estimated was 380±0.23 and 203.7±1.4 mg of gallic acid equivalent per gram extract of S. colebrookiana and S. violacea. CONCLUSIONS: Results indicate that S. colebrookiana and S. violacea are capable of protecting erythrocytes from oxidative damage. This cytoprotective effect of the extract is possibly by its antioxidant property.


Assuntos
Amidinas/farmacologia , Eritrócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Scutellaria/química , Antioxidantes/farmacologia , Células Cultivadas , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Eritrócitos/metabolismo , Ácido Gálico/farmacologia , Glutationa/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Oxidantes/metabolismo , Oxirredução/efeitos dos fármacos , Polifenóis/farmacologia , Scutellaria baicalensis
6.
J Basic Clin Physiol Pharmacol ; 26(5): 509-15, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25915082

RESUMO

BACKGROUND: Estrogen-mediated uterus endometrium instability is considered as one of the etiological factors in dysfunctional uterine bleeding (DUB) and uterine cancer. Saraca asoca (Family: Fabaceae) and its fermented preparation, Asokarishta, are extensively used as uterine tonic to treat gynecological disorders in Ayurveda. The present study evaluated the effect of S. asoca (Asoka) on estrogen-induced endometrial thickening of rat uterus. METHODS: Endometrial thickening was induced by intraperitoneal injection of estradiol (20 µg/kg b.wt) to 8-day-old immature rats for alternate 5 days. Methanolic extract (200 mg/kg b. wt) from S. asoca bark was given orally along with estradiol. Uterus endometrial thickening was analyzed histopathologically and serum estrogen level by radioimmunoassay (RIA). Cyclooxygenase (COX-2) expression in rat uterus was also estimated by Western blot. Anti-inflammatory activity of the extract was analyzed by formalin- and carrageenan-elicited paw edema models in mouse. RESULTS: Uterus endometrium proliferation and keratinized metaplasia with seven to eight stratified epithelial layers on day 16 was observed in rats administered with estradiol. Treatment with S. asoca reduced the thickening to two to four layers and the serum estrogen level diminished significantly to 82.9±12.87 pg/mL compared to rats administered with estrogen alone (111.2±10.68 pg/mL). A reduction of formalin- and carrageenan-induced paw edema in mouse by S. asoca extract was observed. Lower level of lipopolysaccharides (LPS)-induced COX-2 enzyme in rat uterus by the extract further confirms its anti-inflammatory activity. CONCLUSIONS: Present study reveals the antiproliferative and antikeratinizing effects of S. asoca in uterus endometrium possibly through its anti-estrogenic and anti-inflammatory properties.


Assuntos
Estradiol/farmacologia , Fabaceae/química , Metaplasia/induzido quimicamente , Metaplasia/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Carragenina/farmacologia , Ciclo-Oxigenase 2/metabolismo , Edema/tratamento farmacológico , Edema/metabolismo , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Feminino , Metaplasia/metabolismo , Camundongos , Extratos Vegetais/química , Ratos , Ratos Wistar
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