RESUMO
Calligonum polygonoides L. (Phog) is an endemic perennial herb that is highly resistant to all type of abiotic stresses and dominant biomass as well as phytochemicals producer in its natural habitat of the "Thar Desert" of Rajasthan, India. The present study was conducted to evaluate the effect of extreme environmental conditions on the phenolic, flavonoids, tannin content, and total antioxidant activities of C. polygonoides foliage harvested during different months. It exhibited a significant variation in the content of phenolic compounds, flavonoids, tannins, and antioxidant activity with harvesting time and all parameters are positively correlated to each other. The highest phenolic compounds and antioxidant activity was observed during severe winter and summer months, when monthly average environmental temperature was lowest and highest of the year, respectively. On the basis of the results, two harvests of C. polygonoides foliage during June and December are advised to maximize the phenolic compound production with highest antioxidant activity. These results demonstrate C. polygonoides, which is a dominant biomass producer under the harsh climatic conditions, can be an important source for the development of the functional foods rich in antioxidants in hot arid regions.
RESUMO
Flavonoids have been shown to possess central nervous system (CNS) depressant effect mediated through the ionotropic GABAA receptors. In the present study, 5-methoxyflavone was evaluated for sedative-hypnotic like activity in mice and the mechanisms involved by employing a battery of tests including molecular docking studies. In the open field test, 5-methoxyflavone in various doses (50, 100 and 150 mg/kg, i.p) exhibited a significant and dose-dependent reduction in the spontaneous locomotor activity (F (530) = 87.17 P < 0.001). Pretreatment with 5-methoxyflavone decreased the latency to sleep induction after pentobarbitone or ether administration and also significantly increased the duration of sleep (p < 0.001). A significant and dose-dependent myorelaxant effect was observed with 5-methoxyflavone in the inclined plane, horizontal wire test and rota rod test. Pretreatment with picrotoxin, bicuculline, glycine, caffeine or NMDA either decreased or completely abolished the hypnotic effect of 5-methoxyflavone in mice. The above results revealed the involvement of GABAA, adenosine, glycine and NMDA receptors in the hypnotic effect of 5-methoxyflavone. The results of in silico studies indicated that, 5-methoxyflavone exhibits good binding affinity towards these receptors by H-bond interactions. In conclusion, the present study identified a novel and potential sedative-hypnotic like effect of 5-methoxyflavone involving multiple mechanisms.
Assuntos
Flavonas/farmacologia , Hipnóticos e Sedativos/farmacologia , Anestesia , Animais , Sítios de Ligação , Flavonas/química , Hipnóticos e Sedativos/química , Ligantes , Camundongos , Simulação de Acoplamento Molecular , Teste de Desempenho do Rota-Rod , Testes de Toxicidade AgudaRESUMO
Capsaicin (CAP), a constituent of red chilli and red pepper is exposed to exert compelling anticarcinogenic effects. In the present study, we examined the anti-tumorigenic potential of CAP on benzo(a)pyrene-induced mice lung tumorigenesis by analyzing the markers of apoptosis. Intraperitoneal administration of CAP (10mg/kg body weight) to Swiss albino mice suppressed the development of lung carcinoma by amending the protein expressions of apoptotic regulators p53, Bcl-2, Bax and caspase-3. The apoptotic-inducing nature of CAP was further confirmed by DNA agarose gel electrophoresis, transmission electron microscopic study and ethidium bromide/acridine orange staining. The results obtained from the present study show that CAP inhibits the development of mice lung carcinogenesis through its ability to induce apoptosis. Our present findings provide the basis for further clinical exploration of CAP as an anti-carcinogenic compound against lung carcinogenesis.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Capsaicina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Pulmão/efeitos dos fármacos , Animais , Apoptose , Benzo(a)pireno/farmacologia , Capsicum/imunologia , Carcinogênese , Caspase 3/metabolismo , Células Cultivadas , Fragmentação do DNA/efeitos dos fármacos , Injeções Intraperitoneais , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Masculino , Camundongos , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: Lung cancer is a serious health problem in most developed countries and its incidence rate is profusely increasing. Capsaicin, a component of red chilli and red pepper has been studied widely for its chemopreventive properties. The aim of the present study is to explore the anti-tumor activity of capsaicin against benzo(a)pyrene-induced lung tumorigenesis in Swiss albino mice. MATERIALS AND METHODS: Benzo(a)pyrene was administered orally (50 mg/kg body weight) to induce lung cancer in Swiss albino mice. Hematological study (hemoglobin content, RBC, WBC count and differential count), histochemical analysis of mast cells and Western blot analysis of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB) were carried out. RESULTS: Hematological parameters and the histochemical analysis of mast cells showed abnormal changes, and the immunoblotting analysis revealed increased protein expression of TNF-α, IL-6, COX-2 and NF-κB in lung cancer-challenged mice administered with benzo(a)pyrene. Capsaicin (10 mg/kg body weight) supplementation to lung cancer bearing mice considerably prevented all the above abnormalities. CONCLUSION: The results of the present study indicate the protective effect of capsaicin against benzo(a)pyrene-induced lung carcinogenesis in mice.
Assuntos
Antineoplásicos/uso terapêutico , Capsaicina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Benzo(a)pireno , Contagem de Células Sanguíneas , Capsaicina/farmacologia , Ciclo-Oxigenase 2/imunologia , Interleucina-6/imunologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/imunologia , Masculino , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Camundongos , NF-kappa B/imunologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
In the present study, we have assessed the chemopreventive effect of capsaicin (CAP) on glucose metabolism with reference to blood glucose and liver glycogen levels, key glycolytic, and gluconeogenic enzymes along with electron transport chain (ETC) complexes during benzo(a)pyrene (B(a)P)-induced lung cancer in Swiss albino mice. B(a)P (50 mg kg(-1) body weight)-induced lung cancer animals showed marked decline in blood glucose levels, glycogen levels, elevations in the activities of key glycolytic enzymes (hexokinase, phosphoglucoisomerase and aldolase), and gluconeogenic enzymes (glucose-6-phosphatase and fructose-6-phosphatase) together with a decrease in the activities of ETC complexes. Supplementation of CAP (10 mg kg(-1) body weight) inhibited all the above alterations during lung cancer and restored near normalcy. Histochemical analysis by periodic acid Schiff's staining further confirmed the biochemical findings that highlighted the chemopreventive action of CAP during B(a)P-induced experimental lung tumourigenesis.
Assuntos
Antipruriginosos/farmacologia , Glicemia/efeitos dos fármacos , Capsaicina/farmacologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Animais , Benzo(a)pireno/farmacologia , Frutose-Bifosfatase/metabolismo , Glicogênio/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Monoéster Fosfórico Hidrolases/metabolismoRESUMO
Lung cancer is currently a leading cause of death all over the world. Environmental risk factors, particularly genotoxic chemicals such as polycyclic aromatic hydrocarbons (PAH), are likely to account for a much higher mortality. Xenobiotic metabolizing enzymes are potentially chief determinants in both the susceptibility to the mutagenic effects of chemical carcinogens and in the response of tumors to chemotherapy. The well-known carcinogen benzo(a)pyrene (B(a)P) of PAH family was given orally (50 mg/kg body weight) to induce lung cancer in Swiss albino mice. B(a)P induction altered the levels of cytochromes (P450, b5), activities of phase I biotransformation enzymes (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase and epoxide hydrolase), phase II enzymes (glutathione-S-transferase, UDP-glucuronyl transferase and DT-diaphorase), and the levels of serum tumor markers. Treatment with capsaicin (CAP) (10 mg/kg body weight) to the lung carcinoma mice restored back the activities of phase I and II biotransformation enzymes and the levels of tumor markers to near normalcy. The above findings were substantiated by immunoblotting and immunohistochemical analysis of cytochrome P450 1A1 (CYP1A1) in the lung tissues. Our present study unravels that CAP can effectively detoxify the carcinogens which discloses its anti-carcinogenic effect during experimental lung cancer.
Assuntos
Biomarcadores Tumorais/sangue , Capsaicina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/enzimologia , Xenobióticos/metabolismo , Animais , Capsaicina/farmacologia , Citocromo P-450 CYP1A1/metabolismo , Citocromos b5/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Imuno-Histoquímica , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/patologia , Neoplasias Pulmonares/sangue , Masculino , Desintoxicação Metabólica Fase I , Desintoxicação Metabólica Fase II , Camundongos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Neoplasias Experimentais/sangueRESUMO
Spices and vegetables possess antioxidant activity that can be applied for preservation of lipids and lower lipid peroxidation in biological systems. In the present study, we have investigated the effect of capsaicin on lipid metabolism during benzo(a)pyrene induced lung cancer in Swiss albino mice. Benzo(a)pyrene (50 mg/kg wt) induced lung cancer animals showed abnormal changes in the tissue and serum lipids, lipoproteins and lipid metabolizing enzymes. Treatment with capsaicin (10 mg/kg body wt) remarkably attenuated all the above alterations and restored normalcy. These findings reveal the chemomodulatory potential of capsaicin in attenuating the alterations in lipid metabolism during experimental lung carcinogenesis.
Assuntos
Capsaicina/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Animais , Benzo(a)pireno , Capsaicina/administração & dosagem , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Pulmão/metabolismo , Neoplasias Pulmonares/sangue , Masculino , CamundongosRESUMO
OBJECTIVES: The aim of this study was to investigate mechanisms involved in the growth inhibitory effect of silymarin, in humanhepatocellular carcinoma. MATERIALS AND METHODS: The human hepatocellular carcinoma cell line HepG2 was utilized and the MTT assay was performed to study the antiproliferative effect of silymarin. Dual staining was undertaken for ethidium bromide/acridine orange, propidium iodide staining and DNA fragmentation studies were executed to confirm the presence of apoptosis. Cell-cycle analysis was revealed by flow cytometry and mitochondrial transmembrane potential was measured by uptake of the mitochondrial-specific lipophilic cationic dye rhodamine 123. Western blotting analysis for cytochrome c, p53, Bax, Bcl-2, APAF-1, caspase-3, survivin, beta-catenin, cyclin D1, c-Myc and PCNA was carried out. RESULTS: Silymarin inhibited population growth of the hepatocellular carcinoma cells in a dose-dependent manner, and the percentage of apoptotic cells was increased after treatment with 50 and 75 microg/ml silymarin for 24 h. Silymarin treatment increased the proportion of cells with reduced DNA content (sub-G(0)/G(1) or A(0) peak), indicative of apoptosis with loss of cells in the G(1) phase. Silymarin also decreased mitochondrial transmembrane potential of the cells, thereby increasing levels of cytosolic cytochrome c while up-regulating expression of pro-apoptotic proteins (such as p53, Bax, APAF-1 and caspase-3) with concomitant decrease in anti-apoptotic proteins (Bcl-2 and survivin) and proliferation-associated proteins (beta-catenin, cyclin D1, c-Myc and PCNA). CONCLUSIONS: Our results demonstrate that silymarin treatment inhibited proliferation and induced apoptosis in the human hepatocellular carcinoma cell line HepG2.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Silimarina/farmacologia , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina D1/metabolismo , Citocromos c/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Inibidoras de Apoptose , Neoplasias Hepáticas/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Survivina , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , beta Catenina/metabolismoRESUMO
The objective of the present study was to investigate whether lysosome is a target in benzo(a)pyrene-induced, oxidative stress-mediated lung cancer in Swiss albino mice and the plausible role of the phytochemical substance capsaicin in mitigating lysosomal damage. Oxidative stress was assessed based on the level of carbonyl content. The activities of lysosomal proteases like cathepsin-D, cathepsin-B, beta-D-glucosidase, beta-D-galactosidase, beta-D-glucuronidase, beta-D-N-acetylglucosaminidase and acid phosphatase were assessed to evaluate lysosomal function. Administration of benzo(a)pyrene (50 mg/kg body weight) to mice induced a increase in the activities of lysosomal enzymes and oxidative stress was evident by the increase in carbonyl content. Treatment with capsaicin (10 mg/kg body weight) decreased carbonyl content and restored the activities of lysosomal enzymes to near normalcy. Transmission electron microscopic study of lysosomes further showed the defensive action of capsaicin against the lysosomal damage caused in benzo(a)pyrene-induced lung cancer. From the present study, it can be concluded that lysosomal damage is an indispensable event in benzo(a)pyrene-induced lung cancer, and capsaicin was able to effectively prevent it, which proves the chemoprotective effect of capsaicin against benzo(a)pyrene-induced experimental lung carcinogenesis.
Assuntos
Benzo(a)pireno/toxicidade , Capsaicina/farmacologia , Neoplasias Pulmonares/prevenção & controle , Lisossomos/efeitos dos fármacos , Animais , Anticarcinógenos/farmacologia , Carcinógenos/toxicidade , Neoplasias Pulmonares/induzido quimicamente , Lisossomos/enzimologia , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Estresse Oxidativo/efeitos dos fármacos , Peptídeo Hidrolases/efeitos dos fármacos , Peptídeo Hidrolases/metabolismoRESUMO
This study was designed to examine the impact of a principal component of hot red peppers and chilli peppers, capsaicin, on alterations in lipid peroxidation, membrane-bound enzyme profiles and glycoprotein levels during benzo(a)pyrene (BP)-induced lung cancer in Swiss albino mice. BP (50 mgkg(-1)) induced deleterious changes that were that revealed by alterations in lipid peroxidation, membrane-bound enzyme (Na+/K+ ATPase, Ca2+ ATPase and Mg2+ ATPase) activity, levels of total protein and protein-bound carbohydrate components (sialic acid, hexose, hexosamine, hexuronic acid and fucose). Pre-co-treatment with capsaicin (10 mg kg(-1)) restored the detrimental effects induced by BP, indicating its protective role in BP-induced lung cancer.
Assuntos
Anticarcinógenos/farmacologia , Capsaicina/farmacologia , Membrana Celular/efeitos dos fármacos , Neoplasias Pulmonares/prevenção & controle , Animais , Benzo(a)pireno/toxicidade , ATPase de Ca(2+) e Mg(2+)/efeitos dos fármacos , ATPase de Ca(2+) e Mg(2+)/metabolismo , ATPases Transportadoras de Cálcio/efeitos dos fármacos , ATPases Transportadoras de Cálcio/metabolismo , Carcinógenos/toxicidade , Membrana Celular/enzimologia , Glicoproteínas/efeitos dos fármacos , Glicoproteínas/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Camundongos , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
The effect of a pungent ingredient of red pepper, capsaicin, on oxidative stress induced changes in the antioxidant defense system by benzo(a)pyrene in the lungs of mice was studied. Oral gavage administration of benzo(a)pyrene (50 mg/kg body weight) to mice led to a marked increase in oxidative stress indicated by alterations in pulmonary lipid peroxidation, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Pre-co-treatment with capsaicin (10 mg/kg body weight i.p.) restored cellular normalcy, highlighting the antioxidant potential of capsaicin in mitigating the oxidative stress mediated damage produced during benzo(a)pyrene-induced lung cancer.
Assuntos
Antioxidantes/metabolismo , Capsaicina/farmacologia , Neoplasias Pulmonares/prevenção & controle , Pulmão/efeitos dos fármacos , Animais , Ácido Ascórbico/metabolismo , Benzo(a)pireno , Catalase/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase , Vitamina A/metabolismo , Vitamina E/metabolismoRESUMO
The modulatory efficacy of capsaicin on lung mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, key citric acid cycle enzymes and respiratory chain enzymes during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice was studied. Elevations in mitochondrial LPO along with decrements in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, vitamin E and vitamin A), citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha-ketoglutarate dehydrogenase (alpha-KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and respiratory chain enzymes (NADH dehydrogenase and Cytochrome c oxidase) were observed in B(a)P (50mg/kg body weight) administered animals. CAP (10mg/kg body weight) pretreatment decreased lung mitochondrial LPO and augmented the activities of enzymic, non-enzymic antioxidants, citric acid cycle enzymes and respiratory chain enzymes to near normalcy revealing its chemoprotective function during B(a)P induced lung cancer.
Assuntos
Anticarcinógenos/farmacologia , Antioxidantes/metabolismo , Capsaicina/farmacologia , Neoplasias Pulmonares/prevenção & controle , Animais , Benzo(a)pireno/toxicidade , Enzimas/efeitos dos fármacos , Enzimas/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Neoplasias Pulmonares/induzido quimicamente , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/prevenção & controleRESUMO
AIM: To study the effect of silymarin on the levels of tumor markers and MDA (malondialdehyde)-DNA adduct formation during N-nitrosodiethylamine induced hepatocellular carcinoma in male Wistar albino rats. METHODS: The levels of AFP, CEA and activities of liver marker enzymes in serum, MDA-DNA immunohistochemistry were done according to standard procedures in the control and experimental groups of rats. RESULTS: Hepatocellular carcinoma was evidenced from significant (p < 0.05) increases of alpha-fetoprotein, carcinoembryonic antigen, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, acid phosphatase, lactate dehydrogenase, gamma-glutamyltransferase and 5'-nucleotidase in serum and increased MDA-DNA adducts were also observed in the tissue sections of hepatocellular carcinoma. Silymarin treatment significantly attenuated the alteration of these markers and decreased the levels of MDA-DNA adduct formation. CONCLUSION: Silymarin could be developed as a promising chemotherapeutic adjuvant for the treatment of liver cancer.