RESUMO
Patients treated during leukemia face the risk of complications including pulmonary dysfunction that may result from infiltration of leukemic blast cells (LBCs) into lung parenchyma and interstitium. In LBCs, we demonstrated that transient receptor potential vanilloid type 2 channel (TRPV2), reputed for its role in inflammatory processes, exhibited oncogenic activity associated with alteration of its molecular expression profile. TRPV2 was overexpressed in LBCs compared to normal human peripheral blood mononuclear cells (PBMCs). Additionally, functional full length isoform and nonfunctional short form pore-less variant of TRPV2 protein were up-regulated and down-regulated respectively in LBCs. However, the opposite was found in PBMCs. TRPV2 silencing or pharmacological targeting by Tranilast (TL) or SKF96365 (SKF) triggered caspace-mediated apoptosis and cell cycle arrest. TL and SKF inhibited chemotactic peptide fMLP-induced response linked to TRPV2 Ca2+ activity, and down-regulated expression of surface marker CD38 involved in leukemia and lung airway inflammation. Challenging lung airway epithelial cells (AECs) with LBCs decreased (by more than 50%) transepithelial resistance (TER) denoting barrier function alteration. Importantly, TL prevented such loss in TER. Therefore, TRPV2 merits further exploration as a pharmacodynamic biomarker for leukemia patients (with pulmonary inflammation) who might be suitable for a novel [adjuvant] therapeutic strategy based on TL.
Assuntos
Biomarcadores/metabolismo , Leucemia/patologia , Pneumonia/patologia , Canais de Cátion TRPV/metabolismo , ADP-Ribosil Ciclase 1/metabolismo , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Leucemia/complicações , Leucemia/tratamento farmacológico , Leucócitos Mononucleares/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Pneumonia/complicações , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/genética , Regulação para Cima/efeitos dos fármacos , ortoaminobenzoatos/farmacologia , ortoaminobenzoatos/uso terapêuticoRESUMO
Natural products have been gaining recognition and are becoming a significant part of research in the area of drug development and discovery. Phytochemicals derived from these sources have been comprehensively studied and have displayed a wide range of activities against many fatal diseases including cancer. One such product that has gained recognition from its pharmacological properties and nontoxic nature is embelin, obtained from Embelia ribes. Amid all the vivid pharmacological activities, embelin has gained its prominence in the area of cancer research. Embelin binds to the BIR3 domain of XIAP, preventing the association of XIAP and caspase-9 resulting in the suppression of cell growth, proliferation and migration of various types of cancer cells. Furthermore, embelin modulates anti-apoptotic pathways by suppressing the activity of NF-κB, PI3-kinase/AKT, JAK/STAT pathway - among others. The present review summarizes the various reported effects of embelin on different types of cancer cells and highlights the cellular mechanisms of action.
Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Benzoquinonas/química , Benzoquinonas/farmacologia , Embelia/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Benzoquinonas/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Natural compounds capable of inducing apoptosis in cancer cells have always been of considerable interest as potential anti-cancer agents. Many such compounds are under screening and development with their potential evolution as a clinical drug benefiting many of the cancer patients. Guggulsterone (GS), a phytosterol isolated gum resin of the tree Commiphora mukul has been widely used in Indian traditional medicine as a remedy for various diseses. GS has been shown to possess cancer chemopreventive and therapeutic potential as established by in vitro and in vivo studies. GS has been shown to target constitutively activated survival pathways such as PI3-kinase/AKT, JAK/STAT, and NFκB signaling pathways that are involved in the regulation of growth and inflammatory responses via regulation of antiapoptotic and inflammatory genes. The current review focuses on the molecular targets of GS, cellular responses, and the animal model studies in various cancers. The mechanistic action of GS in different types of cancers also forms a part of this review. The perspective of translating this natural compound into a clinically approved drug with its pros and cons is also discussed.
RESUMO
Aloe vera gel is a familiar ingredient in a range of widely available and advertisement healthcare and cosmetic products. As to date there are no documented reports on the standardization of A. vera gel and the following study is an attempt in this direction. A. vera gel was evaluated for its aloeverose content for the first time. Aloeverose, was separated on a thin-layer of silica gel by isocratic gradient elution technique was determined by using HPTLC-photodensitometry. The proposed method is simple and sensitive and can be used for the routine assay of aloeverose in phytomedicines containing A. vera gel.
Assuntos
Aloe/química , Cromatografia Líquida de Alta Pressão/métodos , Densitometria/métodos , Folhas de Planta/química , Preparações de Plantas/química , Cromatografia em Camada Fina/métodos , GéisRESUMO
OBJECTIVES: Curcuma zedoaria Rosc is a perennial herb found in tropical countries, such as India, Japan and Thailand. Various parts of this plant are used in Ayurveda and other folk medicines for the treatment of different ailments such as diarrhoea, cancer, flatulence and dyspepsia. This study is an attempt to compile an up-to-date and comprehensive review of C. zedoaria that covers its traditional and folk medicinal uses, phytochemistry and pharmacology. KEY FINDINGS: Research carried out using different in-vitro and in-vivo techniques of biological evaluation supports most of the claims. SUMMARY: This review presents the botany, chemistry, traditional uses and pharmacological data of the plant.
Assuntos
Curcuma/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Analgésicos/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Etnofarmacologia , Humanos , Estrutura Molecular , Extratos Vegetais/uso terapêuticoRESUMO
We have investigated the possible antihyperglycaemic effects of Sphaeranthus indicus extract in rats rendered diabetic by nicotinamide (120 mgkg(-1) i.p.) and streptozotocin (STZ) (60 mgkg(-1) i.p). Fasting plasma glucose levels, serum insulin levels, serum lipid profiles, magnesium levels, glycosylated haemoglobin, changes in body weight and liver glycogen levels were evaluated in normal and diabetic rats. Oral administration of S. indicus for 15 days resulted in significant decrease in blood glucose levels and increases in hepatic glycogen and plasma insulin levels. Fasting normal rats treated with the alcoholic extract of S. indicus showed significant improvement in oral glucose tolerance test. Glibenclamide was used as a reference standard. The findings demonstrate that the alcoholic S. indicus extract may be useful in the treatment of diabetes.
Assuntos
Asteraceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Hemoglobinas Glicadas/análise , Insulina/sangue , Lipídeos/sangue , Glicogênio Hepático/análise , Magnésio/sangue , Masculino , Niacinamida , Fitoterapia , Ratos , Ratos Wistar , EstreptozocinaRESUMO
The free radical scavenging potential of the plant S. indicus was studied by using different antioxidant models of screening. The ethanolic extract at 1000 microg/ml showed maximum scavenging of the radical cation, 2,2-azinobis-(3-ethylbenzothiazoline-6-sulphonate) (ABTS) observed upto 41.99% followed by the scavenging of the stable radical 1,1-diphenyl, 2-picryl hydrazyl (DPPH) (33.27%), superoxide dismutase (25.14%) and nitric oxide radical (22.36%) at the same concentration. However, the extract showed only moderate scavenging activity of iron chelation (14.2%). Total antioxidant capacity of the extract was found to be 160.85 nmol/g ascorbic acid. The results justify the therapeutic applications of the plant in the indigenous system of medicine, augmenting its therapeutic value.