RESUMO
Macrophages infiltrated in adipose tissue play a key role in obesity. Some traditional pharmaceutical compounds may shift the polarization of recruited macrophages to improve metabolic homeostasis. Tanshinoneâ ¡A (TAN2A) is a major active component of Salvia miltiorrhiza, a traditional anti-inflammatory cardiovascular medicine. In our study, we firstly constructed a phenanthroimidazole derivative of TAN2A named TAN20 by chemical synthesis, then identified its structure by chromatography and hydrogen spectroscopy, and finally examined its effects on immunometabolic responses. We found that TAN20 significantly induced the alternatively-activated (M2) rather than the classically-activated macrophages (M1), mainly through releasing the type II cytokines. Such effects were more pronounced than that from TAN2A. Compared to TAN2A, TAN20 substantially reduced body weight, decreased serum free fatty acid and HOMA-IR, and increased insulin sensitivity in obesity-induced diabetic mice. These effects of TAN20 were further validated on diabetic cynomolgus monkeys, which are closer to human physiological conditions. Taken together, our findings explicitly showed that TAN20 significantly polarized the macrophage and improved metabolic homeostasis in obesity-induced diabetic models, suggesting that TAN20 may be a potential drug against diabetes and obesity.
Assuntos
Abietanos/farmacologia , Tecido Adiposo/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Obesidade/tratamento farmacológico , Fenantrenos/farmacologia , Abietanos/química , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/química , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Citocinas/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos não Esterificados/sangue , Humanos , Hipoglicemiantes/química , Insulina/sangue , Resistência à Insulina , Macaca fascicularis , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/etiologia , Obesidade/genética , Fenantrenos/química , Células RAW 264.7RESUMO
Tibial Dyschondroplasia (TD), a metabolic disease of fast growing poultry birds that effects the growth of bone and cartilage, is characterized by anorexia, mental depression and lameness. Wnt/ß-catenin pathway can mediate the occurrence of TD, and previous study showed the therapeutic effect of Tanshinoneâ ¡A to TD Broilers. However there is no report about the effect of Tanshinoneâ ¡A treating TD broiler chicken through wnt/ß-catenin pathway. The objective of this study was to explore the potential mechanism of how Tanshinone II A treats TD. Hematoxylin and eosin staining was used to study histologic pathology of growth plates. Key gene expressions were tested by western blot and reverse transcription quantitative real-time PCR. Results compared with control groups, showed the TD broilers' growth plate performed significantly better by treating with Tanshinoneâ ¡A. After chickens treated by Tanshinoneâ ¡A, the gene and protein expression of WNT5α and BMP-2 were increased (Pâ¯<â¯0.05), but the ß-catenin were decreased (Pâ¯<â¯0.05), which are all key genes expressed in wnt/ß-catenin pathway. Therefore, Tanshinoneâ ¡A can potentially treat TD by affecting the expression of genes in wnt/ß-catenin pathway and it has availability to use as treatment for TD broilers.
Assuntos
Abietanos/uso terapêutico , Lâmina de Crescimento/efeitos dos fármacos , Osteocondrodisplasias/veterinária , Doenças das Aves Domésticas/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Abietanos/farmacologia , Animais , Galinhas , Lâmina de Crescimento/patologia , Osteocondrodisplasias/induzido quimicamente , Osteocondrodisplasias/tratamento farmacológico , Osteocondrodisplasias/metabolismo , Doenças das Aves Domésticas/induzido quimicamente , Doenças das Aves Domésticas/metabolismo , Tiram/toxicidade , TíbiaRESUMO
In the study, we developed a novel formulation, CD123 mono-antibody (mAb) modified tanshinone â ¡A loaded immunoliposome (CD123-Tanâ ¡A-ILP) to achieve the targeted drug delivery for leukemia cells. Orthogonal test was used to optimize liposome preparation, and the Tanâ ¡A-loaded PEGylated liposomes (Tanâ ¡A-LP) of S100PC-Chol-(mPEG2000-DSPE)-Tanâ ¡A at 19â¶5â¶1â¶1 molar ratio were prepared by the thin film hydration-probe ultrasonic method. A post-insertion method was applied to prepare CD123-Tanâ ¡A-ILP via thiolated mAb conjugated to the terminal of maleimide-PEG2000-DSPE. The cellular uptake assay was measured by flow cytometry, and the inhibitory effect of CD123-Tanâ ¡A-ILP on NB4 cells proliferation was tested by using MTT assay. The results of cellular uptake assay showed that CD123-ILP could significantly increase the drug uptake of NB4 cells as compared with free drugs and LP. The IC50 values at 48 h incubation were 20.87, 11.71, 7.17 µmolâ¢L⻹ respectively for Tanâ ¡Aï¼Tanâ ¡A-LP and CD123-Tanâ ¡A-ILP. CD123-ILP demonstrated a potential and promising targeted drug delivery strategy for acute myelogenous leukemia (AML) treatment.
Assuntos
Abietanos/farmacologia , Anticorpos Monoclonais/química , Antineoplásicos Fitogênicos/farmacologia , Sistemas de Liberação de Medicamentos , Lipossomos/química , Linhagem Celular Tumoral , Humanos , Subunidade alfa de Receptor de Interleucina-3/imunologiaRESUMO
Tanshinoneâ ¡A (Tanâ ¡A) is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen () that has various pharmacological properties, including anti-inflammatory, antibacterial, and antioxidative effects. Sepsis is a life-threatening organ dysfunction induced by a dysregulated host response to infection. Recently, increasing attention has been paid to sepsis-induced dysfunction of the intestine, car-diovascular system, lungs, kidneys, liver, and other organs. Experimental studies have shown that Tanâ ¡A has therapeutic potential for sepsis-induced organ dysfunction owing to its anti-inflammatory, anti-apoptotic and regulatory effects on multiple signalling pathways. The purpose of this article is to evaluate the potential multiorgan protective effects of Tanâ ¡A in sepsis.