RESUMO
Acute kidney injury (AKI) is a life-threatening disease without effective treatment. The utilization of curcumin (Cur) for the treatment of AKI is still facing challenges due to its poor water-solubility and low bioavailability. Herein, kidney-targeted octenyl succinic anhydride-grafted fucoidan loaded with Cur (OSA-Fucoidan/Cur) was fabricated for synergistic treatment of AKI. It was found that OSA-Fucoidan/Cur micelles had a sustained drug release behavior and excellent physicochemical stability. Cellular uptake studies demonstrated that the specific binding between fucoidan and P-selectin overexpressed on H2O2-stimulated HUVECs contributed to the higher internalization of OSA-Fucoidan/Cur micelles by the cells. In addition, OSA-Fucoidan micelles exhibited an ideal kidney-targeted characteristic in lipopolysaccharide (LPS)-induced AKI mice. In vivo studies showed that the combination of Cur and OSA-Fucoidan endowed the OSA-Fucoidan/Cur micelles with synergistically anti-inflammatory and antioxidant abilities, thereby largely enhancing the therapeutic efficacy of AKI. Therefore, OSA-Fucoidan/Cur micelles may represent a potential kidney-targeted nanomedicine for effective treatment of AKI.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Portadores de Fármacos/química , Micelas , Selectina-P/antagonistas & inibidores , Polissacarídeos/química , Injúria Renal Aguda/patologia , Animais , Antioxidantes/farmacologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Meia-Vida , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos Endogâmicos ICR , Anidridos Succínicos/química , Distribuição Tecidual/efeitos dos fármacosRESUMO
Tanshinone IIA (TanIIA)-an active constituent of Salvia miltiorrhiza, a traditional Chinese medicinal plant-is known to have blood circulation promotion and anti-tumor properties. Tan IIA can induce tumor cell death and inhibit tumor growth. However, the functions and underling molecular mechanisms of Tan IIA action on human liver cancer cells remain poorly understand. In this study, we found that Tanshinone IIA mediates SMAD7-YAP interaction to induce liver cancer cell apoptosis and inhibit cell growth and migration by inactivating the transforming growth factor beta (TGF-ß) signaling pathway. Our findings showed that the Tan IIA-SMAD7-YAP regulatory network might be an effective strategy for liver cancer treatment.
Assuntos
Abietanos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Salvia miltiorrhiza , Proteína Smad7/metabolismo , Abietanos/farmacologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Idoso , Antineoplásicos Fitogênicos/farmacologia , Carcinogênese/efeitos dos fármacos , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Fitoterapia , Fatores de Transcrição/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas de Sinalização YAPRESUMO
OBJECTIVE: To evaluate the efficacy and safety of Serenoa repens among patients with benign prostatic hyperplasia (lower urinary tract symptoms/benign prostatic hyperplasia [LUTS/BPH]) in China. METHODS: We conducted a double blind, placebo-controlled study of 354 patients with LUTS/BPH from 19 institutions, to evaluate the efficacy and safety of Serenoa repens. Participants were randomly assigned (1:1) into the Serenoa repens extract (320 mg) or placebo groups for 24 weeks. Primary efficacy parameters were changes in International Prostate Symptom Score and peak urinary flow from baseline to each assessment. Secondary efficacy parameters included improvement of storage symptom and voiding symptom scores, prostate volume, urinary frequency, and total prostate-specific antigen level. Other parameters assessed were quality of life score, a four-item male sexual function questionnaire score, and International Index of Erectile Function score across the consecutive double-blind visits. RESULTS: Statistically significant improvement in the peak urinary flow, International Prostate Symptom Score, scores of storage symptoms and voiding symptoms, quality of life score, four-item male sexual function questionnaire score, and International Index of Erectile Function score were observed in the Serenoa repens extract group compared with those in the placebo group (P <.05). Two (1.18%) of 169 patients in the placebo group and 3 (1.89) of 159 patients in the Serenoa repens extract group experienced 1 or more adverse events. CONCLUSION: The Serenoa repens extract was effective, safe, well-tolerated, and clinically and statistically superior to placebo in the target LUTS/BPH population.