RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence of cardiovascular diseases (CVDs) has been increasing worldwide. Despite significant improvements in therapeutics and on-going developments of novel targeted-treatment regimens, cardiac diseases lack effective preventive and curative therapies with minimal side effects. Therefore, there is an urgent need to identify and propagate alternative and complementary therapies against cardiovascular diseases. Some traditional Chinese medicines can contribute to the prevention and treatment of CVDs and other chronic diseases, with few side effects. Hirudo, a medicinal leech, has been acclaimed for improving blood circulation and overcoming blood stagnation; however, the precise molecular mechanisms of leech extract treatment against pathological cardiac remodeling remain elusive. In this study, we aimed to delineate the molecular mechanisms of medicinal leech extract in the treatment of cardiac hypertrophy and fibrosis, using both in vitro and in vivo assessments. MATERIALS AND METHODS: We conducted in vitro and in vivo animal experiments, including cell-viability assays, fluorescence microscopy, immunoblotting, immunohistochemistry, and Masson's trichrome staining. RESULTS: Pre-treatment with leech extract conferred a survival benefit to spontaneously-hypertensive rats (SHRs) and significantly reduced angiotensin II (ANG II)-induced cardiac hypertrophy and fibrosis. ANG II-stimulated cardiac hypertrophy markers were attenuated by leech extract treatment, versus controls. Translational expression of stress-associated mitogen-activated protein kinases (MAPKs) was also repressed. In vivo, leech extract treatment significantly ameliorated the cardiac hypertrophy phenotype in SHRs and diminished interstitial fibrosis, accompanied with reduced fibrosis markers. CONCLUSION: Leech extract treatment under a hypertensive condition exerted significant cardio-protective benefits by reducing the expression of cardiac hypertrophy-related transcription factors, stress-associated MAPKs, and fibrosis mediators. Our findings imply that medicinal leach extract may be effective against hypertension-induced cardiac hypertrophy and fibrosis.
Assuntos
Cardiomegalia/tratamento farmacológico , Cardiotônicos/uso terapêutico , Hirudo medicinalis , Hipertensão/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Animais , Fatores Biológicos , Cardiomegalia/etiologia , Cardiomegalia/patologia , Cardiotônicos/isolamento & purificação , Cardiotônicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Fibrose , Hipertensão/complicações , Hipertensão/patologia , Sanguessugas , Masculino , Miócitos Cardíacos/patologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Over the past decade, the rise of cancer immunotherapy has coincided with a remarkable breakthrough in cancer therapy, which attracted increased interests in public. The scientific community clearly showed that the emergence of immunotherapy is an inevitable outcome of a holistic approach for cancer treatment. It is well established that traditional Chinese medicine (TCM) utilizes the principle of homeostasis and balance to adjust the healthy status of body. TCM treatment toward cancer has a long history, and the diagnosis and treatment of tumors were discussed in the ancient and classical literatures of Chinese medicine, such as the Yellow Emperor's Inner Canon. Precious heritage has laid the foundation for the innovation and development of cancer treatment with TCM. The modern study indicated that TCM facilitates the treatment of cancer and enhances the survival rate and life expectancy of patients. However, the pharmacological mechanisms underlying these effects are not yet completely understood. In addition, physicians cannot always explain why the TCM treatment is effective and the mechanism of action cannot be explained in scientific terms. Here, we attempted to provide insights into the development of TCM in the treatment and interpret how TCM practitioners treat cancer through six general principles of TCM by using modern scientific language and terms based on newly discovered evidence.
RESUMO
Platycodin D (PD) is the main active saponin isolated from Platycodon grandiflorum (PG) and is reported to exhibit anticancer, anti-angiogenic, anti-inflammation and anti-obesity biological effects. The current study aims to evaluate the therapeutic efficacy of PD in cardiac fibrosis and for hypertrophy in spontaneous hypertension rats (SHRs) and to verify inhibition of the signaling pathway. Significant increases in the cardiac functional indices of left ventricular internal diameter end diastole (LVIDd) and left ventricular internal diameter end systole (LVIDs); the eccentric hypertrophy marker p-MEK5; concentric hypertrophy markers, such as CaMKII[Formula: see text] and calcineurin; and expression levels of NFATc3, p-GATA4 and BNP were observed in spontaneously hypertensive groups. PD treatment reversed these increases in SHRs. In addition, an increase in the fibrosis markers FGF2, uPA, MMP2, MMP9, TGF[Formula: see text]-1 and CTGF during cardiac hypertrophy was detected by western blotting analyses. These results demonstrated that PD treatment considerably attenuates cardiac fibrosis. Histopathological examination revealed that PD treatment remarkably reduced collagen accumulation in contrast to spontaneously hypertensive groups. This study clearly suggests that PD provides myocardial protection by alleviating two damaging responses to hypertension, fibrosis and hypertrophy, in the heart.
Assuntos
Cardiomegalia/tratamento farmacológico , Miocárdio/patologia , Fitoterapia , Saponinas/uso terapêutico , Triterpenos/uso terapêutico , Animais , Cardiomegalia/etiologia , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Colágeno/metabolismo , Modelos Animais de Doenças , Fibrose , Miocárdio/metabolismo , Platycodon/química , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificaçãoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Platycodon grandiflorum (PG) is a Chinese medical plant used for decades as a traditional prescription to eliminate phlegm, relieve cough, reduce inflammation and lower blood pressure. PG also has a significant effect on the cardiovascular systems. MATERIALS AND METHODS: The aqueous extract of Platycodon grandiflorum (JACQ.) A. DC. root was screened for inhibiting Ang II-induced IGF-IIR activation and apoptosis pathway in H9c2 cardiomyocytes. The effects were also studied in spontaneously hypertensive rats (five groups, n=5) using low and high doses of PG for 50 days. The Ang II-induced IGF-IIR activation was analyzed by luciferase reporter, RT-PCR, western blot and surface IGF-IIR expression assay. Furthermore, the major active constituent of PG was carried out by high performance liquid chromatography-mass spectrometry (HPLC-MS). RESULTS: Our results indicate that a crude extract of PG significantly suppresses the Ang II-induced IGF-IIR signaling pathway to prevent cardiomyocyte apoptosis. PG extract inhibits Ang II-mediated JNK activation and SIRT1 degradation to reduce IGF-IIR activity. Moreover, PG maintains SIRT1 stability to enhance HSF1-mediated IGF-IIR suppression, which prevents cardiomyocyte apoptosis. In animal models, the administration of PG markedly reduced this apoptotic pathway in the heart of SHRs. CONCLUSION: Taken together, PG may be considered as an effective treatment for cardiac diseases in hypertensive patients.
Assuntos
Angiotensina II/farmacologia , Apoptose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Platycodon/química , Receptor IGF Tipo 2/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Mioblastos/efeitos dos fármacos , Extratos Vegetais/química , Ratos , Ratos Endogâmicos WKY , Receptor IGF Tipo 2/genética , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Triterpenos/farmacologiaRESUMO
BACKGROUND: The shell of Haliotis diversicolor, or shijueming (SJM), is a type of traditional Chinese medicine. The SJM has appeared in historical records as early as the third and fourth centuries. Historical records have revealed that SJM had mainly been used to treat eye diseases. After the Qing Dynasty (1757), records had emerged, detailing the use of SJM for treating skin injuries, particularly for treating poorly managed ulcers or traumatic wounds. Furthermore, in our anti-inflammation-screening system, SJM significantly inhibited the expression of pro-inflammatory proteins. Previous studies have yet to adopt an animal model to verify the phenomenon and described in the historical records regarding the efficacy of SJM in promoting wound healing. Besides, the mechanism of wound healing effect of SJM is also not clear. METHODS: This study applied in vitro and in vivo models, tissue section analysis, and western blotting to evaluate the effect of SJM on wound healing. The RAW 264.7 cells were used in anti-inflammatory activity assay and phagocytic assay. Male Wistar rats were used to evaluate the effect of SJM on burn injury healing. A copper block (2 × 2 cm, 150 g) preheated to 165 °C in a dry bath was used to contact the skin area for 10 s, thus creating a full-thickness burn injury. The results were analyzed by hematoxylin and eosin staining, picrosirius red staining and Western blotting. RESULTS: The results revealed that in the in vitro model, the presence of SJM decreased the inducible nitric oxide synthase (iNOS) expression and enhanced the functions of macrophages. The results of the rat burn injury model revealed that SJM decreased neutrophil infiltration, promoted wound healing, thus increasing the collagen I content and promoting the expression of transforming growth factor-beta 1 (TGF-ß1) protein. We speculate that the effect and mechanism of SJM on promoting wound healing is related to macrophage activation. In the inflammation phase, SJM alleviates inflammation by inhibiting iNOS expression and removing neutrophils through phagocytosis. Furthermore, SJM induces the secretion of TGF-ß1, converting collagen during the tissue remodeling phase. CONCLUSIONS: According to our review of relevant literature, this is the first study that applied an evidence-based method to verify that SJM alleviates inflammation, enhances phagocytosis, and triggers wound healing after burn injury. The study findings reveal that SJM provides a promising therapeutic option for treating burn injury.