plantamajoside and Disease-Models--Animal

Parkinson's disease (PD) is a common neurodegenerative disorder caused by dopaminergic neuron progressive degeneration. Inhibition of microglial activation may contribute to the treatment and prevention of PD. Plantamajoside (PMS) is a natural compound extracted from plantain seeds. It has a wide range of biological activities, including anti-inflammatory, antioxidative, as well as antitumor effects. However, its possible effects on PD are still unclear. In this study, lipopolysaccharide (LPS) was first injected into the right midbrain substantia nigra (SN) of male C57BL/6 mice to establish the PD mouse model. We found that PMS improved LPS-induced behavioral dysfunction in PD mice. PMS attenuated LPS-induced SN injury in PD mice. PMS could suppress LPS-induced microglial overactivation in PD mice. In addition, MS inhibited LPS-induced activation of the HDAC2/MAPK pathway in PD mice and BV-2 cells. It further revealed that PMS alleviated microglia polarization by inhibiting HDAC2. The limitation of this study was the lack of experiments for investigating the further molecular mechanism and in vivo animal validation, which needs to be further confirmed in the future. Collectively, our data suggested that PMS could serve as a promising drug for PD.

Topics: Animals; Disease Models, Animal; Dopaminergic Neurons; Histone Deacetylase 2; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Microglia; Parkinson Disease; Substantia Nigra

As a compensatory response to cardiac overload, cardiac hypertrophy is closely associated with the occurrence and development of a variety of cardiovascular diseases, in which histone deacetylase 2 (HDAC2) has been reported to play an important role. Plantamajoside (PMS) is an active component extracted from Herba Plantaginis, which is a traditional Chinese medicine, and many biological activities of PMS have been reported. Here, we investigated the effects and mechanism of PMS on isoproterenol (ISO)-induced cardiac hypertrophy. ISO at 10 μmol/L was used in vitro to induce H9c2 cardiomyocyte hypertrophy. Cell viability and cell surface area were determined by MTT assay and immunocytochemistry, respectively. Furthermore, an in vivo, cardiac hypertrophy model was established by subcutaneous injection of ISO. Pathological alterations and fibrosis in the myocardium were studied by H&E and Masson's trichrome staining, respectively. Myocardial injury-related genes and proteins were detected by real-time PCR and western blotting. HDAC2 and its downstream proteins, AKT and GSK3β, were analyzed by western blotting. Our results showed that, in vitro, PMS inhibited the ISO-induced increase in H9c2 cell surface area and the mRNA expression of ANP, BNP and Myh7. In vivo, PMS improved the ISO-induced decrease in cardiac function, inhibited the increase in cardiac anatomical parameters and alleviated the histopathological changes in cardiac tissues. Moreover, PMS inhibited the mRNA and protein expression of ANP, BNP, Myh7, COL1 and COL3. Furthermore, PMS suppressed the activity of HDAC2 and down-regulated the expression of the downstream proteins p-AKT and p-GSK3β both in vitro and in vivo. Overall, our results indicated that PMS exerts significant cardioprotective effects against ISO-induced cardiac hypertrophy, and this protective effect may be mediated by inhibition of the HDAC2 and AKT/GSK-3β signaling pathway.

Topics: Animals; Cardiomegaly; Catechols; Cell Line; Cell Survival; Disease Models, Animal; Glucosides; Glycogen Synthase Kinase 3 beta; Heart Ventricles; Histone Deacetylase 2; Isoproterenol; Male; Mice; Mice, Inbred BALB C; Myocardium; Myocytes, Cardiac; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction