Background: Stroke is the leading cause of long-term motor disability and cognitive impairment. Recently, neurogenesis has become an attractive strategy for the chronic recovery of stroke. It is important to understand the molecular mechanism that promotes neural stem cell (NSC) neurogenesis for future NSC-based therapies. Our previous study showed that Momordica charantia polysaccharides (MCPs) exerted neuroprotective effects on stroke via their anti-oxidant and anti-inflammation activities. However, it remains unknown whether MCPs promote NSC neurogenesis after cerebral ischemic/reperfusion injury (IRI). Methods: We investigated MCPs’ function in differentiation of neural stem cells (NSCs) in vivo and in vitro experiments. Based on a middle cerebral artery occlusion (MCAO) rat model, the effect of MCPs on neuronal differentiation after MCAO was analyzed. Primary NSCs and neural stem cell line C17.2 were cultured and subjected to glutamate stimulation to establish the cell model of IRI. We evaluated the effect of MCPs on NSC differentiation in IRI cell model by Western blot and immunofluorescence staining. The SIRT1 activity of NSCs post glutamate stimulation was also evaluated by CELL SIRT1 COLORIMETRY ASSAY KIT. In addition, molecular mechanism was clarified by employing the activator and inhibitor of SIRT1. Results: MCPs had no effects on the differentiation of neural stem cells under physiological conditions while shifted NSC differentiation potential from the gliogenic to neurogenic lineage under pathological conditions. Activation of SIRT1 with MCPs was responsible for the neuronal differentiation of C17.2-NSCs. The neuronal differentiation effect of MCPs was attributed to upregulation SIRT1-mediated deacetylation of β-catenin. MCP-induced deacetylation via SIRT1 promoted nuclear accumulation of β-catenin in NSCs. Conclusion: Our findings indicate that the deacetylation of β-catenin by SIRT1 represents a critical mechanism of action of MCPs in promoting NSC neuronal differentiation. It provides an improved understanding of molecular mechanism underlying neuroprotective effects of MCPs in IRI, indicating its potential role on treating ischemic stroke especially chronic recovery.
1 January 2021 in Oxidative Medicine and Cellular Longevity
Breast cancer (BCa) is the leading cause of women’s death worldwide; among them, triple‐negative breast cancer (TNBC) is one of the most troublesome subtypes with easy recurrence and great aggressive properties. Spatholobus suberectus Dunn has been used in the clinic of Chinese society for hundreds of years. Shreds of evidence showed that Spatholobus suberectus Dunn has a favorable outcome in the management of cancer. However, the anti‐TNBC efficacy of Spatholobus suberectus Dunn percolation extract (SSP) and its underlying mechanisms have not been fully elucidated. Hence, the present study is aimed at evaluating the anti‐TNBC potential of SSP both in vitro and in vivo, through the cell viability, morphological analysis of MDA‐MB‐231, LDH release assay, ROS assay, and the tests of GSH aborted pyroptotic noninflammasome signaling pathway. Survival analysis using the KM Plotter and TNM plot database exhibited the inhibition of transcription levels of caspase‐4 and 9 related to low relapse‐free survival in patients with BCa. Based on the findings, SSP possesses anti‐TNBC efficacy that relies on ROS‐induced noncanonical inflammasome pyroptosis in cancer cells. In this study, our preclinical evidence is complementary to the preceding clinic of Chinese society; studies on the active principles of SPP remain underway in our laboratory.
29 September 2014 in Journal of Receptors and Signal Transduction
It has been well documented that Momordica charantia polysaccharide (MCP) has multiple biological effects such as immune enhancement, anti-oxidation and anti-cancer. However, the potential protective effects of MCP on stroke damage and its relative mechanisms remain unclear. Our present study demonstrated that MCP could scavenge reactive oxygen species (ROS) in intra-cerebral hemorrhage damage, significantly attenuating the neuronal death induced by thrombin in primary hippocampal neurons. Furthermore, we found that MCP prevented the activation of the c-Jun N-terminal protein kinase (JNK3), c-Jun and caspase-3, which was caused by the intra-cerebral hemorrhage injury. Taken together, our study demonstrated that MCP had a neuroprotective effect in response to intra-cerebral hemorrhage and its mechanisms involved the inhibition of JNK3 signaling pathway.
Spatholobus suberectus Dunn (SSD) has been extensively employed in Traditional Chinese Medicine to treat several ailments. SSD and its active compounds are effective therapeutic agents for treating a variety of diseases with negligible side effects. Therefore, we aimed to investigate its phytochemistry, pharmacology, and potential therapeutic effects exclusively in cancer prevention and treatment. Phytochemical and pharmacological information was collected and arranged in a rational order. SSD has been frequently attributed to having antioxidant, anti-diabetic, anti-inflammatory, hematopoietic, neuroprotective, antimicrobial, and anticancer properties. Evidence has indicated that the bioactive constituents in SSD have attracted increasing scientific attention due to their preventive role in cancers. Further, the present review provides the current information on the health implications of SSD, thus allowing for future clinical trials to explore its restorative benefits. All data of in vitro and animal investigations of SSD, as well as its effect on human health, were obtained from an electronic search and library database. The diverse pharmacological potential of SSD provides an opportunity for preclinical drug discovery, and this comprehensive review strongly indicates that SSD is an excellent anti-tumorigenic agent that modulates or prevents breast cancer.
1 November 2019 in Free Radical Biology and Medicine