ABSTRACT
CONTEXT: Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects millions of elderly people worldwide. However, no efficient therapeutic method for AD has yet been developed. Recently, Salvia miltiorrhiza Bunge (Lamiaceae), a well-known traditional Chinese medicine which is widely used for treating cardio-cerebrovascular, exerts multiple neuroprotective effects and is attracting increased attention for the treatment of AD. OBJECTIVE: The objective of this study is to discuss the neuroprotective effects and neurogenesis-inducing activities of S. miltiorrhiza components. METHODS: A detailed search using major electronic search engines (such as Pubmed, ScienceDirect, and Google Scholar) was undertaken with the search terms: Salvia miltiorrhiza, the components of S. miltiorrhiza such as salvianolic acid B, salvianolic acid A, danshensu, tanshinone I, tanshinone IIA, cryptotanshinone, dihydrotanshinone, and neuroprotection. RESULTS: Salvia miltiorrhiza components exert multiple neuroprotective potentials relevant to AD, such as anti-amyloid-ß, antioxidant, anti-apoptosis, acetylcholinesterase inhibition, and anti-inflammation. Moreover, S. miltiorrhiza promotes neurogenesis of neural progenitor cells/stem cells in vitro and in vivo. CONCLUSIONS: The properties of S. miltiorrhiza indicate their therapeutic potential in AD via multiple mechanisms. In addition, S. miltiorrhiza provides lead compounds for developing new drugs against AD.
Subject(s)
Alzheimer Disease/drug therapy , Brain/drug effects , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Salvia miltiorrhiza/chemistry , Alzheimer Disease/diagnosis , Alzheimer Disease/metabolism , Alzheimer Disease/physiopathology , Alzheimer Disease/psychology , Animals , Brain/metabolism , Brain/pathology , Brain/physiopathology , Humans , Molecular Structure , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plants, Medicinal , Plaque, Amyloid , Structure-Activity RelationshipABSTRACT
Neural stem/progenitor cells (NSPCs) exhibit therapeutic potential in neuronal diseases. Previously, we reported that a sulfated polysaccharide (HS) from the sea cucumber Stichopus japonicus increased the proliferation of NSPCs. Since the formation of neurospheres is related with NSPCs proliferation, we investigated the mechanism leading to neurosphere formation with and without HS. The results showed that HS significantly promoted neurosphere formation in a dose-dependent manner at concentrations between 2 and 8 µg/ml. Cell cycle analysis showed that HS increased the percentage of cells in S phase by 2.8-fold, as compared with the control. On the other hand, we observed a significantly rapid aggregation of NSPCs, resulting in formation of neurospheres as early as 2 h after HS treatment. However, the aggregation was not caused by chemotactic migration of NSPCs, as evidenced by the transwell chamber assay. Furthermore, the effect of HS on NSPCs was similar to the tumor necrosis factor-α (TNF-α) that activated nuclear factor NF-κB. Thus, we demonstrated that HS was able to promote cell proliferation and aggregation of NSPCs which could lead to the formation of neurospheres, and suggested that HS can serve as an adjuvant for promoting proliferation of NSPCs and formation of neurospheres.
Subject(s)
Neurons/drug effects , Polysaccharides/pharmacology , Sea Cucumbers/chemistry , Stem Cells/drug effects , Sulfates/chemistry , Animals , Cell Lineage , Neurons/cytology , Polysaccharides/chemistry , Stem Cells/cytologyABSTRACT
To test the effects of a sulfated polysaccharide, Haishen (HS) on the viability and proliferation of neural stem/progenitor cells (NSPCs), we isolated the polysaccharide from the body wall of the sea cucumber Stichopus japonicus by enzymolysis extraction, anion-exchange and gel-permeation chromatography. HS is a highly sulfated fucoidan with a molecular weight of 4.23x10(5) Da. Due to its safety being of invertebrate origin they are less likely to contain infectious agents, the effects of HS on the viability and proliferation of NSPCs in vitro were examined by MTT assay, BrdU labeling and neurosphere formation assay, respectively. Our results showed that HS alone increased NSPC viability in a dose-dependent manner. Moreover, HS acted synergistically with fibroblast growth factor-2 (FGF-2) but not epidermal growth factor (EGF) to enhance the proliferation of NSPCs. Finally, HS did not induce apoptosis of NSPCs. Our findings suggest that HS can serve as an adjuvant for promoting the proliferation of NSPCs.