Salvia miltiorrhiza is a very important herbal
drug of
traditional Chinese medicine. Bioactive constituents are represented by two main groups of secondary metabolites, the lipophilic diterpenic
quinones known as tanshinones and the hydrophilic
depsides known as salvianolic
acids. S. miltiorrhiza extracts and single constituents have been shown to have positive effects in central nervous system neuronal injury and degeneration in several animal models by various
biological mechanisms. Both tanshinones and
depsides protect against β-
amyloid-induced toxicity, but their mechanisms are complementary due to their different structure, the lipophilic tanshinones and the hydrophilic
depsides. A number of anti-inflammatory mechanisms is also reported for both tanshinones and
depsides. Common mechanisms are the effects on
cytokines,
inducible nitric oxide synthase, and
glial fibrillary acidic protein. In addition,
depsides are inhibitors of
nitric oxide and
cyclooxygenase-2, while tanshinones inhibit
hypoxia-inducible factor-1α and nuclear factor kappa β. Both constituents can also modulate the protection of the central nervous system from oxidative stress with different but complementary mechanisms: tanshinones can enhance the activities of
superoxide dismutase and
glutathione peroxidase, while
depsides can decrease
reactive oxygen species.Furthermore, neuronal death underlies the symptoms of many human
neurological disorders, including Alzheimer's, Parkinson's, and Huntington's diseases,
stroke, and
amyotrophic lateral sclerosis. Both classes of constituents can enhance the antiapoptotic
B-cell leukemia protein-2 family members and decrease the translocation of
cytochrome c, and, in addition,
depsides decrease
caspase-3 and intracellular Ca(2+). Again, both classes of constituents have an activity on
vascular endothelial growth factor but it is opposite, whereas tanshinones are inhibitors of
acetylcholinesterase.Besides the extensive studies reporting on the
biological mechanisms of
depsides and tanshinones, pharmacokinetics studies are still very limited and not conclusive, especially for brain distribution. Further research is warranted to address the mechanisms of the multitarget actions of S. miltiorrhiza constituents and to translate this knowledge into clinical practice.