Effects of Salvia miltiorrhiza on CNS Neuronal Injury and Degeneration: A Plausible Complementary Role of Tanshinones and Depsides.

Salvia miltiorrhiza Bunge (Lamiaceae), is a very important herbal drug of the 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. Salvia miltiorrhiza extracts and single constituents have shown to have positive effects in CNS neuronal injury and degeneration in several animal models by various biological mechanisms. Both tanshinones and depsides are Aβ inhibitors but their mechanisms are complementary due to their different structure, the lipophilic tanshinones and the hydrophilic depsides. A number of anti-inflammatory mechanisms are also reported for both tanshinones and depsides. Common mechanisms are the effects on cytokines, iNOS and GFAP. In addition, depsides are inhibitors of NO and COX2 while tanshinones inhibit HIF-α and NF-kβ. Both constituents can also modulate the protection of CNS from oxidative stress with different but complementary mechanisms: tanshinones can enhance the activities of SOD, and GSH-Px while depsides can decrease reactive ROS. 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 pro-apoptotic Bcl-2 family members and decrease the translocation of cytochrome c, and in addition, depsides decrease caspase-3 and intracellular Ca2+. Again, both classes of constituents have an activity on VEGF but it is opposite, whereas tanshinones are inhibitors of AChE. 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.