The attenuation of HIV-1 Tat-induced neurotoxicity by Salvianic acid A and Danshen granule

Int J Biol Macromol. 2019 Mar 1:124:863-870. doi: 10.1016/j.ijbiomac.2018.11.146. Epub 2018 Nov 29.

Abstract

The neurotoxicity of HIV-1 Tat protein contributes significantly to the pathogenesis of HAND, and hence the attractive therapeutic strategies focusing on Tat-induced neurotoxicity are warranted. Salvia miltiorrhiza have been known to antioxidant property and neuroprotective effects. The Danshen granule is the pharmaceutical dosage forms of Salvia miltiorrhiza and Salvianic acid A is an essential chemical constituent of Salvia miltiorrhiza. However, the protective effects of Salvianic acid A and Danshen granule on Tat-induced neurotoxicity remain unknown. Here, we found that Salvianic acid A and Danshen granule remarkable inhibited Tat-induced cell death, blocked LDH release and rescued dendritic spine loss. Furthermore, Salvianic acid A and Danshen granule significantly ameliorates Tat-induced intracellular ROS and MDA production, attenuates cell apoptosis. In addition, Salvianic acid A and Danshen granule pretreatment obviously increases antioxidant enzymatic activity of CAT, SOD and GSH-Px and inhibits apoptotic pathways. In conclusion, this study demonstrated that Salvianic acid A and Danshen granule provides substantial neuroprotection against Tat-induced neurotoxicity, which may be new therapeutic agent in Tat induced HAND or neurodegenerative diseases.

Keywords: Danshen granule; Neuroprotective effects; Salvianic acid A.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Differentiation
  • Cell Survival / drug effects
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism
  • Gene Expression Regulation / drug effects
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • L-Lactate Dehydrogenase / genetics
  • L-Lactate Dehydrogenase / metabolism
  • Lactates / isolation & purification
  • Lactates / pharmacology*
  • Malondialdehyde / antagonists & inhibitors
  • Malondialdehyde / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microtomy
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Rats
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism
  • Salvia miltiorrhiza / chemistry*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Tissue Culture Techniques
  • tat Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors*
  • tat Gene Products, Human Immunodeficiency Virus / toxicity

Substances

  • Lactates
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • tat Gene Products, Human Immunodeficiency Virus
  • 3,4-dihydroxyphenyllactic acid
  • Malondialdehyde
  • L-Lactate Dehydrogenase
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase