Danhong injection facilitates recovery of post-stroke motion deficit via Parkin-enhanced mitochondrial function

Restor Neurol Neurosci. 2019;37(4):375-395. doi: 10.3233/RNN-180828.

Abstract

Background: A cerebral ischemic stroke involves mitochondrial dysfunction, motor deficits, and paralysis; and Danhong injection (DHI) might possess mitochondrial protection and functional recovery in a stroke subject through promoting expression of parkin, a ubiquitin ligase playing a key role in the regulation of proteins and mitochondria quality control.

Objective: To investigate the therapeutic effects of DHI on the histological, cellular, and functional recovery of Wistar rats after middle cerebral artery occlusion/reperfusion (MCAO/R).

Methods: One hundred and twenty healthy male Wistar rats (250-300 g), were randomly assigned to six groups (twenty rats/group). Rats were subjected to 1 h MCAO/R and subsequently administered the intravenous doses of DHI (0.75, 1.5, and 3 mL/kg) to the respective groups (twice a day for 14 days). Unlike the other groups, the sham group received surgery without vessel occlusion. All the animals were tested for gait behavior using the CatWalk system. The body weight/survival rates were recorded daily for 14 days. The parkin protein expression of the brain tissue was quantified by immunohistochemistry analysis. Additionally, cultured cortical neurons were incubation with DHI or minocycline (MC) and then deprived of oxygen and glucose for 2 h (to resemble ischemic/reperfusion), followed by 4 h reoxygenation. Cellular and mitochondrial phenotypes were assayed by high content analysis.

Results: Neurological integrity and paw parameters of the animals were altered in the model group but significantly ameliorated by DHI administration. Also, the infarct volume and survival rate were significantly improved in DHI groups. DHI enhanced the expression of parkin protein in the brain and improved the relative mitochondrial reductase activity of the cultured neurons.

Conclusions: The overall result shows that daily intervention with DHI provides neuroprotection and survival to improve gait motion in Wistar rats.

Keywords: Ischemic stroke; danhong injection; gait disorder; mitochondrial dysfunction; neurological deficits; parkin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia* / complications
  • Brain Ischemia* / drug therapy
  • Brain Ischemia* / metabolism
  • Cells, Cultured
  • Disease Models, Animal
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Gait Disorders, Neurologic* / etiology
  • Gait Disorders, Neurologic* / metabolism
  • Gait Disorders, Neurologic* / prevention & control
  • Mitochondria* / drug effects
  • Mitochondria* / enzymology
  • Neurons* / drug effects
  • Neurons* / metabolism
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Recovery of Function* / drug effects
  • Stroke* / complications
  • Stroke* / drug therapy
  • Stroke* / metabolism
  • Ubiquitin-Protein Ligases* / drug effects
  • Ubiquitin-Protein Ligases* / metabolism

Substances

  • Drugs, Chinese Herbal
  • Neuroprotective Agents
  • danhong
  • Ubiquitin-Protein Ligases
  • parkin protein