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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (7): 777-783.doi: 10.3736/jcim20120708

• Original Experimental Research • Previous Articles     Next Articles

Selective protection of nigral dopaminergic neurons by echinacoside in a rat model of Parkinson disease induced by rotenone

Feng Xin-ying1,2,Zhu Min3,4,Zhang Qi-qi1,Chen Yi-ping1,Li Wen-wei1,3()   

  1. 1. Laboratory of Neurophysiology and Neurophathology, Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
    2. Quality Control Department of Shanghai Xudong Haipu Pharmaceutical Co., Ltd, Shanghai 201206, China
    3. Institute of Neurology, Fudan University, Shanghai 200040, China
    4. State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China
  • Received:2012-03-15 Accepted:2012-03-31 Online:2012-07-20 Published:2018-07-15
  • Contact: Wen-wei Li E-mail:wenweili2000@yahoo.com.cn

Objective: To observe the protective effects of echinacoside on rotenone-induced damages in rats.
Methods: Healthy male Sprague-Dawley rats, weighing from 200 to 220 g, were randomly divided into five groups with 20 rats in each group: control group, rotenone group and echinacoside groups of low, medium and high doses (20, 40 and 80 mg/(kg·d)). Rats in the rotenone group were injected intraperitoneally for four weeks with rotenone (2.75 mg/(kg·d)), dissolved into dimethyl sulfoxide; rats in the control group were injected intraperitoneally with dimethyl sulfoxide daily, and rats in the echinacoside groups received daily intraperitoneal injection of rotenone along with echinacoside gastric perfusion for four weeks. Modified neurological severity score was used to evaluate neurobehavior of the animals; dopaminergic neurons in substantia nigra were observed by immunochemical method and dopamine concentration in striatum was determined by a fluorescence spectrophotometer. Biomarkers of liver and kidney damage were also measured.
Results: In the rotenone group, the rats suffered from severe neurological disability (P<0.01), and the number of dopaminergic neurons in substantia nigra and dopamine concentration in striatum were decreased (P<0.05) compared with the normal control group; levels of the biomarkers for evaluating liver and kidney damage were increased (P<0.05). In the echinacoside groups, the neurological disability and the loss of dopaminergic neurons in substantia nigra were suppressed and dopamine concentrations in striatum were increased (P<0.05), but the liver and kidney damage was not improved (P>0.05).
Conclusion: Rotenone causes severe damages to dopaminergic neurons, liver and kidney in rats and echinacoside selectively reverses dopaminergic neuronal injury.

Key words: Parkinson disease, rotenone, echinacoside, liver injury, kidney injury, dopaminergic neurons, rats

"

Group n mNSS
Normal control 14 0
Rotenone 14 12.86±2.25**
ECH (20 mg/(kg·d), ip)
plus rotenone
14 8.07±1.73**△
ECH (40 mg/(kg·d), ip)
plus rotenone
14 5.79±1.63**△▲
ECH (80 mg/(kg·d), ip)
plus rotenone
14 3.57±1.65**△▲□

"

Group n ALT AST
Normal control 14 31.75±8.59 85.76±16.41
Rotenone 14 84.57±14.14* 202.74±28.16*
ECH (20 mg/(kg·d), ip) plus rotenone 14 81.45±13.47* 198.62±29.82*
ECH (40 mg/(kg·d), ip) plus rotenone 14 82.95±14.55* 204.35±31.01*
ECH (80 mg/(kg·d), ip) plus rotenone 14 79.35±12.03* 201.16±28.29*

"

Group n Creatinine (μmol/L) Blood urea nitrogen (mmol/L)
Normal control 14 31.32±6.43 4.93±0.85
Rotenone 14 67.21±10.39* 18.81±2.11*
ECH (20 mg/(kg·d), ip) plus rotenone 14 65.78±11.81* 18.35±2.51*
ECH (40 mg/(kg·d), ip) plus rotenone 14 62.38±12.21* 17.55±1.87*
ECH (80 mg/(kg·d), ip) plus rotenone 14 63.99±11.76* 17.36±1.79*

Figure 1

Effects of echinacoside on dopaminergic neurons in substantia nigra of rats exposed to rotenone observed by immunochemical method (Light microscopy, ×100) A: Normal control group; B: Rotenone group; C: Echinacoside (40 mg/(kg·d), ip) plus rotenone group; D: Echinacoside (80 mg/(kg·d), ip) plus rotenone group. ip: intraperitoneal injection."

"

Group n Number of dopaminergic neurons
Normal control 7 118.85±13.18
Rotenone 7 61.29±9.92*
ECH (20 mg/(kg·d), ip) plus rotenone 7 86.71±11.21
ECH (40 mg/(kg·d), ip) plus rotenone 7 96.57±13.43
ECH (80 mg/(kg·d), ip) plus rotenone 7 104.42±11.25

Figure 2

Effects of echinacoside on expression of tyrosine hydroxylase in striatum of rats exposed to rotenone observed by immunochemical method (Light microscopy, ×50) A: Normal control group; B: Rotenone group; C: Echinacoside (80 mg/(kg·d), ip) plus rotenone group."

"

Group n Dopamine concentration (μg/g)
Normal control 7 9.39±1.23
Rotenone 7 5.57±0.71*
ECH (20 mg/(kg·d), ip) plus rotenone 7 8.23±0.91
ECH (40 mg/(kg·d), ip) plus rotenone 7 8.79±0.79
ECH (80 mg/(kg·d), ip) plus rotenone 7 8.83±0.87
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