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Journal of Chinese Integrative Medicine ›› 2012, Vol. 10 ›› Issue (9): 1018-1024.doi: 10.3736/jcim20120911

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Effects of Chinese herbal medicine Tianqi Pingchan Granule on G protein-coupled receptor kinase 6 involved in the prevention of levodopa-induced dyskinesia in rats with Parkinson disease

Na Wu1, Lu Song1, Xin-xin Yang1, Jiang-lei Wei2, Zhen-guo Liu1()   

  1. 1. Department of Neurology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
    2. Department of Emergency, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
  • Received:2012-02-12 Accepted:2012-02-28 Online:2012-09-20 Published:2018-09-15
  • Contact: Zhen-guo Liu E-mail:zhenguoliu2004@yahoo.com.cn

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Objective: To investigate the effects of Tianqi Pingchan (TQPC) Granule, a compound traditional Chinese herbal medicine with antitremor activity, on levodopa-induced dyskinesia and the expression of G protein-coupled receptor kinase 6 (GRK6) in rats with Parkinson disease (PD).

Methods: The hemi-Parkinsonian rat model was established by sterotaxically injecting 6-hydroxydopa (6-OHDA) to the right medial forebrain bundle. Rats with PD were randomly divided into 5 groups with 5 in each. PD group was intraperitoneally injected with vitamin C; levodopa group was intraperitoneally injected with levodopa and benserazide; low-, medium- and high-dose TQPC Granule groups were intraperitoneally injected with levodopa and benserazide and treated with different dosages of TQPC Granule by gavage for 29 d. Another 5 rats were served as control with sham-operation. The behaviors of rats were observed and classified with abnormal involuntary movement (AIM) score. The expression of GRK6 in the striate of rats was detected by immunohistochemical method and Western blotting.

Results: AIM score was increased and the expression of GRK6 protein in lesion side was decreased after the long-tern treatment with levodopa and benserazide in rats. The AIM scores of rats with PD were decreased after TGPC Granule treatment. Immunohistochemical results showed that the number of GRK6-positive cells in medium- and high-dose TQPC Granule groups was increased as compared to that in the levodopa group (P<0.05). The expression level of GRK6 protein was increased in medium-dose TQPC Granule group when compared with the levodopa group (P<0.01), which was observed by Western blotting.

Conclusion: TGPC Granule can increase the expression of GRK6, inhibit the increase of AIM, and reduce the incidence of levodopa-induced dyskinesia in rats with PD.

Key words: Parkinson’s disease;, levodopa, dyskinesia, drugs, Chinese herbal, G-protein-coupled receptor kinase 6, rats

Table 1

AIM scores in different groups （$\overline{x}$±s）"

Time Group n AIM scores
Orolingual Upper limb Axial Locomotor
2 d Levodopa 5 1.44±0.18 1.51±0.22 2.49±0.17 2.67±0.28
Low-dose TQPC Granule 5 1.51±0.17 1.58±0.19 2.42±0.16 2.62±0.23
Medium-dose TQPC Granule 5 1.40±0.19 1.56±0.28 2.51±0.22 2.71±0.34
High-dose TQPC Granule 5 1.42±0.24 1.62±0.26 2.38±0.15 2.62±0.23
8 d Levodopa 5 1.82±0.17 1.93±0.20 2.71±0.41 3.20±0.25
Low-dose TQPC Granule 5 1.89±0.21 1.91±0.19 2.76±0.41 3.16±0.20
Medium-dose TQPC Granule 5 1.56±0.18□ 1.76±0.16 2.58±0.29 2.93±0.19■
High-dose TQPC Granule 5 1.51±0.22 1.67±0.22 2.42±0.24 2.60±0.06
15 d Levodopa 5 2.11±0.22 2.18±0.15 2.93±0.28 3.36±0.28
Low-dose TQPC Granule 5 1.84±0.17 2.09±0.12 2.71±0.37 3.09±0.24
Medium-dose TQPC Granule 5 1.47±0.14□ 1.71±0.22□ 2.69±0.24 2.84±0.19▲
High-dose TQPC Granule 5 1.33±0.11 1.51±0.22 2.38±0.20 2.58±0.15■
22 d Levodopa 5 2.40±0.37 2.56±0.16 3.18±0.15 3.38±0.29
Low-dose TQPC Granule 5 1.96±0.20▲ 2.13±0.14▲ 2.62±0.28▲ 3.11±0.21
Medium-dose TQPC Granule 5 1.49±0.13□ 1.69±0.20□ 2.29±0.13 2.67±0.11▲
High-dose TQPC Granule 5 1.29±0.13■ 1.49±0.23 2.24±0.18 2.53±0.15
29 d Levodopa 5 2.36±0.36 2.60±0.13 3.16±0.13 3.47±0.23
Low-dose TQPC Granule 5 2.04±0.13 2.13±0.20▲ 2.76±0.26▲ 3.24±0.14
Medium-dose TQPC Granule 5 1.33±0.21□ 1.67±0.18□ 2.33±0.16□ 2.56±0.14▲
High-dose TQPC Granule 5 1.20±0.09 1.53±0.21 2.11±0.78■ 2.29±0.10■

Table 2

Effects of different doses of Tianqi Pingchan Granule on striatal GRK6 expression in rats with levodopa-induced PD"

Group n IOD (×103)
Lesioned side Unlesioned side
Sham 5 6.20±0.55 6.03±0.59
PD 5 4.54±0.85** 6.01±0.72
Levodopa 5 3.53±0.71△ 5.90±1.51
Low-dose TQPC Granule 5 4.17±1.20 5.72±1.30
Medium-dose TQPC Granule 5 4.31±0.95▲ 6.35±1.26
High-dose TQPC Granule 5 4.88±1.24▲ 6.03±1.14

Figure 1

Immunohistochemical method confirmed the effects of different doses of TQPC Granule on GRK6 expression in striatum of rats with PD (light microscopy, ×400) 1: Sham group; 2: PD group; 3: Levodopa group; 4: Low-dose TQPC Granule group; 5: Medium-dose TQPC Granule group; 6: High-dose TQPC Granule group. U: Unlesioned side; L: Lesioned side; PD: Parkinson disease; TQPC: Tianqi Pingchan; GRK6: G protein coupled receptor kinase 6."

Figure 2

Western blot results confirmed the effects of different doses of TQPC Granule on GRK6 expression in striatum of rats with PD 1, 2: Sham group; 3, 4: PD group; 5, 6: Levodopa group; 7, 8: Low-dose TQPC Granule group; 9, 10: Medium-dose TQPC Granule group; 11, 12: High-dose TQPC Granule group; 1, 3, 5, 7, 9, 11: Unlesioned side; 2, 4, 6, 8, 10, 12: Lesioned side. PD: Parkinson disease; TQPC: Tianqi Pingchan; GRK6: G protein coupled receptor kinase 6."

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