The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model

doi:10.1016/j.heliyon.2023.e16921

. 2023 Jun 7;9(6):e16921.

doi: 10.1016/j.heliyon.2023.e16921. eCollection 2023 Jun.

The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model

Xiaoyu Liu^{1

2}, Hao Zhang^{1

3

4}, Chuanfen Li⁵, Zhibin Chen^{1

2}, Qian Gao^{1

2}, Muxuan Han^{1

6}, Feng Zhao^{1

3

4}, Dan Chen⁷, Qiuyue Chen^{1

3

4}, Minghui Hu^{1

3

4}, Zifa Li^{1

3

4}, Sheng Wei^{1

3

4}, Xiwen Geng^{1

3

4}

Affiliations

¹ Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China.
² Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.
³ Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China.
⁴ High Level Key Disciplines of Traditional Chinese Medicine: Basic Theory of Traditional Chinese Medicine, National Administration of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
⁵ College of Physical Education, Shandong Normal University, Jinan, China.
⁶ College of Health Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China.
⁷ Shandong University of Traditional Chinese Medicine, Jinan, China.

PMID: 37484231
PMCID: PMC10360947
DOI: 10.1016/j.heliyon.2023.e16921

The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model

Xiaoyu Liu et al. Heliyon. 2023.

. 2023 Jun 7;9(6):e16921.

doi: 10.1016/j.heliyon.2023.e16921. eCollection 2023 Jun.

Authors

Affiliations

¹ Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China.
² Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.
³ Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, China.
⁴ High Level Key Disciplines of Traditional Chinese Medicine: Basic Theory of Traditional Chinese Medicine, National Administration of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
⁵ College of Physical Education, Shandong Normal University, Jinan, China.
⁶ College of Health Sciences, Shandong University of Traditional Chinese Medicine, Jinan, China.
⁷ Shandong University of Traditional Chinese Medicine, Jinan, China.

PMID: 37484231
PMCID: PMC10360947
DOI: 10.1016/j.heliyon.2023.e16921

Abstract

Background: Curcumin is a natural compound with extensive pharmacological effects. This research is to verify the optimal dose and administration duration efficacy of curcumin in alleviating the movement symptoms of Parkinson's disease (PD).

Methods: Wistar rats were divided into six groups including control, model, levodopa treatment and low/middle/high (40/80/160 mg/kg/d) curcumin treatment groups. After stereotactic brain injection of 6-hydroxydopamine (6-OHDA), curcumin was given by intragastric administration for 2 weeks. To evaluate the drug effect, the rats received behavioral tests including apomorphine (APO)-induced rotation test, rotarod test and open field test. Then the rats were sacrificed and the brain slices including substantia nigra pars compacta (SNc) were used for immunofluorescence staining.

Results: After 6-OHDA injection, the model group showed typical movement symptoms including the severe APO-induced rotation to the healthy side, decreased latency in the rotarod with constant or accelerative mode, and decreased total distance and average speed in the open field test. In the results of immunofluorescence staining, the 6-OHDA induced a severe damage of dopaminergic neurons in SNc. The 160 mg/kg/d treatment of curcumin to intervene for 2 weeks alleviated most of the behavioral disorders but the 40/80 mg/kg/d treatment showed limitations. Then, we compared the effect of 1 week intervention to the 2 weeks with 160 mg/kg/d treatment of curcumin to intervene and results indicated that the treatment of 2 weeks could better alleviate the symptoms.

Conclusions: Curcumin alleviated 6-OHDA-induced movement symptoms in a PD rat model. Additionally, the effect of curcumin against PD indicated dose and duration dependent and the intervention of 160 mg/kg/d for 2 weeks showed optimally therapeutic effect.

Keywords: 6-Hydroxydopamine; Behavioral tests; Curcumin; Movement symptoms; Parkinson's disease; Substantia nigra pars compacta.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
Experiment schedule and results of the rat model of Parkinson's disease establishing, treatment and behavioral tests. Data are shown as mean ± standard error of the mean (SEM). (A) After 7 days of adaptive feeding, all rats were injected with 6-hydroxydopamine except for the control group by brain stereotaxic technique. Open field test and rotation experiment were performed at 1 week after operation. In the Curcumin group (including low, middle and high dose) and the l-DOPA group, all rats were performed by intragastric administration for 2 weeks. Then, all rats were carried on the APO induced rotation experiment, open field test, rotation experiment and the immunofluorescence of tyrosine hydroxylase 2 weeks after the administration. (B) The results of APO induced rotation after 2 weeks in intragastric administration, n = 6. (C) The latency of rotation in constant speed mode after 2 weeks of intragastric administration, n = 6. (D) The latency of rotation experiment in accelerative speed after 2 weeks of intragastric administration, n = 6. (E) The drop speed of rotation experiment in accelerative speed after 2 weeks of intragastric administration, n = 6. (F) The total distance of open field test, n = 6. (G) The average speed of open field test, n = 6. (H) The latency of rotation experiment in constant speed mode of rats in the high dose curcumin (160 mg/kg/d) group, n = 6. (I) The latency of rotation experiment in accelerative speed mode of rats in the high dose curcumin (160 mg/kg/d) group, n = 6. (J) The drop speed of rotation experiment in accelerative speed mode of rats in the high dose curcumin (160 mg/kg/d) group, n = 6. (K) The total distance of open field test of rats in the high dose curcumin (160 mg/kg/d) group, n = 6. (L) The average speed of open field test of rats in the high dose curcumin (160 mg/kg/d) group, n = 6. (M) Representative figure of the immunofluorescence detection of rats in brain slices containing substantia nigra pars compacta in the control, model, l-DOPA and curcumin (40/80/160 mg/kg/d) group, n = 3. **p < 0.01, ***p < 0.001, ****p < 0.0001 compared to the control group, #p < 0.05, ##p < 0.01, ###*p <* 0.001, ####*p <* 0.0001 compared to the PD-2W group, $*p <* 0.05, $$p < 0.01 compared the PD + Cur160-1W group.

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References

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[1] Galvan A., Devergnas A., Wichmann T. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state. Front. Neuroanat. 2015;9:5. doi: 10.3389/fnana.2015.00005. - DOI - PMC - PubMed

[2] Galvan A., Devergnas A., Wichmann T. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state. Front. Neuroanat. 2015;9:5. doi: 10.3389/fnana.2015.00005. - DOI - PMC - PubMed

[3] Hussein A., Guevara C.A., Del Valle P., Gupta S., Benson D.L., Huntley G.W. Non-motor symptoms of Parkinson's disease: the neurobiology of early psychiatric and cognitive dysfunction. Neuroscientist. 2021 doi: 10.1177/10738584211011979. - DOI - PMC - PubMed

[4] Hussein A., Guevara C.A., Del Valle P., Gupta S., Benson D.L., Huntley G.W. Non-motor symptoms of Parkinson's disease: the neurobiology of early psychiatric and cognitive dysfunction. Neuroscientist. 2021 doi: 10.1177/10738584211011979. - DOI - PMC - PubMed

[5] Simon D.K., Tanner C.M., Brundin P. Parkinson disease epidemiology, pathology, genetics, and pathophysiology. Clin. Geriatr. Med. 2020;36(1):1–12. doi: 10.1016/j.cger.2019.08.002. - DOI - PMC - PubMed

[6] Simon D.K., Tanner C.M., Brundin P. Parkinson disease epidemiology, pathology, genetics, and pathophysiology. Clin. Geriatr. Med. 2020;36(1):1–12. doi: 10.1016/j.cger.2019.08.002. - DOI - PMC - PubMed

[7] Bastide M.F., Meissner W.G., Picconi B., Fasano S., Fernagut P.O., Feyder M., Francardo V., Alcacer C., Ding Y., Brambilla R., Fisone G., Jon Stoessl A., Bourdenx M., Engeln M., Navailles S., De Deurwaerdere P., Ko W.K., Simola N., Morelli M., Groc L., Rodriguez M.C., Gurevich E.V., Quik M., Morari M., Mellone M., Gardoni F., Tronci E., Guehl D., Tison F., Crossman A.R., Kang U.J., Steece-Collier K., Fox S., Carta M., Angela Cenci M., Bezard E. Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease. Prog. Neurobiol. 2015;132:96–168. doi: 10.1016/j.pneurobio.2015.07.002. - DOI - PubMed

[8] Bastide M.F., Meissner W.G., Picconi B., Fasano S., Fernagut P.O., Feyder M., Francardo V., Alcacer C., Ding Y., Brambilla R., Fisone G., Jon Stoessl A., Bourdenx M., Engeln M., Navailles S., De Deurwaerdere P., Ko W.K., Simola N., Morelli M., Groc L., Rodriguez M.C., Gurevich E.V., Quik M., Morari M., Mellone M., Gardoni F., Tronci E., Guehl D., Tison F., Crossman A.R., Kang U.J., Steece-Collier K., Fox S., Carta M., Angela Cenci M., Bezard E. Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease. Prog. Neurobiol. 2015;132:96–168. doi: 10.1016/j.pneurobio.2015.07.002. - DOI - PubMed

[9] Beudel M., Brown P. Adaptive deep brain stimulation in Parkinson's disease. Park. Relat. Disord. 2016;22(Suppl 1):S123–S126. doi: 10.1016/j.parkreldis.2015.09.028. - DOI - PMC - PubMed

[10] Beudel M., Brown P. Adaptive deep brain stimulation in Parkinson's disease. Park. Relat. Disord. 2016;22(Suppl 1):S123–S126. doi: 10.1016/j.parkreldis.2015.09.028. - DOI - PMC - PubMed

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The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model

Affiliations

The dosage of curcumin to alleviate movement symptoms in a 6-hydroxydopamine-induced Parkinson's disease rat model

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

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