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The neuroprotective effect of curcumin by inhibiting the aggregation of α-synuclein on lipopolysaccharide-induced Parkinson’s disease model

Published on May. 31, 2024Total Views: 1077 times Total Downloads: 471 times Download Mobile

Author: GAN Xiaokui SONG Xiaowei ZHANG Ming FANG Yiming MA Longbiao HUANG Baosheng

Affiliation: Department of Neurosurgery, Sir Run Run Hospital, Nanjing Medical University, Nanjing 211112, China

Keywords: Parkinson's disease Curcumin α-synuclein Oxidative stress Neuroinflammation Lipopolysaccharide

DOI: 10.12173/j.issn.1008-049X.202404171

Reference: GAN Xiaokui, SONG Xiaowei, ZHANG Ming, FANG Yiming, MA Longbiao,HUANG Baosheng.The neuroprotective effect of curcumin by inhibiting the aggregation of α-synuclein on lipopolysaccharide-induced Parkinson’s disease model[J].Zhongguo Yaoshi Zazhi,2023,26(12):779-787.DOI: 10.12173/j.issn.1008-049X.202404171.[Article in Chinese]

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Abstract

Objective  To explore the neuroprotective effect of curcumin (Cur) on Parkinson's disease model and its mechanism.

Methods  Sprague-Dawley rats were randomly divided into the control (CON) group, the model (PD) group, and the low-, medium-, and highdose curcumin (Cur) groups, with ten rats in each group. Lipopolysaccharide was injected into the substantia nigra to establish a Parkinson's disease model. Rats in the Cur groups were administered Cur intraperitoneally at doses of 20 mg/kg, 40 mg/kg, and 60 mg/kg daily for 21 days. α-synuclein (α-syn), nuclear transcription factor κB proteins (NF-κB, IKBα, p-NF-κB, p-IKBα) and the activation levels of astrocytes were detected in rat brain tissues by immunohistochemistry (IHC). mRNA levels of pro-inflammatory cytokines (TNF-α, IL-β, IFN-γ, IL-6), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NADPH oxidase complex (gp47phox, gp91phox, gp67phox), and apoptosis-related factors (Bax, Bcl-2, Caspase-3, and Caspase-9) were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The rotarod and pole climbing tests were used to evaluate the motor coordination of the rats.

Results  Compared to the CON group, PD rats showed significantly increased levels of α-syn, p-NF-κB, p-IKBα proteins, activation of astrocytes, TNF-α, IL-β, IFN-γ, IL-6, iNOS, COX- 2, Bax, Caspase-3, Caspase-9, gp47phox, gp91phox and gp67phox mRNA levels (P<0.05); while the Bcl-2 level was significantly decreased (P<0.05). Compared with the PD group, the medium- and high -dose Cur treatment groups inhibited the aggregation of α-syn protein, reduced the activation of the NF-κB pathway, and the expression of inflammatory and apoptosis-related factors (P<0.05). Moreover, medium and high doses of Cur significantly improved the motor coordination in rats, and compared with the PD group, the performance of rotarod and pole climbing tests was significantly improved (P<0.05).

Conclusion  cur may inhibit the aggregation of α-syn by suppressing neuroinflammation and oxidative stress responses, thereby improving motor coordination in Parkinson's disease rats and exerting neuroprotective effects.

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