Research progress in mechanism of curcumin in treatment of Parkinson disease / 中国药理学与毒理学杂志

ABSTRACT

Curcumin (Cur) is an important bioactive component of polyphenols in the rhizomes of Curcuma longa L., Tulipa gesneriana L. and other Curcuma plants. It has a wide range of pharmacological effects such as anti-tumor, anti-atherosclerosis, anti-inflammatory, and neuroprotection. Parkinson disease (PD) is a neurodegenerative disease that often occurs in the elderly. Its main pathological characteristics are the characteristic loss of substantia nigra dopaminer?gic neurons, the decrease of dopamine content in the striatum, and the formation of Lewy bodies. At present, the main methods of clinical treatment of PD include drug therapy and surgical operation, but due to its complicated pathogene?sis, they can only play a role in relieving, but cannot be completely cured. Modern pharmacological studies have shown that Cur has certain effects in the treatment of PD. ① Anti-oxidative stress oxidative stress is closely related to the degeneration of dopaminergic neurons. Studies have found that Cur can increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce malondialdehyde (MDA) content, thereby reducing oxidative stress damage and protecting dopaminergic neuron.②Reduce inflammation in brain tissueneuroinflammation plays an impor?tant role in the development of PD. Reducing the level of inflammatory factors can have a certain therapeutic effect on PD. Studies have shown that high-dose Cur can reduce the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis fac?tor-α (TNF-α) in brain tissue, reduce inflammation, inhibit further neuronal damage, improve learning and memory, and exert neuroprotective effects. ③ Activation of autophagy the abnormal accumulation of α-Synuclein (α-Syn) in Lewy bodies is closely related to PD, and autophagy dysfunction leads to α-Syn clearance obstacles and an important factor of abnormal aggregation. Cur can increase the expression of microtubule-associated protein 1 light chain 3 (LC3-Ⅱ) and lysosome-associated membrane protein 2A (LAMP2A), and reduce the protein and mRNA expression of α-Syn. It can be seen that Cur promotes the elimination ofα-Syn and protects neurons from damage by activating autophagy.④Inhi?bition of mitochondrial dysfunctionmitochondria plays a central regulatory role in the process of cell apoptosis, and mito?chondrial dysfunction is related to reactive oxygen species, energy and mitochondrial membrane potential, which may cause substantia nigra striatal neuropathy. Experiments have shown that Cur can reduce the active oxygen content in PC12 cells induced by MPP+, maintain the normal membrane potential of mitochondria, thereby stabilizing mitochondrial function and inhibiting PC12 cell apoptosis. This study summarized the action mechanism of Cur in the treatment of PD, and clarified the basis of its pharmacodynamics, providing a reference for the clinical research and new drug develop?ment research of Cur in the treatment of PD.