Advances of curcumin in nervous system diseases: the effect of regulating oxidative stress and clinical studies

Abstract

In recent years, researchers have highly observed that neurological disorders (NSDs) with the aging of the population are a global health burden whose prevalence is increasing every year. Previous evidence suggested that the occurrence of neurological disorders is correlated with predisposing factors such as inflammation, aging, and injury. Particularly, the neuronal cells are susceptible to oxidative stress, leading to lesions caused by high oxygen-consuming properties. Oxidative stress (OS) is a state of peroxidation, which occurs as a result of the disruption of the balance between oxidizing and antioxidizing substances. The oxidative intermediates such as free radicals, hydrogen peroxide (H₂O₂), and superoxide anion (O²-) produced by OS promote disease progression. Curcumin, a natural diketone derived from turmeric, is a natural antioxidant with a wide range of neuroprotective, anti-inflammatory, anti-tumor, anti-aging, and antioxidant effects. Fortunately, curcumin is recognized for its potent antioxidant properties and is considered a promising candidate for the prevention and treatment of neurological diseases. Consequently, this review elucidates the mechanisms by which curcumin mitigates oxidative stress and emphasizes the potential in treating nervous system disorders, including depression, Alzheimer's disease, Parkinson's disease, epilepsy, subarachnoid hemorrhage, and glioblastoma. We aim to provide a new therapeutic option for the management of neurological diseases.

Keywords: antioxidant properties; curcumin; molecular mechanism; neurological disorders; oxidative stress.

FIGURE 1

Schematic diagram of the pharmacokinetics of curcumin in vivo. The administration methods of curcumin (CU) include oral and the injection of the vein and abdominal cavity. CU entering the body is mainly distributed in the liver, kidneys, brain, and lungs. Particularly, CU could cross the blood-brain barrier in the brain, which is the basis for treating neurological disorders. The liver is the main metabolizing organ for curcumin and can generate a range of metabolites such as CU glucosinolates, CU sulfates, and hydrogenated curcuminoids by O-substitution and reduction pathways. Renal excretion is the metabolic pathway for CU glucosinolate and CU sulfate. Meanwhile, CU can be excreted through bile.

FIGURE 2

Mechanisms of Curcumin in the Treatment of Alzheimer’s Disease (AD). The mechanism of AD by affecting oxidative stress with Curcumin (CU). Curcumin reduces the AB and the hyperphosphorylation of tau proteins in the brain. In neuronal cells, curcumin increases the activity of the SOD enzyme to reduce mitochondrial dysfunction caused by oxidative stress. Meanwhile, CU improved the phosphorylation process of the AKT/p38 MAPK pathway to reverse neuronal apoptosis caused by oxidative stress.

FIGURE 3

Mechanisms of curcumin in the treatment of Parkinson’s disease (PD). Curcumin (CU) could inhibit mitochondrial damage by oxidative stress in neuronal cells, and promote degradation of α-syn by autophagy through agonism of the Nrf2 transcription factor. Meanwhile, CU could inhibit inflammatory responses and intracellular antioxidant levels by affecting TLP4/NF-κB and Wnt/β-catenin pathways.