Abstract
Parkinson's disease (PD), the second most common progressive neurodegenerative disorder, is characterized by complex motor and nonmotor symptoms. The clinical diagnosis of PD is defined by bradykinesia and other cardinal motor features, although several nonmotor symptoms are also related to disability, an impaired quality of life, and shortened life expectancy. Levodopa, which is used as a standard pharmacotherapy for PD, has limitations including a short half-life, fluctuations in efficacy, and dyskinesias with long-term use. There have been efforts to develop complementary and alternative therapies for incurable PD. Yokukansan (YKS) is a traditional herbal medicine that is widely used for treating neurosis, insomnia, and night crying in children. The clinical efficacy of YKS for treating behavioral and psychological symptoms, such as delusions, hallucinations, and impaired agitation/aggression subscale and activities of daily living scores, has mainly been investigated in the context of neurological disorders such as PD, Alzheimer's disease, and other psychiatric disorders. Furthermore, YKS has previously been found to improve clinical symptoms, such as sleep disturbances, neuropsychiatric and cognitive impairments, pain, and tardive dyskinesia. Preclinical studies have reported that the broad efficacy of YKS for various symptoms involves its regulation of neurotransmitters including GABA, serotonin, glutamate, and dopamine, as well as the expression of dynamin and glutamate transporters, and changes in glucocorticoid hormones and enzymes such as choline acetyltransferase and acetylcholinesterase. Moreover, YKS has neuroprotective effects at various cellular levels via diverse mechanisms. In this review, we focus on the clinical efficacy and neuropharmacological effects of YKS. We discuss the possible mechanisms underpinning the effects of YKS on neuropathology and suggest that the multiple actions of YKS may be beneficial as a treatment for PD. We highlight the potential that YKS may serve as a complementary and alternative strategy for the treatment of PD.
Highlights
Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder characterized by neuronal loss in the substantia nigra resulting in striatal dopamine deficiency [1]
Yokukansan (YKS), referred to as Yi gan san (YGS), is traditionally used to treat insomnia, night crying in children, and neurosis in Japan and China [3]
PD is characterized by motor symptoms, nonmotor symptoms, and drug-induced adverse events
Summary
Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder characterized by neuronal loss in the substantia nigra resulting in striatal dopamine deficiency [1]. Novel therapies without the limitations of the current standard therapy for PD are required to enable better management of patients with neurodegenerative disorders and improve their quality of life. The dopamine system is the main pharmacological target for the treatment of PD, as disease pathogenesis is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta [1]. YKS has been reported to be clinically effective for the behavioral and psychological symptoms of dementia (BPSD) It improves NPI subscale measures, such as delusions, hallucinations, and agitation/aggression subscales and activities of daily living scores in patients with BPSD [57]. Studies proving the efficacy of YKS for treating PD are limited, we highlight findings from various PD models that have shed light on the possible mechanisms that might underlie the pharmacotherapeutic effects of YKS for PD
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