Neuroprotective Effects of Gagam‐Sipjeondaebo‐Tang, a Novel Herbal Formula, against MPTP‐Induced Parkinsonian Mice and MPP⁺‐Induced Cell Death in SH‐SY5Y Cells

Abstract

Parkinson's disease is a neurodegenerative disease characterized by progressive cell death of dopaminergic neuron and following neurological disorders. Gagam-Sipjeondaebo-Tang (GST) is a novel herbal formula made of twelve medicinal herbs derived from Sipjeondaebo-Tang, which has been broadly used in a traditional herbal medicine. In the present study, we investigated the effects of GST against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor abnormalities in mice and 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in SH-SY5Y cell. First, we found that GST alleviated motor dysfunction induced by MPTP, and the result showed dopaminergic neurons recovery in substantia nigra. In the cell experiment, pretreatment with GST increased the cell viability and attenuated apoptotic cell death in MPP+-treated SH-SY5Y cells. GST also inhibited reactive oxygen species production and restored the mitochondrial membrane potential loss, which were induced by MPP+. Furthermore, GST extract significantly activated ERK and Akt, cell survival-related proteins, in SH-SY5Y cells. The effect of GST preventing mitochondrial dysfunction was antagonized by pretreatment of PD98059 and LY294002, selective inhibitors of ERK and Akt, respectively. Taken together, GST alleviated abnormal motor functions and recovered neuronal cell death, mitochondrial dysfunction, possibly via ERK and Akt activation. Therefore, we suggest that GST may be a candidate for the treatment and prevention of Parkinson's disease.

Efficacy of Hypericum perforatum extract on ultrastructural changes in brain and oxidative damage in Parkinson’s disease

“…More number of dopaminergic neurons and apoptosis was seen in the substantia niagra region in the MPTP group, and treatment with HPE reduced the toxicity of MPTP in brain tissue (Ko et al, 2018). All these indings support that HPE offers neuroprotection against MPTP-induced Parkinson's disease model.…”

“…The fresh brain was serially sectioned and the striatum was separated. The tissue was homogenised in an ice-cold solution of 0.1% M PBS and used for further analysis (Ko et al, 2018).…”

The Neuroprotective Effects of Coreopsis tinctoria and Its Mechanism: Interpretation of Network Pharmacological and Experimental Data

“…In recent years, other herbal extract have also been studied for their neuroprotective effects. Gagam-Sipjeondaebo-Tang (100 μg/ml) could reverse cell viability inhibited by 1 mM MPTP, which was a little weaker compared with the effect of the CT extract here (Ko et al, 2018). Therefore, we suggested that the CT extract might be a candidate for the treatment and prevention of neurodegenerative disease.…”

Co-Administration of Gagam-Sipjeondaebo-Tang and Ibuprofen Alleviates the Inflammatory Response in MPTP-Induced Parkinson’s Disease Mouse Model and RAW264.7 Macrophages

“…SDT was also found to reduce inflammation in a mouse model of muscle atrophy by reducing inflammatory cytokines [17]. In previous studies, GST inhibited neuronal death activation in a PD mouse model [18], but the effect of GST on inflammation has not been well studied. Moreover, co-administration of GST with conventional drugs has not been well studied.…”

“…Experiment groups are as following; control group (administration of saline for 5 day), MPTP group (administration of saline for 5 day, MPTP 20 mg/kg intraperitoneal injections 4 times at 2 h interval), MPTP + GST group (administration of GST 200 mg/kg for 5 day), MPTP + ibuprofen group (administration of ibuprofen 80 mg/kg for 5 day) and MPTP + GST + ibuprofen group (administration of GST 200 mg/kg and ibuprofen 80 mg/kg for 5 day). The dose of all treatments was followed by our previous study [18].…”