Synergistic Neuroprotective Effect of Schisandra chinensis and Ribes fasciculatum on Neuronal Cell Death and Scopolamine-Induced Cognitive Impairment in Rats.

Eunkuk Park,Min Jeong Ryu,Chun Whan Choi,Seon-Yong Jeong,Jun Young Heo,Nam Ki Kim,Youngha Seo,Memoona Kanwal,Subin Yeo,Jeonghyun Kim,Mun Hyoung Bae

doi:10.3390/ijms20184517

Abstract

Mild cognitive impairment (MCI) is considered as a transitional stage between aging and Alzheimer’s disease. In the present study, we examined the protective effect of Schisandra chinensis (SC) and Ribes fasciculatum (RF) on neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley® rats in vivo. A mixture of SC and RF extracts (SC+RF) significantly protected against hydrogen peroxide-induced PC12 neuronal cell death. The neuroprotective effect of SC+RF on scopolamine-induced memory impairment in rats was evaluated using the passive avoidance test and the Morris water maze test. In the passive avoidance test, SC+RF-treated rats showed an increased latency to escape, compared to the scopolamine-treated rats. Moreover, SC+RF treatment significantly reduced escape latency in water maze test, compared to treatment with scopolamine alone. To verify the long-term memory, we performed probe test of water maze test. As a result, rat treated with SC+RF spent more time in the target quadrant. Consistent with enhancement of memory function, the brain derived neurotrophic factor (BDNF) and its downstream molecules (pERK, pATK, and pCREB) are increased in SC+RF treatment in hippocampal area compared with scopolamine treated group. These results suggest that a mixture of SC and RF extracts may be a good therapeutic candidate for preventing mild cognitive impairment.

Highlights

Mild cognitive impairment (MCI) is known as early dementia and isolated memory impairment, which commonly affects elderly people [1]
Cells were treated with various concentrations of H2O2 (0–100 μM) for 1 h and neuronal apoptosis was measured by the was Pmmroeetaaesncut(irSveEedMEbff)y.e*ct:thpeo
The mixture of 50 μg/mL Schisandra chinensis (SC)+Ribes fasciculatum (RF) exerted a greater protective effect than the single extracts of SC or RF at 50 μg/mL (Figure 3B). These results suggested that 30% ethanol extracts of SC and RF at a 7:3 ratio exerted a synergistic protective effect against H2O2-induced cell death in PC12 neuronal cells

Summary

Introduction

Mild cognitive impairment (MCI) is known as early dementia and isolated memory impairment, which commonly affects elderly people [1]. United States Food and Drug Administration (FDA)-approved drugs inhibiting the cholinesterase or N-methyl-d-aspartate receptor, such as Aricept (donepezil), Exelon (rivastigmine), and Namenda (memantine), only mitigate the symptoms of Alzheimer’s disease [4,5,6] Some of these drugs should not be used in the long-term due to how they affect heart rate and the nervous system, causing side effects such as arrhythmia [7]. Schisandra chinensis (SC), a deciduous woody vine, has been used as a traditional herbal medicine for the treatment of cancer and diabetes via immunomodulatory and antioxidant activities [9] Bioactive compounds such as schisandrin B, a dibenzocyclooctadiene derivative isolated from SC, have been studied for their neuroprotective effects in scopolamine-induced amnesia, amyloid beta (Aβ) peptide-induced neurotoxicity, and cisplatin-induced neurotoxicity [10,11]. Protective effects of various extracts of SC were reported on neuronal injury and memory impairment, the underlying mechanism of it still did not defined with the brain derived neurotrophic factor (BDNF) signaling, and revealed that correlation with antioxidant enzyme activation [13,14], NF-kB inhibition [15], and recovered Ach levels [10,16]

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