Active constituent of Polygala tenuifolia attenuates cognitive deficits by rescuing hippocampal neurogenesis in APP/PS1 transgenic mice

Background Alzheimer’s disease (AD) is the most common dementia worldwide, and there is still no satisfactory drug or therapeutic strategy. Polygala tenuifolia is a traditional Chinese medicine with multiple neuroprotective effects. In present study, we investigated the effects of three active constituents [3,6′-disinapoyl sucrose (DISS), onjisaponin B (OB) and tenuifolin (TEN)] of Polygala tenuifolia (PT) on the proliferation and differentiation of neural stem cells (NSCs) to identify the potential active constituent of PT promoting hippocampal neurogenesis. Methods NSCs were isolated from hippocampi of newborn C57BL/6 mice, and transfected with mutant amyloid precursor protein (APP) gene to establish an AD cell model (APP-NSCs). 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were performed, and the proliferation and differentiation of NSCs were assessed by neurosphere formation assay, 5-bromo-2′-deoxyuridine (BrdU) incorporation assay and immunofluorescence (IF) staining analysis. APP/PS1 transgenic mice were administrated with the potential active constituent DISS for 4 weeks. Morris water maze (MWM), Nissl staining assay and IF staining assays were carried out to evaluate the cognitive function, neural damages and hippocampal neurogenesis, respectively. Results DISS exerted the optimal ability to strengthen APP-NSCs proliferation and neuronal differentiation, followed by OB and TEN. Furthermore, DISS treatment for 4 weeks strikingly rescued the cognitive deficits, neuronal injures, and neurogenesis disorder in adult APP/PS1 transgenic mice. Conclusions Our findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.

NEUROBIOLOGICAL EFFECTS OF TENUIGENIN AND THE OPPORTUNITY OF IT’S USING IN THE THERAPY OF ALZHEIMER’S AND PARKINSON’S DISEASES (LITERATURE REVIEW)

В обзоре представлен анализ экспериментальных и отчасти клинических данных по исследованию нейробиологических эффектов тенуигенина - важнейшего биологически активного соединения истода тонколистного (Polygala tenuifolia Willd.). Подробно описывается нейропротекторное и нейротрофическое действие данного вещества. Отмечается, что способности тенуигенина уменьшать секрецию бета-амилоида и защищать нейроны от повреждения уже образовавшимся бета-амилоидом, ингибировать процессы гиперфосфорилирования таубелков и воспалительные реакции в микроглии, а также усиливать основную синаптическую передачу могу быть использованы при разработке эффективных терапевтических средств, направленных на ослабление патогенеза болезни Альцгеймера. Эффекты защиты дофаминергических нейронов и митохондриального мембранного потенциала, а также сниженияфосфорилирования α-синуклеина могут оказывать влияние на процессы, развивающиеся при болезни Паркинсона. Делается общий вывод, что тенуигенин заслуживает дальнейшего изучения и, возможно, сможет найти применение в качестве средства аугментации терапии болезней Альцгеймера и Паркинсона и других нейродегенеративных заболеваний. The analysis of experimental and partially clinical data about researches of neurobiological effects of tenuigenin - the most important bioactive substance of Polygala tenuifolia Willd. in this review was given. The neuroprotective and neurotrophic action of given substance were described in detail. It was noted, that the capacities of the tenuigenin to decrease the secretion of beta amyloid and to protect of neurons from damage by already made beta ameloids, to inhibit the processes of the tau proteins` hyperphosphorylation and inflammations in microglia, as well as increase the main synaptic transmission can be used by the development of effective therapeutic drugs aimed to reduce the pathogenesis of Alzheimer`s disease. The effects of dopaminergic neurons and mitochondrial membrane potential protection as well as reduction of α-synuclein phosphorylation can influence the processes by Parkinson`s disease. It was concluded, that the tenuigenin deserves further study and possibly will be used as augmentation of Alzheimer`s, Parkinson`s and other neurodegenerative diseases therapy.

The Antidepressant-Like Effects of Shen Yuan in a Chronic Unpredictable Mild Stress Rat Model

Depression is a common yet severe neuropsychiatric condition that causes imposes considerable personal, economic, and social burdens worldwide. Medicinal plant species (e.g., Panax ginseng and Polygala tenuifolia) demonstrate potent antidepressant-like effects with less toxicity and other side effects. Shen yuan prescription (SY), composed of Panax ginseng (GT) and Polygala tenuifolia (YT). The present study aimed to elucidate the effects of SY treatment on chronic unpredictable mild stress (CUMS) rats and study the underlying mechanism. Our results indicated that SY (67.5, 135, or 270 mg/kg) significantly reverses the depressive-like behaviors in rats with a 5-week CUMS exposure, as demonstrated by increased sucrose consumption in the sucrose preference test, and decreased immobility time in the tail suspension and forced swim test. Moreover, SY altered serum corticosterone levels, pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), and oxidative markers (SOD, CAT, and MDA), and increased the levels of hippocampal neurotransmitters (5-HT, DA, and NE) in rats exposed to CUMS. Furthermore, rats treated with SY showed a reduction in the protein expression of BDNF, p-TrkB, p-Akt, and p-mTOR proteins induced by CUMS exposure in the hippocampus. In conclusion, SY prevented depressive-like behaviors in CUMS-exposed rats by preventing hypothalamus-pituitary-adrenal axis dysfunction, decreasing the levels of the neurotransmitters, minimizing oxidative stress, suppressing neuroinflammation, and activating the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway, all of which are the key players in the pathological basis of depression.