Liming Dong

Exploring the Effect of Ginsenoside Rh1 in a Sleep Deprivation-Induced Mouse Memory Impairment Model

Panax ginseng C.A. Meyer (Araliaceae) has been used in traditional Chinese medicine for enhancing cognition for thousands of years. Ginsenoside Rh1, a constituent of ginseng root, as with other constituents, has memory‐improving effects in normal mice and scopolamine‐induced amnesic mice. Sleep deprivation (SD) is associated with memory impairment through induction of oxidative stress. The present study investigated the effect of Rh1 against SD‐induced cognitive impairment and attempted to define the possible mechanisms involved. Ginsenoside Rh1 (20 μmol/kg; 40 μmol/kg) and modafinil (0.42 g/kg) were administered to the mice intraperitoneally for 23 days. After 14‐day SD, locomotor activity was examined using the open field test, and the object location recognition and Morris water maze tests were used to evaluate cognitive ability. The cortex and hippocampus were then dissected and homogenized, and levels and activities of antioxidant defense biomarkers were evaluated to determine the level of oxidative stress. The results revealed that Rh1 prevented cognitive impairment induced by SD, and its ability to reduce oxidative stress in cortex and hippocampus may contribute to the mechanism of action. Copyright

Protective effects of linalool against amyloid beta-induced cognitive deficits and damages in mice

Aim: Amyloid‐beta (A&bgr;)‐mediated neurotoxicity plays a pivotal role in the pathogenesis of Alzheimers disease (AD), which induces oxidative stress and apoptosis. Linalool (LI) is a volatile monoterpene showing positive effect in AD treatment. This study was designed to research the protective effect of LI against neurotoxicity and cognitive deficits induced by A&bgr;1–40 in mice. Main methods: A&bgr;1–40 (4 &mgr;g) solution was injected in the bilateral hippocampus to induce cognitive deficits of mice. The protective effects of LI were evaluated by behavioral tests and the related mechanism was further explored by observing the apoptosis and oxidative stress changes in the hippocampus of mice. Key findings: LI (100 mg/kg, i.p.) administration significantly improved the cognitive performance of model mice in Morris water maze test and step‐through test. Meanwhile, LI effectively reversed the A&bgr;1–40 induced hippocampal cell injury in histological examination, apoptosis in TUNEL assay, changes of oxidative stress indicators (SOD, GPX, AChE). Besides, the activated cleaved caspase (caspase‐3, caspase‐9) was suppressed and Nrf2, HO‐1 expression was elevated by LI treatment. Significance: LI could attenuate cognitive deficits induced by A&bgr;, and the neuroprotective effect of LI might be mediated by alleviation of apoptosis, oxidative stress depending on activation of Nrf2/HO‐1 signaling. We could assume that LI has the potential to be a neuroprotective substance for AD therapy.

Protective effect of lavender oil on scopolamine induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells

ETHNOPHARMACOLOGICAL RELEVANCE Lavender essential oil (LO), an aromatic liquid extracted from Lavandula angustifolia Mill., has been traditionally used in the treatments of many nervous system diseases, and recently LO also reported to be effective for the Alzheimers disease (AD). AIM OF THE STUDY The improvement effect of lavender oil (LO) on the scopolamine-induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells have been evaluated. The relevant mechanism was also researched from the perspective of antioxidant effect and cholinergic system modulation. MATERIALS AND METHODS Cognitive deficits were induced in C57BL/6J mice treated with scopolamine (1mg/kg, i.p.) and were assessed by Morris water maze (MWM) and step-through passive avoidance tests. Then their hippocampus were removed for biochemical assays (acetylcholinesterase (AChE), superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA)). In vitro, the cytotoxicity were induced by 4h exposure to H2O2 in PC12 and evaluated by cell viability (MTT), lactate dehydrogenase (LDH) level, nitric oxide (NO) release, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP). RESULTS The results demonstrated that LO (100mg/kg) could improve the cognitive performance of scopolamine induced mice in behavioral tests. Meanwhile, it significantly decreased the AChE activity, MDA level, and increase SOD and GPX activities of the model. Moreover, LO (12μg/mL) protected PC12 cells from H2O2 induced cytotoxicity by reducing LDH, NO release, intracellular ROS accumulation and MMP loss. CONCLUSIONS It was suggested that LO could show neuroprotective effect in AD model in vivo (scopolamine-treated mice) and in vitro (H2O2 induced PC12 cells) via modulating oxidative stress and AChE activity.

The Protective Effect of Lavender Essential Oil and Its Main Component Linalool against the Cognitive Deficits Induced by D-Galactose and Aluminum Trichloride in Mice

Lavender essential oil (LO) is a traditional medicine used for the treatment of Alzheimers disease (AD). It was extracted from Lavandula angustifolia Mill. This study was designed to investigate the effects of lavender essential oil (LO) and its active component, linalool (LI), against cognitive impairment induced by D-galactose (D-gal) and AlCl3 in mice and to explore the related mechanisms. Our results revealed that LO (100 mg/kg) or LI (100 mg/kg) significantly protected the cognitive impairments as assessed by the Morris water maze test and step-though test. The mechanisms study demonstrated that LO and LI significantly protected the decreased activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), and protected the increased activity of acetylcholinesterase (AChE) and content of malondialdehyde (MDA). Besides, they protected the suppressed nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression significantly. Moreover, the decreased expression of synapse plasticity-related proteins, calcium-calmodulin-dependent protein kinase II (CaMKII), p-CaMKII, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were increased with drug treatment. In conclusion, LO and its active component LI have protected the oxidative stress, activity of cholinergic function and expression of proteins of Nrf2/HO-1 pathway, and synaptic plasticity. It suggest that LO, especially LI, could be a potential agent for improving cognitive impairment in AD.

Neuroprotective effects of 20(S)-protopanaxatriol (PPT) on scopolamine-induced cognitive deficits in mice

20(S)‐protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine‐induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 μmol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory‐related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine‐induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory‐improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr‐1, c‐Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimers disease.

Effects of the chronic restraint stress induced depression on reward-related learning in rats

Graphical abstract Figure. No Caption available. HighlightsIt was the first time to evaluate the effects of restraint stress on the performance of reward‐motivated instrumental learning tasks of rats.Chronic restraint stress influenced the Pavlovian conditioning, acquisition and maintenance of instrumental conditioning task of rats.The learning ability of rats faced in higher fixed ratio schedule of instrumental learning task was impaired by chronic restraint stress.Chronic stress induced bad performances in instrumental learning tasks might be related to the reduced motivation and cognitive function. ABSTRACT Chronic mild or unpredictability stress produces a persistent depressive‐like state. The main symptoms of depression include weight loss, despair, anhedonia, diminished motivation and mild cognition impairment, which could influence the ability of reward‐related learning. In the present study, we aimed to evaluate the effects of chronic restraint stress on the performance of reward‐related learning of rats. We used the exposure of repeated restraint stress (6 h/day, for 28 days) to induce depression‐like behavior in rats. Then designed tasks including Pavlovian conditioning (magazine head entries), acquisition and maintenance of instrumental conditioning (lever pressing) and goal directed learning (higher fixed ratio schedule of reinforcement) to study the effects of chronic restraint stress. The results indicated that chronic restraint stress influenced rats in those aspects including the acquisition of a Pavlovian stimulus‐outcome (S‐O) association, the formation and maintenance of action‐outcome (A‐O) causal relation and the ability of learning in higher fixed ratio schedule. In conclusion, depression could influence the performances in reward‐related learning obviously and the series of instrumental learning tasks may have potential as a method to evaluate cognitive changes in depression.

Radioprotective effects of dammarane sapogenins against 60Co-induced myelosuppression in mice

Radiotherapy frequently induces failure of hematopoietic system and leads to myelosuppression. The objective of this study was to investigate the protective effect of dammarane sapogenins (DS), the hydrolysed product of the constituent ginsenosides of Panax ginseng, which are produced by gut metabolism, on radiation‐induced hematopoietic injury. Mice were exposed to 3.5 Gy 60Co γ‐rays of total body radiation at a dose rate of 1.60 Gy per minute and treated with DS or granulocyte colony‐stimulating factor immediately after radiation. The general condition of the mice, the peripheral blood cell counts, multiple colony forming unit (CFU) assays of hematopoietic progenitor cells, hematopoietic stem cell counts, bone marrow histology, and spleen colony forming unit counts were then investigated. Our results indicated that administration with DS could ameliorate 60Co‐irradiation induced damage and significantly increase the number of peripheral blood cells (white blood cells and platelets), 5 types of hematopoietic progenitor cells CFU (CFU‐GM, CFU‐E, BFU‐E, CFU‐Meg, and CFU‐GEMM), hematopoietic stem cell (Lin−c‐kit+Scal‐1+) numbers, and CFUs in the spleen, as well as improved bone marrow histopathology. All together, these results confirmed the enhancement of DS on hematopoiesis.

Antidepressant effects of dammarane sapogenins in chronic unpredictable mild stress-induced depressive mice

Depression is a common, dysthymic, and psychiatric disorder, resulting in enormous social and economic burden. Dammarane sapogenins (DS), an active fraction from oriental ginseng, has shown antidepressant‐like effects in chronic restraint rats and sleep interruption‐induced mice, and the present study aimed to further confirm the antidepressant effects of DS in a model of chronic unpredictable mild stress (CUMS) and to explore the underlying mechanism. Oral administration of DS (20, 40, and 80 mg/kg) markedly improved depressant‐like behaviors, increasing the sucrose intake in the sucrose preference test and reducing the latency in the novelty‐suppressed feeding test, and decreasing the immobility time in both the tail suspension and forced swimming tests, compared with the CUMS mice. Biochemical analysis of brain tissue and serum showed that DS treatment restored the decreased hippocampal neurotransmitter concentrations of serotonin, dopamine, norepinephrine (noradrenaline), and gamma‐aminobutyric acid, and decreased the elevated of serum hormone levels (corticotrophin releasing factor, adrenocorticotrophic hormone, and corticosterone) induced by CUMS. Our findings confirm that DS exerts an antidepressant‐like effect in the CUMS model of depression in mice, and suggest it may be mediated by regulation of neurotransmitters and hypothalamic–pituitary–adrenal axis.

The protective effect of 20(S)-protopanaxadiol (PPD) against chronic sleep deprivation (CSD)-induced memory impairments in mice

Sleep deprivation (SD) is associated with oxidative stress that causes learning and memory impairment. 20(S)-Protopanaxadiol (PPD), one of the protopanaxadiol-type saponins, has antioxidant and neuroprotective effect. This study was designed to research the protective effect of PPD against cognitive deficits induced by chronic sleep deprivation (CSD) in mice. The CSD model was induced by subjecting the mice to our self-made Sleep Interruption Apparatus (SIA) continuously for 14 days. The memory enhancing effects of PPD were evaluated by behavioral tests and the related mechanism was further explored by observing the oxidative stress changes in the cortex and hippocampus of mice. The results revealed that PPD (20 and 40 μmol/kg, i.p.) administration significantly improved the cognitive performance of CSD model mice in object location recognition experiment, novel object recognition task and Morris water maze test. Furthermore, PPD effectively restored the levels/activities of antioxidant defense biomarkers in the cortex and hippocampus, including the superoxide dismutase (SOD) enzyme activity, catalase (CAT) enzyme activity, glutathione (GSH), and lipid peroxidation (LPO). In conclusion, PPD could attenuate cognitive deficits induced by CSD, and the neuroprotective effect of PPD might be mediated by alleviation of oxidative stress. It was assumed that PPD has the potential to be a neuroprotective substance for cognition dysfunction.

Memory enhancement of fresh ginseng on deficits induced by chronic restraint stress in mice

Objectives: Chronic stress exposure can disrupt the balance of organisms, result in learning and memory impairments and induce oxidative stress. However, there is a lack of safe and effective long-term therapeutic agents for stress-related injuries. Fresh ginseng (FG), an unprocessed raw root of ginseng, has antioxidant and neuroprotective activities and has been used as functional health food in Asian countries for many years. The aim of this study was to verify the protective effects of FG on chronic restraint stress (CRS)-induced learning and memory impairments as well as oxidative stress damage in mice. Methods: Animals were subjected to object location recognition test (OLRT) and novel object recognition test (NORT) to evaluate discriminative ability and spatial learning and memory, and Morris water maze test (MWMT) was used to evaluate the acquisition and retention of spatial memory. In addition, oxidative stress parameters were assessed by measuring the malondialdehyde (MDA) and total antioxidant reactivity levels in serum. Results: Experimental results demonstrated that CRS-induced mice exhibited significantly decreased discrimination index (DI) in OLRT and NORT, longer escape latency and swimming distance, and decreased crossing numbers in MWMT. FG (2 and 6 g/kg) treatment markedly enhanced the discriminative ability by elevating DI in OLRT and NORT, improved the acquisition and retention of spatial memory by decreasing escape latency and swimming distance in the acquisition phase, and increased the crossing numbers in the probe phase of MWMT. Administration of FG (2 and 6 g/kg) significantly reduced the elevated MDA level caused by CRS. Discussion: Our results suggest that FG treatment could improve CRS-induced learning and memory impairments and oxidative stress damage. FG is an intriguing therapeutic agent and functional health food in stress-related dementia.