Notoginseng Saponin Rg1 Prevents Cognitive Impairment through Modulating APP Processing in Aβ1–42-injected Rats

Liu, Shang-Zhi; Cheng, Wei; Shao, Jia-Wei; Gu, Yun-Fan; Zhu, Yiyi; Dong, Qi-Jing; Bai, Shuxiong; Wang, Ping; Lin, Li

doi:10.1007/s11596-019-2019-1

Cited by 17 publications

(15 citation statements)

References 25 publications

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“…Many studies showed a noticeable loss of hippocampal neurons in patients and experimental animals with AD [40,41]. Although the mechanisms underlying the loss of neurons in AD are still unclear, there is increasing evidence showing that the neurons in the hippocampus of rats were decreased markedly after Aβ 1−42 injection into the lateral ventricles [42]. Also, APP/PS1 mice and other AD models have also been confirmed to have a decrease in hippocampal neurons [6,43].…”

Section: Discussionmentioning

confidence: 99%

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Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

Long

et al. 2021

Chin Med

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Background Suan-Zao-Ren Decoction (SZRD) has been widely used to treat neurological illnesses, including dementia, insomnia and depression. However, the mechanisms underlying SZRD’s improvement in cognitive function remain unclear. In this study, we examined SZRD’s effect on APP/PS1 transgenic mice and mechanisms associated with SZRD’s action in alleviating neuroinflammation and improving synaptic plasticity. Methods The APP/PS1 mice were treated with different dosages of SZRD (12.96 and 25.92 g/kg/day, in L-SZRD and H-SZRD groups, respectively) for 4 weeks. Morris water maze was conducted to determine changes in behaviors of the mice after the treatment. Meanwhile, in the samples of the hippocampus, Nissl staining and Golgi-Cox staining were used to detect synaptic plasticity. ELISA was applied to assess the expression levels of Aβ1−40 and Aβ1−42 in the hippocampus of mice. Western blot (WB) was employed to test the protein expression level of Aβ1−42, APP, ADAM10, BACE1, PS1, IDE, IBA1, GFAP, PSD95 and SYN, as well as the expressions of JAK2, STAT3 and their phosphorylation patterns to detect the involvement of JAK2/STAT3 pathway. Besides, we examined the serum and hippocampal contents of IL-1β, IL-6 and TNF-α through ELISA. Results Compared to the APP/PS1 mice without any treatment, SZRD, especially the L-SZRD, significantly ameliorated cognitive impairment of the APP/PS1 mice with decreases in the loss of neurons and Aβ plaque deposition as well as improvement of synaptic plasticity in the hippocampus (P < 0.05 or 0.01). Also, SZRD, in particular, the L-SZRD markedly inhibited the serum and hippocampal concentrations of IL-6, IL-1β and TNF-α, while reducing the expression of p-JAK2-Tyr1007 and p-STAT3-Tyr705 in the hippocampus of the APP/PS1 mice (P < 0.05 or 0.01). Conclusions The SZRD, especially the L-SZRD, may improve the cognitive impairment and ameliorate the neural degeneration in APP/PS1 transgenic mice through inhibiting Aβ accumulation and neuroinflammation via the JAK2/STAT3 pathway.

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Section: Discussionmentioning

confidence: 99%

“…Aβ deposition depends on the hydrolysis of APP, which is regulated through α, β, γ secretase [52]. The α-secretase is mainly composed of the ADAM family [42]. ADAM10 can reduce the pathological damage of AD by inhibiting the production of Aβ 1−42 .…”

Section: Discussionmentioning

confidence: 99%

Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

Long

et al. 2021

Chin Med

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“…Crocus sativus L. extracts antagonize memory impairments in different behavioural tasks in the rat [ 70 ]. Panax Notoginseng attenuates impairment of learning and memory in chronic stage ischemia–reperfusion injured rats [ 71 ] and in Aβ (1–42)-injected Rats [ 72 ]. Radix Ophiopogonis , component of Shengmaisan, improves learning and memory abilities of the rats [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

Gao-Zi-Yao improves learning and memory function in old spontaneous hypertensive rats

Han

Jiang

et al. 2022

BMC Complement Med Ther

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Aims Gao-Zi-Yao has long been a unique way for treating various diseases. The present study is to explore the effect of Gao-Zi-Yao on learning and memory function in old spontaneous hypertensive rats (SHR) and its possible mechanism. Method Male old SHR were received different doses of Gao-Zi-Yao for 4 weeks. Systolic blood pressure (SBP) and heart rate were monitored. Serum levels of nitric oxide (NO), interleukin (IL)-1β, IL-2, and tumor necrotic factor (TNF)-α were measured. Morris water maze was performed to test the learning and memory function of the rats. Number of neurons in hippocampus was counted by Nissl staining. Western blot was applied to detect the expressions of learning and memory function related proteins, N-methyl-d-aspartate receptor 2B (NMDAR 2B), glutamate receptor 1 (GluR1), phosphorylated-calmodulin-dependent protein kinase II (p-CaMK II), and phosphorylated-cAMP responsive element-binding protein (p-CREB) in rat hippocampus. Results Data showed that Gao-Zi-Yao reduced SBP in old SHR, elevated NO level, and suppressed levels of IL-1β, IL-2, TNF-α. The results of Morris water maze experiment showed that Gao-Zi-Yao dose-dependently improved learning and memory function. Number of neurons in the hippocampal dentate gyrus (DG) region of the old SHR was increased by Gao-Zi-Yao treatment. In addition, Gao-Zi-Yao elevated the protein expressions of NMDAR 2B, GluR1, p-CaMK II, and p-CREB in hippocampus. Conclusion Gao-Zi-Yao decreases SBP and improves the learning and memory function of the old SHR by regulation of oxidative stress, inflammatory factors and neuron number in hippocampal DG area and the expression of learning and memory function related proteins.

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“…Other P. notoginseng components have been reported to exert anti-aging effects when used to treat many degenerative diseases associated with aging. For example, notoginsenoside Rg1 and R1 improved cognitive impairment and increased neuronal excitability against AD neurotoxicity ( Yan et al, 2014 ; Liu et al, 2019 ), while other notoginsenosides attenuated cardiomyocyte apoptosis via the mitochondrial pathway in naturally aging rats ( Zhou et al, 2018 ). In addition, notoginseng extracts delayed vascular endothelial cell senescence ( Wang and Lei, 2014 ), while active polysaccharide ingredients of P. notoginseng significantly extended the lifespan of C. elegans ( Feng et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides

Zhai

Liu

et al. 2021

Front. Pharmacol.

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Dermal fibroblast replicative senescence that often occurs in aging skin is characterized by loss of cell proliferative capacity, cell cycle arrest, decreased cell elongation, and decreased synthesis of dermal extracellular matrix (ECM) components. Although Panax notoginseng is known for its effectiveness in alleviating many age-related degenerative diseases, few studies have evaluated P. notoginseng components for efficacy or mechanisms of action in delaying cell replicative senescence. In this study, P. notoginseng oligosaccharides (PNO) were isolated using a stepwise purification procedure involving water extraction and alcohol precipitation followed by DEAE Sepharose Fast Flow column chromatography, preparative high performance liquid chromatography, and size-exclusion chromatography. Monosaccharides detected in PNO constituents included mannose, galactose, and sorbitose in relative molar proportions of 14.2:12.3:1, respectively, aligning with PNO absorption spectrum results resembling typical known spectra for sugars. In vitro, PNO treatment of replicative senescent NIH-3T3 fibroblasts significantly promoted cell vitality, inhibited SA-β-galactosidase (SA-β-Gal) activity, and reduced p16 and p21 protein-level expression. Moreover, PNO treatment of senescent fibroblasts led to a lower proportion of G1 phase cells and higher proportion of S phase cells, while also inducing aging NIH-3T3 cells to migrate and synthesize collagen-I (CoL-I). Mechanistically, PNO treatment up-regulated expression of proliferating cell nuclear antigen (PCNA), cyclin E, cyclin D1, and cyclin-dependent kinase 4 (CDK4) proteins and promoted phosphorylation of MEK, p38, and ERK1/2 to trigger cell cycle progression. Additionally, PNO treatment also up-regulated protein-level expression of TGF-β1 and levels of p-Smad2/3, p-FAK, and p-Pax to trigger CoL-I synthesis and cell migration. Taken together, these findings demonstrate that oligosaccharides purified from P. notoginseng could reverse fibroblast replicative senescence by promoting fibroblast cell proliferation, migration, and CoL-I production.

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Notoginseng Saponin Rg1 Prevents Cognitive Impairment through Modulating APP Processing in Aβ1–42-injected Rats

Cited by 17 publications

References 25 publications

Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

Suan-Zao-Ren Decoction ameliorates synaptic plasticity through inhibition of the Aβ deposition and JAK2/STAT3 signaling pathway in AD model of APP/PS1 transgenic mice

Gao-Zi-Yao improves learning and memory function in old spontaneous hypertensive rats

A Novel Biochemical Study of Anti-Dermal Fibroblast Replicative Senescence Potential of Panax Notoginseng Oligosaccharides

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