Panax notoginseng saponins provide neuroprotection by regulating NgR1/RhoA/ROCK2 pathway expression, in vitro and in vivo

Shi, Xiaowei; Yu, Wenjing; Yang, Tiantian; Liu, Wei; Zhao, Yizhou; Sun, Yikun; Chai, Limin; Gao, Yonghong; Dong, Bin; Zhu, Li

doi:10.1016/j.jep.2016.06.017

Cited by 61 publications

(40 citation statements)

References 47 publications

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“…Therefore, our study showed that silencing NgR decreased RhoA and ROCK2 mRNA and protein levels. Previously, it was shown that Nogo-A in combination with NgR activated the Rho-A GTPase, which together with ROCK inhibited neurite growth [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

RNAi targeting Nogo Receptor enhanced survival and proliferation of murine retinal ganglion cells during N-methyl-D-aspartate-induced optic nerve crush

et al. 2017

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We investigated the effects of lentivirus-mediated RNAi targeting of Nogo Receptor (NgR) on the proliferation and survival of murine retinal ganglion cells (mRGCs) in vitro and in vivo. Cultured mRGCs and C57BL/6 male mice were divided into 4 experimental groups: blank, model [100 μM N-methyl-D-aspartate (NMDA)], nscRNA (100 μM NMDA+ nscRNA vectors) and siNgR (100 μM NMDA+ siNgR vectors). CCK-8 and flow cytometry analyses revealed that silencing NgR enhanced proliferation, cell cycling and survival of NMDA-treated mRGCs. H&E staining showed that NgR silencing enhanced mRGC cell density and reduced angiogenesis in NMDA-treated retinal tissues. TUNEL assays showed that mRGC apoptosis was significantly diminished by NgR silencing in NMDA-treated retinal tissues. Western blotting and qRT-PCR analysis in NMDA-treated mRGCs and murine retinal tissues revealed that NgR silencing resulted in downregulation of RhoA signaling (RhoA and ROCK2). Western blotting showed that levels of activated Bax and cleaved caspase 3 were decreased, while Bcl-2 and pro-caspase 3 were increased in NMDA-treated mRGCs and murine retinal tissues, which corroborated the decreased apoptosis. These findings indicate that NgR gene silencing increases proliferation and survival of mRGCs in NMDA-treated murine retinas, which suggests a potential for therapeutic application to preventing optic nerve damage.

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Section: Discussionmentioning

confidence: 99%

RNAi targeting Nogo Receptor enhanced survival and proliferation of murine retinal ganglion cells during N-methyl-D-aspartate-induced optic nerve crush

et al. 2017

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“…PNS, a traditional Chinese herbal medicine, has exhibited a wide range of pharmacological effects, such as angiogenetic, anti-neoplastic, neuroprotective, anti-inflammatory and immunomodulatory effects (31)(32)(33)(34)(35). These well-known effects confer that PNS has a strong ability to suppress pathological bone loss.…”

Section: Discussionmentioning

confidence: 99%

Notoginsenoside R1 significantly promotes in vitro osteoblastogenesis

Liu

Lin

Guo

et al. 2016

International Journal of Molecular Medicine

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Notoginsenoside R1 (NGR1), one of the main effective components of Panax notoginseng, appears to be effective in promoting osteogenesis and treating osteoporosis. However, hitherto, whether NGR1 can directly promote osteoblastogenesis remains to be elucidated. In the present study, we hereby examined the effects of NGR1 on the osteoblastogenesis of a pre-osteoblast cell line (MC3T3-E1) in in vitro time-course and dose-dependent experiments. Its efficacy was evaluated by assessing cell viability (indicator of proliferation), alkaline phosphatase (ALP) activity (a marker of early osteoblastic differentiation), levels of osteocalcin (OCN; a marker of late osteoblastic differentiation), calcium deposition (a marker of final mineralization) and the expression of a series of osteoblastogenic marker genes (such as collagen Iα, Runx2, ALP and OCN) at different time points. When examining the proliferation of and ALP activity in the pre-osteoblasts, a bell-shaped dose-response pattern was observed when the cells were treated with various concentrations of NGR1, with a peak being observed at the concentration of 50 µg/ml. NGR1 markedly increased the expression of OCN at the concentration of 1,000 µg/ml in a dose‑dependent manner. Furthermore, treatment with 1,000 µg/ml NGR1 resulted in the highest mineralization by 4.3- and 5.9-fold on the 21st and 28th day, respectively compared with the control group (no treatment). On the whole, our findings indicate that NGR1 significantly promotes the osteoblastogenesis of pre-osteoblasts, which suggests that NGR1 has potential for use as a bone regeneration agent.

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“…Human neuroblastoma SH-SY5Y cells were considered as a reliable neuron model used to investigate neurite outgrowth. It has been shown that Nogo-A and its receptors, such as NgR and p75NTR are expressed in SH-SY5Y cells, and inhibit neurite outgrowth through their downstream signal RhoA/ ROCK2 pathway [25,26]. As one component of the NgR receptor complex, p75NTR has also been linked to the PirB signal transduction pathway.…”

Section: Effects Of Antisera On the Neurite Outgrowth Of Human Neurobmentioning

confidence: 99%

Nucleic Acid Vaccine Targeting Nogo-66 Receptor and Paired Immunoglobulin-Like Receptor B as an Immunotherapy Strategy for Spinal Cord Injury in Rats

Mao

Xiao

et al. 2019

Neurotherapeutics

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and paired immunoglobulin-like receptor B (PirB) are two common receptors of various myelinassociated inhibitors (MAIs) and, thus, play an important role in MAIs-induced inhibitory signalling of regeneration following spinal cord injury (SCI). Based on the concept of protective autoimmunity, vaccine approaches could induce the production of antibodies against inhibitors in myelin, such as using purified myelin, spinal cord homogenates, or MAIs receptor NgR, in order to block the inhibitory effects and promote functional recovery in SCI models. However, due to the complication of the molecules and the mechanisms involved in MAIs-mediated inhibitory signalling, these immunotherapy strategies have yielded inconsistent outcomes. Therefore, we hypothesized that the choice and modification of self-antigens, and co-regulating multiple targets, may be more effective in repairing the injured spinal cord and improving functional recovery. In this study, NgR and PirB were selected to construct a double-targeted granulocyte-macrophage colony stimulating factor-NgR-PirB (GMCSF-NgR-PirB) nucleic acid vaccine, and investigate the efficacy of this immunotherapy in a spinal cord injury model in rats. The results showed that this vaccination could stimulate the production of antibodies against NgR and PirB, block the inhibitory effects mediated by various MAIs, and promote nerve regeneration and functional recovery after spinal cord injury. These findings suggest that nucleic acid vaccination against NgR and PirB can be a promising therapeutic strategy for SCI and other central nervous system diseases and injuries.

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Panax notoginseng saponins provide neuroprotection by regulating NgR1/RhoA/ROCK2 pathway expression, in vitro and in vivo

Cited by 61 publications

References 47 publications

RNAi targeting Nogo Receptor enhanced survival and proliferation of murine retinal ganglion cells during N-methyl-D-aspartate-induced optic nerve crush

RNAi targeting Nogo Receptor enhanced survival and proliferation of murine retinal ganglion cells during N-methyl-D-aspartate-induced optic nerve crush

Notoginsenoside R1 significantly promotes in vitro osteoblastogenesis

Nucleic Acid Vaccine Targeting Nogo-66 Receptor and Paired Immunoglobulin-Like Receptor B as an Immunotherapy Strategy for Spinal Cord Injury in Rats

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