Ginsenoside Rg1 alleviates Aβ deposition by inhibiting NADPH oxidase 2 activation in APP/PS1 mice

Zhang, Han; Su, Yong; Sun, Zhenghao; Chen, Ming; Han, Yuli; Li, Yan; Dong, Xianan; Ding, Shixin; Fang, Zhirui; Li, Weiping; Li, Weizu

doi:10.1016/j.jgr.2021.03.003

Cited by 46 publications

(35 citation statements)

References 49 publications

(55 reference statements)

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“…Chronic glucocorticoid exposure in mice activates NLRP1 inflammasome-signaling pathways [ 13 , 63 ]. NLRP1 inflammasome inhibition by Ginsenoside Rg1 suppressed chronic glucocorticoid exposure-induced neuronal degenerations in mice [ 30 , 31 ]. Recent studies indicate that pyroptosis could also promote the development of Alzheimer’s disease.…”

Section: Roles Of Nlrp Inflammasome In Neuropsychiatric Disordersmentioning

confidence: 99%

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

et al. 2022

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The NLRP inflammasome is a multi-protein complex which mainly consists of the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain. Its activation is linked to microglial-mediated neuroinflammation and partial neuronal degeneration. Many neuropsychiatric illnesses have increased inflammatory responses as both a primary cause and a defining feature. The NLRP inflammasome inhibition delays the progression and alleviates the deteriorating effects of neuroinflammation on several neuropsychiatric disorders. Evidence on the central effects of the NLRP inflammasome potentially provides the scientific base of a promising drug target for the treatment of neuropsychiatric disorders. This review elucidates the classification, composition, and functions of the NLRP inflammasomes. It also explores the underlying mechanisms of NLRP inflammasome activation and its divergent role in neuropsychiatric disorders, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, depression, drug use disorders, and anxiety. Furthermore, we explore the treatment potential of the NLRP inflammasome inhibitors against these disorders.

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Section: Roles Of Nlrp Inflammasome In Neuropsychiatric Disordersmentioning

confidence: 99%

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

et al. 2022

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“…Interestingly, Rg1 could significantly alleviate IMQ‐induced psoriasis‐like dermatitis to lower the inflammation level by downregulating NF‐κB signaling pathway (Shi et al., 2019). Furthermore, excessive ROS generation could lead oxidative stress damage, however, Rg1 could decrease ROS production and inhibited NOX2 expression to restore cell function (Zhang et al., 2021). Based on these findings, the effects of Rg1 on psoriasis‐like skin and whether it mediated ROS/NLRP3 pathway to perform the protective effects on psoriasis remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rg1 ameliorates psoriasis‐like skin lesions by suppressing proliferation and NLRP3 inflammasomes in keratinocytes

Mao

Zhu

et al. 2022

Journal of Food Biochemistry

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As a common chronic skin disease, psoriasis is characterized by the involvement of congenital acquired inflammatory immune diseases. In the study, our results indicated the effect of ginsenoside Rg1 on psoriasis‐like skin and the potential protection mechanisms that have not yet been investigated. In vivo, psoriasis‐like skin mice model was induced by imiquimod (IMQ), then was treated by ginsenoside Rg1 for consecutive 4 weeks to evaluate its effect, respectively. In vitro, M5 cocktail treatment of human immortalized keratinocyte HaCaT‐induced psoriasis‐like skin cell model, which was exposed to ginsenoside Rg1. The inflammatory cell infiltration, expression level of keratinocyte proliferation marker Ki67, keratinocyte proliferation, inflammatory cytokines, and ROS/NLRP3 pathway‐related proteins in vivo and in vitro were examined by hematoxylin and eosin, immunohistochemistry, ELISA, CCK‐8, flow cytometry, and western blot. All results demonstrated that ginsenoside Rg1 attenuated the injury of psoriasis‐like skin, which inhibited the proliferation of skin keratinocytes and the activation of NLRP3 inflammasome and the level of inflammatory factors such as IL‐1β and IL‐18, and decreased the level of Ki67, NLRP3, and caspase‐1 in mice and HaCaT. Furthermore, NLRP3 overexpression attenuates the effect of ginsenoside Rg1 on M5 cocktail‐induced proliferation and NLRP3 inflammasomes in HaCaT. These results demonstrated that ginsenoside Rg1 could suppress the ROS/NLRP3 pathway to treat psoriasis‐like skin. Practical applications This is the very first study to explore the efficacy of ginsenoside Rg1 against psoriasis‐like skin lesions to reveal the underlying mechanism. In this paper, the detection of skin histopathological analysis, CCK‐8, flow cytometry, western blot, and ELISA analysis shows that ginsenoside Rg1 has preventive effect on psoriasis caused by imiquimod or M5 cocktail through inhibiting NLRP3 inflammasome, which helps in the development of novel nutraceutical/functional food against psoriasis and thus could improve the quality of life in psoriasis patients.

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“…Neuronal damage and loss are the main causes of cognitive dysfunction in AD patients. In this study, the effects of varying formulation on the injury and loss of hippocampal and cortical neurons in APP/PS1 mice were observed by HE staining and Nissl staining (Zhang et al., 2021 ). HE staining showed that the neurons in the blank control group were intact and neatly arranged, while the neurons in the hippocampus and cortex of APP/PS1 mice were in an unhealthy state with disordered arrangement, dark staining, atrophy, or even disappearance of neurons.…”

Section: Resultsmentioning

confidence: 99%

Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease

et al. 2022

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The blood–brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer’s disease (AD). In this work, an anti-AD brain-targeted nanodrug delivery system by co-loading icariin (ICA) and tanshinone IIA (TSIIA) into Aniopep-2-modified long-circulating (Ang2-ICA/TSIIA) liposomes was developed. Low-density lipoprotein receptor-related protein-1 (LRP1) was a receptor overexpressed on the BBB. Angiopep-2, a specific ligand of LRP1, exhibited a high binding efficiency with LRP1. Additionally, ICA and TSIIA, drugs with neuroprotective effects are loaded into the liposomes, so that the liposomes not only have an effective BBB penetration effect, but also have a potential anti-AD effect. The prepared Ang2-ICA/TSIIA liposomes appeared narrow dispersity and good stability with a diameter of 110 nm, and a round morphology. Cell uptake observations, BBB models in vitro , and imaging analysis in vivo showed that Ang2-ICA/TSIIA liposomes not only penetrate the BBB through endocytosis, but also accumulate in N2a cells or brain tissue. The pharmacodynamic analysis in vivo demonstrated that Ang2-ICA/TSIIA liposomes could improve AD-like pathological features in APP/PS1 mice, including inhibiting neuroinflammation and oxidative stress, reducing apoptosis, protecting neurons, and improving cognitive function. Therefore, Ang2-ICA/TSIIA liposomes are considered a potentially effective therapeutic strategy for AD.

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Ginsenoside Rg1 alleviates Aβ deposition by inhibiting NADPH oxidase 2 activation in APP/PS1 mice

Cited by 46 publications

References 49 publications

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

The Significance of NLRP Inflammasome in Neuropsychiatric Disorders

Ginsenoside Rg1 ameliorates psoriasis‐like skin lesions by suppressing proliferation and NLRP3 inflammasomes in keratinocytes

Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer’s disease

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