Ginsenoside Rg1 alleviates lipopolysaccharide‑induced neuronal damage by inhibiting NLRP1 inflammasomes in HT22 cells

Zhang, Yaodong; Ding, Shixin; Chen, Yali; Sun, Zhenghao; Zhang, Junyan; Han, Yuli; Dong, Xianan; Fang, Zhirui; Li, Weizu

doi:10.3892/etm.2021.10214

Cited by 24 publications

(5 citation statements)

References 64 publications

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“…In conclusion, although the mechanism by which Rg1 inhibits cell apoptosis has been widely reported ( 39 – 41 ), to the best of the authors' knowledge, the present study was the first to report that Rg1 exerted an anti-steatotic effect on hepatocyte apoptosis by downregulating a key enzyme, SGPL1, in the sphingosine signaling pathway ( Fig. 5 ).…”

Section: Discussionmentioning

confidence: 51%

Ginsenoside Rg1 exerts anti‑apoptotic effects on non‑alcoholic fatty liver cells by downregulating the expression of SGPL1

Xie

Cao

et al. 2022

Mol Med Rep

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Non-alcoholic fatty liver disease (NAFLD) has a high incidence, and can lead to liver cirrhosis and even hepatocellular carcinoma in severe cases. To the best of our knowledge, there is currently no safe and effective treatment for the management of this disease. Ginsenoside Rg1 (Rg1) is an active monomer derived from ginseng and notoginseng. In the present study, HHL-5 hepatocytes were used to establish an in vitro cell model of NAFLD by medium- and long-chain fat emulsion treatment, and the effects of Rg1 on adipose accumulation, apoptosis and the expression levels of apoptosis-related proteins in HHL-5 hepatocytes were examined. The results demonstrated that Rg1 inhibited the accumulation of fat in HHL-5 cells, while inhibiting apoptosis, and Rg1 downregulated the expression levels of the pro-apoptotic protein Bax and upregulated the expression levels of the anti-apoptotic protein Bcl-2, indicating that Rg1 could promote the stability or integrity of mitochondria and exert an anti-apoptotic effect by regulating Bcl-2 family proteins. In addition, Rg1 markedly downregulated the expression levels of sphingosine-1-phosphate lyase 1 (SGPL1), a key enzyme in the sphingosine signaling pathway, in HHL-5 cells with steatosis, and increased the expression levels of the downstream pro-survival signals phosphorylated (p-)Akt and p-Erk1/2. Furthermore, overexpression of SGPL1 abolished the anti-apoptotic effect of Rg1 on SGPL1-overexpressing HHL-5 cells with steatosis, and downregulated the expression levels of pro-survival proteins, such as Bcl-2, p-Akt and p-Erk1/2, whereas the expression levels of pro-apoptotic Bax were markedly increased. In conclusion, although there are some reports regarding the protective effect of Rg1 on fatty liver cells, to the best of our knowledge, the present study is the first to report that Rg1 may exert an anti-apoptotic effect on fatty liver cells by regulating SGPL1 in the sphingosine signaling pathway. Rg1 is the main component of the prescription drug Xuesaitong in China; therefore, the findings of the present study may provide a theoretical molecular basis for the use of Rg1 or Xuesaitong in the treatment of patients with NAFLD.

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Section: Discussionmentioning

confidence: 51%

Ginsenoside Rg1 exerts anti‑apoptotic effects on non‑alcoholic fatty liver cells by downregulating the expression of SGPL1

Xie

Cao

et al. 2022

Mol Med Rep

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“…These data demonstrated that rg1 may alleviate aβ deposition and learning and memory impairments through inhibiting neuroinflammation. A recent study by the authors suggested that rg1 treatment could improve lPS-induced neuronal injuries by downregulating the expression levels of nlrP1 inflammasomes in HT22 cells (58). Therefore, it was hypothesized that rg1 may delay the progression of AD by inhibiting NLRP1 inflammasome in APP/PS1 mice.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 alleviates learning and memory impairments and Aβ disposition through inhibiting NLRP1 inflammasome and autophagy dysfunction in APP/PS1 mice

Huang

Kong

et al. 2022

Mol Med Rep

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alzheimer's disease (ad) is a common neurodegenerative disorder. amyloid β (aβ) deposition is considered an important pathological feature of ad. Growing evidence has linked neuroinflammation and autophagy to Aβ deposition in the progression of ad. However, there are few drug options for inhibiting neuroinflammation and autophagy to prevent AD. Ginsenoside rg1 (rg1), a steroidal saponin extracted from ginseng, has been reported to possess multiple neuroprotective effects. The present study aimed to evaluate whether rg1 treatment could attenuate cognitive disorders and neuronal injuries by inhibiting NLRP1 inflammasome and autophagy dysfunction in an ad model of aPP/PS1 mice. The results of behavioral tests indicated that rg1 treatment for 12 weeks could significantly improve olfactory dysfunction as well as learning and memory impairments. The results of histopathological tests indicated that rg1 treatment could reduce aβ deposition and neuronal damages in aPP/PS1-9M mice. additionally, the results of immunoblot, reverse transcription-quantitative Pcr or immunohistochemistry demonstrated that rg1 treatment significantly downregulated the expression levels of inflammation-related proteins of nlrP1, caspase1, il-1β and TnF-α, as well as autophagy-related proteins of p-aMPK/aMPK, Beclin1 and lc3 ii/lc3 i, and increased the expression levels of p-mTor/mTor and P62 in aPP/PS1-9M mice. in addition, the molecular docking analysis showed that there was favorable binding result between rg1 and nlrP1. The present study suggested that rg1 may alleviate learning and memory impairments and aβ disposition by inhibiting NLRP1 inflammasome and improving autophagy dysfunction, suggesting that rg1 may be a potential therapeutic agent for delaying ad.

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“…BNCC337616), obtained from BeNa Culture Collection, were cultured in DMEM supplemented with 10% FBS (Gibco; Thermo Fisher Scientific, Inc.) and 1% penicillin/streptomycin in a humidified incubator with 5% CO 2 at 37˚C. HUVECs were treated with different concentrations of Rg1 (1, 5 or 10 µM; Shanghai YaJi Biotechnology Co., Ltd.) for 24 h at 37˚C ( 18 , 19 ). The AMP-activated protein kinase (AMPK) inhibitor compound C (CC; 5 mM; MilliporeSigma) was used to pretreat HUVECs for 2 h at 37˚C.…”

Section: Methodsmentioning

confidence: 99%

Ginsenoside Rg1 ameliorates apoptosis, senescence and oxidative stress in ox‑LDL‑induced vascular endothelial cells via the AMPK/SIRT3/p53 signaling pathway

Lyu

Zhang²,

Liu

2022

Exp Ther Med

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Coronary heart disease (CHD) mainly refers to coronary atherosclerotic heart disease and its pathogenesis is complex. Ginsenoside Rg1 (Rg1) has a wide range of pharmacological activities, such as antitumor effects, enhancing immunity and exerting protective effects on the vascular system. In the present study, the effect of Rg1 on vascular endothelial cells in CHD was investigated. Oxidized low-density lipoprotein (ox-LDL) was used to induce human umbilical vein endothelial cells (HUVECs) and cells were treated with 1, 5 or 10 µM Rg1. Cell Counting Kit-8 assay, TUNEL staining, western blot analysis of apoptosis-related proteins and senescence-related proteins, senescence-associated β-galactosidase staining, ELISA and other techniques including related kits of oxidative stress markers were used to detect the viability, apoptosis, oxidative stress, inflammatory cytokines including IL-1β, IL-6 and TNF-α and senescence of ox-LDL-induced HUVECs induced by Rg1. Western blot analysis was used to detect the expression levels of the AMP-activated protein kinase (AMPK)/sirtuin 3 (SIRT3)/p53 signaling pathway-related proteins. In addition, the associated mechanism was further determined using the AMPK pathway inhibitor compound C (CC). Rg1 increased the viability, and inhibited the apoptosis, senescence, oxidative stress and inflammation of ox-LDL-induced HUVECs. Pretreatment with CC partially reversed the protective effect of Rg1 on ox-LDL-induced HUVECs. In conclusion, Rg1 ameliorated apoptosis, senescence and oxidative stress of ox-LDL-induced HUVECs, at least in part, via the AMPK/SIRT3/p53 signaling pathway.

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Ginsenoside Rg1 alleviates lipopolysaccharide‑induced neuronal damage by inhibiting NLRP1 inflammasomes in HT22 cells

Cited by 24 publications

References 64 publications

Ginsenoside Rg1 exerts anti‑apoptotic effects on non‑alcoholic fatty liver cells by downregulating the expression of SGPL1

Ginsenoside Rg1 exerts anti‑apoptotic effects on non‑alcoholic fatty liver cells by downregulating the expression of SGPL1

Ginsenoside Rg1 alleviates learning and memory impairments and Aβ disposition through inhibiting NLRP1 inflammasome and autophagy dysfunction in APP/PS1 mice

Ginsenoside Rg1 ameliorates apoptosis, senescence and oxidative stress in ox‑LDL‑induced vascular endothelial cells via the AMPK/SIRT3/p53 signaling pathway

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