MiR-155/GSK-3β mediates anti-inflammatory effect of Chikusetsusaponin IVa by inhibiting NF-κB signaling pathway in LPS-induced RAW264.7 cell

Yi, Xin; Qin, Yuan; Liu, Chaoqi; Zhang, Changcheng; Yuan, Ding

doi:10.1038/s41598-020-75358-1

Cited by 24 publications

(14 citation statements)

References 46 publications

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“…Such results could be attributed to LPS directly activating and promoting TLR4 expression, thereby activating the NF-κB site (Dong et al, 2020). When NF-κB is activated, IκBα will be phosphorylated and degraded, and result in phosphorylation of NF-κB heterodimers (p50/p65), which in turn leads to enhanced nuclear translocation activity (Xin et al, 2020). However, the protein expression levels of iNOS, TLR4, and NF-κB p65 were significantly downregulated in cells with LBP pre-treatment.…”

Section: Discussionmentioning

confidence: 99%

Lycium barbarum polysaccharides ameliorate LPS‐induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice

Liu

Zhou

et al. 2021

J Food Biochem

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In the present study, the anti-inflammatory effect of Lycium barbarum polysaccharide (LBP) and the possible molecular mechanism thereof were examined, so as to perceive the pharmacological action of LBP. With acute peritonitis in mice as the inflammatory model, the protective effect of LBP on peritonitis mice was evaluated by recording the effect of behavioral scores, studying the pathological damage of intestine and liver, and detecting the levels of inflammatory cytokines. Additionally, by establishing an lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, the effect of LBP on RAW264.7 cell phenotype and culture supernatant inflammatory markers was observed. Finally, the activation of inflammation-related target genes, such as iNOS, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB) p65, and IκBα, were further detected. The results reveal that pretreatment with LBP could decrease the behavioral score of inflammatory mice, inhibit the secretion of pro-inflammatory factors, and reduce liver and intestine injury. LBP can regulate the effect of lipopolysaccharide on the polarization of RAW264.7 cells, and reduce the production of NO and cytokines (TNFα, IL-1β, IL-6). Further, LBP pretreatment was found to be able to significantly reduce the expression of iNOS, TLR4, NF-κB p65, and IκBα in macrophages. The present research provides evidence that LBP exerts potential antiinflammatory activity in LPS-induced RAW264.7 macrophages via inhibiting TLR4 and NF-κB inflammatory sites and improving the behavior score of peritonitis mice. Practical applicationsIn recent years, the number of deaths worldwide has continued to rise as a result of inflammation. Despite said rise in deaths, many synthetic drugs with anti-inflammatory properties are significantly expensive and also have a host of side effects. Thus, the development of new anti-inflammatory drugs derived from medicinal plants has broad application potential. As such, in the present study, lipopolysaccharide (LPS)induced macrophages were used to establish inflammatory cell models to verify the anti-inflammatory effect of Lycium barbarum polysaccharides (LBP). Findings were made that LBP could reduce the expression levels of inflammatory cytokines and NO by regulating macrophage polarization and NF-κB translocation, and thus, could exert anti-inflammatory activity.

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Section: Discussionmentioning

confidence: 99%

Lycium barbarum polysaccharides ameliorate LPS‐induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice

Liu

Zhou

et al. 2021

J Food Biochem

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“…In mammals, GSK3 exists in two major subtypes, GSK-3α and GSK-3β (Woodgett, 1990). GSK-3 is now known to target a variety of substrates ranging from transcription factors such as NF-κB and CREB (Jope and Johnson, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that freely phosphorylates and regulates a variety of signal-regulated proteins. GSK-3 plays a key role in regulating the production of pro-and anti-inflammatory cytokines (Xin et al, 2020). On the one hand, the effect of GSK-3 on inflammation is due to its ability to regulate the stability and activity of nuclear factor kappa-B (NF-κB), which is known to play an important role in the regulation of inflammation (Kotliarova et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway

Cao

Ren

et al. 2021

Front. Pharmacol.

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Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and LPS-induced RAW264.7 cell ALI model. Mice were pretreated with XBJ before the CLP model was established, and serum and liver tissues were collected at the end of the experiment to assess the levels of inflammatory factors and liver injury. Results showed that XBJ pretreatment reduced liver/body weight, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum, and inhibited levels of pro-inflammatory factors in serum. Cells were treatment with XBJ and modeled by LPS modeling increased cell viability in the XBJ-treated group compared to the model group and XBJ also decreased serum pro-inflammatory factors in a dose-dependent manner. Western blot detected that XBJ also up-regulated the phosphorylated levels of glycogen synthase kinase-3β (p-GSK-3β) and cAMP-response element-binding protein (p-CREB) and down-regulated the phosphorylated level of nuclear factor kappa-B (p-NF-κB) in liver and cell. After overexpression of GSK-3β in cells, the mechanism was further investigated using CO-IP analysis. The binding of p-NF-κB and p-CREB to CREB-binding protein (CBP) was increased and decreased, respectively, indicating that GSK-3β regulated inflammation by regulating the binding of p-NF-κB and p-CREB to CBP. The present studies suggested that the hepatoprotective effect of XBJ may be through up-regulation of GSK-3β (Ser9) and increasing the binding of p-CREB to CBP, thereby alleviating the inflammatory response.

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“…CsV is also detected from Panax japonicus, recognized as a very important medical herb 20,21 . Therefore, we focused on CsV as a drug e cacy marker of GJG.…”

Section: Gjg Decreased the Expression Of Mafbx In C2c12 Cells After Tnf-stimulationmentioning

confidence: 99%

Gosha-jinki-Gan (GJG) shows anti-aging effects through suppression of TNF-α production by Chikusetsusaponin V

Hagihara

Nunomura

Lin

et al. 2022

Gene

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Frailty develops due to multiple factors, such as sarcopenia, chronic pain, and dementia. Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine used for age-related symptoms. We have reported that GJG improved sarcopenia, chronic pain, and central nervous system function through suppression of TNF-α production. In the present study, GJG was found to reduce the production of TNF-α in the soleus muscle of senescence-accelerated mice at 12 weeks and 36 weeks. GJG did not change the differentiation of C2C12 cells with 2% horse serum. GJG signi cantly decreased the expression of MAFbx induced by TNF-α in C2C12 cells on real-time PCR. TNF-α signi cantly decreased the expression of PGC-1α and negated the enhancing effect of GJG for the expression of PGC-1α on digital PCR. Examining 20 chemical compounds derived from GJG, cinnamaldehyde from cinnamon bark and Chikusetsusaponin V (CsV) from Achyrantes Root dose-dependently decreased the production of TNF-in RAW264.7 cells stimulated by LPS. CsV inhibited the nuclear translocation of NF-κB p65 in RAW264.7 cells. CsV showed low permeability using Caco-2 cells. However, the plasma concentration of CsV was detected from 30 minutes to 6 h and peaked at 1 h in the CD1 (ICR) mice after a single dose of GJG. In 8-week-old SAMP8 mice fed 4% (w/w) GJG from one week to four weeks, the plasma CsV concentration ranged from 0.0500 to 10.0 ng/mL. The evidence that CsV plays an important role in various anti-aging effects of GJG via suppression of TNF-expression is presented.

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MiR-155/GSK-3β mediates anti-inflammatory effect of Chikusetsusaponin IVa by inhibiting NF-κB signaling pathway in LPS-induced RAW264.7 cell

Cited by 24 publications

References 46 publications

Lycium barbarum polysaccharides ameliorate LPS‐induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice

Lycium barbarum polysaccharides ameliorate LPS‐induced inflammation of RAW264.7 cells and modify the behavioral score of peritonitis mice

Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway

Gosha-jinki-Gan (GJG) shows anti-aging effects through suppression of TNF-α production by Chikusetsusaponin V

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