Dataset Information

Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation.

ABSTRACT:

Context

Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation.

Objective

To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2).

Materials and methods

Naive CD4⁺T cells were treated with IL-6, IL-23 and TGF-β to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 μg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 μM) and inhibitor (SAICAR, 2, 4, 8 μM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression.

Results

PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 μM) and SAICAR (4 μM), we demonstrated that PNS (10 μg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling.

Discussion and conclusions

PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.

SUBMITTER: Shen MY

PROVIDER: S-EPMC9936999 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

<i>Panax notoginseng</i> saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation.

Shen Mei-Yu MY Di Yu-Xi YX Wang Xiang X Tian Feng-Xiang FX Zhang Ming-Fei MF Qian Fei-Ya FY Jiang Bao-Ping BP Zhou Xue-Ping XP Zhou Ling-Ling LL

Pharmaceutical biology 20231201 1

<h4>Context</h4>Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. <i>Panax notoginseng</i> (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation.<h4>Objective</h4>To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2).<h4>Materials and methods</h4>Naive CD4<sup>+</sup>T cells were treated with IL-6, IL-23 and TGF-β to induce Th17 c ...[more]

PMID: 36794740

Similar Datasets

Project description:Statins cannot be used for some active liver diseases, which limits its application to some extent. The combined use of statins with other drugs may be one of the ways to solve this dilemma.This research aims to evaluate the effects of atorvastatin combined with Panax notoginseng saponins (PNS) on rats with atherosclerosis (AS) complicated with hepatic injury.Seventy-two male Wistar rats were randomly categorized into control group (without any intervention, Group A) and AS model groups, which were divided into hepatic injury (Groups B-E) and nonhepatic injury (Groups F-I) groups. Hepatic and nonhepatic injury groups were intragastrically treated with 5.5 mg/kg·d atorvastatin (Group B, F), 200 mg/kg·d PNS (Group C, G), 5.5 mg/kg·d atorvastatin + 200 mg/kg·d PNS (Group D, H), and normal saline (Group E, I). After 8 weeks, total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol, low density lipoprotein-cholesterol (LDL-C), and serum calcium were analyzed to evaluate the hypolipidemic effect. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, and r-glutamyltransferase levels were measured to assess liver function. The thoracic aortas were used for hematoxylin-eosin staining.In both hepatic injury and nonhepatic injury groups, TC, TG and LDL-C levels significantly decreased in Groups B, D, F, and H. ALT and AST levels significantly increased in Group B, but significantly decreased in Groups C and D. The aortic intima thickness was significantly lower in Groups B, D, F, and H than that in the normal saline group.The combination of atorvastatin and PNS treatment showed a significant hypolipidemic effect and hepatic enzyme stability function.The single use of Panax notoginseng saponins (PNS) in the rat model for atherosclerosis significantly reduced Ca2+ content in serum, whereas the effect of lowing total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C) is not apparent, especially as compared with atorvastatin treatmentPNS combined with atorvastatin treatment of the rat model for atherosclerosis displayed a noticeable, synergistic effect that allowed for better reduction of TC, TG, LDL-C and Ca2+ in the serum than that with the single use of PNS or atorvastatinIn the rat liver injury combined with atherosclerosis model, the single use of PNS significantly improved liver function, whereas atorvastatin alone only aggravated liver injury in the rat model. The effect of PNS combined with atorvastatin on liver function was significantly better than that of atorvastatin aloneThe combined use of PNS and atorvastatin showed good stability of liver function on the liver injury combined with atherosclerosis model. Abbreviations used: PNS: Panax notoginseng saponins; AS: Atherosclerosis; TC: Total cholesterol; TG: Triglyceride; HDL-C: High density lipoprotein-cholesterol; LDL-C: Low density lipoprotein-cholesterol; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; T-BIL: Total bilirubin; r-GT: R-glutamyltransferase; HE: Hematoxylin-eosin.