CP‐25 Alleviates Experimental Sjögren's Syndrome Features in NOD/Ltj Mice and Modulates T Lymphocyte Subsets

Gu, Fei; Xu, Shouping; Zhang, Pengying; Chen, Xiaoyun; Wu, Yujing; Chun, Wang; Gao, Mengchun; Si, Min; Wang, Xinming; Korner, Heinrich; Wu, Huaxun; Wei, Wei

doi:10.1111/bcpt.13025

Cited by 17 publications

(7 citation statements)

References 52 publications

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“…Our lab has reported that CP-25 could reduce pro-inflammatory cytokines production in adjuvant-induced arthritis ( Chang et al, 2016 ). Consistent with another study, CP-25 treatment showed a disease-attenuating effect on modulating T lymphocyte subsets in primary Sjögren’s syndrome mice ( Gu et al, 2018 ). Our previous study presented that paeoniflorin displayed antifibrotic effects on liver fibrosis rats induced by porcine serum ( Sun et al, 2012 ).…”

Section: Introductionsupporting

confidence: 88%

“…The dysregulation of Th1/Th2 would contribute to immunologic disease, such as osteoarthritis, hepatitis, type-1 diabetes and COVID-19 pandemic. Additionally, CP-25 reduced the infiltration of Th1/Th2 cells, and reduced inflammatory cytokines production in autoantigen-induced Sjögren’s syndrome mice ( Gu et al, 2018 ). Then, we paid more attention on the relationship between CP-25 and T cell activation in ConA-induced hepatitis.…”

Section: Discussionmentioning

confidence: 99%

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CP-25 exerts a protective effect against ConA-induced hepatitis via regulating inflammation and immune response

et al. 2022

Front. Pharmacol.

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Hepatitis is a complex multifactorial pathological disorder, which can eventually lead to liver failure and even potentially be life threatening. Paeoniflorin-6′-O-benzene sulfonate (CP-25) has proven to have critical anti-inflammatory effects in arthritis. However, the effects of CP-25 in the pathogenesis of hepatitis remains unclear. In this experiment, mice were intragastrically administered with CP-25 (25, 50 and 100 mg/kg), and then ConA (25 mg/kg) was intravenous injected to establish hepatitis model in vivo. CP-25 administration attenuated liver damage and decreased ALT and AST activities in mice with hepatitis. Besides, CP-25 modulated immune responses including down-regulated the proportions of activated CD4+, activated CD8+ T cells, and ratio of Th1/Th2 in ConA-injected mice. Furthermore, ConA-mediated production of reactive oxygen species (ROS), release of inflammatory cytokines including IFN-γ, TNF-α, activation of MAPK pathways and nuclear translocation of nuclear factor-kappaB (NF-κB) were significantly decreased in CP-25 administrated mice. In ConA-stimulated RAW264.7 cells, CP-25 suppressed inflammatory cytokines secretion and reduced ROS level, which were consistent with animal experiments. Otherwise, the data showed that CP-25 restrained phosphorylation of ERK, JNK and p38 MAPK pathways influenced by ROS, accompanied with inhibiting NF-κB nuclear translocation. In conclusion, our findings indicated that CP-25 protected against ConA-induced hepatitis may through modulating immune responses and attenuating ROS-mediated inflammation via the MAPK/NF-κB signaling pathway.

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Section: Introductionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

CP-25 exerts a protective effect against ConA-induced hepatitis via regulating inflammation and immune response

et al. 2022

Front. Pharmacol.

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“…A concentration of inflammatory cytokines and anti-La/SSB and IgG antibodies in the serum from NOD/Ltj mice was repressed by CP-25. This study suggested that CP-25 is a potential agent for pSS by regulating T lymphocyte subsets (Fang et al, 2018). Taken together, CP-25 was developed which enhanced lipophilicity and strong anti-inflammatory and immune regulatory properties (Table 2).…”

Section: The Pharmacological Effects Of Cp-25mentioning

confidence: 85%

The Regulatory Effects of Paeoniflorin and Its Derivative Paeoniflorin-6′-O-Benzene Sulfonate CP-25 on Inflammation and Immune Diseases

Guo

Hong

et al. 2019

Front. Pharmacol.

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The plant extract “total glucosides of peony” (TGP) constitutes a mixture of glycosides that is isolated from the roots of the well-known traditional Chinese herb Paeonia lactiflora Pall. Paeoniflorin (Pae) is the most abundant component and the main biologically active ingredient of TGP. Pharmacologically, Pae exhibits powerful anti-inflammatory and immune regulatory effects in some animal models of autoimmune diseases including Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). Recently, we modified Pae with an addition of benzene sulfonate to achieve better bioavailability and higher anti-inflammatory immune regulatory effects. This review summarizes the pharmacological activities of Pae and the novel anti-inflammatory and immunomodulatory agent Paeoniflorin-6′-O-benzenesulfonate (CP-25) in various chronic inflammatory and autoimmune disorders. The regulatory effects of Pae and CP-25 make them promising agents for other related diseases, which require extensive investigation in the future.

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“…MDP is a novel active monomer compound, derived from a structural modi cation of paeoni orin (32). MDP has previously been discovered to have anti-in ammatory and immunomodulatory properties in a variety of autoimmune animal models (55)(56)(57). However, the effects and detailed mechanism of MDP in senescence of activated HSCs was not fully understood.…”

Section: Discussionmentioning

confidence: 99%

MDP Induces the Senescence of Activated Hepatic Stellate Cells Through Regulating Ago2/miR-708/ZEB1/p53 Pathway

Yang

Fang

Mei

et al. 2022

Preprint

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Background Extracellular matrix (ECM) is mainly derived from activated hepatic stellate cells (HSC), and its excessive deposition is one of the characteristics of liver fibrosis. Accumulating evidence indicated that the senescence of activated HSCs limits liver fibrosis. Monomer derivative of paeoniflorin (MDP), a derivative of paeoniflorin, inhibits inflammatory responses. However, the role and fundamental mechanism of MDP in liver fibrosis was still unclear. Results We demonstrated that MDP inhibited the progression of liver fibrosis in vivo and in vitro, concomitant with the elevated expression of Ago2, miR-708 and p53 as well as the downregulated expression of ZEB1. Mechanistic investigations revealed that MDP could combined with Ago2, thus promoting the expression of miR-708. Upregulation of miR-708 and p53 and downregulation of ZEB1 increased the number of SA-β-Gal-positive HSCs and the expression levels of p16 and p21 as well as decreased the expression of α-SMA and Col. I in activated HSCs. Meanwhile, further studies revealed that miR-708 directly targeted ZEB1, thus inhibiting the mRNA of ZEB1. More importantly, ZEB1 could bind to the E-box of p53 promoter and restrain its promoter activity as well as thus block the expression of p53. Conclusion MDP could induce senescence of activated HSCs via regulating Ago2/miR-708/ZEB1/p53 aixs and may be applied to treat liver fibrosis.

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CP‐25 Alleviates Experimental Sjögren's Syndrome Features in NOD/Ltj Mice and Modulates T Lymphocyte Subsets

Cited by 17 publications

References 52 publications

CP-25 exerts a protective effect against ConA-induced hepatitis via regulating inflammation and immune response

CP-25 exerts a protective effect against ConA-induced hepatitis via regulating inflammation and immune response

The Regulatory Effects of Paeoniflorin and Its Derivative Paeoniflorin-6′-O-Benzene Sulfonate CP-25 on Inflammation and Immune Diseases

MDP Induces the Senescence of Activated Hepatic Stellate Cells Through Regulating Ago2/miR-708/ZEB1/p53 Pathway

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