Clinical and experimental pharmacology & physiology · 2026
Paeoniflorin-6'-O-Benzenesulfonate Mediates Dendritic Cell Differentiation to Alleviate Diabetic Kidney Disease.
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Liang Wei, Zhu Dongchun, Xiao Lei, Wu Xiaoqian, Zhang Hongwei, Cao Li, Hu Mengxue, Wang Chun, Xiao Feng, Wei Wei, Liu Tingting
Аннотация
AIM: Recent studies demonstrated that the mature dendritic cells (DCs) exhibit renal pathogenicity and promote diabetic kidney disease (DKD). This study investigates the therapeutic potential and mechanisms of paeoniflorin-6'-O-benzene sulfonate (CP-25) to DCs in DKD.
METHODS: DKD mouse model was established by high-fat (HFD) feeding combined with intraperitoneal streptozotocin (STZ) injection. Renal histopathological changes were assessed via haematoxylin and eosin (H&E), masson, and periodic acid-schiff (PAS) staining. Renal function, oxidative stress, and lipid were also quantified. Immune cell differentiation and function were analysed by flow cytometry (FCM). The expression of renal injury markers and fibrosis-associated mRNA and proteins were evaluated by quantitative real-time PCR (qPCR) and western blotting. The target G protein-coupled receptor kinase 2 (GRK2), PI3K-AKT-mTOR, and JAK2-STAT3-SOCS3 pathways were examined to analyse the mechanism of CP-25 to DKD.
RESULTS: CP-25 alleviated renal histopathological damage, inflammatory infiltration, and fibrosis in DKD. CP-25 also reversed renal function, lipid, and oxidative stress indicators of DKD. Additionally, CP-25 inhibited pro-inflammatory cytokines (IL-12) and promoted anti-inflammatory cytokines (IL-4 and IL-10) secretion in the serum of DKD. CP-25 inhibited the differentiation of CD103+DCs and the maturity of DCs in the bone marrow and kidney. Subsequently, CD8+T cells in the spleen and kidney, NKT in the spleen, and Tregs in the spleen and kidney of DKD mice were inhibited by CP-25 treatment. Other immune cells in other immune organs were less affected by CP-25. The communication of DC and T cell was down-regulated by CP-25. The specific mechanism involved CP-25 targeting GRK2 to inhibit the JAK2-STAT3-SOCS3 pathway, thereby suppressing DC maturation and T cell communication in the renal inflammatory response to treat DKD. However, the inhibition of CP-25 to PI3K was indistinctive.
CONCLUSION: CP-25 exhibits therapeutic efficacy against kidney injury in DKD. Its primary mechanism involves modulating the differentiation and function of DCs, which affects the activation of T cells. In terms of mechanism, CP-25 targets the GRK2-mediated JAK2-STAT3-SOCS3 signalling pathway to inhibit inflammation for alleviating DKD.
METHODS: DKD mouse model was established by high-fat (HFD) feeding combined with intraperitoneal streptozotocin (STZ) injection. Renal histopathological changes were assessed via haematoxylin and eosin (H&E), masson, and periodic acid-schiff (PAS) staining. Renal function, oxidative stress, and lipid were also quantified. Immune cell differentiation and function were analysed by flow cytometry (FCM). The expression of renal injury markers and fibrosis-associated mRNA and proteins were evaluated by quantitative real-time PCR (qPCR) and western blotting. The target G protein-coupled receptor kinase 2 (GRK2), PI3K-AKT-mTOR, and JAK2-STAT3-SOCS3 pathways were examined to analyse the mechanism of CP-25 to DKD.
RESULTS: CP-25 alleviated renal histopathological damage, inflammatory infiltration, and fibrosis in DKD. CP-25 also reversed renal function, lipid, and oxidative stress indicators of DKD. Additionally, CP-25 inhibited pro-inflammatory cytokines (IL-12) and promoted anti-inflammatory cytokines (IL-4 and IL-10) secretion in the serum of DKD. CP-25 inhibited the differentiation of CD103+DCs and the maturity of DCs in the bone marrow and kidney. Subsequently, CD8+T cells in the spleen and kidney, NKT in the spleen, and Tregs in the spleen and kidney of DKD mice were inhibited by CP-25 treatment. Other immune cells in other immune organs were less affected by CP-25. The communication of DC and T cell was down-regulated by CP-25. The specific mechanism involved CP-25 targeting GRK2 to inhibit the JAK2-STAT3-SOCS3 pathway, thereby suppressing DC maturation and T cell communication in the renal inflammatory response to treat DKD. However, the inhibition of CP-25 to PI3K was indistinctive.
CONCLUSION: CP-25 exhibits therapeutic efficacy against kidney injury in DKD. Its primary mechanism involves modulating the differentiation and function of DCs, which affects the activation of T cells. In terms of mechanism, CP-25 targets the GRK2-mediated JAK2-STAT3-SOCS3 signalling pathway to inhibit inflammation for alleviating DKD.