peoniflorin and Diabetes-Mellitus--Type-1

This study aimed to explore the effect of PF in regulating the progression of T1D through regulating gut microbiota and inhibiting TLR4-myD88/TRIF pathway. T1D mouse models were established and received PF treatment through intraperitoneal injection. The glucose, sugar tolerance, the incidence of T1D and H&E staining were detected to verify the effect of PF on T1D. Meanwhile, the changes of gut microbiota and the permeability of intestines in mice were also measured. On parallel, the number and function of immune cells were detected by Flow Cytometry. The expressions of ZO-1, ZO-2 and TLR4-myD88/TRIF pathway related proteins were detected by western blotting. Mice received PF treatment had decreased incidence of T1D and inflammatory infiltration in islet tissues compared with those received PBS treatment. In addition to that, PF treated mice had increased Sutterella species and decreased intestinal permeability, in which the decreased ratio of Th1/Th17 and increased Treg cells were also identified. The expression of TLR4-myD88/TRIF pathway was also suppressed in response to PF treatment. Moreover, further treatment with TLR4 agonist, LPS, could reverse the effect of PF on T1D mice. PF can suppress the TLR4 mediated myD88/TRIF pathway to change the distribution of gut microbiota, so as to protect NOD mice from T1D.

Topics: Adaptor Proteins, Vesicular Transport; Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Myeloid Differentiation Factor 88; Signal Transduction; Toll-Like Receptor 4

Paeoniflorin is the main bioactive components of the root of P.lactiflora Pall., and has been widely used as an anti-inflammation and immunomodulatory agent. However, the effect and mechanisms of Paeoniflorin in diabetic nephropathy (DN) remains to be elucidated. In the present study, streptozotocin (STZ)-induced type 1 diabetic mice model was used to investigate the protective effect of Paeoniflorin and the role of the Janus kinase (JAK) 2/signal transducer (STAT) 3 signaling pathway on DN. After treatment with Paeoniflorin at a dose of 25, 50 and 100 mg/kg once a day for 12 weeks, both the functional and histological damage to diabetic mice kidney had been attenuated significantly. Additionally, these reno-protective effects were associated with alleviating macrophage infiltration and inflammatory factors expression as well as suppression of the JAK2/STAT3 signaling pathway. These data reveal that Paeoniflorin attenuates renal lesions in diabetic mice and these protective effects may be associated with the prevention of macrophage infiltration and inhibition of the JAK2/STAT3 signaling pathway.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Glucosides; Humans; Janus Kinase 2; Kidney; Macrophages; Male; Mice; Mice, Inbred C57BL; Monoterpenes; Signal Transduction; STAT3 Transcription Factor; Streptozocin