Renal protective effect of Paeoniflorin by inhibition of JAK2/STAT3 signaling pathway in diabetic mice

Abstract

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.

Neuritin inhibits astrogliosis to ameliorate diabetic cognitive dysfunction

“…LPS induces the activation of retinal astrocytes via the JAK2/STAT3 signaling pathway ( Jang et al 2007 ). The JAK2/STAT3 signaling pathway also contributes to the development of diabetic macrovascular complications by mediating inflammation associated with vascular endothelial cells and/or monocytes ( Yang et al 2017 ) and involves the renal protective effect of paeoniflorin ( Li et al 2018 ).…”

A Protective Role of Paeoniflorin in Fluctuant Hyperglycemia-Induced Vascular Endothelial Injuries through Antioxidative and Anti-Inflammatory Effects and Reduction of PKCβ1

“…Paeoniflorin, a monoterpene glucoside, is the main active ingredient of the root of P. lactiflora and has multiple biological activities such as antioxidation, cognition-enhancing, anticoagulation, anticonvulsant, vasodilation, mild sedation, and potent analgesia [39, 40]. Till now, the protective roles of PF refer to amelioration of DM or its complications, such as diabetic nephropathy [21, 41], and cardiovascular events [19], nothing about PF and hyperglycemia fluctuation. In this study, it demonstrated that PF could alleviate vascular injuries induced by hyperglycemia fluctuations in terms of the release of TNF- α , PECAM-1, oxidative stress, and the expression of PKC β 1 in HUVECs subjected to intermittent glucose levels and in DM rats with fluctuating hyperglycemia.…”

“…Paeoniflorin (PF, Figure 1) is an important component of Paeonia lactiflora Pall that shows various protective effects on the cardio-cerebral vascular system, mediated by antiapoptosis [16], anti-inflammation [17], and antioxidantation [18]. Furthermore, PF is reported to play an essential protective role in both DM-associated macrovascular complications, such as myocardial infarction via the transient receptor potential vanilloid 1/calcitonin gene-related peptide pathway [19], and DM-associated microvascular complications, such as diabetic nephropathy with renal protective effects by prevention of TLR2/4-mediated inflammation [20] or inhibition of the JAK2/STAT3 signaling pathway [21]. However, the effects and mechanisms of PF on glucose fluctuation-induced damages remain to be elucidated.…”

Paeoniflorin Ameliorates Macrophage Infiltration and Activation by Inhibiting the TLR4 Signaling Pathway in Diabetic Nephropathy

“…We speculate, based on these observations, that PF can improve the inflammatory status in DN through inhibiting the TLR4 pathway. Moreover, the anti-inflammatory mechanism of PF is also associated with other signaling pathways (Shao et al, 2016; Li et al, 2018).…”