Abstract

Peiminine, an alkaloid extracted from Fritillaria plants, has been reported to have potent anti-inflammatory properties. However, the anti-inflammatory effect of peiminine on a mouse lipopolysaccharide (LPS)-induced mastitis model remains to be elucidated. The purpose of this experiment was to investigate the effect of peiminine on LPS-induced mastitis in mice. LPS was injected through the canals of the mammary gland to generate the mouse LPS-induced mastitis model. Peiminine was administered intraperitoneally 1 h before and 12 h after the LPS injection. In vitro, mouse mammary epithelial cells (mMECs) were pretreated with different concentrations of peiminine for 1 h and were then stimulated with LPS. The mechanism of peiminine on mastitis was studied by hematoxylin-eosin staining (H&E) staining, western blotting, and enzyme-linked immunosorbent assay (ELISA). The results showed that peiminine significantly decreased the histopathological impairment of the mammary gland in vivo and reduced the production of pro-inflammatory mediators in vivo and in vitro. Furthermore, peiminine inhibited the phosphorylation of the protein kinase B (AKT)/ nuclear factor-κB (NF-κB), extracellular regulated protein kinase (ERK1/2), and p38 signaling pathways both in vivo and in vitro. All the results suggested that peiminine exerted potent anti-inflammatory effects on LPS-induced mastitis in mice. Therefore, peiminine might be a potential therapeutic agent for mastitis.

Highlights

  • It is well known that dairy mastitis is a production-limiting disease that is harmful to the dairy industry

  • LPS induces a strong inflammatory response, through the production of pro-inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) [3,4], and the genes of these pro-inflammatory factors are regulated by the nuclear factor-κB (NF-κB), ERK1/2, and p38 signaling pathways [5]

  • The results showed that compared with the LPS-treated had significantly increased production of TNF-α, IL-6, IL-1β, COX-2, and induced nitric oxide synthase (iNOS), and that peiminine groups production of TNF-α, IL-6, IL-1β,3B–G)

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Summary

Introduction

It is well known that dairy mastitis is a production-limiting disease that is harmful to the dairy industry. The causes of mastitis are different, mainly due to the invasion of bacteria, fungi, and pathogens into mammary epithelial cells. Escherichia coli is the most common pathogenic bacteria [1], and lipopolysaccharide (LPS) from gram-negative bacteria is considered an important factor that is used to establish an animal model of inflammation [2]. LPS induces a strong inflammatory response, through the production of pro-inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) [3,4], and the genes of these pro-inflammatory factors are regulated by the nuclear factor-κB (NF-κB), ERK1/2, and p38 signaling pathways [5]. The advantages of natural Chinese herbal extracts, including little side effects, light damage to substantial organs, and a good effect on inflammation, are increasingly favored by researchers

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