2-Methyl Nonyl Ketone From Houttuynia Cordata Thunb Alleviates LPS-Induced Inflammatory Response and Oxidative Stress in Bovine Mammary Epithelial Cells

Nan Wang,Chunjin Li,Yuxin Luo,Dandan Li,Xu Zhou,Yiqiu Huang,Lu Chen,Yanbin Zhu,Wangdui Basang,Kening Liu

doi:10.3389/fchem.2021.793475

Abstract

Mastitis is one of the most common diseases in dairy cows, causing huge economic losses to the dairy industry every year. Houttuynia Cordata Thunb ( H.cordata ) is a traditional Chinese herbal medicine that is widely used in clinical treatment. However, the therapeutic effect of 2-methyl nonyl ketone (MNK), the main volatile oil component in the aqueous vapor extract of H. cordata, on mastitis has been less studied. The purpose of this study was to investigate the protective effect and mechanism of MNK against lipopolysaccharide (LPS)-induced mastitis in vitro. The results showed that MNK pretreatment of the bovine mammary epithelial cell line (MAC-T) enhanced cell viability and inhibited LPS-induced reactive oxygen species (ROS) production and inflammatory response. MNK reduced the production of pro-inflammatory cytokines such as interleukin (IL) and tumor necrosis factor-α (TNF-α) by repressing LPS-induced activation of Toll-like receptor 4-nuclear factor-κB (TLR4-NF-κB) signaling pathway. In addition, MNK protected cells from inflammatory responses by blocking the downstream signaling of inflammatory factors. MNK also induced Heme Oxygenase-1 ( HO-1 ) production by Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway through AKT and extracellular signal-regulated kinase (ERK) pathways, thereby reducing LPS-induced oxidative damage for MAC-T cells. In conclusion, MNK played a protective role against LPS-induced cell injury. This provides a theoretical basis for the research and development of MNK as a novel therapeutic agent for mastitis.

Highlights

Mastitis is a common infectious disease in dairy cows and is highly influential and recurring (Klaas and Zadoks, 2018)
It was shown that decreased cell viability induced by LPS was reversed by methyl nonyl ketone (MNK) (Figure 2C)
The results showed that Nuclear factor erythroid 2related factor 2 (Nrf2) protein expression was significantly decreased in the LPS group compared to the control group

Summary

Introduction

Mastitis is a common infectious disease in dairy cows and is highly influential and recurring (Klaas and Zadoks, 2018). Mastitis leads to reduced milk production, lower milk quality, shorter productive life and higher culling rates in dairy cows, causing huge economic losses to dairy farming worldwide (Aghamohammadi et al, 2018; Hadrich et al, 2018; Puerto et al, 2021). Mastitis is an inflammation of the Protective Effect of 2-Methyl Nonyl Ketone breast caused by pathogenic microorganisms invading the mammary gland and release large amounts of toxins (Klaas and Zadoks, 2018). LPS is a major component of Gram-negative bacteria and can cause severe mammary immune responses. LPS is commonly used to construct models of inflammatory response (Guo et al, 2019). The traditional therapy of treating mastitis is antibiotics, but this is prone to cause drug residues and drug resistance. The development of alternative drugs for the prevention and treatment of mastitis is necessary

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