scholarly journals Glycerol Monolaurate Attenuated Immunological Stress and Intestinal Mucosal Injury by Regulating the Gut Microbiota and AMPK/NF-κB/Nrf2 Signaling Pathway in Lipopolysaccharide-Challenged Broilers

Author(s):  
Linglian Kong ◽  
Zhenhua Wang ◽  
Chuanpi Xiao ◽  
Qidong Zhu ◽  
Zhigang Song

Abstract Background Antibiotic residues and resistance issues have led to the ban on antibiotic growth promoters in the poultry industry. Targeted dietary supplementation such as glycerol monolaurate (GML) has been found to ameliorate the negative effects of restriction on the use of antibiotic growth promoters by modulating the animal immune system and intestinal health. However, the mechanism by which GML contributes to the health and growth of broilers is indistinct. This study was conducted to investigate the effects of GML on immunity, intestinal barrier function, and cecal microbiota profiles in lipopolysaccharide (LPS)-challenged broilers. Results The results revealed that dietary GML intake augmented serum immunoglobulin A and G levels in LPS-challenged broilers. GML supplementation normalized LPS-induced variations in serum interleukin-6, interferon-γ, and LPS levels; jejunal villus height; and gene expression of interleukin-6, macrophage inflammatory protein-3α, toll-like receptor 4, nuclear factor kappa-B (NF-κB), caspase-1, tight junction proteins, adenosine monophosphate-activated protein kinase α1, nuclear factor-erythroid 2-related factor 2, and superoxide dismutase-1. GML administration ameliorated LPS-induced peroxidation by reducing malondialdehyde content and increasing antioxidant enzyme activity. Dietary GML intake enhanced the abundances of cecal probiotics such as Blautia, Lactobacillus, and Coprobacter in challenged broilers. The LPS-induced reduction in Anaerostipes, Pseudoflavonifractor, and Gordonibacter abundances in the cecum was inhibited by GML supplementation. Dietary GML intake was positively correlated with alterations in antioxidant enzyme activities and adenosine monophosphate-activated protein kinase (AMPK) α1, nuclear factor-erythroid 2-related factor 2 (Nrf2), and zonula occludens-1 levels. The genera Anaerostipes, Lachnospira, Gordonibacter, Lachnospira, Marvinbryantia, Peptococcus, and Pseudoflavonifractor were linked to attenuated inflammation and improved immunity and antioxidant capacity of LPS-challenged broilers. Conclusion Dietary GML intake alleviated LPS-induced immunological stress and intestinal injury in broilers. This beneficial effect of GML supplementation was attributed to the suppression of inflammation and oxidative stress by regulation of cecal microbiota and the AMPK/NF-κB/Nrf2 signaling pathway in LPS-challenged broilers.

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yuanyuan Liu ◽  
Boxi Zhang ◽  
Jiahe Liu ◽  
Chunyu Qiao ◽  
Nianyu Xue ◽  
...  

As innate immune effector cells in the central nervous system (CNS), microglia not only are essential for the normal development of nervous system but also act on different neurological diseases, including Alzheimer’s disease (AD), Huntington's disease (HD), and other neuroinflammatory diseases. Mogroside V (Mog), a natural plant active ingredient and isolated form of Momordica grosvenori, has been shown to possess anti-inflammatory action, but few studies were carried out to investigate the effects of Mog on neuroinflammation. This study aimed to investigate the role of Mog in lipopolysaccharide- (LPS-) induced neuroinflammation and neuronal damage, revealing the underlying mechanisms. Our data indicated that Mog significantly inhibited the LPS-induced production of proinflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-18, IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and high mobility group box 1 (HMGB1) in BV-2 cells. We found that Mog also suppressed toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), the phosphorylation of mitogen-activated protein kinases (MAPKs), adenosine 5′-monophosphate- (AMP-) activated protein kinase (AMPK), nuclear factor kappa-B (NF-κB), and protein kinase B (AKT). Moreover, Mog also enhanced the expression of γ-glutamyl cysteine synthetase catalytic subunit (GCLC), modifier subunit (GCLM), heme oxygenase-1 (HO-1), and quinine oxidoreductase 1 (NQO1) proteins, mostly depending on the nuclear translation of nuclear factor erythroid-2 related factor 2 (Nrf2). In contrast, pretreatment with inhibitors of AKT can suppress the phosphorylation of AMPK, Nrf2, and its downstream proteins expression. In summary, Mog might play a protective role against LPS-induced neurotoxicity by inhibiting the TLR4-MyD88 and activation of AMPK/AKT-Nrf2 signaling pathway.


2021 ◽  
Vol 20 (1) ◽  
pp. 169-176
Author(s):  
Jingfang Hu ◽  
Jie Jin ◽  
Yan Chen ◽  
Jinyi Wei ◽  
Hanbei Chen

Diabetes mellitus is a metabolic disorder characterized by inflammation, abnormal glycolipid metabolism, insulin resistance, and mitochondrial dysfunction leading to hyperglycemia. The aim of the present investigation was to determine the efficacy of lycopsamine in a rat model of diabetes mellitus to understand its mechanism. Lycopsamine treatment markedly lowered the level of total cholesterol, triglyceride, nonesterified fatty acids, and low-density lipoprotein in diabetic rats. There was also a reduction in interleukin-6, interleukin-10, C-reactive protein, and tumor necrosis factor-α levels. Lycopsamine treatment normalized the metabolism of lipid and glucose, insulin resistance, and body weight of diabetic rats. Findings of immunohistochemical analyses exhibited rise in precipitation of immunocytes in renal cells. Results potentially demonstrated that lycopsamine treatment remarkably reduced the nuclear factor-kappa B level and enhanced the 5′ adenosine monophosphate-activated protein kinase expression. Altogether, administration of lycopsamine suppressed the expression of inflammatory cytokines and attenuated the metabolic symptoms in diabetes mellitus experimental rats.


2017 ◽  
Vol 8 ◽  
Author(s):  
Áislan de Carvalho Vivarini ◽  
Teresa Cristina Calegari-Silva ◽  
Alessandra Mattos Saliba ◽  
Viviane Sampaio Boaventura ◽  
Jaqueline França-Costa ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Qinqin Qiao ◽  
Liang Chen ◽  
Xiang Li ◽  
Xiangyang Lu ◽  
Qingbiao Xu

Bioactive peptides (BPs) are fragments of 2–15 amino acid residues with biological properties. Dietary BPs derived from milk, egg, fish, soybean, corn, rice, quinoa, wheat, oat, potato, common bean, spirulina, and mussel are reported to possess beneficial effects on redox balance and metabolic disorders (obesity, diabetes, hypertension, and inflammatory bowel diseases (IBD)). Peptide length, sequence, and composition significantly affected the bioactive properties of dietary BPs. Numerous studies have demonstrated that various dietary protein-derived BPs exhibited biological activities through the modulation of various molecular mechanisms and signaling pathways, including Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/antioxidant response element in oxidative stress; peroxisome proliferator-activated-γ, CCAAT/enhancer-binding protein-α, and sterol regulatory element binding protein 1 in obesity; insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B and AMP-activated protein kinase in diabetes; angiotensin-converting enzyme inhibition in hypertension; and mitogen-activated protein kinase and nuclear factor-kappa B in IBD. This review focuses on the action of molecular mechanisms of dietary BPs and provides novel insights in the maintenance of redox balance and metabolic diseases of human.


PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0171642 ◽  
Author(s):  
Marcio C. Costa ◽  
Jose A. Bessegatto ◽  
Amauri A. Alfieri ◽  
J. Scott Weese ◽  
João A. B. Filho ◽  
...  

2021 ◽  
Vol 1 ◽  
pp. 5
Author(s):  
Ifeoluwa Awogbindin ◽  
Samuel Onasanwo ◽  
Oluwatoyin Ezekiel ◽  
Inioluwa Akindoyeni ◽  
Yusuf Mustapha ◽  
...  

Objectives: Parkinson’s disease (PD) is the most prevalent movement disorder. Available therapies are palliative with no effect on disease progression. We have previously demonstrated that kolaviron (KV), a natural anti-inflammatory and antioxidant agent, suppressed behavioral defect, redo-inflammation, and nigrostriatal pathology in rotenone PD model. The present study investigates the neuroprotective effect of KV focusing on DJ-1/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Material and Methods: All-trans retinoic acid (ATRA, 10 mg/kg/day) was used to inhibit Nrf2. PD was established with four doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (20 mg/kg) at 2 h interval. MPTP mice were pre-treated with either KV (200 mg/kg/day), ATRA or both for 7 days before MPTP. Mice were evaluated for locomotor defects and indices of oxidative stress, neuroinflammation and neurotransmission as well as pathological tyrosine hydroxylase expression PD were evaluated in the striatum. Results: ATRA alone in mice did not exhibit neurobehavioral defect but caused striatal toxicity, mild nigrostriatal pathology, significant nitrosative stress, and Nrf2 cascade inhibition. KV+ATRA mice were slow in movement with frequent short-lived interruptions and oxidative striatal pathology. ATRA aggravated MPTP-associated locomotor incompetence and could not prevent nigrostriatal toxicity with evident vacuolated striosome and pyknotic/degenerating dopaminergic neurons. MPTP induced acute locomotor, exploratory, and motor incompetence, which was prevented by KV treatment. In addition, KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal nitrosative stress, and oxidative damage with elevated DJ-1 level, potentiated Nrf2/NAD(P)H; quinone oxidoreductase-1 cytoprotective capacity, reduced Kelch-like ECH-associated protein 1 expression, and limited striatal pathology. However, ATRA treatment attenuated all the protective effects of KV on MPTP-challenged mice. Meanwhile, other ATRA-combinations elicited significant DJ-1 and Nrf2 induction but are associated striatal toxicity/pathology. Conclusion: This suggests that KV may be conferring protection through a yet-undetermined DJ-1 downstream cytoprotective effect dependent on the KV-mediated attenuation of oxidative environment.


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