Dietary leonurine hydrochloride supplementation attenuates lipopolysaccharide challenge-induced intestinal inflammation and barrier dysfunction by inhibiting the NF-κB/MAPK signaling pathway in broilers

Yang, Li; Liu, Gang; Lian, Kexun; Qiao, Yanjie; Zhang, Baojun; Zhu, Xiongwei; Luo, Yan; Shang, Yunxia; Gu, Xinli

doi:10.1093/jas/skz078

Cited by 46 publications

(38 citation statements)

References 54 publications

(65 reference statements)

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“…Intestinal health is essential for the growth of animals. Many pathogenic factors, including oxidative stress and pathogenic bacterial challenges, especially APEC, can damage the intestinal barrier and cause intestinal inflammation [7,23,24]. Ample pieces of evidence have proven that LPS is able to disrupt the intestinal barrier of broilers by bacterial challenge, which could cause a reduction in feed intake [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…In keeping with our findings, Li et al [8] found that a greater amount of neutrophils could be observed in the duodenum of LPS-challenged broilers. Additionally, several studies have demonstrated that LPS is able to induce gut inflammatory responses in broilers by increasing pro-inflammatory cytokine levels [2,7,8]. The release of pro-inflammatory cytokines requires the activation of TLR4 [29].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, STE supplementation ameliorated the redox damage by reducing malondialdehyde (MDA) content and increasing total antioxidant capacity (T-AOC) and antioxidant enzyme activity. In conclusion, dietary stevioside supplementation could alleviate LPS-induced intestinal mucosal damage through anti-inflammatory and antioxidant effects in broiler chickens.Antioxidants 2019, 8, 575 2 of 20 and oxidative status of the intestine in broiler chickens [7][8][9]. Thus, LPS has been widely applied to establish a model of intestinal mucosal damage in broiler chickens [2,[7][8][9][10].…”

mentioning

confidence: 99%

“…In conclusion, dietary stevioside supplementation could alleviate LPS-induced intestinal mucosal damage through anti-inflammatory and antioxidant effects in broiler chickens.Antioxidants 2019, 8, 575 2 of 20 and oxidative status of the intestine in broiler chickens [7][8][9]. Thus, LPS has been widely applied to establish a model of intestinal mucosal damage in broiler chickens [2,[7][8][9][10]. It is necessary to explore feed additives with therapeutic potential for disrupted intestinal homeostasis of LPS-challenged in broilers.Stevioside (STE) is a natural diterpenoid glycoside extracted from the Stevia rebaudiana (Bertoni), which has been proven to be safe in the food industry [11].…”

mentioning

confidence: 99%

“…Antioxidants 2019, 8, 575 2 of 20 and oxidative status of the intestine in broiler chickens [7][8][9]. Thus, LPS has been widely applied to establish a model of intestinal mucosal damage in broiler chickens [2,[7][8][9][10]. It is necessary to explore feed additives with therapeutic potential for disrupted intestinal homeostasis of LPS-challenged in broilers.…”

mentioning

confidence: 99%

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Dietary Stevioside Supplementation Alleviates Lipopolysaccharide-Induced Intestinal Mucosal Damage through Anti-Inflammatory and Antioxidant Effects in Broiler Chickens

Jiang

et al. 2019

Antioxidants

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The study was conducted to investigate the effects of dietary stevioside (STE) supplementation on the lipopolysaccharide (LPS)-induced intestinal mucosal damage of broiler chickens. A total of 192 one-day-old male Ross 308 broiler chicks were randomly divided into four treatments: (1) basal diet (CON); (2) basal diet supplemented with 250 mg/kg stevioside (STE);(3) basal diet + LPS-challenge (LPS); (4) basal diet supplemented with 250 mg/kg stevioside + LPS-challenge (LPS + STE). LPS-challenged groups received an intraperitoneal injection of LPS at 17, 19 and 21 d, whereas the CON and STE groups received a saline injection. The results showed that dietary STE supplementation normalized LPS-induced changes in protein expression of p-NF-κB and p-IκBα, mRNA expression of inflammatory genes (TLR4, NF-κB, and IFN-γ), tight junction-related genes (CLDN2, OCLN, and ZO-1), and antioxidant genes (Nrf2 and HO-1). LPS-induced decreases in serum diamine oxidase (DAO) level, villus height-to-crypt depth ratio, apoptotic index, and protein expression of proliferating cell nuclear antigen (PCNA) were reversed with dietary STE supplementation. Additionally, STE supplementation ameliorated the redox damage by reducing malondialdehyde (MDA) content and increasing total antioxidant capacity (T-AOC) and antioxidant enzyme activity. In conclusion, dietary stevioside supplementation could alleviate LPS-induced intestinal mucosal damage through anti-inflammatory and antioxidant effects in broiler chickens.Antioxidants 2019, 8, 575 2 of 20 and oxidative status of the intestine in broiler chickens [7][8][9]. Thus, LPS has been widely applied to establish a model of intestinal mucosal damage in broiler chickens [2,[7][8][9][10]. It is necessary to explore feed additives with therapeutic potential for disrupted intestinal homeostasis of LPS-challenged in broilers.Stevioside (STE) is a natural diterpenoid glycoside extracted from the Stevia rebaudiana (Bertoni), which has been proven to be safe in the food industry [11]. A previous study has suggested that STE exerts no harmful effects in the chicken diet with a dose of 667 mg/kg [12]. Despite STE being 250−300 times sweeter than sucrose, it has several nutritional and medical activities such as anti-hyperglycaemic [13], anti-hypertensive [14], and anti-tumor activities [15]. Furthermore, several studies have shown that STE exerts anti-inflammatory and antioxidant effects both in vivo and in vitro [11,14,16]. In rats, STE could prevent liver inflammation through antioxidant activity by activating Nrf2 and anti-inflammatory activity by suppressing NF-κB signaling [11]. In a human colonic cell line, steviol (a derivative of STE) suppressed the IL-8 release induced by TNF-α, and reduced the protein expression of NF-κB [17]. STE could also attenuate the LPS-induced synthesis of pro-inflammatory cytokines by regulating IκBα/NF-κB signaling pathway [16]. In mice, STE promoted macrophage function and increased humoral immune response [18]. STE treatment enhanced antioxidant defense in both the adi...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Dietary Stevioside Supplementation Alleviates Lipopolysaccharide-Induced Intestinal Mucosal Damage through Anti-Inflammatory and Antioxidant Effects in Broiler Chickens

Jiang

et al. 2019

Antioxidants

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Alkaloid leonurine exerts anti‐inflammatory effects via modulating MST1 expression in trophoblast cells

Zong

Zhao

2021

Immunity Inflam & Disease

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Background: Pre-eclampsia (PE) is mainly attributed to the inflammation of trophoblast cells in pregnant women, which results in damage to the maternal organs and growth retardation of the fetus. Alkaloid leonurine (LNR) is a plant compound and has anti-inflammatory effects. Here we aimed to investigate the effects of LNR on human and mouse trophoblast cells and the underlying mechanisms. Methods: The levels of the inflammatory factors in trophoblast cells under lipopolysaccharides (LPS) stimulation were analyzed with ELISA. Western blot was employed to examine the protein expression. Trophoblast cells in Mammalian ste20-like kinase 1 (MST1 −/− ) or wild type (WT) mice were isolated to examine the expression of signal molecules in the nuclear factor-κB (NF-κB) pathway. Concentration-dependent activity of NF-κB was examined.The regulation of LNR and MST1 in MST1 −/− trophoblast cells was studied as well.Results: Our data showed that LNR exhibited anti-inflammatory effects and suppressed the NF-κB signaling by inhibiting LPS-induced inflammation in trophoblast cells. LNR upregulated the expression of MST1, and the antiinflammatory role of LNR was greatly relieved in MST1-knockout trophoblast cells, although it displayed weak roles in NF-κB signaling.Conclusion: LNR exhibits anti-inflammatory effects on human and mouse trophoblast cells by upregulating MST1 in the NF-κB signal pathway.

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Leonurine inhibits the TXNIP/NLRP3 and NF‐κB pathways via Nrf2 activation to alleviate carrageenan‐induced pleurisy in mice

Yan

Hou

et al. 2022

Phytotherapy Research

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Oxidative stress and inflammation play important roles in pleurisy. Leonurine (Leo) has been confirmed to exert antioxidative and antiinflammatory effects in many preclinical experiments, but these effects have not been studied in pleurisy. The aim of this study was to explore the therapeutic effect and mechanism of Leo in a carrageenan (CAR)‐induced pleurisy model. In this study, we found that the increase of reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA) and decrease of glutathione (GSH) induced by CAR could be reversed by the treatment of Leo. Leo effectively reduced the levels of proinflammatory cytokines interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), and the percentages of mature macrophages and increased the levels of antiinflammatory cytokines (IL‐10). Furthermore, Western blotting revealed that Leo significantly activated the Nrf2 pathway to restrain the thioredoxin‐interacting protein/NOD‐like receptor protein 3 (TXNIP/NLRP3) and nuclear factor kappa‐B (NF‐κB) pathways. However, the protective effect of Leo was significantly weakened in Nrf2‐deficient mice. These results indicate that Leo confers potent protection against CAR‐induced pleurisy by inhibiting the TXNIP/NLRP3 and NF‐κB pathways dependent on Nrf2, which may serve as a promising agent for attenuating pleurisy.

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Dietary leonurine hydrochloride supplementation attenuates lipopolysaccharide challenge-induced intestinal inflammation and barrier dysfunction by inhibiting the NF-κB/MAPK signaling pathway in broilers

Cited by 46 publications

References 54 publications

Dietary Stevioside Supplementation Alleviates Lipopolysaccharide-Induced Intestinal Mucosal Damage through Anti-Inflammatory and Antioxidant Effects in Broiler Chickens

Dietary Stevioside Supplementation Alleviates Lipopolysaccharide-Induced Intestinal Mucosal Damage through Anti-Inflammatory and Antioxidant Effects in Broiler Chickens

Alkaloid leonurine exerts anti‐inflammatory effects via modulating MST1 expression in trophoblast cells

Leonurine inhibits the TXNIP/NLRP3 and NF‐κB pathways via Nrf2 activation to alleviate carrageenan‐induced pleurisy in mice

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