The cytoprotective effects of dihydromyricetin and associated metabolic pathway changes on deoxynivalenol treated IPEC-J2 cells

Long, Hongrong; Xin, Zhongquan; Zhang, Fan; Zhai, Zhe; Ni, Xiaojun; Chen, Jialuo; Yang, Kailun; Liao, Pinfeng; Zhang, Limeng; Xiao, Zaili; Sindaye, Daniel; Deng, Baichuan

doi:10.1016/j.foodchem.2020.128116

Cited by 20 publications

(18 citation statements)

References 38 publications

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“…Conventional treatment mainly includes oral intake antibacterial and anti-inflammatory drugs, or taking surgery, etc. In recent years, researchers have found that effective components in plant can be used to prevent or treat intestinal inflammation ( Zhao et al, 2019 ; Long et al, 2021 ). Eucommia ulmoides is a traditional Chinese herbal medicine that has also been approved for use as a functional food.…”

Section: Discussionmentioning

confidence: 99%

The Gut Microbiota-Bile Acids-TGR5 Axis Mediates Eucommia ulmoides Leaf Extract Alleviation of Injury to Colonic Epithelium Integrity

et al. 2021

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Eucommia ulmoides leaves (EL) are rich in phenolic acids and flavonoids, showing enhancing intestinal health effects. The intestinal microbiota-bile acid axis plays important roles in the occurrence and recovery of inflammatory bowel disease (IBD). However, whether EL extract (ELE) has regulatory effects on the intestinal microbiota, bile acid metabolism, and IBD is still unclear. To fill this gap, 2% dextran sulfate sodium (DSS)-induced mild IBD in a C57BL/6J mouse model that was treated with 200 or 400 mg/kg (intake dose/body weight) ELE was used. Oral ELE supplementation alleviated DSS-induced shortening of colon and colonic epithelial injury. Compared with the DSS group, ELE supplementation significantly decreased Toll-like receptor 4 (TLR4) and interlukin-6 (IL-6) and increased occludin and claudin-1 mRNA expression level in the colon (p < 0.05). Combined 16S rRNA gene sequencing and targeted metabolomic analyses demonstrated that ELE significantly improved the diversity and richness of the intestinal microbiota, decreased the abundance of Bacteroidaceae, and increased Akkermansiaceae and Ruminococcaceae abundance (p < 0.05) compared with DSS-induced IBD mice. Moreover, ELE significantly increased the serum contents of deoxycholic acid (DCA) and tauroursodeoxycholic acid (TUDCA), which were highly positively correlated with Akkermansia and unidentified_Ruminococccaceae relative to the DSS group. We then found that ELE increased Takeda G-protein coupled receptor 5 (TGR5), claudin-1, and occludin mRNA expression levels in the colon. In the Caco-2 cell model, we confirmed that activation of TGR5 improved the reduction in transepithelial electoral resistance (TEER) and decreased the permeability of FITC-dextran on monolayer cells induced by LPS (p < 0.05). siRNA interference assays showed that the decrease in TGR5 expression led to the decrease in TEER, an increase in FITC-dextran permeability, and a decrease in claudin-1 protein expression in Caco-2 cells. In summary, ELE alleviated IBD by influencing the intestinal microbiota structure and composition of bile acids, which in turn activated the colonic TGR5 gene expression in the colon and promoted the expression of tight junction proteins. These findings provide new insight for using ELE as a functional food with adjuvant therapeutic effects in IBD.

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Section: Discussionmentioning

confidence: 99%

The Gut Microbiota-Bile Acids-TGR5 Axis Mediates Eucommia ulmoides Leaf Extract Alleviation of Injury to Colonic Epithelium Integrity

et al. 2021

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“…DMY protected chickens from the ileum injury induced by Escherichia coli lipopolysaccharide (LPS), via the suppression of NLRP3 inflammasome and activation of TLR4/NF‐ κB signal axis [100]. DMY had a practical value as an anti‐toxicity additive in food or feed, because it could reduce the deoxynivalenol‐ induced cytotoxicity in porcine jejunum epithelial cell line, IPEC‐J2 possibly via limiting the metabolism of glutamate, arachidonic, as well as histidine [101].…”

Section: Pharmacological Effects and Actions Mechanisms Of Dmymentioning

confidence: 99%

A multifaceted review on dihydromyricetin resources, extraction, bioavailability, biotransformation, bioactivities, and food applications with future perspectives to maximize its value

Zhang

Caprioli²,

Hussain

et al. 2021

eFood

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Natural bioactive compounds present a better alternative to prevent and treat chronic diseases owing to their lower toxicity and abundant resources. (+)-Dihydromyricetin (DMY) is a flavanonol, possessing numerous interesting bioactivities with abundant resources. This review provides a comprehensive overview of the recent advances in DMY natural resources, stereoisomerism, physicochemical properties, extraction, biosynthesis, pharmacokinetics, and biotransformation. Stereoisomerism of DMY should be considered for better indication of its efficacy. Biotechnological approach presents a potential tool for the production of DMY using microbial cell factories. DMY high instability is related to its powerful antioxidant capacity due to pyrogallol moiety in ring B, and whether preparation of other analogues could demonstrate improved properties. DMY demonstrates poor bioavailability based on its low solubility and permeability with several attempts to improve its pharmacokinetics and efficacy. DMY possesses various pharmacological effects, which have been proven by many in vitro and in vivo experiments, while clinical trials are rather scarce, with underlying action mechanisms remaining unclear. Consequently, to maximize the usefulness of DMY in nutraceuticals, improvement in bioavailability, and better understanding of its actions mechanisms and drug interactions ought to be examined in the future along with more clinical evidence.

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“…Numerous studies have confirmed that DON could affect nutrient absorption, disrupt the intestinal barrier integrity, and induce the oxidative stress and inflammation response of pigs ( Liao et al., 2020 ; Martinez et al., 2019 ; Pasternak et al., 2018 ). Regardless of several antioxidants being reported to alleviate DON-induced cytotoxicity, effective treatments for DON oxidative stress and intestinal tight junction require further investigation ( Long et al., 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Phenethyl isothiocyanate as an anti-nutritional factor attenuates deoxynivalenol-induced IPEC-J2 cell injury through inhibiting ROS-mediated autophagy

Liu

Hou

et al. 2022

Animal Nutrition

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Deoxynivalenol (DON) is considered to be the most harmful mycotoxin that affects the intestinal health of animals and humans. Phenethyl isothiocyanate (PEITC) in feedstuff is an anti-nutritional factor and impairs nutrient digestion and absorption in the animal intestinal. In the current study, we aimed to explore the effects of PEITC on DON-induced apoptosis, intestinal tight junction disorder, and its potential molecular mechanism in the porcine jejunum epithelial cell line (IPEC-J2). Our results indicated that PEITC treatment markedly alleviated DON-induced cytotoxicity, decreasing the apoptotic cell percentage and pro-apoptotic mRNA/protein levels, and increasing zonula occludens-1 (ZO-1), occludin and claudin-1 mRNA/protein expression. Meanwhile, PEITC treatment ameliorated DON-induced an increase of the inducible nitric oxide synthase ( iNOS ) and cyclooxygenase 2 ( COX-2 ) mRNA levels and intracellular reactive oxygen species (ROS) level, and a decrease of glutathione peroxidase 1 ( GPx1 ), superoxide dismutase 2 ( SOD2 ), catalase ( CAT ) and heme oxygenase 1 ( HO-1 ) mRNA levels. Additionally, PEITC treatment significantly down-regulated autophagy-related protein 5 (ATG5), beclin-1 and microtubule-associated protein 1 light chain 3B (LC3-Ⅱ) mRNA/protein levels, decreased the number of green fluorescent protein-microtubule-associated protein 1 light-chain 3 (GFP-LC3) puncta and phosphatidylinositol 3 kinase (PI3K) protein expression, and up-regulated phospho-protein kinase B (p-Akt) and phospho-mammalian target of rapamycin (p-mTOR) protein expression against DON. However, the activation of autophagy by rapamycin, an autophagy agonist, abolished the protective effects of PEITC against DON-induced cytotoxicity, apoptosis and intestinal tight junction disorder. Collectively, PEITC could confer protection against DON-induced porcine intestinal epithelial cell injury by suppressing ROS-mediated autophagy.

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The cytoprotective effects of dihydromyricetin and associated metabolic pathway changes on deoxynivalenol treated IPEC-J2 cells

Cited by 20 publications

References 38 publications

The Gut Microbiota-Bile Acids-TGR5 Axis Mediates Eucommia ulmoides Leaf Extract Alleviation of Injury to Colonic Epithelium Integrity

The Gut Microbiota-Bile Acids-TGR5 Axis Mediates Eucommia ulmoides Leaf Extract Alleviation of Injury to Colonic Epithelium Integrity

A multifaceted review on dihydromyricetin resources, extraction, bioavailability, biotransformation, bioactivities, and food applications with future perspectives to maximize its value

Phenethyl isothiocyanate as an anti-nutritional factor attenuates deoxynivalenol-induced IPEC-J2 cell injury through inhibiting ROS-mediated autophagy

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