{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:35:52Z","timestamp":1753893352591,"version":"3.41.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>Intestinal inflammation and barrier damage can inhibit the absorption and transportation of nutrients in the small intestine, and lead to various chronic diseases. Wu Zhi San (WZS) is a traditional Chinese formula composed of Schisandrae, Anemarrhenae, Lonicerae, and Glycyrrhizae that was made to cure intestinal inflammation and barrier damage in broilers. To evaluate the protective effect of WZS on intestinal inflammation and barrier damage of broilers under lipopolysaccharide (LPS) stress, a total of 200 one-day-old broilers were randomly divided into five groups, namely, the CON group, LPS group, and three WZS groups (WZS-H, WZS-M, and WZS-L). The groups were designed for stress phase I (days 15, 17, 19, and 21) and stress phase II (days 29, 31, 33, and 35). The protective effect of WZS on the intestinal tract was evaluated by measuring the levels of serum myeloperoxidase (MPO), diamine oxidase (DAO), super oxide dismutase (SOD), and serum D-lactate (D-LA) and the expression of inflammatory factors in jejunum. The results showed that the diet supplemented with WZS could significantly reduce serum MPO, DAO, and D-LA levels and jejunal CD in broilers (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05), increase serum SOD levels and jejunal VH (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05), significantly downregulate the expression of NF-\u03baB, TLR4, MyD88, and inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6, and IL-10), and upregulate Claudin-1, Occludin-1, and ZO-1 in broiler jejunum mucosa (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). On the other hand, WZS could significantly reduce the protein expression of NF-\u03baB (p65) in broiler jejunum (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). These results indicate that supplementing WZS in the diet can reduce intestinal inflammation and alleviate intestinal barrier damage, and by inhibiting the NF-\u03baB\/TLR4\/MyD88 signaling pathway, supplementation with WZS intervenes in LPS-induced stress injury in broilers.<\/jats:p>","DOI":"10.3389\/fvets.2023.1234769","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T06:10:19Z","timestamp":1701670219000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of Wu Zhi San supplementation in LPS-induced intestinal inflammation and barrier damage in broilers"],"prefix":"10.3389","volume":"10","author":[{"given":"Han","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xirui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bowen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingen","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shijing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dayou","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shining","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"114053","DOI":"10.1016\/j.ecoenv.2022.114053","article-title":"Heat stress-induced intestinal barrier damage and dimethylglycine alleviates via improving the metabolism function of microbiota gut brain axis","volume":"244","author":"Wang","year":"2022","journal-title":"Ecotox Environ Safe"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"105583","DOI":"10.1016\/j.jff.2023.105583","article-title":"Take chicks as an example: Rummeliibacillus stabekisii CY2 enhances immunity and regulates intestinal microbiota by degrading LPS to promote organism growth and development","volume":"105","author":"Chen","year":"2023","journal-title":"J Funct Foods"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.aninu.2023.06.001","article-title":"Probiotic Escherichia coli Nissle 1917 protect chick from damage caused by Salmonella enterica serovar Enteritidis colonization","volume":"14","author":"Wu","year":"2023","journal-title":"Anim Nutr"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e13357","DOI":"10.1111\/asj.13357","article-title":"Regulation of the intestinal barrier by nutrients: the role of tight junctions","volume":"91","author":"Suzuki","year":"2020","journal-title":"Anim Sci J"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"994782","DOI":"10.3389\/fvets.2022.994782","article-title":"Antrodia cinnamomea polysaccharide improves liver antioxidant, anti-inflammatory capacity, and cecal flora structure of slow-growing broiler breeds challenged with lipopolysaccharide","volume":"9","author":"Ye","year":"2022","journal-title":"Front Vet Sci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"102325","DOI":"10.1016\/j.psj.2022.102325","article-title":"Dietary supplementation with anthocyanin attenuates lipopolysaccharide-induced intestinal damage through antioxidant effects in yellow-feathered broiler chicks","volume":"102","author":"Wang","year":"2023","journal-title":"Poult Sci"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.3390\/ani12091100","article-title":"Effects of solid-state fermented wheat bran on growth performance, immune function, intestinal morphology and microflora in lipopolysaccharide-challenged broiler chickens","volume":"12","author":"An","year":"2022","journal-title":"Animals"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1146\/annurev-biochem-060713-035600","article-title":"Biosynthesis and export of bacterial lipopolysaccharides","volume":"83","author":"Whitfield","year":"2014","journal-title":"Annu Rev Biochem"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.intimp.2015.04.054","article-title":"Dietary soy isoflavone attenuated growth performance and intestinal barrier functions in weaned piglets challenged with lipopolysaccharide","volume":"28","author":"Zhu","year":"2015","journal-title":"Int Immunopharmacol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1017\/S0007114518000740","article-title":"Dietary l-threonine supplementation attenuates lipopolysaccharide-induced inflammatory responses and intestinal barrier damage of broiler chickens at an early age","volume":"119","author":"Chen","year":"2018","journal-title":"Br J Nutr"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-kappaB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct Target Ther"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2419","DOI":"10.3382\/ps\/pey076","article-title":"Evaluation of potential antioxidant and anti-inflammatory effects of Antrodia cinnamomea powder and the underlying molecular mechanisms via Nrf2- and NF-kappaB-dominated pathways in broiler chickens","volume":"97","author":"Lee","year":"2018","journal-title":"Poult Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"115570","DOI":"10.1016\/j.jep.2022.115570","article-title":"Protects against DSS-induced colitis in mice: involvement of TLR4\/NF-\u03baB\/NLRP3 inflammasome pathway and gut microbiota","volume":"298","author":"Bian","year":"2022","journal-title":"J Ethnopharmacol"},{"key":"ref14","first-page":"95","article-title":"Schisandra chinensis and its phytotherapeutical applications","volume":"68","author":"Rybnik\u00e1\u0159","year":"2019","journal-title":"Ceska Slov Farm"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1016\/j.fct.2009.04.009","article-title":"Anti-inflammatory effect of anemarsaponin B isolated from the rhizomes of Anemarrhena asphodeloides in LPS-induced RAW 264.7 macrophages is mediated by negative regulation of the nuclear factor-kappaB and p38 pathways","volume":"47","author":"Kim","year":"2009","journal-title":"Food Chem Toxicol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"954","DOI":"10.3109\/14756366.2012.697057","article-title":"(\u2212)-Nyasol, isolated from Anemarrhena asphodeloides suppresses neuroinflammatory response through the inhibition of I-\u03baB\u03b1 degradation in LPS-stimulated BV-2 microglial cells","volume":"28","author":"Lee","year":"2013","journal-title":"J Enzyme Inhib Med Chem"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2880","DOI":"10.1016\/j.apsb.2021.03.011","article-title":"Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation","volume":"11","author":"Lv","year":"2021","journal-title":"Acta Pharm Sin B"},{"key":"ref18","first-page":"9296","article-title":"Effect of Glycyrrhiza uralensis against ulcerative colitis through regulating the signaling pathway of FXR\/P-gp","volume":"13","author":"Lu","year":"2021","journal-title":"Am J Transl Res"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.3382\/ps\/pey084","article-title":"Attenuating effect of melatonin on lipopolysaccharide-induced chicken small intestine inflammation","volume":"97","author":"Li","year":"2018","journal-title":"Poult Sci"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jare.2022.07.005","article-title":"Whole genome analyses reveal novel genes associated with chicken adaptation to tropical and frigid environments","volume":"47","author":"Shi","year":"2022","journal-title":"J Adv Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"3288","DOI":"10.1039\/C7FO00253J","article-title":"Antioxidant and anti-inflammatory effects of cauliflower leaf powder-enriched diet against LPS induced toxicity in rabbits","volume":"8","author":"Larocca","year":"2017","journal-title":"Food Funct"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"878018","DOI":"10.3389\/fvets.2022.878018","article-title":"Ginsenoside Rg3 ameliorates stress of broiler chicks induced by Escherichia coli lipopolysaccharide","volume":"9","author":"Bi","year":"2022","journal-title":"Front Vet Sci"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1053\/gast.2002.30348","article-title":"Matrix metalloproteinase-9 promotes neutrophil migration and alveolar capillary leakage in pancreatitis-associated lung injury in the rat","volume":"122","author":"Keck","year":"2002","journal-title":"Gastroenterology"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.4049\/jimmunol.169.2.1028","article-title":"Inhibition of allergic inflammation in the airways using aerosolized antisense to Syk kinase","volume":"169","author":"Stenton","year":"2002","journal-title":"J Immunol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1017\/S146625230800145X","article-title":"Interactions between commensal bacteria and the gut-associated immune system of the chicken","volume":"9","author":"Brisbin","year":"2008","journal-title":"Anim Health Res Rev"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"575","DOI":"10.3390\/antiox8120575","article-title":"Dietary Stevioside supplementation alleviates lipopolysaccharide-induced intestinal mucosal damage through anti-inflammatory and antioxidant effects in broiler chickens","volume":"8","author":"Jiang","year":"2019","journal-title":"Antioxidants"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"581","DOI":"10.3382\/ps.2013-03455","article-title":"Effect of a probiotic mixture on intestinal microflora, morphology, and barrier integrity of broilers subjected to heat stress","volume":"93","author":"Song","year":"2014","journal-title":"Poult Sci"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"100935","DOI":"10.1016\/j.psj.2020.12.032","article-title":"Dietary supplementation with Bacillus subtilis promotes growth performance of broilers by altering the dominant microbial community","volume":"100","author":"Zhang","year":"2021","journal-title":"Poul Sci"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s40104-022-00749-5","article-title":"Supplementing the early diet of broilers with soy protein concentrate can improve intestinal development and enhance short-chain fatty acidproducing microbes and short-chain fatty acids, especially butyric acid","volume":"13","author":"Zhang","year":"2022","journal-title":"J Anim Sci Biotechno"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.3382\/ps\/pey195","article-title":"The effect of inulin and wheat bran on intestinal health and microbiota in the early life of broiler chickens","volume":"97","author":"Li","year":"2018","journal-title":"Poult Sci"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3382\/ps.2012-02645","article-title":"Effects of feeding fermented Ginkgo biloba leaves on small intestinal morphology, absorption, and immunomodulation of early lipopolysaccharide-challenged chicks","volume":"92","author":"Zhang","year":"2013","journal-title":"Poult Sci"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1182\/blood-2006-06-032961","article-title":"Contribution of toll-like receptors to the innate immune response to gram-negative and gram-positive bacteria","volume":"109","author":"Elson","year":"2007","journal-title":"Blood"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.semcdb.2014.09.003","article-title":"RhoGTPases, actomyosin signaling and regulation of the epithelial apical junctional complex","volume":"36","author":"Quiros","year":"2014","journal-title":"Semin Cell Dev Biol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3830","DOI":"10.1080\/10408398.2016.1152230","article-title":"Regulation of the intestinal tight junction by natural polyphenols: a mechanistic perspective","volume":"57","author":"Yang","year":"2017","journal-title":"Crit Rev Food Sci Nutr"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.ijbiomac.2014.05.004","article-title":"Sulfated Astragalus polysaccharide regulates the inflammatory reaction in LPS-infected broiler chicks","volume":"69","author":"Wang","year":"2014","journal-title":"Int J Biol Macromol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1146\/annurev.physiol.68.040104.131404","article-title":"Claudins and epithelial paracellular transport","volume":"68","author":"Van Itallie","year":"2006","journal-title":"Annu Rev Physiol"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2023.1234769\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T06:10:23Z","timestamp":1701670223000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2023.1234769\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,4]]},"references-count":36,"alternative-id":["10.3389\/fvets.2023.1234769"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2023.1234769","relation":{},"ISSN":["2297-1769"],"issn-type":[{"type":"electronic","value":"2297-1769"}],"subject":[],"published":{"date-parts":[[2023,12,4]]},"article-number":"1234769"}}