{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:40:57Z","timestamp":1786527657907,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Technology Innovation Center for Pratacultural Special Fund for Innovation Platform Construction","award":["CCPTZX2023B06"],"award-info":[{"award-number":["CCPTZX2023B06"]}]},{"name":"Basic Research Fund for Universities in Inner Mongolia Autonomous Region","award":["BR261027"],"award-info":[{"award-number":["BR261027"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>This study investigated the effects of noni fruit flavonoids (NFF) on antioxidant status and anti-inflammatory responses in cashmere goats and explored the underlying mechanisms based on liver transcriptomics and metabolomics. Sixteen male Albas cashmere goats were randomly assigned to two groups: a control (CON) group and a group supplemented with 0.1% NFF. The adaptation and trial periods were 2 and 12 weeks, respectively. The results showed that NFF significantly enhanced antioxidant capacity, with mean increases of 32.9%, 20.7%, and 35.5% for total antioxidant capacity (T-AOC), glutathione peroxidase (GPx), and catalase (CAT) activities, respectively, across serum, liver, spleen, and thymus (p &lt; 0.05). NFF also modulated the inflammatory profile, with a mean increase of 18.0% for interleukin (IL)-10 and mean reductions of 18.6%, 19.4%, and 16.7% for IL-1\u03b2, IL-2, and tumor necrosis factor (TNF)-\u03b1, respectively, across the serum, liver, and thymus (p &lt; 0.05). Integrative transcriptomic and metabolomic analyses suggested that the AMPK signaling pathway, glutathione metabolism, and TGF-\u03b2 signaling pathway may be critically involved in mediating these effects. GPX3, GPX8, GCLM, NFKB1, and IL1B were identified as key candidate genes, while adenosine-5\u2032-monophosphate (AMP), cysteinylglycine, and pyroglutamic acid were key differential metabolites. Dietary supplementation with 0.1% NFF enhanced the antioxidant levels and anti-inflammatory response in cashmere goats.<\/jats:p>","DOI":"10.3390\/antiox15080987","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:38:09Z","timestamp":1786361889000},"page":"987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Liver Multi-Omics Reveals Beneficial Effects and Potential Mechanisms of Noni Fruit Flavonoids on Antioxidant Status and Anti-Inflammatory Responses in Cashmere Goats"],"prefix":"10.3390","volume":"15","author":[{"given":"Shuhui","family":"Dong","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Nutrition and Feed Science of Inner Mongolia Autonomous Region, College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4992-1711","authenticated-orcid":false,"given":"Qingyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Nutrition and Feed Science of Inner Mongolia Autonomous Region, College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Nutrition and Feed Science of Inner Mongolia Autonomous Region, College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Nutrition and Feed Science of Inner Mongolia Autonomous Region, College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0854-6349","authenticated-orcid":false,"given":"Yu","family":"Xin","sequence":"additional","affiliation":[{"name":"National Technology Innovation Center for Prataculture, Hohhot 010010, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Nutrition and Feed Science of Inner Mongolia Autonomous Region, College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Nutrition and Feed Science of Inner Mongolia Autonomous Region, College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Nutrition and Feed Science of Inner Mongolia Autonomous Region, College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumei","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Nutrition and Feed Science of Inner Mongolia Autonomous Region, College of Animal Science, Inner Mongolia Agricultural University, Hohhot 010018, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, X.Y., Shen, W., Wu, P., Wang, C.L., Li, J.H., Wang, D., and Yue, W.F. (2024). How food consumption trends change the direction of sheep breeding in China. Animals, 14.","DOI":"10.3390\/ani14213047"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1071\/RJ20033","article-title":"Chinese degraded grasslands\u2014Pathways for sustainability","volume":"42","author":"Kemp","year":"2020","journal-title":"Rangel. J."},{"key":"ref_3","first-page":"483","article-title":"Influence of goat management systems on hematological, oxidative stress profiles, and parasitic gastrointestinal infection","volume":"16","author":"Sunthamala","year":"2023","journal-title":"Vet. World"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zheng, Q.H., Tan, W.J., Feng, X.L., Feng, K.X., Zhong, W.T., Liao, C.Y., Liu, Y.T., Li, S.J., and Hu, W.Z. (2022). Protective effect of flavonoids from mulberry leaf on AAPH-induced oxidative damage in sheep erythrocytes. Molecules, 27.","DOI":"10.3390\/molecules27217625"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.1080\/1828051X.2022.2124200","article-title":"Influences of naringin supplementation on ruminal fermentation, inflammatory response, antioxidant capacity and bacterial community in high-concentrate diet of fattening goats","volume":"21","author":"Sun","year":"2022","journal-title":"Ital. J. Anim. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1111\/1541-4337.12456","article-title":"Properties and applications of Morinda citrifolia (noni): A review","volume":"18","author":"Almeida","year":"2019","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hou, S.L., Ma, D.Y., Wu, S.F., Hui, Q.Y., and Hao, Z.H. (2025). Morinda citrifolia L.: A comprehensive review on phytochemistry, pharmacological effects, and antioxidant potential. Antioxidants, 14.","DOI":"10.3390\/antiox14030295"},{"key":"ref_8","first-page":"144","article-title":"Comparative study on antioxidant ability of extracts from noni (Morinda citrifolia L.) fruit with different solvents","volume":"37","author":"Zhang","year":"2022","journal-title":"J. Chin. Cereals Oils Assoc."},{"key":"ref_9","first-page":"6459","article-title":"Effects of noni fruit flavonoids on in vitro ruminal fermentation of cashmere goats with high-concentrate substrate","volume":"36","author":"Zhang","year":"2024","journal-title":"Chin. J. Anim. Nutr."},{"key":"ref_10","unstructured":"Zhang, Q.Y. (2023). Alleviating Effect and Mechanism of Noni Fruit Flavonoid on the Decline Ofantioxidant and Immune Function in Cashmere Goatsinduced by High Concentrate Diet. [Ph.D. Thesis, Inner Mongolia Agricultural University]. (In Chinese)."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhang, Q.Y., Dong, S.H., Yu, H., Li, Y.H., Guo, X.Y., Zhao, Y.L., Guo, Y.M., and Yan, S.M. (2023). Effects of Noni (Morinda citrifolia L.) fruit extract supplemented in cashmere goats with a high-concentrate diet on growth performance, ruminal and colonic fermentation and sara. Animals, 13.","DOI":"10.3390\/ani13203275"},{"key":"ref_12","unstructured":"(2021). Nutrient Requirements of Meat-Type Sheep and Goat (Standard No. NY\/ T 816-2021)."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1093\/jas\/skz079","article-title":"Linseed oil and heated linseed grain supplements have different effects on rumen bacterial community structures and fatty acid profiles in cashmere kids1","volume":"97","author":"Wang","year":"2019","journal-title":"J. Anim. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative pcr and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1007\/s00204-023-03562-9","article-title":"Reactive oxygen species, toxicity, oxidative stress, and antioxidants: Chronic Diseases and Aging","volume":"97","author":"Jomova","year":"2023","journal-title":"Arch. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40164-024-00529-z","article-title":"Versatile function of NF-\u0138B in inflammation and cancer","volume":"13","author":"Ma","year":"2024","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ding, H.Y., Li, Y., Zhao, C., Yang, Y., Xiong, C.K., Zhang, D.L., Feng, S.B., Wu, J.J., and Wang, X.C. (2022). Rutin supplementation reduces oxidative stress, inflammation and apoptosis of mammary gland in sheep during the transition period. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.907299"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1002\/vms3.993","article-title":"Effect of Moringa leaf flavonoids on the production performance, immune system, and rumen fermentation of dairy cows","volume":"9","author":"Liu","year":"2023","journal-title":"Vet. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zeng, Y.X., Song, J.J., Zhang, M.M., Wang, H.W., Zhang, Y., and Suo, H.Y. (2020). Comparison of in vitro and in vivo antioxidant activities of six flavonoids with similar structures. Antioxidants, 9.","DOI":"10.3390\/antiox9080732"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ymgme.2021.12.016","article-title":"Disorders of purine biosynthesis metabolism","volume":"136","author":"Dewulf","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41580-022-00547-x","article-title":"New insights into activation and function of the AMPK","volume":"24","author":"Steinberg","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1002\/med.22014","article-title":"Preclinical evidence using synthetic compounds and natural products indicates that AMPK represents a potential pharmacological target for the therapy of pulmonary diseases","volume":"44","author":"Yang","year":"2024","journal-title":"Med. Res. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Keerthana, C.K., Rayginia, T.P., Shifana, S.C., Anto, N.P., Kalimuthu, K., Isakov, N., and Anto, R.J. (2023). The role of AMPK in cancer metabolism and its impact on the immunomodulation of the tumor microenvironment. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1114582"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1017\/anr.2024.27","article-title":"Resveratrol activates PGC-1\u03b1 pathway via PRAKK1 to regulate mitochondrial biogenesis and alleviate inflammatory responses in bovine mammary epithelial cells","volume":"2","author":"Hu","year":"2025","journal-title":"Anim. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cbi.2017.07.016","article-title":"Polyphenols activate energy sensing network in insulin resistant models","volume":"275","author":"Krishnamoorthy","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/bbb\/zbab203","article-title":"Genistein Regulates Adipogenesis by blocking the function of adenine nucleotide translocase-2 in the mitochondria","volume":"86","author":"Ikeda","year":"2022","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mazibuko-Mbeje, S.E., Dludla, P.V., Roux, C., Johnson, R., Ghoor, S., Joubert, E., Louw, J., Opoku, A.R., and Muller, C.J.F. (2019). Aspalathin-enriched green rooibos extract reduces hepatic insulin resistance by modulating PI3K\/AKT and AMPK Pathways. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030633"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"T65","DOI":"10.1111\/j.1750-3841.2010.02033.x","article-title":"Rutin inhibits oleic acid induced lipid accumulation via reducing lipogenesis and oxidative stress in hepatocarcinoma cells","volume":"76","author":"Wu","year":"2011","journal-title":"J. Food Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1194\/jlr.M038786","article-title":"Quercetin reduces obesity-associated ATM infiltration and inflammation in mice: A mechanism including AMPK\u03b11\/SIRT1","volume":"55","author":"Dong","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1177\/1534735417696702","article-title":"Quercetin has antimetastatic effects on gastric cancer cells via the interruption of uPA\/uPAR function by modulating NF-\u03bab, PKC-\u03b4, ERK1\/2, and AMPK\u03b1","volume":"17","author":"Li","year":"2018","journal-title":"Integr. Cancer Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rivera Rivera, A., Castillo-Pichardo, L., Gerena, Y., and Dharmawardhane, S. (2016). Anti-breast cancer potential of quercetin via the Akt\/AMPK\/mammalian target of rapamycin (mTOR) signaling cascade. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157251"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lee, C., Yoon, S., and Moon, J.-O. (2023). Kaempferol suppresses carbon tetrachloride-induced liver damage in rats via the MAPKs\/NF-\u03baB and AMPK\/Nrf2 signaling pathways. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24086900"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6310","DOI":"10.1038\/s41598-017-05812-0","article-title":"An integrated strategy by using target tissue metabolomics biomarkers as pharmacodynamic surrogate indices to screen antipyretic components of Qingkaikling injection","volume":"7","author":"Zhang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/iub.1756","article-title":"The glutathione cycle: Glutathione metabolism beyond the \u03b3-glutamyl cycle","volume":"70","author":"Bachhawat","year":"2018","journal-title":"IUBMB Life"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"545","DOI":"10.17305\/bb.2024.10184","article-title":"Nuclear factor erythroid 2-related factor 2 promotes radioresistance by regulating glutamate-cysteine ligase modifier subunit and its unique immunoinvasive pattern","volume":"24","author":"Xue","year":"2024","journal-title":"Biomol. Biomed."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bao, H., Chen, Y., Meng, Z., and Chu, Z. (2024). The causal relationship between CSF metabolites and GBM: A two-sample mendelian randomization analysis. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12901-7"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"114365","DOI":"10.1016\/j.bcp.2020.114365","article-title":"Insights into the role of GPX3, a highly efficient plasma antioxidant, in cancer","volume":"184","author":"Nirgude","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1089\/ars.2016.6866","article-title":"Regulation of calcium fluxes by GPX8, a type-II transmembrane peroxidase enriched at the mitochondria-associated endoplasmic reticulum membrane","volume":"27","author":"Yoboue","year":"2017","journal-title":"Antioxid. Redox Signal."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Concetti, J., and Wilson, C.L. (2018). NFKB1 and cancer: Friend or foe?. Cells, 7.","DOI":"10.3390\/cells7090133"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1002\/bab.2233","article-title":"Caspase-3: Structure, function, and biotechnological aspects","volume":"69","author":"Asadi","year":"2022","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Petit, P.X. (2025). Multiple entanglements of different cell death pathways, in which caspase-8 and BID interact with cardiolipin*, have been identified. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1667611"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev-pathmechdis-051022-014433","article-title":"Control of cell death in health and disease","volume":"19","author":"Kayagaki","year":"2024","journal-title":"Annu. Rev. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1111\/liv.12570","article-title":"The pan-caspase inhibitor emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis","volume":"35","author":"Barreyro","year":"2015","journal-title":"Liver Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1684\/ecn.2021.0465","article-title":"NLRP12 reduces proliferation and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by regulating the NF-\u03baB and MAPK pathways","volume":"32","author":"Zhang","year":"2021","journal-title":"Eur. Cytokine Netw."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"151301","DOI":"10.1016\/j.bbrc.2025.151301","article-title":"Recent advances in the dual effects of activin a on tumors","volume":"747","author":"Liu","year":"2025","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.34067\/KID.0000000776","article-title":"Activin A antagonism with follistatin reduces kidney fibrosis, injury, and cellular senescence-associated inflammation in murine diabetic kidney disease","volume":"6","author":"Bian","year":"2025","journal-title":"Kidney360"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/8\/987\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T09:22:30Z","timestamp":1786526550000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/8\/987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,9]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["antiox15080987"],"URL":"https:\/\/doi.org\/10.3390\/antiox15080987","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,9]]}}}