{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:17:39Z","timestamp":1785421059093,"version":"3.56.0"},"reference-count":25,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangxi University of Chinese Medicine","award":["2023BS024"],"award-info":[{"award-number":["2023BS024"]}]},{"award":["2023BS024"],"award-info":[{"award-number":["2023BS024"]}],"id":[{"id":"https:\/\/ror.org\/024v0gx67","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine Capacity Building Project","award":["Guike LT2600640036"],"award-info":[{"award-number":["Guike LT2600640036"]}]},{"name":"Guangxi Natural Science Foundation","award":["2025GXNSFBA069256"],"award-info":[{"award-number":["2025GXNSFBA069256"]}]},{"name":"Guangxi Drug Administration","award":["(2023)034"],"award-info":[{"award-number":["(2023)034"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Acute liver failure (ALF) is characterized by a rapid decline in liver function, leading to metabolic and organ failure. This study employed liver metabolomics, Nuclear Factor kappa-B (NF-\u03baB) signaling pathway analysis, and inflammatory factor profiling to investigate the therapeutic mechanisms of xanthoxylin in ALF. Xanthoxylin administration led to increased antioxidant levels and reduced markers of inflammation and tissue damage. Xanthoxylin downregulated the messenger RNA (mRNA) expression of Nitric Oxide Synthase (NOS), Interleukin-1\u03b2 (IL-1\u03b2), Interleukin-6 (IL-6), Tumor Necrosis Factor-\u03b1 (TNF-\u03b1), NF-\u03baB, Inhibitor of NF-\u03baB \u03b1 (I\u03baB\u03b1), and Toll-like receptor 4 (TLR4), and inhibited the protein expression of p-p38 and p-p65 while upregulating B-cell CLL\/Lymphoma 2 (Bcl-2) and B-cell Lymphoma-x (Bcl-xl). Metabolomic analysis identified 41 differentially expressed metabolites, 20 of which showed strong correlations with pharmacodynamic parameters. These 20 candidate metabolite signatures are involved in amino acid and carboxylic acid metabolic pathways, with potential links to glycolysis and the tricarboxylic acid (TCA) cycle. Together, these findings suggest that xanthoxylin exerts therapeutic effects against ALF by modulating the I\u03baB\u03b1\/NF-\u03baB signaling pathway and related metabolic pathways, providing a scientific basis for understanding its multi-target mechanism.<\/jats:p>","DOI":"10.3390\/molecules31132231","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T01:03:56Z","timestamp":1782349436000},"page":"2231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Correlational Analysis of Liver Metabolites and Pharmacodynamic Indexes in Xanthoxylin-Treated Acute Liver Failure"],"prefix":"10.3390","volume":"31","author":[{"given":"Fengfeng","family":"Xie","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine\/University Engineering Research Center of Development and Industrialization of Zhuang and Yao Ethnic Medicinal Materials, Guangxi\/Guangxi Engineering Research Center of Ethnic Medicine Resources and Application, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine\/University Engineering Research Center of Development and Industrialization of Zhuang and Yao Ethnic Medicinal Materials, Guangxi\/Guangxi Engineering Research Center of Ethnic Medicine Resources and Application, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Shen","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine\/University Engineering Research Center of Development and Industrialization of Zhuang and Yao Ethnic Medicinal Materials, Guangxi\/Guangxi Engineering Research Center of Ethnic Medicine Resources and Application, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuqi","family":"Yu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine\/University Engineering Research Center of Development and Industrialization of Zhuang and Yao Ethnic Medicinal Materials, Guangxi\/Guangxi Engineering Research Center of Ethnic Medicine Resources and Application, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dudong","family":"Wei","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine\/University Engineering Research Center of Development and Industrialization of Zhuang and Yao Ethnic Medicinal Materials, Guangxi\/Guangxi Engineering Research Center of Ethnic Medicine Resources and Application, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liba","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine\/University Engineering Research Center of Development and Industrialization of Zhuang and Yao Ethnic Medicinal Materials, Guangxi\/Guangxi Engineering Research Center of Ethnic Medicine Resources and Application, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine\/University Engineering Research Center of Development and Industrialization of Zhuang and Yao Ethnic Medicinal Materials, Guangxi\/Guangxi Engineering Research Center of Ethnic Medicine Resources and Application, Guangxi University of Chinese Medicine, Nanning 530200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1080\/17474124.2025.2551265","article-title":"What\u2019s new in the critical care management of acute liver failure: A focus on global accessibility","volume":"19","author":"Walabh","year":"2025","journal-title":"Expert Rev. Gastroent"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1007\/s11033-022-07251-1","article-title":"Sinapic acid ameliorates paracetamol-induced acute liver injury through targeting oxidative stress and inflammation","volume":"49","author":"Rostami","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.arcmed.2020.10.009","article-title":"Protective Effects of Fisetin on Hepatic Ischemia-reperfusion Injury Through Alleviation of Apoptosis and Oxidative Stress","volume":"52","author":"Li","year":"2021","journal-title":"Arch. Med. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhong, X.Y., Long, L.Z., Yao, H.J., Zhu, Z.Q., Xie, Z.P., Zhang, Y.F., and Chen, F.S. (2025). Ammonium tetrathiomolybdate attenuates acetaminophen-induced acute liver failure by inhibiting the TRPV4\/Calcium\/NF-\u03baB signaling pathway. Biochem. Pharmacol., 237.","DOI":"10.1016\/j.bcp.2025.116917"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zhang, X., Yuan, S.L., Fan, H., Zhang, W., and Zhang, H.G. (2024). Liensinine alleviates sepsis-induced acute liver injury by inhibiting the NF-KB and MAPK pathways in an Nrf2-dependent manner. Chem.-Biol. Interact., 396.","DOI":"10.1016\/j.cbi.2024.111030"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/15593258211025190","article-title":"Mangosteen Hinders Gamma Radiation-Mediated Oxidative Stress and Liver Injury by Down-Regulating TNF-\u03b1\/NF-\u03baB and Pro-Fibrotic Factor TGF-\u03b21 Inducing Inflammatory Signaling","volume":"19","author":"Hassan","year":"2021","journal-title":"Dose-Response"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/hep.25624","article-title":"Fibronectin is essential for survival but is dispensable for proliferation of hepatocytes in acute liver injury in mice","volume":"56","author":"Moriya","year":"2012","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.immuni.2019.11.004","article-title":"Type 1 Innate Lymphoid Cells Protect Mice from Acute Liver Injury via Interferon-\u03b3 Secretion for Upregulating Bcl-xL Expression in Hepatocytes","volume":"52","author":"Nabekura","year":"2020","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"276","DOI":"10.4103\/JPBS.JPBS_333_20","article-title":"Serum Metabolic Disturbances Associated with Acute-on-chronic Liver Failure in Patients with Underlying Alcoholic Liver Diseases: An Elaborative NMR-based Metabolomics Study","volume":"13","author":"Kumar","year":"2021","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jchromb.2019.01.017","article-title":"High-throughput metabolomics screen coupled with multivariate statistical analysis identifies therapeutic targets in alcoholic liver disease rats using liquid chromatography-mass spectrometry","volume":"1109","author":"Fang","year":"2019","journal-title":"J. Chromatogr. B"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41467-024-44939-3","article-title":"Programmable integrated photonics for topological Hamiltonians","volume":"15","author":"On","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s12017-025-08863-z","article-title":"Xanthoxylin Regulating the Inflammatory Microenvironment After Spinal Cord Injury Through Inhibition of the NF-\u03baB Signaling Pathway","volume":"27","author":"Fan","year":"2025","journal-title":"Neuromol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"de Carvalho, N.C., Neves, S.P., Dias, R.B., Valverde, L.D., Sales, C.B.S., Rocha, C.A.G., Soares, M.B.P., dos Santos, E.R., Oliveira, R.M.M., and Carlos, R.M. (2018). A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1\/2-mediated apoptosis in HepG2 cells through a p53-independent pathway. Cell Death Dis., 9.","DOI":"10.1038\/s41419-017-0104-6"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1080\/19768354.2025.2549756","article-title":"Xanthoxyline prevents aging and neuronal damage by activating autophagy and DAF-16 expression in","volume":"29","author":"Kim","year":"2025","journal-title":"Anim. Cells Syst."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Raish, M., Ahmad, A., Alkharfy, K.M., Ahamad, S.R., Mohsin, K., Al-Jenoobi, F.I., Al-Mohizea, A.M., and Ansari, M.A. (2016). Hepatoprotective activity of Lepidium sativum seeds against D-galactosamine\/lipopolysaccharide induced hepatotoxicity in animal model. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1483-4"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s00011-014-0720-x","article-title":"Oxidative stress promotes D-GalN\/LPS-induced acute hepatotoxicity by increasing glycogen synthase kinase 3\u03b2 activity","volume":"63","author":"Wei","year":"2014","journal-title":"Inflamm. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bebnowska, D., Hrynkiewicz, R., Rzeszotek, S., Freus, M., Poniewierska-Baran, A., and Niedzwiedzka-Rystwej, P. (2024). Apoptotic Cell Death in an Animal Model of Virus-Induced Acute Liver Failure-Observations During Lagovirus europaeus\/GI.2 Infection. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020798"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, H., Guo, H.R., Deng, H.D., Cui, H.M., Fang, J., Zuo, Z.C., Deng, J.L., Li, Y.L., Wang, X., and Zhao, L. (2020). Copper induces hepatic inflammatory responses by activation of MAPKs and NF-\u03baB signalling pathways in the mouse. Ecotoxicol. Environ. Safe, 201.","DOI":"10.1016\/j.ecoenv.2020.110806"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.3892\/etm.2016.3850","article-title":"Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-\u03baB and p38 MAPK","volume":"12","author":"Wang","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1002\/ansa.202000167","article-title":"Targeted NMR-based serum metabolic profiling of serine, glycine and methionine in acute-on-chronic liver failure patients: Possible insights into mitochondrial dysfunction","volume":"2","author":"Arya","year":"2021","journal-title":"Anal. Sci. Adv."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Liao, W.T., Jin, Q.W., Liu, J.N., Ruan, Y.L., Li, X.R., Shen, Y.Y., Zhang, Z.C., Wang, Y., Wu, S.M., and Zhang, J.Y. (2021). Mahuang Decoction Antagonizes Acute Liver Failure via Modulating Tricarboxylic Acid Cycle and Amino Acids Metabolism. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.599180"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Leitner, B.P., Lee, W.D., Zhu, W., Zhang, X., Gaspar, R.C., Li, Z., Rabinowitz, J.D., and Perry, R.J. (2023). Tissue-specific reprogramming of glutamine metabolism maintains tolerance to sepsis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0286525"},{"key":"ref_23","unstructured":"Zwingmann, C., Butterworth, R., and Leibfritz, D. (2006). The anaplerotic metabolic flux through pyruvate carboxylase is a prerequisite for ammonia detoxification in acute and chronic liver failure. Proc. Int. Soc. Magn. Reson. Med., 14."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ymgme.2022.03.004","article-title":"Comparative metabolomics in the Pahenu2 classical PKU mouse identifies cerebral energy pathway disruption and oxidative stress","volume":"136","author":"Dobrowolski","year":"2022","journal-title":"Mol. Genet. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.neuint.2005.04.002","article-title":"Cerebral metabolic disturbances in the brain during acute liver failure: From hyperammonemia to energy failure and proteolysis","volume":"47","author":"Ott","year":"2005","journal-title":"Neurochem. Int."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:19:57Z","timestamp":1783397997000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":25,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["molecules31132231"],"URL":"https:\/\/doi.org\/10.3390\/molecules31132231","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]}}}