{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:16:12Z","timestamp":1791918972388,"version":"4.3.4"},"reference-count":63,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82004149"],"award-info":[{"award-number":["82004149"]}]},{"name":"National Natural Science Foundation of China","award":["82274213"],"award-info":[{"award-number":["82274213"]}]},{"name":"National Natural Science Foundation of China","award":["2022-KFKT-2"],"award-info":[{"award-number":["2022-KFKT-2"]}]},{"name":"National Natural Science Foundation of China","award":["02-37"],"award-info":[{"award-number":["02-37"]}]},{"name":"Open Project of Translational Chinese Medicine Key Laboratory of Sichuan Province","award":["82004149"],"award-info":[{"award-number":["82004149"]}]},{"name":"Open Project of Translational Chinese Medicine Key Laboratory of Sichuan Province","award":["82274213"],"award-info":[{"award-number":["82274213"]}]},{"name":"Open Project of Translational Chinese Medicine Key Laboratory of Sichuan Province","award":["2022-KFKT-2"],"award-info":[{"award-number":["2022-KFKT-2"]}]},{"name":"Open Project of Translational Chinese Medicine Key Laboratory of Sichuan Province","award":["02-37"],"award-info":[{"award-number":["02-37"]}]},{"name":"Shanghai Collaborative Innovation Center for Chronic Disease Prevention and Health Services","award":["82004149"],"award-info":[{"award-number":["82004149"]}]},{"name":"Shanghai Collaborative Innovation Center for Chronic Disease Prevention and Health Services","award":["82274213"],"award-info":[{"award-number":["82274213"]}]},{"name":"Shanghai Collaborative Innovation Center for Chronic Disease Prevention and Health Services","award":["2022-KFKT-2"],"award-info":[{"award-number":["2022-KFKT-2"]}]},{"name":"Shanghai Collaborative Innovation Center for Chronic Disease Prevention and Health Services","award":["02-37"],"award-info":[{"award-number":["02-37"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of Gynostemma pentaphyllum extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3\u2013V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as Akkerrmansia and decreased the abundance of opportunistic pathogens such as Klebsiella. Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-\u03b1 (TNF-\u03b1), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.<\/jats:p>","DOI":"10.3390\/nu16111782","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T03:44:35Z","timestamp":1717645475000},"page":"1782","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Gynostemma pentaphyllum Extract Alleviates NASH in Mice: Exploration of Inflammation and Gut Microbiota"],"prefix":"10.3390","volume":"16","author":[{"given":"Feng-Yan","family":"Jiang","sequence":"first","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Ran","family":"Yue","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Yun","family":"Tan","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Tang","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Song","family":"Xu","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Jian","family":"Mao","sequence":"additional","affiliation":[{"name":"China Mengniu Dairy Company Limited, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Sheng","family":"Xue","sequence":"additional","affiliation":[{"name":"China Mengniu Dairy Company Limited, Hohhot 010000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Ping","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2766-9420","authenticated-orcid":false,"given":"Rui-Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cld.2017.08.007","article-title":"Pathophysiology of Nonalcoholic Fatty Liver Disease\/Nonalcoholic Steatohepatitis","volume":"22","author":"Manne","year":"2018","journal-title":"Clin. Liver Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: Trends, predictions, risk factors and prevention","volume":"18","author":"Huang","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: Trends, predictions, risk factors and prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2309000","article-title":"A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis","volume":"390","author":"Harrison","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e31508","DOI":"10.1097\/MD.0000000000031508","article-title":"Pioglitazone on nonalcoholic steatohepatitis: A systematic review and meta-analysis of 15 RCTs","volume":"101","author":"Zhao","year":"2022","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Iwaki, M., Kobayashi, T., Nogami, A., Saito, S., Nakajima, A., and Yoneda, M. (2023). Impact of Sarcopenia on Non-Alcoholic Fatty Liver Disease. Nutrients, 15.","DOI":"10.3390\/nu15040891"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101238","DOI":"10.1016\/j.molmet.2021.101238","article-title":"Metabolic-associated fatty liver disease and lipoprotein metabolism","volume":"50","author":"Heeren","year":"2021","journal-title":"Mol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/hep.26093","article-title":"Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: A connection between endogenous alcohol and NASH","volume":"57","author":"Zhu","year":"2013","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1136\/gutjnl-2021-326789","article-title":"Gut microbiome and health: Mechanistic insights","volume":"71","author":"Tilg","year":"2022","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11070","DOI":"10.1073\/pnas.0504978102","article-title":"Obesity alters gut microbial ecology","volume":"102","author":"Ley","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.cmet.2023.08.002","article-title":"Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations","volume":"35","author":"Ni","year":"2023","journal-title":"Cell Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00281-013-0404-6","article-title":"Microbiota and nonalcoholic steatohepatitis","volume":"36","author":"Imajo","year":"2014","journal-title":"Semin. Immunopathol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Maslennikov, R., Poluektova, E., Zolnikova, O., Sedova, A., Kurbatova, A., Shulpekova, Y., Dzhakhaya, N., Kardasheva, S., Nadinskaia, M., and Bueverova, E. (2023). Gut Microbiota and Bacterial Translocation in the Pathogenesis of Liver Fibrosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216502"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1086078","DOI":"10.3389\/fimmu.2023.1086078","article-title":"Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy","volume":"14","author":"Zhu","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"116927","DOI":"10.1016\/j.jep.2023.116927","article-title":"Chinese herbal medicines: The modulator of nonalcoholic fatty liver disease targeting oxidative stress","volume":"318","author":"Gong","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1007\/s12072-021-10138-1","article-title":"Gut-liver axis modulation of Panax notoginseng saponins in nonalcoholic fatty liver disease","volume":"15","author":"Xu","year":"2021","journal-title":"Hepatol. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"154208","DOI":"10.1016\/j.phymed.2022.154208","article-title":"The improvement of nonalcoholic steatohepatitis by Poria cocos polysaccharides associated with gut microbiota and NF-kappaB\/CCL3\/CCR1 axis","volume":"103","author":"Tan","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/21691401.2023.2203734","article-title":"The seamless integration of dietary plant-derived natural flavonoids and gut microbiota may ameliorate non-alcoholic fatty liver disease: A network pharmacology analysis","volume":"51","author":"Oh","year":"2023","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"154937","DOI":"10.1016\/j.phymed.2023.154937","article-title":"Aqueous extract of Polygala japonica Houtt. ameliorated nonalcoholic steatohepatitis in mice through restoring the gut microbiota disorders and affecting the metabolites in feces and liver","volume":"118","author":"Liao","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wu, Y., Yin, W., Hao, P., Chen, Y., Yu, L., Yu, X., Wu, Y., Li, X., Wang, W., and Zhou, H. (2024). Polysaccharide from Panax japonicus C.A. Mey prevents non-alcoholic fatty liver disease development based on regulating liver metabolism and gut microbiota in mice. Int. J. Biol. Macromol., 260.","DOI":"10.1016\/j.ijbiomac.2024.129430"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1039\/D2FO03028D","article-title":"Tetrastigma hemsleyanum leaf extracts ameliorate NAFLD in mice with low-grade colitis via the gut-liver axis","volume":"14","author":"Xiao","year":"2023","journal-title":"Food Funct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12986-018-0323-6","article-title":"Amelioration of hepatic steatosis is associated with modulation of gut microbiota and suppression of hepatic miR-34a in Gynostemma pentaphylla (Thunb.) Makino treated mice","volume":"15","author":"Jia","year":"2018","journal-title":"Nutr. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Su, C., Li, N., Ren, R., Wang, Y., Su, X., Lu, F., Zong, R., Yang, L., and Ma, X. (2021). Progress in the Medicinal Value, Bioactive Compounds, and Pharmacological Activities of Gynostemma pentaphyllum. Molecules, 26.","DOI":"10.3390\/molecules26206249"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s10719-020-09949-5","article-title":"Effects of extraction methods on antioxidant and immunomodulatory activities of polysaccharides from superfine powder Gynostemma pentaphyllum Makino","volume":"37","author":"Wang","year":"2020","journal-title":"Glycoconj. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1002\/pmic.201500293","article-title":"Mechanistic study of the anti-cancer effect of Gynostemma pentaphyllum saponins in the Apc(Min\/+) mouse model","volume":"16","author":"Tai","year":"2016","journal-title":"Proteomics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8384631","DOI":"10.1155\/2018\/8384631","article-title":"Gynostemma pentaphyllum Attenuates the Progression of Nonalcoholic Fatty Liver Disease in Mice: A Biomedical Investigation Integrated with In Silico Assay","volume":"2018","author":"Hong","year":"2018","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, J., Shi, J., Jia, N., and Sun, Q. (2022). Network pharmacology analysis reveals neuroprotection of Gynostemma pentaphyllum (Thunb.) Makino in Alzheimer\u2019 disease. BMC Complement. Med. Ther., 22.","DOI":"10.1186\/s12906-022-03534-z"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e15225","DOI":"10.7717\/peerj.15225","article-title":"Gypenosides ameliorate high-fat diet-induced nonalcoholic fatty liver disease in mice by regulating lipid metabolism","volume":"11","author":"Zhou","year":"2023","journal-title":"PeerJ"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Oh, J.Y., Kim, S.H., Oh, I.J., Lee, Y.H., Lee, K.W., Lee, W.H., and Kim, J.H. (2020). Pharmaceutical Efficacy of Gypenoside LXXV on Non-Alcoholic Steatohepatitis (NASH). Biomolecules, 10.","DOI":"10.3390\/biom10101426"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15080","DOI":"10.1038\/nrdp.2015.80","article-title":"Nonalcoholic fatty liver disease","volume":"1","author":"Brunt","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/liv.13301","article-title":"Pathology of non-alcoholic fatty liver disease","volume":"37","author":"Bedossa","year":"2017","journal-title":"Liver Int."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4162\/nrp.2022.16.1.14","article-title":"Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1alpha pathway in C2C12 myotubes","volume":"16","author":"Kim","year":"2022","journal-title":"Nutr. Res. Pract."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1007\/s11739-023-03339-z","article-title":"Sarcopenia, a condition shared by various diseases: Can we alleviate or delay the progression?","volume":"18","author":"Tarantino","year":"2023","journal-title":"Intern. Emerg. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.intimp.2017.05.026","article-title":"Rutin exhibits hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease by reducing hepatic lipid levels and mitigating lipid-induced oxidative injuries","volume":"49","author":"Liu","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1002\/ptr.6486","article-title":"Quercetin improves nonalcoholic fatty liver by ameliorating inflammation, oxidative stress, and lipid metabolism in db\/db mice","volume":"33","author":"Yang","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"16210","DOI":"10.1038\/s41598-019-52736-y","article-title":"Isorhamnetin Alleviates Steatosis and Fibrosis in Mice with Nonalcoholic Steatohepatitis","volume":"9","author":"Ganbold","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_39","first-page":"8644","article-title":"Pentoxifylline and its association with kaempferol improve NASH-associated manifestation in mice through anti-apoptotic, anti-necroptotic, antioxidant, and anti-inflammatory mechanisms","volume":"26","author":"Hamouda","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/978-1-4757-5140-6_31","article-title":"The role of 13-hydroxylinoleic acid in the activation of macrophages by lipopolysaccharide","volume":"256","author":"Schade","year":"1990","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8257","DOI":"10.1021\/acs.jafc.1c02596","article-title":"Gamma-Linolenic Acid Prevents Lipid Metabolism Disorder in Palmitic Acid-Treated Alpha Mouse Liver-12 Cells by Balancing Autophagy and Apoptosis via the LKB1-AMPK-mTOR Pathway","volume":"69","author":"Liang","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jordao Candido, C., Silva Figueiredo, P., Del Ciampo Silva, R., Candeloro Portugal, L., Augusto Dos Santos Jaques, J., Alves de Almeida, J., de Barros Penteado, B., Albuquerque Dias, D., Marcelino, G., and Pott, A. (2019). Protective Effect of alpha-Linolenic Acid on Non-Alcoholic Hepatic Steatosis and Interleukin-6 and -10 in Wistar Rats. Nutrients, 12.","DOI":"10.3390\/nu12010009"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5267025","DOI":"10.1155\/2019\/5267025","article-title":"Diabetes Mellitus, Nonalcoholic Fatty Liver Disease, and Conjugated Linoleic Acid (Omega 6): What Is the Link?","volume":"2019","author":"Hegazy","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2238959","DOI":"10.1080\/19490976.2023.2238959","article-title":"Protection against Metabolic Associated Fatty Liver Disease by Protocatechuic Acid","volume":"15","author":"Tan","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.2174\/1381612827666210701145438","article-title":"Vanillic Acid and Non-Alcoholic Fatty Liver Disease: A Focus on AMPK in Adipose and Liver Tissues","volume":"27","author":"Shekari","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s13238-020-00784-w","article-title":"Role of gut microbiota in identification of novel TCM-derived active metabolites","volume":"12","author":"Lin","year":"2021","journal-title":"Protein Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115769","DOI":"10.1016\/j.jep.2022.115769","article-title":"Exploring the active compounds and potential mechanism of the anti-nonalcoholic fatty liver disease activity of the fraction from Schisandra chinensis fruit extract based on multi-technology integrated network pharmacology","volume":"301","author":"Li","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"115268","DOI":"10.1016\/j.jep.2022.115268","article-title":"Integrating metabolomics and network pharmacology to reveal the mechanisms of Delphinium brunonianum extract against nonalcoholic steatohepatitis","volume":"293","author":"Zhang","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"115333","DOI":"10.1016\/j.jep.2022.115333","article-title":"Penthorum chinense Pursh. extract attenuates non-alcholic fatty liver disease by regulating gut microbiota and bile acid metabolism in mice","volume":"294","author":"Li","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1038\/s41467-023-39028-w","article-title":"Bacteriophage targeting microbiota alleviates non-alcoholic fatty liver disease induced by high alcohol-producing Klebsiella pneumoniae","volume":"14","author":"Gan","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Li, D., Huang, X., Rao, H., Yu, H., Long, S., Li, Y., and Zhang, J. (2023). Klebsiella pneumoniae bacteremia mortality: A systematic review and meta-analysis. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1157010"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1080\/10408398.2018.1517725","article-title":"A next generation probiotic, Akkermansia muciniphila","volume":"59","author":"Zhai","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ju\u00e1rez-Fern\u00e1ndez, M., Porras, D., Petrov, P., Rom\u00e1n-Sag\u00fcillo, S., Garc\u00eda-Mediavilla, M.V., Soluyanova, P., Mart\u00ednez-Fl\u00f3rez, S., Gonz\u00e1lez-Gallego, J., Nistal, E., and Jover, R. (2021). The Synbiotic Combination of Akkermansia muciniphila and Quercetin Ameliorates Early Obesity and NAFLD through Gut Microbiota Reshaping and Bile Acid Metabolism Modulation. Antioxidants, 10.","DOI":"10.3390\/antiox10122001"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.jhep.2007.04.019","article-title":"Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis","volume":"47","author":"Rivera","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s00018-020-03656-y","article-title":"TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling","volume":"78","author":"Ciesielska","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"824919","DOI":"10.1155\/2013\/824919","article-title":"CD14 mediates binding of high doses of LPS but is dispensable for TNF-alpha production","volume":"2013","author":"Borzecka","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.4049\/jimmunol.175.6.3940","article-title":"Influence of CD14 on ligand interactions between lipopolysaccharide and its receptor complex","volume":"175","author":"Gangloff","year":"2005","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/ni1207","article-title":"CD14 is required for MyD88-independent LPS signaling","volume":"6","author":"Jiang","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.cell.2011.09.051","article-title":"CD14 controls the LPS-induced endocytosis of Toll-like receptor 4","volume":"147","author":"Zanoni","year":"2011","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"725390","DOI":"10.3389\/fmed.2021.725390","article-title":"Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases","volume":"8","author":"Bruneau","year":"2021","journal-title":"Front. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1080\/13880209.2022.2127153","article-title":"Swertia mussotii prevents high-fat diet-induced non-alcoholic fatty liver disease in rats by inhibiting expression the TLR4\/MyD88 and the phosphorylation of NF-kappaB","volume":"60","author":"Si","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1136\/gutjnl-2023-329996","article-title":"Novel tripeptide RKH derived from Akkermansia muciniphila protects against lethal sepsis","volume":"73","author":"Xie","year":"2023","journal-title":"Gut"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13020-020-00350-w","article-title":"Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4\/Myd88 signaling pathway in mice","volume":"15","author":"He","year":"2020","journal-title":"Chin. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/11\/1782\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:54:31Z","timestamp":1760108071000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/11\/1782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,6]]},"references-count":63,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["nu16111782"],"URL":"https:\/\/doi.org\/10.3390\/nu16111782","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,6]]}}}