{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:51:15Z","timestamp":1789084275401,"version":"build-2803163510"},"reference-count":42,"publisher":"American Association for the Advancement of Science (AAAS)","content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Research"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>\n            Non-alcoholic fatty liver disease, especially nonalcoholic steatohepatitis (NASH), is a leading cause of cirrhosis and liver cancer worldwide; nevertheless, there are no Food and Drug Administration-approved drugs for treating NASH until now. Peroxisome proliferator-activated receptor alpha (PPAR\u03b1) is an interesting therapeutic target for treating metabolic disorders in the clinic, including NASH. Herpetrione, a natural lignan compound isolated from Tibetan medicine\n            <jats:italic>Herpetospermum caudigerum<\/jats:italic>\n            , exerts various hepatoprotective effects, but its efficacy and molecular mechanism in treating NASH have not yet been elucidated. Here, we discovered that herpetrione lessened lipid accumulation and inflammation in hepatocytes stimulated with oleic acid and lipopolysaccharide, and effectively alleviated NASH caused by a high-fat diet or methionine-choline-deficient diet by regulating glucolipid metabolism, insulin resistance, and inflammation. Mechanistically, RNA-sequencing analyses further showed that herpetrione activated PPAR signaling, which was validated by protein expression. Furthermore, the analysis of molecular interactions illustrated that herpetrione bound directly to the PPAR\u03b1 protein, with binding sites extending to the Arm III domain. PPAR\u03b1 deficiency also abrogated the protective effects of herpetrione against NASH, suggesting that herpetrione protects against hepatic steatosis and inflammation by activation of PPAR\u03b1 signaling, thereby alleviating NASH. Our findings shed light on the efficacy of a natural product for treating NASH, as well as the broader prospects for NASH treatment by targeting PPAR\u03b1.\n          <\/jats:p>","DOI":"10.34133\/research.0276","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T16:27:16Z","timestamp":1699892836000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":22,"title":["Herpetrione, a New Type of PPAR\u03b1 Ligand as a Therapeutic Strategy Against Nonalcoholic Steatohepatitis"],"prefix":"10.34133","volume":"6","author":[{"given":"Lang","family":"Linghu","sequence":"first","affiliation":[{"name":"Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, \rSouthwest University, Chongqing 400715, China."},{"name":"School of Pharmacy, \rZunyi Medical University, Zunyi 563000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, \rSouthwest University, Chongqing 400715, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Liao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, \rSouthwest University, Chongqing 400715, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, \rSouthwest University, Chongqing 400715, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fancheng","family":"Meng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, \rSouthwest University, Chongqing 400715, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, \rSouthwest University, Chongqing 400715, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City and Southwest University, TAAHC SWU Medicinal Plant Joint R&amp;D Centre, \rSouthwest University, Chongqing 400715, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhong","family":"Lan","sequence":"additional","affiliation":[{"name":"TAAHC-SWU Medicinal Plant R&amp;D Center, \rTibet Agricultural and Animal Husbandry University, Nyingchi, Tibet 860000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0140-4192","authenticated-orcid":true,"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, \rSouthwest University, Chongqing 400715, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"issue":"4","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi ZM","year":"2023","unstructured":"Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review. Hepatology. 2023;77(4):1335\u20131347.","journal-title":"Hepatology"},{"issue":"1","key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/hep.29466","article-title":"Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease","volume":"67","author":"Estes C","year":"2018","unstructured":"Estes C, Razavi H, Loomba R, Younossi ZM, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. 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