{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:05:59Z","timestamp":1792083959532,"version":"4.4.0"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070671"],"award-info":[{"award-number":["32070671"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p><jats:italic>Trikatu Churna<\/jats:italic> (<jats:italic>TC<\/jats:italic>) comprising <jats:italic>Zingiber officinale<\/jats:italic> rhizome, <jats:italic>Piper longum<\/jats:italic>, and <jats:italic>Piper nigrum<\/jats:italic> fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of <jats:italic>TC<\/jats:italic> in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of <jats:italic>TC<\/jats:italic> as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of <jats:italic>TC<\/jats:italic> was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, <jats:italic>in-vivo<\/jats:italic> studies were performed to validate the potential of <jats:italic>TC<\/jats:italic> (200 mg\/kg and 400 mg\/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of <jats:italic>TC<\/jats:italic> demonstrate significant (<jats:italic>p<\/jats:italic> &amp;gt; 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of <jats:italic>TC<\/jats:italic> showed the presence of piperine. Network pharmacology identifies the role of <jats:italic>TC<\/jats:italic> in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase\/protein kinase B (PI3K\/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of <jats:italic>TC<\/jats:italic> were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of <jats:italic>TC<\/jats:italic> in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms.<\/jats:p>","DOI":"10.3389\/fnut.2022.1063118","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T06:59:27Z","timestamp":1668581967000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation"],"prefix":"10.3389","volume":"9","author":[{"given":"Ruchi","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mangala","family":"Jadhav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Choudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdur","family":"Rauf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Gundamaraju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah F.","family":"AlAsmari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nemat","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev K.","family":"Singla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bairong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"B1","first-page":"2","article-title":"Hepatoprotective activity of Shrikhand Asava\u2014a preclinical study","volume":"15","author":"Sharma","year":"2021","journal-title":"Int J Ayu Pharm Chem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"479","DOI":"10.3904\/kjim.2015.253","article-title":"Diagnostic value of alcoholic liver disease (ALD)\/non-alcoholic fatty liver disease (NAFLD) index combined with gamma-glutamyltransferase in differentiating ALD and NAFLD","volume":"31","author":"Wang","year":"2016","journal-title":"Korean J Intern Med."},{"key":"B3","first-page":"1336","volume-title":"Medical-Surgical Nursing: Clinical Management for Positive OuTComes","author":"Black","year":"2005"},{"key":"B4","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1053\/j.gastro.2011.11.027","article-title":"Granulocyte colony-stimulating factor mobilizes CD34+ cells and improves survival of patients with acute-on-chronic liver failure","volume":"142","author":"Garg","year":"2012","journal-title":"Gastroenterology."},{"key":"B5","first-page":"944","article-title":"Cytochrome P450 CYP 2E1 induction during chronic alcohol exposure occurs by a two-step mechanism associated with blood alcohol concentrations in rats","volume":"264","author":"Ronis","year":"1993","journal-title":"J Pharmacol Exp Therap."},{"key":"B6","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.lfs.2007.05.005","article-title":"Alcohol-induced oxidative stress","volume":"81","author":"Das","year":"2007","journal-title":"Life Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"109128","DOI":"10.1016\/j.biopha.2019.109128","article-title":"Traditional Chinese medicine combined with hepatic targeted drug delivery systems: a new strategy for the treatment of liver diseases","volume":"117","author":"Ma","year":"2019","journal-title":"Biomed Pharmacother."},{"key":"B8","doi-asserted-by":"publisher","first-page":"866343","DOI":"10.3389\/fmed.2022.866343","article-title":"Combination of Vitamin C and curcumin safeguards against methotrexate-induced acute liver injury in mice by synergistic antioxidant effects","volume":"9","author":"Khudhair","year":"2022","journal-title":"Front Med."},{"key":"B9","first-page":"322","volume-title":"Part II. 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