{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:17:12Z","timestamp":1791584232115,"version":"4.3.4"},"reference-count":49,"publisher":"American Chemical Society (ACS)","issue":"4","license":[{"start":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T00:00:00Z","timestamp":1611187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Liver diseases such as hepatic carcinoma are one of the main health problems worldwide. Herbal drugs are largely used to treat liver injury in the indigenous system of medicine and may provide lead compounds for hepatoprotective drug discovery. The present study is investigated to test the Corydalis govaniana Wall. extract, fraction, and isolate therapeutically active constituents to explore their hepatoprotective, anti-inflammatory, and antioxidant activities. For this purpose, the antioxidant activity of govaniadine, caseadine, caseamine, and protopine was performed by assessing the scavenging events of the stable 2,2-diphenyl-1-picrylhydrazyl. Hepatoprotection of govaniadine was assessed in terms of reduction in serum enzymes (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) caused by CCl4-induced liver injury in rats and by histopathological techniques. All the compounds showed significant antioxidant activity with a percentage inhibition of 92.2, 86.7, 85.3, and 79.7, respectively, compared to propyl gallate 90.3%. Treatment with govaniadine reduced the serum enzyme level down to normal levels in the CCl4-treated group while inhibiting the increase of malondialdehyde, and the induction of superoxide dismutase and the glutathione level was upregulated. Histopathology showed \u223c47% damage to the liver cells in the CCl4-treated group; reduction in this damaged area was found to be better upon using govaniadine. Immunohistochemistry results showed that govaniadine as compared to silymarin has exceedingly decreased the inflammation by halting the CCl4-induced activation of hepatic macrophages. In carrageenan-induced paw edema assay, govaniadine significantly alleviated the edema after 1\u20135 h at a dose of 20 mg\/kg (26.00 and 28.5%), 50 mg\/kg (22.05 and 27.0%), and 100 mg\/kg (20.02 and 25.30%), respectively. The results of our experiments suggest that govaniadine showed antioxidant and hepatoprotective activity in liver injury. The hepatoprotective function of govaniadine may be associated to the scavenging of the free radical and attenuation of oxidative stress as well as inflammatory responses in the liver. Hence, govaniadine may be a lead compound for the hepatoprotective drug discovery process and further research is needed to find out their molecular mechanism of protection.<\/jats:p>","DOI":"10.1021\/acsomega.0c02261","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T15:47:10Z","timestamp":1611244030000},"page":"2462-2472","source":"Crossref","is-referenced-by-count":11,"title":["Govaniadine Ameliorates Oxidative Stress, Inflammation,\nand Kupffer Cell Activation in Carbon Tetrachloride-Induced Hepatotoxicity\nin Rats"],"prefix":"10.1021","volume":"6","author":[{"given":"Azra","family":"Jahan","sequence":"first","affiliation":[{"name":"Abdul Wali Khan University , , , ,","place":["Mardan, Khyber Pakhtunkhwa, Pakistan, 23200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumaira","family":"Shams","sequence":"additional","affiliation":[{"name":"Abdul Wali Khan University , , , ,","place":["Mardan, Khyber Pakhtunkhwa, Pakistan, 23200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safdar","family":"Ali","sequence":"additional","affiliation":[{"name":"University of Swabi , , , ,","place":["Anbar, Khyber Pakhtunkhwa, Pakistan, 23561"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samrana","family":"Samrana","sequence":"additional","affiliation":[{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amjad","family":"Ali","sequence":"additional","affiliation":[{"name":"Quaid-i-Azam University , , ,","place":["Islamabad, Pakistan, 15320"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achyut","family":"Adhikari","sequence":"additional","affiliation":[{"name":"University of Karachi , , ,","place":["Karachi, Pakistan, 75270"]},{"name":"Tribhuvan University , , , ,","place":["Kirtipur, Kathmandu, Nepal, 44618"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Sajid","sequence":"additional","affiliation":[{"name":"Hazara University , , , ,","place":["Mansehra, Khyber Pakhtunkhwa, Pakistan, 21300"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abid","family":"Ali","sequence":"additional","affiliation":[{"name":"Zhejiang University , , , ,","place":["Hangzhou, Zhejiang, China, 310058"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3851-3990","authenticated-orcid":true,"given":"Hamid","family":"Ali","sequence":"additional","affiliation":[{"name":"COMSATS University , , ,","place":["Islamabad, Pakistan, 44000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,1,21]]},"reference":[{"key":"2026090212465602700_cit1","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/bf02869152","article-title":"Biochemical\ndiagnosis of liver disease","volume":"14","author":"Wolf","year":"1999","journal-title":"Indian J. 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Toxicol."},{"key":"2026090212465602700_cit5","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.3748\/wjg.v16.i22.2771","article-title":"Protective effect of recombinant\nhuman IL-1Ra on CCl4-induced acute\nliver injury in mice","volume":"16","author":"Zhu","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"2026090212465602700_cit6","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1002\/hep.20969","article-title":"Liver regeneration","volume":"43","author":"Fausto","year":"2006","journal-title":"Hepatology"},{"key":"2026090212465602700_cit7","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/s0300-483x(03)00157-4","article-title":"Carbon tetrachloride-induced\nlipid peroxidation: eicosanoid formation and their regulation by antioxidant\nnutrients","volume":"189","author":"Basu","year":"2003","journal-title":"Toxicology"},{"key":"2026090212465602700_cit8","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1046\/j.1440-1746.2003.03064.x","article-title":"Clinical usefulness\nof edaravone for acute liver injury","volume":"18","author":"Tada","year":"2003","journal-title":"J. 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Technol."},{"key":"2026090212465602700_cit41","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/s0076-6879(85)13073-9","article-title":"Determination\nof glutathione and glutathione disulfide in biological samples","volume":"113","author":"Anderson","year":"1985","journal-title":"Methods Enzymol."},{"key":"2026090212465602700_cit42","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.jep.2005.08.073","article-title":"Hepatoprotective\neffects of rubiadin, a major constituent of Rubia cordifolia Linn","volume":"103","author":"Rao","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"2026090212465602700_cit43","first-page":"2197","article-title":"The protective effect of a novel\ncompound RU-18492\non galactosamine-induced hepaptotoxicity in rats","volume":"26","author":"James","year":"1976","journal-title":"Drug Res."},{"key":"2026090212465602700_cit44","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jep.2004.01.019","article-title":"Evaluation\nof hepatoprotective effects of Helminthostachys zeylanica (L.) Hook against carbon tetrachloride induced liver damage in wistar\nrats","volume":"92","author":"Suja","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"2026090212465602700_cit45","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/s0378-8741(03)00074-6","article-title":"Hepatoprotective activity of leaves\nof Kalanchoe pinnata Pers","volume":"86","author":"Yadav","year":"2003","journal-title":"J. Ethnopharmacol."},{"key":"2026090212465602700_cit46","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/j.fitote.2011.04.009","article-title":"Hepatoprotective\neffects of polyprenols from Ginkgo biloba L. leaves\non CCl4-induced hepatotoxicity in rats","volume":"82","author":"Yang","year":"2011","journal-title":"Fitoterapia"},{"key":"2026090212465602700_cit47","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.jep.2003.09.037","article-title":"Evaluation\nof hepatoprotective effect\nof Amalkadi ghrita against carbon tetrachloride-induced\nhepatic damage in rats","volume":"90","author":"Achliya","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"2026090212465602700_cit48","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3109\/01480547809034433","article-title":"Serum enzymes are\nindicators of chemically induced\nliver damage","volume":"1","author":"Drotman","year":"1978","journal-title":"Drug Chem. Toxicol."},{"key":"2026090212465602700_cit49","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1016\/j.fct.2007.06.007","article-title":"A toxicologist\nguide to the diagnostic interpretation of hepatic biochemical parameters","volume":"45","author":"Ramaiah","year":"2007","journal-title":"Food Chem. 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