{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T18:30:15Z","timestamp":1775586615698,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006701","name":"Umm Al-Qura University","doi-asserted-by":"crossref","award":["25UQU4281227GSSR03"],"award-info":[{"award-number":["25UQU4281227GSSR03"]}],"id":[{"id":"10.13039\/501100006701","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Acute pancreatitis is a significant global disease. This study investigated the phytochemical composition and potential protective effects of Equisetum arvense L. (horsetail) ethanol extract and Olea europaea L. (olive leaves) aqueous extract against metronidazole (MTZ)-induced pancreatic damage in rats. Materials and Methods: Rats were randomly divided into six groups: Group I (control) received saline; Group II (Metronidazole) received only MTZ (400 mg\/kg). Group III (Equisetum arvense group) received E. arvense 100 mg\/kg. Group IV (Olea europaea) received 400 mg\/kg of O. europaea. Group V (MTZ + E. arvense) received both MTZ (400 mg\/kg) and E. arvense (100 mg\/kg). Group VI (MTZ + O. europaea) received MTZ (400 mg\/kg) and O. europaea (400 mg\/kg). All treatments were delivered daily via the oral route. After 60 days, serum amylase, lipase, protease, and glucose levels, oxidative parameters \u201cmalondialdehyde (MDA), catalase (CAT), mRNA relative expression of pancreatic Pik3ca (phosphatidylinosi-tol-4,5-bisphosphate 3-kinase, catalytic subunit alpha), AKT (AKT Serine\/Threonine Kinase 1), Nrf-2 (Nuclear factor, erythroid 2-like 2), TNF\u03b1 (tumor necrosis factor alpha), and IL-1\u03b2 (interleukin-1 beta genes, an apoptotic marker \u201ccaspase-3,\u201d and histopathological changes were estimated. Results: HPLC analysis revealed that horsetail extract contained caffeic acid, catechin, rutin, and kaempferol, while olive leaf extract was dominated by oleuropein. MTZ administration significantly elevated serum levels of pancreatic enzymes (lipase, amylase, and protease) and glucose and increased oxidative stress markers, such as MDA, while reducing catalase (CAT) activity. Co-treatment with MTZ and horsetail, or MTZ and olive extracts, mitigated these effects, especially horsetail, which restored CAT levels and reduced MDA concentrations. qPCR analysis showed MTZ upregulated inflammatory genes (TNF\u03b1, IL-1\u03b2) and downregulated antioxidant and survival-related genes (Pik3ca, AKT, Nrf-2). Horsetail co-treatment significantly reversed these gene expression patterns. Histopathological and immunohistochemical analyses confirmed MTZ-induced pancreatic tissue degeneration and increased cleaved caspase-3 expression, both of which were notably alleviated by horsetail extract. Conclusions: These findings highlight the superior protective efficacy of Equisetum arvense over Olea europaea in ameliorating MTZ-induced pancreatic toxicity, potentially through anti-inflammatory, antioxidant, and anti-apoptotic mechanisms.<\/jats:p>","DOI":"10.3390\/life15121907","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T10:11:23Z","timestamp":1765793483000},"page":"1907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular, Physiological, and Histopathological Insights into the Protective Role of Equisetum arvense and Olea europaea Extracts Against Metronidazole-Induced Pancreatic Toxicity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1674-4020","authenticated-orcid":false,"given":"Manal R.","family":"Bakeer","sequence":"first","affiliation":[{"name":"Physiology Department, Faculty of Veterinary Medicine, Cairo University, P.O. Box 12211, Giza 12613, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7033-7440","authenticated-orcid":false,"given":"Maha M.","family":"Rashad","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asmaa A.","family":"Azouz","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rehab A.","family":"Azouz","sequence":"additional","affiliation":[{"name":"Toxicology and Forensic Medicine Department, Faculty of Veterinary Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0804-2339","authenticated-orcid":false,"given":"Abdulmajeed Fahad","family":"Alrefaei","sequence":"additional","affiliation":[{"name":"Department of Biology, Jamoum University College, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8077-3668","authenticated-orcid":false,"given":"Sultan F.","family":"Kadasah","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science, University of Bisha, Bisha 67714, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0741-3954","authenticated-orcid":false,"given":"Mohamed","family":"Shaalan","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaa M.","family":"Ali","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza 12613, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2181-7090","authenticated-orcid":false,"given":"Marwa Y.","family":"Issa","sequence":"additional","affiliation":[{"name":"Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Giza 12613, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salma I.","family":"El-Samanoudy","sequence":"additional","affiliation":[{"name":"Physiology Department, Faculty of Veterinary Medicine, Cairo University, P.O. Box 12211, Giza 12613, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Del Gaudio, A., Covello, C., Di Vincenzo, F., De Lucia, S.S., Mezza, T., Nicoletti, A., Siciliano, V., Candelli, M., Gasbarrini, A., and Nista, E.C. (2023). Drug-Induced Acute Pancreatitis in Adults: Focus on Antimicrobial and Antiviral Drugs, a Narrative Review. Antibiotics, 12.","DOI":"10.3390\/antibiotics12101495"},{"key":"ref_2","first-page":"4840539","article-title":"Metronidazole-Induced Pancreatitis: Is There Under-recognition? A Case Report and Systematic Review of the Literature","volume":"2019","author":"Youssef","year":"2019","journal-title":"Case Rep. Gastrointest. 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