The hepatoprotective candidates by synergistic formula of marine and terrestrial against Acetaminophen toxicity using in-vitro, in-vivo, and in silico screening approach

Background: One of the most regularly used hepatotoxic medicines is paracetamol (acetaminophen, N- acetyl-p-aminophenol; APAP). It causes liver failure in overdoses but is safe at therapeutic dosages. Combination therapy combining many natural compounds with a synergistic impact as hepatoprotective agents has become an essential therapeutic method against various disorders. Objective: Due to the lack of literature on paracetamol's effects on hematological and hepatic status parameters in male albino mice, the main goal of this study was to compare the hepatoprotective activ-ities of a mixture of three marine-derived polyphenolics and polysaccharides (Sargassum vulgare Bacillus oceanisediminis, and alginic acids) to Chrysanthemum extract and the mixture of them. Methods: Sargassumvulgare, Bacillus Oceanisediminis, and alginate, as well as Chrysanthemum ethanol extracts, were tested for APAP-induced liver damage. Group 1 received saline solution subcutaneously, while Group 2 received 500 mg/kg body weight/day APAP intraperitoneal. Group 3 got 200 mg/day algal extract i.p. As in group 3, group 4 got an i.p. dose of 200 mg of algal extract before the APAP dose. This group was protected by Sargassum vulgare extract. Group 5: Received 200 mg/100 g/body of Bacillus oceanisediminis extracts i.p. for one week. Group 6: Received 200 mg/body of Bacillus oceanisediminis extract i.p. for one week before APAP treatment. Alginate (p200 mg/body weight/day) was given to Group 7. As in group 7, group 8 received 200 mg/body weight/day alginate extract i.p. before APAP. Group 9: Chrysanthemum extracts 200 mg/day for a week. Group 10: got an i.p. dose of Chrysanthemum extracts for one week before the APAP dose. Group 11: Four mixed extracts (Bacillus Oceanisediminis, Sargassum vulgare, Chrysanthemum, and alginate) were i.p200 mg/day for one week as a positive (+ve) control group. Group 12: Received i.p200 mg/kg combination extract for one week before APAP. Results: Due to their synergistic antioxidant and anti-inflammatory actions, marine extracts and combi-nations of marine-derived extracts demonstrated a great effect against APAP toxicity, demonstrating hep-atoprotective potential against APAP-induced liver damage. Conclusion: The synergy of the three marine-derived combinations may lead to novel liver toxicity pre-vention agents.(c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).