Screening of Multitarget Compounds against Acetaminophen Hepatic Toxicity Using In Silico, In Vitro, and In Vivo...

Area of Science:

• Pharmacology and Toxicology
• Natural Product Chemistry
• Hepatology

Background:

• Multitarget drugs and combination therapies are emerging strategies for complex diseases.
• Acetaminophen-induced liver injury is a significant clinical concern requiring novel therapeutic approaches.

Purpose of the Study:

• To screen multitargeting compounds for hepatoprotective effects against acetaminophen-induced liver injury.
• To evaluate the individual and combined effects of selected compounds on liver injury and cancer cell lines.

Main Methods:

• In silico screening of 40 compounds from Curcuma longa and Cinnamomum zeylanicum using molecular docking, ADMET profiling, and Pfizer's rule of five.
• In vitro assessment of hepatoprotective effects by examining biochemical parameters (ALT, AST, ALP, bilirubin) and histological findings.
• Evaluation of anticancer activity against HepG2 and Huh7 cancer cell lines and cytotoxicity on Vero normal cell line.

Main Results:

• Quercetin and curcumin were identified as potent hepatoprotective multitargeting compounds with high binding affinity for CYP2E1, MAPK, and TLR4.
• Both compounds demonstrated significant hepatoprotective effects, reducing liver injury markers and improving histological outcomes.
• Quercetin and curcumin exhibited selective cytotoxicity against HepG2 and Huh7 cancer cells with no adverse effects on normal Vero cells.

Conclusions:

• Quercetin and curcumin are promising multitargeting agents for preventing acetaminophen-induced liver injury.
• These natural compounds possess significant drug-like properties and demonstrate dual therapeutic potential for liver protection and cancer treatment.