| Title | Carveol a Naturally-Derived Potent and Emerging Nrf2 Activator Protects Against Acetaminophen-Induced Hepatotoxicity |
| Authors | Rahman, Zaif Ur Al Kury, Lina Tariq Alattar, Abdullah Tan, Zhen Alshaman, Reem Malik, Imran Badshah, Haroon Uddin, Zia Khalil, Atif Ali Khan Muhammad, Naveed Khan, Saifullah Ali, Amjad Shah, Fawad Ali Li, Jing Bo Li, Shupeng |
| Affiliation | Shenzhen Univ, Clin Res Ctr Neurol Dis, Hlth Management Ctr, Gen Hosp,Clin Med Acad, Shenzhen, Peoples R China Abdul Wali Khan Univ, Dept Pharm, Khyber Pakhtunkhwa, Pakistan Zayed Univ, Coll Nat & Hlth Sci, Abu Dhabi, U Arab Emirates Univ Tabuk, Fac Pharm, Dept Pharmacol & Toxicol, Tabuk, Saudi Arabia Riphah Int Univ, Riphah Inst Pharmaceut Sci, Islamabad, Pakistan COMSATS Univ Islamabad, Dept Pharm, Abbottabad Campus, Abbottabad, Pakistan Natl Univ Med Sci, Dept Biol Sci, Rawalpindi, Pakistan Abasyn Univ Peshawar, Dept Microbiol & Biotechnol, Khyber Pakhtunkhwa, Pakistan Univ Malakand, Dept Bot, Khyber Pakhtunkhwa, Pakistan Peking Univ, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, State Key Lab Oncogen, Shenzhen, Peoples R China |
| Issue Date | 28-Jan-2021 |
| Publisher | FRONTIERS IN PHARMACOLOGY |
| Abstract | Acetaminophen (N-acetyl p-aminophenol or APAP) is used worldwide for its antipyretic and anti-inflammatory potential. However, APAP overdose sometimes causes severe liver damage. In this study, we elucidated the protective effects of carveol in liver injury, using molecular and in silico approaches. Male BALB/c mice were divided into two experimental cohorts, to identify the best dose and to further assess the role of carveol in the nuclear factor E2-related factor; nuclear factor erythroid 2; p45-related factor 2 (Nrf2) pathway. The results demonstrated that carveol significantly modulated the detrimental effects of APAP by boosting endogenous antioxidant mechanisms, such as nuclear translocation of Nrf2 gene, a master regulator of the downstream antioxidant machinery. Furthermore, an inhibitor of Nrf2, called all-trans retinoic acid (ATRA), was used, which exaggerated APAP toxicity, in addition to abrogating the protective effects of carveol; this effect was accompanied by overexpression of inflammatory mediators and liver = 2ltoxicity biomarkers. To further support our notion, we performed virtual docking of carveol with Nrf2-keap1 target, and the resultant drug-protein interactions validated the in vivo findings. Together, our findings suggest that carveol could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating the APAP-induced inflammation and oxidative stress. |
| URI | http://hdl.handle.net/20.500.11897/604943 |
| ISSN | 1663-9812 |
| DOI | 10.3389/fphar.2020.621538 |
| Indexed | SCI(E) |
| Appears in Collections: | 化学生物学与生物技术学院 å å¦ä¸ å å å·¥ç¨ å¦é ¢ |
