title: Aconitum carmichaelii protects against acetaminophen-induced hepatotoxicity via B-cell lymphoma-2 protein-mediated inhibition of mitochondrial dysfunction.
abstract: We previously reported the clinical profile of processed Aconitum carmichaelii (AC, Aconibal(®)), which included inhibition of cytochrome P450 (CYP) 2E1 activity in healthy male adults. CYP2E1 is recognized as the enzyme that initiates the cascade of events leading to acetaminophen (APAP)-induced toxicity. However, no studies have characterized its role in APAP-induced hepatic injury. Here, we investigated the protective effects of AC on APAP-induced hepatotoxicity via mitochondrial dysfunction. AC (5-500 μg/mL) significantly inhibited APAP-induced reduction of glutathione. In addition, AC decreased mitochondrial membrane potential (Δψm) and B-cell lymphoma 2 (Bcl-2)-associated X protein levels (% change 46.63) in mitochondria. Moreover, it increased Bcl-2 (% change 55.39) and cytochrome C levels (% change 38.33) in mitochondria, measured using immunofluorescence or a commercial kit. Furthermore, cell membrane integrity was preserved and nuclear fragmentation inhibited by AC. These results demonstrate that AC protects hepatocytes against APAP-induced toxicity by inhibiting mitochondrial dysfunction.
authors.affiliation: The K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon 305-811, South Korea.
authors.forename: Gunhyuk
authors.initials: G
authors.lastname: Park
authors.affiliation: The KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 305-811, South Korea.
authors.forename: Ki Mo
authors.initials: KM
authors.lastname: Kim
authors.affiliation: The K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon 305-811, South Korea.
authors.forename: Songie
authors.initials: S
authors.lastname: Choi
authors.affiliation: The K-herb Research Center, Korea Institute of Oriental Medicine, Daejeon 305-811, South Korea. Electronic address: dalsoh@gmail.com.
authors.forename: Dal-Seok
authors.initials: DS
authors.lastname: Oh
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D031841:Aconitum; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D005978:Glutathione; D016393:Lymphoma, B-Cell; D008928:Mitochondria; D010936:Plant Extracts / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010936:Plant Extracts; D020011:Protective Agents; D000082:Acetaminophen; D019392:Cytochrome P-450 CYP2E1; D005978:Glutathione
keywords: Acetaminophen; Aconitum carmichaelii; B-cell lymphoma 2; Hepatotoxicity; Mitochondrial dysfunction