Journal
PHYTOTHERAPY RESEARCH
Volume 32, Issue 11, Pages 2235-2246Publisher
WILEY
DOI: 10.1002/ptr.6160
Keywords
acetaminophen; acute liver injury; AMPK pathways; NF-kappa B; oxidative stress; Platycodon grandiflorum saponins
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Funding
- Scientific Research Foundation for the Returned Overseas Chinese Scholars
- Program for the Young Top-notch and Innovative Talents of Jilin Agricultural University [2016]
- Jilin Science & Technology Development Plan [20180201083YY]
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Acute liver injury (ALI) induced by acetaminophen (APAP) overdose is the most common cause of drug-induced liver injury. Saponins from Platycodon grandiflorum (PGSs) ameliorate alcohol-induced hepatotoxicity and enhance human lung carcinoma cell death via AMPK signaling pathway. However, whether PGS could protect from APAP-induced ALI through AMPK activation and its downstream signals is still poorly elucidated. This work investigated the protective effect and the underlying mechanisms of PGS against APAP-induced liver toxicity in mouse. PGS was administered at 15 or 30 mg/kg i.g./day for 1 week before a single injection of APAP (250 mg/kg, i.p.) 1 hr after last treatment of PGS. Serum alanine/aspartate aminotransferases, liver tumor necrosis factor-alpha and interleukin-1 beta levels, liver malondialdehyde formation, liver glutathione depletion, cytochrome P450 E1, and 4-hydroxynonenal levels were measured to demonstrate the protective efficacy of PGS against APAP-induced ALI. Liver histological observation provided further evidence on PGS's protective effects. PGS treatment altered the phosphorylation of AMPK and PI3K/Akt, as well as the downstream signals including Bcl-2 family, caspase, and NF-kappa B in a dose-dependent manner. In conclusion, we demonstrate that PGS exhibits a significant liver protection against APAP-induced ALI, mainly through NF-kappa B and AMPK/PI3K/Akt signaling pathways.
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