Oxidative stress is the major contributor to acetaminophen (AAP)-caused liver damage. It promotes mitochondrial oxidative stress and collapses the mitochondrial membrane potential to cause cell death. We have previously shown that a polyphenol extract of Hibiscus sabdariffa L. (HPE) potentiated the antioxidative effect. We further examined in this study the possible mechanism of HPE against AAP-caused liver damage. BABL/c mice were orally fed with HPE (100, 200 or 300 mg/kg) for two weeks prior to an i.p. injection of 1000 mg/kg of AAP. The mice were decapitated 6 h after the AAP injection to collect the blood and liver for further determination. The results show that pretreating with HPE increased the level of glutathione (GSH), decreased the level of lipid peroxidation, and increased catalase activity in the liver. A histopathological evaluation shows that HPE could decrease AAP-induced liver sterosis accompanied by a decreased expression of AIF, Bax, Bid, and p-JNK in the liver. An in vitro assay revealed that HPE could reduce AAP-induced death of BABL/c normal liver cells (BNLs), reverse the lost mitochondrial potency and improve the antioxidative status, similarly to the results of the in vivo assay. We show in this study that HPE possessed the ability to protect the liver from AAP-caused injury. The protective mechanism might be regulated by decreasing oxidative stress and attenuating the mitochondrial dysfunction.
Taiwania cryptomerioides is a monotypic gymnosperm species, valued for the high decay resistance of its wood. This durability has been attributed to the abundance of terpenoids, especially the major diterpenoid metabolite ferruginol, with antifungal and antitermite activity. Specialized diterpenoid metabolism in gymnosperms primarily recruits bifunctional class-I/II diterpene synthases (diTPSs), whereas monofunctional class-II and class-I enzymes operate in angiosperms. In this study, we identified a previously unrecognized group of monofunctional diTPSs in T. cryptomerioides, which suggests a distinct evolutionary divergence of the diTPS family in this species. Specifically, five monofunctional diTPS functions not previously observed in gymnosperms were characterized, including monofunctional class-II enzymes forming labda-13en-8-ol diphosphate (LPP, TcCPS2) and (+)-copalyl diphosphate (CPP, TcCPS4), and three class-I diTPSs producing biformene (TcKSL1), levopimaradiene (TcKSL3) and phyllocladanol (TcKSL5), respectively. Methyl jasmonate (MeJA) elicited the accumulation of levopimaradiene and the corresponding biosynthetic diTPS genes, TcCPS4 and TcKSL3, is consistent with a possible role in plant defense. Furthermore, TcCPS4 and TcKSL3 are likely to contribute to abietatriene biosynthesis via levopimaradiene as an intermediate in ferruginol biosynthesis in Taiwania. In conclusion, this study provides deeper insight into the functional landscape and molecular evolution of specialized diterpenoid metabolism in gymnosperms as a basis to better understand the role of these metabolites in tree chemical defense.
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