Fraxin Prevents Chemically Induced Hepatotoxicity by Reducing Oxidative Stress

Abstract

Fraxin isolated from Acer tegmentosum is reported to exert potent anti-oxidative stress action. However, pharmacological activities of fraxin remain to be elucidated. This study investigated the potential hepatoprotective effects of fraxin and the underlying signaling mechanism involved. Treatment with fraxin significantly lowered the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a CCl4-induced hepatotoxicity rat model. In the fraxin-treated group, glutathione (GSH) significantly increased, while the malondialdehyde (MDA) in the liver significantly decreased. Fraxin also showed radical-scavenging activity. Furthermore, it significantly reduced the t-BHP-induced cytotoxicity and production of reactive oxygen species (ROS) in Hep G2. Fraxin protected Hep G2 cells through Nrf2 pathway-dependent HO-1 expression. The results of this study indicate that fraxin shows potent hepatoprotective effects in vitro and in vivo, presumably through direct antioxidant activity and the Nrf2-mediated antioxidant enzyme system.

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

“…In an animal model of I/R-induced kidney injury, fraxin exhibited an ameliorative effect mediated through suppressing oxidative DNA damage and NF-κB [203]. Furthermore, Chang et al have pointed to the role of Nrf2 in mediating the hepatoprotective efficacy of fraxin [198]. In their study, fraxin markedly inhibited the t-BHPinduced cytotoxicity and ROS generation in HepG2 through Nrf2 pathway-dependent HO-1 expression.…”

“…)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-2-one) is the main bioactive component of the Chinese traditional herb Cortex Fraxini [196]. This natural coumarin displayed inspiring biological activities, including antiinflammatory [197], antioxidant [197,198], and antihyperuricemic activities [199].…”

“…In their study, fraxin markedly inhibited the t-BHPinduced cytotoxicity and ROS generation in HepG2 through Nrf2 pathway-dependent HO-1 expression. In vivo studies showed that fraxin has potent hepatoprotective effects against CCl 4 -induced hepatotoxicity in rats via direct antioxidant activity and the Nrf2/ARE pathway [198]. [204][205][206].…”

“…[193] Fraxin CCl 4 -induced hepatotoxicity Rats Fraxin ameliorated liver function and lipid peroxidation and increased GSH and Nrf2-mediated antioxidant enzyme system. [198] 10 Oxidative Medicine and Cellular Longevity Nrf2. In contrast, transient knockdown of Nrf2 markedly inhibited hydrangenol-induced HO-1 expression, indicating that hydrangenol-induced Nrf2 is an upstream regulator of HO-1 [252].…”

Oxaloacetate Ameliorates Chemical Liver Injury via Oxidative Stress Reduction and Enhancement of Bioenergetic Fluxes

“…The liver is an important metabolic organ, and its injury can be caused by viral infiltration, drugs, or toxic chemicals via infection or ingestion [ 1 , 2 , 3 ]. Chemical injury is partly due to free radical lipid peroxidation [ 4 ], which can induce oxidative stress and produce a large number of reactive oxygen species (ROS) [ 5 , 6 ]. ROS can induce structural and functional abnormalities in mitochondria [ 7 ].…”