Suppressive effect of Siraitia grosvenorii extract on dicyclanil-promoted hepatocellular proliferative lesions in male mice

Abstract

-Dicyclanil (DC) generates reactive oxygen species (ROS) due to Cyp1a1 induction, and DNA damage caused by oxidative stress is probably involved in hepatocarcinogenesis in mice. To clarify the modifying effect of the Siraitia grosvenorii extract (SGE), which has antioxidative properties, we employed a 2-stage liver carcinogenesis model in partially hepatectomized male ICR mice. Mice maintained on diet containing DC at a concentration of 1,500 ppm for 9 weeks after a single intraperitoneal injection of diethylnitrosamine (DEN) at a dose of 30 mg/kg and they were given water containing 2,500 ppm of SGE for 11 weeks including 2 weeks as pre-administration on DC. SGE inhibited the induction Cyp1a1, all of which were caused by DC. To examine whether SGE indirectly inhibits Cyp1a1 expression induced by inhibition of aryl hydrocarbon receptor (Ahr)-mediated signal transduction caused by DC, mice with high containing tap water for 2 weeks. Cyp1a1 administered DC + SGE than in C57BL/6J mice administered DC alone; there was no difference in the Cyp1a1 expression between DBA/2J mice administered DC + SGE and DC alone. These results suggest that SGE suppresses the induction of Cyp1a1, leading to inhibition of ROS generation and consequently inhibited hepatocarcinogenesis, probably due to suppression of Ahr activity.

Targeting the inflammation in HCV-associated hepatocellular carcinoma: a role in the prevention and treatment

“…Moreover, the preventive effect of flavonoids, quercetin or Acacia nilotica bark extract (ANBE) via oxidant/antioxidant activity was demonstrated on hepatic cancer in rats [83-85]. Recently several other molecules with antioxidative properties were evaluated (for example, Siraitia grosvenorii extract, black tea polyphenols, xanthohumol from hops (Humulus lupulus L.)) [86-88].…”

Mechanistic Study on Hepatocarcinogenesis of Piperonyl Butoxide in Mice

“…To clarify whether ROS-mediated hepatocarcinogenesis in mice given dicyclanil is inhibited by the treatment of the Siraitia grosvenorii extract (SGE), which has antioxidative properties, we employed a two-stage liver carcinogenesis model in partially hepatectomized male mice. As a result, SGE suppressed the induction of Cyp1a1, leading to inhibition of ROS generation and consequently inhibited hepatocarcinogenesis, probably owing to suppression of Ahr activity (Matsumoto et al 2009). To clarify whether hepatocellular tumors are induced in mice given PBO owing to the generation of ROS, it is necessary to perform an additional study as a future work in which ROS-mediated hepatocarcinogenesis in mice given PBO is inhibited by the treatment of ROS quenchers or antioxidants.…”

Trends in use, pharmacology, and clinical applications of emerging herbal nutraceuticals

“…Many animal studies have shown a lack of toxicity of monk fruit extracts (e.g. Jin et al, ; Marone, Borzelleca, Merkel, Heimbach, & Kennepohl, ; Matsumoto et al, ), and in recent human studies, Tey, Salleh, and Henry (, ) found that a beverage containing monk fruit had no effect on total daily energy intake, blood glucose, and insulin responses in healthy human males. Other human studies (not peer reviewed, submitted as part of regulatory applications and not cited) have not given rise to safety concerns.…”