Vitex agnus-castusL. (Verbenaceae) Improves the Liver Lipid Metabolism and Redox State of Ovariectomized Rats

Abstract

Vitex agnus-castus (VAC) is a plant that has recently been used to treat the symptoms of menopause, by its actions on the central nervous system. However, little is known about its actions on disturbances in lipid metabolism and nonalcoholic fat liver disease (NAFLD), frequently associated with menopause. Ovariectomized (OVX) rats exhibit increased adiposity and NAFLD 13 weeks after ovary removal and were used as animal models of estrogen deficiency. The rats were treated with crude extract (CE) and a butanolic fraction of VAC (ButF) and displayed the beneficial effects of a reduction in the adiposity index and a complete reversion of NAFLD. NAFLD reversion was accompanied by a general improvement in the liver redox status. The activities of some antioxidant enzymes were restored and the mitochondrial hydrogen peroxide production was significantly reduced in animals treated with CE and the ButF. It can be concluded that the CE and ButF from Vitex agnus-castus were effective in preventing NAFLD and oxidative stress, which are frequent causes of abnormal liver functions in the postmenopausal period.

17β-estradiol improves hepatic mitochondrial biogenesis and function through PGC1B

“…Consistently with in vivo findings, HepG2 cells treated with E2 increased mitochondrial mass and MMP, thus increasing ATP content and levels of essential proteins involved in oxidative metabolism and mitochondrial biogenesis. OVX rats also exhibited greater hepatic oxidative stress, indicated by reduced SOD activity and higher lipid peroxidation, in agreement with previous studies (Moreno et al 2015). Treatment with E2 increased antioxidant response, thus lowering protein oxidation damage in accordance with E2 involvement in defense against oxidative stress (Borrás et al 2003, Viña et al 2005.…”

“…Research using cell cultures treated with 17β-estradiol (E2) also supports these previous findings in rats, denoting a main role of this hormone in modulating mitochondrial biogenesis and function (Chen et al 1998, Mattingly et al 2008, Capllonch-Amer et al 2013, 2014, Guo et al 2013, Sbert-Roig et al 2016. In postmenoupausal women and in ovariectomized (OVX) rats, estrogen deficiency is associated with body weight gain and abdominal fat deposition (Tchernof et al 2000, Moreno et al 2015, hepatic triglyceride accumulation (Völzke et al 2007, Moreno et al 2015, and increased insulin resistance (Szmuilowicz et al 2009). In this same line, men usually show greater hepatic fat accumulation than premenopausal women, a profile that is inverted when the comparison is made with women after menopause (Park et al 2006).…”

Agnuside Reduces Visceral Adipocyte Size, Improves Insulin Sensitivity and Reverses Hepatic Steatosis in Ovariectomized Rats

“…The AGN-enriched extract also exerted additional hepatoprotective effects, including a reduction in the mitochondrial reactive oxygen species (ROS) generation and a general improvement in the redox status. The content of pure AGN in the AGN-enriched extract has been demonstrated to be 8.75% [12], meaning that other active compounds could also have had a role in the beneficial effects previously found in OVX rats. Therefore, on basis of the very promising properties of AGN in the treatment of metabolic disturbances associated with estrogen deficiency, this study was planned to investigate the effects of pure AGN on the metabolic disturbances of OVX rats.…”

“…Our results revealed that in OVX rats, the crude extract of VAC and its butanolic fraction (enriched in AGN) are effective in reversing several lipid metabolism disorders, including NAFLD and adiposity [12]. The AGN-enriched extract also exerted additional hepatoprotective effects, including a reduction in the mitochondrial reactive oxygen species (ROS) generation and a general improvement in the redox status.…”

“…Liver lipid metabolism is regulated by estrogens through genomic actions; thus, under conditions of estrogen deficiency, the incidence of NAFLD increases considerably [8]. The fat accumulation in the liver, in turn, leads to oxidative cell damage [9][10][11][12].…”