Effects of troxerutin on inflammatory cytokines and BDNF levels in male offspring of high-fat diet fed rats.

OBJECTIVE: In the present study, we aimed to examine the effect of troxerutin treatment on levels of brain-derived neurotrophic factor (BDNF), and tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), as pro-inflammatory cytokines, in the blood and hippocampus of high-fat diet (HFD) fed dams and their male offspring. MATERIALS AND METHODS: Forty virgin female Wistar rats, 3 weeks old, were divided into two groups (n=20/per group) and fed control diet (CD), or HFD for 8 weeks. After mating, pregnant animals were assigned to four subgroups including: control (CD), control+troxerutin (CD+T), high-fat diet (HFD), and HFD+troxerutin (HFD+T) groups. HFD was continued during pregnancy and lactation. Troxerutin (150 mg/kg/day, P.O.) was administered during pregnancy in the CD+T and HFD+T groups. On postnatal day (PND) 21, male offspring were separated and fed a normal diet until PND 90. Inflammatory cytokines (TNF-α, and IL-6) and BDNF levels were measured in the serum and hippocampal samples using rat-specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Our findings showed a significant increase in the serum levels of TNF-α and IL-6, but a decrease in BDNF levels in the serum of HFD-fed dams in comparison with CD group, which was reversed by troxerutin. Moreover, troxerutin treatment, during pregnancy, significantly decreased TNF-α and IL-6 levels, but increased BDNF level in the serum and hippocampus of HFD+T offspring in comparison with HFD offspring. CONCLUSION: These results showed that troxerutin could prevent the harmful effects of maternal HFD on their offspring through inhibition of pro-inflammatory cytokines and elevation of BDNF levels.

Effect of troxerutin on apelin-13, apelin receptors (APJ), and ovarian histological changes in the offspring of high-fat diet fed rats.

OBJECTIVES: Maternal high-fat diet (HFD) consumption has been linked to metabolic disorders and reproductive dysfunctions in offspring. Troxerutin (TRO) has anti-hyperlipidemic, anti-oxidant, and anti-inflammatory effects. This study examined the effects of TRO on apelin-13, its receptors mRNA and ovarian histological changes in the offspring of HFD fed rats. MATERIALS AND METHODS: Female Wistar rats were randomly divided into control diet (CD) or HFD groups and received these diets for eight weeks. After mating, dams were assigned into four subgroups: CD, CD + TRO, HFD, and HFD + TRO, and received their respective diets until the end of lactation. Troxerutin (150 mg/kg/day) was gavaged in the CD + TRO and HFD + TRO groups during pregnancy. On the postnatal day (PND) 21 all female offspring were separated and fed CD until PND 90. On PND 90 animals were sacrificed and ovarian tissue samples were collected for further evaluation. RESULTS: Results showed that HFD significantly decreased serum apelin-13 in the female offspring of the HFD dams, which was significantly reversed by TRO. Moreover, real-time polymerase chain reaction (PCR) analysis revealed that TRO treatment significantly decreased the ovarian mRNA expression of the apelin-13 receptor in the troxerutin-received offspring. Furthermore, histological examination revealed that TRO increased the number of atretic follicles in the ovaries of HFD+TRO offspring. CONCLUSION: Maternal high fat feeding compromises ovarian health including follicular growth and development in the adult offspring and troxerutin treatment improved negative effects of maternal HFD on the apelin-13 level and ovarian development of offspring.

The effect of troxerutin on anxiety- and depressive-like behaviours in the offspring of high-fat diet fed dams.

This study aimed at investigating the metabolic and behavioural effects of troxerutin treatment in the offspring of high fat diet (HFD) fed dams. Female Wistar rats (n = 40) received normal diet (ND) or HFD for 8 weeks prior to breeding. After mating, pregnant animals were assigned to four subgroups: ND, ND + Tro (troxerutin 150 mg/kg/day), HFD, and HFD + Tro. On the 21st day, male offspring were weaned and fed ND until 12 weeks old. Behavioural tests were performed on postnatal day (PND) 80 and 90. Compared to the controls, the HFD offspring showed more anxiety- and depressive-like behaviours, higher blood glucose, cholesterol, and cortisol levels. On the other hand, chronic troxerutin administration during gestation restored metabolic and behavioural changes to normal. In summary, troxerutin improved anxiety- and depressive-like behaviours, as well as metabolic status in the offspring of the HFD fed dams. More studies are needed to determine the underlying mechanisms.

Protective effects of troxerutin on maternal high-fat diet-induced impairments of spatial memory and apelin in the male offspring.

OBJECTIVES: Maternal high-fat diet (HFD) is linked with metabolic and cognitive deficits in offspring. Neuroprotective effects of troxerutin, a natural bioflavonoid, have been reported recently. This study aimed to investigate the effects of troxerutin on spatial memory and serum and hippocampal apelin levels in the male offspring of HFD fed mothers. MATERIALS AND METHODS: Three-week-old female Wistar rats (n= 40) received HFD or control diet (CD) for 8 weeks. After mating, pregnant animals were divided into two subgroups according to the troxerutin (TRO) supplementation: CD, CD+TRO, HFD, and HFD+TRO. HFD continued to the end of lactation in HFD and HFD+TRO groups. TRO was gavaged (150 mg/kg/day) during pregnancy. After weaning, the male offspring were fed a normal diet until 12 weeks of age. Spatial memory was evaluated in the Morris water maze (MWM) on postnatal day (PND) 90. Total apelin concentration was measured in the serum of maternal rats before mating and after lactation and also in the serum and hippocampus of their male offspring. RESULTS: Both traveled distance (P<0.05) and time spent (P<0.05) in the target quadrant were significantly decreased in the offspring of HFD-fed dams, which were reversed by TRO treatment. Moreover, TRO significantly (P<0.05) decreased serum apelin levels in dams. Furthermore, TRO treatment in dams significantly (P<0.05) increased serum and hippocampal levels of apelin in their offspring. CONCLUSION: These results indicated that TRO treatment during pregnancy improved maternal HFD-induced spatial memory impairments of the offspring possibly through modulation of serum and hippocampal apelin levels.