Effect of quercetin administration during the first two weeks post-weaning on the development of non-alcoholic fatty liver disease and dyslipidaemia in Sprague Dawley rats fed a high fructose diet.

Hepatic steatosis and dyslipidaemia are associated with excessive fructose consumption. We investigated the effect of quercetin intake during the early pre-weaning period on metabolic dysfunction caused by a high fructose diet. Sprague Dawley rats, 21-day-old, were weaned onto standard rat chow and randomly allocated to four groups which either water or 20% fructose solution to drink with or without quercetin (100 mg/kg body mass). Quercetin was administered for two weeks. Thereafter, rats continued on their respective diets for six weeks without quercetin. Terminally, serum triglyceride concentrations were not significantly different (p > 0.05) between males across groups. However, females receiving quercetin alone had lower serum triglyceride levels than those receiving fructose (p < 0.01). Quercetin increased the incidence of hepatic steatosis in female rats. Quercetin intake in the immediate post-weaning period may prevent hypertriglyceridemia. However, female rats receiving quercetin alone are predisposed to hepatic steatosis associated with a high fructose diet.

Neonatal administration of fenofibrate had no developmental programming effect on the lipid profile and relative leucocyte telomere lengths of adolescent rats fed a high-fructose diet postnatally.

Telomere length, a marker of ageing, is susceptible to developmental programming that may cause its accelerated attrition. Metabolic syndrome triggers telomere attrition. Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, is protective against telomere attrition. We investigated the impact of fenofibrate administered during suckling on the lipid profile and leucocyte telomere lengths of rats fed a high-fructose diet post-weaning. Suckling Sprague-Dawley pups (n = 119) were allocated to four groups and gavaged with either 10 mL·kg-1 body mass 0.5% dimethyl sulfoxide, 100 mg·kg-1 body mass fenofibrate, fructose (20%, w / v), or a combination of fenofibrate and fructose for 15 days. Upon weaning, each of the initial groups was split into two subgroups: one had plain water while the other had fructose solution (20%, w / v) to drink for 6 weeks. Blood was collected for DNA extraction and relative leucocyte telomere length determination by real-time PCR. Plasma triglycerides and cholesterol were also quantified. The treatments had no effect (p > 0.05) on body mass, cholesterol concentration, and relative leucocyte telomere lengths in both sexes. Post-weaning fructose increased triglyceride concentrations (p < 0.05) in female rats. Fenofibrate administered during suckling did not affect ageing nor did it prevent high fructose-induced hypertriglyceridaemia in female rats.

A 3D-Printed Biomaterial Scaffold Reinforced with Inorganic Fillers for Bone Tissue Engineering: In Vitro Assessment and In Vivo Animal Studies.

This research aimed to substantiate the potential practicality of utilizing a matrix-like platform, a novel 3D-printed biomaterial scaffold, to enhance and guide host cells' growth for bone tissue regeneration. The 3D biomaterial scaffold was successfully printed using a 3D Bioplotter® (EnvisionTEC, GmBH) and characterized. Osteoblast-like MG63 cells were utilized to culture the novel printed scaffold over a period of 1, 3, and 7 days. Cell adhesion and surface morphology were examined using scanning electron microscopy (SEM) and optical microscopy, while cell viability was determined using MTS assay and cell proliferation was evaluated using a Leica microsystem (Leica MZ10 F). The 3D-printed biomaterial scaffold exhibited essential biomineral trace elements that are significant for biological bone (e.g., Ca-P) and were confirmed through energy-dispersive X-ray (EDX) analysis. The microscopy analyses revealed that the osteoblast-like MG63 cells were attached to the printed scaffold surface. The viability of cultured cells on the control and printed scaffold increased over time (p < 0.05); however, on respective days (1, 3, and 7 days), the viability of cultured cells between the two groups was not significantly different (p > 0.05). The protein (human BMP-7, also known as growth factor) was successfully attached to the surface of the 3D-printed biomaterial scaffold as an initiator of osteogenesis in the site of the induced bone defect. An in vivo study was conducted to substantiate if the novel printed scaffold properties were engineered adequately to mimic the bone regeneration cascade using an induced rabbit critical-sized nasal bone defect. The novel printed scaffold provided a potential pro-regenerative platform, rich in mechanical, topographical, and biological cues to guide and activate host cells toward functional regeneration. The histological studies revealed that there was progress in new bone formation, especially at week 8 of the study, in all induced bone defects. In conclusion, the protein (human BMP-7)-embedded scaffolds showed higher regenerative bone formation potential (week 8 complete) compared to the scaffolds without protein (e.g., growth factor; BMP-7) and the control (empty defect). At 8 weeks postimplantation, protein (BMP-7) significantly promoted osteogenesis as compared to other groups. The scaffold underwent gradual degradation and replacement by new bones at 8 weeks in most defects.

ß-sitosterol as an alternative to oxytetracycline: Effect on growth performance, feed intake and utilization efficiency and viscera macromorphometry of Cobb 500 broiler chickens.

Antibiotics are used to fortify broiler chicken feeds as growth promoters. Chronic antibiotic use pollutes the environment and causes the development of antibiotic resistance. Natural alternatives that mimic the properties of antibiotics, without causing health and environmental challenges are required. ß-sitosterol has antimicrobial, antioxidant, digestive and immune system modulating and growth stimulating activities. We evaluated its potential to replace oxytetracycline as a growth-promoter in broiler chicken feeds. Two hundred and forty, one-day-old Cobb 500 broiler chicks were randomly allocated to four diets where ß-sitosterol replaced oxytetracycline at 0 mg/kg (control; fortified with 50 mg/kg oxytetracycline), 500 mg/kg, 1000 mg/kg and 1500 mg/kg (w/w) feed and fed for 6 weeks: 2 weeks for each growth phase. Each diet was replicated thrice with 20 chicks per replicate. Initial, weekly and terminal body mass (TBM) and daily feed intake (FI) were measured. Body mass gain (BMG), average daily gain (ADG) and feed conversion ratio were computed. Terminally, the chickens were fasted for 4 h then slaughtered and dressed. Gastrointestinal tract (GIT) and GIT accessory viscera masses and small and large intestine lengths were measured. Dietary fortification with ß-sitosterol had similar effects (P > 0.05) to oxytetracycline on the chickens' TBM, BMG, ADG, FI and utilisation efficiency and GIT organ macromorphometry. In conclusion, ß-sitosterol can replace oxytetracycline in Cobb 500 broiler chicken feeds without compromising growth performance, feed intake and utilisation efficiency and GIT organ growth and development.

The potential of Artemisia species for use as broad-spectrum agents in the management of metabolic syndrome: a review.

Although the prevalence of metabolic syndrome (MetS), a cluster of cardiometabolic risk factors that predispose to the development of type 2 diabetes mellitus and cardiovascular diseases, is increasing globally, there is no broad-spectrum agent for its holistic treatment. Natural plant-derived products with a wide spectrum of biological activities are currently being explored as alternatives in the management of diseases. Artemisia species are a heterozygous group of plants of the Compositae family that possess several health benefits. Here we highlight their antidiabetic, anti-obesity, anti-hyperlipidaemic, hepatoprotective and cardioprotective properties among others. These activities have been linked to the presence of phytochemicals that act on several molecular targets to exert their effects and the species of Artemisia are considered to be relatively safe. Artemisia species offer significant anti-MetS activity and thus are strong therapeutic candidates for the effective management of MetS.

Neonatal Oral Administration of Chrysin Prevents Long-Term Development of Non-Alcoholic Fatty Liver Disease in a Sexually Dimorphic Manner in Fructose Nurtured Sprague Dawley Rats.

High-fructose diets are linked with the development of non-alcoholic fatty liver disease (NAFLD), the management of which is a burden to society. Interventions with phytochemicals in the early postnatal period may prevent fructose-induced NAFLD later in adulthood. We investigated the protective potential of chrysin against fructose-induced NAFLD. Four-day-old male and female suckling Sprague Dawley rats (N = 112) were randomly grouped and orally gavaged daily with distilled water (negative Control-Cn + W), chrysin(Chr-100 mg/kg), fructose-solution (Fr-20% w/v), and Chr + Fr between postnatal day (PND) 4 and 21 and then weaned onto normal rat chow and plain drinking water to PND 55. From PND 56 to 130, half of the rats continued on plain water, and the rest had Fr as drinking fluid. Terminally, the liver tissue was collected, and the lipid content was determined and histologically assessed for NAFLD. Dietary Fr induced an increased hepatic lipid content (p = 0.0001 vs. Cn + W) both sexes, and it was only attenuated by neonatal Chr in female rats (p < 0.05). Histologically, there was increased microvesicular steatosis (p = 0.0001 vs. Cn + W) in both sexes, and it was prevented by neonatal Chr (p > 0.05). Fr caused macrovesicular steatosis (p = 0.01 vs. Cn + W) in females only, and chrysin did not prevent it (p > 0.05). Fr induced hepatocellular hypertrophy, and inflammation was observed in females only (p = 0.01 vs. Cn + W), and this was prevented by Chr (p > 0.05). The collagen area fraction was increased by Fr (p = 0.02 (males) and p = 0.04 (females) vs. Cn + W, respectively; however, chrysin did not prevent this (p > 0.05). Neonatal chrysin prevented some of the deleterious effects of the high-fructose diet on the liver, suggesting that chrysin should be further explored as a strategic prophylactic neonatal intervention against high-fructose-diet-induced NAFLD.

Neonatal administration of zingerone prevents the subsequent development of high dietary fructose-induced early features of nephropathy in rats.

Excessive consumption of fructose-rich diets in early life stages increases the risk for developing nephropathy in adulthood. We investigated the potential preventive effects of neonatally administered zingerone on the development of dietary fructose-induced nephropathy. Four-day-old suckling male and female rat pups were orally gavaged (10 ml/kg) with: distilled water (Con group), 20% fructose solution (Fru group), 20% fructose solution + 40 mg/kg zingerone in distilled water (ZFru group), or 40 mg/kg of zingerone (Zgr group) for 14 days. Thereafter, Con and Zgr groups continued on plain drinking water while Fru and ZFru groups drank 20% fructose solution ad libitum for 10 weeks. The Fru group had significantly increased plasma concentration of the renal injury marker kidney injury molecule one (KIM-1) and decreased glomerular urinary space area compared to the controls in both sexes (p < 0.05). These alterations were prevented by neonatally administered zingerone. Zingerone administration neonatally is a potential prophylaxis for longterm high-fructose diet-induced nephropathy.

Medicinal Plants, Phytochemicals, and Their Impacts on the Maturation of the Gastrointestinal Tract.

The gastrointestinal tract (GIT) is the first point of contact for ingested substances and thus represents a direct interface with the external environment. Apart from food processing, this interface plays a significant role in immunity and contributes to the wellbeing of individuals through the brain-gut-microbiota axis. The transition of life from the in utero environment, to suckling and subsequent weaning has to be matched by phased development and maturation of the GIT; from an amniotic fluid occupancy during gestation, to the milk in the suckling state and ultimately solid food ingestion at weaning. This phased maturation of the GIT can be affected by intrinsic and extrinsic factors, including diet. Despite the increasing dietary inclusion of medicinal plants and phytochemicals for health benefits, a dearth of studies addresses their impact on gut maturation. In this review we focus on some recent findings mainly on the positive impact of medicinal plants and phytochemicals in inducing precocious maturation of the GIT, not only in humans but in pertinent animals. We also discuss Paneth cells as mediators and potential markers of GIT maturation.

Zingerone Administered Neonatally Prevents the Subsequent Development of High Dietary Fructose-Induced Fatty Liver in Sprague Dawley Rats.

Consumption of high-fructose diets early in life increases the risk of developing metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). Zingerone, an alkaloid isolated from Zingiber officinale, has been demonstrated to reverse obesity and fatty liver in adult male rats. We investigated the potential preventive effects of neonatally administered zingerone on the development of fructose-induced NAFLD in male and female rats. Four-day-old male (n = 35) and female (n = 44) rat pups were randomized and gavaged with: 10 mL/kg body weight (bwt) of distilled water (C), 10 mL/kg bwt of 20% fructose solution (Fr), 10 mL/kg bwt of 20% fructose solution +40 mg/kg bwt of zingerone (ZFr), and 40 mg/kg bwt of zingerone (Z) daily for 14 days. After weaning, all groups continued on unlimited standard rat feed; however, groups C and Z had plain drinking water, whereas groups Fr and ZFr had unlimited 20% fructose solution to drink for 10 weeks. Rats on the high-fructose diet (Fr) compared with the negative controls (C) had significantly increased hepatic lipid content (in %, males: P = .0002; females: P < .0001, analysis of variance [ANOVA]) and hepatic steatosis score (in %, males: P = .0018; females: P < .0022, Kruskal-Wallis ANOVA). Zingerone prevented (P < .05) the fructose-induced increase in hepatic steatosis in both sexes. The plasma alanine aminotransferase activity, levels of uric acid, TBARS (thiobarbituric acid reactive substances), IL-6 (interleukin-6), and TNF-α (tumor necrosis factor alpha) were not different (P > .05, ANOVA) across the different treatment groups in both sexes. No difference (P > .05, ANOVA) was observed between the two sexes for treatment, sex and interaction effects with regard to hepatic lipid content, and measured blood parameters. The use of zingerone neonatally should be further investigated as a strategic prophylactic intervention for the prevention of long-term high-fructose diet-induced NAFLD.

Administration of ursolic acid to new-born pups prevents dietary fructose-induced non-alcoholic fatty liver disease in Sprague Dawley rats.

Overconsumption of fructose time dependently induces the development of non-alcoholic fatty liver disease (NAFLD). We investigated whether ursolic acid (UA) intake by new-born rats would protect against fructose-induced NAFLD. One hundred and seven male and female Sprague Dawley rat pups were randomly grouped and gavaged (10 ml/kg body weight) with either 0.5% dimethylsulphoxide (vehicle control), 0.05% UA, 50% fructose mixed with UA (0.05%) or 50% fructose alone, from postnatal day 6 (P6) to P20. Post-weaning (P21-P69), the rats received normal rat chow (NRC) and water to drink. On P70, the rats in each group were continued on water or 20% fructose to drink, as a secondary high fructose diet during adulthood. After 8 weeks, body mass, food and fluid intake, circulating metabolites, visceral adiposity, surrogate markers of liver function and indices of NAFLD were determined. Food intake was reduced as a result of fructose feeding in both male and female rats (p < 0.0001). Fructose consumption in adulthood significantly increased fluid intake and visceral adiposity in female rats (p < 0.05) and had no apparent effects in male rats (p > 0.05). In both sexes of rats, fructose had no significant (p > 0.05) effects on body mass, circulating metabolites, total calorie intake and surrogate markers of hepatic function. Fructose consumption in both early life and adulthood in female rats promoted hepatic lipid accumulation (p < 0.001), hypertrophy, microvesicular and macrovesicular steatosis (p < 0.05). Early-life UA intake significantly (p < 0.001) reduced fructose-induced hepatic lipid accumulation in both male and female rats. Administration of UA during periods of developmental plasticity shows prophylactic potential against dietary fructose-induced NAFLD.

The effect of dietary Marula nut meal on the physical properties, proximate and fatty acid content of Japanese quail meat.

Soyabean meal (SBM) is the major dietary protein source for the poultry industry in sub-Saharan Africa. Due to inadequate local soyabean production, alternative protein sources are required. Two hundred 9-day old Japanese quail chicks were randomly allocated to grower diets wherein Marula nut meal (MNM) substituted SBM on a crude protein (CP) basis at 0%, 25%, 50%, 75% and 100% and fed for 4 weeks, followed by being fed on similarly formulated finisher diets for 2 weeks, and thereafter they were humanely slaughtered and dressed. Initial pH (pHi) and ultimate (pHu), colour, thawing loss (TL), cooking loss (CL), tenderness, proximate and fatty acid (FA) composition of the breast and thigh meat were determined. The results showed that pHi and pHu of meat from carcasses of quail fed diet 1 was lower, but had lighter and less red meat than that from counterparts fed diet 5 (P < 0.01). Dietary MNM had no effect (P>0.05) on TL, CL and tenderness of the meat. The ash content of the meat increased with an increase in dietary MNM, but its CP and fat decreased (P < 0.05). In addition, the total saturated FA content of meat from birds fed diet 4 was lower (P < 0.05) than other counterparts. Meat from birds fed diets 1 and 2 had a lower oleic acid (OA) content in comparison to meat from birds fed diets 3, 4 and 5. MNM can potentially be utilised in quail feeds without compromising the physical and proximate properties of the meat. Also, it can be used to produce lean but OA-rich meat with possible potential health benefits to consumers.

The Potential Therapeutic Value of Medicinal Plants in the Management of Metabolic Disorders.

Metabolic syndrome (MetS) is a prevalent, multifactorial and complex disease that is associated with an increased risk of developing diabetes and other major cardiovascular complications. The rise in the global prevalence of MetS has been attributed to genetic, epigenetic, and environmental factors. The adoption of sedentary lifestyles that are characterized by low physical activity and the consumption of high-energy diets contributes to MetS development. Current management criteria for MetS risk factors involve changes in lifestyle and the use of pharmacological agents that target specific biochemical pathways involved in the metabolism of nutrients. Pharmaceutical drugs are usually expensive and are associated with several undesirable side effects. Alternative management strategies of MetS risk factors involve the use of medicinal plants that are considered to have multiple therapeutic targets and are easily accessible. Medicinal plants contain several different biologically active compounds that provide health benefits. The impact of phytochemicals present in local medicinal plants on sustainable health and well-being of individuals has been studied for many years and found to involve a plethora of complex biochemical, metabolic, and physiological mechanisms. While some of these phytochemicals are the basis of mainstream prescribed drugs (e.g., metformin, reserpine, quinine, and salicin), there is a need to identify more medicinal plants that can be used for the management of components of MetS and to describe their possible mechanisms of action. In this review, we assess the potential health benefits of South African ethnomedicinal plants in protecting against the development of health outcomes associated with MetS. We aim to provide the state of the current knowledge on the use of medicinal plants and their therapeutically important phytochemicals by discussing the current trends, with critical examples from recent primary references of how medicinal plants are being used in South African rural and urban communities.

ß-Sitosterol mitigates the development of high-fructose diet-induced nonalcoholic fatty liver disease in growing male Sprague-Dawley rats.

Fructose contributes to the development of nonalcoholic fatty liver disease (NAFLD). ß-Sitosterol (Bst), a naturally occurring phytosterol, has antihyperlipidaemic and hepatoprotective properties. This study interrogated the potential protective effect of ß-sitosterol against NAFLD in growing rats fed a high-fructose diet, modelling children fed obesogenic diets. Forty-four 21 day old male rat pups were randomly allocated to and administered the following treatments for 12 weeks: group I, standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II, SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III, SRC + FS + 100 mg/kg fenofibrate in a gelatine cube; group IV, SRC + FS + 20 mg/kg ß-sitosterol gelatine cube (Bst); group V, SRC + PW + Bst. Terminally, the livers were dissected out, weighed, total liver lipid content determined, and histological analyses done. Harvested plasma was used to determine the surrogate biomarkers of liver function. The high-fructose diet caused increased (p < 0.05) hepatic lipid (total) accretion (>10% liver mass), micro- and macrovesicular hepatic steatosis, and hepatic inflammation. ß-Sitosterol and fenofibrate prevented the high-fructose diet-induced macrovesicular steatosis and prevented the progression of NAFLD to steatohepatitis. ß-Sitosterol can prospectively be used to mitigate diet-induced NAFLD.

ß-Sitosterol Shows Potential to Protect Against the Development of High-Fructose Diet-Induced Metabolic Dysfunction in Female Rats.

Metabolic syndrome (MetS) is a combination of risk factors that include insulin resistance, obesity, dyslipidemia, and hypertension. The consumption of high-fructose diets contributes to the development of MetS. ß-sitosterol a naturally occurring phytosterol possesses antiobesogenic and antidiabetic effects. This study evaluated the potential protective effect of ß-sitosterol against the development of metabolic dysfunction in growing female rats fed a high-fructose diet, mimicking children fed obesogenic diets. Thirty-five 21-day-old female Sprague Dawley rat pups were randomly allocated to and administered the following treatments: group 1-standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group 2-SRC + 20% w/w fructose solution (FS) as drinking fluid + PC; group 3-SRC + FS + 100 mg/kg fenofibrate in gelatine cubes; group 4-SRC + FS + 20 mg/kg ß-sitosterol gelatine cube (Bst); and group 5-SRC + PW + Bst. Following 12 weeks of feeding, the rats were fasted overnight, weighed, and then euthanized. Plasma cholesterol, insulin, glucose, triglyceride, and adiponectin concentrations were determined. Visceral fat was dissected out and weighed. The high-fructose diet increased (P < .05) visceral adiposity and plasma triglyceride concentration but decreased (P < .05) plasma adiponectin concentration. ß-sitosterol prevented the high-fructose diet-induced visceral obesity, hypertriglyceridemia, and hypoadiponectinemia. ß-sitosterol alone increased plasma adiponectin concentration and reduced plasma insulin concentration and homeostatic model assessment index. In conclusion, ß-sitosterol could be potentially used to prevent high-fructose diet-induced metabolic dysfunction.

Quercetin administration post-weaning attenuates high-fructose, high-cholesterol diet-induced hepatic steatosis in growing, female, Sprague Dawley rat pups.

BACKGROUND: Fructose and cholesterol-rich diets have been implicated in the upsurge of metabolic syndrome (MetS). Phytochemicals are being explored as alternatives for the prevention and management of MetS. Thirty-six 21-day-old, female Sprague Dawley rats fed a high-fructose, high-cholesterol diet post-weaning were used to investigate the prophylactic potential of quercetin. Group 1 was given standard rat chow (SRC); Group 2: SRC and quercetin (75 mg kg-1 daily); Group 3: SRC and fenofibrate (100 mg kg-1 daily); Group 4 was given a high cholesterol diet (HCD) (2% added dietary cholesterol in SRC), 20% fructose drinking solution (FS); Group 5 was given HCD, 20% FS and quercetin (75 mg kg-1 daily); Group 6: HCD, 20% FS and fenofibrate (100 mg kg-1 daily). Rats were fed ad libitum for 8 weeks, euthanized, and blood and liver samples were collected. RESULTS: The HCD and FS significantly increased (P < 0.05) absolute and relative liver masses and serum cholesterol. Fasting blood glucose, serum triglycerides, alanine transaminase, creatinine, and urea were not significantly different (P > 0.05) between groups. The HCD and FS significantly increased liver lipid yield compared to the SRC and rats receiving SRC with fenofibrate (P < 0.05). Quercetin or fenofibrate together with HCD and FS attenuated the diet-induced increase in liver lipids by approximately 50%, although this was not statistically significant. Liver macro- and micro-steatosis scores were significantly increased (P < 0.05) in rats receiving HCD and FS. Quercetin or fenofibrate administration together with HCD and FS significantly decreased (P < 0.05) liver macro-steatosis scores. CONCLUSION: The prophylactic effect of quercetin on fructose and cholesterol diet-induced liver lipid accumulation may be exploited in the fight against non-alcoholic fatty liver disease (NAFLD). © 2019 Society of Chemical Industry.

The potential developmental programming effect of oral curcumin on the bone health and plasma total osteocalcin of male and female rats fed a high-fructose diet during suckling and post weaning.

We investigated the effect of oral curcumin, on bone health of rats fed a high-fructose diet. Suckling pups (males = 65, females = 63) were gavage with 0.5% DMSO, curcumin (500 mg/kg), fructose (20%, w/v) or a combination of curcumin and fructose daily from postnatal days 6 to 21. Then the rats were weaned onto normal rat feed for six weeks and each group was sub-divided into two subgroups: one had plain tap water and the other had fructose (20%, w/v) to drink. Blood was assayed for plasma total osteocalcin. Morphometry and radiographic bone density assessments were made on the femora and tibiae. The lengths, masses and Seedor indices of the bones were similar (p > 0.05, ANOVA) across the groups. Males that received curcumin with or without fructose during suckling and weaned onto a high-fructose diet had lower (p ≤ 0.05, ANOVA) osteocalcin concentration versus the other males. Similarly, in females rats, curcumin alone or administered with fructose resulted in lower (p ≤ 0.05, ANOVA) osteocalcin concentration versus female rats administered the vehicle control. Neonatal curcumin-induced decrease in plasma total osteocalcin concentration may predispose to adverse consequences on glucose metabolism and bone health.

The long-term protective effects of neonatal administration of curcumin against nonalcoholic steatohepatitis in high-fructose-fed adolescent rats.

There is an increased prevalence of nonalcoholic steatohepatitis (NASH) in adolescents. The suckling period is developmentally plastic, affecting later health outcomes. We investigated whether neonatal administration of curcumin would provide protection against the development of NASH later in adolescence in rats fed a high-fructose diet. From postnatal day (PN) 6 to PN 21, the pups (N = 128) were allocated to four groups and orally gavaged daily with either 0.5% dimethyl sulfoxide solution (vehicle control), curcumin (500 mg·kg-1 ), fructose (20%, w/v) or curcumin and fructose combined. All the pups were weaned and half the rats in each group had tap water, whereas the other received fructose (20%) as their drinking fluid ad libitum for 6 weeks. The rats' liver NASH scores, lipid content, and RNA gene expression ratios of AMPKα and TNFα were determined. Hepatic lipid content was similar across the treatment groups in the males (P > 0.05, ANOVA). In the females, the hepatic lipid content in the treatment groups ranged from 2.7 to 4.3%. The livers of male and female rats that had fructose either as neonates and/or postweaning had significantly marked inflammation (P = 0.0112, Kruskal-Wallis) and fibrosis (P < 0.0001, ANOVA) which were attenuated by curcumin. The hepatic gene expression ratios for AMPKα in both sexes were significantly downregulated (P < 0.0001, ANOVA), whereas the expression ratios of TNFα were significantly upregulated (P < 0.0001) in rats fed a high-fructose diet pre and/or postweaning compared to the other groups. Neonatal curcumin administration is a potential natural pharmacological candidate for the prevention of NASH.

Short-Term Neonatal Oral Administration of Oleanolic Acid Protects against Fructose-Induced Oxidative Stress in the Skeletal Muscles of Suckling Rats.

Nutritional manipulations in the neonatal period are associated with the development of negative or positive health outcomes later in life. Excessive fructose consumption has been attributed to the increase in the global prevalence of metabolic syndrome (MetS) and the development of oxidative stress. Oleanolic acid (OA) has anti-diabetic and anti-obesity effects. We investigated the protective potential of orally administering OA in the neonatal period, to prevent fructose-induced oxidative stress, adverse health outcomes and maturation of the gastrointestinal tract (GIT) in suckling rats. Seven-day old Sprague-Dawley rats (N = 30) were gavaged daily with 10 mL/kg of: distilled water (DW), oleanolic acid (OA; 60 mg/kg), high fructose solution (HF; 20% w/v), or OAHF for 7 days. On day 14, tissue samples were collected to determine clinical health profiles, hepatic lipid content, and activity of anti-oxidant enzymes. Furthermore, biomarkers of oxidative stress and anti-oxidant capacity in the skeletal muscles were assessed. The gastrointestinal tract (GIT) morphometry was measured. Rats in all groups grew over the 7-day treatment period. There were no significant differences in the terminal body masses, GIT morphometry, surrogate markers of general health, liver lipid content across all treatment groups (p < 0.05). Neonatal fructose administration decreased the activity of catalase, depleted GSH and increased lipid peroxidation. However, the level of GSH and catalase activity were improved by neonatal OA treatment. Short-term oral OA administration during the critical developmental period protects against fructose-induced oxidative stress without adverse effects on health outcomes associated with MetS or precocious development of the GIT in suckling male and female rats.