Effects of High-Lipid Dietary Protein Ratio on Growth, Antioxidant Parameters, Histological Structure, and Expression of Antioxidant- and Immune-Related Genes of Hybrid Grouper.

The hybrid grouper (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatus) is a new species of grouper crossed from giant grouper (E. lanceolatus) as the male parent and brown-marbled grouper (E. fuscoguttatus) as the female parent. We hypothesized that optimal levels of dietary protein may benefit liver function. High-lipid diets are energetic feeds that conserve protein and reduce costs, and are a hot topic in aquaculture today. Therefore, the objective of the research is to investigated the effects of dietary protein level in high-lipid diets on serum and liver biochemistry, liver histology, and liver immune and antioxidant indexes and gene mRNA expression of the juvenile hybrid grouper (♀ Epinephelus fuscoguttatus × â™‚ E. lanceolatus). Six iso-lipidic (161 g/kg) diets were formulated containing graded levels of protein (510 as control, 480,450, 420, 390 and 360 g/kg). Each treatment consisted of three replicates and 30 fish (6.70 ± 0.02 g) in one replicate. After an 8-week feeding experiment, the results indicated the following: (1) With the decreasing of dietary protein level, the specific growth rate (SGR) of groupers increased gradually and then decreased; SGRs of the 390 and 360 g/kg groups were significantly lower than other groups (p < 0.05). (2) In terms of serum and liver, the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD), and the total antioxidant capacity (T-AOC) content, and the activity of immune enzymes such as lysozyme (LYS) and immunoglobulin (IgM) was significantly increased under the appropriate protein level. (3) Based on liver histology, we know that high or low dietary protein levels cause liver damage. (4) Dietary protein levels can significantly affect the mRNA expression levels of an anti-inflammatory factor gene (tgfß), pro-inflammatory factor genes (il6, il8), heat shock proteins, and antioxidant and immune genes (hsp70 and hsp90, gpx, nrf2, keap1). It is concluded that the appropriate protein level can promote the growth performance of groupers, improve antioxidant activity and immune enzyme activity in serum and liver, and enhance the expression of immune genes.

The antioxidant effects of hedysarum polybotrys polysaccharide in extending lifespan and ameliorating aging-related diseases in Drosophila melanogaster.

Hedysarum polybotrys polysaccharide (HPS) is one of the main active ingredients of Hedysarum with many health-beneficial properties, including antioxidant property, immunomodulatory, anti-inflammatory, and anti-tumor. However, the effect of HPS on anti-aging is still unclear. This study was to explore the protective function of HPS on aging and age-related diseases using Drosophila melanogaster. The results demonstrated that HPS supplementation promoted hatchability and prolonged lifespan by enhancing the antioxidative capacity. Administraction of HPS ameliorated age-related symptoms such as imbalanced intestinal homeostasis, sleep disturbances, and beta-amyloid (Aß) induced Alzheimer's disease (AD) in flies, but did not modulate neurobehavioral deficits in the AD model of tauopathy and the Parkinson's disease (PD) model of Pink1 mutation. Overall, this study reveals that HPS has strong potential in the prevention of aging and age-related diseases, and provided a new candidate for the development of anti-aging drugs.

Regulation and mechanism of Astragalus polysaccharide on ameliorating aging in Drosophila melanogaster.

Astragalus polysaccharide (APS) is a notable bioactive component of Astragalus membranaceus and has been extensively investigated for its pharmacological activities, including antioxidant, neuroprotection, and anticancer effects. However, the beneficial effects and mechanisms of APS on anti-aging diseases remain largely unknown. Here, we utilized the classic model organism Drosophila melanogaster to investigate the beneficial effects and mechanism of APS on aging-related intestinal homeostasis imbalance, sleeping disorders, and neurodegenerative diseases. The results showed that administration of APS significantly attenuated age-associated disruption of the intestinal barrier, loss of gastrointestinal acid-base balance, reduction in intestinal length, overproliferation of the intestinal stem cells (ISCs), and sleeping disorders upon aging. Furthermore, APS supplementation delayed the onset of Alzheimer's phenotypes in Aß42-induced Alzheimer's disease (AD) flies, including the extension of lifespan and the increase in motility, but without rescuing neurobehavioral deficits in the AD model of taupathy and Parkinson's disease (PD) model of Pink1 mutation. In addition, transcriptomics was used to dissect updated mechanisms of APS on anti-aging, such as JAK-STAT signaling, Toll signaling, and IMD signaling pathways. Taken together, these studies indicate that APS plays a beneficial role in modulating aging-related diseases, thereby as a potential natural drug to delay aging.

Protective effect of astragalus membranaceus and its bioactive compounds against the intestinal inflammation in Drosophila.

Inflammatory bowel disease (IBD) is characterized by chronic and relapsing intestinal inflammation, which currently lacks safe and effective medicines. Astragalus membranaceus (AM), also named Huangqi, is one of the most commonly used fundamental herbs in China. Here, we aimed to investigate mechanism and bioactive compounds of AM on treating sodium dodecyl sulfate (SDS)- induced colitis in Drosophila flies. Our data showed that AM extract (AME) supplementation had no toxic effect in flies, and protected flies against SDS-induced lifespan shortening, intestinal morphological damage, and colon length shortening. Moreover, AME supplementation remarkably rescued SDS-induced intestinal stem cell (ISC) overproliferation and increased reactive oxygen species (ROS) level in the intestine. Mechanistically, AME remarkably rescued the altered expression levels of genes and proteins in c-Jun N-terminal kinase (JNK) and JAK-STAT signaling pathways induced by SDS in gut. Additionally, formononetin, isoliquiritigenin, isorhamnetin, astragaloside I, astragaloside III, vanillic acid, and caffeic acid in AM had protection against SDS-induced inflammatory damage in flies. Taken together, AME could ameliorate the intestinal inflammation partially by suppressing oxidative stress-associated JNK signaling and JAK-STAT signaling pathways. AME may provide a theoretical basis for natural medicine toward treating intestinal inflammatory disease in human.

Substituting fish meal with castor meal in diets of hybrid grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂): Effects on growth performance, immune response, antioxidant and digestive enzyme activities, gut morphology, and inflammatory-related gene expression.

The present study was conducted to investigate the effects of replacing fishmeal (FM) with castormeal (CM) on the growth performance, immune response, antioxidant and digestive enzyme activities, intestinal morphology, and expression of inflammatory-related genes in juvenile hybrid grouper (Epinephelus fuscoguttatus♀ ×E. lanceolatus♂). Six iso-nitrogenous (50% crude protein) and iso-lipidic (10% crude lipid) diets were formulated; namely, a reference diet (FM) containing 50% FM and five experimental diets (4% (CM4), 8% (CM8), 12% (CM12), 16% (CM16), and 20% (CM20)) in which FM protein was substituted with CM at varying levels to feed fish (initial weight: 9.12 ± 0.01 g) for 8 weeks. The results showed that the final weight, weight gain rate, and specific growth rate were highest in the FM, CM4, and CM8 groups, whereas the feed conversion ratio, hepatosomatic and viscerosomatic indexes were significantly enhanced in the CM4 group in comparison to the others. The CM4 and CM12 groups were observed to show the highest intestinal length index values compared to the other groups, with the CM20 revealing the worst growth performance. The serum total protein content first increased (P < 0.05) in the CM4 group and decreased (P < 0.05) afterward. Nonetheless, a decreasing significant (P < 0.05) cholesterol and triglyceride contents were witnessed with the increasing replacement of FM with CM. Compared to the control group, a significant increase (P < 0.05) in the activities of serum and liver immunoglobulin-M, superoxide dismutase, glutathione peroxidase, total antioxidant capacity, and complement-3 (except serum activity for CM12 group); liver lysozyme; intestinal amylase, and lipase, was witnessed in the CM groups. However, the serum lysozyme activity was highest (P < 0.05) in the CM4 group and lowest in the CM20 group. While the least serum malondialdehyde contents were observed in the CM4 group, that of the liver malondialdehyde was least witnessed in the FM, CM4, CM8, CM12, and CM16 groups as compared to the CM20. The intestinal histological examination revealed a significantly decreasing trend for villi height and villi width with increasing replacement levels. However, the muscle thickness, crypt depth, and type II mucus cells first increased upto 4% replacement level and later decreased. The increasing of dietary replacement levels significantly up-regulated pro-inflammatory (il-1ß, tnf-α, myd88, ifn-γ, tlr-22, and il-12p40) and down-regulated anti-inflammatory (il-10, tgf-ß, mhc-iiß) and anti-bacterial peptide (epinecidin and hepcidin) mRNA levels in the intestine. The mRNA levels of il-6 was up-regulated firstly upto 4 and 8% replacement levels, and later down-regulated with increasing replacement. These results suggested that, although higher dietary CM replacement enhances the immune, antioxidant and digestive enzymes, it aggravates intestinal inflammation. Replacing 4 and 8% of FM with CM could enhance the growth performance of fish.

Flos puerariae ameliorates the intestinal inflammation of Drosophila via modulating the Nrf2/Keap1, JAK-STAT and Wnt signaling.

Gut homeostasis is important for human health, and its disruption can lead to inflammatory bowel disease (IBD). Flos Puerariae is a herb with a wide variety of pharmacological activities including antioxidant, antidiabetic, antialcoholismic and anti-inflammatory properties. However, the role of Flos Puerariae on treating IBD remains obscure. Here, we employed Drosophila melanogaster as a model organism to investigate the protective effect of Flos Puerariae extract (FPE) against sodium dodecyl sulfate (SDS)-induced intestinal injury. Our data showed that FPE had no toxic effect in flies, and significantly extended lifespan in SDS-inflamed flies, reduced stem cell proliferation in the midgut, and maintained intestinal morphological integrity. Furthermore, FPE remarkably recused the altered expression level of genes and proteins in Nrf2/Keap1 signaling, JAK-STAT signaling and Wnt signaling pathways in gut of inflammation flies. Thus, FPE has a protective effect against intestinal injury possibly via increasing the Nrf2/keap1 pathway and suppressing the JAK-STAT and Wnt signaling pathways, which would have tremendous potential for treating IBD.

Gastrodin extends the lifespan and protects against neurodegeneration in the Drosophila PINK1 model of Parkinson's disease.

Gastrodin is the main bioactive ingredient of a famous Chinese herb Rhizoma Gastrodiae. Many studies have reported that gastrodin has antioxidative and neuroprotective effects, although its effect on longevity and the mechanism of neuroprotection have not been well studied. Here, we use Drosophila melanogaster as a model to investigate the longevity and neuroprotective effects of gastrodin. Gastrodin significantly extended the lifespan, increased the climbing ability, enhanced the resistance to oxidative stress, increased the enzyme activities of superoxide dismutase (SOD) and catalase (CAT), and promoted the expression of anti-oxidative genes in old flies. The food intake, reproduction and starvation resistance were not affected in flies treated with gastrodin. Moreover, gastrodin delayed the onset of Parkinson-like phenotypes in Pink1B9 mutant flies, including the prolongation of the lifespan, rescue of the climbing ability, rescue of the progressive loss of a cluster of dopaminergic neurons in the protocerebral posterial lateral 1 region, and increase of the dopamine content in the brain. Gastrodin did not ameliorate the tau-induced neurobehavioral deficits in the fly AD model of taupathy. Together, these results indicate that gastrodin could prolong the lifespan by regulating the antioxidant ability, and protect against neurodegeneration in the Pink1B9 model of PD. This suggests that gastrodin can be considered as an ideal therapeutic candidate for drug development towards anti-aging.

Extension of Drosophila Lifespan by Astragalus polysaccharide through a Mechanism Dependent on Antioxidant and Insulin/IGF-1 Signaling.

Historical literature and pharmacological studies demonstrate that Astragalus polysaccharide (APS) has anti-inflammatory and antioxidative effects. Studies into the longevity effects of APS are limited, and the molecular mechanism of lifespan extension by APS is not elucidated yet. Here, the longevity effect of APS was investigated in Drosophila melanogaster by feeding dose-dependent APS. APS significantly extended the lifespan and improved the reproduction. Meanwhile, APS increased locomotion, TAG level, and starvation resistance and reduced the mortality rate induced by hydrogen peroxide. The activities of superoxide dismutase (SOD) and catalase (CAT) were increased in flies treated with APS diet. Moreover, APS significantly enhanced expressions of antioxidant genes (Sod1, Sod2, and Cat), dFoxO, and 4E - BP, decreased the expressions of insulin-like peptides (dilp2, dilp3, and dilp5), and longevity gene MTH. Together, these results indicate that APS can prolong the lifespan by regulating antioxidant ability and insulin/IGF-1 signaling and also enhance the reproduction ability in Drosophila. APS may be explored as a novel agent for slowing the aging process and improving reproduction.