Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway.

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. GAS reduced the accumulation of p-tau and amyloid-beta (Aß). GAS inhibited Pb-induced inflammation in the brain, as indicated by the decreased levels of pro-inflammatory cytokines, including tumor necrosis factor-a (TNF-α), cyclooxygenase-2 (COX-2). GAS increased the expression levels of NR2A and neurotrophin brain-derived neurotrophic factor (BDNF). GAS inhibited Pb-induced apoptosis of neurons in hippocampus tissue, as indicated by the decreased levels of pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the neuroprotective effects of GAS were associated with inhibiting oxidative stress by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. GAS supplement activated the Wnt/ß-catenin signaling pathway and reduced the expression of Wnt inhibitor Dickkopf-1 (Dkk-1). Collectively, this study clarified that GAS exhibited neuroprotective property by anti-oxidant, anti-inflammatory and anti-apoptosis effects and its ability to regulate the Wnt/Nrf2 pathway.

Effects of gastrodin against carbon tetrachloride induced kidney inflammation and fibrosis in mice associated with the AMPK/Nrf2/HMGB1 pathway.

Gastrodin (GAS), the main phenolic glycoside extracted from Gastrodia elata Blume, exhibits potential renoprotective properties. Here, we examined the protective effects of GAS on carbon tetrachloride (CCl4)-induced kidney inflammation and fibrosis in mice, and explored its underlying mechanisms. Our research findings revealed that GAS improved CCl4-induced renal damage in mice. GAS inhibited kidney fibrosis and the deposition of collagen and α-smooth muscle actin (α-SMA). GAS suppressed CCl4-induced inflammation in kidney tissue, as indicated by the decreased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The renoprotective effects of GAS were associated with inhibiting oxidative stress by regulating nuclear factor-erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling and increasing adenosine 5'-monophosphate activated protein kinase (AMPK) activation. Furthermore, GAS supplementation inactivated the receptor for advanced glycation end products (RAGE) and the high-mobility group box-1 (HMGB1) pathway. GAS inhibited the activation of Toll-like receptors (TLRs), nuclear factor-kappa B (NF-κB) and transforming growth factor (TGF)-ß. Collectively, this study clarified that GAS attenuates CCl4-induced kidney inflammation and fibrosis via the AMPK/Nrf2/HMGB1 pathway.

Ampelopsin attenuates carbon tetrachloride-induced mouse liver fibrosis and hepatic stellate cell activation associated with the SIRT1/TGF-ß1/Smad3 and autophagy pathway.

Ampelopsin (Amp), a natural flavonoid found in the vine tea of Ampelopsis grossedentata, exhibited anti-cancer, anti-oxidant, anti-inflammatory, anti-apoptosis and hepatoprotective properties. The current study instigates the protective effect of Amp on carbon tetrachloride (CCl4)-induced hepatic fibrosis and explores its underlying mechanisms. The results indicated Amp decreased the levels of liver injury markers. Amp inhibited liver fibrosis, as indicated by decreases in hepatic collagen deposition, extracellular matrix (ECM) deposition and α-smooth muscle actin (α-SMA). Amp blocked the activation of hepaticstellate cells (HSCs) by decreasing the expression of collage I, α-SMA, tissue inhibitor of matrix metalloproteinases (TIMPs) 1, transforming growth factor (TGF)-ß1, phosphorylated Smad3 (p-Smad3) and increasing the expression of matrix metalloproteinases (MMPs) 9 and SIRT1 in the model of liver fibrosis and cultured HSCs. The sirtuin 1 (SIRT1) specific inhibitor Sirtinol activated the TGF-ß1/Smad3 pathway and enhanced ECM accumulation. Attractively, Amp up-regulates the expression of autophagy-related proteins microtubule-associated protein light chain three II (LC3-II) and Beclin-1 in vivo and in vitro. However, depletion of autophagy by specific inhibitor 3-MA obviously abolished the inhibiting effect of Amp on HSC activation and hepatic fibrosis. Conclusively, these results suggest that Amp could decrease CCl4-induced hepatic fibrosis through regulating the SIRT1/TGF-ß1/Smad3 and autophagy pathway.

Fisetin improves lead-induced neuroinflammation, apoptosis and synaptic dysfunction in mice associated with the AMPK/SIRT1 and autophagy pathway.

Fisetin, a natural flavonoid found in plants, fruits and vegetables, exerts anti-cancer, anti-oxidant, anti-inflammatory and anti-mitotic effects. The current study instigates the protective effect of fisetin against lead-induced synaptic dysfunction, neuroinflammation and neurodegeneration in mice, and explores its underlying mechanisms. The results indicated fisetin can significantly ameliorated behavioral impairments in Pb-treated mice. Fisetin inhibited Pb-induced the apoptotic neurodegeneration, as indicated by the decreased levels of Bax and cleaved caspase-3. Fisetin suppressed activations of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), NF-κB and subsequently inactivate pro-inflammatory factor including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). It can also decrease the accumulation of p-tau and amyloid-beta (Aß) and increased the expression of the Aß remover neprilysin (NEP) in brains of mice. Fisetin also reversed Pb-induced synaptic dysfunction by increasing the levels of synaptosomal associated protein-25 (SNAP-25), postsynaptic density-95 (PSD-95), cyclic-AMP-response element-binding protein (CREB) phosphorylation and calcium/calmodulin kinase II (CaMKII) phosphorylation. Fisetin promoted Pb-induced autophagy in the brains of mice. Moreover, fisetin can increase levels of the denosine 5'-monophosphate-activated protein kinase (AMPK) phosphorylation and SIRT1. Fisetin may be developed as a potential nutritional target for the prevention of Pb-induced neurotoxicity.

Wolbachia Infection Dynamics in Tribolium confusum (Coleoptera: Tenebrionidae) and Their Effects on Host Mating Behavior and Reproduction.

Wolbachia interact with their hosts in a broad variety of relationships that range from parasitism to mutualism. To improve the understanding of complex relationships between Wolbachia and host, we performed not only mating and crossing experiments to investigate effects of Wolbachia on mate choice, mating performance, and reproduction in the confused flour beetles Tribolium confusum (Jacquelin du Val), but also quantitative PCR to determine Wolbachia spatiotemporal infection density dynamics within beetles. Wolbachia induced strong cytoplasmic incompatibility, but had no effects on male mate choice and mating performance. Compared with Wolbachia-uninfected females, infected females had very high fecundity irrespective of male's infection status. Wolbachia infection densities in beetles were higher in eggs and adults and in the reproductive tissues and abdomens, whereas Wolbachia density in adults did not differ between sexes and among different ages. These results suggest that Wolbachia have evolved mutualistic interactions with T. confusum, which provides the first evidence of Wolbachia mutualisms in this beetle species. We discussed these findings and their evolutionary implications in light of Wolbachia-host interactions.

Protective effect of puerarin on lead-induced mouse cognitive impairment via altering activities of acetyl cholinesterase, monoamine oxidase and nitric oxide synthase.

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The present study aimed to investigate the protective effects of puerarin on neurotoxicity in mice exposed to lead. ICR mice were exposed to lead acetate in the drinking water (500 ppm) with or without puerarin coadministration (100 and 200 mgPU/kg intragastrically once daily) for three months. We found puerarin significantly prevented Pb-induced neurotoxicity in a dose-dependent manner, indicated by behavioral indicators. Puerarin also decreased Pb contents in blood and brain. Puerarin increased activities of acetyl cholinesterase (AChE) and monoamine oxidase (MAO) in brain of Pb-treated mice. Moreover, Pb-induced profound elevation of oxidative stress, as evidenced by increasing of lipid peroxidation level and depleting of total antioxidant capacity in brain, were suppressed by treatment with puerarin. Puerarin markedly increased NO production and PKA activity in brain of Pb-treated mice. Western blot analysis showed that puerarin dramatically increased the expression levels of nNOS, eNOS and phosphor-Akt in brains of Pb-treated mice. In conclusion, these results suggested that puerarin can inhibit Pb-induced neurotoxicity, at least in part, by suppressing oxidative stress, reversing the Pb-induced alterations in transmitters and enzymes and modulating the PKA/Akt/NOS signaling pathway.

Sesamin protects mouse liver against nickel-induced oxidative DNA damage and apoptosis by the PI3K-Akt pathway.

Sesamin (Ses), one of the major lignans in sesame seeds and oil, has been reported to have many benefits and medicinal properties. However, its protective effects against nickel (Ni)-induced injury in liver have not been clarified. The aim of the present study was to investigate the effects of sesamin on hepatic oxidative DNA injury and apoptosis in mice exposed to nickel. Kunming mice were exposed to nickel sulfate with or without sesamin coadministration for 20 days. The data showed that sesamin significantly prevented nickel-induced hepatotoxicity in a dose-dependent manner, indicated by both diagnostic indicators of liver damage (serum aminotransferase activities) and histopathological analysis. Moreover, nickel-induced profound elevation of reactive oxygen species (ROS) production and oxidative stress, as evidenced by an increase of the lipid peroxidation level and depletion of the intracellular reduced glutathione (GSH) level in liver, were suppressed by treatment with sesamin. Sesamin also restored the activities of antioxidant enzymes (T-SOD, CAT, and GPx) and decreased 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in nickel-treated mice. Furthermore, a TUNEL assay showed that nickel-induced apoptosis in mouse liver was significantly inhibited by sesamin. Exploration of the underlying mechanisms of sesamin action revealed that activities of caspase-3 were markedly inhibited by the treatment of sesamin in the liver of nickel-treated mice. Sesamin increased expression levels of phosphoinositide-3-kinase (PI3K) and phosphorylated protein kinase B (PBK/Akt) in liver, which in turn inactivated pro-apoptotic signaling events, restoring the balance between pro- and anti-apoptotic Bcl-2 proteins in the liver of nickel-treated mice. In conclusion, these results suggested that the inhibition of nickel-induced apoptosis by sesamin is due at least in part to its antioxidant activity and its ability to modulate the PI3K-Akt signaling pathway.

Influence of nutrition on male development and reproduction in Tribolium castaneum.

Tribolium beetles have evolved over several thousand years to colonize and exploit various food products that vary widely in their nutritional quality. Here Tribolium castaneum was used as a model organism to explore the effect of nutritional quality on male development and reproduction. The results showed, when tested across different qualities of nutritional diets, Tribolium males developed faster and their body size was larger on a high-quality diet, and there were significant correlations between male developmental traits. However, Tribolium males fed different nutritional diets did not show significant variation in olfactory attractiveness, mating rate, insemination rate, sperm defense (P1), sperm offense (P2), and reproductive success within a population context (RSPC). Moreover, there was no significant correlation of male reproductive performances except RSPC with developmental traits, and except for P2 and RSPC, no significant correlations between male reproductive performances. Therefore, although male developmental performance was significantly influenced by diet quality, reproductive performance was not. We discussed these findings and their sexual selection implications in light of its habitat.

Pheromone production by male Tribolium castaneum (Coleoptera: Tenebrionidae) is influenced by diet quality.

Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), the red flour beetle, is a common cosmopolitan pest exploiting a variety of stored products. We experimentally manipulated diet nutritional quality by using non-nutritive filler to examine how this influenced pheromone production and olfactory attractiveness of T. castaneum adult males. Volatiles released by individual males reared on high versus low nutrition diets were collected using solid phase microextraction, and gas chromatography coupled to mass spectrometry was used to identify and quantify the Tribolium aggregation pheromone 4, 8-dimethyldecanal (DMD). Males kept on high nutrition diet showed a three-fold increase in daily DMD production, which suggests the possibility that this pheromone could act as a condition-dependent mating signal. In pitfall trap assays, there was no significant difference in the mean response of virgin females to discs kept with low versus high nutrition males, although discs carrying male cues were significantly more attractive than blank discs. These results suggest that DMD production rates by T. castaneum males will depend on the nutritional quality of various stored products, but such differences may not alter males' ability to attract females.

Genetic basis of sex pheromone blend difference between Helicoverpa armigera (Hübner) and Helicoverpa assulta (Guenée) (Lepidoptera: Noctuidae).

The two closely related moth species, Helicoverpa armigera and H. assulta, are sympatric in China. Both species use a mixture of (Z)-11-hexadecenal (Z11-16:Ald) and (Z)-9-hexadecenal (Z9-16:Ald) as their sex pheromones but in widely different ratios. Hybridization and backcrossing experiments between H. armigera and H. assulta were conducted and sex pheromone compositions of the parent species, their F(1) hybrids and backcrosses were compared to study the genetic basis of the production of their sex pheromone blend composition. Results show that the difference in sex pheromone blend ratios of these Helicoverpa species is mainly controlled by an autosomal locus with two alleles, with the allele from H. armigera being almost completely dominant over that derived from H. assulta.

Mechanisms of premating isolation between Helicoverpa armigera (Hübner) and Helicoverpa assulta (Guenée) (Lepidoptera: Noctuidae).

Helicoverpa armigera and Helicoverpa assulta are sympatric sibling species, and in the laboratory they can interbreed and produce viable offspring. To assess the contributions of temporal barriers and sexual barriers to premating isolation, we investigated both the temporal rhythms of calling behavior and pheromone titers of H. armigera and H. assulta females and the behavioral responses of males to conspecific and heterospecific calling females in a wind tunnel. Both H. armigera and H. assulta females called throughout the scotophase, and there was more calling during the second half of the scotophase than during the first half. Maximal pheromone titer and maximal calling activity in H. armigera synchronously occurred at the sixth hour into the scotophase, whereas, in H. assulta, the maximal pheromone titer occurred 2 h before the peak of calling. Pheromone blend ratios of the two species were opposite and, within each species, changes in the ratio within the scotophase and at different ages were relatively small. Males of both H. armigera and H. assulta responded strongly to their conspecific calling females in the wind tunnel and completed the whole courtship sequence. In contrast, they did not land and had no copulation attempts in response to heterospecific calling females. These results show that the two species do not have obvious temporal differences in calling behavior and pheromone production, and the specificity of sex pheromone blend emitted by females plays a key role in their premating isolation. In addition, we summarized the potential isolation mechanisms of H. armigera and H. assulta.