Hydrangea paniculata coumarins alleviate adriamycin-induced renal lipotoxicity through activating AMPK and inhibiting C/EBPß.

ETHNOPHARMACOLOGICAL RELEVANCE: Throughout Chinese history, Hydrangea paniculata Siebold has been utilized as a traditional medicinal herb to treat a variety of ailments associated to inflammation. In a number of immune-mediated kidney disorders, total coumarins extracted from Hydrangea paniculata (HP) have demonstrated a renal protective effect. AIM OF THE STUDY: To investigate renal beneficial effect of HP on experimental Adriamycin nephropathy (AN), and further clarify whether reversing lipid metabolism abnormalities by HP contributes to its renoprotective effect and find out the underlying critical pathways. MATERIALS AND METHODS: After establishment of rat AN model, HP was orally administrated for 6 weeks. Biochemical indicators related to kidney injury were determined. mRNAs sequencing using kidney tissues were performed to clarify the underlying mechanism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, western blot, molecular docking, and drug affinity responsive target stability (DARTS) assay was carried out to further explore and confirm pivotal molecular pathways and possible target by which HP and 7-hydroxylcoumarin (7-HC) played their renal protection effect via modulating lipid metabolism. RESULTS: HP could significantly improve renal function, and restore renal tubular abnormal lipid metabolism and interstitial fibrosis in AN. In vitro study demonstrated that HP and its main metabolite 7-HC could reduce ADR-induced intracellular lipid deposition and fibrosis characteristics in renal tubular cells. Mechanically, HP and 7-HC can activate AMP-activated protein kinase (AMPK) via direct interaction, which contributes to its lipid metabolism modulation effect. Moreover, HP and 7-HC can inhibit fibrosis by inhibiting CCAAT/enhancer binding protein beta (C/EBPß) expression in renal tubular cells. Normalization of lipid metabolism by HP and 7-HC further provided protection of mitochondrial structure integrity and inhibited the nuclear factor kappa-B (NF-κB) pathway. Long-term toxicity using beagle dogs proved the safety of HP after one-month administration. CONCLUSION: Coumarin derivates from HP alleviate adriamycin-induced lipotoxicity and fibrosis in kidney through activating AMPK and inhibiting C/EBPß.

Dietary L-carnitine supplementation changes lipid metabolism and glucose utilization of Rhynchocypris lagowskii fed diets with different lipid sources.

The widely available crop oil is an effective alternative to the increasingly scarce marine fish oil. However, simple alternative strategies have led to declining growth and the edible value of farmed fish. It is worthwhile to explore the effects of micro supplements in diets to improve the tolerance of fish to different dietary lipid sources, which finally optimizes the feeding strategies. This study aimed to investigate the regulation of L-carnitine and dietary oil conditions on nutrient composition, lipid metabolism, and glucose regulation of Rhynchocypris lagowskii. Four diets were prepared according to fish oil, fish oil supplemented with L-carnitine, corn oil, and corn oil supplemented with L-carnitine, and FO, LCFO, CO, and LCCO were labeled, respectively. R. lagowskii was fed experimental diets for 8 weeks, and the glucose tolerance test was performed. The CO diet significantly resulted in higher crude lipid content in muscle but a lower level of serum lipid parameters of R. lagowskii than the FO diet. However, dietary L-carnitine supplementation significantly reduced the crude lipid content in the hepatopancreas and muscle of the fish fed with the CO diet yet increased the serum lipid parameters. Additionally, the crude lipid content of muscle was reduced in the fish fed with an FO diet supplemented with L-carnitine. Compared with the FO diet, the CO diet significantly reduced the ratio of n3/n6 polyunsaturated fatty acid in the hepatopancreas and muscle of R.lagowskii. Dietary L-carnitine supplementation significantly reduced the contents of total saturated fatty acids and total monounsaturated fatty acids in hepatopancreas under both dietary lipid sources. The CO diet significantly up-regulated the expression of genes related to lipid uptake and adipogenesis in hepatopancreas, including lipoprotein lipase (lpl), acetyl-coenzyme A carboxylase alpha (accα), and sterol regulatory element binding protein-1 (srebp1), compared with the FO diet. While dietary L-carnitine supplementation significantly down-regulated the expressions of lpl, accα, srebp1, and fatty acid synthase in hepatopancreas and muscle of fish under both dietary lipid sources, along with up-regulated expression of carnitine palmitoyltransferase 1 in hepatopancreas. Moreover, the fish fed with a CO diet significantly increased the expression of glucose uptake and clearance and significantly down-regulated the expressions of glucose regulation-related genes, including glucose transporter 1, glycogen synthase 1, and phosphofructokinase in hepatopancreas and muscle, resulting in slower glucose uptake and clearance than fish fed with FO diet. Nevertheless, dietary L-carnitine supplementation up-regulated the expression of gluconeogenesis-related genes, including glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the hepatopancreas of R. lagowskii under both dietary lipid sources. In conclusion, a higher dietary n6 PUFA resulted in lipid deposition, decreased serum lipid parameters, and limited serum glucose utilization of R. lagowskii. While the regulatory effect of L-carnitine on lipid metabolism and glucose utilization of R. lagowskii varies with dietary lipid sources and tissues.

Effect of Bacillus amyloliquefaciens LSG2-8 on the intestinal barrier function of Amur minnow (Rhynchocypris lagowskii).

Probiotics are widely used in aquaculture. This article aims to study the effect of Bacillus amyloliquefaciens LSG2-8 on the intestinal barrier function of Rhynchocypris lagowskii. B. amyloliquefaciens LSG2-8 were added to R. lagowskii basal diets (CK) as additives at four concentrations: 1.0 × 106 (D-6), 1.0 × 107 (D-7), 1.0 × 108 (D-8) and 1.0 × 109 (D-9) CFU g-1 by dry weight of basal diet. After a 56-day feeding experiment, the activities of intestinal digestive enzymes and immunity-related enzymes of R. lagowskii on group D-6, D-7, D-8 and D-9 diet were significantly higher than the control (P < 0.05). In molecular experiments, the authors found that the levels of TGF-ß mRNA, IL-10 mRNA, ZO-1 mRNA and claudin-3 mRNA in group D-8 R. lagowskii were significantly higher (P < 0.05) than those of the control and other groups. Furthermore, the levels of IL-1ß and IL-8 mRNA of R. lagowskii on group D-6, D-7, D-8 and D-9 diet were significantly lower than those of the control (P < 0.05). In addition, the authors found that B. amyloliquefaciens LSG2-8 can regulate the intestinal flora balance and improve the intestinal structure of R. lagowskii. In conclusion, B. amyloliquefaciens LSG2-8 can improve the intestinal barrier function of R. lagowskii and can be used as a feed additive in aquaculture.

Unraveling the mechanism of ethyl acetate extract from Prismatomeris connata Y. Z. Ruan root in treating pulmonary fibrosis: insights from bioinformatics, network pharmacology, and experimental validation.

Introduction: Pulmonary fibrosis is a terminal lung disease characterized by fibroblast proliferation, extracellular matrix accumulation, inflammatory damage, and tissue structure destruction. The pathogenesis of this disease, particularly idiopathic pulmonary fibrosis (IPF), remains unknown. Macrophages play major roles in organ fibrosis diseases, including pulmonary fibrosis. The phenotype and polarization of macrophages are closely associated with pulmonary fibrosis. A new direction in research on anti-pulmonary fibrosis is focused on developing drugs that maintain the stability of the pulmonary microenvironment. Methods: We obtained gene sequencing data and clinical information for patients with IPF from the GEO datasets GSE110147, GSE15197, GSE24988, GSE31934, GSE32537, GSE35145, GSE53845, GSE49072, GSE70864, and GSE90010. We performed GO, KEGG enrichment analysis and GSEA analysis, and conducted weighted gene co-expression network analysis. In addition, we performed proteomic analysis of mouse lung tissue. To verify the results of bioinformatics analysis and proteomic analysis, mice were induced by intratracheal instillation of bleomycin (BLM), and gavaged for 14 days after modeling. Respiratory function of mice in different groups was measured. Lung tissues were retained for histopathological examination, Western Blot and real-time quantitative PCR, etc. In addition, lipopolysaccharide, interferon-γ and interleukin-4 were used to induce RAW264.7 cells for 12h in vitro to establish macrophage inflammation and polarization model. At the same time, HG2 intervention was given. The phenotype transformation and cytokine secretion of macrophages were investigated by Western Blot, RT-qPCR and flow cytometry, etc. Results: Through bioinformatics analysis and experiments involving bleomycin-induced pulmonary fibrosis in mice, we confirmed the importance of macrophage polarization in IPF. The analysis revealed that macrophage polarization in IPF involves a change in the phenotypic spectrum. Furthermore, experiments demonstrated high expression of M2-type macrophage-associated biomarkers and inducible nitric oxide synthase, thus indicating an imbalance in M1/M2 polarization of pulmonary macrophages in mice with pulmonary fibrosis. Discussion: Our investigation revealed that the ethyl acetate extract (HG2) obtained from the roots of Prismatomeris connata Y. Z. Ruan exhibits therapeutic efficacy against bleomycin-induced pulmonary fibrosis. HG2 modulates macrophage polarization, alterations in the TGF-ß/Smad pathway, and downstream protein expression in the context of pulmonary fibrosis. On the basis of our findings, we believe that HG2 has potential as a novel traditional Chinese medicine component for treating pulmonary fibrosis.

The immuneoreaction and antioxidant status of Chinese mitten crab (Eriocheir sinensis) involve protein metabolism and the response of mTOR signaling pathway to dietary methionine levels.

To study the effects of dietary methionine on growth performance, immunity, antioxidant capacity, protein metabolism, inflammatory response and apoptosis factors in Chinese mitten crabs (Eriocheir sinensis). Five diets with different methionine levels (0.63%, 0.85%, 1.06%, 1.25% and 1.47%) were fed to E. sinensis for 8 weeks. Results showed that in the 1.25% Met group, both growth performance and feed utilization were significantly increased. The crude protein content of crab muscle in the 1.06% and 1.25% Met groups was significantly higher than that in the control group. The immune and antioxidant enzyme activities, as well as gene expression levels of anti-lipopolysaccharide factor 1 (ALF1), Crustin-1, prophenoloxidase (proPO), cap 'n' collar isoform C (CncC) in 1.25% Met group were significantly higher than other groups. The activities of adenosine deaminase (ADA) and glutamate transaminase (GPT) in serum decreased first and then increased with the increase of methionine content, while the changes of ADA and GPT in hepatopancreas increased first and then decreased. 1.25% Met group exhibited significantly increased levels of GOT, GPT, and ADA compared to the control group. 1.25% Met diet group significantly up-regulated protein synthesis and anti-apoptotic factors, and significantly down-regulated inflammatory and pro-apoptotic factors in hepatopancreas. At 1.25% in the diet, methionine was found to boost E. sinensis growth, muscle protein deposition and immunity, as well as its antioxidant capacity. Combined with the above results, based on the expression of factors involved in the mammalian target of rapamycin (mTOR) signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway, it is proved that methionine can not only promote protein metabolism, improve feed utilization, but also alleviate the inflammatory response and apoptosis caused by oxidative stress in the body.

Meroterpenoids with unknown skeletons from the leaves of Psidium guajava including one anti-inflammatory and anticoagulant compound: psidial F.

Four unknown meroterpenoids named as psidials D-G (1-4) together with 5 known compounds (5-9) had been obtained from the leaves of Psidium guajava. Their absolute structures were elucidated by spectral and calculated methods. Psidials DF (1-3) represented unknown carbon skeleton of the 3,5-diformylbenzyl phloroglucinol-coupled sesquiterpenoid. The possible biosynthetic pathway for 1-3 was postulated. In the bioactivity assay, psidial F (3) was found to possess anti-inflammatory and anticoagulant activities.

Ferrous Bisglycinate Supplementation Modulates Intestinal Antioxidant Capacity via the AMPK/FOXO Pathway and Reconstitutes Gut Microbiota and Bile Acid Profiles in Pigs.

Multi-omics were applied to compare the risks and benefits of ferrous sulfate (FeSO4) and ferrous bisglycinate (FebisGly) in pigs in the current study. The FebisGly group showed reduced triglyceride (TG) and triglyceride/total cholesterol (TG/CHOL) values in the serum and reduced malondialdehyde (MDA) and increased glutathione (GSH) levels in the duodenum. Transcriptome analysis revealed that differentially expressed genes in the duodenum were enriched in oxidative phosphorylation, AMPK, and FOXO signaling pathways between FeSO4 and FebisGly groups. AMPK phosphorylation and FOXO3 protein expressions were significantly increased in the FebisGly group. Bacterial 16S rRNA gene sequence analysis revealed significantly reduced alpha diversity in the FeSO4 group and increased Firmicutes, reduced Bacteroidetes, and Proteobacteria abundances in the FebisGly group. Targeted metabolome revealed notably increased lithocholic acid (LCA), glycolithocholic acid (GLCA), hyodeoxycholic acid (HDCA), ursodeoxycholic acid (UDCA), and glycoursodeoxycholic acid (GUDCA) in the FebisGly group. RDA analysis indicated that Fusobacteria was positively correlated with TG and TG/high-density lipoprotein in the FeSO4 group while Christensenellaceae_R-7_group, Ruminococcaceae_UCG-002, and Ruminococcaceae_UCG-005 were positively correlated with UDCA and GLCA in the FebisGly group. According to the current study, FebisGly improves serum lipid metabolism, modulates intestinal antioxidant capacity via the AMPK/FOXO pathway, and reconstitutes gut microbiota and bile acid profiles in pigs.

Genomic insights revealed the environmental adaptability of Planococcus halotolerans Y50 isolated from petroleum-contaminated soil on the Qinghai-Tibet Plateau.

The Tibetan Plateau niche provides unprecedented opportunities to find microbes that are functional and commercial significance. The present study investigated the physiological and genomic characteristics of Planococcus halotolerans Y50 that was isolated from a petroleum-contaminated soil sample from the Qinghai-Tibet Plateau, and it displayed psychrotolerant, antiradiation, and oil-degraded characteristics. Whole genome sequencing indicated that strain Y50 has a 3.52 Mb genome and 44.7% G + C content, and it possesses 3377 CDSs. The presence of a wide range of UV damage repair genes uvrX and uvsE, DNA repair genes radA and recN, superoxide dismutase, peroxiredoxin and dioxygenase genes provided the genomic basis for the adaptation of the plateau environment polluted by petroleum. Related experiments also verified that the Y50 strain could degrade n-alkanes from C11-C23, and approximately 30% of the total petroleum at 25 °C within 7 days. Meanwhile, strain Y50 could withstand 5 × 103 J/m2 UVC and 10 KGy gamma ray radiation, and it had strong antioxidant and high radical scavengers for superoxide anion, hydroxyl radical and DPPH. In addition, pan-genome analysis and horizontal gene transfers revealed that strains with different niches have obtained various genes through horizontal gene transfer in the process of evolution, and the more similar their geographical locations, the more similar their members are genetically and ecologically. In conclusion, P. halotolerans Y50 possesses high potential of applications in the bioremediation of alpine hydrocarbons contaminated environment.

Maternal iron supplementation during pregnancy affects placental function and iron status in offspring.

BACKGROUND: Iron deficiency and overload during pregnancy damage to maternal and fetal health. Placenta as an organ for the transport of nutrients between mother and fetus protects fetus from the harmful effects of iron deficiency and iron overload through regulation of placental iron homeostasis. METHODS: To determine the effect of dietary iron supplementation during pregnancy on reproduction and the mechanism of placental iron regulation, we designed dietary high iron (HI: 344 mg/kg), medium iron (MI: 40 mg/kg), low iron (LI: 2 mg/kg) groups of pregnant female mice fed ferrous citrate 2 weeks before mating to 18.5 days of gestation. RESULTS: We find dietary iron supplementation during pregnancy effect maternal liver iron, placental iron, hemoglobin and fetal iron. Dietary iron significantly improves reproductive performance as litter weight and fetal weight. Correlation analysis suggest placental iron increased with liver iron, higher and lower liver iron is not conducive to the accumulation of fetal iron, placental iron deficiency and excess reduce litter weight. Placental transcriptome analysis revealed DEGs with the same trend in HI and LI groups compared with MI group, dietary iron may change biology process of ion transport and gland development in placenta. Granzyme may affect the placental trophoblast structure prior to delivery with iron overload uniquely. CONCLUSION: This research highlights the importance of moderate iron supplements in pregnancy due to damage of reproduction by affecting placental function under different dose of maternal iron supplementation.

Correlations of gestational hemoglobin level, placental trace elements content, and reproductive performances in pregnant sows.

The iron status of sows has a great influence on reproductive performance. Iron deficiency reduces reproductive performance and newborn piglet survival rate of sow. The hemoglobin is a potential predictor for the iron status of sows and is convenient for rapid detection in pig farms. However, the relationship between iron status, hemoglobin, placental trace elements, and reproductive performance remains unclear. In this study, the hemoglobin and reproductive performance of more than 500 sows with first to sixth parities at different gestation stages (25, 55, 75, 95, and 110 d of gestation) in two large-scale sow farms were collected, and the content of placental Fe, Zn, Mn, and Cu was analyzed. The results show that hemoglobin levels of sows during pregnancy (days 75, 95, and 110) decreased significantly (P < 0.001). As the parity increases, the hemoglobin levels of sows at days 25 and 55 of gestation and placental mineral element contents including Fe, Zn, Mn, and Cu at delivery decreased (P < 0.05), while the litter size, birth alive, and litter weights increased gradually (P < 0.001). Furthermore, hemoglobin during pregnancy had a negative linear correlation with litter weight and average weight (P < 0.05), and higher hemoglobin at day 25 of gestation may reduce the number of stillbirths (P = 0.05), but higher hemoglobin at day 110 of gestation may tend to be a benefit for the birth (P = 0.01). And there was a significant positive linear correlation between hemoglobin at day 110 of gestation and placental Fe and Mn levels (P = 0.002, P = 0.013). There was also a significant positive linear correlation among Fe, Zn, Mn, and Cu in the placenta (P < 0.001). The levels of Fe, Zn, and Mn in the placental at delivery were positively related to the average weight of the fetus (P = 0.048, P = 0.027, P = 0.047), and placental Cu was linearly correlated with litter size (P = 0.029). Our research revealed that the requirements for iron during gestation were varied in different gestation periods and parities. The feeds should be adjusted according to the gestation periods, parities, or iron status to meet the iron requirements of sows and fetal pigs.

Iron deficiency and iron excess may cause adverse outcomes during pregnancy. In sows' feed, iron is added as ferrous sulfate, ferrous glycine, or other forms to improve their reproductive performance and prevent iron-deficiency anemia in their offspring. However, it is always ineffective and iron-deficiency anemia often occurs in piglets. To explore the iron requirements in pregnant sows, we conducted a large-scale farm study to track the hemoglobin levels, placental trace element content, and reproductive performances of hundreds of sows. The correlation between the hemoglobin levels, placental trace element content, and reproductive performance indicators of sows during pregnancy at different parities was analyzed. We found that pregnancy hemoglobin level of sows decreases during the gestation and varies at different parities. The hemoglobin level of sows during pregnancy was linearly negatively correlated with reproductive performance. The content of iron, zinc, manganese, and copper in the placenta was linearly positively correlated. Our results revealed that iron deficiency or excess in sows' feed may not be conducive to the improvement of reproductive performance, and the optimal iron supplementation dose during pregnancy may depend on the iron status and number of fetuses of sow.

Total coumarin derivates from Hydrangea paniculata attenuate renal injuries in cationized-BSA induced membranous nephropathy by inhibiting complement activation and interleukin 10-mediated interstitial fibrosis.

BACKGROUND: Total coumarins extracted from Hydrangea. Paniculata, Sieb (HP) have showed renal protective effect in several experimental acute and chronic kidney diseases. PURPOSE: The aim of current study is to evaluate renal protective effect of HP against cationized-BSA (c-BSA) induced experimental membranous nephritis (MN), and further investigate its underlying mechanisms. METHODS: Rat MN model was established by intravenous injection of 5 mg c-BSA for consecutive 14 days, and after albuminuria confirmed, HP was orally administrated with 7.5, 15, 30 mg/kg for nine weeks. The renal function was measured and histopathological injuries were observed. RNA sequencing was used to analyze the altered signaling pathways in kidneys. Pharmacokinetics was performed to investigate the pharmacodynamics of major ingredients in HP and possible metabolites. Discover X platform helped to clarify the possible molecular mechanisms of major compound in HP. RESULTS: HP administration could significantly improve the renal function, and ameliorate the dyslipidemia and histopathological injuries. mRNA sequencing demonstrated that HP had anti-inflammation and anti-fibrosis effects possible through down-regulating the complement activation and PI3K-AKT pathways. Pharmacokinetics demonstrated that skimmin and 7-hydoxycoumarin (7-HC) were major compound or metabolite in plasma after oral administration. Based on Discover X platform, we confirmed that skimmin and 7-HC inhibited the   IL10 production by inflammatory macrophages through blocking PI3K-AKT and NFκB signaling pathways. Finally, we demonstrated that HP protected tubulointerstitium from complement attack by reducing the C3 self-production and auto-cleavage in tubular cells. CONCLUSIONS: HP has a renal protective effect, and its drug development may provide one alternative strategy to treat immune-mediated nephropathy.

Effects of dietary Astragalus Propinquus Schischkin polysaccharides on growth performance, immunological parameters, antioxidants responses and inflammation-related gene expression in Channa argus.

The present study investigated the effects of dietary Astragalus Propinquus schischkin polysaccharides on growth, immune responses, antioxidants responses and inflammation-related genes expression in Channa argus. Channa argus were randomly divided into 5 groups and fed 5 levels diets of A. propinquus schischkin polysaccharides (0, 250, 500, 1000 and 2000 mg/kg) for 56 days. The results showed, dietary A. propinquus schischkin polysaccharides addition can increase the final body weight, weight gain and specific growth rate, decrease the feed conversion ratio of Channa argus. And dietary A. propinquus schischkin polysaccharides supplementation can increase the levels of serum superoxide dismutase, catalase, glutathione peroxidase, lysozyme, complement 3, complement 4, immunoglobulin M and alkaline phosphatase, decrease the levels of serum malondialdehyde, cortisol, aspartate aminotransferase and glutamic-pyruvic transaminase. Furthermore, dietary A. propinquus schischkin polysaccharides can decrease the gene expression levels of interleukin-1ß, interleukin-, tumor necrosis factor-α and nuclear factor-κB, increase the gene expression levels of glucocorticoid receptor in liver, spleen, kidney, intestine. To sum up, dietary A. propinquus schischkin polysaccharides can accelerate growth, enhance immune responses and antioxidants responses, regulate inflammation-related genes expression in Channa argus and the optimum amount is 1000 mg/kg.

New amide alkaloids and carbazole alkaloid from the stems of Clausena lansium.

Five unreported alkaloids including four amide alkaloids (1a, 2a, 3a, and 3b) and one carbazole alkaloid (4) with two known compounds (1b, 2b) were obtained from the stems of Clausena lansium. Their structures were demonstrated by spectroscopic experiments. And the absolute configurations of compounds 1a, 1b, 2b, and 3b were determined by single X-ray diffraction analysis. The neuroprotection assay showed that compound 4 had moderate inhibition effect on PC12 cells induced by serum withdrawal at the concentration of 10 µM. And compounds 1a and 4 had weak protective effects on primary neurons against oxygen glucose deprivation injury at the concentration of 10 µM.

Chemical constituents of Psidium guajava leaves and their antibacterial activity.

Seven undescribed compounds, namely (+)-psiflavanone A, (-)-psiflavanone A, (+)-psiflavanone B, (-)-psiflavanone B, (+)-psiketide, (-)-psiketide, and psidinone, were isolated and chirally separated from the 95%-ethanol extract of Psidium guajava leaves. (+)/(-)-Psiflavanone A and (+)/(-)-psiflavanone B are two pairs of rare enantiomeric C-benzoylated flavanones isolated from the title plant for the first time. (+)/(-)-Psiketide are a pair of enantiomeric aromatic polyketides, and psidinone is the first example of a C18 phenanthrenediquinone with an angle-type 6/6/6 tricyclic skeleton. Their structures were identified by extensive analysis of HRESIMS, UV, IR, NMR, and calculated electronic circular dichroism (ECD) data. Particularly, the structures of (+)-psiflavanone A, (-)-psiflavanone A, (+)-psiflavanone B, and psidinone were further confirmed by X-ray diffraction. Psidinone exhibited antibacterial activity against Staphylococcus aureus, Staphylococcus epidermidis, and Mycobacterium Smegmatis mc2 155, with minimum inhibitory concentrations (MICs) of 16, 8, and 0.5 µM, respectively. These results not only highlight the chemical diversity and biological activity of P. guajava but are also expected to pave way for its further expansion to other applications in future.

Nine prenylated acylphloroglucinols with potential anti-depressive and hepatoprotective activities from Hypericum scabrum.

In our screening program for new biologically active secondary metabolites, nine new polycyclic polyprenyled acylphloroglucinols, hyperscabins D-L, together with three known compounds, were obtained from the aerial parts of Hypericum scabrum. The chemical structures of 1-9 were characterized by extensive spectroscopic analyses, nuclear magnetic resonance calculation with DP4+ probability analysis, and the electronic circular dichroism spectra were calculated. Compound 1 was an unusual prenylated acylphloroglucinol decorated with a 5-oxaspiro [4,5] deca-1,9-dione skeleton. Compound 2 was a newly identified spirocyclic polyprenylated acylphloroglucinol possessing a rare 5,5-spiroketal segment. Compounds 3, 8, and 10 (10 µM) exhibited pronounced hepatoprotective activity against d-galactosamine-induced WB-F344 cell damage in vitro assays. All test compounds (1, 3, and 7-12) demonstrated potential inhibitory effects at 10 µM against noradrenalinet ([3H]-NE) reuptake in rat brain synaptosome.

Dietary supplementation with N-carbamylglycinate (CGly) improved feed source proline absorption and reproductive performance in sows.

Nutrient requirements are increased in the late-gestation period due to the faster growth of the foetal-placental unit and maternal erythrocyte mass. Glycine, proline and arginine are important amino acids that could improve foetal growth and development. The present study aims to investigate the effects of a derivative of glycine (N-carbamylglycinate, CGly) on the amino acid profiles and reproductive performances of late gestation sows. Thirty-two multiparous gestating sows (∼d 80) were selected, and randomly assigned into two groups: (1) control and (2) treatment (CGly, 800 mg kg-1) from day 85 of gestation to parturition. The serum amino acid profiles at day 110 of gestation and reproductive performance were investigated. The results showed that dietary supplementation of CGly in the late gestation period significantly improved the levels of glycine (p < 0.05) and proline (p < 0.01) in the serum of the perinatal sows, and thereafter improved the litter birth weights (p < 0.05) and number born alive (p < 0.1). Based on the in vitro studies, the improvement of proline levels is probably due to the induced expression of SLC6A20 and SLC38A2. Further studies should focus on the details of amino acid absorption, especially the competitive and cooperative absorption processes for different amino acids and derivatives.

Bioactive flavonoid dimers from Chinese dragon's blood, the red resin of Dracaena cochinchinensis.

Seven flavonoid dimers, biflavocochins A-G, together with six known compounds were isolated from the red resins of Dracaena cochinchinensis (Chinese dragon's blood). Their structures were elucidated based on extensive spectroscopic analysis. The absolute configurations of 1-7 was assigned by experimental and quantum chemical calculated ECD spectra, and that of 4 was further established by X-ray diffraction analysis using Cu Kα radiation. Compounds 1-3 are novel dimers of homoisoflavonoid and dihydrochalcone with a unique dibenzopyran ring. Compounds 2, 6, 7 exhibited moderate PTP1B inhibitory activities in an enzyme assay. Compound 1 showed neuroprotective effect on serum deficiency-induced cellular damage in PC12 cells.

Effect of sub-chronic exposure to selenium and astaxanthin on Channa argus: Bioaccumulation, oxidative stress and inflammatory response.

Selenium (Se) is the most common micronutrient and that becomes toxic when present at higher concentrations in aquatic environments. Astaxanthin (AST) has been documented to possess antioxidant and anti-inflammatory properties. The aim of this study was to explore the potential of dietary AST and Se exposure on oxidative stress, and inflammatory response in Channa argus. After acclimation, 540 fish were randomly distributed into nine groups housed in twenty-seven glass tanks. The fish were exposed for 8 weeks to waterborne Se at 0, 100 and 200 µg L-1 or dietary AST at 0, 50 and 100 mg kg-1. The results shown that Se accumulation in the kidney, liver, spleen, intestine and gill were significantly increased following Se exposure, dietary 50 and 100 mg kg-1 AST supplementation decreased the accumulation of Se in the kidney, liver, spleen, and intestine. In addition, AST supplementation can decrease oxidative stress and inflammatory response in the liver and spleen following exposure to waterborne Se. These results indicate that AST has the potential to alleviate the effects of Se toxicity in C. argus.

Novel nitric oxide-releasing derivatives of triptolide as antitumor and anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies.

A series of novel triptolide/furoxans hybrids were designed and synthesized as analogues of triptolide, which is a naturally derived compound isolated from the thunder god vine (Tripterygium wilfordii Hook. F). Some of these synthesized compounds exhibited antiproliferative activities in the nanomolar range. Among them, compound 33 exhibited both good antiproliferative activity and NO-releasing ability and the acute toxicity of compound 33 decreased more than 160 times (LD50 = 160.9 mg/kg) than triptolide. Moreover, compound 33 significantly inhibited the growth of melanoma at a low dose (0.3 mg/kg) and showed strong anti-inflammatory activity in vitro and in vivo. These results indicate that compound 33 could be a promising candidate for further study.

Presence of White Matter Lesions Associated with Diabetes-Associated Cognitive Decline in Male Rat Models of Pre-Type 2 Diabetes.

BACKGROUND The aim of this study was to determine the association between white matter lesions (WML) and diabetes-associated cognitive decline (DACD) in rat models of type 2 diabetes (T2DM). MATERIAL AND METHODS Sixty Sprague-Dawley male rats were divided into 4 groups: control, control+metformin, T2DM, and T2DM+metformin groups. The T2DM groups were fed a diet high in fat and glucose to induce impaired glucose tolerance (IGT) and then were injected with streptozotocin to induce T2DM. The Morris water maze test was used to evaluate cognitive function. Brain diffusion tensor imaging scans were performed for WML. The expression of myelin basic protein (MBP), oligodendrocyte transcription factor 1 (OLIG1), and OLIG2 (markers of brain damage and repair) was determined using immunofluorescence. After IGT, the fractional anisotropy (FA) values of the right thalamus area were significantly lower in both T2DM groups compared with controls. RESULTS Eight weeks after streptozotocin injection, the FA values of the thalamus were lower in the T2DM (bilateral thalamus) group and T2DM+metformin (left thalamus) group than in controls, while the FA values in the left thalamus area were lower in the T2DM+metformin group than in the control and control+metformin groups. The maze escape latency was longer and the number of rats passing through the platform was smaller in the T2DM and T2DM+metformin groups than in the control group. MBP levels were lower and OLIG1 and OLIG2 levels were higher in both T2DM groups than in controls. CONCLUSIONS WML is associated with DACD and appears before the onset of T2DM and signs of DACD and plays a role in diabetes-associated cognitive decline. Metformin reduces WMLs but does not rescue cognitive dysfunction.