Gut microbiota-derived 5-hydroxyindoleacetic acid from pumpkin polysaccharides supplementation alleviates colitis via MAPKs-PPARγ/NF-κB inhibition.

Polysaccharides from Pumpkin (Cucurbita moschata Duchesne) (PPs) have many pharmacological activities, including anti-oxidant, immune, and intestinal microbiota regulation. These activities have provided some reminders of its potential therapeutic effect on ulcerative colitis (UC), but this has not yet been confirmed. This study preliminarily confirmed its significant anti-UC activity superior to Salicylazosulfapyridine. The average molecular weight of PPs was 3.10 × 105 Da, and PPs mainly comprised Mannose, Rhamnose, Galacturonic acid, Galactosamine, Glucose, and Xylose with molar ratios of 1.58:3.51:34.54:1.00:3.25:3.02. PPs (50, 100 mg/kg) could significantly resist dextran sodium sulfate induced UC on C57BL/6 mice by improving gut microbiota dysbiosis, such as the changes of relative abundance of Bacteroides, Culturomica, Mucispirillum, Escherichia-Shigella, Alistipes and Helicobacter. PPs also reverse the abnormal inflammatory reaction, including abnormal level changes of TNF-α, IFN-γ, IL-1ß, IL-4, IL-6, IL-10, and IL-18. Metabolomic profiling showed that PPs supplementation resulted in the participation of PPAR and MAPK pathways, as well as the increase of 5-hydroxyindole acetic acid (5-HIAA) level. 5-HIAA also exhibited individual and synergistic anti-UC activities in vivo. Furthermore, combination of PPs and 5-HIAA could also elevate the levels of PPARγ in nuclear and inhibit MAPK/NF-ĸB pathway in the colon. This study revealed that PPs and endogenous metabolite 5-HIAA might be developed to treat UC.

[Mechanism of Qiwei Guibao Granules in treatment of premature ovarian failure based on proteomics].

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.

The Mechanism and Experimental Validation of Forsythoside A in the Treatment of Male Infertility Were Analyzed Based on Network Pharmacology and Molecular Docking.

Chinese medicine extracts are currently the hotspot of new drug research and development. Herein, we report the mechanism of action of the traditional Chinese medicine extract Forsythiaside A in the treatment of male infertility and experimental verification. We first obtained 95 intersection genes between the target protein of Forsythiaside A and the target genes of male infertility and screened 13 key genes. In molecular docking, Forsythiaside A can each have a higher total docking score with 12 key genes and have a better combination. These 95 intersection genes are mainly related to biological processes such as response to peptide hormone, response to oxidative stress, and participation in the oxidative stress of the forkhead box O (FoxO) signaling pathway. Therefore, we use ornidazole to induce an experimental model of oligoasthenospermia in rats and use different concentrations of Forsythiaside A to intervene. We proved that the semen quality and superoxide dismutase (SOD) activities of model group rats were significantly lower than those of the blank group, and semen quality and SOD activities of the low-dose group and high-dose group were significantly higher than those of the model group. The malondialdehyde (MDA) level of model group rats was significantly higher than that of blank group, while the MDA levels of the low-dose group and high-dose group were significantly lower than that of the model group. Forsythoside A is a potential drug substance for male infertility and improves the semen quality, MDA levels, and SOD activities of rats with oligoasthenospermia.

[Mechanism of paeonol combined with paeoniflorin against myocardial ischemia injury:based on proteomics].

The study aims to investigate the effect of the compatibility of paeonol and paeoniflorin(hereinafter referred to as the compatibility) on the expression of myocardial proteins in rats with myocardial ischemia injury and explore the underlying mechanism of the compatibility against myocardial ischemia injury. First, the acute myocardial infarction rat model was established by ligation of the anterior descending branch of the left coronary artery. The model rats were given(ig) paeonol and paeoniflorin. Then protein samples were collected from rat cardiac tissue and quantified by tandem mass tags(TMT) to explore the differential proteins after drug intervention. The experimental results showed that differential proteins mainly involved phagocytosis engulfment, extracellular space, and antigen binding, as well as Kyoto encyclopedia of genes and genomes(KEGG) pathways of complement and coagulation cascades, syste-mic lupus erythematosus, and ribosome. In this study, the target proteins and related signaling pathways identified by differential proteomics may be the biological basis of the compatibility against myocardial ischemia injury in rats.

Feruloyl sucrose derivatives from the root of Xerophyllum tenax.

A phytochemical investigation of the roots of Xerophyllum tenax led to the isolation of three undescribed feruloyl sucrose derivatives along with two known feruloyl sucrose derivatives, heloniosides A and B. This is the first report of their occurrence in the genus Xerophyllum and the family Melanthiaceae. The structures of these compounds were elucidated on the basis of chemical and spectroscopic analysis including 1D and 2D NMR and analysis of MS-MS fragmentation.

Biflavonoids from Juniperus oblonga inhibit organic anion transporter 3.

Organic anion transporters (OATs in humans, Oats in rodents) play an important role in the distribution and excretion of numerous endogenous metabolic products and exogenous organic anions, including a host of widely prescribed drugs. Their ligand recognition is also important for drug therapy and development. In this study, the n-butanol and dichloromethane soluble fractions of Juniperus oblonga were found to inhibit OAT3 in vitro and three biflavonoids were found to be responsible for this activity. One of these compounds, amentoflavone exhibited stronger inhibition than probenecid, a known strong inhibitor of OAT3. Biological characterization of amentoflavone in vivo also showed inhibition of Oat3. Preliminary observations of structure-activity relationships suggest that the biflavonoids are more potent inhibitors of this transporter than their corresponding monomer, and that methylation of even a single hydroxyl group results in a substantial decrease in activity. This greater potency of the biflavonoids may indicate the need for a more in-depth investigation of the distribution of biflavonoids in plants used as foodstuffs and herbal medicines, due to their potential for causing interactions with OAT3 substrate drugs.

The effects of apple pomace, bentonite and calcium superphosphate on swine manure aerobic composting.

The effects of additives such as apple pomace, bentonite and calcium superphosphate on swine manure composting were investigated in a self-built aerated static box (90 L) by assessing their influences on the transformation of nitrogen, carbon, phosphorous and compost maturity. The results showed that additives all prolonged the thermophilic stage in composting compared to control. Nitrogen losses amounted to 34-58% of the initial nitrogen, in which ammonia volatilization accounted for 0.3-4.6%. Calcium superphosphate was helpful in facilitating composting process as it significantly reduced the ammonia volatilization during thermophilic stage and increased the contents of total nitrogen and phosphorous in compost, but bentonite increased the ammonia volatilization and reduced the total nitrogen concentration. It suggested that calcium superphosphate is an effective additive for keeping nitrogen during swine manure composting.

[Relationship of Chinese medicine syndrome with endothelium-dependent vasodilatation function and carotid intima-media thickness in patients with hypertensive disease].

OBJECTIVE: To explore the relationship of Chinese medicine (CM) syndrome with carotid intima-media thickness (CIMT) and endothelium-dependent vasodilatation function (EDVF) in patients with hypertensive disease (HD) for providing an objective basis of syndrome differentiation in HD patients. METHODS: Color Doppler's ultrasound was used to measure the endothelium-dependent flow-mediated dilation (FMD) of brachial artery and carotid intima-media thickness (CIMT) in 60 HD patients (the HD group) and 30 normal controls (the control group). And the relationship of the outcomes with Chinese medicine syndrome types in patients was analyzed statistically. RESULTS: FMD was lower and CIMT was higher in HD patients of all syndrome types than those in the control group respectively (P<0.01). Comparison between patients of different syndrome types showed that FMD was higher in patients of Gan-fire exuberance type and yin-deficiency and yang-hyperaction type than in those of both yin-yang deficiency type and phlegm-dampness stagnancy type (P<0.01, P<0.05), while CIMT in patients of Gan-fire exuberance type was the lowest in all types, and that in yin-deficiency and yang-hyperaction type was lower than in yin-yang deficiency type (P<0.01). CONCLUSION: CIMT and FMD may be used as a reference index for CM syndrome differentiation in HD patients.