Two new neolignans and an indole alkaloid from the stems of Nauclea officinalis and their biological activities.

A pair of new diastereoisomers neolignans (1-2) and a new alkaloid (7) were isolated from the stems of Nauclea officinalis: naucleaoxyneolignoside A (1), naucleaoxyneolignoside B (2), (2S,3S)-javaniside (7), together with nine known compounds, 2S-3,3-di-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol (3), threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol (4), nauclefine (5), angustidine (6), naucleoxoside A (8), naucleoxoside B (9), angustoline (10), (3S,19S)-3,14-dihydroangustoline (11), and (3S,19R)-3,14-dihydroangustoline (12).The structures of 1, 2 and 7 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparison of their data with those reported in the literature. The absolution configurations of 1, 2, 7,11 and 12 were confirmed by the quantum chemical CD calculation method. Compounds 1-9 showed weak to moderate inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC50 values comparable to that of dexamethasone. In addition, compounds 1-9 were evaluated for the antibacterial and cytotoxic effects, and the results revealed that these compounds showed no anti-bacterial activity, and compounds 3-6 showed modest cytotoxic activity.

A comparative study of bacterial diversity based on effects of three different shade shed types in the rhizosphere of Panax quiquefolium L.

BACKGROUND: Shading is an important factor affecting the cultivation of American ginseng, as it influences crop quality and yield. Rhizosphere microorganisms are also crucial for normal plant growth and development. However, whether different shade types significantly change American ginseng rhizosphere microorganisms is unknown. METHODS: This study evaluated the rhizosphere soils of American ginseng under traditional, high flag and high arch shade sheds. High-throughput 16S rRNA gene sequencing determined the change of rhizosphere bacterial communities. RESULTS: The microbial diversity in rhizosphere soils of American ginseng significantly changed under different shading conditions. The bacteria diversity was more abundant in the high arch shade than flat and traditional shades. Different bacterial genera, including Bradyrhizobium, Rhizobium, Sphingomonas, Streptomyces and Nitrospira, showed significantly different abundances. Different shading conditions changed the microbial metabolic function in the American ginseng rhizosphere soils. The three types of shade sheds had specific enriched functional groups. The abundance of ATP-binding cassette (ABC) transporters consistently increased in the bacterial microbiota. These results help understand the influence of shading systems on the rhizosphere microecology of American ginseng, and contribute to the American ginseng cultivation.

Simultaneous determination of 11 alkaloids in rat plasma by LC-ESI-MS/MS and a pharmacokinetic study after oral administration of total alkaloids extracted from Naucleaofficinalis.

ETHNOPHARMACOLOGICAL RELEVANCE: Nauclea officinalis, a widely used Li medicine, has been used for the treatment of cold, fever, bronchitis, pneumonia, acute tonsillitis, and other ailments. Modern pharmacological studies have demonstrated that the most abundant and active components in N. officinalis are alkaloids, which possess various biological properties such as antibacterial and antitumor activities. AIM OF THE STUDY: To investigate the phytochemical profile of a selected group of alkaloids from the N. officinalis total alkaloids, and to determine the chemical profile of the alkaloids extracted from rat plasma. Further investigation was conducted to determine the pharmacokinetic behaviors of 11 selected major alkaloids, including pumiloside, naucleoxoside A, naucleoxoside B, nauclefine, angustidine, angustoline, (3S,19S)-3,14-dihydroangustoline,[α]D20: (-)191°, (3S,19R)-3,14-dihydroangustoline, [α]D20: (-) 294.7°, strictosamide, angustine, and 3,14-dihydroangustine. MATERIALS AND METHODS: N. officinalis total alkaloids were extracted with 79% ethanol and enriched with AB-8 macroporous resin. The phytochemical profile of alkaloids from the N. officinalis total alkaloids and the chemical profile of the alkaloids extracted from rat plasma were first analyzed by UPLC-Q-TOF-MS/MS. A simple, convenient, and sensitive LC-ESI-MS/MS method was subsequently developed and validated for the simultaneous determination of major active alkaloids in rat plasma after oral administration of N. officinalis total alkaloids. After addition of an internal standard (verapamil), plasma samples were pretreated first by protein precipitation with methanol and then underwent liquid-liquid extraction with ethyl acetate. Chromatographic separation was achieved using a Waters BEH C18 column (2.1 mm × 100 mm, 1.7 µm) at 30 °C, with gradient elution using a mobile phase consisting of 0.1% formic acid aqueous solution (A) and acetonitrile (B), a flow rate of 0.2 mL/min, and a total run time of 30 min. The detection was performed using an electrospray ionization triple quadrupole tandem mass spectrometer with multiple reaction monitoring and positive ionization mode. RESULTS: Based on the fragmentation patterns of 11 authentic alkaloids and previous reports, 55 alkaloids were identified or tentatively identified in the N. officinalis total alkaloids. Among them, 25 alkaloids were absorbed through the gastrointestinal tract in rats after administration of the N. officinalis total alkaloids. The 11 alkaloids were selected for quantitative analysis. The established quantitative method was fully validated and proved to be sensitive and specific. Satisfactory linearity of the 11 alkaloids obtained in the respective concentration ranges (r > 0.9931). The lower limits of quantification for strictosamide was 20.86 ng/ml, and the other ten alkaloids were all less than 4.47 ng/ml in rat plasma. The intra-and inter-day precision was less than 15% for all 11 alkaloids in terms of relative standard deviation, and the accuracies ranged from -11.4% to 11.1% in terms of relative error. Extraction recovery, matrix effect, and stability were within the required limits in rat plasma. CONCLUSION: The validated method was successfully applied to investigate the pharmacokinetics of the 11 alkaloids in rat plasma after oral administration of N. officinalis total alkaloids. Eleven alkaloids were rapidly absorbed to achieve a maximum plasma concentration with Tmax from 0.25 h to 1.5 h after oral administration. The pharmacokinetic parameters and plasma concentration-time profiles will prove valuable in pre-clinical and clinical investigations on the disposition of N. officinalis total alkaloids.

Challenges of pectic polysaccharides as a prebiotic from the perspective of fermentation characteristics and anti-colitis activity.

Several studies are described that contribute to the systematic exploration of new aspects of digestion, fermentation, and biological activities of pectic polysaccharides (PPS) leading to a better understanding of prebiotics. Inflammatory bowel disease (IBD) is thought to be associated with the dysbacteriosis induced by different environmental agents in genetically susceptible persons. PPS are considered as an indispensable gut-microbiota-accessible carbohydrate that play a dominant role in maintaining gut microbiota balance and show a better effect in ameliorating IBD than some traditional prebiotics. The aim of this review is to summarize the fermentation characteristics of PPS, highlight its role in improving IBD, and propose a view that PPS may be a new and effective prebiotic.

[Mechanism research of curcumin on cancer cells based on cell metabolic profiling].

In this study, gas chromatography coupled with mass spectrometry(GC-MS) was used to analyze the changes of 12 kinds of cancer cells treated by curcumin. The related differential metabolites were screened and the metabolic pathways were analyzed to explore the anti-tumor mechanism of curcumin. Methyl thiazol tetrazolium(MTT) assay was used to detect the 50% inhibiting concentration(IC_(50)) of curcumin on 12 human tumor cells. After treatment with curcumin for 48 h, the cells were collected and analyzed by GC-MS, followed by pathway analysis and multivariate data analysis including principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA) and One-way analysis of variance(ANOVA),etc. Overall, 34 metabolites showed significant concentration changes after intervention for 48 h, mainly involving multiple metabolic pathways, including lysine degradation, glycine, serine and threonine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, lysine biosynthesis. In this study, the anti-tumor mechanisms of curcumin interfering with energy metabolism, amino acid metabolism, microtubule system, protein synthesis and oxidative stress response of tumor cells were analyzed from the perspective of metabolism, providing a new reference for further tumor pharmacology study.

The Effects of Tai Chi Intervention on Healthy Elderly by Means of Neuroimaging and EEG: A Systematic Review.

Aging is a process associated with a decline in cognitive and motor functions, which can be attributed to neurological changes in the brain. Tai Chi, a multimodal mind-body exercise, can be practiced by people across all ages. Previous research identified effects of Tai Chi practice on delaying cognitive and motor degeneration. Benefits in behavioral performance included improved fine and gross motor skills, postural control, muscle strength, and so forth. Neural plasticity remained in the aging brain implies that Tai Chi-associated benefits may not be limited to the behavioral level. Instead, neurological changes in the human brain play a significant role in corresponding to the behavioral improvement. However, previous studies mainly focused on the effects of behavioral performance, leaving neurological changes largely unknown. This systematic review summarized extant studies that used brain imaging techniques and EEG to examine the effects of Tai Chi on older adults. Eleven articles were eligible for the final review. Three neuroimaging techniques including fMRI (N = 6), EEG (N = 4), and MRI (N = 1), were employed for different study interests. Significant changes were reported on subjects' cortical thickness, functional connectivity and homogeneity of the brain, and executive network neural function after Tai Chi intervention. The findings suggested that Tai Chi intervention give rise to beneficial neurological changes in the human brain. Future research should develop valid and convincing study design by applying neuroimaging techniques to detect effects of Tai Chi intervention on the central nervous system of older adults. By integrating neuroimaging techniques into randomized controlled trials involved with Tai Chi intervention, researchers can extend the current research focus from behavioral domain to neurological level.

Discovery of aminocyclohexene analogues as selective and orally bioavailable hNav1.7 inhibitors for analgesia.

hNav1.7 receives a lot of attention owing to its attractive mechanism of action in pain processing pathway. We have previously reported our design of a novel series of tetrahydropyridine analogues towards hNav1.7 selective inhibitors. Herein, we disclose further efforts to the optimization of hit compound (-)-6, which led to the identification of aminocyclohexene analogues (-)-9 and (-)-17 with good potency, high selectivity, and minimal CYP inhibition. Both compounds (-)-9 and (-)-17 demonstrated improved pharmacokinetic profiles in rats, and robust efficacy in rat formalin-induced nociception and spinal nerve ligation (SNL) models.

The injury of fine particulate matter from cooking oil fumes on umbilical cord blood vessels in vitro.

Cooking oil fumes (COFs) derived PM2.5 is the major source of indoor air pollution in Asia. For this, a pregnant rat model within different doses of cooking oil fumes (COFs) derived PM2.5 was established in pregnancy in our research. Our previous studies have showed that exposure to COFs-derived PM2.5 was related to adverse pregnancy outcomes. However, the mechanisms of signaling pathways remain unknown. Therefore, this study aimed to investigate the underlying mechanisms induced by COFs-derived PM2.5 injury on umbilical cord blood vessels (UCs) in vitro. Exposure to COFs-derived PM2.5 resulted in changing the expression of eNOS, ET-1, ETRA, and ETRB. In additions, western blot analysis indicated that the HIF-1α/iNOS/NO signaling pathway and VEGF/VEGFR1/iNOS signaling pathway were involved in UCs injury triggered by COFs-derived PM2.5. In conclusion, our data suggested that exposure to COFs-derived PM2.5 resulted in increasing of oxidative stress and inflammation, as well as dysfunction of UCs.

A study on the inhibitory effect of Radix Semiaquilegiae extract on human hepatoma HEPG-2 and SMMC-7721 cells.

The main objective of this paper was to investigate the extraction process of ethanol extract of Radix Semiaquilegiae, as well as its inhibitory activity on human hepatoma HepG-2 and SMMC-7721 cells, and to compare the inhibitory effects of different concentrations of ethanol extracts against these two hepatoma cells. Ethanol reflux extraction and ultrasound-assisted extraction with ethanol at room temperature were used in the extraction process, and MTT assay was mainly used in the activity experiment to perform in-vitro anti HepG-2 and SMMC-7721 cell activity screening of ethanol extract, and to calculate the cell inhibition rates of the extracts. The results showed that among the two types of extracts, ethanol reflux extract had more superior antitumour activity to that of the ultrasonic extract, but all of the extracts obtained had certain anti-cancer activities, and the anti-proliferative activity increased with the increase of concentration.