Iridoid-glycoside isolation and purification from Premna fulva leaves.

Premna fulva Craib, rich in iridoid glycosides, is widely used to treat periarthritis, osteoproliferation, pain, and other diseases. However, no studies have reported effective purification methods for obtaining iridoid glycosides as active materials. This paper describes an efficient strategy for separating iridoid glycosides from Premna fulva leaves using high-speed counter-current chromatography and preparative high-performance liquid chromatography. A two-phase solvent system, ethyl acetate/n-butanol/water (7.5:2.5:10, v/v), was selected for high-speed counter-current chromatography separation. The proposed method effectively separated and purified four iridoid glycosides and four lignans, including three new iridoid glycosides (4-6) and five known compounds (1-3, 7, 8), from Premna fulva leaves, indicating that high-speed counter-current chromatography combined with prep-HPLC can efficiently isolate catalpol derivatives from the genus Premna. Additionally, the in vitro anti-inflammatory activities of all isolated compounds were analyzed using lipopolysaccharide-stimulated RAW 264.7 cells, and the results indicated that six compounds (1 and 3-7) exhibited potential anti-inflammatory activities.

The Triterpenoids from Munronia pinnata and Their Anti-Proliferative Effects.

Six new tirucallane-type triterpenoids, named munropenes A-F (1-6), were extracted from the whole plants of Munronia pinnata using a water extraction method. Their chemical structures were determined based on detailed spectroscopic data. The relative configurations of the acyclic structures at C-17 of munropenes A-F (1-6) were established using carbon-proton spin-coupling constants (2,3JC,H) and inter-proton spin-coupling constants (3JH,H). Furthermore, the absolute configurations of munropenes A-F (1-6) were determined through high-performance liquid chromatography (HPLC), single-crystal X-ray diffraction, and electronic circular dichroism (ECD) analyses. The antiproliferative effects of munropenes A-F were evaluated in five tumor cell lines: HCT116, A549, HepG2, MCF7, and MDAMB. Munropenes A, B, D, and F (1, 2, 4, and 6) inhibited proliferation in the HCT116 cell line with IC50 values of 40.90, 19.13, 17.66, and 32.62 µM, respectively.

Design and synthesis of mogrol derivatives modified on a ring with anti-inflammatory and anti-proliferative activities.

A class of novel mogrol derivatives modified on A ring were synthesized. The screening result showed that indole-fused derivatives exhibited lower toxicity and better anti-inflammatory activity in LPS-induced RAW 264.7 cells model than mogrol and other compounds. Derivative B8 exerted superior inhibitory result of NO production (IC50 = 5.05 µM) and inhibitory ability of TNF-α and IL-6 secretion to mogrol through iNOS/NF-κB pathway. Besides, the CCK8 assay was performed to evaluate their anti-proliferative activity against non-small cell lung cancer including A549, NCI-H460, H1299 and H1975 cells. Compared with mogrol, compound B8 showed moderate anti-proliferative activities against A549 and H1975 cells, while derivatives bearing α, ß-unsaturated ketone scaffold displayed broad-spectrum growth inhibition against four cell lines. Among them, compound A9 showed 12-fold higher activity than mogrol against H1299 and H1975 cells. The suppressive effect on expression level of p-p65 might account for the compound A9-induced growth inhibition and cell cycle arrest at G1 phase.

Synthesis and anti-inflammatory activity of mogrol derivatives modified at C24 site.

Mogrol, the aglycone of well-known sweeter mogrosides, shows potent anti-inflammatory activity. In this study, forty-two mogrol derivatives bearing various pharmacophores with oxygen or nitrogen atoms were designed and synthesized via structural modification at C24 site, and their anti-inflammatory activity were screened against lipopolysaccharide (LPS)-induced RAW264.7 cells. Compared with mogrol, most of derivatives exhibited stronger inhibition of NO production without cytotoxicity. In particular, compound B5 that contained an indole motif effectively suppressed the secretion of inflammatory mediators including TNF-α and IL-6, and inhibited the expression levels of TLR4, p-p65 and iNOS proteins. Molecular docking showed that the active B5 interacted with amino acid residues of iNOS protein through π-π stacking and hydrophobic interactions with binding affinity value of -12.1 kcal/mol, which was much stronger than mogrol (-8.9 kcal/mol). These results suggest that derivative B5 is a promising anti-inflammatory molecule and the strategy of hybridizing indole skeleton on mogrol is worthy for further attention.

The bioactive amide alkaloids from the stems of Piper nigrum.

Piper nigrum is an important aromatic plant, and its fruits (black and white pepper) are commonly used as food additives and spices. However, its stems were disposed as wastes. This research comprehensively investigated bioactive alkaloids of the stems, eight new dimeric amide alkaloids and eight known compounds were obtained. All obtained compounds showed excellent anti-inflammatory activity. Additionally, the dimeric amide alkaloids enhanced the anticancer effect of paclitaxel against cervical cancer cells. These results demonstrate that the stems of P. nigrum could be the sustainable source of bioactive alkaloids for development and utilization in the food and health fields.

Travel route safety estimation based on conflict simulation.

With the aim of providing travelers information about the safety levels of selectable routes, it is necessary to develop a method that can properly estimate the safety of alternative travel routes. This paper proposes a conflict-based approach for travel route safety estimation (TRSE). It is developed on the basis of the classical safety evaluation model where both the amount of exposure to safety risk and the risk under unit exposure are measured to estimate the route safety. A combination of a set of dynamic and static factors related to traffic flow characteristics and roadway features are selected to estimate conflict exposure and potential conflict risk. A route-based method is employed where two parallel estimations of conflict are conducted for both the component segments links and intersection turning links. Three machine learning models (i.e., random forest, k-nearest neighbor, and support vector machine) are tested in conflict risk estimation. A fuzzy reasoning process based on the fuzzy logic algorithm is employed to conduct the route safety estimation. The proposed TRSE is tested on a four-horizontal and six-vertical network extracted from a real road network in China. Conflict simulation results were obtained by Vissim and SSAM tools. The results illustrate the practicability and effectiveness of the proposed TRSE approach.

Accurate extraction of surface water in complex environment based on Google Earth Engine and Sentinel-2.

To realize the accurate extraction of surface water in complex environment, this study takes Sri Lanka as the study area owing to the complex geography and various types of water bodies. Based on Google Earth engine and Sentinel-2 images, an automatic water extraction model in complex environment(AWECE) was developed. The accuracy of water extraction by AWECE, NDWI, MNDWI and the revised version of multi-spectral water index (MuWI-R) models was evaluated from visual interpretation and quantitative analysis. The results show that the AWECE model could significantly improve the accuracy of water extraction in complex environment, with an overall accuracy of 97.16%, and an extremely low omission error (0.74%) and commission error (2.35%). The AEWCE model could effectively avoid the influence of cloud shadow, mountain shadow and paddy soil on water extraction accuracy. The model can be widely applied in cloudy, mountainous and other areas with complex environments, which has important practical significance for water resources investigation, monitoring and protection.

Alkaloids from Piper nigrum Synergistically Enhanced the Effect of Paclitaxel against Paclitaxel-Resistant Cervical Cancer Cells through the Downregulation of Mcl-1.

In the current study, nine amide alkaloids, including two new dimeric amides and a new natural product, were identified from Piper nigrum. Among them, seven compounds sensitized paclitaxel-resistant cervical cancer cells HeLa/PTX to paclitaxel. Piperine was a major component obtained from Piper nigrum, and its sensitization mechanism was investigated. Combination treatment enhanced cell apoptosis, which was mediated by downregulation of phospho-Akt and Mcl-1. Piperine (50 µM) combined with paclitaxel (200 nM) downregulated Mcl-1 protein expression with a decrease of 35.9 ± 9.5% ( P < 0.05). Moreover, overexpression of Mcl-1 attenuated the inhibitory effect of this combination. Furthermore, combination treatments of six dimeric amide alkaloids and paclitaxel all downregulated Mcl-1 protein expression with a decrease ranging from 23.5 ± 9.7% to 41.7 ± 7.2% ( P < 0.05). We reveal, for the first time, that dimeric amide alkaloids from plants possess a remarkable sensitization effect on cancer cells to paclitaxel.

Effects of lactoferrin on X-ray-induced intestinal injury in Balb/C mice.

OBJECTIVE: Intestinal injury is common after radiotherapy. We aim to investigate the effects of lactoferrin (Lf) on X-ray-induced intestinal injury in Balb/C mice. METHODS: In assessing animal survival, a total of 40 animals were assigned randomly to 8Gy group, 2 mg Lf+8Gy group, 4 mg Lf+8Gy group, and 6 mg Lf+8Gy group. Mice were administered with Lf intraperitoneally and exposed to single whole-body X-ray irradiation. Lf administration lasted for 3 days. Survival rate was compared among groups. For the observation of intestinal injury, a total of 60 animals were divided randomly into control group, 5Gy group, 2 mg Lf+5Gy group, and 4 mg Lf+5Gy group. Lf was administered once a day. Five mice in each group were randomly sacrificed at days 1, 3, and 9 after irradiation. Fasting blood was used to determine serum levels of pro-inflammatory cytokines IL-6 and TNF-α, and anti-inflammatorycytokine IL-10. Intestinal tissues were collected to examine histological changes and determine the protein expression levels of NF-κB, IKKα and IKKß. RESULTS: Mean survival time was 4.30 ± 1.34, 4.20 ± 0.71, 5.75 ± 2.44 and 6.70 ± 2.54 days in four groups, respectively, with significantly longer duration in 6 mg Lf+8Gy group than in the 8Gy group. Survival rate was significantly higher in 4 mg Lf+8Gy group and 6 mg Lf+8Gy group, compared with the 8Gy group. For intestinal histology, the radiation-induced injury was considerably improved in the 2 mg Lf+5Gy and 4 mg Lf+5Gy groups. Villus length and its ratio to crypt depth significantly increased in the two Lf intervention groups. Compared with 5Gy group, serum levels of IL-6 and TNF-α significantly decreased in the two Lf intervention groups at days 3 and 9. Furthermore, Lf significantly reduced the radiation-induced expression of IKKα/ß and NF-κB at day 3 and/or day 9. CONCLUSION: Lf extended the survival time of radiated mice and improved intestinal injury by decreasing inflammatory cytokines and downregulating NF-κB expression.

Effect of Pycnogenol Supplementation on Blood Pressure: A Systematic Review and Meta-analysis.

BACKGROUND: Pycnogenol exhibits many biological activities, including control of blood pressure (BP). However, the reported results are inconsistent because of varied characteristics of participants and quality of studies. Thus, a meta-analysis was conducted to examine the effect of Pycnogenol supplementation on BP. METHODS: This literature search of PubMed, the Web of Science and the Cochrane library was performed in May 2016 to identify eligible studies. Reference lists of the retrieved articles were also reviewed. Either a fixed-effects or, in the presence of heterogeneity, a random-effects model was used to calculate the effect of combined treatment. RESULTS: We identified nine trials involving 549 participants who received Pycnogenol supplementation ranging from 150 mg/d to 200 mg/d. Compared with the control, the pooled estimate of change in systolic and diastolic BPs were -3.22 mmHg (95% CI: -6.20, -0.24) and -3.11 mmHg (95% CI: -4.60, -1.62), respectively. Subgroup analyses showed higher BP reduction among hypertensive participants or those who received intervention for more than 12 wk. However, this significant reduction was not observed in well-designed trials. CONCLUSION: This meta-analysis with nine trials provides better evidence that Pycnogenol exerts beneficial effects on BP.

Cheese Consumption and Risk of All-Cause Mortality: A Meta-Analysis of Prospective Studies.

The association between cheese consumption and risk for major health endpoints has been investigated in many epidemiologic studies, but findings are inconsistent. As all-cause mortality can be viewed as the final net health effect of dietary intakes, we conducted a meta-analysis to examine the long-term association of cheese consumption with all-cause mortality. Relevant studies were identified by a search of the PubMed database through May 2016. Reference lists from retrieved articles were also reviewed. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using a random-effects model. Pre-specified stratified and dose-response analyses were also performed. The final analysis included nine prospective cohort studies involving 21,365 deaths. The summary RR of all-cause mortality for the highest compared with the lowest cheese consumption was 1.02 (95% CI: 0.97, 1.06), and little evidence of heterogeneity was observed. The association between cheese consumption and risk of all-cause mortality did not significantly differ by study location, sex, age, number of events, study quality score or baseline diseases excluded. There was no dose-response relationship between cheese consumption and risk of all-cause mortality (RR per 43 g/day = 1.03, 95% CI: 0.99-1.07). No significant publication bias was observed. Our findings suggest that long-term cheese consumption was not associated with an increased risk of all-cause mortality.