Anti-Inflammatory Effect of Izalpinin Derived from Chromolaena leivensis: λ-Carrageenan-Induced Paw Edema and In Silico Model.

The flavonoid izalpinin was isolated from the aerial parts of Chromolaena leivensis. Its structural determination was carried out using MS and NMR spectroscopic techniques (1H, 13C). This compound was evaluated for its anti-inflammatory effect in a rat model on λ-carrageenan-induced plantar edema. Paw inflammation was measured at one-hour intervals for seven hours following the administration of λ-carrageenan. Serum creatine kinase (CK) levels were evaluated, obtaining statistically significant results with the treatments at doses of 10 mg/kg (* p < 0.01) and 20 mg/kg (** p < 0.005). The anti-inflammatory effect of the compound was evaluated by using plethysmography, and the results showed significant differences at the three concentrations (10 mg/kg, 20 mg/kg, 40 mg/kg) in the first and third hours after treatment. * p < 0.05; ** p < 0.001; **** p < 0.0001 vs. the negative control group treated with vehicle (DMSO). Lastly, molecular docking analyses reveal that izalpinin has a strong binding affinity with five target proteins involved in the inflammatory process. The analysis using molecular dynamics allowed demonstrating that the ligand-protein complexes present acceptable stability, with RMSD values within the allowed range.

Oilseed Supplementation Improves Milk Composition and Fatty Acid Profile of Cow Milk: A Meta-Analysis and Meta-Regression.

Oilseed supplementation is a strategy to improve milk production and milk composition in dairy cows; however, the response to this approach is inconsistent. Thus, the aim of this study was to evaluate the effect of oilseed supplementation on milk production and milk composition in dairy cows via a meta-analysis and meta-regression. A comprehensive and structured search was performed using the following electronic databases: Google Scholar, Primo-UAEH and PubMed. The response variables were: milk yield (MY), atherogenic index (AI), Σ omega-3 PUFA, Σ omega-6 PUFA, fat, protein, lactose, linoleic acid (LA), linolenic acid (LNA), oleic acid (OA), vaccenic acid (VA), conjugated linoleic acid (CLA), unsaturated fatty acid (UFA) and saturated fatty acid (SFA) contents. The explanatory variables were breed, lactation stage (first, second, and third), oilseed type (linseed, soybean, rapeseed, cottonseed, and sunflower), way (whole, extruded, ground, and roasted), dietary inclusion level, difference of the LA, LNA, OA, forage and NDF of supplemented and control rations, washout period and experimental design. A meta-analysis was performed with the "meta" package of the statistical program R. A meta-regression analysis was applied to explore the sources of heretogeneity. The inclusion of oilseeds in dairy cow rations had a positive effect on CLA (+0.27 g 100 g−1 fatty acids (FA); p < 0.0001), VA (+1.03 g 100 g−1 FA; p < 0.0001), OA (+3.44 g 100 g−1 FA; p < 0.0001), LNA (+0.28 g 100 g−1 FA; p < 0.0001) and UFA (+8.32 g 100 g−1 FA; p < 0.0001), and negative effects on AI (−1.01; p < 0.0001), SFA (−6.51; p < 0.0001), fat milk (−0.11%; p < 0.001) and protein milk (−0.04%; p < 0.007). Fat content was affected by animal breed, lactation stage, type and processing of oilseed and dietary NDF and LA contents. CLA, LA, OA and UFA, desirable FA milk components, were affected by type, processing, and the intake of oilseed; additionally, the concentrations of CLA and VA are affected by washout and design. Oilseed supplementation in dairy cow rations has a positive effect on desirable milk components for human consumption. However, animal response to oilseed supplementation depends on explanatory variables related to experimental design, animal characteristics and the type of oilseed.

Effect of Sample Sources on Heavy Metal Concentration Measured in Beta Vulgaris Organs.

Aim: Heavy metal concentration [mg/dL, MP] in soil and the transfer to vegetable organs may have a sampling effect. We compared the [MP] in soil and organ samples of Beta vulgaris collected in sites with socioeconomic differences potentially inducing phytotoxicity. Materials and Methods: Samples of Beta vulgaris and soils (n = 4 per sample of soil and plant material) were randomly collected from two distant geographic areas (Mosquera and Sibaté, Cundinamarca, Colombia). We determined the [MP] using acid digestion of HCl : HNO3 [1 : 1]; the [MP] was obtained by atomic absorption in Varian AA-140 and Shimadzu AA-7000 equipment. A two-way ANOVA estimated the effect (partial η2) of the sampling site and metal type on the [MP] and transfer to the vegetable. Results: In Sibaté, the means (SD) of As_1.44 (0.18), Co_1.09 (0.51), Cr_6.21 (0.33), Ni_0.22 (0.02), and Pb_4.17 (0.87) were higher than in Mosquera (As_1.06 (0.21), Co_0.81 (0.19), Cr_3.72 (0.51), Ni_0.13 (0.04), and Pb_1.69 (0.40)) (p value <0.05). The effect of the interaction between the metal type and Beta vulgaris organs on the [MP] (0.801) in Sibaté was more meaningful than in Mosquera (0.430). Additionally, there was a strong correlation (Spearman's ρ > 0.8, p value <0.001) between [MP_soil] and [MP_plants] and between the transfer of metals to the plant and to the leaves. Discussion. The sampling location has a differential effect on the [MP] in soil and the transfer to Beta vulgaris. Given the differential effect described, the monitoring and phytoremediation strategies must be adjusted to scenarios with potentially phytotoxic conditions.

Contamination of staple crops by heavy metals in Sibaté, Colombia.

Heavy metal contamination in water resources, soil, and food sources is an issue that compromises food safety in Sibaté, Colombia. In the present study concentration of heavy metals [HMs], such as Cu, As, Pb, Cr, Zn, Co, Cd and Ni, present in vegetables included in the typical Colombian diet were measured. The study was conducted as follows: samples of parsley, artichoke and carrots produced in a location near the Muña dam were collected, where the Bogotá River water is treated for use as a water resource. To determine food safety, national and international [HMs] established limits were compared with quantified [HMs] in samples of different vegetable parts and of the surrounding soil. Fresh samples were separated in their respective parts for cold acid digestion with HCl and HNO3 (1:1) for 15 days. Heavy metal mean ± standard error (SE) were as follows (mg/kg) As 2.36 ± 0.185, Cd 0.16 ± 0.009, Co 0.43 ± 0.019, Cr 12.1 ± 0.453, Cu 13.1 ± 1.68, Ni 0.00, Pb 7.07 ± 0.482 and Zn 3.976 ± 0.332. Cd, Cr, As, Co and Ni showed high transfer factor in Cynara scolymus. Moreover, high Pb, Cu and Zn transfer factor were present in Petroselinum crispum. Except for Daucus carota roots, there was a high metal transfer specifically in Petroselinum crispum leaves and other different plant parts, with high transfer factor for Cr, As, Co, Pb, Cu and Zn.

Quantification of two isomeric flavones in rat colon tissue using reverse phase high performance liquid chromatography.

BACKGROUND: Antineoplastic activity has been previously shown for two isomeric flavones, 5,7-dihydroxy-3,6,8-trimethoxy flavone (flavone A) and 3,5-dihydroxy-6,7,8-trimethoxy flavone (flavone B), against colon cancer cell lines (Thomas et al. in PLoS ONE 7:e39806, 5). Here, we present modified methods for the extraction and quantification of flavones A and B in rat colon tissue after intravenous dosing via high performance liquid chromatography, from the originally described procedure for extraction and quantification in rat plasma (Whitted et al. in J Chromatogr B Analyt Technol Biomed Life Sci 1001:150-155, 7). RESULTS: Modifications included tissue homogenization (1 g tissue: 2 mL water), filtration of the supernatant with a PVDF membrane, and the use of only one calibration curve to determine the concentration of each flavone in colon tissue. Good separation was achieved and representative equations were linear with r 2  ≥ 0.99 for both flavones. Precision and accuracy for flavone A ranged from 0.88-24.03 and 109-116%. Precision and accuracy for flavone B ranged from 1.62-33.56 and 98-113%. Concentrations of 1639 ± 601 ng/g flavone A and 5975 ± 2480 ng/g of flavone B were detected in rat colon tissue 6 h post dosing. CONCLUSIONS: Modifications to the extraction methods for flavone A and flavone B from rat colon tissue had good separation, precision, and accuracy.

What Medical Directors Need to Know about Dialysis Facility Water Management.

The medical directors of dialysis facilities have many operational clinic responsibilities, which on first glance, may seem outside the realm of excellence in patient care. However, a smoothly running clinic is integral to positive patient outcomes. Of the conditions for coverage outlined by the Centers for Medicare and Medicaid Services, one most critical to quality dialysis treatment is the provision of safe purified dialysis water, because there are many published instances where clinic failure in this regard has resulted in patient harm. As the clinical leader of the facility, the medical director is obliged to have knowledge of his/her facility's water treatment system to reliably ensure that the purified water used in dialysis will meet the standards for quality set by the Association for the Advancement of Medical Instrumentation and used by the Centers for Medicare and Medicaid Services for conditions for coverage. The methods used to both achieve and maintain these quality standards should be a part of quality assessment and performance improvement program meetings. The steps for water treatment, which include pretreatment, purification, and distribution, are largely the same, regardless of the system used. Each water treatment system component has a specific role in the process and requires individualized maintenance and monitoring. The medical director should provide leadership by being engaged with the process, knowing the facility's source water, and understanding water treatment system operation as well as the clinical significance of system failure. Successful provision of quality water will be achieved by those medical directors who learn, know, and embrace the requirements of dialysis water purification and system maintenance.

Qualitative analysis of sequence specific binding of flavones to DNA using restriction endonuclease activity assays.

Flavones, found in nature as secondary plant metabolites, have shown efficacy as anti-cancer agents. We have examined the binding of two flavones, 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone; FlavA) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone; FlavB), to phiX174 RF DNA using restriction enzyme activity assays employing the restriction enzymes Alw44, AvaII, BssHII, DraI, MluI, NarI, NciI, NruI, PstI, and XhoI. These enzymes possess differing target and flanking sequences allowing for observation of sequence specificity analysis. Using restriction enzymes that cleave once with a mixture of supercoiled and relaxed DNA substrates provides for observation of topological effects on binding. FlavA and FlavB show differing sequence specificities in their respective binding to phiX. For example, with relaxed DNA, FlavA shows inhibition of cleavage with DraI (reaction site (5') TTTAAA) but not BssHII ((5') GCGCGC) while FlavB shows the opposite results. Evidence for tolological specificity is also observed, Molecular modeling and conformational analysis of the flavones suggests that the phenyl ring of FlavB is coplanar with the flavonoid ring while the phenyl ring of FlavA is at an angle relative to the flavonoid ring. This may account for aspects of the observed sequence and topological specificities in the effects on restriction enzyme activity.

Anti-neoplastic activity of two flavone isomers derived from Gnaphalium elegans and Achyrocline bogotensis.

Over 4000 flavonoids have been identified so far and among these, many are known to have antitumor activities. The basis of the relationships between chemical structures, type and position of substituent groups and the effects these compounds exert specifically on cancer cells are not completely elucidated. Here we report the differential cytotoxic effects of two flavone isomers on human cancer cells from breast (MCF7, SK-BR-3), colon (Caco-2, HCT116), pancreas (MIA PaCa, Panc 28), and prostate (PC3, LNCaP) that vary in differentiation status and tumorigenic potential. These flavones are derived from plants of the family Asteraceae, genera Gnaphalium and Achyrocline reputed to have anti-cancer properties. Our studies indicate that 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone) displays potent activity against more differentiated carcinomas of the colon (Caco-2), and pancreas (Panc28), whereas 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone) cytototoxic action is observed on poorly differentiated carcinomas of the colon (HCT116), pancreas (Mia PaCa), and breast (SK-BR3). Both flavones induced cell death (>50%) as proven by MTT cell viability assay in these cancer cell lines, all of which are regarded as highly tumorigenic. At the concentrations studied (5-80 µM), neither flavone demonstrated activity against the less tumorigenic cell lines, breast cancer MCF-7 cells, androgen-responsive LNCaP human prostate cancer line, and androgen-unresponsive PC3 prostate cancer cells. 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone) displays activity against more differentiated carcinomas of the colon and pancreas, but minimal cytotoxicity on poorly differentiated carcinomas of these organs. On the contrary, 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone) is highly cytotoxic to poorly differentiated carcinomas of the colon, pancreas, and breast with minimal activity against more differentiated carcinomas of the same organs. These differential effects suggest activation of distinct apoptotic pathways. In conclusion, the specific chemical properties of these two flavone isomers dictate mechanistic properties which may be relevant when evaluating biological responses to flavones.

Chemical and biological activity of leaf extracts of Chromolaena leivensis.

The flavonoids 3,5-dihydroxy-7-methoxy-flavanone, 3,5-dihydroxy-7-methoxyflavone and 3,5,7-trihydroxy-6-methoxyflavone were isolated from the leaves of C. leivensis. Preliminary observations in K562 cells (human erythroleukemia) using the trypan blue test, showed a 90% viability at a concentration of 100 microg/mL; however, further testing of the flavonoids at concentrations of 25, 50 and 100 microg/mL showed toxicity affecting the morphology of human erythroleukemia cells (K562) and human melanoma cells (A375). Induction of apoptosis was produced by 3,5-dihydroxy-7-methoxyflavone at 72 hours after treatment with arrest in the G2 / M phase of the cell cycle. The A375 cells treated with 50 microg/mL of 3,5-dihydroxy-7-methoxy-flavanone for 24, 48 and 72 hours, display effects on the behavior of the cell cycle. The flavonoid 3,5-dihydroxy-7-methoxyflavone has activity on the mitochondrial membrane at concentrations of 25, 50 and 100 microg/mL, at time intervals of 8 to 12 hours. The flavonoids 3,5-dihydroxy-7-methoxy-flavanone and 3,5-dihydroxy-7-methoxyflavone at a concentration of 25 microg/mL increased the expression of costimulatory molecules corresponding to the phenotype presented by mature dendritic cells with differentiation markers CD40, CD83, CD86 and HLA-DR. The two flavonoids at concentrations between 0.39 and 100 microg/mL slightly increased the proliferation of peripheral blood mononuclear cells in the presence and in the absence of phytohemagglutinin. These flavonoids at concentrations of 50 and 100 microg/mL slightly increased the proliferation of fibroblasts.