•Ionic liquids were efficient in extracting resveratrol from P. Cuspidatum.•C4mim+Br− has proven to be more effective in increasing resveratrol yield from P. Cuspidatum than conventional organic ...solvents.•Extraction of resveratrol from P. Cuspidatum was modeled using RSM and ANN-GA.•ANN-GA provided both higher precision and yield in resveratrol extraction from P. Cuspidatum via UEAE than RSM.
This work offered a productive technique for resveratrol extraction from Polygonum Cuspidatum (P. Cuspidatum) using ionic liquids in synergy with ultrasound-enzyme-assisted extraction (UEAE). Firstly, ionic liquids with different carbon chains and anions were evaluated. Subsequently, a comprehensive investigation was carried out to evaluate the effect of seven crucial parameters on the resveratrol yield: pH value, enzyme concentration, extraction temperature, extraction time, ultrasonic power, concentration of ionic liquid (IL concentration) and the liquid–solid ratio. Employing the Plackett-Burman Design (PBD), the critical factors were effectively identified. Building upon this foundation, the process was further optimized through the application of Response Surface Methodology (RSM) and an Artificial Neural Network-Genetic Algorithm (ANN-GA). The following criteria were determined to be the ideal extraction conditions: an enzyme concentration of 2.18%, extraction temperature of 58 °C, a liquid–solid ratio of 29 mL/g, pH value of 5.5, extraction time of 30 min, ultrasonic power of 250 W, and extraction solvent of 0.5 mol/L 1-butyl-3-methylimidazolium bromide. Under these conditions, the resveratrol yield was determined to be 2.90 ± 0.15 mg/g. Comparative analysis revealed that the ANN-GA model provided a better fit to the experimental data of resveratrol yield than the RSM model, suggesting superior predictive capabilities of the ANN-GA approach. The introduction of a novel green solvent system in this experiment not only simplifies the extraction process but also enhances safety and feasibility. This research paves the way for innovative approaches to extracting resveratrol from botanical sources, showcasing its significant potential for a wide range of applications.
Ultrasonic-assisted extraction (UAE), using aqueous ethanol as the solvent, was firstly applied to extract phenolic compounds from Terminalia chebula Retz. fruits (T. chebula fruits). In this study, ...ethanol concentration (%), ultrasonic intensity (W/cm2), particle diameter (mm), extraction temperature (°C), ultrasonic time (min), liquid-solid ratio (mL/g) and extraction cycle were investigated by single-factor experiment and then optimized using a Box-Behnken design. The optimized result for UAE was 68% ethanol concentration, ultrasonic intensity of 3.6 W/cm2, solid-liquid ratio of 23 mg/mL, particle size of 0.18 mm and ultrasonic time of 20 min for 2 times at 70 °C. The yield of total phenolic was 448.7 ± 2.15 mg GAE/g DW under the above optimum conditions, which agreed with the predicted value (447.8 mg GAE/g DW). Compared to conventional solvent extraction (CSE), UAE extracts showed excellent DPPH radical, DPPH, ABTS scavenging activities and reducing power in a dose-dependent manner, and better than that of CSE extracts. Additionally, the extract of the T. chebula fruits was analyzed by HPLC-ESI/MS. In summary, UAE could effectively extract phenolic compounds from T. chebula fruits. In addition, the extract could be used as a potential source of natural antioxidants.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Ionic liquids were efficient in extracting lycopene from guava.•C4mim+Cl− increased the extraction compared to organic solvents.•Extraction of lycopene from guava was modeled using (RSM) and ...(ANN).•ANN-GA showed better precision than RSM for the UAE method of lycopene from guava.
Lycopene-rich guava (Psidium guajava L.) exhibits significant economic potential as a functional food ingredient, making it highly valuable for the pharmaceutical and agro-food industries. However, there is a need to enhance the extraction methods of lycopene to fully exploit its beneficial uses. In this study, we evaluated various ionic liquids to identify the most effective one for extracting lycopene from guava. Among thirteen ionic liquids with varying carbon chains or anions, 1-butyl-3-methylimidazolium chloride demonstrated the highest productivity. Subsequently, a single-factor experiment was employed to test the impact of several parameters on the efficiency of lycopene extraction using this selected ionic liquid. These parameters included extraction time, ultrasonic power, liquid-solid ratio, concentration of the ionic liquid, as well as material particle size. Moreover, models of artificial neural networks using genetic algorithms (ANN-GA) and response surface methodology (RSM) were employed to comprehensively assess the first four key parameters. The optimized conditions for ionic liquid ultrasound-assisted extraction (IL-UAE) were determined as follows: 33 min of extraction time, 225 W of ultrasonic power, 22 mL/g of liquid-solid ratio, 3.0 mol/L of IL concentration, and extraction cycles of three. Under these conditions, lycopene production reached an impressive yield of 9.35 ± 0.36 mg/g while offering advantages such as high efficiency, time savings, preservation benefits, and most importantly environmental friendliness.
The anionic peroxidases play an important role in a variety of plant physiological processes. We characterized and isolated the Zmap promoter (PZmap) at the 5' flanking region in order to better ...understand the regulatory mechanisms of Zmap gene expression. A series of PZmap deletion derivatives, termed a1 -a6, at positions -1694, -1394, -1138, -784, -527 and -221 from the translation start site were blended to the β-glucuronidase reporter gene. Agrobacterium-mediated transformation method was used to study each deletion construct in tobaccos. Sequence analysis showed that several cis-acting elements (MYB binding site, Box-II, a TGACG-element, a CGTCA-element and a low temperature responsive element) were located within the promoter. Deletion analysis suggested the sequence between -1,694 and -1394bp may contain cis-elements associated with GUS up regulation. The MYB binding site (-757) might act as a negative drought-responsive element. There might be repressor elements located in the region (-1,694 to -1394bp) to repress Zmap expression under 4°C. The characterized promoter would be an ideal candidate for genetic engineering for improving the resistance of maize to different stressors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, a series of novel 3-(5-fluoropyridine-3-yl)-2-oxazolidinone derivatives were designed and synthesized based on compounds previously reported, and their antibacterial activity was ...investigated. Then their antibacterial activity was investigated for the first time. Preliminary screening results showed that all these compounds exhibited antibacterial activity against gram-positive bacteria, including 7 drug-sensitive strains and 4 drug-resistant strains, among which compound
exhibited an 8-fold stronger inhibitory effect than linezolid, with a minimum inhibitory concentration (MIC) value of 0.25 µg/mL. Further molecular docking studies predicted the possible binding mode between active compound
and the target. Interestingly, these compounds could not only hamper the formation of biofilms, but also have better safety, as confirmed by cytotoxicity experiments. All these results indicate that these 3-(5-fluoropyridine-3-yl)-2-oxazolidinone derivatives have the potential to be developed into novel candidates for the treatment of gram-positive bacterial infections.
Acute diarrhea is still a common and serious disease. The causes of acute diarrhea are very complicated. Therefore, we need to find a medicine to control diarrhea symptoms, save time for diagnosis of ...pathogens, and prevent drug abuse. Ellagic acid (EA), a natural polyphenol drug, has anti-diarrhea effects. However, the action mechanisms of EA for non-specific diarrhea have not been characterized.
To study the mechanisms of EA, mice were divided into four groups. Group C were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml physiological saline, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group D were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group E were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml). Group V were intraperitoneally injected with 0.1ml GW9662 (1m g/ml) and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml). Transcriptome were performed on ileum tissues of mice in group D and E. Histological examination and qRT-PCR were performed on ileum tissues of mice in group C, D, E, and V.
We found that a total of 273 differentially expressed genes (DEGs) were obtained, including 160 up-regulated DEGs and 113 down-regulated DEGs. The DEGs were enriched in 458 Gene Ontology (GO) terms and 15 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. The peroxisome proliferator activated receptor (PPAR) signaling pathway was the most significantly enriched in KEGG pathways. We used the PPAR-specific antagonist GW9662 to validate the anti-diarrhea and anti-inflammatory effect of EA in group V compared with group E. Conclusively, EA protected ileums against castor oil-induced inflammation and diarrhea by activating the PPAR signaling pathway and a method was used to study the mechanism of EA.
(CF) is a natural medicinal plant widely used for its various pharmacological properties. Natural products used to cure several diseases have been considered safe thanks to their little or no side ...effects. However, in recent years, a hepatotoxic effect has been found due to the abuse of herbal medicine. CF has been reported to have hepatotoxicity, but the mechanism is unclear. In this experiment, the toxic aspect and mechanism of CF action were evaluated by transcriptome analysis. Components of toxic CF fractions were identified by LC-MS, and hepatotoxic toxic components in toxic CF fractions were predicted by molecular docking. The results showed that the ethyl acetate part of CF was the main toxic fraction, and transcriptome analysis found that the toxic mechanism was highly related to lipid metabolism-related pathways, and CFEA could inhibit the PPAR signaling pathway. Molecular docking results showed that 3'-
-methyl-4-
-(n″-
-galloyl-β-d-xylopyranosyl) ellagic acid (
= 2, 3 or 4) and 4-
-(3″,4″-
-digalloyl-α-l-rhamnosyl) ellagic acid have better docking energies with PPARα protein and FABP protein than other components. In summary, 3'-
-methyl-4-
-(n″-
-galloyl-β-d-xylopyranosyl) ellagic acid (
= 2, 3 or 4) and 4-
-(3″,4″-
-digalloyl-α-l-rhamnosyl) ellagic acid were the main toxic components, which may play a toxic role by inhibiting the PPAR signaling pathway and affect lipid metabolism.
(Willd.) R. Br. (
) is a perennial herb known for its chemotherapeutic properties, strong feeding additive, and potential antidiarrheal drug. Despite its therapeutic potentials, its clinical ...applications are hindered by an apparent lack of toxicity data. In this study, the toxic ingredients of this plant were investigated using a bioactivity-guided approach. Two compounds, protopine and allocryptopine, were purified and elucidated by LC-MS,
H-NMR, and
C-NMR. Protopine, a primary component in
, had an LD
of 313.10 mg/kg i.e., which was considered toxic. An autopsy was performed on protopine-administered mice, and the histopathology of the kidney, liver, brain, heart, lung, and spleen was determined. Autopsy findings included hemorrhage in the respiratory system, lung congestion, and hemorrhage and edema in the parenchymatous organs (heart, liver, kidney, and brain). Histopathology confirmed the pathological changes in the brain, liver, and kidney. Protopine is one of the principal bioactive constituents of many phytopreparations used in veterinary and human medicine, such as Sangrovit and Iberogast. Our findings indicated that phytopreparations containing protopine might pose a serious health threat to humans and animals.
Diarrhea continues to be a major public health problem and is thought to be the cause of 525,000 child fatalities annually. Studies have shown that
Macleaya cordata
(Willd.) R.Br., Papaveraceae, has ...a good therapeutic effect on diarrhea due to its action on ion channels. However, its antidiarrheal mechanisms and key targets are not supported by scientific research. This study aimed to identify the mechanisms of action and targets of the primary active antidiarrheal compounds of
M. cordata
. We used network pharmacology and molecular docking to identify the antidiarrheal mechanisms and the key targets of
M. cordata
and its main chemical constituents. Subsequently, the experiments performed with dihydrosanguinarine (25, 50, and 100 mg/kg), which included the evaluation of the inhibitory potential of the epidermal growth factor receptor in osimertinib-induced diarrhea, real-time quantitative PCR, and western blotting, were performed for further verification of its mechanism of action. The findings revealed that of all the genes, tyrosine-protein kinase Lck, receptor tyrosine-protein kinase Erbb2, and epidermal growth factor receptor had the highest capacity of action, and the NF-kappa B and the calcium signaling pathways may play essential roles in
M. cordata
against diarrhea. Dihydrosanguinarine is the most active ingredient, and it significantly inhibits the increase in incidence and decreased the fecal water content of osimertinib-induced diarrhea. Western blot and qRT-PCR showed that dihydrosanguinarine works as an antidiarrheal agent by upregulating the expression of the core target epidermal growth factor receptor, affecting the NF-kappa B and the calcium ion signaling pathways, downregulating the expression of calcium-activated chloride channel and NK-kappa B P-65.
Graphical Abstract
Trimethyltin chloride (TMT), a common component in fungicides and plastic stabilizers, presents environmental risks, particularly to fish farming. The precise toxicological mechanisms of TMT in L8824 ...grass carp liver cells remain undefined. Our study investigates TMT's effects on these cells, focusing on its potential to induce hepatotoxicity via oxidative stress and NF-κB pathway activation. First, we selected 0, 3, 6, and 12 μM as the challenge doses, according to the inhibitory concentration of 50% (IC50) of TMT. Our results demonstrate that TMT decreases cell viability dose-dependently and triggers oxidative stress, as evidenced by increased ROS staining and MDA content. Concurrently, it inhibited the antioxidant activities of T-AOC, T-SOD, CAT, and GSH. The activation of the NF-κB pathway was confirmed by gene expression changes. Furthermore, we observed an increase in cell apoptosis rate by AO/EB staining and cell flow cytometry, and the downregulation of Bcl-2 and the upregulation of Bax, Cytc, Caspase-9, and casp3 verified that TMT passed through the BCL2/BAX/casp3 pathway induces apoptosis. DNA damage was validated by the comet assay and γH2AX gene overexpression. Lastly, our data showed increased expression of TNF-α, IL-1β, IL-6, and INF-γ and decreased antimicrobial peptides, validating immune dysfunction. In conclusion, our findings establish that TMT induces apoptosis and DNA damage via ROS/NF-κB in grass carp liver cells, causing immune dysfunction. This study provides novel insights into the toxicology research of TMT and sheds light on the immunological effects of TMT toxicity, enriching our understanding of the immunotoxicity of TMT on aquatic organisms and contributing to the protection of ecosystems.
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•Trimethyltin chloride exposure induces damage to grass carp liver cells via the ROS/NF-κB pathway.•Trimethyltin chloride exposure induces BCL2/BAX/Casp3-cascaded apoptosis.•Trimethyltin chloride exposure induces DNA damage.•Trimethyltin chloride exposure induces immune dysfunction.
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