Safe Compounds Research Articles

Exploring the mechanism of Glycyrrhiza glabra and Curcuma domestica against skin photoaging based on network pharmacology

Excessive exposure to UV radiation results in skin photoaging, which may be prevented or treated using natural plant compounds. Herbal cosmetics and medicines have grown in popularity due to the abundance of relatively safe compounds. This research aims to explore the network pharmacology of Glycyrrhiza glabra (GG) and Curcuma domestica (CD) against skin photoaging. Active compounds from GG‐CD were sourced from databases including TCSMP, KnapSack, TCMID, and published literature, while disease targets were collected from GeneCards and OMIM databases. The STRING database was utilized to construct the protein‐protein interaction (PPI) network. Enrichment analyses for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed using Metascape. The herb‐compounds‐target‐pathway‐disease (H‐C‐T‐P‐D) network was visualized using Cytoscape software. A total of 529 compounds, 2,335 active compound targets, and 120 skin aging targets were obtained. GO enrichment revealed 1,635 biological processes, 67 cellular components, and 121 molecular functions. The study suggests that GG and CD have the potential to treat skin photoaging by targeting multiple targets, such as TP53, TNF, AKT1, IL6, and IL‐1B, as well as multiple pathways, such as those in cancer, apoptosis, TNF, IL‐17, and the AGE‐RAGE signaling pathway. Experiment validation is necessary to confirm the preliminary network pharmacology results.

Synthesis of novel chitosan-Schiff bases nanoparticles for high efficiency Helicobacter pylori inhibition

Two chitosan Schiff bases were synthesized by condensation of chitosan with 2-(4-formylphenoxy)-N-phenylacetamide and N-(4-bromophenyl)-2-(4-formylphenoxy) acetamide denoted as Cs-SBA and Cs-SBBr, respectively. The molecular structures of the resulting chitosan derivatives were characterized using FTIR and 1HNMR and their thermal properties were investigated by TGA. These derivatives were treated with sodium tripolyphosphate (TPP) to produce Cs Schiff base nanoparticles. The nanoparticles physicochemical properties were determined by FTIR, XRD, TEM, and zeta potential analysis. The antimicrobial action against Helicobacter pylori (H. pylori) was evaluated and the results indicated that the anti-H. pylori activity had minimal inhibitory concentration MIC values of 15.62 ± 0.05 and 3.9 ± 0.03 μg/mL for Cs-SBA and Cs-SBBr nanoparticles (Cs-SBA NPs and Cs-SBBr NPs), respectively. The better biologically active nanoparticles, Cs-SBBr NPs, were tested for their cyclooxygenases (COX-1 and COX-2) inhibitory potential. Cs-SBBr NPs demonstrated COX enzyme inhibition activity against COX-2 (IC50 4.5 ± 0.165 μg/mL) higher than the conventional Indomethacin (IC50 0.08 ± 0.003 μg/mL), and Celecoxib (IC50 0.79 ± 0.029 μg/mL). Additionally, the cytotoxicity test of Cs-SBBr NPs showed cytotoxic effect on Vero cells (CCL-81) with IC50 = 17.95 ± 0.12 μg/mL which is regarded as a safe compound. Therefore, Cs-SBBr NPs may become an alternative to cure H. pylori and prevent gastric cancer.

Cannabigerol-A useful agent restoring the muscular phospholipids milieu in obese and insulin-resistant Wistar rats?

Numerous strategies have been proposed to minimize obesity-associated health effects, among which phytocannabinoids appear to be effective and safe compounds. In particular, cannabigerol (CBG) emerges as a potent modulator of the composition of membrane phospholipids (PLs), which plays a critical role in the development of insulin resistance. Therefore, here we consider the role of CBG treatment on the composition of PLs fraction with particular emphasis on phospholipid subclasses (e.g., phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI)) in the red gastrocnemius muscle of Wistar rats fed the standard or high-fat, high-sucrose (HFHS) diet. The intramuscular PLs content was determined by gas-liquid chromatography and based on the composition of individual FAs, we assessed the stearoyl-CoA desaturase 1 (SCD1) index as well as the activity of n-3 and n-6 polyunsaturated fatty acids (PUFAs) pathways. Expression of various proteins engaged in the inflammatory pathway, FAs elongation, and desaturation processes was measured using Western blotting. Our research has demonstrated the important association of obesity with alterations in the composition of muscular PLs, which was significantly improved by CBG supplementation, enriching the lipid pools in n-3 PUFAs and decreasing the content of arachidonic acid (AA), which in turn influenced the activity of PUFAs pathways in various PLs subclasses. CBG also inhibited the local inflammation development and profoundly reduced the SCD1 activity. Collectively, restoring the PLs homeostasis of the myocyte membrane by CBG indicates its new potential medical application in the treatment of obesity-related metabolic disorders.

Vitamin C: Overview of drugs and dietary supplements and analytical methods for determining its content

Vitamin C is one of the most well-known and most frequently used substances found in various pharmaceutical preparations. Patients consider it as a safe compound with multidirectional beneficial effects, while chemists have been presenting various possibilities for its determination for many years. The aim of this review is to present the current range of drugs and dietary supplements containing vitamin C available in Poland, divided into appropriate categories, taking into account doses, forms and other ingredients. The second goal is to summarize the main analytical methods for determining the content of ascorbic acid. A review of available preparations showed disproportions between a small group of drugs and a very large group of dietary supplements, which turned out to be significantly diversified in various aspects. In turn, the review of analytical methods clearly indicates the dominant share of spectroscopic ones and the fact that researchers focus primarily on improving basic, commonly known techniques.

Thiazole, Isatin and Phthalimide Derivatives Tested in vivo against Cancer Models: A Literature Review of the Last Six Years.

Cancer is a disease characterized by the abnormal multiplication of cells and is the second leading cause of death in the world. The search for new effective and safe anticancer compounds is ongoing due to factors such as low selectivity, high toxicity, and multidrug resistance. Thus, heterocyclic compounds derived from isatin, thiazole and phthalimide that have achieved promising in vitro anticancer activity have been tested in vivo and in clinical trials. This review focused on the compilation of promising data from thiazole, isatin, and phthalimide derivatives, reported in the literature between 2015 and 2022, with in vivo anticancer activity and clinical trials. A bibliographic search was carried out in the PUBMED, MEDLINE, ELSEVIER, and CAPES PERIODIC databases, selecting relevant works for each pharmacophoric group with in vivo antitumor activity in the last 6 years. In our study, 68 articles that fit the scope were selected and critically analyzed. These articles were organized considering the type of antitumor activity and their year of publication. Some compounds reported here demonstrated potent antitumor activity against several tumor types. This review allowed us to highlight works that reported promising structures for the treatment of various cancer types and also demonstrated that the privileged structures thiazole, isatin and phthalimide are important in the design of new syntheses and molecular optimization of compounds with antitumor activity.

Design, synthesis and inhibitory activity against Candida albicans of a series of derivatives with 5-nitrofuran scaffold.

The increasing resistance of Candida albicans against the currently available antifungal drugs has exerted enormous damage to human health. To develop novel and efficient antifungal agents with unique structure, a series of derivatives containing 5-nitrofuran scaffold (33 examples) were designed, synthesized, and screened the in vitro antifungal activities. Bioassay results disclosed that 5-nitrofuran derivatives could dramatically inhibit the growth of six strains of Candida albicans, particularly the drug-resistant clinical ones. There were ten kinds of compounds exhibited stronger inhibitory activities against tested fungi than those of fluconazole. For all tested fungi, B5 showed the highest activity with the MIC80 values of 0.25-8 µg/mL. The results of cytotoxicity assay displayed that B5 hardly influenced the growth of HL-7702 cell lines, consequently, it was safe for people and animals. The preliminary exploration of antifungal mechanism documented that B5 could destroy the morphology of tested fungi, facilitate the formation of reactive oxygen species, ultimately inhibited the proliferation of the tested fungi. In conclusion, a new and safe lead compound was successfully developed for the treatment of Candida albicans infection.

Microenvironment-triggered cascade metal-polyphenolic nanozyme for ROS/NO synergistic hyperglycemic wound healing

Wound infection of hyperglycemic patient often has extended healing period and increased probability due to the high glucose level. However, achieving precise and safe therapy of the hyperglycemic wound with specific wound microenvironment (WME) remains a major challenge. Herein, a WME-activated smart L-Arg/GOx@TA-Fe (LGTF) nanozymatic system composed of generally recognized as safe (GRAS) compound is engineered. The nanozymatic system combining metal-polyphenol nanozyme (tannic acid-Fe3+, TA-Fe) and natural enzyme (glucose oxidase, GOx) can consume the high-concentration glucose, generating reactive oxygen species (ROS) and nitric oxide (NO) in situ to synergistically disinfect hyperglycemia wound. In addition, glucose consumption and gluconic acid generation can lower glucose level to promote wound healing and reduce the pH of WME to enhance the catalytic activities of the LGTF nanozymatic system. Thereby, low-dose LGTF can perform remarkable synergistic disinfection and healing effect towards hyperglycemic wound. The superior biosafety, high catalytic antibacterial and beneficial WME regulating capacity demonstrate this benign GRAS nanozymatic system is a promising therapeutic agent for hyperglycemic wound.

Inhibition of NF-kB and COX-2 by andrographolide regulates the progression of cervical cancer by promoting PTEN expression and suppressing PI3K/AKT signalling pathway

In the face of recent advances in Cervical cancer (CC) treatment, therapeutic and surgical procedures for CC management are still inadequate. In the current study for the first time Andrographolide (Andro) has been explored for its multitarget therapeutic efficacy on NF-kB, COX-2, and PI3K/AKT expressions together in CC. The expression levels of NF-kB, COX-2, PI3K and PTEN in the CC patient samples, both at mRNA and protein levels have shown significant association with poor survival and increased tumor aggressiveness. The binding efficacy of Andro was investigated using molecular docking and molecular dynamic simulations, and the protein and ligand complex for NF-kB and COX-2 has shown high binding energy. Andro displayed cytotoxicity by impeding the in-vitro proliferation of CC cells. Andro significantly supressed the NF-kB, COX-2, and PI3K expression and enhanced the expression levels of PTEN at protein levels in-vitro. Andro induced apoptosis in a dose dependent manner and significantly inhibited the migration and invasion of CC cells. Andro exhibited similar activity in-vivo and suppressed the CC tumor growth in xenograft C57BL/6 mice model. The anti-tumor activity of Andro, both in-vitro and in-vivo has shown considerable downregulation of NF-kB and COX-2 and induced apoptosis through impeding the PI3K/AKT signalling pathway. These findings from the above study projects, administration of Andro as an effective alternate safe compound to curtail and impede cervical cancer progression.

The anticancer impact of folate-linked ZnO-decorated bovine serum albumin/silibinin nanoparticles on human pancreatic, breast, lung, and colon cancers

In the current study, we aimed to design an individual hybrid silibinin nano-delivery system consisting of ZnO and BSA components to study its antioxidant activity and apoptotic potential on human pancreatic, breast, lung, and colon cancer cell lines. The folate-linked ZnO-decorated bovine serum albumin/silibinin nanoparticles (FZBS-NP) were synthesized and characterized by FTIR, FESEM, DLS, and zeta potential analysis. The FZBS-NP’s cytotoxicity was evaluated by measuring the cancer cells’ (MCF-7, A549, HT-29, and Panc) viability. Moreover, the apoptotic potential of the nanoparticles was studied by conducting several analyses including AO/PI and DAPI cell staining analysis, apoptotic gene expression profile (BAX, BCL2, and Caspase-8) preparation, and FITC Annexin V/PI flow cytometry. Finally, both antioxidant assays (ABTS and DPPH) were utilized to analyze the FZBS-NPs’ antioxidant activities. The 152-nm FZBS-NP significantly induced the selective apoptotic death on the MCF-7, A549, HT-29, Panc, and Huvec cancer cells by increasing the SubG1 cell population following the increased treatment concentrations of FZBS-NP. Moreover, the FZBS-NPs exhibited powerful antioxidant activity. The BSA component of the FZBS-NPs delivery system improves the ability of the nanoparticles to gradually release silibinin and ZnO near the cancer cells. On the other hand, considering the powerful antioxidant activity of FZBS-NP, they have the potential to selectively induce apoptosis in human colon and breast cancer cells and protect normal types, which makes it an efficient safe anticancer compound. However, to verify the FZBS-NP anti-cancer efficiency further cancer and normal cell lines are required to measure several types of apoptotic gene expression.

Single-cell ionic current phenotyping elucidates non-canonical features and predictive potential of cardiomyocytes during automated drug experiments.

All new drugs must go through preclinical screening tests to determine their proarrhythmic potential. While these assays effectively filter out dangerous drugs, they are too conservative, often misclassifying safe compounds as proarrhythmic. In this study, we attempt to address this shortcoming with a novel, medium-throughput drug-screening approach: we use an automated patch-clamp system to acquire optimized voltage clamp (VC) and action potential (AP) data from human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) at several drug concentrations (baseline, 3×, 10× and 20× the effective free plasma concentrations). With our novel method, we show correlations between INa block and upstroke slowing after treatment with flecainide or quinine. Additionally, after quinine treatment, we identify significant reductions in current during voltage steps designed to isolate If and IKs. However, we do not detect any IKr block by either drug, and upon further investigation, do not see any IKr present in the iPSC-CMs when prepared for automated patch experiments (i.e. in suspension) - this is in contrast to similar experiments we have conducted with these cells using the manual patch setup. In this study, we: (1) present a proof-of-concept demonstration of a single-cell medium-throughput drug study, and (2) characterize the non-canonical electrophysiology of iPSC-CMs when prepared for experiments in a medium-throughput setting. KEY POINTS: Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer potential as an in vitro model to study the proarrhythmic potential of drugs, but insights from these cells are often limited by the low throughput of manual patch-clamp. In this study, we use a medium-throughput automated patch-clamp system to acquire action potential (AP) and complex voltage clamp (VC) data from single iPSC-CMs at multiple drug concentrations. A correlation between AP upstroke and INa transients was identified and drug-induced changes in ionic currents found. We also characterize the substantially altered physiology of iPSC-CMs when patched in an automated system, suggesting the need to investigate differences between manual and automated patch experiments.

Phytochemical Characterization and Biological Activities of Essential Oil from Satureja montana L., a Medicinal Plant Grown under the Influence of Fertilization and Planting Dates.

The rising demand for safe plant compounds and herbal products that contribute positively to human health is in line with current market trends. Plants belonging to the Satureja genus, particularly the aromatic medicinal S. montana L. from the Lamiaceae family, are well suited to these trends as they serve as pharmaceutical raw materials. This research aimed to assess the influence of sowing date and fertilization doses, as well as their interaction, on the fresh weight, essential oil content, and composition of S. montana. Experimental cultivation involved varying nitrogen and phosphorus levels. The second cut had the highest fresh weight and oil production compared to the first cut. The highest total plant biomass was achieved with autumn sowing and fertilization at 55 kg N/ha and 37 kg P/ha, whereas Spring sowing exhibited higher essential oil production, with the maximum oil % with 74 kg P/ha and oil yield after applying 55 kg N/ha and 74 kg P/ha. The GC-MS analysis revealed that carvacrol was the predominant compound, with it being recommended to grow S. montana in Spring at doses of 55 kg N/ha and 74 kg P/ha for the superior oil yield. Additionally, S. montana essential oil demonstrated notable biological and antimicrobial activity, positioning it as a potential alternative to chemical food preservatives.

Marine Microalgae Schizochytrium sp. S31: Potential Source for New Antimicrobial and Antibiofilm Agent.

The rise of antibiotic-resistant bacteria necessitates the discovery of new, safe, and bioactive antimicrobial compounds. The antibacterial and antibiofilm activity of microalgae makes them a potential candidate for developing natural antibiotics to limit microbial infection in various fields. This study aimed to analyze the antibacterial effect of the methanolic extract of Schizochytrium sp. S31 microalgae by broth microdilution and spot plate assays. The antibacterial effects of Schizochytrium sp. S31 extract was studied on gramnegative pathogens, Pseudomonas aeruginosa, Escherichia coli 35218, Klebsiella pneumonia, which cause many different human infections, and the gram-positive pathogen Streptococcus mutans. At the same time, the antibiofilm activity of the Schizochytrium sp. S31 extract on Pseudomonas aeruginosa and Escherichia coli 35218 bacteria were investigated by crystal violet staining method. Schizochytrium sp. S31 extract at a 60% concentration for 8 hours displayed the highest antibacterial activity against P. aeruginosa, E. coli 35218, and K. pneumonia, with a decrease of 87%, 92%, and 98% in cell viability, respectively. The experiment with Streptococcus mutans revealed a remarkable antibacterial effect at a 60% extract concentration for 24 hours, leading to a notable 93% reduction in cell viability. Furthermore, the extract exhibited a dose-dependent inhibition of biofilm formation in P. aeruginosa and E. coli 35218. The concentration of 60% extract was identified as the most effective dosage in terms of inhibition. This research emphasizes the potential of Schizochytrium sp. S31 as a natural antibacterial and antibiofilm agent with promising applications in the pharmaceutical sectors. This is the first study to examine the antibacterial activity of Schizochytrium sp. S31 microalgae using broth microdilution, spot plate assays, and the antibiofilm activity by a crystal staining method. The findings of this study show that Schizochytrium sp. S31 has antibacterial and antibiofilm activities against critical bacterial pathogens.

Gliphosate and aminomethylphosphonic acid in the environment and their microbial transformation

Analysis of domestic and international literature indicates that the global use of glyphosate (GP), due to its effectiveness, low price and creation of herbicide-resistant agricultural crop varieties, resulted in nearly universal presence of the rest quantities of the herbicide and its main metabolite, aminomethylphosphonic acid (АМPA) in the environment: air, soil, water and crop products. Scientific information on glyphosate influence on the environment and living organisms is presented in this paper. The necessity is substantiated for periodic remediation for reducing the negative consequences of the repeated application of herbicide and detoxification of its residual quantities with the use of destructor-bacteria, capable of decomposing glyphosate and AMPA to ecologically safe compounds. The ways for glyphosate microbial transformation are reviewed. Ecologically safe detoxification assumes the use of bacterial destructors, which are destroying the phosphonic bond in glyphosate molecule. Although the bacteria of different genera are showing capacity for GP biodegradation, commercial products for the safe detoxification of glyphosate have not yet been developed due to the high level of strain specificity associated with the different ways of GF catabolism. The most perspective is the search for GP and AMPA destructors among rhizosphere bacteria, intended for application as inoculants. Complexity of the problem of GP and AMPA detoxification as well as the high level of strain specificity of bacterial destructors significantly restrain development of commercial preparations for GP and AMPA detoxification.

The impact of Withania somnifera and carbamazepine on epileptic phenotype in Drosophila temperature-sensitive mutants

BackgroundEpilepsy, a prevalent neurological disorder affecting individuals across all age groups, often requires treatment with antiepileptic drugs (AEDs). While Carbamazepine (CBZ) serves a commonly prescribed first-line medication, its efficacy is limited in 30–40 % of patients. In exploring alternative treatment options. Herbal medicines like Withania somnifera (W. somnifera) offer promising benefits with reduced adverse effects. This study aims to assess the therapeutic impacts of W. somnifera and CBZ on behavioral paralysis, reproductive abilities, and lifespan in a Drosophila paralytic temperature-sensitive mutant (paraST76). MethodsparaST76 flies were exposed to three distinct concentrations of W. somnifera or CBZ added to wheat flour-agar media. ResultsThe results indicate that high concentration of W. somnifera effectively extended the lifespan of Drosophila paraST76 without compromising fecundity and fertility. Conversely, exposure to 40 μg/ml of CBZ resulted in a shortened lifespan and decreased reproductive ability in the paraST76 mutant. Importantly, our findings demonstrate that neither W. somnifera nor CBZ exerted any notable impact on behavioral paralysis, as per our dataset analysis. ConclusionThis study exhibits that W. somnifera is a safe compound, devoid of any adverse effects, and possesses the capability to prolong the lifespan of Drosophila. Nevertheless, it does not affect the voltage-gated sodium channel of the paraST76 mutant.

704 Hydroxocobalamin Is Not Associated with Methemoglobinemia in Patients with Inhalation Injury and Suspected Cyanide Toxicity

Abstract Introduction Cyanide poisoning is a serious threat to burn patients, especially those exposed to smoke from fires, often leading to cyanide toxicity and cardiovascular collapse. Cyanokit, a widely used hydroxocobalamin product able to convert cyanide molecules into safe compounds, is known for its potential to avoid methemoglobinemia, a side effect of other treatments. Concerns about cyanokit's safety, especially in burn patients, have arisen due to recent cases with elevated methemoglobin levels. This study investigates methemoglobin levels in burn patients treated with Cyanokit, aiming to enhance our understanding of cyanide antidote therapy complexities, ultimately leading to safer treatment strategies. Methods A retrospective study was conducted of burn patients admitted to a single institution from 2013-2023 with inhalation injury treated with cyanokit for suspected cyanide toxicity. We also analyzed a control cohort of similar patients with inhalation injury not treated with cyanokit. We analyzed changes and peaks in methemoglobin, lactate levels, kidney function tests, ventilator days, % total body surface area (TBSA), medications and dressings, and mortality. Results In the study, 36 patients with suspected inhalation injury were treated with cyanokit, compared to 32 patients with inhalation injury who weren't treated with cyanokit. Baseline characteristics showed no statistically significant differences between the groups, including age, gender, BMI, and %TBSA. No significant differences were found in initial, final, peak, or change in methemoglobin levels, initial lactate levels, mortality, Baux score, kidney function tests, ventilator days, surgeries, or use of medications/treatments (e.g., Silvadene dressings, Vitamin C) between the two groups (Table 1). When controlling for covariates, multiple linear regression analysis (age, gender, and %TBSA) indicated that cyanokit administration was not significantly associated with changes in methemoglobin or mortality. Conclusions Contrary to our initial hypothesis, our study did not find significant harm or benefit of cyanokit in burn patients during the acute phase. Methemoglobin, lactate levels, mortality, and kidney function remained largely unchanged. This study's limitations, particularly the rarity of inhalation injury cases with concern for cyanide toxicity, warrant consideration. Further research is required to comprehensively elucidate the impact of cyanokit administration on burn patients' outcomes. Applicability of Research to Practice Given the high stakes involved in treating cyanide poisoning promptly, our study holds significance for refining treatment strategies and enhancing patient safety. This insight is vital for medical practitioners making critical decisions in managing cyanide poisoning in burn patients, while also underlining the need for further research to fully understand the broader impact of cyanokit administration in this context.

Syringic acid attenuates acute lung injury by modulating macrophage polarization in LPS-induced mice

BackgroundAcute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, characterized by a syndrome of uncontrolled systemic inflammation that often leads to significant morbidity and death. Anti-inflammatory is one of its treatment methods, but there is no safe and available drug therapy. Syringic acid (SA) is a natural organic compound commonly found in a variety of plants, especially in certain woody plants and fruits. In modern pharmacological studies, SA has anti-inflammatory effects and therefore may be a potentially safe and available compound for the treatment of acute lung injury. PurposeThis study attempts to reveal the protective mechanism of SA against ALI by affecting the polarization of macrophages and the activation of NF-κB signaling pathway. Trying to find a safer and more effective drug therapy for clinical use. MethodsWe constructed the ALI model using C57BL/6 mice by intratracheal instillation of LPS (10 mg/kg). Histological analysis was performed with hematoxylin and eosin (H&E). The wet-dry ratio of the whole lung was measured to evaluate pulmonary edema. The effect of SA on macrophage M1-type was detected by flow cytometry. BCA protein quantification method was used to determine the total protein concentration in bronchoalveolar lavage fluid (BALF). The levels of Interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in BALF were determined by the ELISA kits, and RT-qPCR was used to detect the expression levels of IL-6, IL-1β and TNF-α mRNA of lung tissue. Western blot was used to detect the expression levels of iNOS and COX-2 and the phosphorylation of p65 and IκBα in the NF-κB pathway in lung tissue. In vitro experiments were conducted with RAW267.4 cell inflammation model induced by 100 ng/ml LPS and A549 cell inflammation model induced by 10 μg/ml LPS. The effects of SA on M1-type and M2-type macrophages of RAW267.4 macrophages induced by LPS were detected by flow cytometry. The toxicity of compound SA to A549 cells was detected by MTT method which to determine the safe dose of SA. The expressions of COX-2 and the phosphorylation of p65 and IκBα protein in NF-κB pathway were detected by Western blot. ResultsWe found that the pre-treatment of SA significantly reduced the degree of lung injury, and the infiltration of neutrophils in the lung interstitium and alveolar space of the lung. The formation of transparent membrane in lung tissue and thickening of alveolar septum were significantly reduced compared with the model group, and the wet-dry ratio of the lung was also reduced. ELISA and RT-qPCR results showed that SA could significantly inhibit the production of IL-6, IL-1β, TNF-α. At the same time, SA could significantly inhibit the expression of iNOS and COX-2 proteins, and could inhibit the phosphorylation of p65 and IκBα proteins. in a dose-dependent manner. In vitro experiments, we found that flow cytometry showed that SA could significantly inhibit the polarization of macrophages from M0 type macrophages to M1-type macrophages, while SA could promote the polarization of M1-type macrophages to M2-type macrophages. The results of MTT assay showed that SA had no obvious cytotoxicity to A549 cells when the concentration was not higher than 80 μM, while LPS could promote the proliferation of A549 cells. In the study of anti-inflammatory effect, SA can significantly inhibit the expression of COX-2 and the phosphorylation of p65 and IκBα proteins in LPS-induced A549 cells. ConclusionSA has possessed a crucial anti-ALI role in LPS-induced mice. The mechanism was elucidated, suggesting that the inhibition of macrophage polarization to M1-type and the promotion of macrophage polarization to M2-type, as well as the inhibition of NF-κB pathway by SA may be the reasons for its anti-ALI. This finding provides important molecular evidence for the further application of SA in the clinical treatment of ALI.

Lethal and sublethal effects of carlina oxide on the aphid Metopolophium dirhodum and its non-target impact on two biological control agents

This study was designed to investigate the acute toxicity (mortality) and sublethal effects (fertility and potential natality) of carlina oxide, the main constituent of Carlina acaulis essential oil (EO), against adults of Metopolophium dirhodum (Walker) (Hemiptera: Aphididae). Moreover, its toxicity was evaluated against two aphid natural enemies, i.e., Aphidoletes aphidimyza Rondani (Diptera: Cecidomyiidae) and Chrysoperla carnea Stephens (Neuroptera: Chrysopidae). The highest tested concentration (3.0 mL L−1) resulted in 96.7% mortality of adults of the target pest, highlighting that this concentration of carlina oxide had a similar effectiveness as the positive control we used. Furthermore, probit analysis allowed the estimation of a LC50 of 1.06 mL L−1 and a LC90 of 2.58 mL L−1 for the target pest, which resulted in a much higher mortality rate than that found on natural enemies, i.e., A. aphidimyza (6.7 ± 4.7% ± SD when exposed to the aphid LC90) and C. carnea (7.0 ± 5.5% ± SD when exposed to the aphid LC90), showing the limited non-target impact of carlina oxide. The use of LC30 and LC50 of this compound allowed the fertility inhibition of the target pest by 35.68 ± 6.21% and 23.66 ± 10.58%, respectively, and potential natality inhibition of the target pest by 52.78 ± 4.48% and 59.69 ± 5.60%, respectively. Of note, carlina oxide showed excellent insecticidal activity against M. dirhodum, comparable to the commercial insecticide considered. Overall, the low toxicity of carlina oxide toward A. aphidimyza and C. carnea makes it a safe compound for non-target organisms as well as suitable for developing a green insecticide for the management of M. dirhodum and perhaps other insects of agricultural or medical and veterinary interest.

RESEARCH PROGRESS OF CURCUMIN IN THE TREATMENT OF SEPSIS.

Sepsis is a life-threatening organ dysfunction caused by an unregulated host response to infection. It is an important clinical problem in acute and critical care. In recent years, with the increasing research on the epidemiology, and pathogenesis, diagnostic and therapeutic strategies of sepsis, great progress has been made in clinical practice, but there is still a lack of specific and effective treatment plans. Curcuma longa , a leafy plant of the ginger family, which is a common and safe compound, has multiple pharmacological actions, including, but not limited to, scavenging of oxygen free radicals, attenuation of inflammatory response, and antifibrotic effects. Great progress has been made in the study of sepsis-associated rodent models and in vitro cellular models. However, the evidence of curcumin in the clinical management practice of sepsis is still insufficient; hence, it is very important to systematically summarize the study of curcumin and sepsis pathogenesis.

Disclosing the Functional Potency of Three Oxygenated Monoterpenes in Combating Microbial Pathogenesis: From Targeting Virulence Factors to Chicken Meat Preservation.

During the last few decades, there has existed an increased interest in and considerable consumer preference towards using natural and safe compounds derived from medicinal plants as alternatives to synthetic preservatives to combat microbial pathogenicity. In this regard, the present study investigated the possible synergistic interactions of the anti-foodborne bacterial capacity of linalool (L), eucalyptol (E), and camphor (C). The antibacterial synergistic effect was determined against Staphylococcus aureus, Listeria monocytogenes, Salmonella enterica Typhimurium, and Escherichia coli. The optimal predicted mixture showed the highest antibacterial activity at 33.5%, 33.2%, and 33.4% of L, E, and C, respectively. Molecular docking simulations displayed that the studied monoterpenes have effective antibacterial inhibitory effects by impeding specific virulence factors such as sortase A, listeriolysin O, L, D-Transpeptidase, and polyphosphate kinase. The selected triple combination of L, E, and C was applied as a natural preservative in minced chicken breast meat. In this regard, 1 MIC (16 µg/mL), 1.5 MIC (24 µg/mL), and 2 MIC (32 µg/mL) of L. monocytogenes were used, and the microbiological, physicochemical, and sensory analyses were monitored for 14 days of storage at 4 °C. The L/E/C mixture at different levels could delay lipid and protein oxidation, inhibit the microorganisms, and maintain the sensory attributes. Additionally, by using chemometric tools, strong connections between physicochemical properties, microbiological parameters, and organoleptic attributes were established. Concisely, this research confers the importance of the use of blended monoterpenes and highlights their antibacterial mode of action, effectiveness, and synergistic effects as a powerful and safe bio-preservative formulation in chicken meat products.

Screening and evaluation of antioxidants for retinal pigment epithelial cell protection: L-ergothioneine as a novel therapeutic candidate through NRF2 activation

The continual exposure of retinal tissues to oxidative stress leads to discernible anatomical and physiological alterations. Specifically, the onslaught of oxidative damage escalates the irreversible death of retinal pigmented epithelium (RPE) cells, pinpointed as the fundamental pathological event in dry age-related macular degeneration (AMD). There is a conspicuous lack of effective therapeutic strategies to counteract this degenerative process. This study screened a library of antioxidants for their ability to protect RPE cells against oxidative stress and identified L-ergothioneine (EGT) as a potent cytoprotective agent. L-ergothioneine provided efficient protection against oxidative stress-damaged RPE and maintained cell redox homeostasis and normal physiological functions. It maintained the normal structure of the retina in mice under oxidative stress conditions. Transcriptomic analysis revealed that EGT counteracted major gene expression changes induced by oxidative stress. It upregulated antioxidant gene expression and inhibited NRF2 translocation. The inhibition of NRF2 abolished EGT's protective effects, suggesting that NRF2 activation contributes to its mechanism of action. In conclusion, we identified EGT as a safe and effective small-molecule compound that is expected to be a novel antioxidative agent for treating AMD.