A novel natural Syk inhibitor suppresses IgE-mediated mast cell activation and passive cutaneous anaphylaxis.

Spleen tyrosine kinase (Syk) plays a crucial role as a target for allergy treatment due to its involvement in immunoreceptor signaling. The purpose of this study was to identify natural inhibitors of Syk and assess their effects on the IgE-mediated allergic response in mast cells and ICR mice. A list of eight compounds was selected based on pharmacophore and molecular docking, showing potential inhibitory effects through virtual screening. Among these compounds, sophoraflavanone G (SFG) was found to inhibit Syk activity in an enzymatic assay, with an IC50 value of 2.2 µM. To investigate the conformational dynamics of the SYK-SFG system, we performed molecular dynamics simulations. The stability of the binding between SFG and Syk was evaluated using root mean square deviation (RMSD) and root mean square fluctuation (RMSF). In RBL-2H3 cells, SFG demonstrated a dose-dependent suppression of IgE/BSA-induced mast cell degranulation, with no significant cytotoxicity observed at concentrations below 10.0 µM within 24 h. Furthermore, SFG reduced the production of TNF-α and IL-4 in RBL-2H3 cells. Mechanistic investigations revealed that SFG inhibited downstream signaling proteins, including phospholipase Cγ1 (PLCγ1), as well as mitogen-activated protein kinases (AKT, Erk1/2, p38, and JNK), in mast cells in a dose-dependent manner. Passive cutaneous anaphylaxis (PCA) experiments demonstrated that SFG could reduce ear swelling, mast cell degranulation, and the expression of COX-2 and IL-4. Overall, our findings identify naturally occurring SFG as a direct inhibitor of Syk that effectively suppresses mast cell degranulation both in vitro and in vivo.

CuMoO4/Ti3C2Tx nanocomposite layers perform as an ultrasensitive electrochemical sensor for the detection of antioxidant rutin.

The focus of this paper is laid on synthesizing layered compounds of CuMoO4 and Ti3C2Tx using a simple wet chemical etching method and sonochemical method to enable rapid detection of rutin using an electrochemical sensor. Following structural examinations using XRD, surface morphology analysis using SEM, and chemical composition state analysis using XPS, the obtained CuMoO4/Ti3C2Tx nanocomposite electrocatalyst was confirmed and characterized. By employing cyclic voltammetry and differential pulse voltammetry, the electrochemical properties of rutin on a CuMoO4/Ti3C2Tx modified electrode were examined, including its stability and response to variations in pH, loading, sweep rate, and interference. The CuMoO4/Ti3C2Tx modified electrode demonstrates rapid rutin sensing under optimal conditions and offers a linear range of 1 µΜ to 15 µΜ, thereby improving the minimal detection limit (LOD) to 42.9 nM. According to electrochemical analysis, the CuMoO4/Ti3C2Tx electrode also demonstrated cyclic stability and long-lasting anti-interference capabilities. The CuMoO4/Ti3C2Tx nanocomposite demonstrated acceptable recoveries when used to sense RT in apple and grape samples. In comparison to other interfering sample analytes encountered in the current study, the developed sensor demonstrated high selectivity and anti-interference performance. As a result, our research to design of high-performance electrochemical sensors in the biomedical and therapeutic fields.

The quality evaluation of 30 Asparagus officinalis L. varieties.

Asparagus, a vital economic contributor, is a well-liked vegetable grown around the globe, and some secondary metabolites in its spear are beneficial to human health. Asparagus spears possess a significant quantity of nutrients and phytochemicals; however, the difference in these chemical compositions among various varieties has not been sufficiently studied. This work aimed to detect the chemical compositions of 30 varieties of asparagus and to assess them by principal component analysis (PCA). The results showed that the contents of these chemical compositions varied in varieties. Selenium (Se, 1.12-2.9 µg/100 g dry-weight [DW]) was abundant in asparagus, with an average dry matter content of 8.25%. Free amino acids (5.60-9.98 g/100 g DW) and polyphenols (6.34-8.67 mg/g DW) were both present in high amounts, along with flavonoids (4.218-8.22 mg/g DW) and protodioscin (0.44-1.96 mg/g DW). Correlation analysis, PCA, and hierarchical cluster analysis were used to conduct a comprehensive evaluation of asparagus. Atlas, Appolo, Jinggang 111, Jingke 2, and WS-1 were the top five varieties with comprehensive scores. This study provided valuable data for the breeding, quality improvement, processing, and utilization of asparagus varieties in the future.

Rutin Attenuates Gentamycin-induced Hair Cell Injury in the Zebrafish Lateral Line via Suppressing STAT1.

Aminoglycoside antibiotics, including gentamicin (GM), induce delayed ototoxic effects such as hearing loss after prolonged use, which results from the death of hair cells. However, the mechanisms underlying the ototoxicity of aminoglycosides warrant further investigation, and there are currently no effective drugs in the clinical setting. Herein, the therapeutic effect of the flavonoid compound rutin against the ototoxic effects of GM in zebrafish hair cells was investigated. Animals incubated with rutin (100-400 µmol/L) were protected against the pernicious effects of GM (200 µmol/L). We found that rutin improves hearing behavior in zebrafish, and rutin was effective in reducing the number of Tunel-positive cells in the neuromasts of the zebrafish lateral line and promoting cell proliferation after exposure to GM. Subsequently, rutin exerted a protective effect against GM-induced cell death in HEI-OC1 cells and could limit the production of cytosolic reactive oxygen species (ROS) and diminish the percentage of apoptotic cells. Additionally, the results of the proteomic analysis revealed that rutin could effectively inhibit the expression of necroptosis and apoptosis related genes. Meanwhile, molecular docking analysis revealed a high linking activity between the molecular docking of rutin and STAT1 proteins. The protection of zebrafish hair cells or HEI-OC1 cells from GM-induced ototoxicity by rutin was attenuated by the introduction of STAT1 activator. Finally, we demonstrated that rutin significantly improves the bacteriostatic effect of GM by in vitro experiments, emphasising its clinical application value. In summary, these results collectively unravel a novel therapeutic role for rutin as an otoprotective drug against the adverse effects of GM.

The combined application of rutin and silicon alleviates osmotic stress in maize seedlings by triggering accumulation of osmolytes and antioxidants' defense mechanisms.

Silicon (Si) has been shown to improve plant defenses against a variety of stresses. However, how rutin (Rut) affects stress factors is yet to be fully explored. Moreover, their combined role in osmotic stress response remains unclear. The current study was performed to determine how the use of Rut and Si, both separately and in combination, improved the physiological resilience of maize seedlings to two levels of osmotic stress (induced by polyethylene glycol (PEG) 6000). We aimed to enhance osmotic stress tolerance with the simultaneous use of Rut and Si. First, we selected the best water status and the lowest membrane damage enhancing concentration of Rut (60 ppm) and Si (1 mM) to research their tolerance and resistance to osmotic stress (moderate: 10% PEG, severe: 15% PEG). The application of Rut and Si separately and together reduced oxidative stress by decreasing the reactive oxygen species and improved the relative water content, osmoprotectants (proline, total soluble sugar, and glycine-betaine), ascorbate level, and some antioxidant defense-related enzyme activities and their gene expression in maize seedlings under osmotic stress. However, these effects were more promising under moderate stress. As a result, findings from the study indicate the synergistic effect of combined Rut and Si on osmotic stress tolerance in maize seedlings. Overall, the combination of Rut and Si was more effective than independent Rut and Si in reducing osmotic stress in maize seedlings. Here, it was clear that Rut played an active role in alleviating stress. This combined application can be useful for developing drought tolerance in crops for the agriculture sector.

Biomarkers and signaling pathways of diabetic nephropathy and peripheral neuropathy: possible therapeutic intervention of rutin and quercetin.

Diabetic nephropathy and peripheral neuropathy are the two main complications of chronic diabetes that contribute to high morbidity and mortality. These conditions are characterized by the dysregulation of multiple molecular signaling pathways and the presence of specific biomarkers such as inflammatory cytokines, indicators of oxidative stress, and components of the renin-angiotensin system. In this review, we systematically collected and collated the relevant information from MEDLINE, EMBASE, ELSEVIER, PUBMED, GOOGLE, WEB OF SCIENCE, and SCOPUS databases. This review was conceived with primary objective of revealing the functions of these biomarkers and signaling pathways in the initiation and progression of diabetic nephropathy and peripheral neuropathy. We also highlighted the potential therapeutic effectiveness of rutin and quercetin, two plant-derived flavonoids known for their antioxidant and anti-inflammatory properties. The findings of our study demonstrated that both flavonoids can regulate important disease-promoting systems, such as inflammation, oxidative stress, and dysregulation of the renin-angiotensin system. Importantly, rutin and quercetin have shown protective benefits against nephropathy and neuropathy in diabetic animal models, suggesting them as potential therapeutic agents. These findings provide a solid foundation for further comprehensive investigations and clinical trials to evaluate the potential of rutin and quercetin in the management of diabetic nephropathy and peripheral neuropathy. This may contribute to the development of more efficient and comprehensive treatment approaches for diabetes-associated complications.

Dietary rutin improves the antidiarrheal capacity of weaned piglets by improving intestinal barrier function, antioxidant capacity and cecal microbiota composition.

BACKGROUND: Early weaning is prone to damage intestinal barrier function, resulting in diarrhea, whereas rutin, as a natural flavonoid with multiple biological functions, shows potential in piglets. Therefore, the effects of dietary rutin on growth, antidiarrheal, barrier function, antioxidant status and cecal microbiota of weaned piglets were investigated with the control group (CON) (basal diet) and Rutin (basal diet+500 mg kg-1 rutin) groups fed for 14 days. RESULTS: The results showed that dietary 500 mg kg-1 rutin significantly decreased diarrhea index, serum diamine oxidase activity and total aerobic bacterial population in mesenteric lymph nodes, whereas it significantly increased the gain-to-feed ratio (G:F) and serum growth hormone content, jejunal villus height and villus height to crypt depth ratio, and also enhanced jejunal claudin-1 and zonula occludens-1 mRNA and protein expression. Meanwhile, dietary rutin significantly decreased inflammation-associated mRNA expression, malondialdehyde (MDA) content, swollen mitochondrial number and mitochondrial area in the jejunum, whereas it increased the total superoxide dismutase (T-SOD) and glutathione peroxidase activities and activated the Nrf2 signaling pathway. Moreover, dietary rutin significantly increased Firmicutes abundance and decreased Campylobacterota abundance, which were closely associated with the decreased diarrhea index and MDA content or increased Claudin-1 expression and T-SOD activity. CONCLUSION: Dietary 500 mg kg-1 rutin increased G:F by improving intestinal morphology, and alleviated diarrhea by enhancing intestinal barrier, which might be associated with the enhanced antioxidant capacity via activating the Nrf2/Keap1 signaling pathway and the improved cecal microbial composition in weaned piglets. © 2024 Society of Chemical Industry.

Alleviative Effect of Rutin on Zearalenone-Induced Reproductive Toxicity in Male Mice by Preventing Spermatogenic Cell Apoptosis and Modulating Gene Expression in the Hypothalamic-Pituitary-Gonadal Axis.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin found in many agricultural products and can cause reproductive disorders, mainly affecting spermatogenesis in male animals. Rutin (RUT) is a natural flavonoid compound recognized for its significant antioxidant, anti-inflammatory and estrogenic properties. The present study aimed to determine the protective role of RUT against ZEN-induced reproductive toxicity in male mice. Twenty-four adult Kunming male mice were divided into four groups: control, RUT (500 mg/kg RUT), ZEN (10 mg/kg ZEN), ZEN + RUT (500 mg/kg RUT + 10 mg/kg ZEN), with six replicates per treatment. The results indicated that RUT mitigated ZEN-induced disruption in spermatogenic cell arrangement, decreased spermatozoa count, and increased sperm mortality in the testes. RUT significantly restored ZEN-induced reduction in T, FSH, LH, and E2 serum levels. Moreover, RUT mitigated ZEN-induced apoptosis by increasing the mRNA expression level of bcl-2, decreasing the mRNA expression level of kiss1-r, and decreasing the protein expression level of caspase 8 in reproductive tissues. These findings indicate the protective role of RUT against ZEN-induced reproductive toxicity in male mice by regulating gonadotropin and testosterone secretions to maintain normal spermatogenesis via the HPG axis, which may provide a new application direction for RUT as a therapeutic agent to mitigate ZEN-induced reproductive toxicity.

Rutin alleviates lupus nephritis by inhibiting T cell oxidative stress through PPARγ.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by complex clinical symptoms and multi-organ damage. One of the most prevalent complications of SLE is lupus nephritis (LN). Rutin, a natural flavonoid compound found in various plants used in traditional Chinese medicine, has shown promising anti-inflammatory, antioxidant, and renal protective effects. In our study, we treated MRL/lpr mice, a model known for spontaneously developing LN, with Rutin. Our findings reveal that Rutin markedly reduced serum cytokine and autoantibody levels and decreased inflammatory cell infiltration in renal tissues, thereby ameliorating kidney pathology. In vitro experiments indicated that Rutin's therapeutic effect on LN is linked to its significant reduction of oxidative stress in T cells. Further investigations suggest that Rutin enhances oxidative stress management through the modulation of Peroxisome proliferator-activated receptor gamma (PPARγ). We observed that Rutin modulates PPARγ activity, leading to reduced transcriptional activity of NF-κB and STAT3, which in turn inhibits the secretion of inflammatory cytokines such as IL-6, TNF-α, and IL-17. In summary, Rutin can exert an antioxidant effect by regulating PPARγ and shows therapeutic action against LN.

Rutin mitigates fluoride-induced nephrotoxicity by inhibiting ROS-mediated lysosomal membrane permeabilization and the GSDME-HMGB1 axis involved in pyroptosis and inflammation.

Fluoride is known to induce nephrotoxicity; however, the underlying mechanisms remain incompletely understood. Therefore, this study aims to explore the roles and mechanisms of lysosomal membrane permeabilization (LMP) and the GSDME/HMGB1 axis in fluoride-induced nephrotoxicity and the protective effects of rutin. Rutin, a naturally occurring flavonoid compound known for its antioxidative and anti-inflammatory properties, is primarily mediated by inhibiting oxidative stress and reducing proinflammatory markers. To that end, we established in vivo and in vitro models. In the in vivo study, rats were exposed to sodium fluoride (NaF) throughout pregnancy and up until 2 months after birth. In parallel, we employed in vitro models using HK-2 cells treated with NaF, n-acetyl-L-cysteine (NAC), or rutin. We assessed lysosomal permeability through immunofluorescence and analyzed relevant protein expression via western blotting. Our findings showed that NaF exposure increased ROS levels, resulting in enhanced LMP and increased cathepsin B (CTSB) and D (CTSD) expression. Furthermore, the exposure to NaF resulted in the upregulation of cleaved PARP1, cleaved caspase-3, GSDME-N, and HMGB1 expressions, indicating cell death and inflammation-induced renal damage. Rutin mitigates fluoride-induced nephrotoxicity by suppressing ROS-mediated LMP and the GSDME/HMGB1 axis, ultimately preventing fluoride-induced renal toxicity occurrence and development. In conclusion, our findings suggest that NaF induces renal damage through ROS-mediated activation of LMP and the GSDME/HMGB1 axis, leading to pyroptosis and inflammation. Rutin, a natural antioxidative and anti-inflammatory dietary supplement, offers a novel approach to prevent and treat fluoride-induced nephrotoxicity.

Engineering a Dual-Functionalized PolyHIPE Resin for Photobiocatalytic Flow Chemistry.

The use of a dual resin for photobiocatalysis, encompassing both a photocatalyst and an immobilized enzyme, brings several challenges, including effective immobilization, maintaining photocatalyst and enzyme activity and ensuring sufficient light penetration. However, the benefits, such as integrated processes, reusability, easier product separation, and potential for scalability, can outweigh these challenges, making dual resin systems promising for efficient and sustainable photobiocatalytic applications. In this study, we employed a photosensitizer-containing porous emulsion-templated polymer as a functional support that is used to covalently anchor a chloroperoxidase from Curvularia inaequalis (CiVCPO). We demonstrate the versatility of this heterogeneous photobiocatalytic material, which enables the bromination of four aromatic substrates, including rutin-a natural occurring flavonol-under blue light (456 nm) irradiation and continuous flow conditions.

RUTIN, a widely consumed flavonoid, that commonly induces hormetic effects.

Rutin is a flavonoid present in numerous fruits and vegetables and therefore widely consumed by humans. It is also a popular dietary supplement of 250-500 mg/day. There is considerable consumer interest in rutin due to numerous reports in the biomedical literature of its multi-system chemo-preventive properties. The present paper provides the first assessment of rutin-induced hormetic concentration/dose responses, their quantitative features and mechanistic basis, along with their biological, biomedical, clinical, and public health implications. The findings indicate that rutin-induced hormetic dose responses are widespread, being reported in numerous biological models and cell types for a wide range of endpoints. Of critical importance is that the optimal hormetic findings shown in in vitro systems are currently not achievable for human populations due to low gastrointestinal tract bioavailability. These findings have the potential to strengthen future experimental studies with rutin, particularly concerning study design parameters.

Tartary buckwheat rutin: Accumulation, metabolic pathways, regulation mechanisms, and biofortification strategies.

Rutin is a significant flavonoid with strong antioxidant property and various therapeutic effects. It plays a crucial role in disease prevention and human health maintenance, especially in anti-inflammatory, antidiabetic, hepatoprotective and cardiovascular effects. While many plants can synthesize and accumulate rutin, tartary buckwheat is the only food crop possessing high levels of rutin. At present, the rutin content (RC) is regarded as the key index for evaluating the nutritional quality of tartary buckwheat. Consequently, rutin has become the focus for tartary buckwheat breeders and has made considerable progress. Here, we summarize research on the rutin in tartary buckwheat in the past two decades, including its accumulation, biosynthesis and breakdown pathways, and regulatory mechanisms. Furthermore, we propose several strategies to increase the RC in tartary buckwheat seeds based on current knowledge. This review aims to provide valuable references for elevating the quality of tartary buckwheat in the future.

Neuroprotective effects of rutin against cuprizone-induced multiple sclerosis in mice.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system that injures the myelin sheath, provoking progressive axonal degeneration and functional impairments. No efficient therapy is available at present to combat such insults, and hence, novel safe and effective alternatives for MS therapy are extremely required. Rutin (RUT) is a flavonoid that exhibits antioxidant, anti-inflammatory, and neuroprotective effects in several brain injuries. The present study evaluated the potential beneficial effects of two doses of RUT in a model of pattern-III lesion of MS, in comparison to the conventional standard drug; dimethyl fumarate (DMF). Demyelination was induced in in male adult C57BL/6 mice by dietary 0.2% (w/w) cuprizone (CPZ) feeding for 6 consecutive weeks. Treated groups received either oral RUT (50 or 100 mg/kg) or DMF (15 mg/kg), along with CPZ feeding, for 6 consecutive weeks. Mice were then tested for behavioral changes, followed by biochemical analyses and histological examinations of the corpus callosum (CC). Results revealed that CPZ caused motor dysfunction, demyelination, and glial activation in demyelinated lesions, as well as significant oxidative stress, and proinflammatory cytokine elevation. Six weeks of RUT treatment significantly improved locomotor activity and motor coordination. Moreover, RUT considerably improved remyelination in the CC of CPZ + RUT-treated mice, as revealed by luxol fast blue staining and transmission electron microscopy. Rutin also significantly attenuated CPZ-induced oxidative stress and inflammation in the CC of tested animals. The effect of RUT100 was obviously more marked than either that of DMF, regarding most of the tested parameters, or even its smaller tested dose. In silico docking revealed that RUT binds tightly within NF-κB at the binding site of the protein-DNA complex, with a good negative score of -6.79 kcal/mol. Also, RUT-Kelch-like ECH-associated protein 1 (Keap1) model clarifies the possible inhibition of Keap1-Nrf2 protein-protein interaction. Findings of the current study provide evidence for the protective effect of RUT in CPZ-induced demyelination and behavioral dysfunction in mice, possibly by modulating NF-κB and Nrf2 signaling pathways. The present study may be one of the first to indicate a pro-remyelinating effect for RUT, which might represent a potential additive benefit in treating MS.

Chenopodium Ambrosioides Linn Mitigates Bone Loss in Rats with Periodontitis.

Statement of the Problem: Periodontitis is an inflammatory disease that causes bone loss. Some patients do not respond well to the classic treatment and need therapies that minimize bone loss, the main sequel of the disease. Chenopodium ambrosioides L. has stood out due to its anti-inflammatory and anti-oxidative activities. However, no study has yet investigated its effect on periodontitis. Purpose: This study aimed to evaluate the bone protective effect of Chenopodium ambrosioides L. (CAL) extract on ligature-induced periodontitis model in rats. Materials and Method: For this, a pre-clinical assay was performed, using male Wistar rats divided into 3 groups: Naive (N) (n=6), not submitted to any procedure; Saline (SAL) (n=6), submitted to ligature-induced periodontitis and receiving 2 ml/kg of 0.9% saline solution; and CAL extract, which was subdivided into 3 subgroups (n=6/subgroup) receiving the CAL at 3 (CAL3), 10 (CAL10) or 30 mg/kg (CAL30). All agents were given, by oral gavage, 30 min before periodontitis induction and daily until euthanasia (11th day). By then, maxillae were removed for macroscopic, histological, and histometric analyses. Kidneys, liver, and stomach were collected to evaluate the safety of CAL extract. High-performance liquid chromatography (HPLC) assay was used to investigate the flavonoid content in the extract. Results: Chenopodium ambrosioides L. extract at 30mg/kg showed a reduction by 58% in bone loss marked by an increase (+35%) in the number of osteoblasts and a reduction (-51%) on the number of osteoclasts (p< 0.05). No significant alteration in the liver, kidney, or stomach was seen. Rutin was the main flavonoid found. Conclusion: In summary, it was observed that Chenopodium ambrosioides L. extract has shown important anti-inflammatory and bone anabolic and anti-resorptive properties without causing toxicity in the main organs. Rutin, as the main flavonoid of the extract, seems to be responsible for the beneficial effect of this agent.

Spectrophotometric and Chromatographic Assessment of Total Polyphenol and Flavonoid Content in Rhododendron tomentosum Extracts and Their Antioxidant and Antimicrobial Activity.

In the literature, the chemical composition of Rhododendron tomentosum is mainly represented by the study of isoprenoid compounds of essential oil. In contrast, the study of the content of flavonoids will contribute to the expansion of pharmacological action and the use of the medicinal plant for medical purposes. The paper deals with the technology of extracts from Rh. tomentosum shoots using ethanol of various concentrations and purified water as an extractant. Extracts from Rh. tomentosum were obtained by a modified method that combined the effects of ultrasound and temperature to maximize the extraction of biologically active substances from the raw material. Using the method of high-performance thin-layer chromatography in a system with solvents ethyl acetate/formic acid/water (15:1:1), the following substances have been separated and identified in all the extracts obtained: rutin, hyperoside, quercetin, and chlorogenic acid. The total polyphenol content (TPC) and total flavonoid content (TFC) were estimated using spectrophotometric methods involving the Folin-Ciocalteu (F-C) reagent and the complexation reaction with aluminum chloride, respectively. A correlation analysis was conducted between antioxidant activity and the polyphenolic substance content. Following the DPPH assay, regression analysis shows that phenolic compounds contribute to about 80% (r2 = 0.8028, p < 0.05) of radical scavenging properties in the extract of Rh. tomentosum. The extract of Rh. tomentosum obtained by ethanol 30% inhibits the growth of test cultures of microorganisms in 1:1 and 1:2 dilutions of the clinical strains #211 Staphylococcus aureus and #222 Enterococcus spp. and the reference strain Pseudomonas aeruginosa ATCC 10145.

Bisphosphonate's effect on the tongue in adult male albino rats and the possible protective role of rutin: light and scanning electron microscopic study.

Alendronate sodium (ALS) is a nitrogen-containing bisphosphonate used for the treatment of different bone disorders. However, its adverse effect on oral soft tissue has been detected. Rutin (RUT) is natural flavonoid with antioxidant and anti-inflammatory properties. This work aimed to investigate the possible effect of ALS on the tongue of adult male albino rats and to evaluate the possible protective role of RUT. Forty adult male albino rats were equally divided into four groups: group I (control), group II (RUT): Received RUT 50 mg/kg, group III (ALS): Received ALS 1 mg/kg, group IV (ALS+RUT): Received ALS and RUT with the same doses as pervious groups. The drugs were given once daily for 5 weeks. Tongue specimens were taken and processed for light and scanning electron microscopic inspection. ALS treated group revealed structural changes in the tongue in the form of decrease in the height of the filiform papillae with blunt ends, marked atrophy in some papillae with areas of focal loss, loss of some epithelial cells, pyknotic nuclei and cytoplasmic vacuoles in some epithelial cells. The lamina propria showed inflammatory cellular infiltration with congested blood vessels. Statistically, there were highly significant decrease in the number of proliferating cell nuclear antigen immunopositive cells, area percentage of Bcl-2 immunoexpression and highly significant increase in the collagen content compared to control group. Administration of RUT with ALS minimizes these changes. RUT protected the rat tongue against the histological and immunohistochemical changes induced by ALS through its antioxidant and anti-inflammatory properties.

Positive effects of rutin on female reproduction.

This article reviews the source and properties of rutin (vitamin P), its general physiological and medicinal effects and their mechanisms, but the main subject of it is the currently available knowledge concerning the character and mechanisms of action of rutin on female reproductive processes. The available data demonstrate the stimulatory action of rutin on female reproductive processes: it can promote ovarian follicles development and ovulation, ovarian cyclicity, and viability of ovarian cells. On the other hand, it can suppress ovarian cancer cell and tumour development by inhibition of cell proliferation and growth and activation of their apoptosis and death. Furthermore, it could be able to prevent other reproductive disorders (ischaemia, polycystic ovarian syndrome, toxic effects of chemotherapy, nanoparticles and toluene). Rutin could exert its effects via changes in the release and reception of gonadotropin, ovarian steroid hormones, prostaglandins, cytokines, VEGF, as well as in intracellular regulators and markers of oxidative and inflammatory processes, proliferation, apoptosis and angiogenesis.

Rutin Linoleate Triggers Oxidative Stress-Mediated Cytoplasmic Vacuolation in Non-Small Cell Lung Cancer Cells.

Lung cancer (LC) represents one of the most prevalent health issues globally and is a leading cause of tumor-related mortality. Despite being one the most attractive compounds of plant origin due to its numerous biological properties, the therapeutic applications of rutin (RUT) are limited by its disadvantageous pharmacokinetics. Thus, the present study aimed to evaluate in vitro the application of two RUT fatty acids bioconjugates, rutin oleate (RUT-O) and rutin linoleate (RUT-L), as potential improved RUT-based chemotherapeutics in non-small cell lung cancer (NSCLC) treatment. The results indicate that both compounds lacked cytotoxic potential in EpiAirway™ tissues at concentrations up to 125 µM. However, only RUT-L exerted anti-tumorigenic activity in NCI-H23 NSCLC cells after 24 h of treatment by reducing cell viability (up to 47%), proliferation, and neutral red uptake, causing cell membrane damage and lactate dehydrogenase (LDH) leakage, affecting cytoskeletal distribution, inducing cytoplasmic vacuolation, and increasing oxidative stress. The cytopathic effects triggered by RUT-L at 100 and 125 µM are indicators of a non-apoptotic cell death pathway that resembles the characteristics of paraptosis. The novel findings of this study stand as a basis for further investigations on the anti-cancer properties of RUT-L and their underlying mechanisms.

Rutin/Sulfobutylether-ß-Cyclodextrin as a Promising Therapeutic Formulation for Ocular Infection.

Ocular pathologies present significant challenges to achieving effective therapeutic results due to various anatomical and physiological barriers. Natural products such as flavonoids, alone or in association with allopathic drugs, present many therapeutic actions including anticancer, anti-inflammatory, and antibacterial action. However, their clinical employment is challenging for scientists due to their low water solubility. In this study, we designed a liquid formulation based on rutin/sulfobutylether-ß-cyclodextrin (RTN/SBE-ß-CD) inclusion complex for treating ocular infections. The correct stoichiometry and the accurate binding constant were determined by employing SupraFit software (2.5.120) in the UV-vis titration experiment. A deep physical-chemical characterization of the RTN/SBE-ß-CD inclusion complex was also performed; it confirmed the predominant formation of a stable complex (Kc, 9660 M-1) in a 1:1 molar ratio, with high water solubility that was 20 times (2.5 mg/mL) higher than the free molecule (0.125 mg/mL), permitting the dissolution of the solid complex within 30 min. NMR studies revealed the involvement of the bicyclic flavonoid moiety in the complexation, which was also confirmed by molecular modeling studies. In vitro, the antibacterial and antibiofilm activity of the formulation was assayed against Staphylococcus aureus and Pseudomonas aeruginosa strains. The results demonstrated a significant activity of the formulation than that of the free molecules.