Multilayer Ti3C2-CNTs-Au Loaded with Cyclodextrin-MOF for Enhanced Selective Detection of Rutin.

In this work, multi-layer Ti3C2 - carbon nanotubes - gold nanoparticles (Ti3C2-CNTs-Au) and cyclodextrin metal-organic framework - carbon nanotubes (CD-MOF-CNTs) have been prepared by in situ growth method and used to construct the ultra-sensitive rutin electrochemical sensor for the first time. Among them, the large number of metal active sites of Ti3C2, the high electron transfer efficiency of CNTS, and the good catalytic properties of AuNPs significantly enhance the electrochemical properties of the composite carbon nanomaterials. Interestingly, CD-MOF has a unique host-guest recognition and a large number of cavities, molecular gaps, and surface reactive groups, which gives the composite outstanding accumulation properties and selectivity for rutin. Under the optimized conditions, the constructed novel sensor has satisfactory detection performance for rutin in the range of 2 × 10-9 to 8 × 10-7 M with a limit of detection of 6.5 × 10-10 M. In addition, the sensor exhibits amazing anti-interference performance against rutin in some flavonoid compounds and can be used to test natural plant samples (buckwheat, Cymbopogon distans, and flos sophorae immaturus). This work has promising applications in the field of environmental and food analysis, and exploring new directions for the application of Mxene-based composites.

Major quality regulation network of flavonoid synthesis governing the bioactivity of black wolfberry.

Black wolfberry (Lycium ruthenicum Murr.) contains various bioactive metabolites represented by flavonoids, which are quite different among production regions. However, the underlying regulation mechanism of flavonoid biosynthesis governing the bioactivity of black wolfberry remains unclear. Presently, we compared the bioactivity of black wolfberry from five production regions. Multi-omics were performed to construct the regulation network associated with the fruit bioactivity. The detailed regulation mechanisms were identified using genetic and molecular methods. Typically, Qinghai (QH) fruit exhibited higher antioxidant and anti-inflammatory activities. The higher medicinal activity of QH fruit was closely associated with the accumulation of eight flavonoids, especially Kaempferol-3-O-rutinoside (K3R) and Quercetin-3-O-rutinoside (rutin). Flavonoid biosynthesis was found to be more active in QH fruit, and the upregulation of LrFLS, LrCHS, LrF3H and LrCYP75B1 caused the accumulation of K3R and rutin, leading to high medicinal bioactivities of black wolfberry. Importantly, transcription factor LrMYB94 was found to regulate LrFLS, LrCHS and LrF3H, while LrWRKY32 directly triggered LrCYP75B1 expression. Moreover, LrMYB94 interacted with LrWRKY32 to promote LrWRKY32-regulated LrCYP75B1 expression and rutin synthesis in black wolfberry. Transgenic black wolfberry overexpressing LrMYB94/LrWRKY32 contained higher levels of K3R and rutin, and exhibited high medicinal bioactivities. Importantly, the LrMYB94/LrWRKY32-regulated flavonoid biosynthesis was light-responsive, showing the importance of light intensity for the medicinal quality of black wolfberry. Overall, our results elucidated the regulation mechanisms of K3R and rutin synthesis, providing the basis for the genetic breeding of high-quality black wolfberry.

Rutinosides-derived from Sarocladium strictum 6-O-α-rhamnosyl-ß-glucosidase show enhanced anti-tumoral activity in pancreatic cancer cells.

BACKGROUND: Low targeting efficacy and high toxicity continue to be challenges in Oncology. A promising strategy is the glycosylation of chemotherapeutic agents to improve their pharmacodynamics and anti-tumoral activity. Herein, we provide evidence of a novel approach using diglycosidases from fungi of the Hypocreales order to obtain novel rutinose-conjugates therapeutic agents with enhanced anti-tumoral capacity. RESULTS: Screening for diglycosidase activity in twenty-eight strains of the genetically related genera Acremonium and Sarocladium identified 6-O-α-rhamnosyl-ß-glucosidase (αRßG) of Sarocladium strictum DMic 093557 as candidate enzyme for our studies. Biochemically characterization shows that αRßG has the ability to transglycosylate bulky OH-acceptors, including bioactive compounds. Interestingly, rutinoside-derivatives of phloroglucinol (PR) resorcinol (RR) and 4-methylumbelliferone (4MUR) displayed higher growth inhibitory activity on pancreatic cancer cells than the respective aglycones without significant affecting normal pancreatic epithelial cells. PR exhibited the highest efficacy with an IC50 of 0.89 mM, followed by RR with an IC50 of 1.67 mM, and 4MUR with an IC50 of 2.4 mM, whereas the respective aglycones displayed higher IC50 values: 4.69 mM for phloroglucinol, 5.90 mM for resorcinol, and 4.8 mM for 4-methylumbelliferone. Further, glycoconjugates significantly sensitized pancreatic cancer cells to the standard of care chemotherapy agent gemcitabine. CONCLUSIONS: αRßG from S. strictum transglycosylate-based approach to synthesize rutinosides represents a suitable option to enhance the anti-proliferative effect of bioactive compounds. This finding opens up new possibilities for developing more effective therapies for pancreatic cancer and other solid malignancies.

Rutin attenuates ensartinib-induced hepatotoxicity by non-transcriptional regulation of TXNIP.

Ensartinib, an approved ALK inhibitor, is used as a first-line therapy for advanced ALK-positive non-small cell lung cancer in China. However, the hepatotoxicity of ensartinib seriously limits its clinical application and the regulatory mechanism is still elusive. Here, through transcriptome analysis we found that transcriptional activation of TXNIP was the main cause of ensartinib-induced liver dysfunction. A high TXNIP level and abnormal TXNIP translocation severely impaired hepatic function via mitochondrial dysfunction and hepatocyte apoptosis, and TXNIP deficiency attenuated hepatocyte apoptosis under ensartinib treatment. The increase in TXNIP induced by ensartinib is related to AKT inhibition and is mediated by MondoA. Through screening potential TXNIP inhibitors, we found that the natural polyphenolic flavonoid rutin, unlike most reported TXNIP inhibitors can inhibit TXNIP by binding to TXNIP and partially promoting its proteasomal degradation. Further studies showed rutin can attenuate the hepatotoxicity of ensartinib without antagonizing its antitumor effects. Accordingly, we suggest that TXNIP is the key cause of ensartinib-induced hepatotoxicity and rutin is a potential clinically safe and feasible therapeutic strategy for TXNIP intervention.

Anticancer effects of rutin from Fagopyrum tataricum (tartary buckwheat) against osteosarcoma cell line.

BACKGROUND: The present study is analysisof the seeds of buckwheat (Fagopyrum sp.),member of the Polygonaceae family for isolation of rutin and its anticancer property againstOsteosarcoma celllines (SAOS2). The selected plant is traditionally used for diabetes and cancer. It has several biological properties such as antibacterial, antioxidant and anti-aging. PURPOSE: Thirty-five buckwheat cultivars were obtained from Nepal Agriculture Genetic Resources Centre (NAGRC) Khumaltar, Kathmandu, Nepal, and Kumrek Sikkim. These plant varieties are scientifically evaluated their biological properties. METHODS: Rutin wasfractionated from buckwheat seeds using methanol fraction and analysed for quality by HPLC method. The rutin fraction of the cultivar NGRC03731 a tartary buck wheat and standard rutin was used against Osteosarcoma cell lines (SAOS2) and human gingival fibroblast cells (hGFs) for anticancer activity. The cell viability using rutin fraction and standard rutin treated with SAOS2 cells were assessed by MTT assay. For further research, the best doses (IC-50: 20 g/ml) were applied. By using AO/EtBr dual staining, the effects of Rutin fraction on SAOS2 cell death were analysed. The scratch wound healing assay was used to analyse cell migration. Real-time PCR was used to analyse the pro-/anti-apoptotic gene expression. RESULTS: The seeds with the highest rutin content, NGRC03731 seeds, had 433 mg/100 g of rutin.The rutin fraction treatment and standard rutin significantly reduced cell viability in the MTT assay, and osteosarcoma cells were observed on sensitive to the IC-50 dose at a concentration of 20 g/ml after 24 h.The SAOS2 cells exposed to rutin fraction at 20 g/ml and standard rutin at 10 g/ml exhibited significant morphological alterations, cell shrinkage and decreased cell density, which indicate apoptotic cells.Rutin-fraction treated cells stained with acridine orange/ethidium bromide (AO/EtBr) dual staining cells turned yellow, orange, and red which indicatesto measure apoptosis.The anti-migration potential of rutin fraction, results prevented the migration of SAOS2 cancer cells.Rutin-fraction significantly increased the expression of pro-apoptotic proteinsBad, using real-time PCR analysis (mRNA for Bcl-2 family proteins) resulted Bcl-2's expression is negatively regulated. CONCLUSION: Osteosarcoma (SAOS2) cell lines' proliferation, migration, and ability to proliferate were reduced markedly by rutin fraction and it also causes apoptosis of Osteosarcoma cell lines (SAOS2).

Protective effect of rutin on acrylamide induced ovarian inflammation, oxidative stress, DNA damage, and hormonal changes: Based on in silico and in vivo study.

Acrylamide (AA) is a carcinogenic compound that affects people due to its frequent use in laboratories and industry as well as the high-temperature cooking of foods with high hydrocarbon content. AA is known to cause severe reproductive abnormalities. The main aim of this study is to evaluate the protective effect of rutin (RU), a phytoactive compound, against AA-induced reproductive toxicity in female rats. Initially, rats were exposed to AA (40 mg/kg for 10 days). Therapy of RU was given after AA intoxication consecutively for 3 days. After 24 h of the last treatment, all the animals were sacrificed. The study evaluated reproductive hormones, oxidative stress markers, membrane-bound enzymes, DNA damage, histological findings, and an in silico approach to determine the protective efficacy of RU. The results indicated that RU significantly protected against inflammation, oxidative stress, and DNA damage induced by AA, likely due to its antioxidant properties.

Exploring the therapeutic potential of rutin through investigating its inhibitory mechanism on lactate dehydrogenase: Multi-spectral methods and computer simulation.

Lactate dehydrogenase (LDH), a crucial enzyme in anaerobic glycolysis, plays a pivotal role in the energy metabolism of tumor cells, positioning it as a promising target for tumor treatment. Rutin, a plant-based flavonoid, offers benefits like antioxidant, antiapoptotic, and antineoplastic effects. This study employed diverse experiments to investigate the inhibitory mechanism of rutin on LDH through a binding perspective. The outcomes revealed that rutin underwent spontaneous binding within the coenzyme binding site of LDH, leading to the formation of a stable binary complex driven by hydrophobic forces, with hydrogen bonds also contributing significantly to sustaining the stability of the LDH-rutin complex. The binding constant (Ka) for the LDH-rutin system was 2.692 ± 0.015 × 104 M-1 at 298 K. Furthermore, rutin induced the alterations in the secondary structure conformation of LDH, characterized by a decrease in α-helix and an increase in antiparallel and parallel ß-sheet, and ß-turn. Rutin augmented the stability of coenzyme binding to LDH, which could potentially hinder the conversion process among coenzymes. Specifically, Arg98 in the active site loop of LDH provided essential binding energy contribution in the binding process. These outcomes might explain the dose-dependent inhibition of the catalytic activity of LDH by rutin. Interestingly, both the food additives ascorbic acid and tetrahydrocurcumin could reduce the binding stability of LDH and rutin. Meanwhile, these food additives did not produce positive synergism or antagonism on the rutin binding to LDH. Overall, this research could offer a unique insight into the therapeutic potential and medicinal worth of rutin.

Rutin alleviates psoriasis-related inflammation in keratinocytes by regulating the JAK2/STAT3 signaling.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease that can cause systemic inflammation in various organs. Rutin has been suggested to fight psoriasis, but the signaling pathways by which it works need to be explored. MATERIALS AND METHODS: HaCaT cells co-stimulated with interleukin (IL)-17, IL-22, tumor necrosis factor-alpha (TNF-α), IL-1α, and oncostatin M (M5) were used as an in vitro cell model of psoriasis. The proliferation and viability of HaCaT cells were determined by 5-ethynyl-2'-deoxyuridine and cell counting assays. Relative mRNA levels of IL-6, TNF-α, chemokines (CXCL1 and CXCL2), and anti-microbial peptides (S100A7 and S100A8) were detected by reverse transcriptase-quantitative PCR. Release of IL-6 and TNF-α from HaCaT cells was measured by enzyme-linked immunosorbent assay. Keratin1, Keratin5, p-JAK2, and p-STAT3 protein levels were estimated with western blotting. Molecular docking predicted binding sites for Rutin and STAT3. RESULTS: Rutin treatment undercut M5-urged viability increase and proliferation boost in HaCaT cells. Moreover, M5 stimulation mediated upregulation of IL-6, TNF-α, CXCL1, CXCL2, S100A7, and S100A8 was partially reversed after Rutin treatment. In addition, M5 stimulation induced downregulation of Keratin1 and Keratin5 proteins as well as upregulation of p-JAK2 and p-STAT3 proteins were attenuated in response to Rutin treatment, manifesting that Rutin treatment inhibited M5-promoted aberrant differentiation and impaired M5-mediated activation of the JAK2/STAT3 signaling in HaCaT cells. Molecular docking discovered that residues GLN326 and ASP334 in STAT3 might bind to Rutin. CONCLUSION: Rutin treatment blocked the JAK2/STAT3 signaling, thus attenuating psoriasis-related inflammation and anomalous differentiation in keratinocytes.

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.

Rutin targets AKT to inhibit ferroptosis in ventilator-induced lung injury.

Our previous research confirmed that rutin reduced ventilator-induced lung injury (VILI) in mice. Ferroptosis has been reported to participate in the pathogenic process of VILI. We will explore whether rutin inhibits ferroptosis to alleviate VILI. A mouse model of VILI was constructed with or without rutin pretreatment to perform a multiomics analysis. Hematoxylin-eosin (HE) staining and transmission electron microscopy were used to evaluate lung injury in VILI mice. Dihydroethidium (DHE) staining and the malondialdehyde (MDA) and superoxide dismutase (SOD) levels were detected. Molecular docking was performed to determine the binding affinity between rutin and ferroptosis-related proteins. Western blot analysis, real-time PCR (RT-PCR) and immunohistochemical (IHC) staining were conducted to detect the expression levels of GPX4, XCT, ACSL4, FTH1, AKT and p-AKT in lung tissues. Microscale thermophoresis (MST) was used to evaluate the binding between rutin and AKT1. Transcriptomic and proteomic analyses showed that ferroptosis may play a key role in VILI mice. Metabolomic analysis demonstrated that rutin may affect ferroptosis via the AKT pathway. Molecular docking analysis indicated that rutin may regulate the expression of ferroptosis-related proteins. Moreover, rutin upregulated GPX4 expression and downregulated the expression of XCT, ACSL4 and FTH1 in the lung tissues. Rutin also increased the ratio of p-AKT/AKT and p-AKT expression. MST analysis showed that rutin binds to AKT1. Rutin binds to AKT to activate the AKT signaling pathway, contributing to inhibit ferroptosis, thus preventing VILI in mice. Our study elucidated a possible novel strategy of involving the use of rutin for preventing VILI.

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.

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.

Assessment of Anti-Inflammatory and Antioxidant Activities of a Proprietary Preparation of Quercetin-Rutin Blend (SophorOx™) in Exercised Rats.

Objectives: Flavonoids comprise a huge class of phenolic compounds widely distributed throughout the plant kingdom. Although quercetin and rutin have been studied individually for their therapeutic value, the synergistic effect of combining the two has previously not been measured. The objective of this trial was to evaluate the anti-inflammatory and antioxidant properties of both quercetin and rutin when combined in the form of SophorOx™ (a proprietary preparation of quercetin-rutin) in exercised rats. Methods: Sprague-Dawley rats were orally administered SophorOx™ at 500 mg·kg-1·b.w. and subjected to daily exercise on a fabricated treadmill for 4 weeks. A total of 24 animals were randomly divided into four groups. All the animals were examined for body weight, feed consumption, signs of clinical abnormalities, and morbidity. In addition, serum collected on days 8, 15, 22, and 29 were measured for the liver function test (LFT), random blood sugar (RBS), inflammatory markers C-reactive protein (CRP), oxidative stress markers (8-isoprostane (8-iso-PGF2α), malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and cytokine levels interleukin-1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α)) by the ELISA method. Results: Rats that received SophorOx™ showed no signs of adverse effects, and no significant changes were observed in body weight, feed consumption, liver enzymes, and blood glucose levels. The exercise-treated rats administered with SophorOx™ exhibited a significant reduction in oxidative and inflammatory marker levels, viz., CRP (113.32 ng·mL-1) and oxidative stress markers 8-OHdG (19.32 pg·mL-1), MDA (1.06 nmol·mL-1), 8-iso-PGF2α (1.29 ng·mL-1), IL-1ß (0.77 pg·mL-1), and IL-6 (317.14 pg·mL-1) in comparison to those rodents that were exercised without SophorOx™. Conclusion: Oral administration of SophorOx™ significantly reduced oxidative stress and inflammatory marker levels when measured in the rodents subjected to high-intensity exercise.

Simultaneous assessment of absorption and pharmacokinetic characteristics of four active flavonoids from Chimonanthus nitens Leaf Granules using LC-MS determination: in vivo and in vitro.

A sensitive UPLC-HRMS method was developed and validated for simultaneous quantification of four active flavonoids from Chimonanthus nitens Leaf Granules (CNLG) in biological matrix. The method was utilized in pharmacokinetic study of the four flavonoids in rats as well as other evaluation assays in vitro. It was revealed that rutin, nicotiflorin, and astragalin had poor oral bioavailability in rats possibly due to low intestinal permeability and metabolism in intestinal flora. Kaempferol underwent rapid glucuronidation and sulphation in rat plasma with medium permeability coefficient. The results provided valuable data for future research and development of CNLG flavonoids.

Effect of the Flavonoid Rutin on the Modulation of the Myenteric Plexuses in an Experimental Model of Parkinson's Disease.

Recent discoveries have shown that enteric glial cells play an important role in different neurodegenerative disorders, such as Parkinson's disease (PD), which is characterized by motor dysfunctions caused by the progressive loss of dopaminergic neurons in the substance nigra pars compacta and non-motor symptoms including gastrointestinal dysfunction. In this study, we investigated the modulatory effects of the flavonoid rutin on the behavior and myenteric plexuses in a PD animal model and the response of enteric glia. Adult male Wistar rats were submitted to stereotaxic injection with 6-hydroxydopamine or saline, and they were untreated or treated with rutin (10 mg/kg) for 14 days. The ileum was collected to analyze tissue reactivity and immunohistochemistry for neurons (HuC/HuD) and enteric glial cells (S100ß) in the myenteric plexuses. Behavioral tests demonstrated that treatment with rutin improved the motor capacity of parkinsonian animals and improved intestinal transit without interfering with the cell population; rutin treatment modulated the reactivity of the ileal musculature through muscarinic activation, reducing relaxation through the signaling pathway of nitric oxide donors, and increased the longitudinal contractility of the colon musculature in parkinsonian animals. Rutin revealed modulatory activities on the myenteric plexus, bringing relevant answers regarding the effect of the flavonoid in this system and the potential application of PD adjuvant treatment.

In Silico Assessment of Chemical Disinfectants on Surface Proteins Unveiled Dissimilarity in Antiviral Efficacy and Suitability towards Pathogenic Viruses.

Viral pathogens pose a substantial threat to public health and necessitate the development of effective remediation and antiviral strategies. This short communication aimed to investigate the antiviral efficacy of disinfectants on the surface proteins of human pathogenic viruses. Using in silico modeling, the ligand-binding energies (LBEs) of selected disinfectants were predicted and combined with their environmental impacts and costs through an eco-pharmaco-economic analysis (EPEA). The results revealed that the binding affinities of chemical disinfectants to viral proteins varied significantly (p < 0.005). Rutin demonstrated promising broad-spectrum antiviral efficacy with an LBE of -8.49 ± 0.92 kcal/mol across all tested proteins. Additionally, rutin showed a superior eco-pharmaco-economic profile compared to the other chemicals, effectively balancing high antiviral effectiveness, moderate environmental impact, and affordability. These findings highlight rutin as a key phytochemical for use in remediating viral contaminants.

Molecular-Scale Investigations Reveal the Effect of Natural Polyphenols on BAX/Bcl-2 Interactions.

Apoptosis signaling controls the cell cycle through the protein-protein interactions (PPIs) of its major B-cell lymphoma 2-associated x protein (BAX) and B-cell lymphoma 2 protein (Bcl-2). Due to the antagonistic function of both proteins, apoptosis depends on a properly tuned balance of the kinetics of BAX and Bcl-2 activities. The utilization of natural polyphenols to regulate the binding process of PPIs is feasible. However, the mechanism of this modulation has not been studied in detail. Here, we utilized atomic force microscopy (AFM) to evaluate the effects of polyphenols (kaempferol, quercetin, dihydromyricetin, baicalin, curcumin, rutin, epigallocatechin gallate, and gossypol) on the BAX/Bcl-2 binding mechanism. We demonstrated at the molecular scale that polyphenols quantitatively affect the interaction forces, kinetics, thermodynamics, and structural properties of BAX/Bcl-2 complex formation. We observed that rutin, epigallocatechin gallate, and baicalin reduced the binding affinity of BAX/Bcl-2 by an order of magnitude. Combined with surface free energy and molecular docking, the results revealed that polyphenols are driven by multiple forces that affect the orientation freedom of PPIs, with hydrogen bonding, hydrophobic interactions, and van der Waals forces being the major contributors. Overall, our work provides valuable insights into how molecules tune PPIs to modulate their function.

Acerola (Malpighia emarginata) Anti-Inflammatory Activity-A Review.

The manuscript provides an overview of recent scientific reports on the properties and range of health-promoting effects of acerola (Malpighia emarginata DC) fruits and leaves. Acerola is a natural raw material that, in its unprocessed form, is known to be a rich source of vitamin C and polyphenolic compounds. For this reason, the consumption of acerola may provide a number of health-promoting benefits, particularly related to its strong anti-free radical effects. The review discusses anti-inflammatory and anticancer effects of acerola fruit and leaves as well as its therapeutic effects on selected physiological processes in the human system. Their biochemical mechanisms are also explained. Recommendations for the consumption of acerola in the prevention of inflammatory and free radical diseases are presented. The part of the article devoted to anticancer effects of acerola describes the possibilities of using the edible parts of this raw material to obtain products and preparations of potential use in cancer prevention and therapy.

Design, Synthesis and Antitumor Activity of Quercetin Derivatives Containing a Quinoline Moiety.

Quercetin is a flavonoid with significant biological and pharmacological activity. In this paper, quercetin was modified at the 3-OH position. Rutin was used as a raw material. We used methyl protection, Williamson etherification reactions, and then substitution reactions to prepare 15 novel quercetin derivatives containing a quinoline moiety. All these complexes were characterized by 1H NMR, 13C NMR, IR and HRMS. Of these, compound 3e (IC50 = 6.722 µmol·L-1) had a better inhibitory effect on human liver cancer (HepG-2) than DDP (Cisplatin) (IC50 = 26.981 µmol·L-1). The mechanism of the action experiment showed that compound 3e could induce cell apoptosis.

Optimized Conditions for the Extraction of Phenolic Compounds from Aeginetia indica L. and Its Potential Biological Applications.

Aeginetia indica L., a parasitic root in the Orobanchaceae family, is used as a food colorant in traditional Thai desserts. However, scant information is available on its food applications as well as medicinal properties, while overharvesting by the local people has severely depleted wild plant populations. This research, thus, aimed to extract optimized total phenolic content (TPC) in varying extraction conditions using response surface methodology (RSM) and the Box-Behnken design (BBD). Results indicated that an extraction temperature of 90 °C, 80% (v/v) aqueous ethanol, and 0.5% (w/v) solid-to-liquid ratio yielded the highest TPC at 129.39 mg gallic acid equivalent (GAE)/g dry weight (DW). Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) identified the predominant phenolics as apigenin (109.06 mg/100 g extract) and luteolin (35.32 mg/100 g extract) with trace amounts of naringenin and rutin. Under the optimal extraction condition, the plant extract exhibited antioxidant activities of 5620.58 and 641.52 µmol Trolox equivalent (TE)/g DW determined by oxygen radical absorbance capacity (ORAC) and ferric ion reducing antioxidant power (FRAP) assay, while the scavenging capacity of total radicals at 50% (SC50) was determined to be 135.50 µg/mL using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The plant extract also exhibited inhibitory activities against the key enzymes relevant to type II diabetes, obesity, and Alzheimer's disease, suggesting the potential for medicinal applications.