Integrative analysis of the metabolome and transcriptome reveals the mechanism of polyphenol biosynthesis in Taraxacum mongolicum.

Introduction: Dandelion is widely used in clinical practice due to its beneficial effects. Polyphenolic compounds are considered the main anti-inflammatory active ingredient of dandelion, but the gene expression patterns of polyphenolic compounds in different dandelion tissues are still unclear. Methods: In this study, we combined a nontargeted metabolome, PacBio Iso-seq transcriptome, and Illumina RNA-seq transcriptome to investigate the relationship between polyphenols and gene expression in roots, flowers, and leaves of flowering dandelion plants. Results: Eighty-eight flavonoids and twenty-five phenolic acids were identified, and 64 candidate genes involved in flavonoid biosynthesis and 63 candidate genes involved in chicoric acid biosynthesis were identified. Most flavonoid and chicoric acid-related genes demonstrated the highest content in flowers. RNA-seq analysis revealed that genes involved in polyphenol biosynthesis pathways, such as CHS, CHI, F3H, F3'H, FLS, HQT, and CAS, which are crucial for the accumulation of flavonoids and chicoric acid, were upregulated in flowers. Discussion: The combination of transcriptomic and metabolomic data can help us better understand the biosynthetic pathways of polyphenols in dandelion. These results provide abundant genetic resources for further studying the regulatory mechanism of dandelion polyphenol biosynthesis.

Exogenous salicylic acid treatment enhances the disease resistance of Panax vietnamensis by regulating secondary metabolite production.

Introduction: Salicylic acid (SA) is a phenolic compound widely found in plants. It plays a key role in exerting plant disease resistance. Panax vietnamensis Ha & Grushv., a valuable medicinal plant, contains high levels of phenolic compounds, which contribute significantly to the resilience of the plant against stress. However, the precise role of SA in regulating the synthesis of secondary metabolites in P.vietnamensis remains elusive. Methods: Two-year-old P. vietnamensis seedlings were treated with exogenous SA. We systematically assessed the changes in the physiological parameters of SA-treated P. vietnamensis leaves, employing transcriptome and metabolome analyses to elucidate the underlying mechanisms. Results: Our results revealed a significant improvement of the plant's antioxidant capacity at 6 h post-treatment. Furthermore, exogenous SA treatment promoted the biosynthesis of lignin and flavonoids such as rutin, coumarin, and cyanidin. In addition, it increased the levels of endogenous SA and jasmonic acid (JA), promoting the disease resistance of the plants. Thus, SA pretreatment enhanced the defense of P. vietnamensis against pathogens. Conclusions: Our study provided novel insights into the potential molecular mechanisms underlying SA-mediated biosynthesis of secondary metabolites. Furthermore, our results provided a theoretical foundation for optimizing the cultivation practices of P.vietnamensis and the application of SA as a plant immunomodulator.

Physiological, transcriptomic, and metabolomic analyses reveal that Pantoea sp. YSD J2 inoculation improves the accumulation of flavonoids in Cyperus esculentus L. var. sativus.

Plant growth-promoting microorganisms (PGPMs), such as Pantoea sp. YSD J2, promote plant development and stress resistance, while their role in flavonoids accumulation still needs to be further understood. To investigate the complex flavonoid biosynthesis pathway of Cyperus esculentus L. var. sativus (tigernut), we compared Pantoea sp. YSD J2 inoculation (YSD J2) and water inoculation (CK) groups. YSD J2 significantly elevated the content of indole-3-acetic acid (IAA) and orientin. Furthermore, when analyzing flavonoid metabolome, YSD J2 caused increased levels of uralenol, petunidin-3-O-glucoside-5-O-arabinoside, luteolin-7-O-glucuronide-(2 â†’ 1)-glucuronide, kaempferol-3-O-neohesperidoside, cyanidin-3-O-(2″-O-glucosyl)glucoside, kaempferol-3-O-glucuronide-7-O-glucoside, quercetin-3-O-glucoside, luteolin-7-O-glucuronide-(2 â†’ 1)-(2″-sinapoyl)glucuronide, and quercetin-4'-O-glucoside, which further enhanced antioxidant activity. We then performed RNA-seq and LC-MS/MS, aiming to validate key genes and related flavonoid metabolites under YSD J2 inoculation, and rebuild the gene-metabolites regulatory subnetworks. Furthermore, the expression patterns of the trans cinnamate 4-monooxygenase (CYP73A), flavonol-3-O-L-rhamnoside-7-O-glucosyltransferase (UGT73C6), shikimate O-hydroxycinnamoyltransferase (HCT), chalcone isomerase (CHI), flavonol synthase (FLS), and anthocyanidin synthase (ANS) genes were confirmed by qRT-PCR. Additionally, 4 transcription factors (TF) (especially bHLH34, Cluster-37505.3) under YSD J2 inoculation are also engaged in regulating flavonoid accumulation. Moreover, the current work sheds new light on studying the regulatory effect of Pantoea sp. YSD J2 on tigernut development and flavonoid biosynthesis.

Nano-Rutin: A Promising Solution for Alleviating Various Disorders.

BACKGROUND: Rutin, often known as vitamin P, is a natural flavonoid compound, which offers a broad spectrum of therapeutic potentials. Rutin is metabolised to different compounds by the gut bacteria after consumption, therefore, very little is absorbed. Higher plants contribute to rutin synthesis in large quantities, and it may also be found in many fruits and fruity rinds, particularly citrus fruits and berries. OBJECTIVE: The present paper highlights several studies conducted on rutin along with its nanoformulations regarding its broad spectrum of therapeutic potentials. METHOD: Numerous electronic databases, including Springer, PubMed, Science Direct, Pubchem, etc. were searched to extract relevant published literature demonstrating rutin effectiveness in various ailments. RESULTS: The reviewed literature showed that rutin and related flavonoids possess a variety of physiological properties that protects human beings, plants and animals. Antioxidant, anti-inflammatory, anti-allergic, cytoprotective, vasoprotective, anticarcinogenic, neuroprotective, cardioprotective, antibacterial, antiviral, antiprotozoal, antitumor, anti-hypertensive antiplatelet, antispasmodic and hypolipidemic, activities. Nanotechnology has been implemented for the improvement of the bioavailability of rutin using novel drug-delivery carriers. CONCLUSION: The study concludes that the development of rutin nanoformulations for multiple therapeutic approaches contributes towards enhanced aqueous solubility as well as tailored pharmacokinetics compared to conventional delivery of rutin. However, more investigations should be conducted to confirm the improved bioavailability of the rutin nanoformulations.

Correlation between Honey Parameters and Wound Healing Properties: The Case of Piedmont (Italy) Samples.

INTRODUCTION: Honey possesses several positive properties, making it effective in wound healing mechanisms. However, very little information is available on the different honey types for wound healing activity. METHOD: In the first "Academy of Sciences", a public engagement project with high school students, we assessed the properties of thirteen kinds of honey from the Piedmont area (Nord West Italy). In particular, we characterized the color intensity (by Pfund scale), total phenolic content (TPC), total flavonoid content (TFC), H2O2 production, and wound closure rate. RESULTS: Then, we tried to verify the presence of a correlation between these parameters, finding a positive correlation between H2O2 and wound closure rate. CONCLUSION: These data pave the way to characterize different types of Italian honey to completely understand its potential.

Effect of baicalin and baicalin-bovine serum albumin nanoparticle against bendiocarb exposure in rats.

Background: The aim of the study was to investigate the effect of baicalin and baicalin-bovine serum albumin nanoparticles against bendiocarb exposure in rats. Methods: Eighty male Wistar Albino rats aged 4-6 weeks were used. Corn oil (vehicle) alone was administered to the control group. To other groups, BSA-nanoparticle equivalent to that binding baicalin at a dose of 20 mg/kg.bw, 20 mg/kg.bw baicalin, baicalin-BSA nanoparticle equivalent to that binding baicalin at a dose of 20 mg/kg.bw, 4 mg/kg.bw bendiocarb, combination of 4 mg/kg.bw bendiocarb and 20 mg/kg.bw baicalin, combination of 4 mg/kg.bw bendiocarb and BSA-nanoparticle equivalent to that binding baicalin at a dose of 20 mg/kg.bw and combination of 4 mg/kg.bw bendiocarb and baicalin-BSA nanoparticle equivalent to that binding baicalin at a dose of 20 mg/kg.bw was administered to animals by oral gavage with vehicle for 21 days, after which organs (liver, kidney, brain, testes, heart and lung) and blood samples were collected. Blood/tissue oxidative stress (MDA, NO, GSH, SOD, CAT, GSH-Px, GR, GST, G6PD), serum biochemical (glucose, triglyceride, cholesterol, BUN, creatinine, uric acid, total protein, albumin, LDH, AST, ALT, ALP and pseudocholinesterase) and liver and kidney apoptotic/anti-apoptotic (caspase 3, 9, p53, Bcl-2 and Bax) parameters were evaluated. Body weights/organ weights and plasma/liver bendiocarb analyses were obtained. Conclusion: While bendiocarb administered alone caused oxidative stress/tissue damage, baicalin and baicalin-BSA nanoparticle showed a mitigating effect. However, this effect was more pronounced in the baicalin-BSA nanoparticle group. BSA-nanoparticle alone did not have a significant effect in reversing the adverse effect caused by bendiocarb.

Enhancing therapy with nano-based delivery systems: exploring the bioactive properties and effects of apigenin.

Apigenin, a potent natural flavonoid, has emerged as a key therapeutic agent due to its multifaceted medicinal properties in combating various diseases. However, apigenin's clinical utility is greatly limited by its poor water solubility, low bioavailability and stability issues. To address these challenges, this review paper explores the innovative field of nanotechnology-based delivery systems, which have shown significant promise in improving the delivery and effectiveness of apigenin. This paper also explores the synergistic potential of co-delivering apigenin with conventional therapeutic agents. Despite the advantageous properties of these nanoformulations, critical challenges such as scalable production, regulatory approvals and comprehensive long-term safety assessments remain key hurdles in their clinical adoption which must be addressed for commercialization of apigenin-based formulations.

Apigenin is a natural substance found in plants that might help treat illnesses like cancer, diabetes, heart problems and brain disorders. But it doesn't work very well because it doesn't dissolve in water, is hard for the body to use and isn't very stable. To fix this, scientists are putting apigenin inside tiny carriers called nanocarriers. These tiny carriers help apigenin dissolve better, be absorbed by the body more easily and work better.There are different kinds of nanocarriers, like tiny fat bubbles, tiny solid particles and tiny gels. These can be made to target specific parts of the body, which helps reduce side effects. Apigenin can also be mixed with other medicines in these carriers to work even better.However, there are big challenges in making these treatments widely available, like making enough of them, getting permission from health authorities and making sure they are safe for a long time. This review talks about the latest progress and future possibilities in using nanotechnology to deliver apigenin, aiming to make it better for treating diseases.

The Houttuynia cordata genome provides insights into the regulatory mechanism of flavonoid biosynthesis in Yuxingcao.

Houttuynia cordata Thunb., also known as Yuxingcao in Chinese, is a perennial herb in the Saururaceae family. It is highly regarded for its medicinal properties, particularly in treating respiratory infections and inflammatory conditions, as well as boosting the human immune system. However, the lack of genomic information has hindered research on the functional genomics and potential improvements of H. cordata. In this study, we present the assembly of a near-complete genome of H. cordata and investigate the biosynthesis pathway of flavonoids, specifically quercetin, using genomics, transcriptomics, and metabolomics analysis. The genome of H. cordata diverged from Saururus chinensis around 33.4 million years ago and consists of 2.24 Gb with 76 chromosomes (4n = 76), which underwent three whole-genome duplication (WGD) events. These WGDs played a crucial role in shaping H. cordata's genome and influencing gene families associated with its medicinal properties. Through metabolomics and transcriptomics analysis, we identified key genes involved in the ß-oxidation process for houttuynin biosynthesis, one of the volatile oils responsible for its fishy-smell. Additionally, utilizing the reference genome, we effectively identified genes involved in flavonoid biosynthesis, particularly quercetin metabolism in H. cordata. This discovery has paramount implications for understanding the regulatory mechanisms of active pharmaceutical ingredient production in traditional Chinese medicine. Overall, the high-quality genome of H. cordata serves as a crucial resource for future functional genomics research and provides a solid foundation for genetic improvement of H. cordata for the benefit of human health.

The molecular basis of flavonoid biosynthesis response to water, light, and temperature in grape berries.

Flavonoids, including proanthocyanidins (PAs), anthocyanins and flavonols are essential secondary metabolites that contribute to the nutritional value and sensory quality of grape berry and red wine. Advances in molecular biology technology have led to substantial progress in understanding the regulation of flavonoid biosynthesis. The influence of terroir on grape berries and wine has garnered increasing attention, yet its comprehensive regulatory network remains underexplored. In terms of application, environmental factors such as water, light, and temperature are more easily regulated in grapevines compared to soil conditions. Therefore, we summarize their effects on flavonoid content and composition, constructing a network that links environmental factors, hormones, and metabolites to provide a deeper understanding of the underlying mechanisms. This review enriches the knowledge of the regulatory network mechanisms governing flavonoid responses to environmental factors in grapes.

Low Dietary Flavonoid Consumption Is Associated to Severe Inflammatory Bowel Disease.

Background and Aims: Associations between diet habits and inflammatory bowel disease (IBD) have been widely described. Flavonoids are taken with vegetables, fruits, and green tea. Because of barrier-protective and anti-inflammatory effects, flavonoid consumption (FC) may influence the severity of IBD. The aim of this study was to reveal the role of FC in the course and severity of IBD. Methods: A prospective cohort study including 204 IBD patients (Crohn's disease n = 126, ulcerative colitis n = 78) was conducted between 2016 and 2021. FC was calculated using questionnaires. In addition to standard activity scores and different treatments, a "severity index" was related to individual FC. Differences between groups and odds ratios were analyzed. Results: Inverse correlation (r = -0.0549; P = .01) between FC and severity of IBD was found. Patients were assigned to 3 different severity index ranges: mild, moderate, and severe disease. FC of patients with severe disease (331 ± 330 mg/week) was less than FC of patients with mild (1404 ± 1086 mg/ week) disease (P < .001). The risk of IBD patients with low FC (1000 mg/week) experiencing overall severe disease was 17 times increased (P < .001) compared to patients with high FC (>1000 mg/week). Patients with UC and low FC had a 9.6-times higher risk for disease progression (P < .001). Conclusion: Consumption of dietary flavonoids and the overall severity of IBD are inversely correlated. Patients with mild diseases consume higher amounts of flavonoids than patients with severe diseases. Low dietary flavonoids were related to a considerable risk of severe IBD.

Macroporous polymeric resin for the purification of flavonoids from medicinal plants: A review.

The purification of flavonoids using the macroporous polymer resin method has gained attention in recent years due to its simplicity, precision, cost-effectiveness, and the ability to separate flavonoids from other constituents. Several studies have been conducted to investigate the efficiency and effectiveness of macroporous polymer resin in purifying flavonoids from various plant sources. This review aims to evaluate the existing literature on macroporous polymer resin purification of flavonoids and provide a comprehensive analysis of the current research trends and advancements in this field. It also highlights the importance of optimizing the adsorption parameters and conditions such as resin type, resin concentration, pH, and temperature for efficient purification of flavonoids using macroporous polymer resin. The key findings of this review reveal that macroporous resins with weak polarity, large surface areas, and pore diameters have a stronger adsorption capacity for flavonoids compared to polar resins. Furthermore, ultrasonic-solvent assisted extraction often combines with macroporous resin for effective the extraction and purification of flavonoids.

Unveiling the mechanism of hesperidin-induced LdTopI-mediated cell death pathway in protozoan parasite Leishmania donovani.

Unicellular protozoan parasite Leishmania donovani is the causative agent for visceral leishmaniasis (VL) or Kala-azar, a neglected fatal parasitic disease. The conventional treatment of VL consists of therapeutic agents having several shortcomings such as toxicity, high cost, efficacy variance and increased drug resistance. Therefore, there is a desperate need to develop an effective treatment against the parasite. Previous reports suggested that flavonoids can inhibit the enzyme Leishmania donovani DNA topoisomerase I (LdTopILS). Therefore, for the first time in this present study, we divulge HSP (one of the natural sources of flavonoids), as a potent natural antileishmanial compound with efficacy in BALB/c mice at 20 mg/kg of body weight, inhibits LdTopILS at 97 % of its activity at 160 µM in preincubation condition (competitively). It binds with free enzyme and does not allow it to bind with the substrate DNA. Moreover, HSP does not stabilize DNA-topoisomerase I cleavable complex. Thus, HSP acts a catalytic topoisomerase I inhibitor, which inhibits complete activity by binding with Lys269 and Thr411 of large subunit of the enzyme. On the other hand, HSP induces the topo I-mediated programmed cell death process by the formation of cellular reactive oxygen species, resulting in depolarization of mitochondrial membrane potential, followed by fragmentation of nuclear DNA. Therefore, the present study illuminates a natural flavonoid that in future might be a promising lead for the treatment of VL.

Advances in Flavonoid and Derivative Biosynthesis: Systematic Strategies for the Construction of Yeast Cell Factories.

Flavonoids, a significant group of natural polyphenolic compounds, possess a broad spectrum of pharmacological effects. Recent advances in the systematic metabolic engineering of yeast cell factories (YCFs) provide new opportunities for enhanced flavonoid production. Herein, we outline the latest research progress on typical flavonoid products in YCFs. Advanced engineering strategies involved in flavonoid biosynthesis are discussed in detail, including enhancing precursor supply, cofactor engineering, optimizing core pathways, eliminating competitive pathways, relieving transport limitations, and dynamic regulation. Additionally, we highlight the existing problems in the biosynthesis of flavonoid glucosides in yeast, such as endogenous degradation of flavonoid glycosides, substrate promiscuity of UDP-glycosyltransferases, and an insufficient supply of UDP-sugars, with summaries on the corresponding solutions. Discussions also cover other typical postmodifications like prenylation and methylation, and the recent biosynthesis of complex flavonoid compounds in yeast. Finally, a series of advanced technologies are envisioned, i.e., semirational enzyme engineering, ML/DL algorithn, and systems biology, with the aspiration of achieving large-scale industrial production of flavonoid compounds in the future.

Intake of dietary flavonoids in relation to overactive bladder among U.S. adults: a nutritional strategy for improving urinary health.

Background: The increasing influence of overactive bladder (OAB) on physical as well as mental health of individuals is becoming more pronounced annually, as evidenced by the urge urinary incontinence and nocturia. Symptoms in OAB patients may be influenced by inflammation and oxidative stress. Flavonoids are recognized as significant anti-inflammatory and antioxidant agents, which are commonly available in fruits, tea, vegetables, etc. Previous research has demonstrated the therapeutic potential of flavonoids and their subclasses in treating inflammation, and oxidative stress. Despite this, there remains a paucity of research exploring the potential correlation between flavonoid consumption, specifically within distinct subclasses, and OAB. Thus, our study aims to investigate the relationship between flavonoid intake and OAB to identify possible dietary interventions for OAB management. Methods: We utilized the survey data from the National Health and Nutrition Examination Survey (NHANES) and the USDA Food and Nutrient Database for Dietary Studies (FNDDS) to investigate the relationship between dietary intake of total and subclass flavonoids and the risk of OAB based on 13,063 qualified American adults. The dietary flavonoid intake was estimated from two 24-h dietary recalls. Weighted multivariate logistic regression model, quantile-based g-computation, restricted cubic spline model, and stratified analysis were used to explore the association between flavonoid intake and OAB, respectively. Results: The participants diagnosed with OAB exhibited a higher percentage of being female, older, Non-Hispanic Black, unmarried, former drinkers, having a lower annual household income, lower poverty to income ratio, lower educational attainment, and a higher likelihood of being obese and smokers. Upon adjusting for confounding factors, the weighted logistic regression models revealed that the third quartile of consumption of anthocyanidin and the second quartile of consumption of flavone were significantly associated with the reduced odds of OAB, while total flavonoid consumption did not show a significant correlation with the risk of OAB. The quantile-based g-computation model indicated that flavone, anthocyanidin and flavonol were the primary contributors to the observed negative correlation. Furthermore, the restricted cubic spline models demonstrated a J-shaped non-linear exposure-response association between anthocyanidin intake and the risk of OAB (P nonlinear = 0.00164). The stratified and interaction analyses revealed that the relationship between anthocyanidin intake and the risk of OAB was significantly influenced by age (P interaction = 0.01) and education level (P interaction = 0.01), while the relationship between flavone intake and the risk of OAB was found to vary by race (P interaction = 0.02) and duration of physical activity (P interaction = 0.05). Conclusion: Our research suggests that consuming a diet rich in flavonoid subclass anthocyanidin and flavone is associated with a reduced risk of OAB, potentially offering clinical significance in the prevention of OAB development. This underscores the importance of dietary adjustments in the management of OAB symptoms.

Phytochemical profile and antioxidant capacity of the endemic species Bellevalia sasonii Fidan.

The study investigated total phenolic-flavonoid content, antioxidant activity, and phytochemical compounds across various parts (bulb, stem, leaf, and flower) of the endemic Bellevalia sasonii, commonly known as hyacinth, belonging to the Asparagaceae family. Phenolic content was highest in bulb extracts (117.28 µg GAE) and lowest in stems (45.11 µg GAE). Conversely, leaf extracts exhibited the highest flavonoid content (79.44 µg QEs), while stems showed the lowest (22.77 µg QEs). When the antioxidant activities were compared, by DPPH method leaf = flower > bulb > stem; in ABTS and CUPRAC methods bulb > flower > leaf > stem, respectively. Considering the results in general, it was revealed that bulbs and flowers displayed higher activity, while stem exhibited lower activity compared to other parts. The phytochemical analysis identified 53 active substances, with 27 absent in any extract and 15 detected across all extracts. The distribution of phytochemicals varied among parts, with bulbs, stems, flowers, and leaves also different numbers. The LC-MS/MS analysis revealed prominent metabolites including fumaric acid in leaves, caffeic acid in bulbs, and cosmosiin and quinic acid in flowers. This study provides foundational insights into B. sasonii, an important endemic plant in Türkiye, laying the groundwork for future research on its medicinal and ecological roles.

Integrative Transcriptomic and Metabolic Analyses Reveal That Flavonoid Biosynthesis Is the Key Pathway Regulating Pigment Deposition in Naturally Brown Cotton Fibers.

Brown cotton is a major cultivar of naturally colored cotton, and brown cotton fibers (BCFs) are widely utilized as raw materials for textile industry production due to their advantages of being green and dyeing-pollution-free. However, the mechanisms underlying the pigmentation in fibers are still poorly understood, which significantly limits their extensive applications in related fields. In this study, we conducted a multidimensional comparative analysis of the transcriptomes and metabolomes between brown and white fibers at different developmental periods to identify the key genes and pathways regulating the pigment deposition. The transcriptomic results indicated that the pathways of flavonoid biosynthesis and phenylpropanoid biosynthesis were significantly enriched regulatory pathways, especially in the late development periods of fiber pigmentation; furthermore, the genes distributed in the pathways of PAL, CHS, F3H, DFR, ANR, and UFGT were identified as significantly up-regulated genes. The metabolic results showed that six metabolites, namely (-)-Epigallocatechin, Apiin, Cyanidin-3-O-glucoside, Gallocatechin, Myricetin, and Poncirin, were significantly accumulated in brown fibers but not in white fibers. Integrative analysis of the transcriptomic and metabolomic data demonstrated a possible regulatory network potentially regulating the pigment deposition, in which three MYB transcription factors promote the expression levels of flavonoid biosynthesis genes, thereby inducing the content increase in (-)-Epigallocatechin, Cyanidin-3-O-glucoside, Gallocatechin, and Myricetin in BCFs. Our findings provide new insights into the pigment deposition mechanism in BCFs and offer references for genetic engineering and breeding of colored cotton materials.

Kuwanon C Inhibits Tumor Cell Proliferation and Induces Apoptosis by Targeting Mitochondria and Endoplasmic Reticulum.

Kuwanon C is a unique flavonoid found in the mulberry family, characterized by two isopentenyl groups. While previous research has focused on various properties of kuwanon C, such as antioxidant, hypoglycemic, antimicrobial, food preservation, skin whitening, and nematode lifespan extension, little attention has been given to its potential role in oncological diseases. In this study, we investigate the antitumor effect of kuwanon C in cervical cancer cells and elucidate its specific mechanism of action. We assessed the antitumor effects of kuwanon C using various experimental techniques, including cell proliferation assay, wound healing assays, EdU 488 proliferation assay, mitochondrial membrane potential assay, ROS level assay, cell cycle, apoptosis analysis, and studies on kuwanon C target sites and molecular docking. The results revealed that kuwanon C significantly impacted the cell cycle progression of HeLa cells, disrupted their mitochondrial membrane potential, and induced a substantial increase in intracellular ROS levels. Moreover, kuwanon C exhibited notable anti-proliferative and pro-apoptotic effects on HeLa cells, surpassing the performance of commonly used antitumor drugs such as paclitaxel and cisplatin. Notably, kuwanon C demonstrated superior efficacy while also being more easily accessible compared to paclitaxel. Our study demonstrates that kuwanon C exerts potent antitumor effects by its interaction with the mitochondrial and endoplasmic reticulum membranes, induces a significant production of ROS, disrupts their normal structure, inhibits cell cycle progression, and stimulates apoptotic signaling pathways, ultimately resulting in the death of HeLa tumor cells. As an isopentenyl compound derived from Morus alba, kuwanon C holds great promise as a potential candidate for the development of effective antitumor drugs.

Molecular Pro-Apoptotic Activities of Flavanone Derivatives in Cyclodextrin Complexes: New Implications for Anticancer Therapy.

This study evaluates the antiproliferative potential of flavanones, chromanones and their spiro-1-pyrazoline derivatives as well as their inclusion complexes. The main goal was to determine the biological basis of molecular pro-apoptotic activities and the participation of reactive oxygen species (ROS) in shaping the cytotoxic properties of the tested conjugates. For this purpose, changes in mitochondrial potential and the necrotic/apoptotic cell fraction were analyzed. Testing with specific fluorescent probes found that ROS generation had a significant contribution to the biological anticancer activity of complexes of flavanone analogues. TT (thrombin time), PT (prothrombin time) and APTT (activated partial tromboplastin time) were used to evaluate the influence of the compounds on the extrinsic and intrinsic coagulation pathway. Hemolysis assays and microscopy studies were conducted to determine the effect of the compounds on RBCs.

An international observational study assessing conservative management in hemorrhoidal disease: results of CHORALIS (aCute HemORrhoidal disease evALuation International Study).

Aim: Real-world evidence on the management of hemorrhoidal disease (HD) is limited. This international study collected clinical practice data on the effectiveness of conservative treatments for acute HD on symptoms and quality of life (QoL), providing perspectives of treatment modalities from different continents. Patients & methods: The 4-week observational prospective CHORALIS study involved adult outpatients consulting for spontaneous complaints of hemorrhoids (graded using Goligher classification) and prescribed conservative treatments according to usual clinical practice. Assessments were: anal pain/discomfort (visual analog scale [VAS]), other signs/symptoms (patient questionnaire), Patient Global Impression of Change (PGI-C) questionnaire and disease-specific QoL (HEMO-FISS-QoL questionnaire). Results: Of 3592 participants, 3505 were analyzed (58.4% male; age 40.5 ± 13.7 years; history of HD in 48.4%; 72.1% Goligher grade I and II). Pain and discomfort were the most common symptoms. Most treatments were venoactive drugs (VADs; 90.9%), particularly micronized purified flavonoid fraction (MPFF; 73.7%) and diosmin (14.6%). All VAD-based therapies improved signs/symptoms (number/intensity/frequency of pain, discomfort, bleeding, swelling, itching and soiling) and QoL. MPFF was associated with a significantly greater proportion of patients with no symptoms (48.8 vs diosmin 34.4%, p < 0.001), pain disappearance (69.7 vs diosmin 52.8%, p < 0.001), treatment impact at 1 week rated on PGI-C as 'very much better' (30.5 vs diosmin 17.9%, p < 0.001) and shorter times to improvement (mean ± SD 3.9 ± 1.5 days vs diosmin 4.2 ± 1.7 days). Conclusion: In this prospective real-world study of patients with acute HD, conservative therapies consisting mainly of VADs, including MPFF, improved the clinical signs and symptoms of disease, as well as QoL. This study evidence supports clinical advantages associated with VADs, mostly MPFF, for effectively managing acute HD.