Search

The VHL-containing cullin-RING E3 ubiquitin ligase (CRL2VHL) complex is an E3 ligase commonly used in targeted protein degradation (TPD). Hydroxyproline-based ligands that mimic VHL substrates have been developed as anchor molecules for proteolysis-targeting chimeras (PROTACs) in TPD. To expand the chemical space for VHL ligands, we conducted fragment screening using VHL–ELOB–ELOC (VBC) proteins. We found that certain 7-hydroxycoumarin derivatives (7HCs), rather than VHL, would bind to the ELOC component of the VBC complex. The 7HC binding site overlapped with the CUL2 binding interface on ELOC but did not overlap with the CUL5 binding interface, suggesting that 7HCs may influence the formation of CRL2 but not CRL5. Although the binding affinities of these 7HCs to the VBC complex were relatively low, they represent novel and promising foundational agents for the development of chemical probes or inhibitors that target ELOC-containing CRLs. [ABSTRACT FROM AUTHOR]

Acrylamide (ACR) is a toxic, probably carcinogenic compound commonly found in fried foods and used in the production of many industrial consumer products. ACR-induced acute kidney injury is mediated through several signals. In this research, we investigated, for the first time, the therapeutic effects of phytochemicals apocynin (APO) and/or umbelliferone (UMB) against ACR-induced nephrotoxicity in rats and emphasized the underlying molecular mechanism. To achieve this goal, five groups of rats were randomly assigned: the control group received vehicle (0.5% CMC; 1 ml/rat), ACR (40 mg/kg, i.p.), ACR + APO (100 mg/kg, P.O.), ACR + UMB (50 mg/kg, P.O.), and combination group for 10 days. In ACR-intoxicated rats, there was a significant reduction in weight gain while the levels of blood urea, uric acid, creatinine, and Kim-1 were elevated, indicating renal injury. Histopathological injury was also observed in the kidneys of ACR-intoxicated rats, confirming the biochemical data. Moreover, MDA, TNF-α, and IL-1β levels were raised; and GSH and SOD levels were decreased. In contrast, treatment with APO, UMB, and their combination significantly reduced the kidney function biomarkers, prevented tissue damage, and decreased inflammatory cytokines and MDA. Mechanistically, it suppressed the expression of NLRP-3, ASC, GSDMD, caspase-1, and IL-1β, while it upregulated Nrf-2 and HO-1 in the kidneys of ACR-intoxicated rats. In conclusion, APO, UMB, and their combination prevented ACR-induced nephrotoxicity in rats by attenuating oxidative injury and inflammation, suppressing NLRP-3 inflammasome signaling, enhancing antioxidants, and upregulating Nrf-2 and HO-1 in the kidneys of ACR-induced rats. [ABSTRACT FROM AUTHOR]

Melanin overexpression causes skin hyperpigmentation, which is associated with various skin disorders and cosmetic concerns. Umbelliferone, a natural coumarin found widely in plant species, has been noted for its antioxidant and anti-inflammatory effects but has received little attention for its impact on melanogenesis. Here, the effects of umbelliferone on melanogenesis were investigated in vitro and in clinical studies. The results showed that umbelliferone was non-cytotoxic to human skin and B16F10 melanoma cells. It also exhibited significant anti-melanogenic effects, reducing both melanin production and tyrosinase activity in a dose-dependent manner. This effect was achieved through a decrease in tyrosinase mRNA levels. Furthermore, umbelliferone in a formulation was stable under different temperature conditions, and after four weeks of topical application, it significantly decreased the melanin index and increased skin lightness (L*) values compared to those at the baseline. Overall, these findings demonstrate the potential of umbelliferone as a promising skin-lightening agent in the cosmetics industry. [ABSTRACT FROM AUTHOR]

Skin wound healing is a complex process involving various cellular and molecular events. However, chronic wounds, particularly in individuals with diabetes, often experience delayed wound healing, potentially leading to diabetic skin complications. In this study, we examined the effects of umbelliferone on skin wound healing using dermal fibroblasts and skin tissues from a type 2 diabetic mouse model. Our results demonstrate that umbelliferone enhances several crucial aspects of wound healing. It increases the synthesis of key extracellular matrix components such as collagen I and fibronectin, as well as proteins involved in cell migration like EVL and Fascin-1. Additionally, umbelliferone boosts the secretion of angiogenesis factors VEGF and HIF-1α, enhances the expression of cell adhesion proteins including E-cadherin, ZO-1, and Occludin, and elevates levels of skin hydration-related proteins like HAS2 and AQP3. Notably, umbelliferone reduces the expression of HYAL, thereby potentially decreasing tissue permeability. As a result, it promotes extracellular matrix deposition, activates cell migration and proliferation, and stimulates pro-angiogenic factors while maintaining skin barrier functions. In summary, these findings underscore the therapeutic potential of umbelliferone in diabetic wound care, suggesting its promise as a treatment for diabetic skin complications. Key messages: Umbelliferone suppressed the breakdown of extracellular matrix components in the skin dermis while promoting their synthesis. Umbelliferone augmented the migratory and proliferative capacities of fibroblasts. Umbelliferone activated the release of angiogenic factors in diabetic wounds, leading to accelerated wound healing. Umbelliferone bolstered intercellular adhesion and reinforced the skin barrier by preventing moisture loss and preserving skin hydration. Summary of the protective impact of umbelliferone against delayed wound healing and skin barrier impairment in diabetic dermal fibroblasts and skin tissues. [ABSTRACT FROM AUTHOR]

The present investigation aims to determine the effect of Umbelliferone (UMB) on pharmacokinetic (PK) and pharmacodynamic (PD) parameters of Glibenclamide (GLB) in diabetic rats. Simultaneously, the effect was studied in normal rats. Diabetes in rats was induced by Streptazocin (STZ). The PK parameters are calculated in normal and diabetic rats. PD studies were performed only on diabetic rats. From the PK results, about 2.0-fold improvement in the oral bioavailability of GLB in diabetic rats was observed when treated with GLB in normal rats. A single-dose (SD) and multi-dose (MD) administration of GLB + UMB showed about 3.8 and 4.0- fold enhancement in oral bioavailability of GLB, respectively in the diabetic group compared with the normal GLB-treated group. Similarly, SD and MD of GLB + UMB showed 2.8-folds and 2.7-folds, respectively in diabetic rats when compared with SD and MD of GLB + UMB in normal rats. Further, the rate of clearance and also the volume of distribution significantly changed in diabetic rats. No significant differences were observed in the PK parameters of SD and MD of GLB+ UMB treated groups in diabetic rats. The blood glucose levels were significantly (p<0.05) reduced (12.0 and 13.5% after SD and MD of GLB + UMB treatment, respectively) compared to GLB alone treated diabetic rats during a period of 24 h were noticed from PD studies. The maximum reduction was observed at 2 h (44.3 and 45.6 % after SD and MD of GLB + UMB treatment, respectively) compared with standard GLB treatment (32.1%). [ABSTRACT FROM AUTHOR]

Roots and aerial parts are the agricultural by-products of caraway (Carum carvi L.) fruit production. Hereto, the anti-obesity and hypolipidemic effects of caraway waste were assessed using different in vitro and in vivo tests performed on total ethanol extract (TEE), as well as its fractions. The ethyl acetate fraction (EtOAc fr.) exhibited the highest inhibitory activity on pancreatic lipase (PL), a-amylase and DPPH free radical. Accordingly, it showed the highest ameliorative activity against dyslipidaemia among other fractions and the total extract when tested on a high fat diet-fed mice model. It attenuated hepatic steatosis, reduced adipocyte size, ameliorated the lipid profile, and suppressed leptin concentrations as revealed by the histopathological and biochemical examinations. Umbelliferone, p-coumaric acid and isoquercitrin were isolated from the bioactive EtOAc fr. and quantified in both, the EtOAc fr. and TEE, using HPLC. Isoquercitrin displayed the highest inhibitory activity towards DPPH and PL (IC50: 10 ± 2.50 and 93.54± 2.62 µg/mL, respectively), whereas umbelliferone was the most active against a-amylase (IC50: 50.70 ± 2.83 µg/mL). Molecular docking was carried out to uncover the binding affinities to the enzymes' active sites. Isoquercitrin demonstrated strong interaction in the binding site of lipase (-130.87 kcal·mol-1), via H-bonding with Asp79, Ile78, Arg256, Ser152 and Tyr114, whereas, umbelliferone formed H-bonding with Tyr59 and Leu142 and H-Pi interaction with Gln63 in the amylase enzyme's active site (-65.99 kcal·mol-1). The current research highlights the great potential for caraway waste as a multitarget remedy against obesity, which incites further molecular and clinical studies. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI), formerly known as acute renal failure, refers to a sudden and often reversible decline in kidney function. Inflammatory reaction and oxidative stress play a crucial role in the expansion of renal disease. In this experimental study, we scrutinized the renal protective effect of umbelliferone against gentamicin induced renal injury in the rats and explore the mechanism. Wistar rats were used in this study and Gentamicin was used for the induction the AKI in the rats and rats were received the oral administration of umbelliferone. The body weight, organ weight, renal, oxidative stress, cytokines, inflammatory parameters were estimated. The mRNA expression caspase-3, Bax, Bcl-2, TNF-α, IL-1β, IL-6, IL-10, HO-1, and Nrf2 were estimated. Umbelliferone remarkably improved the body weight and altered the absolute and relative weight of hepatic and renal tissue. Umbelliferone significantly suppressed the level of BUN, Scr, magnesium, calcium, phosphorus, sodium, and potassium along with altered the level of oxidative stress parameters like CAT, SOD, GSH, LPO, and GPx. Umbelliferone altered the level of cytokines viz., TNF-α, Il-1β, IL-6, IL-10; inflammatory parameters like PGE2, COX-2, TGF-β, NF-κB, respectively. Umbelliferone significantly altered the mRNA expression of caspase-3, Bax, Bcl-2, TNF-α, IL-1β, IL-6, IL-10, HO-1, and Nrf2. The result showed the renal protective effect of umbelliferone against gentamycin induced renal disease via alteration of HO-1/Nrf2 and NF-κB Signaling Pathway. [ABSTRACT FROM AUTHOR]

Abstract Pain is a normal response of the central nervous system to trauma, infections, neoplasms, neuropathies, and inflammation. It can arise from physical, emotional, or cognitive conditions, and is classified as orofacial pain when it affects the mouth and face. Umbelliferone, a coumarin from the umbelliferous plant family, is an important component of essential oils, and possesses antioxidant, curative, anti-inflammatory, and anti-tumor activity. The aim of this study was to investigate the orofacial antinociceptive and anti-inflammatory effects of umbelliferone in Swiss male mice Mus musculus, at 3 months of age. Test groups received different doses of umbelliferone (25, 50, or 75 mg/kg, i.p.). The negative control received 0.9% sodium chloride and Tween 80, with the positive control receiving morphine (5 mg/kg, i.p.) or dexamethasone (2 mg/kg, s.c.). We observed a significant reduction in acetic acid-induced abdominal writhing (p

Copyright of Erzincan University Journal of Science & Technology is the property of Erzincan Binali Yildirim Universitesi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: A highly malignant tumor, Breast Cancer (BC) has a poor prognosis for patients with the highest mortality rates in women. BC is currently treatable with a limited number of therapeutic strategies. Aim: Natural compounds with anti-proliferative capabilities are gaining popularity as a way to mitigate the toxicity of radiation and synthetic anti-tumor drugs. Umbelliferone has been reported to possess diverse pharmacological activities, like anti-cancer, anti-inflammation and anti-oxidation properties. Materials and Methods: In the current investigation, the potential of umbelliferone as an anti-cancer agent for breast cancer was evaluated in MDA-MB-231 cell lines. The influence of umbelliferone on cell viability AO/EtBr, apoptotic induction, MMP levels, ROS generation, cell adhesion assays, apoptotic marker levels and anti-inflammatory has been examined. Results: The impact of umbelliferone on the cell viability revealed that its cytotoxic potential increased in a dose-dependent pattern and IC50 concentrations were chosen for further experiments. The results showed that apoptosis was induced by umbelliferone in MDA-MB-231 cells by staining with AO/EtBr, triggering ROS pathway and DNA damage level of MMP. The caspase and inflammatory marker levels were also increased upon umbelliferone treatment. Conclusion: Umbelliferone cytotoxic potential in cells is mediated by inducing apoptosis, which is supported by significant levels of ROS and MMP level as well as the findings of the staining. All these results suggest that umbelliferone can be used as a potent anti-cancer drug for breast cancer cells. [ABSTRACT FROM AUTHOR]

Previous and recent literature acquisitions suggested that cultured calli are an efficient and meaningful model to investigate the extent and fate of prenylation of phenylpropanoid cores in plants belonging to the Rutaceae and Apiaceae families upon administration of putative biosynthetic precursors. To this concern, in the present manuscript, we investigated the effect of supplementation of ferulic acid and umbelliferone on the biosynthesis of their oxyprenylated counterparts in Ferulago campestris (Besser) Grecescu (Fam. Apiaceae) cultured calli. Dried plant biomass material has been extracted by an ultrasound-assisted extraction with EtOH. O-prenyl secondary metabolites, namely 3,3-dimethylallyloxy, geranyloxy, and farnesyloxy derivatives of both ferulic acid and umbelliferone, were identified and quantified by HPLC/DAD analyses. Supplementation with ferulic acid was the only treatment providing appreciable results. Quite surprisingly, its addition to cultured calli did not affect the formation of its oxyprenylated phytochemicals but boosted the biosynthesis of umbelliferone and its farnesyloxy-derivative umbrelliprenin. The findings reported herein enforce and underline the role of ferulic acid as an elicitor of selected classes of secondary metabolites in apiaceous species, as recently observed. In addition to these results, a novel hitherto unknown metabolite from F. campestris, namely 7-[[(2E)-7-hydroxy-3,7-dimethyl-2-octen-1-yl]oxy]-2H-1-benzopyran-2-one, was characterized by NMR and LC–MS analyses. [ABSTRACT FROM AUTHOR]

The research investigates the stability of 7-hydroxy coumarin i.e. umbelliferone, a compound with diverse applications, through forced degradation studies under various conditions. These investigations aim to comprehend its susceptibility to degradation and provide insights crucial for its safe handling and formulation. Umbelliferone displays differing degrees of vulnerability to distinct stressors: it exhibits higher susceptibility to alkali-induced and photolytic degradation, signaling the necessity for cautious management under these conditions. Conversely, it demonstrates moderate susceptibility to acid and water-induced degradation. The findings underscore the importance of handling umbelliferone carefully, particularly in environments, where it is more prone to degradation. Furthermore, the study suggests future explorations to elucidate the structures of degradation products, potentially enhancing our understanding of its stability profile. This comprehensive analysis not only elucidates umbelliferone's stability nuances but also accentuates the significance of forced degradation studies in evaluating the inherent stability of pharmaceutical compounds, offering crucial insights for formulation and storage practices. [ABSTRACT FROM AUTHOR]

Breast cancer stands as the predominant malignancy and primary cause of cancer‐related mortality among females globally. Approximately 25% of breast cancers exhibit HER2 overexpression, imparting a more aggressive tumor phenotype and correlating with poor prognoses. Patients with metastatic breast cancer receiving HER2 tyrosine kinase inhibitors (HER2 TKIs), such as Lapatinib, develop acquired resistance within a year, posing a critical challenge in managing this disease. Here, we explore the potential of Artemisia argyi, a Chinese herbal medicine known for its anti‐cancer properties, in mitigating HER2 TKI resistance in breast cancer. Analysis of the Cancer Genome Atlas (TCGA) revealed diminished expression of transmembrane serine protease 2 (TMPRSS2), a subfamily of membrane proteolytic enzymes, in breast cancer patients, correlating with unfavorable outcomes. Intriguingly, lapatinib‐responsive patients exhibited higher TMPRSS2 expression. Our study unveiled that the compounds from Artemisia argyi, eriodictyol, and umbelliferone could inhibit the growth of lapatinib‐resistant HER2‐positive breast cancer cells. Mechanistically, they suppressed HER2 kinase activation by enhancing TMPRSS2 activity. Our findings propose TMPRSS2 as a critical determinant in lapatinib sensitivity, and Artemisia argyi emerges as a potential agent to overcome lapatinib via activating TMPRSS2 in HER2‐positive breast cancer. This study not only unravels the molecular mechanisms driving cell death in HER2‐positive breast cancer cells induced by Artemisia argyi but also lays the groundwork for developing novel inhibitors to enhance therapy outcomes. [ABSTRACT FROM AUTHOR]

Abstract The neuroprotective effects of umbelliferone (UMB) were visualized in three-dimensional (3D) images on vesicle density changes of organotypic hippocampal slice tissues (OHSCs) induced by scopolamine by high voltage electron microscopy. Observations revealed that the number of vesicles decreased in OHSCs induced by scopolamine, and UMB was found to inhibit scopolamine-induced reduction in vesicles, resulting in an increase in vesicle count. These 3D models provide valuable insight for understanding the increase of synapse vesicles in hippocampal tissues treated with UMB.

The medicinal importance of the genus Daphne L. is related to the richness in the expansive range of different classes of natural products and bioactive phytochemicals, such as coumarins, flavonoids, lignans and different classes of terpenes. The current study reports on the lipid peroxidation effect of diethyl-ether macerate of Daphne mezereum L. flowers and of two coumarins we have isolated from the aqueous subfraction of the crude diethyl-ether extract. All three tested samples, D. mezereum flowers extract (IC50 = 25.1 ± 2.9 mM) and isolated coumarins: umbelliferone (IC50 = 7.1 ± 2.6 mM) and herniarin (IC50 = 19.0 ± 1.3 mM), exhibited notable antioxidative potential in lipid peroxidation assay. None of the samples, however, had an inhibitory effect as pronounced as standardly applied antioxidants Trolox (IC50 = 22 ± 6 μM), caffeic acid (IC50 = 15 ± 3 μM) and quercetin (IC50 = 23 ± 6 μM). Taken altogether, the results of our studies bring forward new data regarding the antioxidant activities of D. mezereum species. [ABSTRACT FROM AUTHOR]

[Objectives] To establish a TLC and content determination method of Pileostegia tomentellal, with umbelliferone as the indicator component. [Methods] TLC identification was performed by silica gel G thin layer plate with n-hexane-ethyl acetate (4:3) as the developing agent, and the plate was examined by UV lamp (365 nm). The umbelliferone content was determined by HPLC; Inertsil ODS-3 C18 column (4.60 mm x 250 mm, 5 µm); mobile phase acetonitrile-0.2% phosphoric acid gradient elution; detection wavelength 320 nm, flow rate 1.0 mL/min, column temperature 30 °C, injection volume 10 µL. [Results] The chromatogram of P. tomentellal showed the same color spot in the same position as that of reference medicinal material, and the spot was clear with good specificity. Umbelliferone showed a good linear relationship when the injection volume was 2.63 - 131.27 µg/mL (R² = 0.999 7). The average recovery of umbelliferone in the low, middle and high adding groups of P. tomentellal was 99.57% and the RSD was 2.15%. [Conclusions] The method can effectively identify Yao medicine P. tomentellal and accurately determine the content of umbelliferone in medicinal materials, which will provide a scientific basis for the development and utilization of medicinal resources of Yao medicine P. tomentellal. [ABSTRACT FROM AUTHOR]

The development of rapid, sensitive, and intuitive intelligent fluorescent materials (IFMs) for monitoring beverage safety is important for human health. In this study, an emerging IFM, a dual‐emitting Eu3+‐functionalized hydrogen‐bonded organic framework (Eu@HOF, Eu@1), is fabricated through coordination post‐synthetic modification. The ligand‐to‐metal charge transfer‐induced energy transfer (LMCT‐ET) from 1 to Eu3+ provides Eu@1 with palpable red fluorescence. Eu@1 as a sensor can specifically discriminate coumarin (Cou), a common spice used in beverages but a suspected carcinogen, with high sensitivity, high efficiency, and excellent anti‐interference. Eu@1 can also quantitatively distinguish 7‐hydroxycoumarin (umbelliferone, Ulf), a metabolite of Cou, in chromatic and ratiometric modes. In realistic milk and soy milk samples, the detection limits (DL) of Eu@1 for Cou are 0.0979 and 0.0511 mg L−1, respectively, whereas that of Ulf in practical serum samples is 0.0099 mg L−1. Furthermore, based on the polyethylene‐vinyl acetate (PEVA) films, three digital anti‐counterfeiting platforms with multiple encryption information are constructed, assisted by a support vector machine. This work proposes a facile pathway for preparing Eu@HOF fluorescent sensors to determine beverage safety and opens the possibility of designing an efficient and precise multifunctional digital anti‐counterfeiting platform via machine learning. [ABSTRACT FROM AUTHOR]

Umbelliferone (UMB), known as 7-hydroxycoumarin, hydrangine, or skimmetine, is a naturally occurring coumarin in the plant kingdom, mainly from the Umbelliferae family that possesses a wide variety of pharmacological properties. In addition, the use of nanoparticles containing umbelliferone may improve anti-inflammatory or anticancer therapy. Also, its derivatives are endowed with great potential for therapeutic applications due to their broad spectrum of biological activities such as anti-inflammatory, antioxidant, neuroprotective, antipsychotic, antiepileptic, antidiabetic, antimicrobial, antiviral, and antiproliferative effects. Moreover, 7-hydroxycoumarin ligands have been implemented to develop 7-hydroxycoumarin-based metal complexes with improved pharmacological activity. Besides therapeutic applications, umbelliferone analogues have been designed as fluorescent probes for the detection of biologically important species, such as enzymes, lysosomes, and endosomes, or for monitoring cell processes and protein functions as well various diseases caused by an excess of hydrogen peroxide. Furthermore, 7-hydroxy-based chemosensors may serve as a highly selective tool for Al3+ and Hg2+ detection in biological systems. This review is devoted to a summary of the research on umbelliferone and its synthetic derivatives in terms of biological and pharmaceutical properties, especially those reported in the literature during the period of 2017–2023. Future potential applications of umbelliferone and its synthetic derivatives are presented. [ABSTRACT FROM AUTHOR]

Abstract Background Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study. Results Among the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice. Conclusions Eriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2.

Limei Lin, Yin Zhang Department of Pharmacy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, People’s Republic of ChinaCorrespondence: Yin Zhang, Department of Pharmacy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, People’s Republic of China, Tel +86 13328579972, Email zyin1973@163.comPurpose: To evaluate the dichloromethane extract of Ficus carica leaves (FCL) had a hypoglycemic impact in diabetic mice, as well as to identify the bioactive components in the extract and analyze their anti-hyperglycemia potential in HepG2 cells.Material and Methods: The antidiabetic activity of dichloromethane extract of Ficus carica leaves was evaluated in diabetic mice induced by streptozotocin (STZ,100 mg/kg) combined with high-fat diet. The fasting blood glucose (FBG), blood lipids, oral glucose tolerance, glycated hemoglobin (HbA1c), and pathological change effects of the extract were measured after administering two doses of the extract (500 and 1000 mg/kg). On the other hand, we used column chromatography to isolate the dichloromethane extract, and we structurally identified the compounds based on 1H NMR and 3C NMR spectra. The hypoglycemic activity of isolated compounds was investigated in palmitic acid (PA)-induced HepG2 cells.Results: FCL extract lowers blood glucose and improves blood lipids and the pancreatic β-cell also tend to recover whether the psoralen is removed or not. Meanwhile, three coumarins except psoralen were isolated from dichloromethane extract: 3,4-dihydropsoralen, umbelliferone and 7-hydroxyl-6-methylcoumarin. Psoralen and umbelliferone promoted glucose uptake in HepG2 cells.Discussion and Conclusion: In vivo experiments, dichloromethane extract of FCL has potential antidiabetic activity, mainly by lowering blood glucose, improving blood lipids, glucose tolerance and repairing pancreatic islet damage, which justifies its use in the treatment of diabetes in Spanish folklore. Additionally, in vitro experiments, psoralen and umbelliferone demonstrated substantial glucose-lowering activity.Graphical Abstract: Keywords: FCL, diabetes, dichloromethane extract, psoralen, umbelliferone

Like other members of the viola family, Viola odorata may be found naturally occurring in Europe and Asia. This little plant is tough and perennially herbaceous. It's also known as sweet violet and English violet. There are several medicinal uses for this flowering plant, including its ability to fight cancer, bacteria, and inflammation., antioxidant activity, and antipyretic activity. The phytochemical studies of different parts of Viola odorata resulted in the isolation of different chemical constituents such as Coumarins, caffeic acid, methyl salicylate, flavonoids (Quercetin, kaempferol), glycosides (Rutin), and terpenoids (stigma sterol). Coumarins are important natural phenolic compounds of the family of benzopyrone. Coumarin's basic structure consists of a pyrone ring fused with a benzene ring. Umbelliferone and esculetin are the most common simple coumarins in nature. Coumarins become an attractive backbone drug with innovative impacts on illnesses and reduced side effects on healthy cells. Anti-inflammatory, anti-carcinogenic, and other biological properties are among those attributed to coumarins derivatives. In this study, Umbelliferone and esculetin of Viola odorata were identified by TLC, and HPTLC.

Background and Objectives: Both primary and secondary cancers require the involvement of glycolytic pathways. Cancer cell proliferation leads to the upregulation of glycolysis, which results in increased glucose consumption. For demonstrating that umbelliferone can effectively bind to several proteins involved in the glycolytic pathway, thereby inhibiting glycolysis and reducing cancer cell proliferation. Materials and Methods: This study uses transcriptomics, network pharmacology, and molecular docking to predict the potential targets and possible pathways of umbelliferone against cancer and microscale thermophoresis (MST) to detect the affinity between umbelliferone and potential targets. Results: Transcriptomic analysis revealed that differentially expressed genes were primarily associated with glycolytic and other metabolic pathways and proteins. According to network pharmacology and molecular docking results, glycolysis-related proteins such as glucose-6-phosphate isomerase (GPI), glycerol-3-phosphate dehydrogenase, mitochondrial (GPD2), phosphoglycerate kinase 2 (PGK2), and heat shock protein HSP-90 alpha (Hsp90AA1) are potential targets of umbelliferone against tumors. MST confirmed that umbelliferous lactone binds strongly to GPI, GPD2, and PGK2 but not to Hsp90AA1. Conclusion: By binding to the glycolysis-related proteins such as GPI, GPD2, and PGK2, umbelliferone acts as an anti-tumor agent by inhibiting glycolysis, cutting off the energy supply to tumor tissue, and reducing tumor growth. It was suggested that umbelliferone might be a brand-new tumor glycolysis inhibitor and that these glycolysis-related proteins might be potential new targets for cancer therapy. This finding helped to establish a solid foundation for the anti-cancer action of umbelliferone. [ABSTRACT FROM AUTHOR]

Background and Objective: Fasciolosis is a zoonotic disease, which is transmitted by Lymnaea acuminata snails of the Lymnaidae family and causes the disease in human and herbivorous mammals in all over the world. One of the suitable approaches for the control of fasciolosis is the snail control. The snail control by snail attractant pellets is a new technique because there is no any side effect on other biota/human/natural environment. Material and Methods: The influence of various abiotic factors and umbelliferone toxicity in bait against the vector snail Lymnaea acuminata was checked in different months of the years 2018-2019. Result: After 24h of molluscicide exposure, it was found that LC50 values 4.37, 4.22 and 5.66 % in SAP containing starch + umbelliferone and 4.02, 4.33, and 4.76 % in SAP containing proline + umbelliferone during May, June and July, respectively, were most effective treatments in killing the snails. While SAP containing starch + umbelliferone was 9.84% and proline + umbelliferone was 8.94% were minimum effective in January in 24h toxicity. Conclusion: This study indicates that various abiotic factors significantly changed the toxicity of umbelliferone; so, the snails can be controlled by snail attractant pellets containing umbelliferone will be applied in a particular month rather than the whole month of the year. [ABSTRACT FROM AUTHOR]

Coumarin, a plant secondary metabolite, has various pharmacological activities, including antioxidant stress and anti-inflammatory effects. Umbelliferone, a common coumarin compound found in almost all higher plants, has been extensively studied for its pharmacological effects in different disease models and doses with complex action mechanisms. This review aims to summarize these studies and provide useful information to relevant scholars. The pharmacological studies demonstrate that umbelliferone has diverse effects such as anti-diabetes, anti-cancer, anti-infection, anti-rheumatoid arthritis, neuroprotection, and improvement of liver, kidney, and myocardial tissue damage. The action mechanisms of umbelliferone include inhibition of oxidative stress, inflammation, and apoptosis, improvement of insulin resistance, myocardial hypertrophy, and tissue fibrosis, in addition to regulation of blood glucose and lipid metabolism. Among the action mechanisms, the inhibition of oxidative stress and inflammation is the most critical. In short, these pharmacological studies disclose that umbelliferone is expected to treat many diseases, and more research should be conducted. [ABSTRACT FROM AUTHOR]

Cisplatin (CIS) is an effective chemotherapy against different solid cancers. However, the adverse effects, including hepatotoxicity, limit its clinical use. 7-hydroxycoumarin (7-HC) possesses antioxidant and hepatoprotective activities, but its protective effect against CIS hepatotoxicity has not been investigated. This study evaluated the effect of 7-HC on liver injury, oxidative stress (OS), and inflammation provoked by CIS. Rats received 7-HC (25, 50, and 100 mg/kg) orally for 2 weeks followed by intraperitoneal injection of CIS (7 mg/kg) at day 15. CIS increased serum transaminases, alkaline phosphatase (ALP), and bilirubin and provoked tissue injury accompanied by elevated reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO). Liver nuclear factor (NF)-κB p65, inducible NO synthase (iNOS), pro-inflammatory cytokines, Bax, and caspase-3 were upregulated, and antioxidant defenses and Bcl-2 were decreased in CIS-treated rats, while 7-HC prevented liver injury and ameliorated OS, inflammatory and apoptosis markers. In addition, 7-HC enhanced nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase (HO)-1 in CIS-administered rats and in silico studies revealed its binding affinity toward HO-1. In conclusion, 7-HC protected against CIS hepatotoxicity by mitigating OS and inflammatory response and modulating Nrf2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

Like other members of the viola family, Viola odorata may be found naturally occurring in Europe and Asia. This little plant is tough and perennially herbaceous. It's also known as sweet violet and English violet. There are several medicinal uses for this flowering plant, including its ability to fight cancer, bacteria, and inflammation., antioxidant activity, and antipyretic activity. The phytochemical studies of different parts of Viola odorata resulted in the isolation of different chemical constituents such as Coumarins, caffeic acid, methyl salicylate, flavonoids (Quercetin, kaempferol), glycosides (Rutin), and terpenoids (stigma sterol). Coumarins are important natural phenolic compounds of the family of benzopyrone. Coumarin's basic structure consists of a pyrone ring fused with a benzene ring. Umbelliferone and esculetin are the most common simple coumarins in nature. Coumarins become an attractive backbone drug with innovative impacts on illnesses and reduced side effects on healthy cells. Anti-inflammatory, anti-carcinogenic, and other biological properties are among those attributed to coumarins derivatives. In this study, Umbelliferone and esculetin of Viola odorata were identified by TLC, and HPTLC. [ABSTRACT FROM AUTHOR]

The neuroprotective effects of umbelliferone (UMB) were visualized in three-dimensional (3D) images on vesicle density changes of organotypic hippocampal slice tissues (OHSCs) induced by scopolamine by high voltage electron microscopy. Observations revealed that the number of vesicles decreased in OHSCs induced by scopolamine, and UMB was found to inhibit scopolamine-induced reduction in vesicles, resulting in an increase in vesicle count. These 3D models provide valuable insight for understanding the increase of synapse vesicles in hippocampal tissues treated with UMB. [ABSTRACT FROM AUTHOR]

Background: Artemisia argyi (A. argyi), also called Chinese mugwort, has been widely used to control pandemic diseases for thousands of years since ancient China due to its anti-microbial infection, anti-allergy, and anti-inflammation activities. Therefore, the potential of A. argyi and its constituents in reducing the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was investigated in this study. Results: Among the phytochemicals in A. argyi, eriodictyol and umbelliferone were identified to target transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) proteins, the essential factors for the cellular entry of SARS-CoV-2, in both FRET-based enzymatic assays and molecular docking analyses. These two ingredients of A. argyi suppressed the infection of ACE2-expressed HEK-293 T cells with lentiviral-based pseudo-particles (Vpp) expressing wild-type and variants of SARS-CoV-2 spike (S) protein (SARS-CoV-2 S-Vpp) via interrupting the interaction between S protein and cellular receptor ACE2 and reducing the expressions of ACE2 and TMPRSS2. Oral administration with umbelliferone efficiently prevented the SARS-CoV-2 S-Vpp-induced inflammation in the lung tissues of BALB/c mice. Conclusions: Eriodictyol and umbelliferone, the phytochemicals of Artemisia argyi, potentially suppress the cellular entry of SARS-CoV-2 by preventing the protein binding activity of the S protein to ACE2. [ABSTRACT FROM AUTHOR]

Umbelliferone (UB) is a phenylpropanoid-based pharmacologically active agent with promising anti-tumor activities. However, complete elucidation of its therapeutic efficacy remains challenging due to low solubility and bioavailability. The present study aimed to develop a liposomal delivery system for UB to enhance its therapeutic efficacy against Dalton's ascites lymphoma tumor model. Umbelliferone-encapsulated nanoliposomes (nLUB) were prepared using the thin-film hydration method and performed a series of characterizations to confirm successful development. The nLUB showed a particle size of 116 ± 3.2 nm with a negative surface charge and encapsulation efficiency of 78%. In vitro study results showed that nLUB treatment significantly enhanced cellular uptake and apoptosis induction in lymphoma cells compared to free UB. nLUB treatment significantly stabilized body weight, reduced tumor growth, and improved the serum biochemical and hematological parameters of experimental animals, thereby improving their overall survivability compared to an free UB. Our result indicates that nanoencapsulation enhanced the therapeutic potential of UB, which may find its way to clinical application in the near future. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the cholinergic hypothesis proposes that AD symptoms are a result of reduced synthesis of acetylcholine (ACh). A non-selective antagonist of the muscarinic ACh receptor, scopolamine (SCOP) induced cognitive impairment in rodents. Umbelliferone (UMB) is a Apiaceae-family-derived 7-hydeoxycoumarin known for its antioxidant, anti-tumor, anticancer, anti-inflammatory, antibacterial, antimicrobial, and antidiabetic properties. However, the effects of UMB on the electrophysiological and ultrastructure morphological aspects of learning and memory are still not well-established. Thus, we investigated the effect of UMB treatment on cognitive behaviors and used organotypic hippocampal slice cultures for long-term potentiation (LTP) and the hippocampal synaptic ultrastructure. A hippocampal tissue analysis revealed that UMB attenuated a SCOP-induced blockade of field excitatory post-synaptic potential (fEPSP) activity and ameliorated the impairment of LTP by the NMDA and AMPA receptor antagonists. UMB also enhanced the hippocampal synaptic vesicle density on the synaptic ultrastructure. Furthermore, behavioral tests on male SD rats (7–8 weeks old) using the Y-maze test, passive avoidance test (PA), and Morris water maze test (MWM) showed that UMB recovered learning and memory deficits by SCOP. These cognitive improvements were in association with the enhanced expression of BDNF, TrkB, and the pCREB/CREB ratio and the suppression of acetylcholinesterase activity. The current findings indicate that UMB may be an effective neuroprotective reagent applicable for improving learning and memory against AD. [ABSTRACT FROM AUTHOR]

Purpose: Among the characteristics of non-alcoholic fatty liver disease (NAFLD), hepatic steatosis is due to excessive fat accumulation and causes liver damage and lipotoxicity, which are associated with insulin resistance, endoplasmic reticulum (ER) stress, and apoptosis. Umbelliferone (UMB) has various powerful pharmacological properties, such as antioxidant, anti-hyperglycemic, anti-viral, and anti-inflammatory effects. However, the mechanism of action in hepatic steatosis and lipid-induced ER stress is still unclear. Thus, the efficacy of UMB in hepatic steatosis and palmitate (PA)-induced hepatocellular lipotoxicity was evaluated in the present study. Materials and Methods: Male C57BL/6J mice (n=40) were divided into four groups: regular diet (RD), UMB-supplemented RD, high-fat diet (HFD), and UMB-supplemented HFD. All mice were fed orally for 12 weeks. In addition, the effects of UMB on lipotoxicity were investigated in AML12 cells treated with PA (250 μM) for 24 h; Western blot analysis was used to evaluate the changes in ER stress and apoptotic-associated proteins. Results: Administration with UMB in HFD-fed mice reduced lipid accumulation and hepatic triglyceride (TG) as well as serum insulin and glucose levels. In AML12 cells, UMB treatment reduced lipid accumulation as indicated by decreases in the levels of lipogenesis markers, such as SREBP1, FAS, PPAR-γ, and ADRP. Furthermore, UMB reduced both oxidative stress and ER stress-related cellular apoptosis. Conclusion: UMB supplementation ameliorated hepatic steatosis and improved insulin resistance by inhibiting lipid accumulation and regulating ER stress. These findings strongly suggest that UMB may be a potential therapeutic compound against NAFLD. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MGO), a cytotoxic metabolite of glycolysis, can cause endothelial cells impairment, which is tightly associated with diabetic vascular complication. Umbelliferone, a derivative of coumarin, participates in various pharmacological activities. This study aimed to determine the effectiveness of umbelliferone in MGO‐induced apoptosis and oxidative stress in endothelial cells. In this study, it has been indicated that umbelliferone inhibited MGO‐induced human umbilical vein endothelial cells (HUVECs) cytotoxicity, apoptosis, Bax/Bcl‐2 protein ratio, the activity of cleaved‐caspase‐3, and mitochondrial membrane potential loss. Furthermore, we found that umbelliferone inhibited MGO‐induced activation of mitogen‐activated protein kinases and nuclear factor‐κB signaling pathways in HUVECs. In addition, umbelliferone could suppress oxidative stress, as evidenced by decrease of reactive oxygen species and malondialdehyde (MDA) generation, and increase of superoxide dismutase and glutathione peroxidase contents. Moreover, we found that umbelliferone can activate Nrf2/HO‐1 signaling. Importantly, silencing of Nrf2 signaling clearly eliminated the anti‐oxidative stress of umbelliferone, whereas umbelliferone pretreatment had no effect on Nrf2 overexpressing HUVECs. Altogether, this study suggested that umbelliferone pretreatment has a protective effect on MGO‐induced endothelial cell dysfunction through inhibiting apoptosis and oxidative stress. Umbelliferone exhibits various pharmacological activities. Herein, we aimed to investigate the role of umbelliferone in methylglyoxal (MGO)‐induced human umbilical vein endothelial cells (HUVECs). Our results indicated that umbelliferone protects HUVECs against MGO‐induced injury through inhibiting apoptosis and oxidative stress via mitogen‐activated protein kinases/ nuclear factor‐κB and Nrf2/HO‐1 signaling pathway, respectively. This study demonstrated that umbelliferone may have a protective effect against MGO and potentially may serve as a clinical agent for vascular complications of diabetes. [ABSTRACT FROM AUTHOR]

Umbelliferone (UMB), 7‐hydroxycoumarin, is a naturally occurring coumarin derivative that has a plethora of biological and therapeutic activities. The focus of this research was to elucidate the curative effects of two different doses of UMB on diabetic cardiomyopathy (DCM) in a type 2 diabetic rat model induced by 50 mg/kg body weight of streptozotocin (STZ). Diabetic rats orally received 10 or 30 mg/kg of UMB daily for 8 weeks. Compared to the nontreated diabetic group, both UMB treatment doses significantly decreased glucose levels, glycated hemoglobin (HbA1c), tumor necrosis factor alpha (TNF‐α), interleukin‐6 (IL‐6), creatine kinase MB (CK‐MB), cardiovascular risk indices, and oxidative stress by reducing malondialdehyde (MDA) and increasing the activity of the antioxidant enzymes. The hypercholesterolemia and hypertriglyceridemia also dramatically decreased in diabetic groups with UMB treatments accompanied by an improvement in insulin, and insulin sensitivity indices (HOMA‐IR and QUICKI). Furthermore, the cardiac gene expressions and protein levels of Janus kinase2 (JAK2), signal transducer and activator of transcription3 (STAT3), and transforming growth factor beta1 (TGF‐β1) were also markedly downregulated in a dose‐dependent manner by UMB treatments. Finally, the biochemical results were assured by the reduction of histological alterations in cardiac tissues. In conclusion, UMB is a propitious substance for the treatment of DCM by virtuousness of its antihyperglycemic, antihyperlipidemic, antioxidant, and anti‐inflammatory properties through modulating the JAK/STAT signaling pathway that may be the underlying mechanism in UMB action. [ABSTRACT FROM AUTHOR]

Abstract Background Coumarin and fatty alcohol are abundant in nature, particularly in plants, and have been reported to have therapeutic uses. Strychnos innocua (Loganiaceae family) is commonly utilized for medicinal purposes in several African countries. Ethyl acetate extract of the plant (root bark) was subjected to chromatography separation, leading to the isolation of Umbelliferone (1) and 2,13-octadecadien-1-ol (2). Results Their structures were verified using mass spectrometry (MS) and nuclear magnetic resonance (NMR) and then compared with published data. This is the first time these compounds (1 and 2) have been isolated from S. innocua root bark. In the molecular docking analysis, the binding scores of the compounds (1 and 2) with the binding sites of Staphylococcus aureus pyruvate carboxylase (PDB: 3HO8) and Pseudomonas aeruginosa virulence factor regulator (PDB: 2OZ6) were − 5.6 and − 4.7 kcal/mol, and − 6.9 and − 5.7 kcal/mol, respectively. These were compared with ciprofloxacin (standard drug), which had docking scores of -6.6 and -8.7 kcal/mol, respectively. Conclusions In conclusion, this study established the rich presence of Umbelliferone and 2,13-octadecadien-1-ol in the plant root bark, and their docking studies revealed moderate binding potential with the binding sites of S. aureus and P. aeruginosa. Graphical Abstract

Biosynthetic potential of fungal endophytes from medicinal plants represents an attractive source for discovery of new bioactive metabolites. Present study involved characterizing metabolite(s) of non-pathogenic, endophytic Fusarium oxysporum designated ZzEF8 which was identified previously from Zingiber zerumbet rhizome to display antagonism towards Pythium myriotylum [62.2 ± 2.58% percent of inhibition (PoI)], an oomycetous phytopathogen of significant economic concern. Efficacy of ZzEF8 in suppressing soft rot by P. myriotylum was further evaluated by planting ginger rhizomes primed with ZzEF8 conidial suspension (106 conidia/ ml) followed by transplanting the primed rhizome in sterile soil infested with P. myriotylum (103 zoospores/g soil). Batch fermentation followed by solvent extraction yielded a dark red solid (0.45 mg/ml) which after fractionation by silica column (500 × 30 mm) chromatography (100–200µ) using chloroform: methanol (8:2) solvent yielded three fractions, F1-3. Validation of inhibitory activity of the fractions by disc diffusion assay identified F2 to exhibit absolute P. myriotylum growth inhibition (100%) while F1 and F3 showed 57.62% and 10.73% inhibition respectively. Further purification of F2 by silica column chromatography (300 × 10 mm) yielded three sub-fractions viz., F2a-c. Further LC/Q –TOF MS-analysis of the three sub-fractions identified F2a to contain umbelliferone (tR 6.93 min) as major metabolite. Batch fermentation under submerged conditions was thence optimized for optimal metabolite production. Evaluation of cytotoxicity of F2a and F2b fractions in HeLa cell lines revealed F2a to display cytotoxic effect with IC50 value of 57.9 µg/ml. Anti-Pythium activity of ZzEF8 and anti-cancer activity of ZzEF8 metabolites identified in present experiments signifies its potential for use in pharmaceutical and agricultural industry. [ABSTRACT FROM AUTHOR]

Copyright of ESPOCH Congresses: The Ecuadorian Journal of S.T.E.A.M. is the property of Knowledge E DMCC and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Chemotherapy-induced immunosuppression significantly impacts patient's quality of life. Umbelliferone (UMB) is known for its anti-inflammatory, antioxidant, and anti-apoptotic properties, but its effects on cyclophosphamide (CTX)-induced immunosuppression need further study., Methods: We established a CTX-induced immunosuppressed mouse model and administered varying doses of UMB. Immune function was assessed by evaluating white blood cells, lymphocytes, thymus and spleen indices, and CD4+/CD8+ T cell ratios. Serum levels of IL-2, IFN-γ, IgA, IgM, and IgG, along with macrophage phagocytic activity, NK cytotoxicity, and lymphocyte proliferation, were measured. Untargeted metabolomics was used to identify key pathways regulated by UMB, and RT-qPCR and Western blotting were performed to analyze the expression of related enzymes and metabolites., Results: UMB intervention increased white blood cells, lymphocytes, thymus and spleen indices, and CD4+/CD8+ T cell ratios in CTX-immunosuppressed mice. It reversed reduced levels of serum IL-2, IFN-γ, IgA, IgM, and IgG and improved macrophage phagocytic activity, NK cytotoxicity, and lymphocyte proliferation. Key pathways identified by metabolomics included histidine and purine metabolism. UMB improved levels of histamine, L-glutamate, L-aspartate, xanthine, dAMP, deoxyinosine, xanthosine, and cGMP and upregulated HDC, ASPA, and PNP while downregulating XDH, PDE5, ROS, and MDA in spleen tissue. UMB enhanced SOD activity and GSH levels and reduced apoptosis, as indicated by lower TUNEL-positive expression., Conclusion: UMB enhanced immune function in CTX-immunosuppressed mice through the regulation of histidine and purine metabolism, exhibiting antioxidant and anti-apoptotic effects. These findings highlight the potential of UMB in mitigating immunosuppression., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Furanocoumarins (FCs) are plant defence compounds derived from the phenylpropanoid pathway via the coumarin umbelliferone that harbour some therapeutic benefits yet are the underlying cause of 'grapefruit-drug interactions' in humans. Most of the pathway genes have not been identified in citrus. We employed a genetic/Omics approach on citrus ancestral species and F1 populations of mandarin × grapefruit and mandarin × pummelo. Enzyme specificity was characterized by In vivo 2-oxoglutarate-dependent dioxygenase family (2OGD) activity assays. We identified a 2OGD multi-gene cluster involved in coumarin/FC/pyranocoumarin biosynthesis; Species lacking FCs in leaves/fruit were homozygous for a 655-base solo-LTR frame-disrupting insertion within one dual specificity C2'H/F6'H encoding 2OGD gene, demonstrating that integrity of this gene is fully correlated with the capacity to biosynthesize metabolites of the extended FC pathway in leaves/fruit. A second 2OGD is the prominent gene expressed in citrus roots, which contain a unique pattern of extended FC pathway metabolites, including the predominant pyranocoumarins. A third 2OGD gene encodes a single activity F6'H, which appears to be induced at the transcript level by citrus pathogens. The results provide insights into the genetic basis underlying the difference between citrus fruit FC producers (grapefruit and pummelo) and nonproducers (mandarin and orange) and provide a gene target to breed for FC-free varieties by marker-assisted breeding or genome editing., (© 2025 The Author(s). New Phytologist © 2025 New Phytologist Foundation.)

Background: Glioblastoma multiforme (GBM) is the most aggressive brain tumor malignancy in adults, accounting for nearly 50% of all gliomas. Current medications for GBM frequently lead to drug resistance., Objectives: Umbelliferone (UMB) is found extensively in many plants and shows numerous pharmacological actions against inflammation, degenerative diseases and cancers. However, its anticancer effects on GBM cells have not yet been explored., Material and Methods: This research intended to assess the antitumor efficacy of UMB and the molecular mechanism of cell-cell adhesion proteins in human U-87 GBM cells. The cytotoxicity assay, intracellular reactive oxygen species (ROS), cell adhesion proteins, and cell apoptosis actions of UMB were assessed using 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT), dichlorodihydrofluorescein diacetate (DCFH-DA), 4',6-diamidino-2-phenylindole (DAPI), acridine orange/ethidium bromide (AO/EB), and western blot., Results: The findings revealed that UMB reduced the proliferation of GBM cells and cell adhesion proteins, while augmenting apoptosis through the elevation of cellular ROS. Bcl-2 family protein levels of Bcl-2 and Bcl-XL were mitigated; conversely, the pro-apoptotic proteins Bad and Bim were elevated upon treatment with UMB in a quantity-dependent way. Furthermore, UMB-treated GBM cells suppressed N-cadherin, β-catenin, Slug, and matrix metalloproteinase 2 (MMP-2) expression, whereas they showed enhanced TIMP protein and E-cadherin levels., Conclusions: Our findings suggest that UMB can prevent proliferation and metastasis and stimulate apoptosis in GBM cells.

Umbelliferone (UMB), a natural coumarin compound, has been reported to possess anti-rheumatic effects on rheumatoid arthritis (RA) experimental models, but its potential role of UMB in regulating migration, invasion and inflammation of RA fibroblast-like synoviocytes (FLS) remain unclear. Herein, MTT assay was performed to confirm the non-cytotoxic concentrations (10, 20, and 40 μ M) and the treatment time (24 h) of UMB on TNF- α -stimulated RA FLS (MH7A cells) in vitro. Results of wound-healing, transwell and phalloidin staining assays revealed that UMB inhibited TNF- α -induced migration, invasion and F-actin cytoskeletal reorganization in MH7A. Results of ELISA, western blot and gelatin zymography indicated that UMB decreased the productions of pro-inflammatory factors, including IL-1 β , IL-6, IL-8, MMP-2 and MMP-9, and inhibited MMP-2 activity in TNF- α -stimulated MH7A cells. In vivo, UMB (25 mg/kg and 50 mg/kg) relieved the joint damage and synovial inflammation in rats with adjuvant-induced arthritis (AIA). Mechanistically, UMB could suppress Wnt/ β -catenin signaling both in TNF- α -induced MH7A cells and in AIA rat synovium, evidenced by decreasing Wnt1 protein level, activating GSK-3 β kinase by blocking GSK-3 β (Ser9) phosphorylation, and reducing the protein level and nuclear translocation of β -catenin. Importantly, combined use of lithium chloride (a Wnt/ β -catenin signaling agonist) eliminated the inhibitory effects of UMB on migration, invasion and inflammation in vitro and the anti-arthritic effects of UMB in vivo. We concluded that UMB inhibited TNF- α -induced migration, invasion and inflammation of RA FLS and attenuated the severity of rat AIA through its ability to block Wnt/ β -catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa easily adapts to newer environments and acquires several genome flexibilities to overcome the effect of antibiotics during therapeutics, especially in cystic fibrosis patients. During adaptation to the host system, the bacteria employ various tactics including virulence factor production and biofilm formation to escape from the host immune system and resist antibiotics. Hence, identifying alternative strategies to combat recalcitrant pathogens is imperative for the successful elimination of drugresistant microbes. In this context, this study portrays the anti-virulence efficacy of umbelliferone (UMB) against P. aeruginosa. UMB (7-hydroxy coumarin) is pervasively found among the plant family of Umbelliferae and Asteraceae. The UMB impeded biofilm formation in the P. aeruginosa reference strain and clinical isolates on polystyrene and glass surfaces at the concentration of 125 µg/ml. Global proteomic analysis of UMB-treated cells revealed the downregulation of major virulence-associated proteins such as RhlR, LasA, AlgL, FliD, Tpx, HtpG, KatA, FusA1, Tsf, PhzM, PhzB2, CarB, DctP, MtnA, and MscL. A functional interaction study, gene ontology, and KEGG pathway analysis revealed that UMB could modulate the global regulators, enzymes, co-factors, and transcription factors related to quorum sensing (QS), stress tolerance, siderophore production, motility, and microcolony formation. In vitro biochemical assays further affirmed the anti-virulence efficacy of UMB by reducing pyocyanin, protease, elastase, and catalase production in various strains of P. aeruginosa. Besides the antibiofilm activity, UMB-treated cells exhibited enhanced antibiotic susceptibility to various antibiotics including amikacin, kanamycin, tobramycin, ciprofloxacin, and cefotaxime Furthermore, in vitro cytotoxicity analysis revealed the biocompatibility of UMB, and the IC50 value was determined to be 249.85 µg/ml on the HepG2 cell line. Altogether, the study substantiates the anti-virulence efficacy of UMB against P. aeruginosa, and the proteomic analysis reveals the differential expression of the regulators related to QS, stress response, and motility factors. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVD) are the deadliest noncommunicable disease worldwide. Hypertension is the most prevalent risk factor for the development of CVD. Although there is a wide range of antihypertensive drugs, there still remains a lack of blood pressure control options for hypertensive patients. Additionally, natural products remain crucial to the design of new drugs. The natural product 7-hydroxycoumarin (7-HC) exhibits pharmacological properties linked to antihypertensive mechanisms of action. This study aimed to evaluate the vascular effects of 7-HC in an experimental model of essential hypertension. The isometric tension measurements assessed the relaxant effect induced by 7-HC (0.001 μM–300 μM) in superior mesenteric arteries isolated from hypertensive rats (SHR, 200–300 g). Our results suggest that the relaxant effect induced by 7-HC rely on K+-channels (KATP, BKCa, and, to a lesser extent, Kv) activation and also on Ca2+ influx from sarcolemma and sarcoplasmic reticulum mobilization (inositol 1,4,5-triphosphate (IP3) and ryanodine receptors). Moreover, 7-HC diminishes the mesenteric artery's responsiveness to α1-adrenergic agonist challenge and improves the actions of the muscarinic agonist and NO donor. The present work demonstrated that the relaxant mechanism of 7-HC in SHR involves endothelium-independent vasorelaxant factors. Additionally, 7-HC reduced vasoconstriction of the sympathetic agonist while improving vascular endothelium-dependent and independent relaxation. [ABSTRACT FROM AUTHOR]

Coumarins and furanocoumarins are plant secondary metabolites with known biological activities. As they are present in low amounts in plants, their heterologous production emerged as a more sustainable and efficient approach to plant extraction. Although coumarins biosynthesis has been positively established, furanocoumarin biosynthesis has been far more challenging. This study aims to evaluate if Escherichia coli could be a suitable host for furanocoumarin biosynthesis. The biosynthetic pathway for coumarins biosynthesis in E. coli was effectively constructed, leading to the production of umbelliferone, esculetin and scopoletin (128.7, 17.6, and 15.7 µM, respectively, from tyrosine). However, it was not possible to complete the pathway with the enzymes that ultimately lead to furanocoumarins production. Prenyltransferase, psoralen synthase, and marmesin synthase did not show any activity when expressed in E. coli. Several strategies were tested to improve the enzymes solubility and activity with no success, including removing potential N-terminal transit peptides and expression of cytochrome P450 reductases, chaperones and/or enzymes to increase dimethylallylpyrophosphate availability. Considering the results herein obtained, E. coli does not seem to be an appropriate host to express these enzymes. However, new alternative microbial enzymes may be a suitable option for reconstituting the furanocoumarins pathway in E. coli. Nevertheless, until further microbial enzymes are identified, Saccharomyces cerevisiae may be considered a preferred host as it has already been proven to successfully express some of these plant enzymes. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the chemical profile, antihyperglycemic and antilipidemic effect of total methanolic extract (TME) of Bassia eriophora and isolated pure compound umbelliferone (UFN) in high-fat diet (HFD)- and streptozotocin (STZ)- induced diabetic rats. TME was subjected to various techniques of chromatography to yield UFN. Diabetes was induced after eight weeks of HFD by administration of STZ (40 mg/kg) intraperitoneally, and experimental subjects were divided into five groups. The diabetic control showed an increase in levels of blood glucose throughout the experiment. Treatments were initiated in the other four groups with glibenclamide (GLB) (6 mg/kg), TME (200 mg/kg and 400 mg/kg) and isolated UFN (50 mg/kg) orally. The effect on blood glucose, lipid profile and histology of the pancreatic and adipose tissues was assessed. Both 200 and 400 mg/kg of TME produced a comparably significant decrease in blood glucose levels and an increase in insulin levels with GLB. UFN began to show a better blood sugar-lowering effect after 14 days of treatment, comparatively. However, both 400 mg/kg TME and UFN significantly returned blood glucose levels in diabetic rats compared to normal rats. Analysis of the lipid profile showed that while HFD + STZ increased all lipid profile parameters, TME administration produced a significant decrease in their levels. Histopathological examinations showed that treatment with TME and UFN revealed an improved cellular architecture, with the healthy islets of Langerhans and compact glandular cells for pancreatic cells distinct from damaged cells in non-treated groups. Conversely, the adipose tissue displayed apparently normal polygonal fat cells. Therefore, these results suggest that TME has the potential to ameliorate hyperglycemia conditions and control lipid profiles in HFD + STZ-induced diabetic rats. [ABSTRACT FROM AUTHOR]

A. hydrophila is an important pathogen that mainly harms aquatic animals and has exhibited resistance to a variety of antibiotics. Here, to seek an effective alternative for antibiotics, the effects of umbelliferone (UM) at sub-MICs on A. hydrophila virulence factors and the quorum-sensing system were studied. Subsequently, RNA sequencing was employed to explore the potential mechanisms for the antivirulence activity of umbelliferone. Meanwhile, the protective effect of umbelliferone on grass carp infected with A. hydrophila was studied in vivo. Our results indicated that umbelliferone could significantly inhibit A. hydrophila virulence such as hemolysis, biofilm formation, swimming and swarming motility, and their quorum-sensing signals AHL and AI-2. Transcriptomic analysis showed that umbelliferone downregulated expression levels of genes related to exotoxin, the secretory system (T2SS and T6SS), iron uptake, etc. Animal studies demonstrated that umbelliferone could significantly improve the survival of grass carps infected with A. hydrophila, reduce the bacterial load in the various tissues, and ameliorate cardiac, splenic, and hepatopancreas injury. Collectively, umbelliferone can reduce the pathogenicity of A. hydrophila and is a potential drug for treating A. hydrophila infection. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) plays a crucial role in a variety of physiological and pathological processes, similar to other gaseous signaling molecules. The significant pathophysiological functions of H2S have sparked a great deal of interest in the creation of fluorescent probes for H2S monitoring and imaging. Using 3-cyanoumbelliferone as the push–pull fluorophore and a dinitrophenyl substituent as the response site, herein we developed a umbelliferone-based fluorescent probe 1 for H2S, which exhibited a remarkable turn-on fluorescence response with a low detection limit (79.8 nM), high sensitivity and selectivity. The H2S-sensing mechanism could be attributed to the cleavage of the ether bond between the dinitrophenyl group and the umbelliferone, leading to the recovery of an intermolecular charge transfer (ICT) process. Moreover, the probe had negligible cytotoxicity and good cell membrane permeability, which was successfully applied to image H2S in MCF-7 cells and zebrafish. [ABSTRACT FROM AUTHOR]