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AbstractObjectivesMethodsResultsConclusionFive solvent extracts (n-hexane, ethyl acetate, ethanol, ethanol/water (70%), and water) of Gladiolus italicus Mill. from Turkey were evaluated for chemical and biological properties.Antioxidant activities, inhibitory properties against key enzymes involved in the etiology of chronic diseases were tested, as well as cytotoxic effects on different cell lines. Chemical characterization was also carried out to determine the most abundant compounds of each extract.The highest total phenolic content (TPC) was observed in the water extract while highest TFC in ethanol/water extract. The most abundant compounds in the extracts were hyperoside (69041.06 mg kg−1), isoquercitrin (46239.49 mg kg−1), delphindin-3,5-diglucoside (42043.81 mg kg−1), myricetin (21486.61 mg kg−1), and kaempferol-3-glucoside (21199.76 mg kg−1). Molecular dynamic (MD) simulations confirmed the structural stability and dynamic conformational integrity of these complexes over a period of 100 ns. In network pharmacology, A total of 657 unique target genes were screened: 52 associated with programmed cell death-1 (PD-1), 85 with vascular endothelial growth factor receptor-2 (VEGFR2), and 130 with fibroblast growth factor receptor-2 (FGFR2), identifying crucial gene interactions for these proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, revealing significant interactions and pathways such as the advanced glycation end products (AGE) and their receptors (RAGE) signaling pathway in diabetic complications and T- helper 17 (Th17) cell differentiation, among others. This elucidation of complex networks involving key genes like AKT Serine/Threonine Kinase 1 (AKT1), MYC proto-oncogene (MYC), tumor protein 53 (TP53), Interleukin 6 (IL6), and tumor necrosis factor (TNF) provides a promising foundation for the development of targeted therapies in the treatment of non-communicable diseases.These results show that G. italicus could be a natural source of potent antioxidants and enzyme inhibitors which need to be further explored for the development of biopharmaceuticals. [ABSTRACT FROM AUTHOR]

Radioresistance poses a significant obstacle in cancer treatment. Lotus seedpod extract (LSE) has demonstrated anticancer effects in various cancer cells. However, its potential against radioresistant tumors remains unclear. In this study, we aimed to investigate the effect of LSE on radioresistant breast cancer cells, explore the underlying mechanism, and identify the major constituents responsible for its cytotoxic effect. LSE, extracted using 70% ethanol, exhibited selective cytotoxic effects against radioresistant breast cancer cells compared with their parental cells. Chemical analysis identified quercetin and its derivatives, hyperoside and miquelianin, as the major constituents responsible for these selective effects. Notably, quercetin displayed the most potent cytotoxicity against radioresistant breast cancer cells compared with hyperoside and miquelianin. Further investigation revealed that these compounds inhibited the activation of DNA repair systems, leading to the accumulation of DNA damage and the induction of apoptosis. Importantly, they efficiently suppressed the expression of ACSL4, a factor previously associated with radioresistance. In an in vivo study, quercetin exhibited a significant suppression of tumor growth in radioresistant tumor‐bearing mice. Taken together, our findings highlight the potential of LSE and its major constituents, quercetin and its derivatives, in overcoming radioresistance in breast cancer. This study provides compelling evidence to support the use of LSE as a medicinal source for the future adjunctive therapy to combat radioresistance in breast cancers. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic cancer (PC) is a particularly aggressive malignancy with limited therapeutic options. The search for innovative treatments has focused on traditional Chinese medicine, specifically epimedium. This research investigates epimedium's active ingredients, potential targets, and underlying mechanisms in treating PC. Methods: High-performance liquid chromatography (HPLC) was used to quantify the active components of epimedium and HPLC-Q-TOF-MS was employed for qualitative identification. Potential targets of epimedium's active ingredients were identified using the TCMSP, ETCM, CTD, and Swiss Target Prediction databases. Potential PC-related targets were sourced from DisGeNET, GeneCards, and OMIM databases. A Venn diagram was utilized to identify overlapping PCrelated and epimedium targets. Core targets and pathways were elucidated through protein-protein interaction (PPI) network analysis, Gene Ontology (GO) assessments, and Reactome pathway enrichment analyses. Molecular docking techniques investigated interactions between active compounds and these targets. The expression and prognostic implications of target genes were evaluated using GEPIA2 and the Human Protein Atlas (HPA) databases. In vitro studies assessed the impact of epimedium extract (EPE) on Panc-1 cell viability, and Western blot analysis examined the expression levels of key targets. Results: Network pharmacological indicate that epimedium econtains active components such as baohuoside I, icariin, hyperoside, and epimedin B, which have potential therapeutic effects against PC. In vitro assays confirmed that EPE significantly reduced the viability of Panc-1 cells. Western blot analysis revealed a considerable decrease in the expression of key targets in EPE-treated cells, including AKT1, EGFR, p-EGFR, JUN, BCL2, IL6, and SRC. The R-HSA-1280215: Interleukin-4 and Interleukin-13 signaling pathways involving these genes were identified as potential therapeutic targets. Discussion: Epimedium holds promise as a candidate for treating PC. The modulation of interleukin-4 and interleukin-13 signaling pathways could be a pivotal mechanism by which epimedium impedes tumor development. Further research is warranted to validate these findings and explore the clinical applicability of epimedium in PC treatment. [ABSTRACT FROM AUTHOR]

Abstract This study investigated the anti-inflammatory compounds in Ogaza, Acanthopanax sessiliflorus fruit, and their extracts using metabolomic screening. Ogaza extracts were obtained in various solvents, such as 70% ethanol, 70% methanol, and water. The anti-inflammatory activity was estimated by evaluating nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 cells treated with the extracts. The 70% ethanol extract (EO) showed the most effective anti-inflammatory activity, inhibiting nitric oxide production by approximately 50% and downregulating iNOS expression. The 70% ethanol extract was further fractionated into three partial subfractions by preparative LC to identify the anti-inflammatory compounds. Assessment of the anti-inflammatory activity of each subfraction revealed that the third subfraction (E-F3) showed the highest inhibitory activity against nitric oxide. E-F3 effectively suppressed iNOS expression. Subsequently, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and multivariate statistical analyses were performed to identify the compounds that significantly contributed to the anti-inflammatory activity of the Ogaza extract. Fourteen and 16 compounds in the negative- and positive-ion modes, respectively, were identified as significant constituents of Ogaza. Compounds like quercetin, hyperoside, acanthoside D, oleanolic acid, and scopoletin were identified as potential anti-inflammatory components in Ogaza extract. This study characterized the functional properties of Acanthopanax sessiliflorus fruit and indicated the possibility that other compartments of Acanthopanax sessiliflorus may also serve as natural sources of nutraceuticals.

Abstract Activated microglia play an important role in driving photoreceptor degeneration-associated neuroinflammation in the retina. Controlling pro-inflammatory activation of microglia holds promise for mitigating the progression of photoreceptor degeneration. Our previous study has demonstrated that pre-light damage treatment of hyperoside, a naturally occurring flavonol glycoside with antioxidant and anti-inflammatory activities, prevents photooxidative stress-induced photoreceptor degeneration and neuroinflammatory responses in the retina. However, the direct impact of hyperoside on microglia-mediated neuroinflammation during photoreceptor degeneration remains unknown. Upon verifying the anti-inflammatory effects of hyperoside in LPS-stimulated BV-2 cells, our results here further demonstrated that post-light damage hyperoside treatment mitigated the loss of photoreceptors and attenuated the functional decline of the retina. Meanwhile, post-light damage hyperoside treatment lowered neuroinflammatory responses and dampened microglial activation in the illuminated retinas. With respect to microglial activation, hyperoside mitigated the pro-inflammatory responses in DNA-stimulated BV-2 cells and lowered DNA-stimulated production of 2′3′-cGAMP in BV-2 cells. Moreover, hyperoside was shown to directly interact with cGAS and suppress the enzymatic activity of cGAS in a cell-free system. In conclusion, the current study suggests for the first time that the DNA sensor cGAS is a direct target of hyperoside. Hyperoside is effective at mitigating DNA-stimulated cGAS-mediated pro-inflammatory activation of microglia, which likely contributes to the therapeutic effects of hyperoside at curtailing neuroinflammation and alleviating neuroinflammation-instigated photoreceptor degeneration.

Abstract The physiological changes caused by the decline in estrogen levels due to menopause are linked to an increased risk of depression. This study investigated the antidepressant effects of hyperoside (HYP), a natural flavonol glycoside, and its associated molecular mechanisms in primary hippocampal neurons and ovariectomized (OVX) mice. HYP treatment increased nitric oxide (NO) production and neuronal nitric oxide synthase (nNOS) expression in primary hippocampal neurons; additionally, it upregulated the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin receptor kinase B (TrkB). In OVX mice, HYP treatment significantly improved depression-like behaviors in an open field test to a level comparable to estrogen treatment. Furthermore, HYP treatment upregulated OVX-induced decreased nNOS expression and BDNF-TrkB signaling in the hippocampus. Therefore, this study suggests that HYP exhibits antidepressant potential by addressing estrogen deficiency-induced alterations, specifically by restoring nNOS expression, promoting NO production, and concurrently enhancing BDNF-TrkB signaling in OVX mice.

This study investigated the anti-inflammatory compounds in Ogaza, Acanthopanax sessiliflorus fruit, and their extracts using metabolomic screening. Ogaza extracts were obtained in various solvents, such as 70% ethanol, 70% methanol, and water. The anti-inflammatory activity was estimated by evaluating nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 cells treated with the extracts. The 70% ethanol extract (EO) showed the most effective anti-inflammatory activity, inhibiting nitric oxide production by approximately 50% and downregulating iNOS expression. The 70% ethanol extract was further fractionated into three partial subfractions by preparative LC to identify the anti-inflammatory compounds. Assessment of the anti-inflammatory activity of each subfraction revealed that the third subfraction (E-F3) showed the highest inhibitory activity against nitric oxide. E-F3 effectively suppressed iNOS expression. Subsequently, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and multivariate statistical analyses were performed to identify the compounds that significantly contributed to the anti-inflammatory activity of the Ogaza extract. Fourteen and 16 compounds in the negative- and positive-ion modes, respectively, were identified as significant constituents of Ogaza. Compounds like quercetin, hyperoside, acanthoside D, oleanolic acid, and scopoletin were identified as potential anti-inflammatory components in Ogaza extract. This study characterized the functional properties of Acanthopanax sessiliflorus fruit and indicated the possibility that other compartments of Acanthopanax sessiliflorus may also serve as natural sources of nutraceuticals. [ABSTRACT FROM AUTHOR]

The antidepressant effect of hyperoside (HYP), which is the main component of Hypericum perforatum , is not established. This study aimed to determine the effects of HYP on depression. The antidepressant-like effect of HYP was studied in mice induced by chronic restraint stress (CRS). The effects of HYP on behavior, inflammation, neurotransmitters, gut microbiota, and short-chain fatty acids (SCFAs) were studied in CRS mice. HYP improved depressive-like behavior in mice induced by CRS. Nissl staining analysis showed that HYP improved neuronal damage in CRS mice. Western blot (WB) analysis showed that HYP increased the expression levels of BDNF and PSD95 in the hippocampus of CRS mice. The results of ELISA showed that HYP down-regulated the expression levels of IL-6, IL-1β, TNF-α, and CORT in the hippocampus, blood, and intestinal tissues of mice and up-regulated the expression levels of 5-HT and BDNF. Hematoxylin and eosin (HE) staining results indicate that HYP can improve the intestinal histopathological injury of CRS mice. The results of 16S rRNA demonstrated that HYP attenuated the dysbiosis of the gut microbiota of depressed mice, along with altering the concentration of SCFAs. In the present study, direct evidence that HYP improves depressive behaviors via gut microbiota and SCFAs is lacking, and only female mice were evaluated, which limits the understanding of the effects of HYP on both sexes. HYP can improve CRS-induced depressive-like behaviors in mice, which is associated with regulating the gut microbiota and SCFAs concentration. [Display omitted] • Hyperoside can improve CRS-induced depressive-like behaviors in mice. • Hyperoside can improve gut microbiota and SCFAs concentrations in CRS mice. • SCFAs and the gut microbiota play a role in hyperoside's antidepressant action. [ABSTRACT FROM AUTHOR]

Activated microglia play an important role in driving photoreceptor degeneration-associated neuroinflammation in the retina. Controlling pro-inflammatory activation of microglia holds promise for mitigating the progression of photoreceptor degeneration. Our previous study has demonstrated that pre-light damage treatment of hyperoside, a naturally occurring flavonol glycoside with antioxidant and anti-inflammatory activities, prevents photooxidative stress-induced photoreceptor degeneration and neuroinflammatory responses in the retina. However, the direct impact of hyperoside on microglia-mediated neuroinflammation during photoreceptor degeneration remains unknown. Upon verifying the anti-inflammatory effects of hyperoside in LPS-stimulated BV-2 cells, our results here further demonstrated that post-light damage hyperoside treatment mitigated the loss of photoreceptors and attenuated the functional decline of the retina. Meanwhile, post-light damage hyperoside treatment lowered neuroinflammatory responses and dampened microglial activation in the illuminated retinas. With respect to microglial activation, hyperoside mitigated the pro-inflammatory responses in DNA-stimulated BV-2 cells and lowered DNA-stimulated production of 2′3′-cGAMP in BV-2 cells. Moreover, hyperoside was shown to directly interact with cGAS and suppress the enzymatic activity of cGAS in a cell-free system. In conclusion, the current study suggests for the first time that the DNA sensor cGAS is a direct target of hyperoside. Hyperoside is effective at mitigating DNA-stimulated cGAS-mediated pro-inflammatory activation of microglia, which likely contributes to the therapeutic effects of hyperoside at curtailing neuroinflammation and alleviating neuroinflammation-instigated photoreceptor degeneration. [ABSTRACT FROM AUTHOR]

At present, ulcerative colitis (UC) has become a global disease due to its high incidence. Hyperoside (HYP) is a naturally occurring flavonoid compound with many pharmacological effects. This study aimed to develop HYP-loaded mixed micelles (HYP-M) to improve oral bioavailability of HYP and to evaluate its therapeutic effect on UC. The prepared HYP-M exhibited stable physical and chemical properties, smaller particle size (PS) (21.48 ± 1.37 nm), good polydispersity index (PDI = 0.178 ± 0.013), negative Zeta potential (ZP) (− 20.00 ± 0.48 mV) and high entrapment rate (EE) (89.59 ± 2.03%). In vitro release and in vivo pharmacokinetic results showed that HYP-M significantly increased the releasing rate of HYP, wherein its oral bioavailability was 4.15 times higher than that of free HYP. In addition, HYP-M was more effective in the treatment of UC than free HYP. In conclusion, HYP-M could serve as a novel approach to improve bioavailability and increase anti-UC activity of HYP. [ABSTRACT FROM AUTHOR]

The physiological changes caused by the decline in estrogen levels due to menopause are linked to an increased risk of depression. This study investigated the antidepressant effects of hyperoside (HYP), a natural flavonol glycoside, and its associated molecular mechanisms in primary hippocampal neurons and ovariectomized (OVX) mice. HYP treatment increased nitric oxide (NO) production and neuronal nitric oxide synthase (nNOS) expression in primary hippocampal neurons; additionally, it upregulated the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin receptor kinase B (TrkB). In OVX mice, HYP treatment significantly improved depression-like behaviors in an open field test to a level comparable to estrogen treatment. Furthermore, HYP treatment upregulated OVX-induced decreased nNOS expression and BDNF-TrkB signaling in the hippocampus. Therefore, this study suggests that HYP exhibits antidepressant potential by addressing estrogen deficiency-induced alterations, specifically by restoring nNOS expression, promoting NO production, and concurrently enhancing BDNF-TrkB signaling in OVX mice. [ABSTRACT FROM AUTHOR]

Equine herpesvirus type 8 (EHV-8) causes abortion and respiratory disease in horses and donkeys, leading to serious economic losses in the global equine industry. Currently, there is no effective vaccine or drug against EHV-8 infection, underscoring the need for a novel antiviral drug to prevent EHV-8-induced latent infection and decrease the pathogenicity of this virus. The present study demonstrated that hyperoside can exert antiviral effects against EHV-8 infection in RK-13 (rabbit kidney cells), MDBK (Madin-Darby bovine kidney), and NBL-6 cells (E. Derm cells). Mechanistic investigations revealed that hyperoside induces heme oxygenase-1 expression by activating the c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis, alleviating oxidative stress and triggering a downstream antiviral interferon response. Accordingly, hyperoside inhibits EHV-8 infection. Meanwhile, hyperoside can also mitigate EHV-8-induced injury in the lungs of infected mice. These results indicate that hyperoside may serve as a novel antiviral agent against EHV-8 infection. IMPORTANCE Hyperoside has been reported to suppress viral infections, including herpesvirus, hepatitis B virus, infectious bronchitis virus, and severe acute respiratory syndrome coronavirus 2 infection. However, its mechanism of action against equine herpesvirus type 8 (EHV-8) is currently unknown. Here, we demonstrated that hyperoside significantly inhibits EHV-8 adsorption and internalization in susceptible cells. This process induces HO-1 expression via c-Jun N-terminal kinase/nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 axis activation, alleviating oxidative stress and triggering an antiviral interferon response. These findings indicate that hyperoside could be very effective as a drug against EHV-8. [ABSTRACT FROM AUTHOR]

Background and Aim: African swine fever (ASF) causes disease in pigs with up to 100% mortality rates. There is no effective vaccine to protect against it. This study aimed to perform in silico docking of ASF virus (ASFV) pNP868R protein with potential flavonoid ligands to identify ligands that interfere with mRNA cap formation. Materials and Methods: The ASFV pNP868R protein was tested with hyperoside, isoquercetin, quercetin, and quercitrin in this in silico simulation. ASFV pNP868R protein was extracted from the Research Collaboration for Structural Bioinformatics P rotein Data Bank (RCSB PDB) database with PDB ID 7D8U (https://www.rcsb.org/structure/7D8U). Standard ligands were separated from proteins using UCSF Chimera 1.13. The standard ligand was redocked to protein using AutoDockTools 1.5.6 with the AutoDock4 method for validation. In the docking process, the grid box size was 40 × 40 × 40 Å3 with x, y, and z coordinates of 16.433, −43.826, and −9.496, respectively. The molecular docking process of the proposed ligand–protein complex can proceed if the standard ligand position is not significantly different from its original position in the viral protein’s pocket. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (RoG) of the hyperoside with the lowest energy binding need to be analyzed with molecular dynamics using Groningen machine for chemical simulation 5.1.1. Results: Molecular docking and dynamic simulation revealed that hyperoside had the most stable and compact binding to the pNP868R protein. Hyperoside binds to the protein at the minimum energy of −9.07 KJ/mol. The RMSD, RMSF, and RoG values of 0.281 nm, 0.2 nm, and 2.175 nm, respectively, indicate the stability and compactness of this binding. Conclusion: Hyperoside is the most likely antiviral candidate to bind to the pNP868R protein in silico. Therefore, it is necessary to test whether this flavonoid can inhibit mRNA capping in vitro and elicit the host immune response against uncapped viral mRNA.

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

Background and Aim: African swine fever (ASF) causes disease in pigs with up to 100% mortality rates. There is no effective vaccine to protect against it. This study aimed to perform in silico docking of ASF virus (ASFV) pNP868R protein with potential flavonoid ligands to identify ligands that interfere with mRNA cap formation. Materials and Methods: The ASFV pNP868R protein was tested with hyperoside, isoquercetin, quercetin, and quercitrin in this in silico simulation. ASFV pNP868R protein was extracted from the Research Collaboration for Structural Bioinformatics P rotein Data Bank (RCSB PDB) database with PDB ID 7D8U (https://www.rcsb.org/structure/7D8U). Standard ligands were separated from proteins using UCSF Chimera 1.13. The standard ligand was redocked to protein using AutoDockTools 1.5.6 with the AutoDock4 method for validation. In the docking process, the grid box size was 40 × 40 × 40 Å3 with x, y, and z coordinates of 16.433, -43.826, and -9.496, respectively. The molecular docking process of the proposed ligand-protein complex can proceed if the standard ligand position is not significantly different from its original position in the viral protein's pocket. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (RoG) of the hyperoside with the lowest energy binding need to be analyzed with molecular dynamics using Groningen machine for chemical simulation 5.1.1. Results: Molecular docking and dynamic simulation revealed that hyperoside had the most stable and compact binding to the pNP868R protein. Hyperoside binds to the protein at the minimum energy of -9.07 KJ/mol. The RMSD, RMSF, and RoG values of 0.281 nm, 0.2 nm, and 2.175 nm, respectively, indicate the stability and compactness of this binding. Conclusion: Hyperoside is the most likely antiviral candidate to bind to the pNP868R protein in silico. Therefore, it is necessary to test whether this flavonoid can inhibit mRNA capping in vitro and elicit the host immune response against uncapped viral mRNA. [ABSTRACT FROM AUTHOR]

In the present study, we focused our attention on Crataegus laciniata Ucria (Rosaceae), which is wild growing in western Sicily (Italy). The chemical profile of the C. laciniata flower's (CLF) ethanolic (70%) extract showed the presence of both C-flavonoid and O-flavonoid derivatives. Beyond the main metabolites, like hyperoside and vitexin, there are several luteolin derivates, in addition to catechin and epicatechin dimers or trimers. Regarding the antioxidant activities, CLF showed a strong ability to scavenge DPPH and ABTS radicals and a good Fe3+-reducing antioxidant power. The investigation into the key enzymes in diabetes showed strong inhibition on α-amylase and α-glucosidase, whereas the skin-whitening properties are linked to inhibitory effects on tyrosinase. Moreover, we employed Danio rerio (zebrafish) for toxicity assessment, as it represents an ideal in vivo model due to its high correlation with humans in response to pharmaceutical and cosmetic testing. Zebrafish embryos exposed to CLF (25–100 µg/mL) showed marked depigmentation compared to phenylthiourea (PTU), in addition to a high survival percentage and the absence of malformations. In conclusion, this experimental study outlines that C. laciniata flowers could be a potential source of bioactive compounds for application in the pharmaceutical and cosmeceutical industries. [ABSTRACT FROM AUTHOR]

Some ingredients from herbal medicine can significantly affect the activity of CYP2D6, thus leading to serious interactions between herbs and drugs. Quercetin and hyperoside are active ingredients widely found in vegetables, fruits, and herbal medicines. Quercetin and hyperoside have many biological activities. In this work, the characteristic bindings of CYP2D6 with quercetin/hyperoside are revealed by multi‐spectroscopy analysis, molecular docking, and molecular dynamics simulations. The fluorescence of CYP2D6 is statically quenched by quercetin and hyperoside. The binding constant (Ka) values of CYP2D6–quercetin/hyperoside range from 104 L mol−1, which indicates that these two flavonoids bind moderately to CYP2D6. Meanwhile, quercetin has a stronger quenching ability to CYP2D6 than that of hyperoside. The secondary structure of CYP2D6 is obviously changed by binding with quercetin/hyperoside. The docking results reveal that the quercetin/hyperoside enters the active site of CYP2D6 near heme and binds to CYP2D6 by hydrogen bonds and van der Waals forces. The molecular dynamics simulation results indicate that the binding of quercetin/hyperoside can stabilize the two complexes, enhance the flexibility of CYP2D6 backbone atoms, and make a more unfolded and looser structure of CYP2D6. [ABSTRACT FROM AUTHOR]

Objective: To establish a HPLC method for simultaneous determination of rutin, hyperoside, quercetin in Xiang lotus. Methods: The HPLC method was performed on an Agilent ZORBAX SB-C18 column (4.6 mm×250 mm, 5 m) with gradient elution of methanol and 0.6% phosphoric acid solution. The flow rate was 1.0 mL/min. The column temperature was 30 ℃ and the detection wavelength was set at 255 nm. Results: The contents of rutin, hypericin and quercetin in 20 batches of lotus samples were 1.32~2.06, 1.36~2.43, 1.41~3.26 mg/kg, respectively. The linear range of the concentration of rutin, hypericin and quercetin was 5~200 g/mL (R2=0.999 9), the three flavonoids showed a good linearity, a high sensitivity, and good serviceability. The relative standard deviation (RSD) for precision, stability, repeatability, and recoveries test were all less than 4.0%, and the average recovery rate of added standard were 96.6%, 96.9%, 97.4%, respecitvely. Conclusion: The method is convenient and accurate, and can be used for the content determination and quality evaluation of flavonoids in Xiang lotus.

Kaiyang Wang,1,&ast; Huhai Zhang,2,&ast; Lie Yuan,3,4 Xiaoli Li,3,4 Yongqing Cai1 1Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Nephrology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 4Chongqing Key Research Laboratory for Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongqing Cai, Department of Pharmacy, Daping Hospital, Army Medical University, No. 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Tel +86 023 68746950, Email cy0721@163.com Xiaoli Li, Department of Pharmacology, College of Pharmacy, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 023 63657050, Email lixiaoli@cqmu.edu.cnAbstract: Hyperoside is a flavonol glycoside mainly found in plants of the genera Hypericum and Crataegus, and also detected in many plant species such as Abelmoschus manihot, Ribes nigrum, Rosa rugosa, Agrostis stolonifera, Apocynum venetum and Nelumbo nucifera. This compound exhibits a multitude of biological functions including anti-inflammatory, antidepressant, antioxidative, vascular protective effects and neuroprotective effects, etc. This review summarizes the quantification, original plant, chemical structure and property, structure–activity relationship, pharmacologic effect, pharmacokinetics, toxicity and clinical application of hyperoside, which will be significant for the exploitation for new drug and full utilization of this compound.Keywords: hyperoside, original plant, chemical structure, pharmacology, pharmacokinetics, toxicity

Two polyphenols–hyperoside (HYP) and protocatechuic acid (PCA) were reported to exert antidepressant activity in rodents after acute treatment. Our previous study also showed that this activity might have been influenced by the monoaminergic system and the upregulation of the brain-derived neurotropic factor (BDNF) level. A very long-term pharmacological therapy is required for the treatment of a patient with depression. The repetitive use of antidepressants is recognized to impact the brain structures responsible for regulating both emotional and cognitive behaviors. Thus, we investigated the antidepressant, anxiolytic, and procognitive effects of HYP and PCA in mice after acute and prolonged treatment (14 days). Both polyphenols induced an anxiogenic-like effect after acute treatment, whereas an anxiolytic effect occurred after repetitive administration. PCA and HYP showed procognitive effects when they were administered acutely and chronically, but it seems that their influence on long-term memory was stronger than on short-term memory. In addition, the preset study showed that the dose of 7.5 mg/kg of PCA and HYP was effective in counteracting the effects of co-administered scopolamine in the long-term memory impairment model induced by scopolamine. Our experiments revealed the compounds have no affinity for 5-HT1A and 5-HT2A receptors, whereas a significant increase in serum serotonin level after prolonged administration of PCA and HYP at a dose of 3.75 mg/kg was observed. Thus, it supports the involvement of the serotonergic system in the polyphenol mechanisms. These findings led us to hypothesize that the polyphenols isolated from Impatiens glandulifera can hold promise in treating mental disorders with cognitive dysfunction. Consequently, extended studies are necessary to delve into their pharmacological profile. [ABSTRACT FROM AUTHOR]

Leaves of species of the genus Juglans L. of the Juglandaceae family hold promise as officinal medicinal plant materials whose preparations have an antimicrobial and general tonic effect. In our opinion, the contribution to the antimicrobial activity is made, along with naphthoquinones, by the flavonoids contained in the leaves of various species of the genus Juglans L. This creates the need to determine the chemical composition of the leaves of species of the genus Juglans L. using modern methods of analysis. This article discusses the results of studying the component composition of the leaves of Juglans nigra L., Juglans regia L., and Juglans cinerea L. by microcolumn high performance liquid chromatography (HPLC) at an analytical wavelength of 360 nm. The chromatographic separation conditions were established for the analysis of extracts from the leaves of the species of the genus Juglans L. It was determined that use of HPLC allows identification in the leaves of Juglans nigra L. of the dominant and diagnostically significant for this raw material flavonoids, myricitrin and quercitrin. Also, this medicinal plant was found to contain the aglycone of myricitrin, myricetin. A similar flavonoid profile was revealed for two medicinal plant raw materials represented by leaves of Juglans regia L. and of Juglans cinerea L. Hyperoside, quercitrin, and juglanin were found in these species. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicines such as hyperoside-rich Acanthopanax senticosus and Crataegus pinnatifida have been confirmed to exhibit anti-oxidative stress properties. Hyperoside, the main ingredient of numerous antioxidant herbs, may have the ability to postpone the onset of neurodegenerative diseases. This study investigates the possible therapeutic mechanism of hyperoside as a natural antioxidant against Alzheimer's disease (AD) in Caenorhabditis elegans and PC12 cells. Specifically, hyperoside reduced reactive oxygen species (ROS) level and Aβ42-induced neurotoxicity in C. elegans worms. Meanwhile, hyperoside reduced ROS production and increased mitochondrial membrane potentialin Aβ42-induced PC12 cells, which possibly due to the increase of antioxidant enzymes activity and the diminution of malondialdehyde levels. Hoechst 33,342 staining and flow cytometry analysis results suggested that hyperoside reverses cell apoptosis. Network pharmacology predicts potentially relevant hyperoside targets and pathways in AD therapy. As anticipated, hyperoside reversed Aβ42-stimulated downregulation of the PI3K/Akt/Nrf2/HO-1. The PI3K inhibitor LY294002 partially abolished the protective capability of hyperoside. The results of molecular docking further indicated that the PI3K/Akt pathways may be involved in the protection of Aβ42-induced PC12 cells by hyperoside treatment. The study provides theoretical information for research and development of hyperoside as an antioxidant dietary supplement. [ABSTRACT FROM AUTHOR]

Renal tubular injury is a key factor in the progression of diabetic kidney disease to end‐stage renal disease. Hyperoside, a natural flavonol glycoside in various plants, is a potentially effective drug for the clinical treatment of diabetic kidney disease. However, the specific mechanisms remain unknown. Therefore, this study will explore the effect and mechanism of hyperoside on renal tubulointerstitium in diabetic kidney disease. db/db mouse (C57BL/KsJ) is a model of type 2 diabetes resulting from Leptin receptor point mutations, with the appearance of diabetic kidney disease. Therefore, db/db mice were used for in vivo experimental studies. In vitro, human renal tubular epithelial cells were incubated with bovine serum albumin to simulate the injury of renal tubular epithelial cells caused by excessive albumin in primary urine. The experimental results showed that hyperoside could improve kidney function and reduce kidney tissue damage in mice, and could inhibit oxidative stress, extracellularly regulated protein kinases 1/2 signaling activation, and pyroptosis in human renal tubular epithelial cells. Therefore, hyperoside inhibited oxidative stress by regulating the activation of the extracellularly regulated protein kinases 1/2/mitogen‐activated protein kinase signaling pathway, thereby alleviating proteinuria‐induced pyroptosis in renal tubular epithelial cells. This study provides novel evidence that could facilitate the clinical application of hyperoside in diabetic kidney disease treatment. [ABSTRACT FROM AUTHOR]

The antibacterial activities of quercetin and hyperoside were evaluated towards two major spoilage bacteria in fish, Pseudomonas aeruginosa (PA) and Shewanella putrefaciens (SP). Hyperoside showed a lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) towards both spoilage bacteria, PA and SP, than quercetin. Cell membrane morphology was affected when treated with hyperoside and quercetin. The release of content from the treated cells occurred, as ascertained by the release of potassium and magnesium ions and the increase in conductivity of the culture media. The morphology of cells was significantly changed, in which shrinkage and pores were obtained, when observed using SEM. Both compounds negatively affected the motility, both swimming and swarming, and the formation of extracellular polymeric substance (EPS), thus confirming antibiofilm activities. Agarose gel analysis revealed that both compounds could bind to or degrade the genomic DNA of both bacteria, thereby causing bacterial death. Molecular docking indicated that the compounds interacted with the minor groove of the DNA, favoring the adenine–thymine-rich regions. Thus, both quercetin and hyperoside could serve as potential antimicrobial agents to retard the spoilage of fish or perishable products. [ABSTRACT FROM AUTHOR]

Vision loss and blindness are frequently caused by photoreceptor degeneration, for example in age‐related macular degeneration and retinitis pigmentosa. However, there is no effective medicine to treat these photoreceptor degeneration‐related diseases. Cell senescence is a common phenotype in many diseases; however, few studies have reported whether it occurs in photoreceptor degeneration diseases. Herein, we identified that cell senescence is associated with photoreceptor degeneration induced by N‐methyl‐N‐nitrosourea (MNU, a commonly used photoreceptor degeneration model), presented as increased senescence‐associated β‐galactosidase activity, DNA damage, oxidative stress and inflammation‐related cytokine Interleukin 6 (IL6), and upregulation of cyclin p21 or p16. These results suggested that visual function might be protected using anti‐aging treatment. Furthermore, Hyperoside is reported to help prevent aging in various organs. In this study, we showed that Hyperoside, delivered intravitreally, alleviated photoreceptor cell senescence and ameliorated the functional and morphological degeneration of the retina in vivo and in vitro. Importantly, Hyperoside attenuated the MNU‐induced injury and aging of photoreceptors via AMPK‐ULK1 signaling inhibition. Taken together, our results demonstrated that Hyperoside can prevent MNU‐induced photoreceptor degeneration by inhibiting cell senescence via the AMPK‐ULK1 pathway. [ABSTRACT FROM AUTHOR]

Oligoasthenozoospermia is becoming a serious problem, but effective prevention or treatment is lacking. Hyperoside, one of the main active ingredients in traditional Chinese medicine, may be effective in the treatment of oligoasthenozoospermia. In this study, we used cyclophosphamide (CTX: 50 mg/kg) to establish a mouse model of Oligoasthenozoospermia to investigate the therapeutic effect of hyperoside (30 mg/kg) on CTX-induced oligoasthenozoospermia. All mice were divided into four groups: blank control group (Control), treatment control group (Hyp), disease group (CTX) and treatment group (CTX + H). Mice body weight, testicular weight, sperm parameters and testicular histology were used to assess the reproductive capacity of mice and to explore the underlying mechanism of hyperoside in the treatment of oligoasthenozoospermia by assessing hormone levels, protein levels of molecules related to hormone synthesis and transcript levels of important genes related to spermatogenesis. Treatment with hyperoside significantly improved sperm density, sperm viability and testicular function compared to untreated oligoasthenozoospermia mice. In mechanism, treatment with hyperoside resulted in significant improvement in pathological changes in spermatogenic tubules, with an increase in testosterone production, and upregulations of Protein Kinase CAMP-Activated Catalytic Subunit Beta (PRKACB), Steroidogenic Acute Regulatory Protein (STAR), and Cytochrome P450 Family 17 Subfamily A Member 1 (CYP17A1) for testosterone production. Hyperoside also promoted the cell cycle of germ cells and up-regulated meiosis and spermatogenesis-related genes, including DNA Meiotic Recombinase 1 (Dmc1), Ataxia telangiectasia mutated (Atm) and RAD21 Cohesin Complex Component (Rad21). In conclusion, hyperoside exerted protective effects on oligoasthenozoospermia mice by regulating testosterone production, meiosis and sperm maturation of germ cells. [ABSTRACT FROM AUTHOR]

A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was built to determine icarside, hyperoside and psoralen in food. The samples were extracted with 70% methanol, the solid and semi-solid hotpot seasoning samples were purified by solid phase extraction column, and then determined by HPLC-MS/MS. Acetonitrile and 0.1% formic acid solution were used as the mobile phase, and the gradient elution was adopted for analysis. As shown in the results, the analytes had good linearity in the range of 0.05−100 ng/mL, and the correlation coeffificients (R2) were greater than 0.999. In this method, the limits of quantitation (LOQ) of psoralen, icariside and hyperoside in liquid samples were 1.25, 25.0 and 12.5 μg/L respectively; while the LOQs of psoralen, icariside and hyperoside in solid samples and hotpot seasoning samples were 1.25, 25.0 and 12.5 μg/kg, respectively. The liquid beverage, solid beverage, health food (in the form of oral liquid, capsule, tablet), integrated alcoholic beverage and solid hotpot seasoning were selected as representative samples and used for method validation. The average spiked recoveries at 3 levels (LOQ, 2 LOQ, 10 LOQ) were in the range of 83.7%−115.0%, and the relative standard deviations were in range of 0.5%−9.4% (n = 6). The method is rapid, accurate and sensitive, which is suitable for the simultaneous determination of icariside, hyperoside and psoralen in different food matrices.

Abstract Background Photoreceptor degeneration underpinned by oxidative stress-mediated mitochondrial dysfunction and cell death leads to progressive and irreversible vision impairment. Drug treatments that protect against photoreceptor degeneration are currently available in the clinical settings. It has been shown that hyperoside, a flavonol glycoside, protects against neuronal loss in part by suppressing oxidative stress and maintaining the functional integrity of mitochondria. However, whether hyperoside protects against photoreceptor degeneration remains unknown. Methods To address the pharmacological potentials of hyperoside against oxidative stress-mediated photoreceptor degeneration on molecular, cellular, structural and functional levels, multiple in vitro and in vivo methodologies were employed in the current study, including live-cell imaging, optical coherence tomography, electroretinography, histological/immunohistochemical examinations, transmission electron microscopy, RNA-sequencing and real-time qPCR. Results The in vitro results demonstrate that hyperoside suppresses oxidative stress-mediated photoreceptor cell death in part by mitigating mitochondrial dysfunction. The in vivo results reveal that hyperoside protects against photooxidative stress-induced photoreceptor morphological, functional and ultrastructural degeneration. Meanwhile, hyperoside treatment offsets the deleterious impact of photooxidative stress on multiple molecular pathways implicated in the pathogenesis of photoreceptor degeneration. Lastly, hyperoside attenuates photoreceptor degeneration-associated microglial inflammatory activation and reactive Müller cell gliosis. Conclusions All things considered, the present study demonstrates for the first time that hyperoside attenuates oxidative stress-induced photoreceptor mitochondrial dysfunction and cell death. The photoreceptor-intrinsic protective effects of hyperoside are corroborated by hyperoside-conferred protection against photooxidative stress-mediated photoreceptor degeneration and perturbation in retinal homeostasis, warranting further evaluation of hyperoside as a photoreceptor protective agent for the treatment of related photoreceptor degenerative diseases.

Summary: Textural, rheological, structural and sensorial properties of threadfin bream surimi as influenced by the addition of hyperoside (HyS) at various levels (0%–4%; w/w) were investigated. Surimi gel added with 1% and 2% HyS (HyS1 and HyS2, respectively) had the highest breaking force and deformation (P < 0.05). HyS2 showed the maximum water‐holding capacity, followed by HyS1 (P < 0.05). Whiteness of gel was decreased when the concentration of HyS was higher than 1%. Hardness, springiness, gumminess and chewiness increased with the addition of 1%–2% HyS (P < 0.05). HyS enhanced the connections between surimi proteins as supported by the appearance of some polymerised proteins. No major changes in the secondary structure of myofibrillar proteins in gel were noticed as determined by FTIR. Microstructure also revealed the formation of higher connectivity in the gel network with the addition of 1%–2% HyS. Likeness score for taste and flavour slightly decreased (P < 0.05), but the overall likeness score for HyS1 was still higher than the acceptable limit (score of 5). Therefore, the addition of HyS improved the gelling properties of threadfin surimi gel, which could be claimed as a functional food due to the several health benefits of HyS. Nevertheless, future studies should be conducted to reduce the bitterness associated with HyS incorporation. [ABSTRACT FROM AUTHOR]

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Clinical application of doxorubicin (Dox) in cancer chemotherapy is limited by its cardiotoxicity. Present study aimed to demonstrate the effect and mechanism of hyperoside in Dox‐induced cardiotoxicity. C57BL/6 mice were injected with 12 mg/kg of Dox, and 1 μM Dox was exposed to primary cardiomyocytes. Cardiac function was evaluated by echocardiographic and myocardial enzyme levels. Cardiomyocyts apoptosis was analyzed by TUNEL staining and flow cytometry. Network pharmacology and molecular docking were utilized to explore potential targets of hyperoside. Protein expressions were detected by western blot and enzyme activities were determined by colorimetry. Cardiac dysfunction and cardiomyocyte apoptosis induced by Dox were attenuated by hyperoside. Mechanism of hyperoside was mainly related to "oxidative stress" pathway. Hyperoside exhibited strong binding activities with nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs, the main source of ROS in cardiomyocytes) and cyclooxygenases (COXs). Experiments proved that hyperoside suppressed the ROS generation and the elevated activities of NOXs and COXs induced by Dox. Dox also triggered the activation of NLRP3 inflammasome, which was reversed by hyperoside. Hyperoside bound to NOXs and COXs, which prevents Dox‐induced cardiotoxicity by inhibiting NOXs/ROS/NLRP3 inflammasome signaling pathway. Hyperoside holds promise as a therapeutic strategy for Dox‐induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Background: Photoreceptor degeneration underpinned by oxidative stress-mediated mitochondrial dysfunction and cell death leads to progressive and irreversible vision impairment. Drug treatments that protect against photoreceptor degeneration are currently available in the clinical settings. It has been shown that hyperoside, a flavonol glycoside, protects against neuronal loss in part by suppressing oxidative stress and maintaining the functional integrity of mitochondria. However, whether hyperoside protects against photoreceptor degeneration remains unknown. Methods: To address the pharmacological potentials of hyperoside against oxidative stress-mediated photoreceptor degeneration on molecular, cellular, structural and functional levels, multiple in vitro and in vivo methodologies were employed in the current study, including live-cell imaging, optical coherence tomography, electroretinography, histological/immunohistochemical examinations, transmission electron microscopy, RNA-sequencing and real-time qPCR. Results: The in vitro results demonstrate that hyperoside suppresses oxidative stress-mediated photoreceptor cell death in part by mitigating mitochondrial dysfunction. The in vivo results reveal that hyperoside protects against photooxidative stress-induced photoreceptor morphological, functional and ultrastructural degeneration. Meanwhile, hyperoside treatment offsets the deleterious impact of photooxidative stress on multiple molecular pathways implicated in the pathogenesis of photoreceptor degeneration. Lastly, hyperoside attenuates photoreceptor degeneration-associated microglial inflammatory activation and reactive Müller cell gliosis. Conclusions: All things considered, the present study demonstrates for the first time that hyperoside attenuates oxidative stress-induced photoreceptor mitochondrial dysfunction and cell death. The photoreceptor-intrinsic protective effects of hyperoside are corroborated by hyperoside-conferred protection against photooxidative stress-mediated photoreceptor degeneration and perturbation in retinal homeostasis, warranting further evaluation of hyperoside as a photoreceptor protective agent for the treatment of related photoreceptor degenerative diseases. [ABSTRACT FROM AUTHOR]

1. Cisplatin is a widely used chemotherapeutic agent to treat solid tumours in clinics. However, cisplatin-induced acute kidney injury (AKI) limits its clinical application. This study investigated the effect of hyperoside (a flavonol glycoside compound) on regulating AKI. 2. The model of cisplatin-induced AKI was established, and hyperoside was preadministered to investigate its effect on improving kidney injury. 3. Hyperoside ameliorated renal pathological damage, reduced the accumulation of SCr, BUN, Kim-1 and indoxyl sulphate in vivo, increased the excretion of indoxyl sulphate into the urine, and upregulated the expression of renal organic anion transporter 1 (Oat1). Moreover, evaluation of rat kidney slices demonstrated that hyperoside promoted the uptake of PAH (p-aminohippurate, the Oat1 substrate), which was confirmed by transient over-expression of OAT1 in HEK-293T cells. Additionally, hyperoside upregulated the mRNA expression of Oat1 upstream regulators hepatocyte nuclear factor-1a (HNF-1a) and pregnane X receptor (PXR). 4. These findings indicated hyperoside could protect against cisplatin-induced AKI by promoting indoxyl sulphate excretion through regulating the expression and function of Oat1, suggesting hyperoside may offer a potential tactic for cisplatin-induced AKI treatment. [ABSTRACT FROM AUTHOR]

Pyrrolizidine alkaloids (PAs) are potent hepatotoxins that can cause liver damage. Hyperoside (Hyp), a natural flavonoid, can be extracted from medicinal plants. Hyp displays hepatoprotective activity in various liver diseases. However, the potential effect and mechanism of action of Hyp in ameliorating PA-induced liver injury remain obscure. This study aimed to explore the protective effect of Hyp against PA-induced hepatotoxicity and its underlying mechanism. We established an in vitro model of PAs in mouse primary hepatocytes and developed a mouse model of acute PA toxicity to investigate the protective effect of Hyp. We found that Hyp notably attenuated PA-induced hepatotoxicity. RNA-sequencing showed that the beneficial effect of Hyp against PA-induced hepatotoxicity was associated with the transcription factor EB (TFEB)-peroxisome proliferator-activated receptor-γ coactivator-1-α (PGC1α) pathway. Our results confirmed that both the autophagy-lysosomal pathway and mitochondrial biogenesis were induced by Hyp through TFEB nuclear translocation in PA-induced liver injury. Furthermore, we demonstrated that activation of the mechanistic target of rapamycin complex 1 (mTORC1) by MHY 1485 decreased TFEB nuclear translocation and abrogated the protective effect of Hyp against PA-induced liver injury in mice. In contrast, inhibition of mTORC1 activity increased the level of TFEB and reduced hepatotoxicity induced by PAs in mouse livers. Likewise, Hyp-induced TFEB activation was validated in vitro. In conclusion, Hyp can activate the TFEB-mediated autophagy-lysosomal pathway and mitochondrial biogenesis through inhibition of mTORC1 activity, alleviating the liver injury induced by PAs, thus suggesting the potential value of Hyp in the treatment of PA-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Problem: Postmenopausal osteoporosis (PMO) is a common osteoporosis. Hyperoside (Hyp), a natural flavonoid compound, has anti‐osteoporotic effects, but the underlying mechanisms remain poorly understood. Inflammatory cytokine IL‐17A is upregulated in PMO and plays vital roles in bone loss, but the upstream regulatory factors and mechanisms are still unknown. Method of study: Twenty PMO patients and 20 healthy control subjects were included to analyze IL‐17A expression changes and screen dys‐regulated miRNAs in the peripheral blood of PMO patients. miR‐19a‐5p mimics and inhibitor were transfected into RAW264.7 osteoclasts, and injected into bilateral ovariectomized (OVX) mice to explore the regulatory effect of miR‐19a‐5p on IL‐17A. OVX mice were randomly grouped and treated with different doses of Hyp to uncover the effective targets for the medicine in PMO disease. Results: MiR‐19a‐5p was downregulated in PMO patients and the expression level was negatively correlated with that of IL‐17A. miR‐19a‐5p could directly bind to the 3′UTR of IL‐17A and regulate its expression. Both in vitro and in vivo studies demonstrated that miR‐19a‐5p mimics decreased the expression of IL‐17A, RANK and Cathepsin K, while miR‐19a‐5p inhibitor significantly increased the expression of IL‐17A, RANK, and Cathepsin K. Importantly, the Hyp could improve bone structure of OVX mice by enhancing miR‐19a‐5p‐mediated IL‐17A downregulation. Conclusion: Overall, these data demonstrated that miR‐19a‐5p/IL‐17A axis might serve as novel therapeutic candidate for PMO. Hyp could relieve bone resorption by targeting the miR‐19a‐5p/IL‐17A axis in OVX mice and exhibited prospective for the treatment of PMO. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies 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.)

The pharmacognostical study of Bauhinia aurea was conducted, in order to establish the identification method and content determination method and solve the problem of its authenticity, and to analyze the reasons for its different clinical efficacies. The methods of primary identification, morphological identification, microscopic identification, TLC identification and HPLC were used in the pharmacognostical study of B. aurea. The results were as follows: (1) It is a perennial stout woody vine with reddish brown hairs on the surface of stems, leaves, flowers and fruits. (2) A large number of stone cell groups and crystal fiber could be seen in the cortex of the transverse section of stems. The calcium oxalate cluster crystals and square crystals were scattered in the parenchyma of pith. The cross section of the leaves showed that the leaves were bifacial leaves. Calcium oxalate cluster crystals and square crystals were commonly found in the cortex. Secretory cavities were arranged intermittently into a ring in the phloem. Crystal fibers were often seen around the phloem. Calcium oxalate cluster crystals, crystal fibers, stone cells, bordered pit vessels, non-glandular hairs and stomata could be found in the powder. (3) The spots of samples were displayed in the same color as the reference substances in the same position of the TLC figure. (4) The linear ranges of astilbin and quercitin were 0.005 888-2.355 μg (r=0.999 6) and 0.039 55-1.582 μg (r=0.999 8). The average recoveries (n=6) were 96.42% (RSD=2.55%) and 104.20% (RSD=1.79%). In this study, pharmacognostical identification methods and a HPLC method for simultaneous content determination of two components astilbin and quercitin in B. aurea were developed. The methods are simple, stable, accurate, which can be used as the basis to set up its quality standard.

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

Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective. [ABSTRACT FROM AUTHOR]

Sorbitol is an important signaling molecule in fruit trees. Here, we observed that sorbitol increased during flower bud differentiation (FBD) in loquat (Eriobotrya japonica Lindl.). Transcriptomic analysis suggested that bud formation was associated with the expression of the MADS‐box transcription factor (TF) family gene, EjCAL. RNA fluorescence in situ hybridization showed that EjCAL was enriched in flower primordia but hardly detected in the shoot apical meristem. Heterologous expression of EjCAL in Nicotiana benthamiana plants resulted in early FBD. Yeast‐one‐hybrid analysis identified the ERF12 TF as a binding partner of the EjCAL promoter. Chromatin immunoprecipitation‐PCR confirmed that EjERF12 binds to the EjCAL promoter, and β‐glucuronidase activity assays indicated that EjERF12 regulates EjCAL expression. Spraying loquat trees with sorbitol promoted flower bud formation and was associated with increased expression of EjERF12 and EjCAL. Furthermore, we identified EjUF3GaT1 as a target gene of EjCAL and its expression was activated by EjCAL. Function characterization via overexpression and RNAi reveals that EjUF3GaT1 is a biosynthetic gene of flavonoid hyperoside. The concentration of the flavonoid hyperoside mirrored that of sorbitol during FBD and exogenous hyperoside treatment also promoted loquat bud formation. We identified a mechanism whereby EjCAL might regulate hyperoside biosynthesis and confirmed the involvement of EjCAL in flower bud formation in planta. Together, these results provide insight into bud formation in loquat and may be used in efforts to increase yield. [ABSTRACT FROM AUTHOR]

Background. Cardiotoxicity is a side effect of the anthracycline broad-spectrum antitumor agent, doxorubicin (DOX). Hyperoside, a flavonoid glycoside extracted from many herbs, has anti-apoptotic and anticancer properties. However, its impact on the alleviation of DOX-induced apoptosis in cardiomyocytes remains elusive. Methods. The HL-1 cell line was treated with 100 µ M hyperoside for 1 h prior to treatment with 100 µ M hyperoside and 1 µ M DOX for 24 h. The cell counting kit-8 (CCK-8) assay was used to detect cell viability; DCFH-DA fluorescent probe was used to detect (reactive oxygen species) ROS; biochemical methods were used to detect the activity of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA); the degree of apoptosis following DOX insult was assessed using immunofluorescence staining and terminal deoxynucleotidyl transferase mediated deoxy uridine triphosphate nick end labeling (TUNEL) assay; the change in protein expression of apoptosis signal-regulating kinase 1 (ASK1), p38, and apoptosis markers was determined using western blot. Results. Hyperoside ameliorated DOX-induced oxidative stress in HL-1 cells, up- regulated GSH, SOD and CAT activity, reduced ROS production and inhibited MDA overproduction. Moreover, in addition to promoting HL-1 cell apoptosis, DOX administration also increased B-cell lymphoma (Bcl)-2-associated X-protein and cleaved caspase-3 protein levels and decreased Bcl-2 protein level. Hyperoside therapy, however, significantly reversed the impact of DOX on the cardiomyocytes. Mechanically, DOX treatment increased the phosphorylation of the ASK1/p38 axis whereas hyperoside treatment attenuated those changes. In a further step, hyperoside synergizes with DOX to kill MDA-MB-231 cells. Conclusions. Hyperoside protects HL-1 cells from DOX-induced cardiotoxicity by inhibiting the ASK1/p38 signaling pathway. Meanwhile, hyperoside maintained the cytotoxicity of DOX in MDA-MB-231 cells. [ABSTRACT FROM AUTHOR]

Over 750 million cases of COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), have been reported since the onset of the global outbreak. The need for effective treatments has spurred intensive research for therapeutic agents based on pharmaceutical repositioning or natural products. In light of prior studies asserting the bioactivity of natural compounds of the autochthonous Peruvian flora, the present study focuses on the identification SARS-CoV-2 Mpro main protease dimer inhibitors. To this end, a target-based virtual screening was performed over a representative set of Peruvian flora-derived natural compounds. The best poses obtained from the ensemble molecular docking process were selected. These structures were subjected to extensive molecular dynamics steps for the computation of binding free energies along the trajectory and evaluation of the stability of the complexes. The compounds exhibiting the best free energy behaviors were selected for in vitro testing, confirming the inhibitory activity of Hyperoside against Mpro, with a Ki value lower than 20 µM, presumably through allosteric modulation. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and mechanism of hyperoside on the biological behavior such as cell proliferation, migration and invasion of nasopharyngeal carcinoma cells. Methods SUNE1 cells were incubated with hyperin medium of 10 mg/L, 20 mg/L and 40 mg/L, and cells were divided into the low, the medium and the high dose groups. The lncRNA PAX8-AS1 overexpression or knockdown plasmid and miR-494-3p mimic were transfected into 40 mg/L hypericin-treated SUNE1 cells respectively. The activity, clonal formation, migration and invasion of SUNE1 cells were detected by CCK-8 assays, plate cloning experiment and Transwell assays. Western blot assay was used to analyze the expression of matrix metalloproteinase (MMP) -2 and MMP-9 proteins. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of long non-coding RNA (lncRNA) paired-box gene 8 antisense RNA 1 (PAX8-AS1) and miR-494-3p. Dual luciferase report experiment and RT-qPCR were used to determine the targeting relationship between lncRNA PAX8-AS1 and miR-494-3p. Results Low, medium and high dose-hyperoside significantly reduced the cell viability, migration number and invasion number of SUNE1 cells, and down-regulated expression levels of MMP-2 protein, MMP-9 protein and miR-494-3p, and up-regulated the expression level of lncRNA PAX8-AS1 (P＜0.05). lncRNA PAX8-AS1 negatively regulated miR-494-3p expression. lncRNA PAX8-AS1 overexpression significantly enhanced inhibitory effects of 40 mg/L hyperoside on SUNE1 cell viability, migration and invasion, and MMP-2 and MMP-9 protein expression (P＜0.05). Knockdown of lncRNA PAX8-AS1 and overexpression of miR-494-3p significantly reduced inhibitory effects of 40 mg/L hyperoside on SUNE1 cell viability, migration, invasion and MMP-2 and MMP-9 protein expression (P＜0.05). Conclusion Hyperoside may inhibit the proliferation and migration, and invasion of nasopharyngeal carcinoma cells by up-regulating the lncRNA PAX8-AS1 /miR-494-3p axis. [ABSTRACT FROM AUTHOR]

In this study, the allelopathic properties of Medicago sativa L. (alfalfa) seedling exudates on the germination of seeds of various species were investigated. The compounds responsible for the allelopathic effects of alfalfa were identified and characterized by employing liquid chromatography ion mobility high-resolution mass spectrometry. Crude exudates inhibited the germination of seeds of all various plant species tested. Overall, nine compounds in alfalfa were identified and quantified. The most predominant compounds were a hyperoside representing a flavonoid glucoside, the non-proteinogenic amino acid canavanine, and two dipeptides, identified as H-Glu-Tyr-OH and H-Phe-Glu-OH. The latter corresponds to the first finding that dipeptides are exuded from alfalfa seedlings. In addition, the antibacterial and antibiofilm activities of alfalfa exudate and its identified compounds were elucidated. Both hyperoside and canavanine revealed the best antibacterial activity with minimum inhibitory concentration (MIC) values that ranged from 8 to 32 and 32 to 256 µg/mL, respectively. Regarding the antibiofilm action, hyperoside and canavanine caused a decline in the percentage of E. coli isolates that possessed a strong and moderate biofilm-forming potential from 68.42% to 21.05% and 31.58%, respectively. Studies on their inhibiting effects exhibit that these major substances are predominantly responsible for the allelopathic and antimicrobial effects of the crude exudates. [ABSTRACT FROM AUTHOR]

Introduction: The formation of color in plants is significantly dependent on anthocyaninpigments. Grape species vary in color due to the differences in anthocyanin accumulation. It is widely recognized that both biotic and abiotic conditions may have an impact on anthocyanin synthesis in plants. The underlying molecular mechanisms by which external application of hyperoside impacts anthocyanin formation in grapes, however, have received little attention. Methods: In the current study, the transcriptome of Gemstone seedless grape was examined using high-throughput RNA sequencing at various developmental stages reply to both control and hyperoside treatments. Results: The results of this study suggested that the major genes controlling anthocyanin accumulation in response to the externalinjection of hyperoside could be VvMYB62, VvPAL, VvCHS, and VvF3'5'H.Quantitative reverse transcription PCR (RT-qPCR) results were used to confirm the changes in the expression levels of the genes encoding the anthocyanin biosynthesis pathway under the control and hyperoside treatments. Using a transient transformation system, itwas discovered that VvMYB62 was shown to regulate the anthocyanin accumulation at both the transcriptional and posttranslational levels and could be influenced by the external administration of hyperoside. In grape embryogenic calli, hyperoside could specifically suppress theexpression of VvMYB62 and anthocyanin accumulation. In this instance, the VvMYB62 characterisation brought attention to the significance of exogenous hyperoside-induced anthocyanin accumulation. Therefore, the results demonstrated that VvMYB62 could be hindered in the process of grape during anthocyanin accumulation caused by hyperoside. Discussion: These findings offer excellent candidate genes in the future breeding of novel grape varieties in addition to serving as a crucial reference for understanding the underlying molecular processes of hyperoside suppression of anthocyanin formation in plants. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disease characterized by the pathological loss of nigrostriatal dopaminergic neurons, which causes an insufficient release of dopamine (DA) and then induces motor and nonmotor symptoms. Hyperoside (HYP) is a lignan component with anti-inflammatory, antioxidant, and neuroprotective effects. In this study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active neurotoxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) were used to induce dopaminergic neurodegeneration. The results showed that HYP (100 µg/mL) reduced MPTP-mediated cytotoxicity of SH-SY5Y cells in vitro, and HYP [25 mg/(kg d)] alleviated MPTP-induced motor symptoms in vivo. HYP treatment reduced the contents of nitric oxide (NO), H2O2, and malondialdehyde (MDA), as well as the mitochondrial damage of dopaminergic neurons, both in vitro and in vivo. Meanwhile, HYP treatment elevated the levels of neurotrophic factors such as glial cell line–derived neurotrophic factor, brain-derived neurotrophic factor, and recombinant cerebral dopamine neurotrophic factor in vivo, but not in vitro. Finally, Akt signaling was activated after the administration of HYP in MPP+/MPTP-induced dopaminergic neurodegeneration. However, the blockage of the Akt pathway with Akt inhibitor did not abolish the neuroprotective effect of HYP on DA neurons. These results showed that HYP protected the dopaminergic neurons from the MPP+- and MPTP-induced injuries, which did not rely on the Akt pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hyperoside has many pharmacological effects such as anti-inflammation and anti-oxidation, but there are few studies on its application in repairing endometrial injury. OBJECTIVE: To prepare hyperoside nanoparticles and to study the repairing effect of poloxamer 407 carrying hyperoside nanoparticles on endometrial injury in model rats. METHODS: Hyperoside nanoparticles, poloxamer 407 hydrogel and poloxamer 407 hydrogel with hyperoside nanoparticles were prepared separately. Twentyfour female SD rats were randomly divided into four groups (n=6): model group, blank control group, hydrogel group, and drug-loaded hydrogel group. Rat models of endometrial injury were established by scratching method in the model group, hydrogel group and drug-loaded hydrogel group. PBS, poloxamer 407 hydrogel and poloxamer 407 hydrogel with hyperoside nanoparticles were injected into the uterus of rats in the model group, hydrogel group and drugloaded hydrogel group. The blank control group received only laparotomy without modeling. The model was taken 7 days after the injection. The morphological changes of rat endometrium were observed by hematoxylin-eosin staining. The expression of interleukin-1β, interleukin-8, and tumor necrosis factor-α in the endometrial tissue of rats in each group was detected by ELISA. Immunofluorescence staining was used to detect the expression of vascular endothelial growth factor, keratin and vimentin in endometrial tissue. RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining showed that compared with the blank control group, the endometrial layer of the rats in the model group became thinner, the endometrial structure was incomplete, and the blood vessels and glands were significantly reduced and sparse. Compared with the model group, the endometrium of the rats in the hydrogel group was thickened and the endometrial structure was relatively complete. The endometrial structure of the rats in the drug-loaded hydrogel group was thickened, the endometrial structure was relatively complete, and the glands were more abundant. (2) Compared with the blank control group, the levels of interleukin-1β, interleukin-8, and tumor necrosis factor-α were all increased in the model group (P < 0.01). Compared with the model group, the levels of interleukin-1β, interleukin-8, tumor necrosis factor-α decreased in the hydrogel group and drug-loaded hydrogel group (P < 0.01). (3) Immunofluorescence staining showed that compared with the blank control group, the expression levels of vascular endothelial growth factor, keratin and vimentin were decreased in the model group (P < 0.01). Compared with the model group, the expression levels of vascular endothelial growth factor, keratin and vimentin were all increased in the drug-loaded hydrogel group (P < 0.01), and the expression of vascular endothelial growth factor was increased in the poloxamer 407 group (P < 0.01). (4) These results confirm that hydrogel carrying hyperoside nanoparticles has a repairing effect on the rat endometrial injury model. [ABSTRACT FROM AUTHOR]

The pharmacognostical study of Bauhinia aurea was conducted, in order to establish the identification method and content determination method and solve the problem of its authenticity, and to analyze the reasons for its different clinical efficacies. The methods of primary identification, morphological identification, microscopic identification, TLC identification and HPLC were used in the pharmacognostical study of B. aurea. The results were as follows:(1)It is a perennial stout woody vine with reddish brown hairs on the surface of stems, leaves, flowers and fruits.(2)A large number of stone cell groups and crystal fiber could be seen in the cortex of the transverse section of stems. The calcium oxalate cluster crystals and square crystals were scattered in the parenchyma of pith. The cross section of the leaves showed that the leaves were bifacial leaves. Calcium oxalate cluster crystals and square crystals were commonly found in the cortex. Secretory cavities were arranged intermittently into a ring in the phloem. Crystal fibers were often seen around the phloem. Calcium oxalate cluster crystals, crystal fibers, stone cells, bordered pit vessels, non-glandular hairs and stomata could be found in the powder.(3)The spots of samples were displayed in the same color as the reference substances in the same position of the TLC figure.(4)The linear ranges of astilbin and quercitin were 0.005 888-2.355 μg(r=0.999 6)and 0.039 55-1.582 μg(r=0.999 8). The average recoveries(n=6)were 96.42%(RSD=2.55%)and 104.2%(RSD=1.79%). In this study, pharmacognostical identification methods and a HPLC method for simultaneous content determination of two components astilbin and quercitin in B. aurea were developed. The methods are simple, stable, accurate, which can be used as the basis to set up its quality standard. [ABSTRACT FROM AUTHOR]

Background: Women with antiphospholipid syndrome (APS) or antiphospholipid antibodies (aPLs) are at high risk for obstetric complications, including recurrent pregnancy loss (RPL). However, effective treatments for RPL are lacking. Objective: This study aimed to reveal the function and underlying mechanism of hyperoside (Hyp) in RPL associated with antiphospholipid antibodies (aCLs). Methods: The pregnant rats (N = 24) were divided randomly into four groups: normal human-IgG (NH-IgG); aCL-pregnancy loss (aCL-PL); aCL-PL + Hyp (40 mg/kg/day); aCL-PL + low molecular weight heparin (LMWH, 525 μg/kg/day). HTR‐8 cells were treated with 80 μg/mL aCL to establish the cell models of miscarriage. Results: In pregnant rats, aCL-IgG injection raised the abortion rate of embryos, while Hyp treatment inhibited the effects. Additionally, Hyp inhibited the platelet activation and uteroplacental insufficiency caused by aCL. In vivo and in vitro experiments further suggested that Hyp suppressed aCL-induced inflammation and apoptosis by downregulating NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-related factors and decreasing apoptotic rates. After aCL administration, Hyp therapy downregulated the expression of purinergic ligand-gated ion channel 7 (P2X7), which is reported to induce cytokine release and apoptosis. Furthermore, we found that the treatment of 3′-O-(4-Benzoyl) benzoyl-ATP (BzATP, an agonist of the P2X7 receptor) reversed the inhibitory effects of Hyp on cell function. Conclusions: Hyp exerts protective effects on aCL-induced pregnancy loss by preventing platelet activation-mediated P2X7/NLRP3 pathway. Therefore, Hyp may provide a feasible pharmaceutical strategy for the treatment of RPL. Graphical Abstract [ABSTRACT FROM AUTHOR]