Effects Of Hyperoside Research Articles

Effect of hyperoside on osteoporosis in ovariectomized mice through estrogen receptor α/ITGβ3 signaling pathway

Osteoporosis is a highly prevalent bone metabolic disease in menopause due to estrogen deficiency. Hyperoside is a main compound in Semen cuscutae. Our team previously reported that Semen cuscutae has anti osteoporosis effect on ovariectomized mice by inhibiting bone resorption of osteoclasts. However, it is still unclear whether hyperoside affects osteoclast differentiation and bone resorption, and whether its anti-osteoporosis effect is related to an estrogen-like effect. This study investigates the potential mechanism of hyperoside's anti-osteoporotic effect by examining its impact on osteoclast differentiation and its relationship with the estrogen receptor. DXA, Micro-CT, TRAP staining, HE, and ELISA were used to assess the impact of hyperoside on OVX-induced osteoporosis. The effect of hyperoside on octeoclast differentiation was evaluated using TRAP activity assay, TRAP staining, F-actin staining. The activation of the estrogen receptor by hyperoside and its relationship with osteoclast differentiation were detected using dual-luciferase reporter assay and estrogen receptor antagonists. Our findings revealed that hyperoside (20–80 mg/kg) protect against OVX-induced osteoporosis, including increasing BMD and BMC and improving bone microstructure. Hyperoside inhibited osteoclast differentiation in a concentration dependent manner, whereas estrogen receptor α antagonists reversed its inhibitory effect osteoclast differentiation. Western blot results suggested that hyperoside inhibited TRAP, RANKL, c-Fos and ITG β3 protein expression in osteoclast or femoral bone marrow of ovariectomized mice. Our findings suggest that hyperoside inhibits osteoclast differentiation and protects OVX-induced osteoporosis through the ERα/ITGβ3 signaling pathway.

The protective effects of hyperoside on Ang II-mediated apoptosis of bEnd.3 cells and injury of blood-brain barrier model in vitro

BackgroundHypertension and its associated dysfunction of the blood-brain barrier (BBB) are considered to contribute to cerebral small vessel disease (cSVD). Angiotensin II (Ang II), as an important vasoactive peptide of the renin-angiotensin system (RAS), is not only a pivotal molecular signal in hypertension, but also causes BBB leakage, cSVD and its related cognitive impair. Hyperoside (Hyp), a flavone glycoside, has antioxidant, antiphlogistic and anti-apoptosis effects. In this study, we investigate the protection of Hyp on apoptosis of bEnd.3 cells and BBB disruption in vitro induced by Ang II.MethodsWe used bEnd.3 cells to imitate a BBB monolayer model and explored the protection of Hyp on Ang II-induced BBB leakage. The apoptotic activity was assessed by TUNEL staining and flow cytometry. The expression of apoptosis pathway related proteins, tight junction proteins and transcytosis related proteins were detected by western blot assay. The BBB model permeability was detected through measuring the flux of sodium fluorescein (Na-F).ResultsWe found that Hyp can not only effectively inhibit the apoptosis of bEnd.3 induced by Ang II, but also protect the structural soundness and functional integrity of BBB model by affecting the expression levels of junctional adhesion molecule A (JAM-A), Claudin-5, zonula occludens-1 (ZO-1), Caveolin-1 (Cav-1) and major facilitator superfamily domain-containing protein 2a (Mfsd2a).ConclusionHyp might be a potent compound for preventing Ang II-induced BBB disruption.

Effect of Hyperoside on the Gene Expression and Production of Mucin and EGFR-p44/42-Sp1signaling Pathway in Airway Epithelial Cells

Hyperoside is an anti-inflammatory natural product derived from a medicinal plant Houttuynia cordata, empirically used as remedies for controlling the pulmonary inflammatory diseases in folk medicine. In this study, hyperoside was investigated for its potential effect on the gene expression and production of airway mucin 5AC (MUC5AC). Human airway epithelial NCI-H292 cells were pretreated with hyperoside for 30 min and stimulated with epidermal growth factor (EGF) for the following 24 h. For the elucidation of the action mechanism of hyperoside, EGFinduced epidermal growth factor receptor (EGFR) signaling pathway was investigated. Hyperoside inhibited EGF-induced gene expression and production of MUC5AC mucin through regulating the phosphorylation of EGFR, phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These results suggest hyperoside could regulate the gene expression and production of MUC5AC by modulating the EGFR signaling pathway in human airway epithelial cells.

Inhibitory effects of hyperoside and quercitrin from Zanthoxylum bungeanum Maxim. leaf on 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine formation by trapping phenylacetaldehyde

2-amino-1-methyl-6-phenylimidazole[4,5-b]pyridine (PhIP) is one of the most abundant Heterocyclic amines (HAs) in meat products. Zanthoxylum bungeanum Maxim. leaf (ZML) extract has been shown to be rich in polyphenols, which are gaining increasing interest as efficient tools for inhibiting the formation of HAs. In the present work, the effects of ZML extract, major polyphenols, chlorogenic acid, hyperoside and quercitrin on the formation of PhIP in both roast beef patties and chemical model systems were investigated. UPLC-MS showed that ZML extract and those three polyphenols effectively inhibited PhIP formation. Additionally, GC-MS analysis showed that those three polyphenols significantly reduced the content of phenylacetaldehyde in the model systems, a key intermediate involved in PhIP formation. The subsequent UPLC-MS and TOF-MS/MS analysis found that hyperoside and quercitrin reacted with phenyacetaldehyde to form those four adducts, 8-C-(E-Phenylethenyl)hyperoside, 6-C-(E-Phenylethenyl)hyperoside, 8-C-(E-Phenylethenyl)quercitrin and 6-C-(E-Phenylethenyl)quercitrin, respectively. The results revealed that hyperoside and quercitrin could trap phenylacetaldehyde to form adducts, thereby, retarding the reaction of phenylacetaldehyde and creatinine, blocking the generation of PhIP.

Hyperoside promotes pollen tube growth by regulating the depolymerization effect of actin-depolymerizing factor 1 on microfilaments in okra

Mature pollen germinates rapidly on the stigma, extending its pollen tube to deliver sperm cells to the ovule for fertilization. The success of this process is an important factor that limits output. The flavonoid content increased significantly during pollen germination and pollen tube growth, which suggests it may play an important role in these processes. However, the specific mechanism of this involvement has been little researched. Our previous research found that hyperoside can prolong the flowering period of Abelmoschus esculentus (okra), but its specific mechanism is still unclear. Therefore, in this study, we focused on the effect of hyperoside in regulating the actin-depolymerizing factor (ADF), which further affects the germination and growth of pollen. We found that hyperoside can prolong the effective pollination period of okra by 2–3-fold and promote the growth of pollen tubes in the style. Then, we used Nicotiana benthamiana cells as a research system and found that hyperoside accelerates the depolymerization of intercellular microfilaments. Hyperoside can promote pollen germination and pollen tube elongation in vitro. Moreover, AeADF1 was identified out of all AeADF genes as being highly expressed in pollen tubes in response to hyperoside. In addition, hyperoside promoted AeADF1-mediated microfilament dissipation according to microfilament severing experiments in vitro. In the pollen tube, the gene expression of AeADF1 was reduced to 1/5 by oligonucleotide transfection. The decrease in the expression level of AeADF1 partially reduced the promoting effect of hyperoside on pollen germination and pollen tube growth. This research provides new research directions for flavonoids in reproductive development.

Flos lonicerae flavonoids attenuate experimental ulcerative colitis in rats via suppression of NF-κB signaling pathway.

This study sought to isolate active Flos lonicerae flavonoids and evaluate their anti-oxidative and anti-inflammatory effects as well as investigate the molecular mechanistic action of these flavonoids in the rat model of ulcerative colitis (UC). Total flavonoids and three flavonoids (hyperoside, lonicerin, and luteolin) were isolated from honeysuckle and purified via column purification. Rat model of UC was established via 2,4,6-trinitrobenzene sulfonic acid (TNBS) intoxication. The anti-oxidative and anti-inflammatory effects of the three flavonoids against TNBS-induced UC were evaluated by measuring appropriate biomarkers via assay kit. The effects of hyperoside, lonicerin, and luteolin on the regulation of nuclear factor-kappa B (NF-κB) pathway were investigated using Western blot (WB) and real-time polymerase chain reaction (RT-PCR) while their protective effects on UC were also elucidated. Pretreatment with flavonoids (hyperoside, lonicerin, and luteolin at 25-100mg/kg) and sulfasalazine (SSZ, positive control at 100mg/kg) substantially attenuated TBNS-induced UC. Also, the flavonoids significantly reduced the levels of respective serum oxidative and proinflammatory markers such as superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), prostaglandins E2 (PGE2), tumor necrosis factor-alpha (TNF-α), interleukin-beta (IL-β), and C-reactive protein (CRP). In addition, the flavonoids remarkably inhibited the expression of NF-κB signaling pathway. F. lonicerae flavonoids (hyperoside, lonicerin, and luteolin) demonstrated potent anti-UC activities in TBNS-induced UC rat model via anti-oxidative and anti-inflammatory effects through the inhibition of NF-κB signaling pathway.

Effect of hyperoside on cervical cancer cells and transcriptome analysis of differentially expressed genes

BackgroundHyperoside (Hy) is a plant-derived quercetin 3-d-galactoside that exhibits inhibitory activities on various tumor types. The objective of the current study was to explore Hy effects on cervical cancer cell proliferation, and to perform a transcriptome analysis of differentially expressed genes.MethodsCervical cancer HeLa and C-33A cells were cultured and the effect of Hy treatment was determined using the Cell Counting Kit-8 (CCK-8) assay. After calculating the IC50 of Hy in HeLa and C-33A cells, the more sensitive to Hy treatment cell type was selected for RNA-Seq. Differentially expressed genes (DEGs) were identified by comparing gene expression between the Hy and control groups. Candidate genes were determined through DEG analysis, protein interaction network (PPI) construction, PPI module analysis, transcription factor (TF) prediction, TF-target network construction, and survival analysis. Finally, the key candidate genes were verified by RT-qPCR and western blot.ResultsHy inhibited HeLa and C33A cell proliferation in a dose- and time-dependent manner, as determined by the CCK-8 assay. Treatment of C-33A cells with 2 mM Hy was selected for the subsequent experiments. Compared with the control group, 754 upregulated and 509 downregulated genes were identified after RNA-Seq. After functional enrichment, 74 gene ontology biological processes and 43 Kyoto Encyclopedia of Genes and Genomes pathways were obtained. According to the protein interaction network (PPI), PPI module analysis, TF-target network construction, and survival analysis, the key genes MYC, CNKN1A, PAX2, TFRC, ACOX2, UNC5B, APBA1, PRKACA, PEAR1, COL12A1, CACNA1G, PEAR1, and CCNA2 were detected. RT-qPCR was performed on the key genes, and Western blot was used to verify C-MYC and TFRC. C-MYC and TFRC expressions were lower and higher than the corresponding values in the control group, respectively, in accordance with the results from the RNA-Seq analysis.ConclusionHy inhibited HeLa and C-33A cell proliferation through C-MYC gene expression reduction in C-33A cells and TFRC regulation. The results of the current study provide a theoretical basis for Hy treatment of cervical cancer.

Hyperoside promotes ex vivo expansion of hematopoietic stem/progenitor cells derived from cord blood by reducing intracellular ROS level

Abstract Intracellular reactive oxygen species (ROS) accumulation during culture process compromise cord blood-derived hematopoietic stem/progenitor cells (CB-HSPCs) proliferation potential dramatically. In this work, the effects of hyperoside (Hyp) on CD34+ cells were investigated by the analysis of cell expansion and secondary expansion potential, with the objective to optimize the culture conditions for ex vivo expansion of HSPCs. The results showed that the expansion of total cells treated with 1 μM Hyp reached 54.9 ± 9.6 folds, which was significantly higher than that of control cells (42.0 ± 8.1 folds, P

Hyperoside inhibits biofilm formation of Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is a common pathogen in hospital-acquired infection and is readily able to form biofilms. Due to its high antibiotic resistance, traditional antibacterial treatments exert a limited effect on P. aeruginosa biofilm infections. It has been indicated that hyperoside inhibits P. aeruginosa PAO1 (PAO1) biofilm formation without affecting growth. Therefore, the current study examined the biofilm formation and quorum sensing (QS) system of PAO1 in the presence of hyperoside. Confocal laser scanning microscopy analysis demonstrated that hyperoside significantly inhibited biofilm formation. It was also observed that hyperoside inhibited twitching motility in addition to adhesion. Data from reverse transcription-quantitative polymerase chain reaction indicated that hyperoside inhibited the expression of lasR, lasI, rhlR and rhlI genes. These results suggest that the QS-inhibiting effect of hyperoside may lead to a reduction in biofilm formation. However, the precise mechanism of hyperoside on P. aeruginosa pathogenicity remains unclear and requires elucidation in additional studies.

Effect of hyperoside on the apoptosis of A549 human non‑small cell lung cancer cells and the underlying mechanism.

Hyperoside (HY) is a major pharmacologically active component from Prunella vulgaris L. and Hypericum perforatum. The present study aimed to determine the anticancer effect of HY and determine the underlying mechanisms involved. Human A549 cells were treated with HY (10, 50 and 100 µM), and cell viability was detected by an MTT assay. Cell apoptosis and mitochondrial membrane potential were determined by flow cytometry. Western blot analysis was used to identify the expression of apoptosis-associated proteins and phosphorylation of MAPK. The present study demonstrated that HY significantly inhibited the viability of A549 cells in a time- and dose-dependent manner, and enhanced the percentage of apoptotic cells. HY also significantly increased the protein phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), disrupted mitochondrial membrane penetrability, and triggered the release of mitochondrial cytochrome c and apoptosis-inducing factor into the cytosol. Treatment with HY also activated the expression of caspase-9 and caspase-3. These results suggested that HY-induced apoptosis was associated with activation of the p38 MAPK- and JNK-induced mitochondrial death pathway. HY may offer potential for clinical applications in treating human non-small cell lung cancer and improving cancer chemotherapy.

Hyperoside inhibits the effects induced by oxidized low-density lipoprotein in vascular smooth muscle cells via oxLDL-LOX-1-ERK pathway

Hyperoside is a major active constituent in many medicinal plants traditionally used in Chinese medicines for their anti-inflammatory, antioxidative, and vascular protective effects. Recent studies have focused on the protective effects of hyperoside on hyperlipidemia. However, the molecular mechanisms underlying these effects are unknown. In this study, vascular smooth muscle cells (VSMCs) were treated in vitro with oxidized low-density lipoprotein (oxLDL) in the presence or absence of hyperoside. Western blotting, quantitative PCR, and tetrazolium assay were used to detect lectin-like oxLDL receptor-1 (LOX-1) expression and extracellular signal-regulated kinases (ERK) activation, and to determine VSMCs viability. The results demonstrated that oxLDL promoted LOX-1 expression, ERK activation, and proliferation in VSMCs. Hyperoside significantly inhibited the oxLDL-stimulated effects after long time exposure. However, it promoted ERK activation directly following a short incubation duration (25 min). In conclusion, hyperoside inhibits oxLDL-induced LOX-1 expression, ERK activation, and cell proliferation through the oxLDL-LOX-1-ERK pathway in VSMCs. Our findings suggest a novel role of hyperoside in treating and preventing atherosclerosis.

The effect of hyperoside on the functional recovery of the ischemic/reperfused isolated rat heart: Potential involvement of the extracellular signal-regulated kinase 1/2 signaling pathway

One of the leading causes of death in the world is ischemia/reperfusion (I/R)-mediated acute myocardial infarction. There are a lot of Chinese traditional patent medicines, such as Xin'an capsules, Xin Xuening tablets, and so on, which have protective effects against myocardial I/R injury and have been routinely used in treating cardiac diseases for a long time in China. Hyperoside (Hyp) is the chief component of these medicines. This study investigated the action of Hyp in isolated myocardial I/R injury, as well as its possible mechanisms. Using the Langendorff model, isolated Sprague–Dawley rat hearts were subjected to 30min of global ischemia and 50min of reperfusion. Cardiac function was measured, and infarct size was evaluated by triphenyltetrazolium chloride staining at the end of the reperfusion. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK). Myocardium was also measured for total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. Phosphorylation of extracellular signal-regulated protein kinase (ERK) was analyzed by Western blotting. We report for the first time that administration of Hyp before/after I/R significantly improved heart contraction and limited the infarct size and CK and LDH leakage from the damaged myocardium after I/R. The activity of SOD and the MDA content remarkably changed in the presence of Hyp as well. Phosphorylation of ERK was significantly increased in Hyp-treated hearts compared to controls (p<0.01). Hyp-induced ERK phosphorylation was inhibited by PD98059. We therefore conclude that Hyp can protect cardiomyocytes from I/R-induced oxidative stress through the activation of ERK-dependent signaling.

Protective Effects of Hyperoside from Hawthorn against Endothelia Cell Apoptosis Induced by H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;

Hyperoside is a flavonol glycoside extraction from Hawthorn (Crataegus), and it has been reported that hyperoside process anti-inflammatory and anti-oxidative effectin vivo. In this paper, we studied the effects of hyperoside on apoptosis, necrosis, intracellular ROS level, mitochondrial transmembrane potential, and expression of Bax and Bcl-2 of endothelial cells subjected to H2O2,. The results showed that hyperoside treatment (50 μmol/L and 200 μmol/L ) significantly reduced apoptosis and necrosis, intracellular ROS and the expression of Bax in endothelial cell subjected to H2O2, and increased mitochondrial transmembrane potential and Bcl-2 expression. In conclusion, the present study indicates that hyperoside is in favor of endothelial cell protection.