Hyperoside CAS NO.482-36-0

Hyperoside downregulates the receptor for advanced glycation end products (RAGE) and promotes proliferation in ECV304 cells via the c-Jun N-terminal kinases (JNK) pathway following stimulation by advanced glycation end-products in vitro.[Pubmed: 24252909]

Int J Mol Sci. 2013 Nov 18;14(11):22697-707.

Hyperoside is a major active constituent in many medicinal plants which are traditionally used in Chinese medicines for their neuroprotective, anti-inflammatory and antioxidative effects. The molecular mechanisms underlying these effects are unknown.
METHODS AND RESULTS:
In this study, quiescent ECV304 cells were treated in vitro with advanced glycation end products (AGEs) in the presence or absence of Hyperoside. The results demonstrated that AGEs induced c-Jun N-terminal kinases (JNK) activation and apoptosis in ECV304 cells. Hyperoside inhibited these effects and promoted ECV304 cell proliferation. Furthermore, Hyperoside significantly inhibited RAGE expression in AGE-stimulated ECV304 cells, whereas knockdown of RAGE inhibited AGE-induced JNK activation. These results suggested that AGEs may promote JNK activation, leading to viability inhibition of ECV304 cells via the RAGE signaling pathway. These effects could be inhibited by Hyperoside.
CONCLUSIONS:
Our findings suggest a novel role for Hyperoside in the treatment and prevention of diabetes.

Antifungal activity of camptothecin, trifolin, and hyperoside isolated from Camptotheca acuminata.[Pubmed: 15631505]

J Agric Food Chem. 2005 Jan 12;53(1):32-7.

Leaf spots and root rots are major fungal diseases in Camptotheca acuminata that limit cultivation of the plant for camptothecin (CPT), a promising anticancer and antiviral alkaloid.
METHODS AND RESULTS:
Bioassays showed that pure CPT and flavonoids (trifolin and Hyperoside) isolated from Camptotheca effectively control fungal pathogens in vitro, including Alternaria alternata, Epicoccum nigrum, Pestalotia guepinii, Drechslera sp., and Fusarium avenaceum, although antifungal activity of these compounds in the plant is limited. CPT inhibited mycelial growth by approximately 50% (EC50) at 10-30 microg/mL and fully inhibited growth at 75-125 microg/mL. The flavonoids were less effective than CPT at 50 microg/mL, particularly within 20 days after treatment, but more effective at 100 or 150 microg/mL.
CONCLUSIONS:
CPT, trifolin, and Hyperoside may serve as leads for the development of fungicides.

Hyperoside protects primary rat cortical neurons from neurotoxicity induced by amyloid β-protein via the PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway.[Pubmed: 21978835 ]

Eur J Pharmacol. 2011 Dec 15;672(1-3):45-55.

Amyloid β-protein (Aβ), which is deposited in neurons as neurofibrillary tangles, is known to exert cytotoxic effects by inducing mitochondrial dysfunction. Additionally, the PI3K/Akt-mediated interaction between Bad and Bcl(XL) plays an important role in maintaining mitochondrial integrity. However, the application of therapeutic drugs, especially natural products in Alzheimer's disease therapy via PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway has not aroused extensive attention.
METHODS AND RESULTS:
In the present study, we investigated the neuroprotective effects of Hyperoside, a bioactive flavonoid compound from Hypericum perforatum, on Aβ(25-35)-induced primary cultured cortical neurons, and also examined the potential cellular signaling mechanism for Aβ detoxication. Our results showed that treatment with Hyperoside significantly inhibited Aβ(25-35)-induced cytotoxicity and apoptosis by reversing Aβ-induced mitochondrial dysfunction, including mitochondrial membrane potential decrease, reactive oxygen species production, and mitochondrial release of cytochrome c. Further study indicated that Hyperoside can activate the PI3K/Akt signaling pathway, resulting in inhibition of the interaction between Bad and Bcl(XL), without effects on the interaction between Bad and Bcl-2. Furthermore, Hyperoside inhibited mitochondria-dependent downstream caspase-mediated apoptotic pathway, such as that involving caspase-9, caspase-3, and poly ADP-ribose polymerase (PARP).
CONCLUSIONS:
These results demonstrate that Hyperoside can protect Aβ-induced primary cultured cortical neurons via PI3K/Akt/Bad/Bcl(XL)-regulated mitochondrial apoptotic pathway, and they raise the possibility that Hyperoside could be developed into a clinically valuable treatment for Alzheimer's disease and other neuronal degenerative diseases associated with mitochondrial dysfunction.

Anti-inflammatory effects of hyperoside in human endothelial cells and in mice.[Pubmed: 25097077]

Inflammation. 2015 Apr;38(2):784-99.

High-mobility group box 1 (HMGB1) was recently shown to be an important extracellular mediator of systemic inflammation, and endothelial cell protein C receptor (EPCR) has been shown to be involved in vascular inflammation. Hyperoside is an active compound isolated from Rhododendron brachycarpum G. Don (Ericaceae) that was reported to have anti-oxidant, anti-hyperglycemic, anti-cancer, and anti-coagulant activities.
METHODS AND RESULTS:
Here, we show, for the first time, the anti-septic effects of Hyperoside in HMGB1-mediated inflammatory responses and on the shedding of EPCR in vitro and in vivo. The data showed that Hyperoside posttreatment suppressed lipopolysaccharide (LPS)-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangement. Hyperoside also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in septic mice and phorbol-12-myristate 13-acetate (PMA) of cecal ligation and puncture (CLP)-induced EPCR shedding. In addition, Hyperoside inhibited the production of tumor necrosis factor-α (TNF-α) and the HMGB1-mediated activation of Akt, nuclear factor-κB (NF-κB), and extracellular regulated kinase (ERK) 1/2 in HUVECs. Hyperoside also reduced the CLP-induced release of HMGB1, the production of interleukin (IL)-1β, and septic mortality.
CONCLUSIONS:
Collectively, these results suggest Hyperoside as a candidate therapeutic agent for the treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

Selective inhibition of the cytochrome P450 isoform by hyperoside and its potent inhibition of CYP2D6.[Pubmed: 23835282]

Induction of Nur77 by hyperoside inhibits vascular smooth muscle cell proliferation and neointimal formation.[Pubmed: 25316569]

Biochem Pharmacol. 2014 Dec 15;92(4):590-8.

Nur77 is an orphan nuclear receptor that belongs to the nuclear receptor 4A (NR4A) subfamily, which has been implicated in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 has recently been shown to be beneficial for the treatment of cardiovascular and metabolic diseases. The purpose of this study is to identify novel natural Nur77 activators and investigate their roles in preventing vascular diseases.
METHODS AND RESULTS:
By measuring Nur77 expression using quantitative RT-PCR, we screened active ingredients extracted from Chinese herb medicines with beneficial cardiovascular effects. Hyperoside (quercetin 3-D-galactoside) was identified as one of the potent activators for inducing Nur77 expression and activating its transcriptional activity in vascular smooth muscle cells (VSMCs). We demonstrated that Hyperoside, in a time and dose dependent manner, markedly increased the expression of Nur77 in rat VSMCs, with an EC50 of ～0.83 μM. Mechanistically, we found that Hyperoside significantly increased the phosphorylation of ERK1/2 MAP kinase and its downstream target cAMP response element-binding protein (CREB), both of which contributed to the Hyperoside-induced Nur77 expression in rat VSMCs. Moreover, through activation of Nur77 receptor, Hyperoside markedly inhibited both vascular smooth muscle cell proliferation in vitro and the carotid artery ligation-induced neointimal formation in vivo.
CONCLUSIONS:
These findings demonstrate that Hyperoside is a potent natural activator of Nur77 receptor, which can be potentially used for prevention and treatment of occlusive vascular diseases.

Food Chem Toxicol. 2013 Sep;59:549-53.

Hyperoside, quercetin-3-O-galactoside, is a flavonoid isolated from Oenanthe javanica.
METHODS AND RESULTS:
In the present study, we investigated potential herb-drug inhibitory effects of Hyperoside on nine cytochrome P450 (CYP) isoforms in pooled human liver microsomes (HLMs) and human recombinant cDNA expressed CYP using a cocktail probe assay. Hyperoside strongly inhibited CYP2D6-catalyzed dextromethorphan O-demethylation, with IC?? values of 1.2 and 0.81 μM after 0 and 15 min of preincubation, and a Ki value of 2.01 μM in HLMs, respectively. Hyperoside strongly decreased CYP2D6 activity dose-, but not time-, dependently in HLMs. In addition, the Lineweaver-Burk and Secondary plots for the inhibition of CYP2D6 in HLMs fitted a competitive inhibition mode. Furthermore, Hyperoside decreased CYP2D6-catalyzed dextromethorphan O-demethylation activity of human recombinant cDNA-expressed CYP2D6, with an IC?? value of 3.87 μM. However, other CYPs were not inhibited significantly by Hyperoside.
CONCLUSIONS:
In conclusion, our data demonstrate that Hyperoside is a potent selective CYP2D6 inhibitor in HLMs, and suggest that Hyperoside might cause herb-drug interactions when co-administrated with CYP2D substrates.

In vivo and in vitro antiviral activity of hyperoside extracted from Abelmoschus manihot (L) medik.[Pubmed: 17303004 ]

Acta Pharmacol Sin. 2007 Mar;28(3):404-9.

To assess the anti-hepatitis B virus (HBV) effect of Hyperoside extracted from Abelmoschus manihot (L) medik.
METHODS AND RESULTS:
The human hepatoma Hep G2.2.15 cell culture system and duck hepatitis B virus (DHBV) infection model were used as in vivo and in vitro models to evaluate the anti-HBV effects. In the cell model, the 50% toxic concentration of Hyperoside was 0.115 g/L; the maximum nontoxic concentration was 0.05 g/L. On the maximum nontoxic concentrations, the inhibition rates of Hyperoside on HBeAg and HBsAg in the 2.2.15 cells were 86.41% and 82.27% on d 8, respectively. In the DHBV infection model, the DHBV-DNA levels decreased significantly in the treatment of 0.05 g x kg(-1 ) x d(-1 ) and 0.10 g x kg(-1) x d(-1) dosage groups of Hyperoside (P<0.01). The inhibition of the peak of viremia was at the maximum at the dose of 0.10 g x kg(-1 ) x d(-1) and reached 60.79% on d 10 and 69.78% on d 13, respectively.
CONCLUSIONS:
These results suggested that Hyperoside is a strong inhibitor of HBsAg and HBeAg secretion in 2.2.15 cells and DHBV-DNA levels in the HBV-infected duck model.

Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice.[Pubmed: 21428416 ]

J Nat Prod. 2011 May 27;74(5):1055-60.

In this study, the hepatoprotective effects of Hyperoside (1), a flavonoid glycoside isolated from Artemisia capillaris, have been examined against carbon tetrachloride (CCl4)-induced liver injury.
METHODS AND RESULTS:
Mice were treated intraperitoneally with vehicle or 1 (50, 100, and 200 mg·kg(-1)) 30 min before and 2 h after CCl4 (20 μL·kg(-1)) injection. Levels of serum aminotransferases were increased 24 h after CCl4 injection, and these increases were attenuated by 1. Histological analysis showed that 1 prevented portal inflammation, centrizonal necrosis, and Kupffer cell hyperplasia. Lipid peroxidation was increased and hepatic glutathione content was decreased significantly after CCl4 treatment, and these changes were reduced by administration of 1. Protein and mRNA expression of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) and nuclear protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) significantly increased after CCl4 injection. Compound 1 suppressed TNF-α, iNOS, and COX-2 protein and mRNA expression and augmented HO-1 protein and mRNA expression and Nrf2 nuclear protein expression.
CONCLUSIONS:
These results suggest that 1 has protective effects against CCl4-induced acute liver injury, and this protection is likely due to enhancement of the antioxidative defense system and suppression of the inflammatory response.