PMID: 

Biomed Pharmacother. 2019 Jan ;109:1120-1125. Epub 2018 Nov 6. PMID: 30551362

Abstract Title: 

Chrysin attenuates inflammatory and metabolic disorder indices in aged male rat.

Abstract: 

Advanced age is a major risk factor for metabolic disorders. Accelerated inflammatory processes with increased age can contribute to the pathogenesis of metabolic disturbances. Chrysin is a natural flavonoid ingredient of honey and propolis. Chrysin has been effective in decreasing cholesterol and glucose levels preventing metabolic disturbances. The aim of this study was to evaluate the effects of chrysin against age-associated inflammation, hyperglycemia, and hypercholesterolemia. Male Wistar rats (2, 10, and 20 month-old) were intraperitoneally (i.p.) injected with chrysin (20 mg/kg) for 30 days. The findings showed elevated inflammatory cytokines, glucose, and lipid parameters in the sera of aged rats when compared with young ones. However, chrysin treatment ameliorated these alterations. Furthermore, chrysin reduced the levels of adiponectin, HDL-C, and insulin in 20month-old rats. The current study showed that chrysin was effective in attenuating age-related lipid abnormalities, glucose elevation, and inflammation.

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PMID: 

Biomed Pharmacother. 2019 Jan ;109:2387-2395. Epub 2018 Nov 30. PMID: 30551498

Abstract Title: 

Chrysin (5,7-dihydroxyflavone) exerts anxiolytic-like effects through GABAreceptors in a surgical menopause model in rats.

Abstract: 

The present study investigated the effects of the flavonoid chrysin (5,7-dihydroxyflavone) on anxiety-like behavior in rats in a model of surgical menopause and evaluated the participation ofγ-aminobutyric acid-A (GABA) receptors in these actions. At 12 weeks post-ovariectomy, the effects of different doses of chrysin (0.5, 1, 2, and 4 mg/kg) were evaluated in the elevated plus maze, light/dark test, and locomotor activity test, and comparisons were made with the clinically effective anxiolytic diazepam. The participation of GABAreceptors in the actions of chrysin was explored by pretreating the rats with the noncompetitive GABAchloride ion channel antagonist picrotoxin (1 mg/kg). The results showed that chrysin (2 and 4 mg/kg) reduced anxiety-like behavior in both the elevated plus maze and light/dark test, and these effects were similar to diazepam. Pretreatment with picrotoxin had no effects on its own but prevented the anxiolytic-like effects of chrysin in both tests. Chrysin also increased rearing and grooming, without significantly altering the number of crossings in the locomotor activity test; these effects were also similar to diazepam. In conclusion, the flavonoid chrysin produced anxiolytic-like effects through actions on GABAreceptors in a model of surgical menopause in rats. These findings support the hypothesis that this flavonoid could be a future natural alternative for ameliorating symptoms of anxiety after surgical menopause in women.

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PMID: 

Environ Toxicol. 2019 Apr ;34(4):434-442. Epub 2018 Dec 22. PMID: 30578657

Abstract Title: 

Chrysin inhibit human melanoma A375.S2 cell migration and invasion via affecting MAPK signaling and NF-κB signaling pathway in vitro.

Abstract: 

Numerous evidences have shown that chrysin induced cytotoxic effects via induced cell cycle arrest and induction of cell apoptosis in human cancer cell lines, however, no information showed that chrysin inhibited skin cancer cell migration and invasion. In this study, we investigated anti-metastasis mechanisms of chrysin in human melanoma cancer A375.S2 cells in vitro. Under sub-lethal concentrations of chrysin (0, 5, 10, and 15 μM) which inhibits cell mobility, migration and invasion of A375.S2 cells that were assayed by wound healing and Transwell filter. That chrysin inhibited MMP-2 activity in A375.S2 cells was investigated by gelatin zymography assay. Western blotting was used to examine protein expression and results indicated that chrysin inhibited the expression of GRB2, SOS-1, PKC, p-AKT (Thr308), NF-κBp65, and NF-κBp50 at 24 and 48 hours treatment, but only at 10-15 μM of chrysin decreased Ras, PI3K, p-c-Jun, and Snail only at 48 hours treatment and only decrease p-AKT(Ser473) at 24 hours treatment. Furthermore, chrysin (5-15 μM) decreased the expression of uPA, N-cadherin and MMP-1 at 24 and 48 hours treatment but only decreased MMP-2 and VEGF at 48 hours treatment at 10-15 μM and 5-15 μM of chrysin, respectively, however, increased E-cadherin at 5-15 μM treatment. Results of confocal laser microscopy systems indicated that chrysin inhibited expression of NF-κBp65 in A375.S2 cells. Based on these observations, we suggest that chrysin can be used in anti-metastasis of human melanoma cells in the future.

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PMID: 

Anticancer Res. 2019 Feb ;39(2):695-701. PMID: 30711947

Abstract Title: 

Chrysin-induced ERK1/2 Phosphorylation Enhances the Sensitivity of Human Hepatocellular Carcinoma Cells to Sorafenib.

Abstract: 

BACKGROUND/AIM: Sorafenib is now standard treatment for advanced hepatocellular carcinoma (HCC). However, therapeutic efficacy is not as good as was predicted. Many efforts are being made to improve HCC sensitivity to sorafenib. Our previous study demonstrated that co-treatment with chrysin enhanced sorafenib sensitivity through inhibition of ATP-binding cassette super-family G member 2 (ABCG2). Whether there is another mechanism other than inhibition of ABCG2 underlying chrysin-mediated synergistic effect is still not completely elucidated.MATERIALS AND METHODS: Phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) was examined by western blot. Cell viability was examined by crystal violet staining. The importance of ERK1/2 phosphorylation was assessed by overexpression and blockage of mitogen-activated protein kinase kinase 1 (MEK1).RESULTS: Chrysin induced sustained ERK1/2 phosphorylation of HCC cells in both time- and dose-dependent manners. Overexpression of MEK1 enhanced, whereas blockage of MEK1 led to loss of chrysin-synergized sorafenib effect, through modulating ERK1/2 phosphorylation level.CONCLUSION: These results identify another novel mechanism underlying chrysin-mediated synergistic effect on sorafenib activity in HCC cells.

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PMID: 

Brain Behav Immun. 2019 07 ;79:228-235. Epub 2019 Feb 7. PMID: 30738841

Abstract Title: 

A20 as a novel target for the anti-neuroinflammatory effect of chrysin via inhibition of NF-κB signaling pathway.

Abstract: 

Neuroinflammation is now recognized to be a feature of many neurological disorders. More accumulated evidences suggested chrysin which was contained in honey, propolis, vegetables, fruits and plants can exert biological activities including anti-neuroinflammatory effects. However, the precise molecular mechanisms of anti-neuroinflammatory effects remain unclear. In the present study, we explored a novel molecular mechanism involved in the anti-neuroinflammatory effect of chrysin. Firstly, we investigated the anti-neuroinflammatory effects of chrysin in LPS-induced BV2, primary microglial cells and mice. Next, we found chrysin can inhibit NF-κB pathway and TRAF6 expression, but upregulate the expression of zinc-finger protein A20. Further studies have revealed upregulation of A20 can regulate the inhibitory effects of chrysin on NF-κB pathways via regulation of TRAF6 polyubiquitination. This present study demonstrates that chrysin exerts an anti-neuroinflammatory effect via a novel mechanism, the upregulation of A20 expression, also validates A20 is a novel effective pharmacological target for developing agents in the treatment of neuroinflammation-related diseases.

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PMID: 

Drug Chem Toxicol. 2020 Feb 3:1-7. Epub 2020 Feb 3. PMID: 32013615

Abstract Title: 

Suppression of glomerular damage and apoptosis and biomarkers of acute kidney injury induced by acetaminophen toxicity using a combination of resveratrol and quercetin.

Abstract: 

Acute renal failure induced by a toxic dose of acetaminophen (also known as paracetamol, or APAP) is common in both humans and experimental animal models. Glomerular ultrastructural alterations induced by APAP overdose associated with the suppression of biomarkers of kidney injury have not been investigated before. Also, we investigated whether the combined polyphenolic antioxidants and anti-inflammatory compounds, resveratrol (RES) and quercetin (QUR) can protect against APAP-induced nephrotoxicity. Rats either received a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pretreated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. APAP significantly ( 

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PMID: 

Chem Biol Interact. 2019 Apr 1 ;302:123-134. Epub 2019 Feb 19. PMID: 30794797

Abstract Title: 

Effect of chrysin on the formation of N-acetyl-p-benzoquinoneimine, a toxic metabolite of paracetamol in rats and isolated rat hepatocytes.

Abstract: 

Paracetamol (N-acetyl-para amino phenol) is the most commonly used analgesic and antipyretic around the world. Its causes hepatotoxicity and nephrotoxicity at overdose or even at therapeutic doses. It is primarily metabolized by glucuronidation and sulfate conjugation. It is also metabolized by cytochrome-P450 system (CYP2E1, CYP1A2 and CYP 3A4), leading to the formation of N-acetyl-p-benzoquinoneimine (NAPQI). The present study was planned to investigate the influence of chrysin (known CYP2E1 and CYP3A4 inhibitor) on the bioactivation of paracetamol to NAPQI using rat liver microsomes in vitro and rats in vivo. Paracetamol (80 mg/kg) was administered orally without or with silymarin (100 mg/kg), a known CYP2E1 inhibitor and chrysin (100 and 200 mg/kg) to rats for 15 consecutive days. The area under the plasma concentration-time curve (AUC) and the peak plasma concentration (C) of paracetamol were dose-dependently increased with chrysin (100 and 200 mg/kg) compared to paracetamol control group. On the other hand, the AUCand Cof NAPQI were decreased significantly with chrysin (100 and 200 mg/kg). The elevated liver and kidney function markers were significantly reduced by chrysin and silymarin compared to paracetamol control group (P 

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PMID: 

Biomed Pharmacother. 2019 Apr ;112:108619. Epub 2019 Feb 20. PMID: 30797156

Abstract Title: 

Chrysin attenuates global cerebral ischemic reperfusion injury via suppression of oxidative stress, inflammation and apoptosis.

Abstract: 

Global cerebral ischemia is a leading cause of mortality worldwide. Several biomechanisms play a role in the pathology of cerebral ischemia reperfusion damage, such as oxidative stress, inflammation, apoptosis and excitotoxicity. Chrysin, a natural flavonoid with many important biological activities, was investigated in the present study for its possible neuroprotective properties in a rat model of global ischemia reperfusion. Male Wistar rats were allocated into three groups: sham-operated, ischemia/reperfusion, and chrysin (30 mg/kg) groups. All animals were subjected to ischemia for 15 min followed by reperfusion for 60 min, except for the sham-operated group. Rats were decapitated, then both hippocampi were rapidly excised to evaluate several biomarkers that reflect ischemic injury. The obtained results showed that pre-treatment with chrysin attenuated ischemia-induced oxidative stress by: (i) restoring the glutathione level; and (ii) depressing the levels/activities of thiobarbituric acid reactive substances, the hippocampal NADPH, as well as the xanthine oxidase. Exposure to chrysin also suppressed the inflammation accompanying the ischemia/reperfusion (I/R) damage, through increasing the interleukin-10 level, while decreasing the levels of both interleukin-6 and tumour necrosis factor-alpha. Moreover, an increase in Bcl2 and a decrease in both BAX and Hsp90 levels were recorded following chrysin exposure, which was also accompanied with elevated glutamate and aspartate levels. In conclusion, chrysin has demonstrated an anti-ischemic potential, through attenuation of the mechanisms underlying I/R injury. These data add to the knowledge on the significance of natural flavonoids as neuroprotective agents.

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PMID: 

J Biochem Mol Toxicol. 2019 Feb 22:e22313. Epub 2019 Feb 22. PMID: 30801880

Abstract Title: 

The antidiabetic and anticholinergic effects of chrysin on cyclophosphamide-induced multiple organ toxicity in rats: Pharmacological evaluation of some metabolic enzyme activities.

Abstract: 

Chrysin (CH) or 5,7-dihydroxyflavone is a flavonoid present in various plants, bee propolis, and honey. Cyclophosphamide (CYP) is a chemotherapeutic drug, which is extensively used in the treatment of multiple human malignancies. In our study, we aimed to investigate the effects of CYP and CH on some metabolic enzymes including carbonic anhydrase, aldose reductase, paraoxonase-1, α-glycosidase, acetylcholinesterase, and butyrylcholinesterase enzyme activities in the brain, heart, testis, liver, and kidney tissues of rats. Thirty-five adult male Wistar rats were used. The animals were pretreated with CH (25 and 50 mg/kg b.w.) for seven days before administering a single dose of CYP (200 mg/kg b.w.) on the seventh day. In all the tissues, the treatment of CH significantly regulated these enzyme activities in CYP-induced rats. These results showed that CH exhibited an ameliorative effect againstCYP-induced brain, heart, liver, testis, and kidney toxicity.

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PMID: 

Exp Ther Med. 2019 Mar ;17(3):2256-2262. Epub 2019 Jan 21. PMID: 30867710

Abstract Title: 

Chrysin protects against renal ischemia reperfusion induced tubular cell apoptosis and inflammation in mice.

Abstract: 

Renal ischemia reperfusion (IR) is a major cause of acute kidney injury with no effective treatment. Chrysin is an anti-inflammatory, anti-oxidant and anti-cancer agent. However, the effect of chrysin on renal IR injury remains unknown. In this study, sham operation, IR and IR+chrysin group mice were treated with or without renal IR injury. For renal IR, bilateral renal pedicles were clamped for 30 min and then released for 48 h of reperfusion. Blood and kidney samples were collected for analysis. Results demonstrated that chrysin pretreatment remarkably decreased the levels of serum creatinine and blood urea nitrogen and attenuated morphological abnormalities in renal IR injury. Consistently, tubular cell apoptosis and inflammation were more attenuated in the chrysin pretreatment group compared with the IR group. Chrysin pretreatment decreased the expression of Bax and cleaved caspase-3 and increased the expression of Bcl-2 in renal IR injury. Furthermore, chrysin administration decreased the mRNA and protein levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Furthermore, the IκBα/nuclear factor-κB signaling pathway was more suppressed in the chrysin pretreatment group compared with the IR group. In conclusion, chrysin protects against tubular cell apoptosis and inflammation in renal IR injury.

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