Chrysin restores MPTP induced neuroinflammation, oxidative stress and neurotrophic factors in an acute Parkinson’s disease mouse model.

PMID: 

Neurosci Lett. 2019 Sep 14 ;709:134382. Epub 2019 Jul 17. PMID: 31325581

Abstract Title: 

Chrysin restores MPTP induced neuroinflammation, oxidative stress and neurotrophic factors in an acute Parkinson's disease mouse model.

Abstract: 

Parkinson disease occurs due to the depletion of dopaminergic neurons in brain resulting in decreased dopamine level and abnormal protein aggregation. Chrysin is a flavonoid which possesses pharmacological properties against various diseases like hypertension, diabetes, cancer, etc. According to the recent literatures, it is evidenced that chrysin protects mice against Focal Cerebral Ischemia/Reperfusion Injury. The present study aimed to elucidate the effect of chrysin on neuronal restoration in MPTP intoxicated acute mice model. From the results, it is revealed that the pre-treatment with chrysin protected MPTP induced degeneration of nigra-striatal neurons. It is observed that chrysin also ameliorates MPTP induced oxidative stress in mice by upregulating GSH, SOD and downregulating LPO levels. The motor dysfunction is also found to be enhanced which was evidenced through Beam walk, Horizontal grid and vertical grid tests. Pre-treatment with chrysin also averted MPTP induced alterations in neurotrophic factors, inflammatory markers and Dopamine contents. The findings of the present study clearly indicated that the chrysin reversed the neurochemical deficits, oxidative stress and behavioral abnormalities in PD mice and offers promising strategy for the treatment of neurodegenerative diseases.

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Chrysin ameliorates nonalcoholic fatty liver disease in rats.

PMID: 

Naunyn Schmiedebergs Arch Pharmacol. 2019 Dec ;392(12):1617-1628. Epub 2019 Aug 1. PMID: 31372694

Abstract Title: 

Chrysin ameliorates nonalcoholic fatty liver disease in rats.

Abstract: 

Nonalcoholic fatty liver disease (NAFLD) is regarded as the hepatic manifestation of the metabolic syndrome. It begins with the accumulation of fat in the liver (simple steatosis), which if untreated can progress to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. Chrysin is a flavonoid present in bee propolis and many other plants. The objective of this study was to determine if chrysin can ameliorate NAFLD induced by feeding a high fructose diet (HFD) in rats. The rats were divided into five groups: normal control, HFD control, chrysin (25, 50, and 100 mg/kg p.o. body weight). Biochemical estimations were carried out in the serum and liver of rats. The gene expressions of SREBP-1c and PPAR α were determined in the liver. The histopathology of the liver was also studied. Chrysin caused a significant decrease in the serum fasting glucose and improved the insulin resistance, dyslipidemia, and liver enzymes. It caused a significant decrease in the liver weight and hepatic free fatty acids, triglyceride, and cholesterol content. Chrysin exerted antioxidant effects, reduced carbonyl content, advanced glycation end products, collagen, TNF-α, and IL-6 concentrations in the liver. Chrysin significantly reduced the hepatic gene expression of SREBP-1c and increased that of PPAR-α. The histopathology of liver of rats treated with chrysin showed significant decrease in the steatosis, ballooning, and lobular inflammation when compared to the HFD control group. Thus, chrysin demonstrated anti-steatotic, antiglycating, antioxidant, anti-inflammatory, and antifibrotic effects and seems to be a promising molecule for the management of NAFLD.

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The results indicate the possibility of applying ethanol extracts from Polish propolis to protect food against microbiological spoilage.

PMID: 

Molecules. 2019 Aug 15 ;24(16). Epub 2019 Aug 15. PMID: 31443325

Abstract Title: 

Growth Biocontrol of Foodborne Pathogens and Spoilage Microorganisms of Food by Polish Propolis Extracts.

Abstract: 

Propolis is a natural mixture produced by bees from plant resin substances. This study focuses on the general characteristics of five samples of Polish extract propolis originating from agricultural areas. Chemical composition with high performance liquid chromatography‒diode array detector method, total content of flavonoids and polyphenols, and antioxidative activity were determined in the ethanol extracts of propolis (EEP) samples. Minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC) and time-kill curves were studiedfor foodborne pathogens and food spoilage microorganisms. In EEPs the predominant flavonoid compounds were pinocembrin, chrysin, pinobanksin, apigenin, and kaempferol and the predominant phenolic acids were p-coumaric acid, ferulic acid, and caffeic acid. A strong antioxidative action of propolis in vitro was observed (ICfor DPPH radical was at the level of 0.9-2.1µg/mL). EEPs had MIC values for bacteria in the range of 1-16 mg/mL, whereas MIC for fungi ranged from 2 to 32 mg/mL. Extract of propolis originating from southern Poland was distinguished by higher content of bioactive components, and stronger antioxidative and antimicrobial activity than EPPs from the remaining areas of Poland. The results indicate the possibility of applying ethanol extracts from Polish propolis to protect food against microbiological spoilage.

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European propolis is highly active against trypanosomatids including Crithidia fasciculata.

PMID: 

Sci Rep. 2019 Aug 6 ;9(1):11364. Epub 2019 Aug 6. PMID: 31388043

Abstract Title: 

European propolis is highly active against trypanosomatids including Crithidia fasciculata.

Abstract: 

Extracts of 35 samples of European propolis were tested against wild type and resistant strains of the protozoal pathogens Trypanosoma brucei, Trypanosoma congolense and Leishmania mexicana. The extracts were also tested against Crithidia fasciculata a close relative of Crithidia mellificae, a parasite of bees. Crithidia, Trypanosoma and Leishmania are all members of the order Kinetoplastida. High levels of activity were obtained for all the samples with the levels of activity varying across the sample set. The highest levels of activity were found against L. mexicana. The propolis samples were profiled by using liquid chromatography with high resolution mass spectrometry (LC-MS) and principal components analysis (PCA) of the data obtained indicated there was a wide variation in the composition of the propolis samples. Orthogonal partial least squares (OPLS) associated a butyrate ester of pinobanksin with high activity against T. brucei whereas in the case of T. congolense high activity was associated with methyl ethers of chrysin and pinobanksin. In the case of C. fasciculata highest activity was associated with methyl ethers of galangin and pinobanksin. OPLS modelling of the activities against L. mexicana using the mass spectrometry produced a less successful model suggesting a wider range of active components.

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Chrysin suppress immune responses and protects from experimental autoimmune encephalomyelitis in mice.

PMID: 

J Neuroimmunol. 2019 Oct 15 ;335:577007. Epub 2019 Jul 16. PMID: 31376787

Abstract Title: 

Chrysin suppress immune responses and protects from experimental autoimmune encephalomyelitis in mice.

Abstract: 

We investigated the effects of chrysin in the experimental autoimmune encephomyelitis (EAE), a multiple sclerosis (MS) animal model. EAE was induced using myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide in C57BL/6 mice. Chrysin reduced weight loss, attenuated clinical signs and blunted the EAE-induced increase in histone deacetylase (HDCA) activity, glycogen synthase kinase-3β (GSK-3β) levels and pro-inflammatory cytokine levels as well as in the EAE-induced decrease in histone acetyltransferases 3 and 4 (HAT3, HAT4). Altogether, results demonstrate beneficial effects and potential targets of chrysin in EAE.

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Chrysin possesses strong antihypertensive and antioxidant properties in L-NAME induced hypertensive rats.

PMID: 

Indian J Clin Biochem. 2019 Jul ;34(3):288-295. Epub 2018 Jun 14. PMID: 31391718

Abstract Title: 

Chrysin Pretreatment Improves Angiotensin System, cGMP Concentration in L-NAME Induced Hypertensive Rats.

Abstract: 

N-nitro-l-arginine methyl ester (L-NAME) is a non-specific nitric oxide (NO) synthase inhibitor, commonly used for the induction of NO-deficient hypertension. The objective of the present study was to investigate the effects of chrysin with flavnoids, on L-NAME-induced hypertensive rats. Methods: An experimental hypertensive animal (180-220 g) model was induced by L-NAME intake on rats. In treatment chrysin was orally administered 25 mg/kg body weight (b.w.). Blood pressure was measured by tail cuff plethysmography system. Cardiac and vascular function was evaluated by Langendorff isolated heart system with Angiotensin II (Ang-II),Hexo oxygenase (HO-1), cyclic guanosine monophosphate (cGMP) concentration in tissues respectively. Rats with hypertension showed an elevated blood pressure (BP), left ventricular functions, ang II, and decreased cGMP concentration of tissues. Treatment of chrysin is reverse to near normal in left ventricular functions, Ang-II, Ho-1 and decreased cGMP concentration of tissues. The antihypertensive effect of chrysin appears to be mediated by a reduction in left ventricular functions, cardiac oxidative stress and Ang-II, an increase in cardiac HO-1, cGMP concentration and a prevention of plasmanitric oxide loss.

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chrysin may be useful as an adjuvant chemotherapy in lung squamous cell carcinoma.

PMID: 

Sci Rep. 2019 Sep 24 ;9(1):13753. Epub 2019 Sep 24. PMID: 31551535

Abstract Title: 

Chrysin enhances anticancer drug-induced toxicity mediated by the reduction of claudin-1 and 11 expression in a spheroid culture model of lung squamous cell carcinoma cells.

Abstract: 

The aberrant expression of claudins (CLDNs), which are tight junctional proteins, is seen in various solid tumors, but the regulatory mechanisms and their pathophysiological role are not well understood. Both CLDN1 and CLDN11 were highly expressed in human lung squamous cell carcinoma (SCC). Chrysin, found in high concentration in honey and propolis, decreased CLDN1 and CLDN11 expression in RERF-LC-AI cells derived from human lung SCC. The phosphorylation level of Akt was decreased by chrysin, but those of ERK1/2 and c-Jun were not. LY-294002, an inhibitor of phosphatidylinositol 3-kinase, inhibited the phosphorylation of Akt and decreased the expression levels of CLDN1 and CLDN11. The association between phosphoinositide-dependent kinase 1 (PDK1) and Akt was inhibited by chrysin, but the phosphorylation of PDK1 was not. Immunoprecipitation and quartz-crystal microbalance assays revealed that biotinylated-chrysin binds directly to Akt. The knockdown of CLDN1 and CLDN11 using small interfering RNAs increased the transepithelial flux of doxorubicin (DXR), an anthracycline anticancer drug. Similarly, both chrysin and LY-294002 increased DXR flux. Neither CLDN1 knockdown, CLDN11 knockdown, nor chrysin changed the anticancer drug-induced cytotoxicity in a two-dimensional culture model, whereas they enhanced cytotoxicity in a spheroid culture model. Taken together, chrysin may bind to Akt and inhibit its phosphorylation, resulting in the elevation of anticancer drug-induced toxicity mediated by reductions in CLDN1 and CLDN11 expression in RERF-LC-AI cells. We suggest that chrysin may be useful as an adjuvant chemotherapy in lung SCC.

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Chrysin has a protective effect against cyclophosphamide -induced hepatorenal toxicity.

PMID: 

Naunyn Schmiedebergs Arch Pharmacol. 2019 Oct 16. Epub 2019 Oct 16. PMID: 31620822

Abstract Title: 

Protective effect of chrysin on cyclophosphamide-induced hepatotoxicity and nephrotoxicity via the inhibition of oxidative stress, inflammation, and apoptosis.

Abstract: 

Cyclophosphamide (CYP) is a chemotherapeutic agent used in the treatment of autoimmune disorders and malignant diseases. However, its usage is restricted due to its severe side effects, especially hepatotoxicity and nephrotoxicity. This study aimed to investigate the protective role of chrysin (CH) against CYP-induced hepatotoxicity and nephrotoxicity in rats. In the present study, 35 male Wistar rats were randomly divided into 5 groups with each group consisting of 7 rats. The rats were pretreated with CH orally in doses of 25- and 50-mg/kg body weight for 7 consecutive days, and CYP (200-mg/kg body weight, i.p.) was administrated on the 7th day 1 h after the last dose of CH. It was found that CH could ameliorate CYP-induced elevations of ALT, ALP, AST, urea, creatinine, MDA, and hepatorenal deterioration, and enhance antioxidant enzymes' activities such as SOD, CAT, and GPx, and GSH's level. Furthermore, CH reversed the changes in levels of inflammatory, apoptotic, and autophagic parameters such as NF-κB, TNF-α, IL-1β, IL-6, iNOS, COX-2, Bax, Bcl-2, and LC3B in liver and kidney tissues. To conclude, the findings of this study demonstrated that CH has a protective effect against CYP-induced hepatorenal toxicity.

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Chrysin prevents the necrosis and injury of acute acetaminophen-induced hepatotoxicity.

PMID: 

Chem Res Toxicol. 2019 Nov 18 ;32(11):2329-2337. Epub 2019 Nov 1. PMID: 31625388

Abstract Title: 

Chrysin Effect in Prevention of Acetaminophen-Induced Hepatotoxicity in Rat.

Abstract: 

Acetaminophen is a commonly used analgesic drug that induces hepatotoxicity at high doses and produces the acetaminophen metabolite-acetyl–benzoquinone imine (NAPQI) through oxidase isoenzyme system. The antioxidant and anti-inflammatory activity of flavonoid chrysin has been reported in different studies. The present study was conducted to investigate the protective effect of chrysin on acute acetaminophen-induced hepatotoxicity. The cytotoxicity of chrysin on fibroblast cells was evaluated using MTT assay, and then, 54 rats were divided into nine groups of six, and acetaminophen (1500 mg/kg) was administered in all groups except for the control group, second and the seventh groups (40 mg/kg), and all groups were treated with chrysin for 14 days. Liver enzymes, inflammatory factors TNF-α and IL-2, and total antioxidant activity were measured in serum while liver tissue was histopathologically examined. Based on the MTT assay results, 31.25, 62.5, 125, 250, and 500 μg/mL chrysin had no adverse effects on healthy fibroblast cells (

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Chrysin and docetaxel loaded biodegradable micelle for combination chemotherapy of cancer stem cell.

PMID: 

Pharm Res. 2019 Oct 23 ;36(12):165. Epub 2019 Oct 23. PMID: 31646391

Abstract Title: 

Chrysin and Docetaxel Loaded Biodegradable Micelle for Combination Chemotherapy of Cancer Stem Cell.

Abstract: 

PURPOSE: Cancer stem cells (CSCs) have been suggested to represent the main cause of tumour progression, metastasis and drug resistance. Therefore, these cells can be an appropriate target to improve cancer treatment.METHODS: A novel biodegradable brush copolymeric micelle was synthesized by the ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The obtained micelle was used for co-delivery of the anticancer drug docetaxel (DTX) and Chrysin (CHS) as an adjuvant on the CSCs originated from Human colon adenocarcinoma cell line. Cancer stem cells were enriched by MACS technique and characterized by flow cytometry analysis against CD133 marker.RESULTS: Data demonstrated that the micelles harbouring DTX@CHS had potential to reduce cancer stem cell viability compared to free DTX@CHS, single-drug formulations and the control group (p 

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