chrysin and Body-Weight

Cadmium (Cd) is a toxic heavy metal that targets the kidney directly in the body. Chrysin (CHR) is a natural flavonoid with many properties such as antioxidant, anti-inflammatory and anti-apoptotic. The current study discloses new evidence as regards of the curative effects of CHR on Cd-induced nephrotoxicity by regulating oxidative stress, apoptosis, autophagy, and inflammation. Cd was administered orally at a dose of 25 mg/kg body weight alone or in combination with orally administered CHR (25 and 50 mg/kg body weight) for 7 days. Biochemical, molecular, and histological methods were used to investigate inflammation, apoptosis, autophagy, and oxidant pathways in renal tissue. Renal function tests were also evaluated. Cd caused an increase in serum toxicity markers, lipid peroxidation and a decrease in the activities of antioxidant enzymes. Nrf-2 triggered inflammatory responses by suppressing HO-1 and NQO1 mRNA transcripts and increasing NF-κB, TNF-α, IL-1β and iNOS mRNA transcripts. Cd caused inflammasome by increasing RAGE and NLRP3 mRNA transcripts. In addition, Cd application caused apoptosis by increasing Bax, Apaf-1 and Caspase-3 mRNA transcripts and decreasing Bcl-2 mRNA transcript level. It caused autophagy by increasing the activity of Beclin-1 level. CHR treatment had the opposite effect on all these values and reduced the damage caused by all these signal pathways. Overall, the data of this study indicate that renal damage associated with Cd toxicity could be ameliorated by CHR administration.

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Body Weight; Cadmium; Caspase 3; Flavonoids; Inflammation; Kidney Diseases; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Rats; Rats, Wistar; RNA, Messenger; Signal Transduction

Chrysin (Chy) is known for various biological proprieties such as inhibitory effects on inflammation, cancer, oxidative stress, aging, and atherosclerosis. However, the hypolipidemic activity of Chy and its mechanistic action remains unclear in cardiovascular diseases (CVD). In this study, we focused on the hypolipidemic proprieties of Chy in hypercholesterolemia-induced atherosclerosis. Male Wistar rats (150-220 g) were divided into four groups as follows: Group I control was fed with standard laboratory chow. Rats in Group II were fed a high-fat diet (HFD) for 60 days. After 60 days of HFD, Group III rats received Chy (100 mg/kg body weight); Group IV rats received Atorvastatin (Atv; 10 mg/kg body weight) for 30 days. Biochemical studies showed Chy, Atv treatment decreased the activities of liver marker enzymes and the levels of Reactive Oxygen Species (ROS) and lipid profile. Gene expression analysis on nuclear factor erythroid 2-related factor 2 (Nrf2) and its regulated genes were significantly reduced in the intestine and increased in the aorta by Chy and Atv. Gut microbial species such as Bacteroidetes, Lactobacillus, Enterococcus, and Clostridium leptum copy numbers were significantly increased by Chy and Atv treatment. In addition, Chy and Atv modulated the expression of inflammatory genes including TLR4, TNFα, NLRP3, and IL-17 in the aorta and intestine compared with hypercholesterolemic control rats. Chy and Atv effectively increased the caspase-3 mRNA expression in the intestine, but these decreased in the aorta. The present study concludes that by reducing oxidative stress and increasing gut microbial colonization, Chy may provide an effective therapeutic approach for the prevention of hypercholesterolemia-mediated atherosclerosis. PRACTICAL APPLICATIONS: Our study focused on a therapeutic model representing the clinical presentation of atherosclerosis in humans. Statins are commonly used in the treatment of cardiovascular complications, patients with hypercholesterolemia face difficulties in the continuation of statin therapy. The reason for statin discontinuation has been associated with toxicological effects. It is necessary to investigate the potentiality of the natural compound as an alternative medicine to statin with fewer side effects. The main theme of our study is to compare the therapeutic potential of Chy and Atv. Chy is a natural bioflavonoid that could be considered as an alternative medicinal compound to statins and to avoid tox

Topics: Animals; Apoptosis; Atherosclerosis; Body Weight; Flavonoids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Oxidative Stress; Rats; Rats, Wistar

Chrysin (CH) is a natural flavone which possesses antioxidant, anti-cancer, and anti-inflammatory properties. The aim of the present study was to investigate the effects of CH on biochemical parameters, histopathological changes, and genotoxicity and hematological indices in diazinon (DZN)-induced toxicity in BALB/c mice. We induced sub-acute toxicity in mice using DZN (20 mg/kg/day) and treated them with CH at the 12.5, 25, and 50 mg/kg/day five times/week in 28 days. In our study, DZN increased lipid profile and liver function tests (LFTs) and creatinine (Cr) but decreased the red blood cell acetylcholinesterase (RBC-AChE) activity and glucose level. Also, CH when co-treated with DZN changed the LFTs, lipid profile, creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and bilirubin total (Bili-T). Moreover, a significant decrease in RBCs, hemoglobin (Hgb), hematocrit (HCT) level, and platelet counts were seen in DZN group but WBCs, lymphocytes, and neutrophils count increased. CH 25 and 50 mg/kg significantly improved alterations of WBCs, RBCs, Hgb, HCT, lymphocytes, neutrophils, and reticulocytes count when co-treated with DZN. Moreover, the co-administration of CH plus DZN recovered histopathological alterations in liver and kidney, as well as, improved the absolute and relative weight of kidney and liver. DZN induced the formation of bone marrow micronuclei (MN) but CH 50 mg/kg decreased the MN formation when co-treated with DZN. These results suggest that CH not only restores renal and hepatic markers, and histopathological alterations but also improves hematological and genotoxicity indices induced by DZN in mice.

Topics: Animals; Body Weight; Diazinon; Flavonoids; Kidney; Lipids; Liver; Male; Mice; Mice, Inbred BALB C; Micronucleus Tests; Protective Agents

Chrysin (5,7-dihydroxyflavone) is a major component of some traditional medicinal herbs present in honey, propolis and many plant extracts. The study was aimed to illuminate the effect of chrysin in the pathogenesis of ammonium chloride (NH4Cl) induced hyperammonemic rat model in a dose dependent manner. Rats were injected with NH4Cl (100mg/kg b.w.) by intraperitonially (i.p) thrice a week for 8 consecutive weeks for the induction of experimental hyperammonemia. Hyperammonemic rats were treated with chrysin by orally at a dose of 25, 50 & 100mg/kg b.w. respectively. Protective effect of chrysin against hyperammonemia was evaluated by performing biochemical estimations and morphopathological investigations of hematoxylin and eosin stained sections of liver, brain and kidney tissues. Supplementation of chrysin reinstated the levels of blood ammonia, plasma urea, uric acid, total bilirubin, creatinine, brain glutamate, glutamine, nitric oxide (NO) and the activities of Na(+)/K(+)-ATPase, and liver marker enzymes. On the other hand increased level of plasma urea was observed in chrysin treated rats as compared with hyperammonemic rats. Chrysin administration caused distortion of hepatic, brain and kidney architecture as shown by histological examination. Chrysin at a dose (100mg/kg b.w.) showed an utmost decline in the level of all biochemical estimations. Both biochemical and morphological studies clearly revealed that chrysin protects against cell injury induced by ammonia intoxication in a dose-response manner with respect to endogenous antioxidants and hypoammonemic effects.

Topics: Ammonia; Animals; Bilirubin; Biomarkers; Body Weight; Brain; Creatinine; Dose-Response Relationship, Drug; Flavonoids; Glutamic Acid; Glutamine; Hyperammonemia; Kidney; Liver; Male; Models, Biological; Nitric Oxide; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Urea; Uric Acid

Guillain-Barré syndrome (GBS) is an acute, post-infectious, immune-mediated, demyelinating disease of peripheral nerves and nerve roots. Experimental autoimmune neuritis (EAN) is an animal model of GBS. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. This study was designed to investigate the anti-inflammatory and neuroprotective properties of preventative and therapeutic chrysin treatment in EAN rats. For preventative treatment, chrysin was administered orally from day 1 to day 16 (50mg/kg once daily) while, for therapeutic treatment, rats received chrysin from day 7 to day 16 at the same dose once daily. Control animals received the same volume of the vehicle (phosphate-buffered saline/2% dimethylsulfoxide). Regardless of the treatment regimen, chrysin attenuated the severity and duration of the clinical course of EAN and reduced inflammatory cell infiltration and demyelination of sciatic nerves. In the sciatic nerves, the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor kappa B was reduced. Furthermore, chrysin inhibited the splenic mononuclear cell secretion of interleukin-1β, interleukin-2, interleukin-6, inteleukin-12, interferon γ and tumor necrosis factor α, and elevated the level of inteleukin-4. In summary, our data demonstrate that chrysin is a potentially useful agent for the treatment of EAN with its anti-inflammatory and neuroprotective effects.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cell Proliferation; Cyclooxygenase 2; Flavonoids; Guillain-Barre Syndrome; Interferon-gamma; Interleukins; Neuritis, Autoimmune, Experimental; NF-kappa B; Nitric Oxide Synthase Type II; Random Allocation; Rats; Rats, Inbred Lew; Sciatic Nerve; Severity of Illness Index; T-Lymphocytes; Time Factors; Tumor Necrosis Factor-alpha

Chrysin (CH) is an important natural plant flavonoid and possesses diverse pharmacological activities. Our present investigations aimed to assess the neuroprotection of CH against diabetes-associated cognitive decline (DACD) in a rat model of diabetes and exploring its potential mechanism. Diabetic model was induced by intraperitoneal injection of streptozotocin. Then, they were treated with vehicle or CH by doses of 30 and 100 mg/kg for 26 days. Learning and memory function was evaluated by Morris water maze test. The oxidative indicators [malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH)], NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured in cerebral cortex and hippocampus using corresponding commercial kits. The diabetic rats showed marked reductions in body weight, percentage of time spent in target quadrant and number of times of crossing platform, coupled with increases in plasma glucose levels, escape latency, mean path length and oxidative stress (increased MDA level and decreased CAT and SOD as well as reduced GSH), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Moreover, CH supplement dramatically reversed the corresponding behavioral, biochemical and molecular alterations in diabetes. The alterations of swimming speed among different groups were not observed after CH adminstration. In conclusion, our current work discloses that CH remarkably alleviates DACD and suggests that oxidative stress, inflammation and apoptotic cascades are linked with diabetes-associated cognitive deficits. These findings point toward the therapeutic potential of CH in DACD.

Topics: Animals; Blood Glucose; Body Weight; Cerebral Cortex; Cognition Disorders; Diabetes Complications; Disease Models, Animal; Encephalitis; Flavonoids; Male; Maze Learning; Oxidative Stress; Rats; Rats, Wistar; Streptozocin

Flavonoids possess strong anti-oxidant and cancer chemopreventive activities. Chrysin (5,7-dihydroxyflavone) occurs naturally in many plants, honey, and propolis. In vitro, chrysin acts as a general anti-oxidant, causes cell cycle arrest and promotes cell death. However, the mechanism by which chrysin inhibits cancer cell growth and the subcellular pathways activated remains poorly understood. Effect of dietary supplementation with chrysin on proliferation and apoptosis during diethylnitrosamine (DEN)-induced early hepatocarcinogenesis was investigated in male Wistar rats. To induce hepatocarcinogenesis, rats were given DEN injections (i.p., 200 mg/kg) three times at a 15 day interval. An oral dose of chrysin (250 mg/kg bodyweight) was given three times weekly for 3 weeks, commencing 1 week after the last dose of DEN. Changes in the mRNA expression of COX-2, NFkB p65, p53, Bcl-xL and β-arrestin-2 were assessed by quantitative real-time PCR. Changes in the protein levels were measured by western blotting. Chrysin administration significantly (P<0.001) reduced the number and size of nodules formed. Also, a significant (P<0.01) reduction in serum activities of AST, ALT, ALP, LDH and γGT was noticed. Expression of COX-2 and NFkB p65 was significantly reduced whereas that of p53, Bax and caspase 3 increased at the mRNA and protein levels. Likewise, a decrease in levels of β-arrestin and the anti-apoptotic marker Bcl-xL was also noted. These findings suggest that chrysin exerts global hepato-protective effect and its chemopreventive activity is associated with p53-mediated apoptosis during early hepatocarcinogenesis.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Apoptosis Regulatory Proteins; Arrestins; beta-Arrestin 2; beta-Arrestins; Biomarkers; Body Weight; Cell Cycle Proteins; Cell Proliferation; Cell Transformation, Neoplastic; Cyclooxygenase 2; Diethylnitrosamine; Flavonoids; Glutathione S-Transferase pi; Liver; Liver Neoplasms, Experimental; Male; Organ Size; Precancerous Conditions; Rats; Rats, Wistar; Time Factors; Transcription Factor RelA; Tumor Suppressor Protein p53

The aim of this study is to investigate the effects of the quercetin (Q) and chrysin (CH) on oxidative stress, cytokines levels and body weights in rats induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Rats were divided randomly into six equal groups. TCDD, Q and CH were administered by gavages dissolved in corn oil at the doses of 2 µg/kg/week, 20 mg/kg/day and 50 mg/kg/day, respectively. The blood samples were taken from all rats at 60th days to be analyzed for the determination of thiobarbituric acid reactive substances (TBARS), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). The results indicated that although TCDD increased significantly TBARS and TNF-α levels, it caused a decline in the levels of IFN-γ and body weight. In contrast, these effects of TCDD on TBARS, TNF-α, IFN-γ levels and body weight were significantly prevented by treatments of Q and CH. In conclusion, it was determined that TCDD caused the adverse effects on immune functions, body weight and oxidative stress in rats. However, Q and CH administered with TCDD eliminated these adverse effects. These results suggest that Q and CH may play a protective role against TCDD toxicity.

Topics: Animals; Body Weight; Flavonoids; Interferon-gamma; Male; Oxidative Stress; Polychlorinated Dibenzodioxins; Quercetin; Rats; Rats, Wistar; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha

The effects of an oral daily dose (20 mg kg(-1)) of the flavonoid chrysin for 6 weeks in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) were analysed. Chrysin reduces SHR elevated blood pressure, cardiac hypertrophy and functional vascular changes, but is without effect in WKY. These protective effects were associated with a reduced oxidative status due to the antioxidant properties of the drug.

Topics: Animals; Antihypertensive Agents; Aorta; Blood Pressure; Body Weight; Cardiomegaly; Endothelium, Vascular; Flavonoids; Hypertension; In Vitro Techniques; Male; Oxidation-Reduction; Oxidative Stress; Phytotherapy; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reactive Oxygen Species; Vasoconstriction; Vasodilation