Chrysin alleviates chronic hypoxia-induced pulmonary hypertension.

PMID: 

J Cardiovasc Pharmacol. 2019 Nov ;74(5):426-435. PMID: 31725079

Abstract Title: 

Chrysin Alleviates Chronic Hypoxia-Induced Pulmonary Hypertension by Reducing Intracellular Calcium Concentration in Pulmonary Arterial Smooth Muscle Cells.

Abstract: 

Chrysin (CH), the main ingredient of many medicinal plants, has been reported to be a very potent flavonoid possessing a large number of pharmacological activities. Recent studies have shown that CH significantly improves hemodynamic parameters such as right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in a rat model of chronic hypoxia-induced pulmonary hypertension (CHPH). These improvements are through the inhibition of NOX4 expression, reactive oxygen species and malondialdehyde production, pulmonary arterial smooth muscle cell (PASMC) proliferation, and collagen accumulation. In this study, we investigated another mechanism by which CH alleviates CHPH by regulating intracellular calcium concentrations ([Ca]i) in PASMCs, as well as the underlying signaling pathway. The results show that (1) in CHPH model rats, CH substantially attenuated elevated right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; (2) in cultured rat distal PASMCs, CH inhibited the hypoxia-triggered promotion of cell proliferation, store-operated Ca entry and [Ca]i; and (3) CH significantly suppressed the hypoxia-upregulated HIF-1α, BMP4, TRPC1, and TRPC6 expression in distal pulmonary arteries (PAs) and cultured rat distal PASMCs. These results indicate that CH likely exerts its CHPH protective activity by regulating [Ca]i, which may result from the downregulation of HIF-1α, BMP4, TRPC1, and TRPC in PASMCs.

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Neuroprotective potential of chrysin in Parkinson’s disease: Molecular mechanisms and clinical implications.

PMID: 

Neurochem Int. 2020 Jan ;132:104612. Epub 2019 Nov 27. PMID: 31785348

Abstract Title: 

Neuroprotective potential of chrysin in Parkinson's disease: Molecular mechanisms and clinical implications.

Abstract: 

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, with current treatment being mainly symptomatic and often accompanied by serious side effects. In search of novel and safe therapeutic agents for PD, natural flavonoids have been shown to exert significant neuroprotective effects. Among them, chrysin (5,7-dihydroxyflavone) has been demonstrated to exhibit anti-oxidative effects to dopaminergic neurons mainly by increasing the expression of Nuclear Factor Erythroid 2 -related factor 2 (NRF2) which reduces intracellular nitric oxide (NO) levels and regulates anti-oxidant pathways. Moreover, chrysin activates Myocyte Enhancer factor 2D (MEF2D), a critical transcription factor involved in dopaminergic survival. It suppresses the MPP-induced upregulation of c-caspase and Bax as well as the downregulation of anti-apoptotic protein Bcl 2. Chrysin also enhances the production of neurotrophic factors, contributing to neuronal survival. Of interest, the combination of chrysin with protocatechuic acid (PCA) has been demonstrated to inhibit neuronal loss in PD animal models. Along with anti-inflammatory properties, chrysin has also been shown to increase dopamine levels in the striatum via monoamino-oxidase B (MAO-B) inhibition while it restores the behavioral deficits in PD animal models. In this review, we discuss the molecular mechanisms that underlie the possible neuroprotective effects of chrysin in PD pathogenesis along with its therapeutic potential.

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Protective effects of Chrysin against memory impairment, cerebral hyperemia and oxidative stress after cerebral hypoperfusion and reperfusion.

PMID: 

Metab Brain Dis. 2020 Feb ;35(2):401-412. Epub 2019 Dec 18. PMID: 31853830

Abstract Title: 

Protective effects of Chrysin against memory impairment, cerebral hyperemia and oxidative stress after cerebral hypoperfusion and reperfusion in rats.

Abstract: 

Stroke is devastating and a leading cause of morbidity and mortality worldwide. Cerebral ischemia-reperfusion and its subsequent reactive hyperemia lead to neuronal damage in the hippocampus and cognitive decline. Chrysin (5, 7-dihydroxyflavone) is a well-known member of the flavonoid family with antioxidant and neuroprotective effects. Therefore, in the present study, the aim was to investigate whether chrysin will be able to recover the brain function caused by ischemia-reperfusion (I/R) in rats. Adult male Wistar rats (250-300 g) were randomly divided into five groups: and submitted to cerebral I/R or a sham surgery after three-weeks of pretreatment with chrysin (CH; 10, 30 and 100 mg/kg; P.O.) and/or normal saline containing %5 DMSO. Subsequently, sensorimotor scores, cognition, local cerebral blood flow, extracellular single unit, and histological parameters were evaluated following I/R. Hippocampus was used to evaluate biomarkers including: oxidative stress parameters and prostaglandin E2 (PGE2) using ELISA kits. Data showed that pretreatment with chrysin significantly improved sensorimotor signs, passive avoidance memory, and attenuated reactive hyperemia, and increased the average number of spikes/bin (p 

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NF-κB/Twist axis is involved in chysin inhibition of ovarian cancer stem cell features induced by co-treatment of TNF-α and TGF-β.

n/a

PMID: 

Int J Clin Exp Pathol. 2019 ;12(1):101-112. Epub 2019 Jan 1. PMID: 31933724

Abstract Title: 

NF-κB/Twist axis is involved in chysin inhibition of ovarian cancer stem cell features induced by co-treatment of TNF-α and TGF-β.

Abstract: 

Chrysin (ChR) inhibits various cancer cells and possesses anti-inflammatory activities. NF-kB has been shown to regulate the expression of genes involved in epithelial-mesenchymal transformation (EMT) by upregulation of TWIST1. This study aimed to assess whether ChR can inhibit EMT phenotype and cancer stem-like cell (CSLC) features in ovarian cancer cells co-treated with TNF-α and TGF-β. Here, OVCAR-3 cells were co-treated with TNF-α and TGF-β in the presence or absence of ChR. Then, the expression levels of E-cadherin, N-cadherin, CD133, CD44, NF-κBp65, and TWIST1 were analyzed by western blotting. Wound healing and tumor sphere formation assays were performed toassess the migration and sphere-forming capabilities of cells, respectively. Overexpression and/or knockdown of NF-κBp65 and/or TWIST1 were used to explore the molecular mechanisms. We showed that ChR inhibited EMT and CSLC properties in ovarian cancer cells administered TNF-α after prolonged TGF-β treatment, in a dose-dependent manner. Also, knockdown of NF-κBp65 and ChR cooperatively enhanced the inhibition of NF-κBp65 and TWIST1 expression, EMT phenotype, and CSLC properties. Conversely, overexpression of NF-κBp65 antagonized the above-mentioned activities of ChR. Furthermore, TWIST1silencing or overexpression did not affect the ChR treatment effect on NF-κBp65 levels, but it reduced or enhanced EMT and CSLC properties. In conclusion, ChR can inhibit a proinflammatory cytokine to induce EMT and CSLC characteristics in OVCAR-3 cells, which may be involved in blocking the NF-κB/Twist axis.

Chrysin modulates genes related to inflammation, tissue remodeling, and cell proliferation in the gastric ulcer healing.

PMID: 

Int J Mol Sci. 2020 Jan 23 ;21(3). Epub 2020 Jan 23. PMID: 31979417

Abstract Title: 

Chrysin Modulates Genes Related to Inflammation, Tissue Remodeling, and Cell Proliferation in the Gastric Ulcer Healing.

Abstract: 

Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 () and 9 (), caspase-3, cyclooxygenase 1 () and 2 (), epidermal growth factor (), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.

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Cyclohexane extract of walnut leaves improves indices of oxidative stress, total homocysteine and lipids profiles in streptozotocin-induced diabetic rats.

PMID: 

Physiol Rep. 2020 Jan ;8(1):e14348. PMID: 31960621

Abstract Title: 

Cyclohexane extract of walnut leaves improves indices of oxidative stress, total homocysteine and lipids profiles in streptozotocin-induced diabetic rats.

Abstract: 

This study aimed to evaluate the effect of two doses of cyclohexane extract of walnut leaves on total homocysteine, lipids profiles, and indices of oxidative stress including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and malondialdehyde (MDA) in diabetic rats. Diabetes was induced by a single intraperitoneal (IP) injection of streptozotocin (50 mg/kg BW). Twenty-eight male Sprague Dawley rats were randomly divided into four groups, group I: control (received sesame oil as vehicle), group II: diabetic control (received sesame oil), group III and IV: diabetic rats treated by 150 and 250 mg/kg body weight (BW) per day extract of walnut leaves, respectively. All groups were treated for 28 days via oral gavage. Fasting blood glucose (FBG) level and body weight measured before injection, 3 days after injection, and on days 0, 7, 14, 21, and 28 of treatment. At the end the 28th day of the experiment, blood samples collected via heart puncture and the sera were used for estimation of the above-mentioned parameters. The results showed a decrease in FBS, TC, TG, LDL-c, VLDL-c, homocysteine, and MDA level and increase in the level of HDL-c in diabetics treated by walnut leave extracts in a dose-dependent manner after 28 days. The activity of antioxidant enzymes significantly increased in treated groups compared with diabetic control. It can be concluded that cyclohexane extract of walnut leaves has an overall beneficial effect on body weight, fasting blood glucose, lipids profile, antioxidant enzyme activities, and homocysteine.

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Flaxseed supplementation improves serum total cholesterol, triglyceride, and LDL-C, which could delay the progression of heart disease.

PMID: 

Pharmacol Res. 2019 Dec 30 ;152:104622. Epub 2019 Dec 30. PMID: 31899314

Abstract Title: 

Effect of flaxseed supplementation on lipid profile: An updated systematic review and dose-response meta-analysis of sixty-two randomized controlled trials.

Abstract: 

Raised plasma lipids are one the most important risk factors for cardiovascular disease. Flaxseed contains considerable amounts ofα-linolenic acid, phenolic compounds, and lignans, which each have the capacity to reduce circulating lipid concentrations. This study aimed to systematically review current evidence to identify the potential effects of flaxseed supplementation on blood lipid profiles using a meta-analysis of randomized controlled trials (RCTs). PubMed, Scopus, Web of Science, and Google Scholar databases were searched for publications between January 1900 and May 2019. Weighted mean differences (WMDs) were analyzed using a random-effects model. The Cochrane Collaboration tool was also used to assess the riskof bias of the studies included. Sixty-two RCTs with a total of 3772 participants met the eligibility criteria. Our analysis showed that flaxseed supplementation significantly reduced total cholesterol (TC) (WMD = -5.389 mg/dL; 95% CI: -9.483, -1.295, p = 0.010), triglyceride (TG) (WMD = -9.422 mg/dL; 95% CI: -15.514, -3.330, p = 0.002), and low-density lipoprotein cholesterol (LDL-C) (WMD = -4.206 mg/dl; 95% CI: -7.260, -1.151, p = 0.007) concentrations. However, it had no effects on high-density lipoprotein cholesterol (WMD = 0.047 mg/dl; 95% CI: -0.777, 0.872, p = 0.910). This meta-analysis suggested that flaxseed supplementation improves serum TC, TG, and LDL-C, which could delay the progression of heart disease. Further studies with large-scale and better design are now needed to confirm these results.

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Flaxseed consumption can be considered as a useful therapeutic approach for reducing lipid profile and anthropometric indices.

PMID: 

Int J Prev Med. 2019 ;10:218. Epub 2019 Dec 10. PMID: 31929865

Abstract Title: 

Effect of Flaxseed Powder on Cardiovascular Risk Factor in Dyslipidemic and Hypertensive Patients.

Abstract: 

Background: Hyperlipidemia and hypertension are the most important causes of ischemic heart disease. There is evidence that flaxseed powder can improve lipid profile and blood pressure. In this study, we want to investigate the effects of flaxseed powder consumption on patients with hyperlipidemia and hypertension.Methods: This randomized double-blind placebo-controlled clinical trial was performed on 80 hyperlipidemic and hypertensive patients (men and women between 20 and 60 years old). In this study, participants were recruited from Imam Khomeini hospital clinics of Shiraz University of Medical Sciences in 2017 randomly allocated to flaxseed powder group and placebo group. The intervention group received 36 g of flaxseed sachet (= 40), and control group received 12 g placebo sachet (= 40) for 8 weeks. Serum lipid profiles, blood pressure, fasting blood sugar, and anthropometric indices were measured. Data were analyzed by using SPSS.Results: We found significant reduction (

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The beneficial effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome.

PMID: 

Nutr J. 2020 Jan 24 ;19(1):8. Epub 2020 Jan 24. PMID: 31980022

Abstract Title: 

The effects of flaxseed supplementation on metabolic status in women with polycystic ovary syndrome: a randomized open-labeled controlled clinical trial.

Abstract: 

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is known as the most common endocrine disorder of women in reproductive ages. With the increasing prevalence of PCOS in different countries, the use of herbal medicine as an alternative treatment is growing in these patients. This study aimed to evaluate the effects of flaxseed powder supplementation on metabolic biomarkers of patients with PCOS.METHODS: This randomized open-labeled controlled clinical trial was conducted on 41 patients with PCOS. The participants were randomized to take either flaxseed powder (30 g/day) plus lifestyle modification or only lifestyle modification for 12 weeks. Anthropometric and biochemical evaluations were performed for all patients at the beginning and end of the study.RESULTS: The flaxseed group showed a significant reduction in body weight, insulin concentration, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Triglycerides (TG), high-sensitivity C-Reactive Protein (hs-CRP), and leptin and an increase in Quantitative Insulin-Sensitivity Check Index (QUICKI), High Density Lipoprotein (HDL), and adiponectin compared to the baseline (p 

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