PMID: 

Food Sci Biotechnol. 2018 Oct ;27(5):1475-1484. Epub 2018 Sep 19. PMID: 30319858

Abstract Title: 

Protective effect ofL. seed on oxidative stress and cognitive impairment induced by chronic alcohol consumption in mice.

Abstract: 

Chronic alcohol consumption induces damage to the brain that can cause various forms of dementia. An abundance of acetaldehyde is produced by excessive alcohol consumption and accumulates in the body to induce oxidative stress, apoptosis, and inflammation in neuronal cells, which results in learning and cognitive decline. In the present study, C57BL/N mice were orally administered alcohol (16%) andL. seed (CTS) (100 and 200 mg/kg/day). Behavioral experiments showed that memory and cognitive abilities were significantly higher in the CTS groups than the alcohol-treated control group in the T-maze test, novel object recognition test, and Morris water maze test. In addition, CTS inhibited alcohol-induced lipid peroxidation and nitric oxide production in the brain, kidney, and liver. Moreover, alcohol increased acetylcholinesterase activity in the brain, but this was significantly decreased by the administration of CTS. Therefore, CTS may play role in the prevention of alcohol-related dementia.

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PMID: 

Ann Anat. 2019 Mar ;222:120-128. Epub 2018 Dec 24. PMID: 30590121

Abstract Title: 

Carthamus Tinctorius L. extract attenuates cardiac remodeling in L-NAME-induced hypertensive rats by inhibiting the NADPH oxidase-mediated TGF-β1 and MMP-9 pathway.

Abstract: 

Carthamus tinctorius L. (CT) has been widely used in Asian countries as a beverage and a folk medicine. The current study investigates the effect of CT extract on cardiac remodeling and possible mechanisms involved in N-nitro-l-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Male Sprague-Dawley rats were administrated with L-NAME (40mg/kg/day) for five weeks to induce hypertension. Hypertensive rats were treated with CT extract (300mg/kg/day) or captopril (5mg/kg/day) or vehicle for a further two weeks. Treatment of hypertensive rats with CT extract or captopril significantly decreased systolic blood pressure, left ventricular (LV) hypertrophy and fibrosis, small intramyocardial coronary artery remodeling, and cardiac weight index. CT extract or captopril increased plasma nitric oxide metabolite (NOx) levels and reduced plasma transforming growth factorβ1 (TGF-β1) level, together with downregulation of cardiac TGF-β1 and matrix metalloproteinases-9 (MMP-9) expression. In addition, decreased plasma malondialdehyde (MDA) levels, consistent with downregulation of NADPH oxidase subunit gp91expression in heart tissue, was also observed after CT extract or captopril treatment. These findings suggest that CT extract alleviates cardiac remodeling in L-NAME-induced hypertensive rats, which is possibly related to inhibition of the NADPH oxidase-mediated TGF-β1-MMP-9 pathway.

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PMID: 

Food Funct. 2019 Jun 19 ;10(6):3650-3659. PMID: 31165850

Abstract Title: 

Safflower (Carthamus tinctorius L.) seed attenuates memory impairment induced by scopolamine in mice via regulation of cholinergic dysfunction and oxidative stress.

Abstract: 

Cholinergic dysfunction and oxidative stress are the most common causes of Alzheimer's disease (AD). Safflower seed contains various anti-oxidant and cholinergic improvement compounds, such as serotonin and its derivatives. In the present study, we investigated the protective effects and mechanisms of a safflower seed extract on scopolamine-induced memory impairment in a mouse model. The safflower seed extract was orally administered at a dose of 100 mg kg-1 day-1, and then behavior tests (such as T-maze and novel object recognition tests) were conducted. Acetyl cholinesterase (AChE) activity, reactive oxygen species (ROS) production, and antioxidant enzymes in the brain were measured. In behavior tests, the novel route exploration and object recognition were improved by the administration of the safflower seed extract, which suggests that the safflower seed extract improves memory function in the scopolamine-treated mouse model. In addition, the safflower seed extract-administered group showed inhibition of the AChE activity and improved cholinergic dysfunction. Furthermore, the administration of the safflower seed extract resulted in lower ROS production and higher antioxidant enzyme levels as compared to the scopolamine-treated group, suggesting the protective role of the safflower seed extract against oxidative stress. The results of the present study suggest that the safflower seed extract improves scopolamine-induced memory deficits via the inhibition of cholinergic dysfunction and oxidative stress. Therefore, safflower seeds might become a promising agent for memory improvement in AD patients.

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PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:6479136. Epub 2019 May 30. PMID: 31275414

Abstract Title: 

andExtract Prevents Cardiac Fibrosis and Dysfunction after Myocardial Infarction by Epigenetically Inhibiting Smad3 Expression.

Abstract: 

The incidence of cardiac dysfunction after myocardial infarction (MI) continues to increase despite advances in treatment. Excessive myocardial fibrosis plays a vital role in the development of adverse cardiac remodeling and deterioration of cardiac function. Understanding the molecular and cellular mechanism of the fibrosis process and developing effective therapeutics are of great importance.andextract (SCE) is indicated for angina pectoris and other ischemic cardiovascular diseases in China. SCE has been shown to inhibit the platelet activation and aggregation, ameliorate ROS-induced myocardial necrosis by inhibiting mitochondrial permeability transition pore opening, and promote angiogenesis by upregulating the expression of vascular endothelial growth factor (VEGF). However, whether SCE has effect on cardiac fibrosis after MI is not fully clear. Here, a mouse model of MI was established to observe the effect of SCE upon survival, cardiac function, myocardial fibrosis, and inflammation. Quantitative PCR and western blot assays were used to determine the expression of genes related to transforming growth factor-(TGF-) cascade and inflammatory responses. Additionally, the effects of SCE upon the collagen production, TGF-/Smad3 (SMAD family member 3) signaling, and the levels of histone methylation in primary cardiac fibroblasts were detected. We found that SCE treatment significantly improved survival and left ventricular function in mice after MI. Inhibition of inflammation and fibrosis, as well as decreased expression of Smad3, was observed with SCE treatment. In TGF–stimulated cardiac fibroblasts, SCE significantly decreased the expression of collagen,-smooth muscle actin (-SMA), and Smad3. Furthermore, SCE treatment downregulated the levels of H3K4 trimethylation (H3K4me3) and H3K36 trimethylation (H3K36me3) at thepromoter region of cardiac fibroblasts, leading to inhibition oftranscription. Our findings suggested that SCE prevents myocardial fibrosis and adverse remodeling after MI with a novel mechanism of suppressing histone methylation of thepromoter and its transcription.

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PMID: 

J Pharmacopuncture. 2018 Mar ;21(1):35-40. Epub 2018 Mar 31. PMID: 30151303

Abstract Title: 

Antidepressant effects of aqueous extract of saffron and its effects on CREB, P-CREB, BDNF, and VGF proteins in rat cerebellum.

Abstract: 

Objective: The role of BDNF (brain-derived neurotrophic factor), CREB (cAMP response element binding) and VGF neuropeptide has been proved in antidepressant activity of long term saffron administration in the rat hippocampus. In this study we evaluated the role of these proteins in antidepressant activity of saffron in long term administration in the rat cerebellum.Methods: Saffron aqueous extract (40 and 80 mg/kg/day) and imipramine (10 mg/kg/day) were administered intraperitoneally for 21 days to rats. At the end of experiment, animals were sacrificed and cerebellums were separated. The protein levels of BDNF, VGF, CREB and P- CREB in the rat cerebellum were evaluated using western blot analysis.Results: Saffron aqueous extract (80mg/kg/day) caused significant increase in protein level of P-CREB in long term treatment in the rat cerebellum. The increases in the protein levels of VGF, CREB and BDNF were not significant.Conclusion: In summary, our results showed that antidepressant effect of saffron in rat cerebellum might be due to the enhanced phosphorylation of CREB.

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PMID: 

Nutr Cancer. 2019 ;71(3):491-507. Epub 2018 Oct 1. PMID: 30273051

Abstract Title: 

Crocus sativus L. Causes a Non Apoptotic Calpain Dependent Death in C6 Rat Glioma Cells, Exhibiting a Synergistic Effect with Temozolomide.

Abstract: 

Crocus sativus L., a dietary herb, has been used for various diseases including cancer. This is an in vitro study investigating the antineoplastic effect of the extract of the plant against C6 glioma rat cell line. The mechanism of cellular death and the synergistic effect of the extract with the alkylating agent temozolomide (TMZ) were investigated. Cellular viability was examined in various concentrations of the extract alone or in combination with TMZ. Apoptosis was determined with flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and autophagy by western blotting of the light chain 3 (LC3)-II. Cellular viability was reduced after exposure to the extract with half maximal inhibition concentration at 3 mg/ml. Flow cytometry and TUNEL assay suggested that the extract does not induce apoptosis. Moreover, their combination increased the ratio dead/apoptotic cells 10-fold (P 

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PMID: 

Avicenna J Phytomed. 2018 Nov-Dec;8(6):513-523. PMID: 30456199

Abstract Title: 

Saffron () versus duloxetine for treatment of patients with fibromyalgia: A randomized double-blind clinical trial.

Abstract: 

Objective: Saffron was found efficient and safe in treatment of neuropsychiatric disorders, in particular depression. We compared the efficacy of saffron with duloxetine in treatment of patients with fibromyalgia.Materials and Methods: In this double-blind parallel-group clinical trial, outpatients with fibromyalgia were randomized to receive either saffron 15 mg or duloxetine 30 mg starting with 1 capsule per day in the first week followed by 2 capsules per day from week 2 until the end of week 8. Participants were men and women aged 18-60 years diagnosed with fibromyalgia based on the American College of Rheumatology 2010 criteria who also had a pain score≥40 based on visual analogue scale. Participants were excluded in case they had rheumatologic diseases, inflammatory/infectious/autoimmune arthritis, comorbid neuropsychiatric disorders except depressive disorders, pain due to traumatic injuries, drug history of duloxetine or saffron use, currentuse of psychoactive medications, recent use of muscle relaxants, steroids, opioid analgesics, benzodiazepines, anti-epileptics, or injective analgesics. Primary outcomes included differences in mean score changes from baseline to endpoint between the treatment arms for Hamilton Rating Scale for Depression, Fibromyalgia Impact Questionnaire, and Brief Pain Inventory.Results: Socio-demographic characteristics and baseline scores were similarly distributed between the two treatment arms (2n=46). No significant difference was detected for any of the scales neither in terms of score changes from baseline to endpoint between the two treatment arms (Mean score changes: -4.26 to 2.37; p-values: 0.182-0.900) nor in terms of timetreatment interactions (p-values: 0.209-0.964).Conclusions: Saffron and duloxetine demonstrated comparable efficacy in treatment of fibromyalgia symptoms.

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The research continues to accumulate: Fluoride exposure harms the brain and reduces IQ. 

The U.S. Centers for Disease Control and Prevention considers community water fluoridation one of the ten greatest public health achievements of the 20th century. The view of US regulatory agencies has also been the dominate view of the medical community. Have these long-held beliefs stood the test of scientific rigor?

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PMID: 

Mol Cell Biochem. 2010 Dec ;345(1-2):91-104. Epub 2010 Aug 22. PMID: 20730621

Abstract Title: 

Metals, oxidative stress and neurodegenerative disorders.

Abstract: 

The neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD), are age-related disorders characterized by the deposition of abnormal forms of specific proteins in the brain. AD is characterized by the presence of extracellular amyloid plaques and intraneuronal neurofibrillary tangles in the brain. Biochemical analysis of amyloid plaques revealed that the main constituent is fibrillar aggregates of a 39-42 residue peptide referred to as the amyloid-β protein (Aβ). PD is associated with the degeneration of dopaminergic neurons in the substantia nigra pars compacta. One of the pathological hallmarks of PD is the presence of intracellular inclusions called Lewy bodies that consist of aggregates of the presynaptic soluble protein called α-synuclein. There are various factors influencing the pathological depositions, and in general, the cause of neuronal death in neurological disorders appears to be multifactorial. However, it is clear, that the underlying factor in the neurological disorders is increased oxidative stress substantiated bythe findings that the protein side-chains are modified either directly by reactive oxygen species (ROS) or reactive nitrogen species (RNS), or indirectly, by the products of lipid peroxidation. The increased level of oxidative stress in AD brain is reflected by the increased brain content of iron (Fe) and copper (Cu) both capable of stimulating free radical formation (e.g. hydroxyl radicals via Fenton reaction), increased protein and DNA oxidation in the AD brain, enhanced lipid peroxidation, decreased level of cytochrome c oxidase and advanced glycation end products (AGEs), carbonyls, malondialdehyde (MDA), peroxynitrite, and heme oxygenase-1 (HO-1). AGEs, mainly through their interaction with receptors for advanced glycation end products (RAGEs), further activate signaling pathways, inducing formation of proinflammatory cytokines such as interleukin-6 (IL-6). The conjugated aromatic ring of tyrosine residues is a target for free-radical attack, and accumulation of dityrosine and 3-nitrotyrosine has also been reported in AD brain. The oxidative stress linked with PD is supported by both postmortem studies and by studies showing the increased level of oxidative stress in the substantia nigra pars compacta, demonstrating thus the capacity of oxidative stress to induce nigral cell degeneration. Markers of lipid peroxidation include 4-hydroxy-trans-2-nonenal (HNE), 4-oxo-trans-2-nonenal (4-ONE), acrolein, and 4-oxo-trans-2-hexenal, all of which are well recognized neurotoxic agents. In addition, other important factors, involving inflammation, toxic action of nitric oxide (NO·), defects in protein clearance, and mitochondrial dysfunction all contribute to the etiology of PD. It has been suggested that several individual antioxidants or their combinations can be neuroprotective and decrease the risk of AD or slow its progression. The aim of this review is to discuss the role of redox metals Fe and Cu and non-redox metal zinc (Zn) in oxidative stress-related etiology of AD and PD. Attention is focused on the metal-induced formation of free radicals and the protectiverole of antioxidants [glutathione (GSH), vitamin C (ascorbic acid)], vitamin E (α-Tocopherol), lipoic acid, flavonoids [catechins, epigallocatechin gallate (EGCG)], and curcumin. An alternate hypothesis topic in AD is also discussed.

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PMID: 

J Control Release. 2014 Jan 10 ;173:148-57. Epub 2013 Nov 1. PMID: 24188959

Abstract Title: 

Aluminum hydroxide nanoparticles show a stronger vaccine adjuvant activity than traditional aluminum hydroxide microparticles.

Abstract: 

Aluminum hydroxide is used as a vaccine adjuvant in various human vaccines. Unfortunately, despite its favorable safety profile, aluminum hydroxide can only weakly or moderately potentiate antigen-specific antibody responses. When dispersed in an aqueous solution, aluminum hydroxide forms particulates of 1-20μm. There is increasing evidence that nanoparticles around or less than 200nm as vaccine or antigen carriers have a more potent adjuvant activity than large microparticles. In the present study, we synthesized aluminum hydroxide nanoparticles of 112nm. Using ovalbumin and Bacillus anthracis protective antigen protein as model antigens, we showed that protein antigens adsorbed on the aluminum hydroxide nanoparticles induced a stronger antigen-specific antibody response than the same protein antigens adsorbed on the traditional aluminum hydroxide microparticles of around 9.3μm. The potent adjuvant activity of the aluminum hydroxide nanoparticles was likely related to their ability to more effectively facilitate the uptake of the antigens adsorbed on them by antigen-presenting cells. Finally, the local inflammation induced by aluminum hydroxide nanoparticles in the injection sites was milder than that induced by microparticles. Simply reducing the particle size of the traditional aluminum hydroxide adjuvant into nanometers represents a novel and effective approach to improve its adjuvanticity.

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