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PMID: 

Pharmacol Res. 2019 Jul 8:104346. Epub 2019 Jul 8. PMID: 31295570

Abstract Title: 

MicroRNA targeting by quercetin in cancer treatment and chemoprotection.

Abstract: 

A growing number of evidences from clinical and preclinical studies have shown that dysregulation of microRNA (miRNA) function contributes to the progression of cancer and thus miRNA can be an effective target in therapy. Dietary phytochemicals, such as quercetin, are natural products that have potential anti-cancer properties due to their proven antioxidant, anti-inflammatory, and anti-proliferative effects. Available experimental studies indicate that quercetin could modulate multiple cancer-relevant miRNAs including let-7, miR-21, miR-146a and miR-155, thereby inhibiting cancer initiation and development. This paper reviews the data supporting the use of quercetin for miRNA-mediated chemopreventive and therapeutic strategies in various cancers, with the aim to comprehensively understand its health-promoting benefits and pharmacological potential. Integration of technology platforms for miRNAs biomarker and drug discovery is also presented.

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PMID: 

Artif Cells Nanomed Biotechnol. 2019 Dec ;47(1):2909-2916. PMID: 31307244

Abstract Title: 

Quercetin supports cell viability and inhibits apoptosis in cardiocytes by down-regulating miR-199a.

Abstract: 

Hypoxia-caused cardiocytes insults are closely correlated with ectopic expression of genes, which might be modulated by microRNAs (miRs). Quercetin exhibits a profound protective function against hypoxic damages in cardiomyocytes. Here, we aimed to investigate a possible underpinning. H9c2 cells were pre-administrated using quercetin before hypoxia treatment. The damages were assessed using viability, apoptosis and alteration of proteins associated with apoptosis and adenosine monophosphate-activated protein (AMPK) pathway. Transfection was conducted to enforce overexpression of miR-199a or silence of sirtuin 1 (sirt1) which were confirmed by qRT-PCR. Sirt1 protein was quantified by immunoblotting. A luciferase reporter was exploited to confirm the target relationship between miR-199a and sirt1 3'-untranslated region (3'-UTR). We found quercetin mitigated hypoxia-caused viability reduction and apoptosis with restoring apoptosis-associated protein and rescuing phosphorylation of AMPK. Quercetin flattened hypoxia-evoked overexpression of miR-199a. miR-199a abrogated the protective effects of quercetin against hypoxia-elicited damages. Quercetin elevated sirt1 which was repressed by hypoxia, while this effect was slight in miR-199a-overexpressed cells. miR-199a negatively mediated sirt1 expression through directly binding its 3'-UTR. Further, quercetin facilitated the phosphorylation of AMPK by up-regulating sirt1. Collectively, quercetin participated in repressing miR-199a which negatively modulated sirt1. Mechanically, through activating AMPK, quercetin protected cardiomyocytes cells against hypoxia-caused insults. Highlights Quercetin ameliorates hypoxia-evoked apoptosis and blockage of AMPK phosphorylation; The elevated miR-199a level is eased by quercetin, which might be a protective mechanism; Quercetin restores sirt1 level by repressing miR-199a expression; By mediating miR-199a and sirt1, AMPKphosphorylation is fortified by quercetin.

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PMID: 

Nutrients. 2019 Mar 28 ;11(4). Epub 2019 Mar 28. PMID: 30925824

Abstract Title: 

Rice Bran Supplement Containing A Functional Substance, the Novel Peptide Leu-Arg-Ala, has Anti-Hypertensive Effects: A Double-Blind, Randomized, Placebo-Controlled Study.

Abstract: 

The anti-hypertensive effect of processed rice bran (PRB) was recently reported, for which the novel peptide Leu-Arg-Ala (LRA) was identified as the functional substance. The purpose of this study was to assess the anti-hypertensive effects of a rice bran supplement containing PRB in individuals with high-normal blood pressure (systolic blood pressure (SBP): 130⁻139 mmHg and/or diastolic blood pressure (DBP): 85⁻89 mmHg) or grade 1 hypertension (SBP: 140⁻159 mmHg and/or DBP: 90⁻99 mmHg). One hundred individuals with high-normal blood pressure or grade 1 hypertension were recruited to participate in this double-blind, randomized, placebo-controlledstudy. Participants were randomly allocated to the placebo group (= 50) or the test group (n = 50). Each group took four test tablets (43μg LRA/day) or four placebo tablets daily. The decrease in blood pressure in the test group compared with the placebo group was the primary outcome. Adverse events were recorded and hematological/urinary parameters measured to determine the safety of the supplement, which was the secondary outcome.In total, 87 participants completed the study. The SBP of the test group at 12 weeks was significantly lower than that of the placebo group (p = 0.0497). No serious adverse events were observed. Daily consumption of a rice bran supplement containing PRB can safely improve mildly elevated blood pressure.

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PMID: 

Behav Brain Res. 2019 Jun 15 ;372:112023. Epub 2019 Jun 15. PMID: 31212238

Abstract Title: 

Music exposure attenuates anxiety- and depression-like behaviors and increases hippocampal spine density in male rats.

Abstract: 

Epidemiological and clinical studies suggest that early-life stress (ELS) may lead to the development of mental disorders in adulthood. Maternal separation (MS) is a valid animal model of ELS that produces detrimental effects on brain and behavior of experimental animals. Positive environmental stimuli have been shown to counteract the behavioral deficits of ELS and enhance neuroplasticity. Recent data indicate that music may serve as a form of environmental enrichment in experimental animals. However, the underlying mechanisms through which musical enrichment exerts its effects are poorly understood. Male Sprague-Dawley rats were submitted to a 3 h MS protocol during postnatal days (PND) 2-14, while another group was left undisturbed. Half of the animals within each group were exposed from PND 21 to PND 76 for 12 h/day to Mozart K. 448. At approximately three months of age, elevated plus maze procedure, forced swim test and social approach task were applied to test whether music exposure can mitigate the effects of MS stress on animal emotional behaviors. Moreover, we investigated the effects of these treatments on dendritic spine density in the CA1 region of hippocampus. As expected, MS rats showed decreased sociability, increased anxiety- and depressive-like behaviors, and decreased mature dendritic spines in the CA1 region of hippocampus in adulthood. Musical enrichment reversed these effects. Our results suggest that musical enrichment can reverse the negative effects of MS on anxiety, depression, and sociability in adult rats and modulate neuronal plasticity and provide additional data for a new therapeutic intervention to rescue emotional symptoms.

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PMID: 

Food Funct. 2017 Mar 22 ;8(3):935-943. PMID: 28224159

Abstract Title: 

Rice bran constituents: immunomodulatory and therapeutic activities.

Abstract: 

Rice bran, one of the most abundant and valuable byproducts produced during the rice milling process, is of steadily growing interest in recent years due to its potential health benefits. Evidence is rapidly accumulating for the beneficial effects of nutraceuticals. However, the potential benefits of rice bran are found in several of its bioactive ingredients including oils, polysaccharides, proteins, and micronutrients. In addition, a significant advantage of rice bran is that it contains more than 100 antioxidants and several categories of bioactive phytonutrients, such as polyphenols, phytosterols, tocotrienols,γ-oryzanol, B vitamins, minerals, and trace minerals. As an immunomodulator, rice bran has beneficial constituents such as polysaccharides, proteins, and oils. Numerous studies also reported that potent antioxidants in rice bran included immune system enhancing compounds, such as phytosterols, polysaccharides, minerals and trace minerals including magnesium, selenium, zinc, vitamin E, omega-3 fatty acids and several other phytonutrients. We believe that this review will be a valuable resource for more studies on rice barn as a dietary source.

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PMID: 

Molecules. 2019 Jun 6 ;24(11). Epub 2019 Jun 6. PMID: 31174320

Abstract Title: 

Protective Effects of Defatted Sticky Rice Bran Extracts on the Early Stages of Hepatocarcinogenesis in Rats.

Abstract: 

Use of natural products is one strategy to lessen cancer incidence. Rice bran, especially from colored rice, contains high antioxidant activity. Cancer chemopreventive effects of hydrophilic purple rice bran extract (PRBE) and white rice bran extract (WRBE) on carcinogen-induced preneoplastic lesion formation in livers of rats were investigated. A 15-week administration of PRBE and WRBE did not induce hepatic glutathione-transferase placental form (GST-P) positive foci formation as the biomarker of rat hepatocarcinogenesis. PRBE and WRBE at 500 mg/kg body weight significantly decreased number and size of GST-P positive foci in diethylnitrosamine (DEN)-initiated rats. The number of proliferating nuclear antigen positive hepatocytes were also reduced in preneoplastic lesions in both PRBE and WRBE fed DEN-treated rats. Notably, the inhibitory effect on GST-P positive foci formation induced by DEN during the initiation stage was found only in rats treated by PRBE for five weeks. Furthermore, PRBE attenuated the expression of proinflammatory cytokines involving genes including TNF-α, iNOS, and NF-κB. PBRE contained a higher number of anthocyanins and other phenolic compounds and vitamin E. PRBE might protect DEN-induced hepatocarcinogenesis in rats via attenuation of cellular inflammation and cell proliferation. Anthocyanins and other phenolic compounds, as well as vitaminE, might play a role in cancer chemopreventive activity in rice bran extract.

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PMID: 

Saudi Pharm J. 2019 Jul ;27(5):643-649. Epub 2019 Mar 15. PMID: 31297018

Abstract Title: 

Contribution of momilactones A and B to diabetes inhibitory potential of rice bran: Evidence from in vitro assays.

Abstract: 

This study was the first to detect the presence of the two compounds momilactone A (MA) and momilactone B (MB) in rice bran using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). By in vitro assays, both MA and MB exhibited potent inhibitory activities on pancreaticα-amylase and α-glucosidase which were significantly higher than γ-oryzanol, a well-known diabetes inhibitor. Remarkably, MA and MB indicated an effective inhibition on trypsin with the ICvalues of 921.55 and 884.03 µg/mL, respectively. By high-performance liquid chromatography (HPLC), quantities of MA (6.65 µg/g dry weight) and MB (6.24 µg/g dry weight) in rice bran were determined. Findings of this study revealed the α-amylase, α-glucosidase and trypsin inhibitors MA and MB contributed an active role to the diabetes inhibitory potential of rice bran.

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PMID: 

J Diabetes Metab Disord. 2019 Jun ;18(1):89-97. Epub 2019 Mar 9. PMID: 31275879

Abstract Title: 

Rice bran oil ameliorates hepatic insulin resistance by improving insulin signaling in fructose fed-rats.

Abstract: 

Background: Insulin resistance is an inadequate metabolic response of the peripheral tissue to circulating insulin. It plays an important pathophysiological role in type 2 diabetes mellitus. The purpose of the study was to investigate the molecular effects of rice bran oil (RBO) on the gene expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), glucose transporters-4 and 5 (GLUT-4 and 5) in insulin-resistant rats induced by high fructose diet (HFD).Methods: Rats were divided into six groups (10 rats each) as follows: Groups 1 and 2: rats received a standard diet with corn oil or RBO (as the sole source of fat), respectively. Group 3: animals fed on HFD, which was furtherly divided into 2 sub-groups: rats fed HFD either for one (HFD1) or for 2 months (HFD2). Group 4, rats fed HFD containing RBO for 1 month (HFD1 + RBO), while rats in group 5 fed HFD for 30 days then RBO was added to the diet for another 30 days (HFD2 + RBO). Serum levels of glucose and insulin, as well as hepatic gene expression of insulin receptors and glucose transporters were determined. Livers were isolated for histopathological study.Results: HFD induced insulin resistance with a reduction in the hepatic level of insulin receptor and glucose transporters at both protein and molecular levels. Addition of RBO improved the insulin sensitivity and up-regulated the expression of the tested genes.Conclusion: HFD impaired the insulin sensitivity of the hepatocytes by down-regulating the insulin receptor genes. Addition of RBO alleviated all the hazardous effects.

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I want to share with you how CBD has helped my dog.  Meet Darby!!   She is our 11ish year old dachshund mut.  We got her for Christmas in 2008 from Santa (or the SPCA).  So we are not sure of her exact age.  For the past 11 years Darby has been as much a part of our family as any of our kids.  She has always loved to go on walks.  She would get so excited when we would just pick up her leash or mention the word “walk”.  However, a few months ago, we were taking her for a walk and she would not go past our next door neighbor’s house.  She refused to walk any farther and wanted to turn around and go back home.  We didn’t think much of it.  But, a couple of days later the same thing happened again.  We were going to take her for a walk.  She made it to the neighbor’s house and would not go any farther.  Now we knew something was wrong.  This was two walks she has refused to go on.  Over the next couple of days we noticed that her breathing was labored and she had very little energy.  So I took her to the vet.  He diagnosed her with a heart murmur.  With her age he said she was in the beginning stages of heart failure.  But, good news!  There is medication to help the murmur and make the heart function better.  He said the medicine would really help her with her breathing and her energy.  We did notice a little bit of improvement, but not a lot.

A few weeks later, Darby had a seizure one morning.  I really thought she was going to die.  I did not know what was happening so I immediately took her to the vet.  Again, because of her age he said “well, she likely has a brain tumor”.  Apparently, it’s common in dogs her age.  He told us she would have more seizures and we needed to start keeping a log of them.  He said it could be next week or months from now before her next one.  Well it wasn’t even a full week.  Then another one a few days after that.  And then they started happening every day.  And then they started getting longer in duration.  They went from less than a minute to 3 or 4 minutes long.  It was awful to watch.  And Darby’s health was going down hill very quickly.  I knew if her seizures continued like this, she would not be around much longer.  I called the vet back and good news again!!  He said that he wanted to start her on seizure medication right away.

As I was getting ready to head up to the vet’s office to pick up her medication, A thought came to me as if something had smacked me right in the face.  What is the one thing that CBD has been proven to help with and the one thing that the FDA has approved it’s use for?  SEIZURES!!  Duh.  And we sell CBD.  And we have a ton of CBD at our house because we sample everything we sell.  I called the vet back and told him I wanted to try CBD before we start her on seizure medication.  He was a little hesitant and told me he could not recommend that.  But, we finally agreed to try the CBD for a couple of weeks and if no improvement, we would start her on the medication.

I immediately starting giving her CBD drops twice a day with her food.  And GREAT NEWS!!  The CBD has helped my dog!!  She has not had one seizure since I started giving her the drops!!  She went from having them everyday to none!!  And her energy is back and she loves going on walks again!!

I’m not saying that the CBD has cured her seizures or her heart murmur.  But, for now – today, we have our old Darby back.  The Darby with energy that loves to be outside and going for walks.

If you have a dog that is getting up there in age and his or her health is starting to decline, try our CBD products for pets.  CBD helped my dog.  It won’t hurt them.  And maybe, it will improve their quality of life enough that they will be around for a few more years longer then they would without it.

 

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