PMID: 

Front Neurosci. 2019 ;13:1361. Epub 2020 Jan 14. PMID: 32009871

Abstract Title: 

Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential.

Abstract: 

The accumulating knowledge of the host-microbiota interplay gives rise to the microbiota-gut-brain (MGB) axis. The MGB axis depicts the interkingdom communication between the gut microbiota and the brain. This communication process involves the endocrine, immune and neurotransmitters systems. Dysfunction of these systems, along with the presence of gut dysbiosis, have been detected among clinically depressed patients. This implicates the involvement of a maladaptive MGB axis in the pathophysiology of depression. Depression refers to symptoms that characterize major depressive disorder (MDD), a mood disorder with a disease burden that rivals that of heart diseases. The use of probiotics to treat depression has gained attention in recent years, as evidenced by increasing numbers of animal and human studies that have supported the antidepressive efficacy of probiotics. Physiological changes observed in these studies allow for the elucidation of probiotics antidepressive mechanisms, which ultimately aim to restore proper functioning of the MGB axis. However, the understanding of mechanisms does not yet complete the endeavor in applying probiotics to treat MDD. Other challenges remain which include the heterogeneous nature of both the gut microbiota composition and depressive symptoms in the clinical setting. Nevertheless, probiotics offer some advantages over standard pharmaceutical antidepressants, in terms of residual symptoms, side effects and stigma involved. This review outlines antidepressive mechanisms of probiotics based on the currently available literature and discusses therapeutic potentials of probiotics for depression.

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PMID: 

Int Immunopharmacol. 2020 Jan 30 ;81:106217. Epub 2020 Jan 30. PMID: 32007794

Abstract Title: 

Hyperlipidemia-induced lipotoxicity and immune activation in rats are prevented by curcumin and rutin.

Abstract: 

We assessed the effects of curcumin, rutin, and the association of rutin and curcumin in organs of hyperlipidemic rats. Rutin and curcumin have notable antioxidant and anti-inflammatory actions, so we hypothesized that their association would enhance their beneficial effects. Hyperlipidemia results in lipotoxicity and affects several organs. Lipotoxicity is not only an outcome of lipid accumulation in non-adipose tissues but also a result of the hyperlipidemia-associated inflammation and oxidative stress. Wistar rats were treated with rutin and curcumin for 30 days before the induction of acute hyperlipidemia by Poloxamer-407. After 36 h, the animals were euthanized for collection of blood and organs. Untreated hyperlipidemic rats showed higher uric acid and albumin levels in the serum and increased spleen size and ADA activity. Rutin, curcumin and theassociation reduced the spleen size by 20% and ADA activity by 23, 28, and 27%, respectively. Rats pretreated with rutin showed reduced lipid damage in the liver (40%) and the kidney (44%), and the protein damage was also reduced in the liver (75%). The lipid damage was decreased by 40% in the liver, and 56% in the kidney of rats pretreated with curcumin. The association reduced lipid damage by 50% and 36%, and protein damage by 77% and 64% in the liver and kidney, respectively. Rutin better prevented the decrease in the antioxidant defenses, increasing SOD by 34%, CAT by 246% and GST by 84%in the liver, as well as SOD by 119% and GST by 190% in the kidney. Also, analyses of blood and spleen parameters of untreated and pretreated non-hyperlipidemic rats showed no signs of immunotoxicity. Despite showing protective effects, the association did not perform better than the isolated compounds. Here, we showed that rutin and/or curcumin reestablished the immune homeostasis and redox balance disrupted by hyperlipidemia in peripheral organs of rats.

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PMID: 

Mol Biol Rep. 2020 Feb 6. Epub 2020 Feb 6. PMID: 32030599

Abstract Title: 

Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation and apoptosis in rat brain associated with the CREB/BDNF expressions.

Abstract: 

The purpose of the current study was to examine the neuroprotective effect of rutin against colistin-induced neurotoxicity in rats. Thirty-five male Sprague Dawley rats were randomly divided into 5 groups. The control group (orally received physiological saline), the rutin group (orally administered 100 mg/kg body weight), the colistin group (i.p. administered 15 mg/kg body weight), the Col + Rut 50 group (i.p. administered 15 mg/kg body weight of colistin, and orally received 50 mg/kg body weight of rutin), the Col + Rut 100 group (i.p. administered 15 mg/kg body weight of colistin,and orally received 100 mg/kg body weight of rutin). Administration of colistin increased levels of glial fibrillary acidic protein and brain-derived neurotrophic factor and acetylcholinesterase and butyrylcholinesterase activities while decreasing level of cyclic AMP response element binding protein and extracellular signal regulated kinases 1 and 2 (ERK1/2) expressions. Colistin increased oxidative impairments as evidenced by a decrease in level of nuclear factor erythroid 2-related factor 2 (Nrf-2), glutathione, superoxide dismutase, glutathione peroxidase and catalase activities, and increased malondialdehyde content. Colistin also increased the levels of the apoptotic and inflammatoric parameters such as cysteine aspartate specific protease-3 (caspase-3), p53, B-cell lymphoma-2 (Bcl-2), nuclear factor kappa B (NF-κB), Bcl-2 associated X protein (Bax), tumor necrosis factor-α (TNF-α) and neuronal nitric oxide synthase (nNOS). Rutin treatment restored the brain function by attenuating colistin-induced oxidative stress, apoptosis, inflammation, histopathological and immunohistochemical alteration suggesting that rutin supplementation mitigated colistin-induced neurotoxicity in male rats.

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PMID: 

PLoS One. 2020 ;15(2):e0229029. Epub 2020 Feb 14. PMID: 32059038

Abstract Title: 

Gut dysbiosis is prevailing in Sjögren's syndrome and is related to dry eye severity.

Abstract: 

OBJECTIVE: To investigate gut dysbiosis in patients with Sjögren's syndrome (SS) or dry eye syndrome (DES) compared to normal subjects and to evaluate the association of dysbiosis with dry eye severity.METHODS: 10 subjects with SS, 14 subjects with DES and 12 controls were enrolled. Corneal staining, tear break up time (TBUT) and tear secretion were evaluated. Bacterial genomic 16s rRNA from stool samples were analyzed. Main outcomes were microbiome compositional differences among groups and their correlation to dry eye signs.RESULTS: Gut microbiome analysis revealed significant compositional differences in SS compared to controls and DES. In phylum, Bacteriodetes increased, while Firmicutes/Bacteroidetes ratio and Actinobacteria decreased (p

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PMID: 

Curr Opin Neurobiol. 2020 Feb 14 ;62:92-101. Epub 2020 Feb 14. PMID: 32066076

Abstract Title: 

Gut-brain communication in demyelinating disorders.

Abstract: 

Multiple Sclerosis (MS) is an autoimmune demyelinating disorder resulting from the interplay of genetic predisposition and environmental variables, including gut microbiota, diet and life style factors. Here, we first discuss the evidence supporting the effect of early life events, diet and body mass index on the composition of the microbiota, and then review studies on gut dysbiosis conducted in MS patients and in animal models. We address the effect of disease, immunomodulatory therapies, diet and probiotics on enrichment or depletion of gut microbial species. Finally, we discuss the ability of gut bacteria to produce toxins and metabolites which serve as signals for the cross-talk between the gut and the brain.

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PMID: 

Front Cell Infect Microbiol. 2020 ;10:18. Epub 2020 Jan 31. PMID: 32083022

Abstract Title: 

Gut Microbial Dysbiosis Is Associated With Profibrotic Factors in Liver Fibrosis Mice.

Abstract: 

Continuous development will evolve into end-stage liver disease. Profibrotic factors NOX4 and RhoA participate in the activation of HSC and accelerate the development of liver fibrosis. Abnormal intrahepatic metabolism during liver fibrosis interferes with intestinal homeostasis through the liver-gut axis.Wild-type (WT), NOX4 knockout, RhoA expression inhibition C57BL/6 mice were randomly divided into 6 groups as follows: control group, CClgroup, NOX4group, AP group, RhoAi group, and FA group.The results of alpha-diversity suggest that the diversity and abundance of intestinal flora in liver fibrosis mice is lower than that in normal mice, but there is some recovery in liver fibrosis mice with NOX4 or RhoA intervention. The flora structure showed that the intestinal flora of the control group, NOX4group, AP group, RhoAi group, and FA group belonged to one type, while the intestinal flora of the CClgroup belonged to another type. In addition, analysis of the composition of the flora at the level of the phylum and genus also suggested the decline in Firmicutes andcaused by liver fibrosis has partially restore in the liver fibrosis mice with NOX4 or RhoA intervention. In terms of functional prediction, the"Secondary metabolites biosynthesis, transport and catabolism,""Infectious diseases,"and"Xenobiotics biodegradation and metabolism"signaling pathways are mainly enriched in liver fibrosis mice, and the"Energy production and conversion,""Defense mechanisms,"and"Carbohydrate metabolism"signaling pathways are mainly enriched in the NOX4 and RhoA intervention groups.In the case of liver fibrosis, the intestinal flora is disordered, and the disorder is related to NOX4 and RhoA. This study provides theoretical support for a better understanding of the underlying mechanisms of liver fibrosis development.

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PMID: 

Chem Phys Lipids. 2020 Feb 4 ;228:104890. Epub 2020 Feb 4. PMID: 32032570

Abstract Title: 

Role of Rutin Nanoemulsion in Ameliorating Oxidative Stress: Pharmacokinetic and Pharmacodynamics Studies.

Abstract: 

Parkinson's disease is caused due to free radical generation in dopamine neurons leading to oxidative stress induced damage. The aim of this work was to ameliorate the free radical induced oxidative stress in rats by using TPGS (Tocopheryl polyethylene glycol 1000 succinate) loaded rutin nanoemulsion after oral administration. For this purpose, pharmacokinetic and pharmacodynamics studies were performed in albino wistar rats. Various behavioural tests (photoactometer test, rota rod, akinesia and catalepsy) and biochemical estimations for determination of GSH, TBARS and SOD were carried out. The results showed an increase in relative bioavailability of rutin after oral administration of nanoemulsion as compared to pure drug suspension. The AUC and Cof rutin nanoemulsion after oral administration were 1.8-fold and 1.9-fold higher than those of drug suspension respectively. Pharmacodynamic studies have shown good results with the rutin nanoemulsion than pure drug suspension. The rats treated with the rutin nanoemulsion exhibited significantly greater locomotor activity, better muscle coordination and improvement in cataleptic behaviour than the normal and haloperidol-induced rats (p

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PMID: 

Semin Immunopathol. 2020 Feb 18. Epub 2020 Feb 18. PMID: 32072252

Abstract Title: 

Dysbiosis of the gut and lung microbiome has a role in asthma.

Abstract: 

Worldwide 300 million children and adults are affected by asthma. The development of asthma is influenced by environmental and other exogenous factors synergizing with genetic predisposition, and shaping the lung microbiome especially during birth and in very early life. The healthy lung microbial composition is characterized by a prevalence of bacteria belonging to the phyla Bacteroidetes, Actinobacteria, and Firmicutes. However, viral respiratory infections are associated with an abundance of Proteobacteria with genera Haemophilus and Moraxella in young children and adult asthmatics. This dysbiosis supports the activation of inflammatory pathways and contributes to bronchoconstriction and bronchial hyperresponsiveness. Exogenous factors can affect the natural lung microbiota composition positively (farming environment) or negatively (allergens, air pollutants). It is evident that also gut microbiota dysbiosis has a high influence on asthma pathogenesis. Antibiotics, antiulcer medications, and other drugs severely impair gut as well as lung microbiota. Resulting dysbiosis and reduced microbial diversity dysregulate the bidirectional crosstalk across the gut-lung axis, resulting in hypersensitivity and hyperreactivity to respiratory and food allergens. Efforts are undertaken to reconstitute the microbiota and immune balance by probiotics and engineered bacteria, but results from human studies do not yet support their efficacy in asthma prevention or treatment. Overall, dysbiosis of gut and lung seem to be critical causes of the increased emergence of asthma.

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PMID: 

Br J Nutr. 2020 Feb 20:1-28. Epub 2020 Feb 20. PMID: 32077397

Abstract Title: 

Yogurt consumption and colorectal polyps.

Abstract: 

Diet modifies the risk of colorectal cancer (CRC) and inconclusive evidence suggests yogurt may protect against CRC. We analyzed data collected from two separate colonoscopy-based case-control studies. The Tennessee Colorectal Polyp Study (TCPS) and Johns Hopkins Biofilm Study included 5446 and 1061 participants, respectively, diagnosed with hyperplastic polyp (HP), sessile serrated polyp (SSP), adenomatous polyp (AP), or without any polyps. Multinomial logistic regression models were used to derive OR and 95 % CI to evaluate comparisons between cases and polyp-free controls and case-case comparisons between different polyp types. We evaluated the association between frequency of yogurt intake and probiotic use with the diagnosis of colorectal polyps. In the TCPS, daily yogurt intake v. no/rare intake was associated with decreased odds of HP (OR 0·54; 95 % CI 0·31, 0·95) and weekly yogurt intake was associated with decreased odds of AP among women (OR 0·73; 95 % CI 0·55, 0·98). In the Biofilm study, both weekly yogurt intake and probiotic use were associated with a non-significant reduction in odds of overall AP (OR 0·75; 95 % CI 0·54, 1·04) and (OR 0·72; 95 % CI 0·49, 1·06) in comparison to no use, respectively. In summary, yogurt intake may be associated with decreased odds of HP and AP and probiotic use may be associated with decreased odds of AP. Further prospective studies are needed to verify these associations.

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PMID: 

Biomolecules. 2020 Feb 4 ;10(2). Epub 2020 Feb 4. PMID: 32033222

Abstract Title: 

Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells.

Abstract: 

The renal cell carcinoma (RCC) is the most common type of kidney cancer. Identifying novel and more effective therapies, while minimizing toxicity, continues to be fundamental in curtailing RCC. Rutin, a bioflavonoid widely found in nature, has shown promising anticancer properties, but with limited applicability due to its poor water solubility and pharmacokinetics. Thus, the potential anticancer effects of rutin toward a human renal cancer cell line (786-O), while considering its safety in Vero kidney cells, was assessed, as well as the applicability of ionic liquids (ILs) to improve drug delivery. Rutin (up to 50µM) did not show relevant cytotoxic effects in Vero cells. However, in 786-O cells, a significant decrease in cell viability was already observed at 50 µM. Moreover, exposure to rutin caused a significant increase in the sub-G1 population of 786-O cells, reinforcing the possible anticancer activity of this biomolecule. Two choline-amino acid ILs, at non-toxic concentrations, enhanced rutin's solubility/loading while allowing the maintenance of rutin's anticancer effects. Globally, our findings suggest that rutin may have a beneficial impact against RCC and that its combination with ILs ensures that this poorly soluble drug is successfully incorporated into ILs-nanoparticles hybrid systems, allowing controlled drug delivery.

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