PMID: 

Scand J Clin Lab Invest. 2011 Jul ;71(4):330-9. Epub 2011 Mar 17. PMID: 21413848

Abstract Title: 

Insulin induces fatty acid desaturase expression in human monocytes.

Abstract: 

Increasing evidence suggests that fatty acid desaturases, rate-limiting enzymes in unsaturated fatty acid biosynthesis, are important factors in the pathogenesis of lipid-induced insulin resistance. The conversion of dihomogamma linolenic acid (DGLA) into arachidonic acid (AA) in human plasma phospholipids has been shown to be regulated by insulin, suggesting a role for insulin in fatty acid desaturase 1 regulation. However insulin's role in monocyte inflammation associated with obesity and lifestyle disease development is uncertain. We therefore investigated if insulin is able to induce expression of stearoyl-CoA desaturase (SCD,Δ9 desaturase), fatty acid desaturase 1 (FADS1, Δ5 desaturase), and fatty acid desaturase 2 (FADS2, Δ6 desaturase), as well as the sterol regulatory element binding transcription factor 1-c (SREBP-1c) in monocytes. Here, for the first time, we demonstrate that THP-1 monocytes are insulin-responsive in inducing expression of SCD, FADS1, and FADS2 in a time- and dose-dependent manner. Understanding secondary consequences of postprandial hyperinsulinemia may open up new strategies for prevention and/or treatment of obesity-related metabolic complications.

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PMID: 

Biomed Res Int. 2015 ;2015:285135. Epub 2015 Aug 2. PMID: 26301244

Abstract Title: 

Omega-3 PUFAs Lower the Propensity for Arachidonic Acid Cascade Overreactions.

Abstract: 

A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic window which is widened by n-3 nutrients. The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions. Recognizing the factors that predispose the cascade to an unwanted overactivity gives a rational approach for arranging beneficial interactions between the n-3 and n-6 essential nutrients that are initial components of the cascade. Much detailed evidence for harmful cascade actions was collected by pharmaceutical companies as they developed drugs to decrease those actions. A remaining challenge is to understand the factors that predispose the cascade toward unwanted outcomes and create the need for therapeutic interventions. Such understanding involves recognizing the similar dynamics for dietary n-3 and n-6 nutrients in forming the immediate precursors of the cascade plus the more vigorous actions of the n-6 precursor, arachidonic acid, in forming potent mediators that amplify unwanted cascade outcomes. Tools have been developed to aid deliberate day-to-day quantitative management of the propensity for cascade overactivity in ways that can decrease the need for drug treatments.

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PMID: 

Prostaglandins Leukot Essent Fatty Acids. 1998 Mar ;58(3):185-91. PMID: 9610840

Abstract Title: 

Dietary alpha-linolenic acid increases TNF-alpha, and decreases IL-6, IL-10 in response to LPS: effects of sesamin on the delta-5 desaturation of omega6 and omega3 fatty acids in mice.

Abstract: 

Sesamin (a non-fat portion of sesame seed oil) inhibits delta-5 desaturase activity resulting in an accumulation of dihomo-gamma-linolenic acid (DGLA) which can displace arachidonic acid (AA) and decrease the formation of pro-inflammatory mediators. We investigated the effects of consumption of diets containing 0.25wt% sesamin and 15 wt% safflower oil (SO) (providing 12% of the added fat as linoleic acid) or a 15 wt% 2:1 mixture of linseed oil and SO (LOSO) (providing 6% alpha-linolenic acid and 6% linoleic acid) for 3 weeks on the liver membrane fatty acid composition and on the production of prostaglandin (PG) E2, TNF-alpha, IL-6 and IL10 in mice. Consumption of sesamin-supplemented SO and LOSO diets resulted in a significant increase in the levels of 20:3omega6 (DGLA), suggesting that sesamin inhibited delta-5 desaturation of omega6 fatty acids. In animals fed LOSO diets, the levels of alpha-linolenic acid, eicosapentaenoic acid (EPA) and of docosahexaenoic acid (DHA) were elevated with a concomitant decrease of arachidonic acid (AA) in the liver membrane phospholipids. Further, in animals fed LOSO diets with or without sesamin, an increase in the circulating levels of TNF-alpha was associated with a concomitant decrease in PGE2. Despite a lack of differences in the levels of AA, the PGE2 levels were significantly lower in mice fed sesamin-supplemented SO compared to those fed SO alone. Thus, these data suggest that irrespective of the availability of a specific fatty acid as a substrate, through regulating the PGE2 synthesis, the production of TNF-alpha could be modulated.

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PMID: 

Lipids Health Dis. 2017 Aug 14 ;16(1):150. Epub 2017 Aug 14. PMID: 28806965

Abstract Title: 

Decreased circulating dihomo-gamma-linolenic acid levels are associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure.

Abstract: 

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have important roles in the pathogenesis of cardiovascular diseases. However, the clinical significance of omega-6 PUFAs in acute cardiovascular disease remains unknown.METHODS: We enrolled 417 consecutive patients with acute cardiovascular disease admitted to the cardiac intensive care unit at Juntendo University Hospital between April 2012 and October 2013. We investigated the association between serum PUFA levels and long-term mortality. Blood samples were collected after an overnight fast, within 24 h of admission. We excluded patients who received eicosapentaenoic acid therapy and those with malignancy, end-stage kidney disease, chronic hepatic disease, and connective tissue disease.RESULTS: Overall, 306 patients (mean age: 66.4 ± 15.0 years) were analysed. During the follow-up period of 2.4 ± 1.2 years, 50 patients (16.3%) died. The dihomo-gamma-linolenic acid (DGLA) levels, arachidonic acid (AA) levels, and DGLA/AA ratio were significantly lower in the nonsurvivor group than in the survivor group (DGLA: 23.2 ± 9.8 vs. 31.5 ± 12.0 μg/ml, AA: 151.1 ± 41.6 vs. 173.3 ± 51.6 μg/ml, and DGLA/AA: 0.16 ± 0.05 vs. 0.19 ± 0.06, all p 

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PMID: 

Biol Trace Elem Res. 2019 Jul 21. Epub 2019 Jul 21. PMID: 31327124

Abstract Title: 

Selenium-Rich Yeast Mitigates Aluminum-Mediated Testicular Toxicity by Blocking Oxidative Stress, Inhibiting NO Production, and Disturbing Ionic Homeostasis.

Abstract: 

Aluminum (Al) poisoning has been linked to the development of several reproductive system dysfunctions. Dietary supplementation with selenium-rich yeast (SeY) has been shown to prevent a variety of pathologic conditions. In the present study, the potential protect role of SeY on Al-induced testicular toxicity was evaluated, and the possible underlying mechanisms were discussed. Mice were treated with SeY (0.1 mg/kg) and/or Al (10 mg/kg) by oral gavage for 4 weeks. Histopathologic changes were observed in the testes of Al-treated mice. Oxidative stress, ionic disturbances, and the generation of NO systems are believed to have resulted in the observed pathology. Interestingly, SeY supplementation significantly inhibited the Al-induced histopathological and molecular changes and restored these indicators to levels observed in the control animals. These results suggest that SeY exerts a testis-protective effect against Al-induced toxicity through the reduction of oxidative stress, NO production, and the maintenance of ionic homeostasis.

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PMID: 

J Cell Mol Med. 2019 Aug ;23(8):5193-5199. Epub 2019 May 31. PMID: 31148371

Abstract Title: 

Ginkgo biloba extract protects human melanocytes from HO-induced oxidative stress by activating Nrf2.

Abstract: 

Vitiligo is a common skin depigmenting disorder characterized by the loss of functional melanocytes. Its pathogenesis is complicated and oxidative stress plays a critical role in the development of vitiligo. Thus, antioxidant therapy is a promising therapeutic strategy to prevent or even reverse the progression of depigmentation. Ginkgo biloba extract EGb761 has been confirmed to have protective effects on neurons against oxidative stress. Notably, several clinical trials have shown that patients with stable vitiligo achieved repigmentation after taking EGb761. However, the exact mechanism underlying the protective effects of EGb761 on melanocytes against oxidative stress has not been fully elucidated. In the present study, we found that EGb761 effectively protected melanocytes against oxidative stress-induced apoptosis and alleviated the excessive accumulation of reactive oxygen species (ROS) and lipid peroxidation by enhancing the activity of antioxidative enzymes. Furthermore, the antioxidative effect of EGb761 was achieved by activating Nrf2 and its downstream antioxidative genes. In addition, interfering Nrf2 with siRNA abolished the protective effects of EGb761 on melanocytes against oxidative damage. In conclusion, our study proves that EGb761 could protect melanocytes from HO-induced oxidative stress by activating Nrf2. Therefore, EGb761 is supposed to be a potential therapeutic agent for vitiligo.

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PMID: 

Planta Med. 2019 Jul 2. Epub 2019 Jul 2. PMID: 31266069

Abstract Title: 

Neuroprotective Potential of Ginkgo biloba in Retinal Diseases.

Abstract: 

Like other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this,is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion thatextracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy ofin these retinal degenerative processes.

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PMID: 

Am J Chin Med. 2019 Jul 21:1-17. Epub 2019 Jul 21. PMID: 31327236

Abstract Title: 

Pretreatment Attenuates Myocardial Ischemia-Reperfusion Injury via mitoBK.

Abstract: 

extracts (EGb) alleviate myocardial ischemia/reperfusion (MI/R) injury. However, the underlying mechanisms have not yet been characterized. This study aimed to investigate whether activation of large-conductance Ca-activated Kchannels at the inner mitochondrial membrane (mitoBKof cardiomyocytes is involved inextract-mediated cardioprotection. Shuxuening injection (SXNI, 12.5ml/kg/d), a widely prescribed herbal medicine containingextracts in China, or vehicle, was administered to C57BL/6 mice via tail vein injection for one week prior to surgical procedures. The mitoBKblocker paxilline (PAX) (1ml/kg, 115 nM) was administered via tail vein injection 30min prior to the onset of ischemia. The mice were randomly divided into the following groups: Sham, MI/R, MI/R+SXNI, and MI/R+SXNI+PAX. MI/R was induced by ligating the left anterior descending coronary artery for 30min with subsequent reperfusion for 24h. SXNI pretreatment conferred cardioprotective effects against MI/R injury as evidenced by reduced infarct size, improved cardiac function, and improved mitochondrial function. However, these effects were abrogated by co-administration with PAX. In addition, activation of mitoBKbyextract EGb761 reduced hypoxia/reoxygenation (H/R)-induced cardiomyocyte injurythrough the inhibition of mitochondrial fragmentation, restoration of the mitochondrial membrane potential, decreased generation of superoxide, and inhibition of apoptosis which is associated with alleviating mitochondrial Caoverload. These results indicated thatextracts pretreatment protected against MI/R injury via activation of mitoBK.

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PMID: 

Environ Sci Pollut Res Int. 2019 Jul 18. Epub 2019 Jul 18. PMID: 31321719

Abstract Title: 

Ginkgo biloba attenuates aluminum lactate-induced neurotoxicity in reproductive senescent female rats: behavioral, biochemical, and histopathological study.

Abstract: 

Extensive use of aluminum (Al) in industry, cooking utensils, and wrapping or freezing the food items, due to its cheapness and abundance in the environment, has become a major concern. Growing evidence supports that environmental pollutant Al promotes the aggregation of amyloid beta (Aβ) in the brain, which is the main pathological marker of Alzheimer's disease (AD). Further, AD- and Al-induced neurotoxic effects are more common among women following reproductive senescence due to decline in estrogen. Though clinically Ginkgo biloba extract (GBE) has been exploited as a memory enhancer, its role in Al-induced neurotoxicity in reproductive senescent female rats needs to be evaluated. Animals were exposed to intraperitoneal dose (10 mg/kg b.wt) of Al and oral dose (100 mg/kg b.wt.) of GBE daily for 6 weeks. A significant decline in the Al-induced Aβ aggregates was observed in hippocampal and cortical regions of the brain with GBE supplementation, as confirmed by thioflavin (ThT) and Congo red staining. GBE administration significantly decreased the reactive oxygen species, lipid peroxidation, nitric oxide, and citrulline levels in comparison to Al-treated rats. Onthe contrary, a significant increase in the reduced glutathione, GSH/GSSG ratio as well as in the activities of antioxidant enzymes was observed with GBE administration. Based on the above results, GBE prevented the neuronal loss in the hippocampus and cortex, hence caused significant improvement inthe learning and memory of the animals in terms of AChE activity, serotonin levels, Morris water maze, and active and passive avoidance tests. In conclusion, GBE has alleviated the behavioral, biochemical, and histopathological alterations due to Al toxicity in rats. However, molecular studies aregoing on to better understand the mechanism of GBE protection against the environmental toxicant Al exposure. Graphical abstract .

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PMID: 

J Neurogastroenterol Motil. 2019 Jul 1 ;25(3):363-376. PMID: 31327219

Abstract Title: 

Parkinson's Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation.

Abstract: 

The role of the microbiome in health and human disease has emerged at the forefront of medicine in the 21st century. Over the last 2 decades evidence has emerged to suggest that inflammation-derived oxidative damage and cytokine induced toxicity may play a significant role in the neuronal damage associated with Parkinson's disease (PD). Presence of pro-inflammatory cytokines and T cell infiltration has been observed in the brain parenchyma of patients with PD. Furthermore, evidence for inflammatory changes has been reported in the enteric nervous system, the vagus nerve branches and glial cells. The presence ofα-synuclein deposits in the post-mortem brain biopsy in patients with PD has further substantiated the role of inflammation in PD. It has been suggested that the α-synuclein misfolding might begin in the gut and spread"prion like"via the vagus nerve into lower brainstem and ultimately to the midbrain; this is known as the Braak hypothesis. It is noteworthy that the presence of gastrointestinal symptoms (constipation, dysphagia, and hypersalivation), altered gut microbiota and leaky gut have been observed in PD patients several years prior to the clinical onset of the disease. These clinical observations have been supported by in vitro studies in mice as well, demonstrating the role of genetic (α-synuclein overexpression) and environmental (gut dysbiosis) factors in the pathogenesis of PD. The restoration of the gut microbiome in patients with PD may alter the clinical progression of PD and this alteration can be accomplished by carefully designed studies using customized probiotics and fecal microbiota transplantation.

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