Article

Hypotensive and neurometabolic effects of intragastric Reishi ( Ganoderma lucidum ) administration in hypertensive ISIAH rat strain

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Abstract

Background: As the standard clinically used hypotensive medicines have many undesirable side effects, there is a need for new therapeutic agents, especially ones of a natural origin. Purpose: One possible candidate is extract from the mushroom Reishi (Ganoderma lucidum), which is used in the treatment and prevention of many chronic diseases. Study design and methods: To study the effectiveness of Reishi, which grows in the Altai Mountains, as an antihypertensive agent, we intragastrically administered Reishi water extract to adult male hypertensive ISIAH (inherited stress-induced arterial hypertension) rats. Results: After seven weeks, Reishi therapy reduced blood pressure in experimental animals at a level comparable to that of losartan. Unlike losartan, intragastric Reishi introduction significantly increases cerebral blood flow and affects cerebral cortex metabolic patterns, shifting the balance of inhibitory and excitatory neurotransmitters toward excitation. Conclusion: Changes in cerebral blood flow and ratios of neurometabolites suggests Reishi has a potential nootropic effect.

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... Hypertension, or high BP, is a major risk factor for CVD. Ganoderma sp. has been investigated for its potential to regulate BP and maintain cardiovascular homeostasis (Shevelev et al., 2018). Triterpenoids and extract of Ganoderma lingzhi have been shown to modulate RAS, a key regulator of BP. ...
... These polysaccharides have also stimulated the release of vasodilatory factors, such as NO and prostacyclin, which have promoted blood vessel relaxation . In various in vivo studies, G. lucidum supplementation has been associated with significant reductions in both systolic and diastolic BP in hypertensive rats (Shevelev et al., 2018). These findings all in all indicated the potential of Ganoderma sp. as a natural adjunct for managing hypertension and improving cardiovascular health. ...
Chapter
Cardiovascular disease, renowned for its catastrophic implications, currently stands as a significant contributor to global mortality and debilitating health conditions. Its genesis lies in the narrowing of arteries resulting in many dire physical consequences, especially fatal strokes or heart attacks in advanced stages. Primarily attributed to atherosclerosis characterized by the accumulation of plaques composed of fats, cholesterol, and other substances within arteries. These blockages present formidable obstacles to the vital circulation of blood within critical organs such as the lungs, brain, and heart. Recent findings suggest that Ganoderma sp. can act as potential protector being able to lower cholesterol levels, reduce inflammation, enhance blood vessel function, and mitigate free radical damage. The present chapter thus focuses on the ability of Ganoderma sp. as a promising natural agent for the prevention and management of cardiovascular diseases, atherosclerosis, and hypertension. Future studies should aim to elucidate the specific mechanisms and optimal dosages for achieving maximum cardiovascular benefits, with the goal of improving public health and reducing the burden of these prevalent conditions.
... Всего было исследовано 12 метаболитов (Nацетиласпартат, гаммааминомасляная кислота, аланин, аспартат, суммарные холиновые соединения, сумма креатин + фосфокреатин, сумма глу та мин + глутамат, миоинозитол, таурин, глицин, лактат и фосфорилэтаноламин), исходя из текущих технических возможностей. Такой набор нейрометаболитов позволяет дать интегральную оценку нейрональной активности (Hemanth Kumar et al., 2012;Гулевич и др., 2015;Shevelev et al., 2018), поскольку отражает баланс между тормозными (ГАМК) и возбуждающими нейромедиаторами (глутамат + глутамин), содержит маркер жизнеспособности нейронов (Nацетиласпартат), ключевые аминокислоты (аланин, аспартат), модераторы нейропередачи (таурин), фосфатного метаболизма (креатин + фосфокреатин), отражает синтез мембран и пролиферацию клеток (холин, миоинозитол, фосфорилэтаноламин). ...
... Обнаружен ные различия в поведенческих стратегиях крыс на предаторный стресс нашли отражение в уровне нейрометаболитов отдельных структур головного мозга. Полученные нами результаты изучения отдельных метаболитов гиппокампа свидетельствуют о более низком уровне Nаце тиласпартата -метаболита, характеризующего жизнеспособность нейронов в целом (Moffett et al., 2007;Shevelev et al., 2018), у крыс второго фенотипа, реализующих ак тивную поведенческую реакцию (SR), по сравнению как с крысами первого фенотипа, которые демонстрировали пассивную поведенческую реакцию (S) в ответ на предаторный стресс, так и с контрольными животными. Этот результат соотносится с данными работы (Hemanth Kumar et al., 2012) на модели хронического стресса у крыс, где наблюдалось снижение Nацетиласпартата в гиппокам пе. ...
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Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding. 2019;23(5):582-587 (in Russian) Page 587, in Acknowledgements instead of The animals and behavioral testing are supported by the budget project (No. 0324-2019-0041). The MRI study is supported by the budget project (No. 0259-2019-0004). All studies are implemented using the equipment of Center for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (Unique ID# of the project: RFMEFI62117X0015). should read The animals and behavioral testing are supported by the budget project (No. 0324-2019-0041). The MRI study is supported by the budget project (No. 0259-2019-0004). All studies are implemented using the equipment of Center for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (Unique ID# of the project: RFMEFI62117X0015). The study was conducted within the basic part of the state task of the Ministry of Science and Higher Education of the Russian Federation (No. 17.7255.2017/8.9). The original article can be found under DOI 10.18699/VJ19.528.
... G. lucidum has been found to have a hypotensive effect. While this can be beneficial for people with hypertension, it may cause complications for those with already low blood pressure or people taking drugs to lower blood pressure [202]. There is also concern about the quality and purity of G. lucidum supplements, as many products on the market may contain harmful contaminants or low levels of the active ingredients. ...
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Currently, the modeling of complex chemical-physical processes is drastically influencing industrial development. Therefore, the analysis and study of the combustion process of the boilers using machine learning (ML) techniques are vital to increase the efficiency with which this equipment operates and reduce the pollution load they contribute to the environment. This work aims to predict the emissions of CO, CO2, NOx, and the temperature of the exhaust gases of industrial boilers from real data. Different ML algorithms for regression analysis are discussed. The following are input variables: ambient temperature, working pressure, steam production, and the type of fuel used in around 20 industrial boilers. Each boiler's emission data was collected using a TESTO 350 Combustion Gas Analyzer. The modeling, with a machine learning approach using the Gradient Boosting Regression algorithm, showed better performance in the predictions made on the test data, outperforming all other models studied. It was achieved with predicted values showing a mean absolute error of 0.51 and a coefficient of determination of 99.80%. Different regression models (DNN, MLR, RFR, GBR) were compared to select the most optimal. Compared to models based on Linear Regression, the DNN model has better prediction performance. The proposed model provides a new method to predict CO2, CO, NOx emissions, and exhaust gas outlet temperature.
... G. lucidum has been found to have a hypotensive effect. While this can be beneficial for people with hypertension, it may cause complications for those with already low blood pressure or people taking drugs to lower blood pressure [202]. There is also concern about the quality and purity of G. lucidum supplements, as many products on the market may contain harmful contaminants or low levels of the active ingredients. ...
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Ganoderma lucidum is a versatile mushroom. Polysaccharides and triterpenoids are the major bioactive compounds and have been used as traditional medicinal mushrooms since ancient times. They are currently used as nutraceuticals and functional foods. G. lucidum extracts and their bioactive compounds have been used as an alternative to antioxidants and antimicrobial agents. Secondary metabolites with many medicinal properties make it a possible substitute that could be applied as immunomodulatory, anticancer, antimicrobial, anti-oxidant, anti-inflammatory, and anti-diabetic. The miraculous properties of secondary metabolites fascinate researchers for their development and production. Recent studies have paid close attention to the different physical, genetic, biochemical, and nutritional parameters that potentiate the production of secondary metabolites. This review is an effort to collect biologically active constituents from G. lucidum that reveal potential actions against diseases with the latest improvement in a novel technique to get maximum production of secondary metabolites. Studies are going ahead to determine the efficacy of numerous compounds and assess the valuable properties achieved by G. lucidum in favor of antimicrobial and antioxidant outcomes.
... A 5 µl culture medium was introduced to animals from the control group according to a similar scheme. Tumor size was measured in vivo on a horizontal tomograph with a magnetic field strength of 11.7 Tesla (Biospec 117/16, Bruker, USA) [40]. After that, animals of experimental and corresponding control groups were removed from the experiment by decapitation on days 7 and 21 after injection. ...
... Additionally, the extract showed a beneficial effect on cerebral blood flow and the regulation of the balance between inhibitory and excitatory neurotransmitters. These properties indicate the nootropic potential of the extract studied [115]. Compared with the aqueous extract, the extract prepared from G. lucidum using proteases isolated from this species showed a stronger antihypertensive activity, which was used to hydrolyze proteins and obtain an ADR (autodigested Reishi extract) extract. ...
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This paper presents the current state of knowledge on the biological activity and possible medicinal applications of selected species of the genus Ganoderma: Ganoderma adspersum (Schulzer) Donk, Ganoderma applanatum (Pers.) Pat., Ganoderma carnosum Pat., Ganoderma lucidum (Curtis) P. Karst., Ganoderma pfeifferi Bres., Ganoderma resinaceum Boud. These inedible, wood-decaying fungi are pathogens that cause the enzymatic decomposition of wood. They are a valued natural medicinal resource and have been used in traditional Far Eastern medicine for centuries. Research conducted on these species using modern analytical methods has led to advances in knowledge of the potential therapeutic use of compounds isolated not only from basidiocarps but also from biomass obtained by in vitro methods. Recent pharmacological studies have confirmed the known traditional uses of these species, elucidated previously unknown mechanisms of biological action, and found evidence of new biological activities, such as anticancer, cytotoxic, antiallergic, and neuroprotective activities. Furthermore, the article updated the state of knowledge on the general mycological characteristics of these species.
... Each group consisted of 10 individuals. The dynamics of the tumor growth was estimated by means of T2-weighted images [15]. The experiments were carried out in compliance with the principles of humanity according to directive 86/609/EEC of the European Community. ...
... G. lucidum has been recorded in the oldest Chinese herbal encyclopedia, called Shen-Nong-Ben-Cao-Jing ("The Herbal Classic of the Divine Plowman") [5], edited during the Han Dynasty in China in about 2700 BC, and used in Oriental traditional medicine. Nowadays, it is utilized due to its beneficial effects, including antitumor [6], anti-angiogenic [7], anti-inflammatory [8], anti-herpetic [9], anti-microbial [10], antihypertensive [11], hypocholesterolemic [12], anti-histamine [13], anti-complement [14], hepatoprotective [15], and radioprotective [3] among other properties [16], this last effect being detected in the extracts and in isolated polysaccharide components [17]. The use of radioprotective compounds in research are applied in a radioactive environment, such as in space exploration, for individuals handling nuclear emergencies, radiation workers, and individuals subjected to diagnostic and therapeutic radiation exposures, as the compounds can minimize the effects of singlestrand breaks, double-strand breaks (DSB), base damage and DNA-protein cross-links [18]. ...
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For millennia, naturopaths and physicians have used Ganoderma lucidum (reishi mushroom) for its diverse therapeutic properties, as recorded in the oldest Chinese herbal encyclopedia. Indeed, a radioprotective effect has been reported in the isolated components of its extracts. A systematic review and meta-analyses (PRISMA) was conducted in March 2020, searching databases including PubMed, Scopus, Embase, and Google Scholar, along with Clinical Trials. The inclusion criteria were ex vivo, in vitro, and in vivo studies, with full texts in English, conducted to determine the radioprotective benefits of G. lucidum, or reports in which ionizing radiation was used. From a total number of 1109 records identified, 15 full text articles were eligible, none of them were clinical trials. In vivo studies reveal the efficiency of G. lucidum aqueous extracts of polysaccharides and triterpenes in mice exposed to γ-rays. In plasmid, they can reduce radiation damage as an increment of the open circular form, as well as increase the DNA extension, as shown in vitro studies. Ex vivo studies conducted in human blood cells show the radioprotective effect of β-glucan of aqueous extract of G. lucidum, nevertheless, its implementation as radioprotector to humans is in need of further clinical research studies.
... With regard to regulation of high BP, a study conducted on adult male hypertensive rats that received G. lucidum water extracts intra-gastrically for seven weeks found that the experimental rats BP was reduced to a level comparable to that of rats on losartan (angiotensin II receptor antagonist) (Shevelev et al., 2018) G. lucidum to the Clinic Antioxidants are potentially therapeutic substances that can be used to prevent atherosclerosis as well as a variety of other diseases. Several in vitro and in vivo preclinical studies have shown that G. lucidum constituents possess antioxidant activities, but evidence for such activities in human subjects was lacking. ...
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... Une expérience menée sur un coeur isolé de rat, montre également que Ganoderma lucidum diminue la nécrose des cellules cardiaques et réduit la contracture lors de la reprise de perfusion (Lazukova et al., 2015). Chez le rat sujet à l'hypertension artérielle héréditaire, le reishi abaisse le niveau de tension artérielle (Shevelev et al., 2018). ...
Thesis
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Medicinal mushrooms have been used for several hundred years, mainly in Asian countries, for the treatment of various pathologies. More recently, they have been used in the treatment of cancer. As part of this thesis, we are particularly interested in the lingzhi mushroom (Ganoderma lucidum) also called immortality fungus, for its anticancer properties. We therefore reported on the mechanisms of action of both the total extracts of Ganoderma lucidum and the two main bioactive molecules groups, i.e., polysaccharides and triterpenes. Their efficiencies have been demonstrated through in vitro tests and clinical studies. Although these natural compounds have been shown to be effective as a standard therapy treatment in the treatment of cancer (used as monotherapy or in combination with radiotherapy or chemotherapy) in Japan and China for over 30 years, it is fundamental to mention that they can also have significant side effects requiring advices of uses for human health. RESUME : Les champignons médicinaux sont utilisés depuis plusieurs centaines d'années, principalement dans les pays asiatiques, pour le traitement de différentes pathologies. Plus récemment, ils ont été utilisés dans le traitement du cancer. Dans le cadre de cette thèse, nous nous sommes particulièrement intéressés au ganoderme luisant (Ganoderma lucidum) également appelé champignon de l’immortalité, pour ses propriétés anticancéreuses. Nous avons donc étudié les mécanismes d’action à la fois des extraits totaux de Ganoderma lucidum et des deux principaux groupes de molécules bioactives : les polysaccharides et les triterpènes. Leurs efficacités ont été mises en évidence au travers de tests in vitro et d’études cliniques. Bien que ces composés naturels aient prouvé leur efficacité en tant que traitement de support aux thérapeutiques standards dans le traitement du cancer (utilisations en monothérapie ou en association avec la radiothérapie ou la chimiothérapie) au Japon et en Chine depuis plus de 30 ans, il est fondamental de mentionner qu’ils peuvent également présenter des effets indésirables non négligeables nécessitant des conseils d’utilisations pour la santé humaine. MOTS-CLES : Cancer, Ganoderma lucidum, mécanismes d’action, polysaccharides, triterpènes
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Hypertension is one of the most common human diseases. This disease leads to serious disturbances such as myocardial infarction and stroke. Due to the development of nuclear magnetic resonance spectroscopy (NMRS), a decrease in neuron viability in different parts of the brain in humans with hypertension has been shown. Translation of NMRS tools to the clinic requires the accumulation of empirical data about neurometabolic changes in a strictly controlled experiment. It is particularly interesting to compare the metabolic parameters of laboratory animals with normal and high blood pressure kept in the standard conditions on exactly the same diet. In this study, cortex and hypothalamus metabolites of ISIAH and Wistar male rats at the age of 8–9 weeks were examined. Cortex and hypothalamus metabolites were measured in animals under isoflurane anesthesia using proton magnetic resonance spectroscopy (1 Н MRS). Processing of primary data using Partial least squares Discriminant Analysis (PLS-DA) allowed us to identify the main discriminating axis (Y 1), its variations reflecting the predominance of excitatory neurometabolites (glutamine and glutamate) over inhibitory ones (GABA and glycine). In the cortex, the values of the Y 1-axis were lower in ISIAH than in Wistar rats. This fact indicates a decrease in cortical excitability in hypertensive animals. By contrast, in the hypothalamus, the values of the Y 1-axis were higher in ISIAH than in Wistar rats and the predominance of excitatory neurometabolites positively correlated with the level of mean blood pressure, which agrees well with the view of caudal hypothalamic activation in hypertensive animal models.
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Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (designed as MAK), which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis) induced by hypoxia/ischemia (H/I) in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2 for 20 min) and subsequent reoxygenation. Pretreatment with MAK (1 g/kg, p.o.) for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice.
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Reishi (Ganoderma lingzhi) has been used as a traditional medicine for millennia. However, relatively little is known about this mushroom's proteins and their bioactivities. In this study, we used reishi's own proteases to hydrolyze its protein and obtained auto-digested reishi (ADR) extract. The extract was subjected to in vitro assays and administered to spontaneous hypertensive rats (SHRs) to determine its potential for use as a hypotensive medication. Bioassay-guided fractionation and de novo sequencing were used for identifying the active compounds. After 4 h administration of ADR, the systolic pressure of SHRs significantly decreased to 34.3 mmHg (19.5% change) and the effect was maintained up to 8 h of administration, with the decrease reaching as low as 26.8 mmHg (15% reduction–compare to base line a decrease of 26.8 mmHg is less than a decrease of 34.3 mmHg so it should give a smaller % reduction). Eleven peptides were identified and four of them showed potent inhibition against ACE with IC 50 values ranging from 73.1 μM to 162.7 μM. The results showed that ADR could be a good source of hypotensive peptides that could be used for antihypertensive medication or incorporation into functional foods.
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Ganoderma lucidum has been purported as a potent remedy in the treatment and prevention of several ailments, including hypertension. This study aimed to explore the anti-ACE potential of protein fractions from the mycelia of G. lucidum. Ganoderma lucidum mycelia were cultivated by submerged fermentation in a liquid medium containing brown sugar and spent brewer's yeast. Intracellular proteins were fractionated from mycelia crude water extract by ammonium sulphate precipitation, and their angiotensin converting enzyme inhibitory activity was evaluated. The potential anti-ACE protein fractions were further separated by RP-HPLC and characterised using proteomics platforms. Preliminary result demonstrated that the mycelia crude water extract inhibited ACE at IC50 value of 1.134 +/- 0.036 mg/mL. Following protein fractionation and HPLC purification, the presence of highly potential anti-ACE proteins with the IC50 values less than 200 mug/mL was detected. Characterisation of these proteins demonstrated the presence of four different antihypertensive-related proteins involved in the regulation of blood pressure through different mechanisms. This study suggests that the mycelia of G. lucidum has high potential in lowering blood pressure level due to the presence of several antihypertensive-related proteins such as cystathionine beta synthase-like protein, DEAD/DEAH box helicase-like protein, paxillin-like protein, and alpha/beta hydrolase-like protein.
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The effects of a fermentation filtrate of Ganoderma lucidum (FGL) on carbon tetrachloride (CCl(4))-induced hepatic fibrosis were investigated in rats. Male Sprague-Dawley rats were orally administered with FGL (20 or 100 mg/kg) for 33 days, and orally administered with CCl(4) (1.0 mL/kg; 2 mL/kg of 50% in corn oil) at 3-day intervals 1 h after FGL treatment. Body and liver weights, blood and histopathological findings in accordance with hydroxyproline concentrations were analyzed. Chronic exposure to CCl(4) reduced the body weight gain, but increased liver weights and fibrosis, resulting in 3.35-fold increase in hydroxyproline level. Although FGL did not significantly reduce the CCl(4)-induced body and liver weight changes, it attenuated the increases in the hepatic fibrosis and hydroxyproline contents. Taken together, it is suggested that FGL might prevent hepatic fibrosis, and that FGL or its ingredient could be a potential candidate for the prevention of chronic hepatic disorders.
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Plant volatiles (PVOCs) are important targets for studies in natural products, chemotaxonomy and biochemical ecology. The complexity of PVOC profiles often limits research to studies targeting only easily identified compounds. With the availability of mass spectral libraries and recent growth of retention index (RI) libraries, PVOC identification can be achieved using only gas chromatography coupled to mass spectrometry (GCMS). However, RI library searching is not typically automated, and until recently, RI libraries were both limited in scope and costly to obtain. To automate RI calculation and lookup functions commonly utilised in PVOC analysis. Formulae required for calculating retention indices from retention time data were placed in a spreadsheet along with lookup functions and a retention index library. Retention times obtained from GCMS analysis of alkane standards and Koeberlinia spinosa essential oil were entered into the spreadsheet to determine retention indices. Indices were used in combination with mass spectral analysis to identify compounds contained in Koeberlinia spinosa essential oil. Eighteen compounds were positively identified. Total oil yield was low, with only 5 ppm in purple berries. The most abundant compounds were octen-3-ol and methyl salicylate. The spreadsheet accurately calculated RIs of the detected compounds. The downloadable spreadsheet tool developed for this study provides a calculator and RI library that works in conjuction with GCMS or other analytical techniques to identify PVOCs in plant extracts.
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This study was conducted to determine the effects of depression and/or insomnia on masked hypertension (MHT) compared with other types of HT and on variability in home-measured blood pressure (HBP) and clinic BP (CBP). Three hundred and twenty-eight hypertensives (132 women) aged 68±10 years were classified into four BP types: controlled HT (CHT), white-coat HT, MHT and sustained HT (SHT), based on CBP (140/90 mm Hg) and morning HBP (135/85 mm Hg) measurements. A score of ⩾16 on the Center for Epidemiologic Studies Depression Scale (CES-D) was defined as depression. The mean values and s.d. of BP were calculated from measurements taken during the 14 consecutive days just before the CES-D evaluation. Compared with the CHT group, the risk of depression was 2.77-fold higher in the SHT group and even higher in the MHT group (7.02-fold). The association between depression and MHT was augmented in the presence of insomnia and was somewhat stronger in women. A HBP variability index defined as s.d./mean BPs in both morning and night time was significantly higher in MHT than in the other BP types, whereas that of CBP was not. Both morning and night-time HBP variability were significantly higher in depressive patients than in non-depressives. These suggest that depression is associated with MHT and that increases both morning and night-time HBP variability but not CBP variability. Physicians should be mindful of mental stresses such as depression in their hypertensive patients when forming strategies to control BP over the diurnal cycle.Hypertension Research advance online publication, 2 July 2015; doi:10.1038/hr.2015.75.
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Background The medications produced from natural products are widely used as prophylactics for sickness induced by alcohol consumption. One such prophylactic is produced from the Reishi mushroom, Ganoderma lucidum. Because of the antioxidant properties of these preparations, we expect neuroprotective prophylactic effects of Reishi-based medications in alcohol-treated animals.Methods The Reishi (R) suspension was produced as water extract from Altaian mushrooms. Sprague–Dawley male rats were separated into the following 3 experimental groups: Group A + R received R (6 days per week) starting 1 week before alcohol exposure, and during the next 3 weeks, they received both R and alcohol; group A received alcohol; and group C received water. At the end of experiment, we determined the metabolic profile using proton magnetic resonance spectroscopy (1H MRS) of the brain cortex and phosphorus magnetic resonance spectroscopy of the liver. Additionally, the blood cells were collected, and the serum biochemistry and liver histology were performed after euthanasia.ResultsPartial least squares discriminant analysis processing of the brain 1H MRS gave 2 axes, the Y1 axis positively correlated with the level of taurine and negatively correlated with the level of lactate, and the Y2 axis positively correlated with the content of GABA and glycine and negatively correlated with the sum of the excitatory neurotransmitters, glutamate and glutamine. The Y1 values reflecting the brain energetics for the A + R group exceeded the corresponding values for groups C and A. The maximal level of Y2 reflecting the prevalence of inhibitory metabolites in the brain was observed in the rats exposed to alcohol. Moderate alcohol consumption did not cause significant pathological changes in the livers of the experimental animals. However, 20 days of alcohol consumption significantly increased the number of binuclear hepatocytes compared to the control. This effect was mitigated in the rats that received the Reishi extract.Conclusions Regular administration of the Reishi suspension improved the energy supply to the brain cortex and decreased the prevalence of inhibitory neurotransmitters that are characteristic of alcohol consumption. The alcohol-induced increase in liver proliferation was significantly suppressed by regular administration of the G. lucidum water suspension.
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High-dimensional data common in genomics, proteomics, and chemometrics often contains complicated correlation structures. Recently, partial least squares (PLS) and Sparse PLS methods have gained attention in these areas as dimension reduction techniques in the context of supervised data analysis. We introduce a framework for Regularized PLS by solving a relaxation of the SIMPLS optimization problem with penalties on the PLS loadings vectors. Our approach enjoys many advantages including flexibility, general penalties, easy interpretation of results, and fast computation in high-dimensional settings. We also outline extensions of our methods leading to novel methods for non-negative PLS and generalized PLS, an adoption of PLS for structured data. We demonstrate the utility of our methods through simulations and a case study on proton Nuclear Magnetic Resonance (NMR) spectroscopy data.
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In vivo proton magnetic resonance spectroscopy ((1) H MRS) of outbred stock ICR male mice (originating from the Institute of Cancer Research) was used to study the brain (hippocampus) metabolic response to the pro-inflammatory stimulus and to the acute deficiency of the available energy, which was confirmed by measuring the maximum oxygen consumption. Inhibition of glycolysis by means of an injection with 2-deoxy-d-glucose (2DG) reduced the levels of gamma-aminobutyric acid (GABA, p < 0.05, in comparison with control, least significant difference (LSD) test), N-acetylaspartate (NAA, p < 0.05, LSD test) and choline compounds, and at the same time increased the levels of glutamate and glutamine. An opposite effect was found after injection with bacterial lipopolysaccharide (LPS) - a very common pro-inflammatory inducer. An increase in the amounts of GABA, NAA and choline compounds in the brain occurred in mice treated with LPS. Different metabolic responses to the energy deficiency and the pro-inflammatory stimuli can explain the contradictory results of the brain (1) H MRS studies under neurodegenerative pathology, which is accompanied by both mitochondrial dysfunction and inflammation. The prevalence of the excitatory metabolites such as glutamate and glutamine in 2DG treated mice is in good agreement with excitation observed during temporary reduction of the available energy under acute hypoxia or starvation. In turn, LPS, as an inducer of the sickness behavior, which was manifested as depression, sleepiness, loss of appetite etc., shifts the brain metabolic pattern toward the prevalence of the inhibitory neurotransmitter GABA. Copyright © 2014 John Wiley & Sons, Ltd.
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Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by transverse aortic constriction, leading to alterations typical of Alzheimer disease, such as amyloid plaques, neuroinflammation, blood-brain barrier dysfunction, and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer disease of hypertensive mice. We focused on receptor for advanced glycation end products (RAGE) that critically regulates Aβ transport at the blood-brain barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE upregulation in brain vessels of the cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal Aβ deposition. The increased RAGE expression in transverse aortic coarctation mice was induced by increased circulating advanced glycation end products and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an advanced glycation end product inhibitor or antioxidant prevented the development of Alzheimer traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal Aβ deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer disease.
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Diets consisting of food ingredients of both plant and animal origin contain a complex mixture of sterols in the lipid fraction. Analysis of these complex mixtures of sterols is generally accomplished by capillary column GC and GC–MS. A very low polarity liquid phase (methylsilicone) and medium polarity columns of various dimensions are used for the separation and quantitation of sterols. However, these columns may not be able to separate some of the sterols in the mixture. The objective of this study was to accomplish the complete separation of a complex mixture of sterols by GC. In order to achieve this objective, a fused-silica capillary column (14% cyanopropyl-phenyl-methylpolysiloxane) of low/medium polarity was used. Excellent separation of campesterol and campestanol, and sitosterol, sitostanol and Δ5-avenasterol was achieved. In addition to GC resolution, a few critical points for the analysis of sterols are presented.
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In an effort to understand the mechanism of cardiovascular actions of Ganoderma lucidum which was cultivated in Korea, the mycelium was isolated for a large-scale culture. Water extract of the mycelia was evaluated for its cardiovascular activity in anesthetized rabbits and rats. The left femoral artery and vein were cannulated for the measurement of arterial pressure and subsequent delivery of drugs. The left kidney was exposed retroperitoneally and a branch of the renal nerve was used to integrate renal efferent or afferent nerve activities. The extract decreased systolic and diastolic blood pressure, which was accompanied by an inhibition of renal efferent sympathetic nerve activity. The extract did not decrease heart rate in these animals, although there was clear hypotension in the extract dose dependent manner. This suggests that the hypotension induced by the treatment of the extract was secondary to the primary effect of the extract in the central nerve system, which suppressed the sympathetic outflow. Therefore we concluded that the mechanism of hypotensive action of Ganoderma lucidum was due to its central inhibition of sympathetic nerve activity.
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The LCModel method analyzes an in vivo spectrum as a Linear Combination of Model spectra of metabolite solutions in vitro. By using complete model spectra, rather than just individual resonances, maximum information and uniqueness are incorporated into the analysis. A constrained regularization method accounts for differences in phase, baseline, and lineshapes between the in vitro and in vivo spectra, and estimates the metabolite concentrations and their uncertainties. LCModel is fully automatic in that the only input is the time-domain in vivo data. The lack of subjective interaction should help the exchange and comparison of results. More than 3000 human brain STEAM spectra from patients and healthy volunteers have been analyzed with LCModel. N-acetylaspartate, cholines, creatines, myo-inositol, and glutamate can be reliably determined, and abnormal levels of these or elevated levels of lactate, alanine, scyllo-inositol, glutamine, or glucose clearly indicate numerous pathologies. A computer program will be available.
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A-II exerts its activity on various target tissues by binding to its receptors. The discovery of local RASs and A-II receptors within various tissues has generated interest in the clinical usefulness of RAS inhibition by directly blocking the action of A-II at the receptor level. Different A-II receptor subtypes have been identified and subsequently termed AT1 and AT2. AT1-receptor subtypes are the predominant receptor subtypes existing in most organs and, by coupling to a transmembrane G protein, seem to be the main subtypes participating in the vasoactive responses of A-II.
  • O B Shevelev
O.B. Shevelev et al. Phytomedicine 41 (2018) 1-6
Brain metabolites of ISIAH and Wistar rats. Vavilovskii Zhurnal Genetiki i Selektsii -Vavilov
  • O B Shevelev
  • A A Seryapina
  • A L Markel
  • M P Moshkin
Shevelev, O.B., Seryapina, A.A., Markel, A.L., Moshkin, M.P., 2015b. Brain metabolites of ISIAH and Wistar rats. Vavilovskii Zhurnal Genetiki i Selektsii -Vavilov J. Genet. Breed. 19 (4), 427-431.
  • B Shevelev
B. Shevelev et al. Phytomedicine 41 (2018) 1-6