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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... 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). ...
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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.
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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.
... 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. ...
... 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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Cardiovascular diseases (CVDs) are a significant health burden with an ever-increasing prevalence. They remain the leading causes of morbidity and mortality worldwide. The use of medicinal herbs continues to be an alternative treatment approach for several diseases including CVDs. Currently, there is an unprecedented drive for the use of herbal preparations in modern medicinal systems. This drive is powered by several aspects, prime among which are their cost-effective therapeutic promise compared to standard modern therapies and the general belief that they are safe. Nonetheless, the claimed safety of herbal preparations yet remains to be properly tested. Consequently, public awareness should be raised regarding medicinal herbs safety, toxicity, potentially life-threatening adverse effects, and possible herb–drug interactions. Over the years, laboratory data have shown that medicinal herbs may have therapeutic value in CVDs as they can interfere with several CVD risk factors. Accordingly, there have been many attempts to move studies on medicinal herbs from the bench to the bedside, in order to effectively employ herbs in CVD treatments. In this review, we introduce CVDs and their risk factors. Then we overview the use of herbs for disease treatment in general and CVDs in particular. Further, data on the ethnopharmacological therapeutic potentials and medicinal properties against CVDs of four widely used plants, namely Ginseng, Ginkgo biloba, Ganoderma lucidum, and Gynostemma pentaphyllum, are gathered and reviewed. In particular, the employment of these four plants in the context of CVDs, such as myocardial infarction, hypertension, peripheral vascular diseases, coronary heart disease, cardiomyopathies, and dyslipidemias has been reviewed, analyzed, and critically discussed. We also endeavor to document the recent studies aimed to dissect the cellular and molecular cardio-protective mechanisms of the four plants, using recently reported in vitro and in vivo studies. Finally, we reviewed and reported the results of the recent clinical trials that have been conducted using these four medicinal herbs with special emphasis on their efficacy, safety, and toxicity.
... 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
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
Chapter
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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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Hypertension is one of the most common human diseases, which leads to serious disturbances, such as myocardial infarction and stroke. A decrease in the neuron viability in different parts of the brain in humans with hypertension has been shown by nuclear magnetic resonance spectroscopy (NMRS). Translation of NMRS tools to the clinical practice requires the accumulation of empirical data on neurometabolic changes in a strictly controlled experiment. It is particularly interesting to compare the metabolic parameters of laboratory animals with the normal and high blood pressure maintained under standard conditions on the same diet. In this study, we examined the cortex and hypothalamus metabolites of ISIAH and Wistar male rats at the age of 8–9 weeks. The cortex and hypothalamus metabolites were measured in animals under isoflurane anesthesia using proton magnetic resonance spectroscopy (1Н MRS). Processing the primary data using the Partial Least Squares Discriminant Analysis (PLS-DA) allowed us to identify the main discriminating axis (Y 1) and its variations, which showed the predominance of the excitatory neurometabolites (glutamine and glutamate) over the inhibitory ones (GABA and glycine). In the cortex, the Y 1 axis values were lower in ISIAH rats than in Wistar rats. This indicates a decrease in the cortical excitability in hypertensive animals. In contrast, in the hypothalamus, the Y 1 axis values were higher in ISIAH rats than in Wistar rats, and the predominance of the excitatory neurometabolites was positively correlated to the level of the mean blood pressure, which agrees well with the idea of caudal hypothalamic activation in hypertensive animal models.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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