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Therapeutic effects of garlic in cardiovascular atherosclerotic disease

Chinese Journal of natural Medicines 2019年第10期17卷 721-728页

作者： Igor A.Sobenin Veronika A.Myasoedova Maria I.Iltchuk ZHAnG Dong-Wei alexander n.orekhov national Medical Research Center of Cardiology 121552 MoscowRussian Federation Institute of General Pathology and Pathophysiology 125315 MoscowRussian Federation Research Institute of Threpsology and Healthy Lo ngevity Plekhanov Russian University of Economics117997 MoscowRussian Federation Diabetes Research Center Traditional Chinese Medicine SchoolBeijing University of Chinese MedicineBeijing 100029China Institute of Human Morphology 117418 MoscowRussian Federation

Garlic(Allium sativum) is a widely known medicinal plant, potential of which remains to be fully evaluated. Its wide-range beneficial effects appear to be relevant for treatment and prevention of atherosclerosis and related diseases. It is generally believed that garlic-based preparations are able to improve lipid profile in humans, inhibit cholesterol biosynthesis, suppress low density lipoprotein oxidation, modulate blood pressure, suppress platelet aggregation, lower plasma fibrinogen level and increase fibrinolytic activity, thus providing clinically relevant cardioprotective and anti-atherosclerotic effects. It is important to assess the level of evidence available for different protective effects of garlic and to understand the underlying mechanisms. This information will allow adequate integration of garlic-based preparations to clinical practice. In this review, we discuss the mechanisms of anti-atherosclerotic effects of garlic preparations, focusing on antihyperlipidemic, hypotensive, anti-platelet and direct anti-atherosclerotic activities of the medicinal plant. We also provide an overview of available meta-analyses and a number of clinical trials that assess the beneficial effects of garlic.

关键词： Atherosclerosis Dyslipidemia Cardiovascular disease natural medicines Garlic

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Chlorogenic acid ameliorates heart failure by attenuating cardiomyocyte ferroptosis

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Journal of Traditional Chinese Medical Sciences 2024年第2期11卷 191-198页

作者： Kai Huang Fanghe Li Jiayang Tang Haiyin Pu Vasily Sukhorukov alexander n.orekhov Shuzhen Guo School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing102488China Laboratory of Angiopathology Institute of General Pathology and PathophysiologyRussian Academy of Medical SciencesMoscow125315Russia

Objective:To elucidate the effects of chlorogenic acid(CGA),a bioactive polyphenol compound prevalent in traditional Chinese medicine and various foods,including Lonicera japonica Thunb.(Jin Yin Hua),Eucommia ulmoides Oliv.(Du Zhong Ye),tea,and coffee,on cardiomyocyte ferroptosis and heart ***: We assessed the effect of CGA on cardiac function using a mouse model of heart failure induced by transverse aortic constriction(TAC).These indicators included the left ventricular ejection fraction(LVEF),fractional shortening(LVFS),end-systolic volume(LVESV),end-diastolic volume(LVEDV),end-systolic diameter(LVESD),and end-diastolic diameter(LVEDD).An isoprenaline hydrochloride(ISO)-induced H9c2 cardiomyocyte cell model was also established,and the cells were treated with various concentrations of *** assess the effect of CGA on ferroptosis in cardiomyocytes,we measured cell viability and evaluated the levels of intracellular reactive oxygen species(ROS),ferrous ions(Fe^(2+)),and lipid peroxidation using fluorescent *** clarify the ferroptosis signaling pathway regulated by CGA,western blotting was used to examine the expression of ferroptosis biomarkers,specifically solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),in H9c2 cardiomyocytes and mouse myocardial ***: CGA significantly enhanced cardiac performance indices such as LVEF,LVFS,LVESV,LVEDV,LVESD,and LVEDD.H9c2 cardiomyocytes exposed to ISO showed decreased cell viability and increased ROS levels,Fe^(2+)content,and lipid peroxidation ***,CGA treatment significantly ameliorated these ***,in both H9c2 cardiomyocytes and myocardial tissue obtained from mice with TAC,CGA increased the expression of ferroptosis-related proteins,including SLC7A11 and ***: CGA has the potential to enhance cardiac function and diminish lipid peroxidation and ROS levels in cardiomyocytes via the SLC7A11/GPX4 signaling *** process allev

关键词： Chlorogenic acid Heart failure Ferroptosis H9c2 cardiomyocyte Traditional Chinesemedicine

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Atherosclerosis originating from childhood:Specific features

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Journal of Biomedical Research 2024年第3期38卷 233-240页

作者： Anastasia V.Poznyak Alexey A.Yakovlev MikhailА.Popov Elena B.Zhigmitova Vasily n.Sukhorukov alexander n.orekhov Institute for Atherosclerosis Research Moscow 121609Russia Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology Moscow 109240Russia Department of Cardiac Surgery Moscow Regional Research and Clinical InstituteMoscow 129110Russia Laboratory of Angiopathology Institute of General Pathology and PathophysiologyMoscow 125315Russia

Atherosclerosis is extremely ***,it is considered a disease of older people,who most often experience problems with the heart and blood *** much attention from the scientific community has been paid to studying the association between aging and atherosclerosis,as well as its consequences,there is evidence that atherosclerosis occurs at an early *** may form both during intrauterine development and in *** plays an important role in childhood atherosclerosis,along with previous infectious diseases and excess weight of both the child and the *** the present review,we examined the development of atherosclerosis and the prerequisites in childhood.

关键词： atherosclerosis childhood pediatrics cardiovascular disease

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Intracellular Cholesterol Retention—new Target for Direct Anti-Atherosclerotic Therapy

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Open Journal of Endocrine and Metabolic Diseases 2013年第4期3卷 9-17页

作者： alexander n. orekhov Institute for Atherosclerosis Research Skolkovo Innovative Center Moscow Russia

Accumulation of cholesterol in arterial cells, intracellular cholesterol retention, may be responsible for all major manifestations of atherosclerosis on a cellular level. Previously we have shown that intracellular cholesterol retention is the principal event in the genesis of atherosclerotic lesions. This allows us to consider cellular retention of cholesterol as a novel target for anti-atherosclerotic therapy. In this case the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review describes our approach based on the use of cultured human arterial cells for the development of direct anti-atherosclerotic therapy. We use natural products as the basis of promising drugs for anti-atherosclerotic therapy. Using natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured cells. Our knowledge of the mechanisms of atherosclerosis is the foundation on which we have developed drugs that have a direct anti-atherosclerotic effect, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with allicor or inflaminat has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Karinat prevents the development of carotid atherosclerosis in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinical practice. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and the efficacy of novel drugs developed on the basis our methodology.

关键词： Allicor Anti-Atherosclerotic Therapy Atherosclerosis Cell Culture Drugs Imaging natural Products

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Direct anti-atherosclerotic therapy preventing intracellular cholesterol retention

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Health 2013年第7期5卷 11-18页

作者： alexander n. orekhov Institute for Atherosclerosis Research Skolkovo Innovative Center Moscow Russia

The key initiating process in atherogenesis is the subendothelial cholesterol retention, which is both necessary and sufficient to provoke lesion initiation. Retention of cholesterol transported by low density lipoprotien (LDL) in subendothelial cells of arterial wall, is an absolute requirement for lesion development. This allows us to consider intracellular cholesterol retention as a novel target for anti-atherosclerotic therapy. In this case, the target is not the level of blood cholesterol but the level of cholesterol in vascular cells. This review summarizes the results of our basic studies shedding light on the mechanisms of intracellular cholesterol retention. We describe our cellular models to search for anti-atherosclerotic agents and demonstrate the use of these models for the development of anti-atherosclerotic drugs. We use natural products as the basis of anti-atherosclerotic drugs because anti-atherosclerotic therapy should be long-term or even lifelong. Using cellular models and natural products, we have developed an approach to prevent intracellular cholesterol retention in cultured subendothelial aortic cells. We have developed drugs that reduce intracellular cholesterol retention, namely Allicor on the basis of garlic powder, anti-inflammatory drug Inflaminat (calendula, elder, and violet) possessing anti-cytokine activity and phytoestrogen-rich drug Karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid). Treatment with Allicor or Inflaminat caused regression of carotid atherosclerosis in asymptomatic men. Karinat prevented the development of new atherosclerotic plaques in postmenopausal women. Thus, the main findings of our basic research have been successfully translated into clinics. As a result, this translation, a novel approach to the development of anti-atherosclerotic therapy, has been established. Our clinical trials have confirmed the suitability of innovative approach and

关键词： Allicor Anti-Atherosclerotic Therapy Atherosclerosis Cell Culture Drugs Imaging Intracellular Cholesterol Retention natural Products

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Intimal pericytes as the second line of immune defence in atherosclerosis

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World Journal of Cardiology 2015年第10期7卷 583-593页

作者： Ekaterina A Ivanova Yuri V Bobryshev alexander n.orekhov Department of Development and Regeneration Biomedical Sciences Group KU LeuveLeuvenBelgium Faculty of Medicine School of Medical Sciences University of New South Wales School of Medicine University of Western Sydney Laboratory of Angiopathology Institute of General Pathology and Pathophysiology Russian Academy of Sciences Institute for Atherosclerosis Research Skolkovo Innovative Center Department of Biophysics Faculty of Biology Lomonosov Moscow State University

Inflammation plays an essential role in the development of atherosclerosis. The initiation and growth of atherosclerotic plaques is accompanied by recruitment of inflammatory and precursor cells from the bloodstream and their differentiation towards pro-inflammatory phenotypes. This process is orchestrated by the production of a number of pro-inflammatory cytokines and chemokines. Human arterial intima consists of structurally distinct leaflets, with a proteoglycan-rich layer lying immediately below the endothelial lining. Recent studies reveal the important role of stellate pericyte-like cells(intimal pericytes) populating the proteoglycan-rich layer in the development of atherosclerosis. During the pathologic process, intimal pericytes may participate in the recruitment of inflammatory cells by producing signalling molecules and play a role in the antigen presentation. Intimal pericytes are also involved in lipid accumulation and the formation of foam cells. This review focuses on the role of pericytelike cells in the development of atherosclerotic lesions.

关键词： Atherosclerosis Arteries Intima Immune-inflammator

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How big can a walking fish be?A theoretical inference based on observations on four land-dwelling fish genera of South Vietnam

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Integrative Zoology 2022年第5期17卷 849-878页

作者： alexander n.KUZnETSOV Borissiak Paleontological Institute Russian Academy of SciencesMoscowRussia

Comparative study of terrestrial locomotion of 4ﬁsh genera including Anabas,Channa,Clarias,and Monopterus,was performed in experimental setting with the substrate surface of wet *** special adaptations for terrestrial locomotion were ***ﬁsh uses for propulsion on land what it already ***-shaped Monopterus crawls by body undulations in a serpentine or sidewinding technique,the latter of which was not previously observed beyond *** other 3ﬁsh genera walk by body oscillations using stiff appendages as *** they are located anteriorly,as the serrate operculum in Anabas and the preaxial spine of the pectoralﬁn in Clarias,the propulsion is termed prolocomotor,when posteriorly,as the spiny analﬁn in Channa—*** is the heaviestﬁsh walking out of water in our days,quite comparable in size withﬁrst Devonian tetrapods Acan-thostega and Tulerpeton.A theoretical calculation is suggested for the upper size limit of aﬁsh capable of terrestrial walking without special locomotor *** should be roughly 20 cm in the vertical dimension of the trunk,which is just a little above the known size of Devonian tetrapodomorphﬁshes Panderichthys and *** metalocomotor walking technique of Channa is suggested as the closest extant model for terrestrial locomotion at theﬁsh-tetrapod *** major difference is that the metalocomotor propulsor in Channa is represented by the analﬁn,while in tetrapodomorphs by the pelvicﬁ*** sprawled pelvicﬁns were advantageous in respect of reduced requirement for side-to-side tail swinging.

关键词： ﬁsh-tetrapod transition metalocomotor propulsion prolocomotor propulsion snakehead

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A novel strategy of smart manipulation by micro-scale oscillatory networks of the reactionary zones for enhanced extreme thrust control of the next-generation solid propulsion systems

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Defence Technology（防务技术） 2018年第5期14卷 635-642页

作者： alexander n.Lukin Bldg.9 Tupik ZvezdniyTuapseKrasnodar TerritoryRU 352808Russian Federation

The main aim of this research is to get a better knowledge and understanding of the micro-scale oscillatory networks behavior in the solid propellants reactionary zones. Fundamental understanding of the micro-and nano-scale combustion mechanisms is essential to the development and further improvement of the next-generation technologies for extreme control of the solid propellant thrust. Both experiments and theory confirm that the micro-and nano-scale oscillatory networks excitation in the solid propellants reactionary zones is a rather universal phenomenon. In accordance with our concept,the micro-and nano-scale structures form both the fractal and self-organized wave patterns in the solid propellants reactionary zones. Control by the shape, the sizes and spacial orientation of the wave patterns allows manipulate by the energy exchange and release in the reactionary zones. A novel strategy for enhanced extreme thrust control in solid propulsion systems are based on manipulation by selforganization of the micro-and nano-scale oscillatory networks and self-organized patterns formation in the reactionary zones with use of the system of acoustic waves and electro-magnetic fields, generated by special kind of ring-shaped electric discharges along with resonance laser radiation. Application of special kind of the ring-shaped electric discharges demands the minimum expenses of energy and opens prospects for almost inertia-free control by combustion processes. nano-sized additives will enhance self-organizing and self-synchronization of the micro-and nano-scale oscillatory networks on the nanometer scale. Suggested novel strategy opens the door for completely new ways for enhanced extreme thrust control of the solid propulsion systems.

关键词： Solid propulsion systems Extreme thrust control Reactionary zones Micro-scale oscillatory networks Self-organized wave patterns Energy-releasing areas

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new characterizations of finite supersoluble groups

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Science China Mathematics 2008年第5期51卷 827-841页

作者： alexander n SKIBA Department of Mathematics Gomel State University of F.Skorina

Let A be a subgroup of a group G and X a nonempty subset of G. A is called an X-semipermutable subgroup of G if A has a supplement T in G such that for every subgroup T 1 of T there exists an element x ∈ X such that ... 详细信息

关键词： finite groups supplement 2-maximal subgroups X-semipermutable supersoluble groups 20D10

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Mitochondrial dysfunction and mitochondrial DnA mutations in atherosclerotic complications in diabetes

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World Journal of Cardiology 2012年第5期4卷 148-156页

作者： Dimitry A Chistiakov Igor A Sobenin Yuri V Bobryshev alexander n.orekhov Department of Medical nanobiotechnology Pirogov Russian State Medical University117997 MoscowRussia Institute for Atherosclerosis Research Skolkovo Innovative Centre121609 MoscowRussia Institute of General Pathology and Pathophysiology Russian Academy of Medical Sciences125315 MoscowRussia Russian Cardiology Research and Production Complex 121552 MoscowRussia Faculty of Medicine School of Medical SciencesUniversity of New South WalesNSW 2052SydneyAustralia

Mitochondrial DnA(mtDnA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair *** explains an increased mutation rate of mtDnA that results in heteroplasmy,e.g.,the coexistence of the mutant and wild-type mtDnA molecules within the same *** diabetes mellitus,glycotoxicity,advanced oxidative stress,collagen cross-linking,and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction,which in turn further contributes to the oxidative damage of the diabetic vascular wall,endothelial dysfunc-tion,and atherosclerosis.

关键词： Mitochondrial DnA Mutation Heteroplasmy Atherosclerosis Diabetes Oxidative stress Ultrastructure

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