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Effects of omega-3 supplementation on components of the endocannabinoid system and metabolic and inflammatory responses in adipose and liver of peripartum dairy cows

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Journal of Animal Science and Biotechnology 2023年第1期14卷 378-389页

作者： Gitit Kra Jayasimha Rayalu Daddam Uzi Moallem Hadar Kamer Radka Kočvarova Alina Nemirovski GAndres Contreras Joseph Tam Maya Zachut Department of Ruminant Science Institute of Animal SciencesARO Volcani InstituteRishon LeZionIsrael. Department of Animal Science The Robert H.Smith Faculty of AgricultureFood and EnvironmentThe Hebrew University of JerusalemRehovotIsrael. Obesity and Metabolism Laboratory The Institute for Drug ResearchSchool of PharmacyFaculty of MedicineThe Hebrew University of JerusalemJerusalemIsrael. Department of Large Animal Clinical Sciences College of Veterinary MedicineMichigan State UniversityEast LansingMichiganUSA.

Background:Dietary supplementation of omega-3 fatty acids can reduce the activation of the endocannabinoid system(ECS)by decreasing the availability of arachidonic acid,thus lowering endocannabinoids(e CBs)levels.The ECS is a modulator of energy metabolism,stress response and inflammation in mammals,yet there is little information on the roles of the ECS in transition dairy cows.During the periparturient period,the adipose tissue and liver are the main metabolic organs that participate in the adaptations of dairy cows to onset of lactation;however,exceeded adipose tissue lipolysis and accumulation of lipids in the liver have adverse effects on cows'physiology.Here we aimed to examine whether omega-3 supplementation during the transition period will modulate ECS activation and affect metabolic and inflammatory indices in postpartum dairy cows,by supplementing twenty-eight transition Holstein dairy cows with either saturated fat(CTL)or encapsulated flaxseed oil(FLX).Components of the ECS,metabolic and inflammatory markers were measured in blood,liver,and subcutaneous adipose tissue.Results:FLX supplementation reduced feed intake by 8.1%(P<0.01)and reduced plasma levels of arachidonic acid(by 44.2%;P=0.02)and anandamide(by 49.7%;P=0.03)postpartum compared to CTL.The m RNA transcription levels of the cannabinoid receptor 1(CNR1/CB1)tended to be lower(2.5 folds)in white blood cells of FLX than in CTL(P=0.10),and protein abundance of ECS enzyme monoacylglycerol lipase was higher in peripheral blood mononuclear cells of FLX than in CTL(P=0.04).In adipose tissue,palmitoylethanolamide levels were lower in FLX than in CTL(by 61.5%;P=0.02),relative m RNA transcription of lipogenic genes were higher,and the protein abundance of cannabinoid receptor 2(P=0.08)and monoacylglycerol lipase(P=0.10)tended to be higher in FLX compared to CTL.Hepatic 2-arachidonoylglycerol tended to be higher(by 73.1%;P=0.07),and interlukin-6 m RNA transcription level was 1.5 folds lower in liver of FLX than in CTL(P=0.03).Conclusions:Nutritional sup

关键词： Adipose Dairy cows endocannabinoid system Liver Omega-3

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Role of cannabinoids and the endocannabinoid system in modulation of diabetic cardiomyopathy

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World Journal of Diabetes 2022年第5期13卷 387-407页

作者： Mona F El-Azab Ahmed E Wakiel Yossef K Nafea Mahmoud E Youssef Department of Pharmacology and Toxicology Faculty of PharmacySuez Canal UniversityIsmailia 41522Egypt Program of Biochemistry McMaster UniversityHamilton L8S 4L8OntarioCanada Department of Pharmacology and Biochemistry Delta University for Science and TechnologyMansoura 35511New CairoEgypt

Diabetic complications,chiefly seen in long-term situations,are persistently deleterious to a large extent,requiring multi-factorial risk reduction strategies beyond glycemic control.Diabetic cardiomyopathy is one of the most common deleterious diabetic complications,being the leading cause of mortality among diabetic patients.The mechanisms of diabetic cardiomyopathy are multi-factorial,involving increased oxidative stress,accumulation of advanced glycation end products(AGEs),activation of various pro-inflammatory and cell death signaling pathways,and changes in the composition of extracellular matrix with enhanced cardiac fibrosis.The novel lipid signaling system,the endocannabinoid system,has been implicated in the pathogenesis of diabetes and its complications through its two main receptors:Cannabinoid receptor type 1 and cannabinoid receptor type 2,alongside other components.However,the role of the endocannabinoid system in diabetic cardiomyopathy has not been fully investigated.This review aims to elucidate the possible mechanisms through which cannabinoids and the endocannabinoid system could interact with the pathogenesis and the development of diabetic cardiomyopathy.These mechanisms include oxidative/nitrative stress,inflammation,accumulation of AGEs,cardiac remodeling,and autophagy.A better understanding of the role of cannabinoids and the endocannabinoid system in diabetic cardiomyopathy may provide novel strategies to manipulate such a serious diabetic complication.

关键词： Δ9-tetrahydrocannabinol Autophagy Cannabinoid receptors Diabetic cardiomyopathy endocannabinoid system Inflammation

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Physical exercise and synaptic protection in human and pre-clinical models of multiple sclerosis

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Neural Regeneration Research 2024年第8期19卷 1768-1771页

作者： Federica Azzolini Ettore Dolcetti Antonio Bruno Valentina Rovella Diego Centonze Fabio Buttari Unit of Neurology IRCCS NeuromedPozzilliItaly Department of system Medicine University of Tor VergataRomeItaly Synaptic Immunopathology Lab Department of Systems MedicineTor Vergata UniversityRomeItaly

In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.

关键词： disease-modifying behaviour endocannabinoid system long-term potentiation multiple sclerosis neuroplasticity neuroprotection physical exercise synaptopathy

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A proposed modulatory role of the endocannabinoid system on adipose tissue metabolism and appetite in periparturient dairy cows

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Journal of Animal Science and Biotechnology 2021年第3期12卷 995-1007页

作者： Madison N.Myers Maya Zachut Joseph Tam G.Andres Contreras Department of Large Animal Clinical Sciences College of Veterinary MedicineMichigan State UniversityEast LansingMI 48824USA Department of Ruminant Science Institute of Animal SciencesAgricultural Research Organization/Volcani Center7505101 Rishon LeZionIsrael Obesity and Metabolism Laboratory The Institute for Drug ResearchSchool of PharmacyFaculty of MedicineThe Hebrew University of Jerusalem9112001 JerusalemIsrael

To sustain the nutrient demands of rapid fetal growth,parturition,and milk synthesis,periparturient dairy cows mobilize adipose tissue fatty acid stores through lipolysis.This process induces an inflammatory response within AT that is resolved as lactation progresses;however,excessive and protracted lipolysis compounds the risk for metabolic and inflammatory diseases.The suppression of lipolytic action and inflammation,along with amplification of adipogenesis and lipogenesis,serve as prospective therapeutic targets for improving the health of periparturient dairy cows.Generally,the activation of cannabinoid receptors by endocannabinoids enhances adipogenesis and lipogenesis,suppresses lipolysis,and increases appetite in mammals.These biological effects of activating the endocannabinoid system open the possibility of harnessing the endocannabinoid system through nutritional intervention in dairy herds as a potential tool to improve dairy cows’health,although much is still to be revealed in this context.This review summarizes the current knowledge surrounding the components of the endocannabinoid system,elaborates on the metabolic effects of its activation,and explores the potential to modulate its activity in periparturient dairy cows.

关键词： Adipogenesis Adipose tissue Dairy cow health endocannabinoids endocannabinoid system Lipogenesis Lipolysis

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Medicinal cannabis products for the treatment of acute pain

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World Journal of Clinical Cases 2023年第12期11卷 2670-2676页

作者： Marco Fiore Aniello Alfieri Sveva Di Franco Stephen Petrou Giovanni Damiani Maria Caterina Pace Department of Women Child and General and Specialized SurgeryUniversity of Campania“Luigi Vanvitelli”Naples 80138Italy Department of Emergency Medicine University of California San FranciscoSan FranciscoCA 94143United States Department of Biomedical Surgicaland Dental SciencesUniversity of MilanMilan 20122Italy

For thousands of years,medicinal cannabis has been used for pain treatment,but its use for pain management is still controversial.Meta-analysis of the literature has shown contrasting results on the addition of cannabinoids to opioids compared with placebo/other active agents to reduce pain.Clinical studies are mainly focused on medicinal cannabis use in chronic pain management,for which the analgesic effect has been proven in many studies.This review focuses on the potential use of medical cannabis for acute pain management in preclinical studies,studies on healthy subjects and the few pioneering studies in the clinical setting.

关键词： Cannabis Cannabinoids endocannabinoid system 2-arachidonoylglycerol Anandamide Analgesia Acute pain

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Should gastroenterologists prescribe cannabis? The highs, the lows and the unknowns

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World Journal of Clinical Cases 2023年第18期11卷 4210-4230页

作者： Sonia Samuel Mark Michael Micheal Tadros Department of Internal Medicine Albany Medical CenterAlbanyNY 12208United States Department of Gastroenterology and Hepatology Albany Medical CenterAlbanyNY 12208United States

Cannabis,commonly known as marijuana,is a drug extracted from the Cannabis plant known for its psychotropic and medicinal properties.It has been used for healing purposes during ancient times,although its psychoactive components led to its restricted use in medicine.Nonetheless,cannabis is found to have modulatory effects on the endocannabinoid system exhibiting its medicinal role in the gastrointestinal(GI)system.Emerging animal and human studies demonstrate the influential effects of cannabis on a variety of GI diseases including inflammatory bowel disease,motility disorders and GI malignancies.It also has a regulatory role in GI symptoms including nausea and vomiting,anorexia,weight gain,abdominal pain,among others.However,both its acute and chronic use can lead to undesirable side effects such as dependency and addiction,cognitive impairment and cannabinoid hyperemesis syndrome.We will discuss the role of cannabis in the GI system as well as dosing strategies to help guide gastroenterologists to assess its efficacy and provide patient counseling before prescription of medical marijuana.

关键词： Marijuana cannabis endocannabinoid system Side effects Gastrointestinal disorders

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Cannabis and male reproduction:Impact on offspring via sperm epigenome

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BIOCELL 2022年第2期46卷 301-304页

作者： PAOLA GRIMALDI Department of Biomedicine and Prevention University of Rome Tor VergataRome00133Italy

Cannabis is the most widely used drug in theWestern societies particularly among adolescent and young adults.Epidemiological studies demonstrate that men use cannabis more frequently than women with higher risk in developing cannabis-related disorders.Although the direct adverse effects of cannabis on male reproductive functions have been studied both in humans and animal models,the possible long-term risks for the health of the users and their offspring are still an area of active research.

关键词： Cannabis endocannabinoid system Sperm Paternal inheritance

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Mechanisms of repetitive transcranial magnetic stimulation for antidepression: Evidence from preclinical studies

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World Journal of Psychiatry 2020年第10期10卷 223-233页

作者： Di Luan Ming-Ge Zhao Ya-Chen Shi Ling Li Yu-Jia Cao Hai-Xia Feng Zhi-Jun Zhang Department of Neurology Affiliated Zhongda HospitalResearch Institution of NeuropsychiatrySchool of MedicineSoutheast UniversityNanjing 210009Jiangsu ProvinceChina Department of Nursing School of MedicineSoutheast UniversityNanjing 210009Jiangsu ProvinceChina Department of Psychology Xinxiang Medical UniversityXinxiang 453003Henan ProvinceChina Mental Health Center Zhejiang University School of MedicineHangzhou 310013Zhejiang provinceChina

This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies,including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway,anti-oxidative stress effects,enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway,increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway,and reducing the activity of the hypothalamic-pituitary-adrenocortical axis.We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning,shallow depth of stimulation,and difficulty in elucidating the neural circuit mechanism up-and down-stream of the stimulation target brain region.

关键词： Repetitive transcranial magnetic stimulation Anti-depressant mechanisms Nuclear factor-e2-related factor 2 endocannabinoid system Monoamine oxidase Hypothalamic-pituitary-adrenocortical axis Brain derived neurotrophic factor

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Comparison between cannabidiol and sertra⁃line in modulation of post-traumatic stress dis⁃order-like behaviors and fear memory in mice

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中国药理学与毒理学杂志 2021年第9期35卷 680-681页

作者： HAN Xiao SONG Xian-kui SONG Da-ke XIE Guan-bo GUO Hong-yan WU Ning LI Jin Beijing Key Laboratory of Neuropsychopharma-cology State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Institute of Pharmacology and ToxicologyBeijing 100850China Shanxi Medical University School and Hospital of Stomatology Taiyuan 030001China

OBJECTIVE Post-traumatic stress disorder(PTSD)is characterized by poor adapta⁃tion to a traumatic experience and disturbances in fear memory regulation,and currently lacks effective medication.Cannabidiol(CBD)is the primary component of the Cannabis sativa plant;it does not have any psychoactive effects and has been implicated in modulating fear learning in mammals.The present study investigated the effect of CBD on PTSD-like behaviors in a mouse pre-shock model,the effect of CBD in the modulation of trauma-related fear memory,a crucial process leading to core symptoms of PTSD.METHODS Pre-shock model was applied in which mice were submitted to training with two days of 0.8 mA×12 times of foot-shock,and PTSD-like behaviors was evaluated during 3 and 26 d,including freezing time to the conditioned context,open field test,elevated plus maze test and social interaction test.RESULTS CBD(10 mg·kg^(-1))administration alleviated main PTSD-like symptoms in the mouse pre-shock model by attenuating trauma-related fear memory,decreasing anxiety-like behavior,and increasing social interaction behavior.However,sertraline(15 mg·kg^(-1))was only effective when adminis⁃tered throughout the test period.Furthermore,CBD reduced the formation,retrieval,and recon⁃solidation of trauma-related fear memory,whereas sertraline only reduced fear-memory retrieval.Neither CBD nor sertraline influenced the acquisi⁃tion of trauma-related fear memory.CONCLU⁃SION CBD produced anti-PTSD-like actions in mice,and could disrupt trauma-related fear mem⁃ory by interfering with multiple aspects of fear memory processing in mice.These findings indi⁃cate that CBD may be a promising candidate for treating PTSD.

关键词： post-traumatic stress disorder can⁃nabidiol sertraline trauma-related fear memory processing endocannabinoid system

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