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Role of polyphenols in epilepsy: from the perspective of gut microbiota

Food Science and Human Wellness 2024年

作者： Xiaoxue Xu Jian Shi Yinsi Tang Guiyang Cai Chao Ma Wuyang Wang Rui Feng Tomasz Boczek Zhenwei He Feng Guo Department of Pharmaceutical toxicology， School of Pharmacy， China Medical University Shenyang Department of Neurology， the First Hospital of China Medical University Department of Pharmacy， the Fourth Affiliated Hospital of China Medical University Department of Gastroenterology， the Fourth Affiliated Hospital of China Medical University Department of Obstetrics and Gynecology， Shengjing Hospital of China Medical University Key Laboratory of Structure-Based drug Design & Discovery of Ministry of Education， School of Pharmaceutical Engineering， Shenyang Pharmaceutical University Jiangsu Province Key Laboratory of Anesthesiology， Xuzhou Medical University Department of Molecular Neurochemistry， Medical University of Lodz Department of Neurology， the Fourth Affiliated Hospital of China Medical University

Epilepsy is a devastating neurological condition that affects over 70 million people worldwide. Apart from idiopathic epilepsy， numerous diseases have been reported to cause secondary epilepsy. Polyphenols， ubiquitously existing in fruits and vegetables， has become a promising neuroprotective candidate against multiple neurological abnormalities due to its interplay with gut microbiome composed of the bacterial population in gastrointestinal system. This bioactive compound is also being tested for the management of epileptogenesis. However， there is still insufficient evidence from mechanistic studies to demonstrate the causal relationship between anti-epileptic effect of polyphenols and microbial alteration. In this review， we provide the brief overview of epilepsy， polyphenols and gut microbiota. We then analysis the association of polyphenols and gut microbiota particularly in the epilepsy and symptomatic seizures-induced by epilepsy-related disorders. We also discuss the possibility for the combined application with probiotics to improve the bioavailability and bioaccessibility of polyphenols for expanding its anti-epileptic function. We finally summarize the therapeutic potential of anti-seizure polyphenols through affecting gut microbiome， and propose that the anti-epileptic effect of polyphenols may be tightly relevant to intestinal bacterial flora for overcoming epilepsy and its comorbidities simultaneously. Therefore， the dietary polyphenols targeting specific bacteria may achieve the outcome of ‘one stone， two birds’.

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The Role of toxicology in Evaluating Marketing Applications for Prescription drug Products in the united States

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毒理学杂志 2005年第S1期 169-170页

作者： Kenneth L Hastings,P.H.,D.A.B.T. Associate Director Office of New drugs Center for drug Evaluation and Research US Food and drug Administration Associate Director Office of New drugs Center for drug Evaluation and Research US Food and drug Administration Dr. Associate Director Office of New drugs Center for drug Evaluation and Research US Food and drug Administration

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Hydroxychloroquine in SARS-CoV-2 infection:Understanding the misadventure

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Journal of Acute Disease 2024年第2期13卷 45-52页

作者： David Banji Otilia J F Banji Department of Pharmacology&toxicology College of PharmacyJazan UniversitySaudi Arabia Department of Clinical Pharmacy College of PharmacyJazan UniversitySaudi Arabia

The widespread outbreak of SARS-CoV-2 was declared a public health emergency by the World Health Organization and various governments *** prompted the implementation of stringent infection control measures to curb the spread of the *** this,the medical community faced the challenge of treating the virus without specific therapies or a vaccine,leading to reliance on empirical treatment *** this context,hydroxychloroquine,an antimalarial and antirheumatic drug,gained attention as a potential treatment *** its theoretical benefits,such as inhibiting viral entry,reducing inflammation,and modulating immune responses,empirical studies yielded inconsistent *** indicated a potential for symptom relief,while others showed no significant improvement in patient *** initial enthusiasm waned as the lack of substantial evidence led to revoking its Emergency Use Authorization,and several clinical trials were prematurely *** review in question critically examines the factors contributing to the ineffectiveness of hydroxychloroquine in treating SARS-CoV-2 infection,highlighting the complexities of drug repurposing during a rapidly evolving pandemic.

关键词： SARS-CoV-2 Hydroxychloroquine Pharmacogenomics TLR signaling Cardiotoxicity

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Salvianolic acid A attenuates ischemia reperfusion induced rat brain damage by protecting the blood brain barrier through MMP-9 inhibition and anti-inflammation

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Chinese Journal of Natural Medicines 2018年第3期16卷 184-193页

作者： ZHANG Wen SONG Jun-Ke ZHANG Xue ZHOU Qi-Meng HE Guo-Rong XU Xiao-Na Yan Rong ZHOU Wen-Xia DU Guan-Hua Beijing Key Laboratory of drug Target Identification and drug Screening Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Department of Neuroimmunopharmacology Beijing Institute of Pharmacology and Toxicology State Key Laboratory of Toxicology and Medical Countermeasures

Salvianolic acid A （SAA） is a water-soluble component from the root of Salvia Miltiorrhiza Bge, a traditional Chinese medicine, which has been used for the treatment of cerebrovascular diseases for centuries. The present study aimed to determine the brain protective effects of SAA against cerebral ischemia reperfusion injury in rats, and to figure out whether SAA could protect the blood brain barrier （BBB） through matrix metallopeptidase 9 （MMP-9） inhibition. A focal cerebral ischemia reperfusion model was induced by middle cerebral artery occlusion （MCAO） for 1.5-h followed by 24-h reperfusion. SAA was administered intravenously at doses of 5, 10, and 20 ***-l. SAA significantly reduced the infarct volumes and neurological deficit scores. Immunohistochemical analyses showed that SAA treatments could also improve the morphology of neurons in hippocampus CA1 and CA3 regions and increase the number of neurons. Western blotting analyses showed that SAA downregulated the levels of MMP-9 and upregulated the levels of tissue inhibitor of metalloproteinase 1 （TIMP-1） to attenuate BBB injury. SAA treatment significantly prevented MMP-9-induced degradation of ZO-1, claudin-5 and occludin proteins. SAA also prevented cerebral NF-κB p65 activation and reduced inflammation response. Our results suggested that SAA could be a promising agent to attenuate cerebral ischemia reperfusion injury through MMP-9 inhibition and anti-inflammation activities.

关键词： Salvianolic acid A Ischemia MCAO Blood brain barrier NF-κB MMP-9

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Safety Evaluation of a Potent Tetanus Vaccine (250 Lf) in Guinea Pigs (Cavia procellus)

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Biomedical and Environmental Sciences 1990年第3期3卷 364-371页

作者： N.SETHI R.K.SRIVASTAVA R.K.SINGH S.SRIVASTAVA Division of toxicology Central Drug Research Institute Lucknow-226001 India

A subacute toxicity study of a potent tetanus toxoid (250 Lf) was carried out in guinea *** toxoid was injected subcutaneously at the nape of the neck at dose levels of 1.0, *** 2.0 ml in Groups Ⅱ. Ⅲ. and Ⅳ, *** the controls (Group Ⅰ) 2.0 ml of aluminum phosphate suspension was given in each *** evaluations of body weight, food/water intake, general observable behavior, *** blood chemistry in toxoid-injected guinea pigs were similar to those in control guinea ***, the toxoid did not cause any side effects up to four times the dose proposed for humans.1990 Academic Press, Inc.

关键词： Cavia procellus Safety Evaluation of a Potent Tetanus Vaccine Lf in Guinea Pigs

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Biliary excretion and enterohepatic circulation of thienorphine and its glucuronide conjugate in rats

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Acta Pharmaceutica Sinica B 2012年第2期2卷 174-180页

作者： Jingting Deng Xiaomei Zhuang Guolin Shen Hua Lin Zehui Gong Laboratory of drug metabolism Beijing Institute of Pharmacology and ToxicologyBeijing 100850China

Thienorphine(TNP)is a new partial opioid agonist currently developed as a promising drug candidate with the intended clinical indication for the treatment of opioid *** pharmacokinetic profile and biliary excretion of TNP and its glucuronide conjugate(TNP-Glu)were investigated after oral administration of TNP in *** concentrations of TNP and TNP-Glu were simultaneously quantified using a LC-MS/MS method.A double peak phenomenon was observed in TNP plasma concentration–time curves with the secondary peak appeared at 6–8 h.A slower decline of plasma concentrations in the terminal phase was observed for TNP with T1/2 of 7.01 ***-Glu was the predominant component in rat plasma and *** plasma level was about 10 times higher than TNP and the 24 h accumulative bile excretion rate was 23%.Enterohepatic circulation of TNP and TNP-Glu was evaluated using a paired rat *** bile-donor rats,no double-peak was detected and the elimination half life of TNP was significantly shortened(3.71 h)when compared to intact rats(7.01 h,Pdrug and the metabolite,*** deconjugation of the glucuronide conjugate and the reabsorption of free TNP were further confirmed in in situ perfused rat intestinal *** results indicate that the enterohepatic circulation has a significant influence on the systemic exposure of the parent drug and its glucuronide conjugate,particularly on the terminal elimination of TNP,which may result in the prolonged retention of the drug in body.

关键词： Thienorphine Glucuronide conjugate Biliary excreation Enterohepatic circulation LC-MS/MS

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Population pharmacokinetic model of valproate and prediction of valproate serum concentrations in children with epilepsy

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Acta Pharmacologica Sinica 2004年第12期25卷 10-17页

作者： De-chun JIANG, Li WANG2 Department of Pediatrics, Peking University First Hospital, Therapeuticdrug Monitoring and Clinical toxicology, Center of Peking University, Beijing 100034, China Department of Pediatrics Peking University First Hospital Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University Beijing 100034 China

AIM: Using sparse data of valproate (VPA) serum concentrations to build a population pharmacokinetic (PPK) model of VPA in Chinese children with epilepsy and to predict serum concentrations for new patients using a Bayesian approach. METHODS: Two hundred epileptic children, whose VPA serum concentrations were collected, were divided randomly into two groups (A and B, n=100 each). The PPK parameter values of group A were calculated to establish a PPK Model by using the NPEM Program of USC*PACK software. Based on it, VPA serum concentrations of group B were predicted with the Bayesian Fitting Program of the USC*PACK software. To assess the accuracy and precision of prediction, a paired-comparisons t-test was run between predicted and ob- served concentrations, and then the mean prediction error (MPE), mean square prediction error (MSPE), root mean square prediction error (RMSPE), and coincidence rates for different percentages of prediction error were all calculated. RESULTS: Optimum PPK parameters were: Ka, 2.522±2.743 h-1; Vs, 0.329±0.496 L/kg; and Kel, 0.0438±0.0384 h-1. For group B, there was no significant difference between predicted and observed concentrations. MPE was -0.43 mg/L, MSPE was 115.40 (mg/L)2, and RMSPE was 5.47 mg/L. The coincidence rates for percent- ages of prediction error, which were less than 5 %, 10 %, 15 %, 20 %, 25 %, and 30 %, were 62 %, 74 %, 82 %, 85 %, 89 %, and 93 %, respectively. CONCLUSION: A PPK model of VPA in epileptic children was successfully established. Based on it, VPA serum concentrations can be predicted accurately with a Bayesian approach.

关键词： pharmacokinetics valproic acid epilepsy Bayes theorem USC*PACK software

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Oligodendrocyte precursor cell maturation: role of adenosine receptors

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Neural Regeneration Research 2021年第9期16卷 1686-1692页

作者： Federica Cherchi Anna Maria Pugliese Elisabetta Coppi Department of Neuroscience PsychologyDrug Research and Child Health-Neurofarba-Division of Pharmacology and ToxicologyUniversity of FlorenceFlorenceItaly

Oligodendrocyte-formed myelin sheaths allow fast synaptic transmission in the brain and their degeneration leads to demyelinating diseases such as multiple sclerosis. Remyelination requires the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes but, in chronic neurodegenerative disorders, remyelination fails due to adverse environment. Therefore, a strategy to prompt oligodendrocyte progenitor cell differentiation towards myelinating oligodendrocytes is required. The neuromodulator adenosine, and its receptors(A1, A(2A), A(2B) and A3 receptors: A1R, A(2A)R, A(2B)R and A3R), are crucial mediators in remyelination processes. It is known that A1Rs facilitate oligodendrocyte progenitor cell maturation and migration whereas the A3Rs initiates apoptosis in oligodendrocyte progenitor cells. Our group of research contributed to the field by demonstrating that A(2A)R and A(2B)R inhibit oligodendrocyte progenitor cell maturation by reducing voltage-dependent K^+ currents necessary for cell differentiation. The present review summarizes the possible role of adenosine receptor ligands as potential therapeutic targets in demyelinating pathologies such as multiple sclerosis.

关键词： adenosine receptors K^+channels oligodendrocyte differentiation oligodendrocyte progenitor cells remyelination

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Interferon-gamma and neuropathy: balance between pain and neuroprotection

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Neural Regeneration Research 2022年第12期17卷 2700-2701页

作者： Valentina Ferrara Alessandra Toti Carla Ghelardini Lorenzo Di Cesare Mannelli Department of Neuroscience PsychologyDrug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology SectionUniversity of FlorenceFlorenceItaly

Chronic pain is sustained by a phenomenon of hyper-activation of nociceptive neurons both at peripheral(peripheral sensitization)and central(central sensitization)*** onset and maintenance of pain,however,is to be found in the interaction among the various cell populations in the nervous tissue including neurons and glia(Nam et al.,2016).The pathogenesis of neuropathic pain is extremely complex depending on the primary cause of nerve damage,*** nerve injury is associated with a robust inflammatory response while chemotherapy-induced pain is characterized by a modest phlogistic component(Di Cesare Mannelli et al.,2013).Despite these differences,a powerful common concept to explain the cellular mechanisms underlying pain is the activation of glia.

关键词： pain sustained

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Prevalence of latent eosinophilia among occupational gardeners at Babcock University,Nigeria

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Asian Pacific Journal of Tropical Biomedicine 2016年第6期6卷 511-515页

作者： Ayodele Olushola Ilesanmi Ginnikachi Jennifer Ekwe Rosemary Isioma Ilesanmi Damilola Temitope Ogundele Jacob Kehinde Akintunde Oluwasogo Adewole Olalubi Department of Medical Laboratory Science Babcock University Department of Medical Microbiology Olabisi Onabanjo University Department of Chemical Geological & Physical SciencesChemistry UnitKwara State University drug metabolism and Molecular Environmental toxicology unit Biochemistry OptionDepartment of Bioscience and BiotechnologyCollege of Pure and Applied SciencesKwara State University School of Allied Health & Environmental Sciences Department of Allied HealthPublic Health UnitKwara State University

Objective: To determine the level of eosinophils present in the blood and sputum samples, presumably as a result of continual occupational exposure to allergens while on duty, as gardeners at Babcock University, ***: Haemocytometer and Olympus microscope were utilized to estimate eosinophils population in 44 blood samples and 21 sputum samples ***: Relationship between the occurrence of eosinophil in blood and the exposure period among Babcock University gardeners had a positive correlation(r = + 0.08,t = 4.55, P < 0.05). It was found that blood eosinophil count in these workers correlated with the length of exposure ***: The nature and the gardening activities are not a risk factor that significantly affect eosinophil level but duration of exposure to allergens. However, all safety precautionary kits and wears should be enforced and embraced by the concerned occupational gardeners so as to avert and subvert its pre-disposing deleterious effect on them.

关键词： Eosinophilia Occupational Exposure Gardeners Duration Allergens

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