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Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

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Neural Regeneration Research 2025年第8期20卷 2325-2336页

作者： Yafan Bai Hui Ma Yue Zhang Jinfeng Li Xiaojuan Hou Yixin Yang Guyan Wang Yunfeng Li department of Anesthesiology Beijing Tongren HospitalCapital Medical UniversityBeijingChina Beijing Institute of Basic Medical Sciences BeijingChina Hebei North University ZhangjiakouHebei ProvinceChina Beijing Institute of pharmacology and toxicology State Key Laboratory of Toxicology and Medical CountermeasuresBeijing Key Laboratory of NeuropsychopharmacologyBeijingChina

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary *** this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain *** experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain ***,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 ***,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain ***,YL-0919 effectively combated oxidative stress both in vivo and in *** protective effects of YL-0919 were partially inhibited by *** results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist ***-0919 may have potential as a new treatment for traumatic brain injury.

关键词： antidepressant drug blood-brain barrier cognitive function hypidone hydrochloride(YL-0919) neurological function nuclear factor-erythroid 2 related factor 2 oxidative stress sigma-1 receptor superoxide dismutase traumatic brain injury

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Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

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Neural Regeneration Research 2025年第1期20卷 191-192页

作者： Narek Manukjan Daniel Fulton Zubair Ahmed WMatthijs Blankesteijn Sébastien Foulquier department of pharmacology and toxicology Maastricht UniversityMaastrichtThe Netherlands CARIM-School for Cardiovascular Diseases Maastricht UniversityMaastrichtThe Netherlands Neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK Centre for Trauma Sciences Research University of BirminghamEdgbastonBirminghamUK MHeNs-School for Mental Health and Neuroscience Maastricht UniversityMaastrichtThe Netherlands department of Neurology Maastricht University Medical CenterMaastrichtThe Netherlands

As the population ages,the burden of age-related diseases becomes ***,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common ***,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of *** term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

关键词： pathology becoming white

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Silibinin alleviates N-nitrosodimethylamine-induced glutathione dysregulation and hepatotoxicity in rats

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Chinese Journal of Natural Medicines 2016年第1期14卷 40-47页

作者： Devaraj Ezhilarasan Slvanesan Karthikeyan Food and Hepatotoxicology Laboratory Department of Pharmacology and Environmental Toxicology University of MadrasTaramani Chennai 600113 India

The present study was designed to evaluate the hepatoprotective and antioxidant potentials of silibinin(SBN)against N-nitrosodimethylamine(DMN)-induced toxic insults in the rat *** liver damage was induced in Wistar albino rats by repeated administration of DMN(10 mg·kg-1 b.w.,i.p.)on 3 consecutive days per week for 3 ***(100 mg·kg-1 b.w.,p.o.)was given daily to the DMN treated rats for two *** marker enzymes of liver toxicity and second-line enzymic and non-enzymic antioxidants were evaluated in serum and liver tissues before and after SBN *** of the liver was evaluated by H & E *** DMN treatment produced a progressive increase in all the serum marker enzymes(AST,ALT,ALP,LDH,and γ-GT),peaking on Day *** treatment produced highly significant decreases in all the second-line antioxidant parameters(GSH,GST,GR,GPx,and vitamins C and E).The SBN treatment significantly reversed the DMN-induced damages,towards *** studies confirmed the development of liver toxicity in DMN-treated rats,which was reversed by SBN treatment in corroboration with the aforementioned biochemical results,indicating the hepatoprotective and antioxidant properties of *** conclusion,the DMN-induced degenerative changes in the liver were alleviated by SBN treatment and this protective ability may be attributed to its antioxidant,free radical scavenging,and membrane stabilizing properties.

关键词： Dimethylnitrosamine Silibinin Oxidative stress Hepatotoxicity Glutathione dysregulation

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Effects of halobenzoquinone and haloacetic acid water disinfection byproducts on human neural stem cells

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Journal of environmental Sciences 2017年第8期29卷 239-249页

作者： Katherine Z.Fu Jinhua Li Sai Vemula Birget Moe Xing-Fang Li Division of Analytical&environmental toxicology Department of Laboratory Medicine&PathologyFaculty of Medicine&DentistryUniversity of Alberta Alberta Centre for toxicology Department of Physiology&PharmacologyFaculty of MedicineUniversity of Calgary

Human neural stem cells（h NSCs） are a useful tool to assess the developmental effects of various environmental contaminants; however, the application of h NSCs to evaluate water disinfection byproducts（DBPs） is scarce. Comprehensive toxicological results are essential to the prioritization of DBPs for further testing and regulation. Therefore, this study examines the effects of DBPs on the proliferation and differentiation of h NSCs. Prior to DBP treatment, characteristic protein markers of h NSCs from passages 3 to 6 were carefully examined and it was determined that h NSCs passaged 3 or 4 times maintained stem cell characteristics and can be used for DBP analysis. Two regulated DBPs, monobromoacetic acid（BAA） and monochloroacetic acid（CAA）, and two emerging DBPs, 2,6-dibromo-1,4-benzoquinone（2,6-DBBQ） and 2,6-dichloro-1,4-benzoquinone（2,6-DCBQ）, were chosen for h NSC treatment. Both 2,6-DBBQ and 2,6-DCBQ induced cell cycle arrest at S-phase at concentrations up to 1 μmol/L. Comparatively, BAA and CAA at 0.5 μmol/L affected neural differentiation. These results suggest DBP-dependent effects on h NSC proliferation and differentiation. The DBP-induced cell cycle arrest and inhibition of normal h NSC differentiation demonstrate the need to assess the developmental neurotoxicity of DBPs.

关键词： Disinfection byproducts Human neural stem cells Differentiation Halobenzoquinones Haloacetic acids Cell cycle arrest

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Effect of extract of Abrus precatorius on blood glucose concentration of alloxan induced diabetic Albino Wistar Rats

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Asian Pacific Journal of Tropical Medicine 2009年第6期2卷 16-17页

作者： Georgewill OA Georgewill UO department of pharmacology and toxicology

Objective:To evaluate the effect of extract of Abrus precatorius on blood glucose of alloxan induced albino wistar ***:Experimental animals received daily oral administration of extract of Abrus precatorius for 14 *** effect of 200 mg/kg dose was studied during the treatment ***:There was a significant reduction in blood glucose concentration(P < 0.05) with the mean blood glucose of the different groups as 5.0±0.3 for normal control,7.0±0.4 for diabetic control group and 4.0±0.2 for diabetic treated group. Conclusion:The findings of this study suggest that extract of Abrus precatorius has hypoglycemic effect.

关键词： Abrus precatorius Hypoglycemia Diabetes Hyperglycemia

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Increased salt sensitivity induced by sensory denervation: role of superoxide

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Acta Pharmacologica Sinica 2004年第12期25卷 60-66页

作者： Alex F CHEN,Donna H WANG department of Medicine and pharmacology & toxicology Michigan State University East Lansing MI 48824 USA department of Medicine and pharmacology & toxicology Michigan State University East Lansing MI 48824 USA

AIM: To test the hypothesis that production of superoxide in mesenteric resistance arteries is increased and con- tributes to the development of hypertension induced by sensory denervation plus high salt intake. METHODS: Newborn Wistar rats were given capsaicin 50 mg/kg sc on the 1st and 2nd d of life. After weaning, male rats were grouped as follows and treated for 3 weeks with: capsaicin pretreatment plus normal sodium diet (0.5 %, CAP-NS), CAP plus high sodium diet (4 %, CAP-HS), control plus NS (CON-NS), or CON-HS. Both tail-cuff systolic blood pressure and mean arterial pressure (MAP) were measured in each of the groups. Western blot analysis was used for measurement of manganese superoxide dismutase (MnSOD) and endothelial nitric oxide synthase (eNOS) in the mesenteric resistance arteries. Lucigenin chemiluminescence assay was used for superoxide production in the mesenteric resistance arteries. The Griess method was used for measurement of nitrite/nitrate levels in plasma. RESULTS: Both tail-cuff pressure and MAP were higher in CAP-HS compared with CAP-NS, CON-HS, and CON- NS rats (P<0.05). Both MnSOD and eNOS in the mesenteric resistance arteries were increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, nitrite/nitrate levels in plasma were not different among 4 groups. Acute iv administration of tempol, a membrane-permeable superoxide scavenger, de- creased MAP in both CAP-HS and CON-HS when compared with their respective controls. However, the de- creases of MAP between these two groups were not different. Chronic treatment with tempol failed to prevent the development of hypertension in CAP-HS rats. Superoxideproduction in the mesenteric resistance arteries was increased in CAP-HS compared with CAP-NS, CON-HS, and CON-NS (P<0.05). However, chronic treatment with tempol did not prevent the increase of mesenteric superoxideproduction in CAP-HS rats. CONCLUSIONS: Regardless of increased vascular MnSOD levels, salt

关键词： superoxides tempol afferent neurons capsaicin denervation dietary sodium chloride nitric oxide

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Role of farnesoid X receptor and bile acids in alcoholic liver disease

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Acta Pharmaceutica Sinica B 2015年第2期5卷 158-167页

作者： Sharon Manley Wenxing Ding department of pharmacology Toxicology and Therapeutics the University of Kansas Medical Center

Alcoholic liver disease(ALD) is one of the major causes of liver morbidity and mortality worldwide. Chronic alcohol consumption leads to development of liver pathogenesis encompassing steatosis, inflammation, fibrosis, cirrhosis, and in extreme cases, hepatocellular carcinoma. Moreover,ALD may also associate with cholestasis. Emerging evidence now suggests that farnesoid X receptor(FXR) and bile acids also play important roles in ALD. In this review, we discuss the effects of alcohol consumption on FXR, bile acids and gut microbiome as well as their impacts on ALD. Moreover, we summarize the findings on FXR, Fox O3a(forkhead box-containing protein class O3a) and PPARα(peroxisome proliferator-activated receptor alpha) in regulation of autophagy-related gene transcription program and liver injury in response to alcohol exposure.

关键词： Farnesoid X receptor Bile acids Autophagy Alcoholic liver disease FoxO3

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Modern Issues in Food Safety - A Perspective

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Journal of Integrative Agriculture 2012年第1期11卷 9-13页

作者： James N Seiber department of environmental toxicology University of California

There is much current interest worldwide in food safety. This results in large part from well publicized outbreaks due to foodborne pathogens, chemical food safety related to pesticides, and from persistent organic po... 详细信息

关键词： Modern Issues in Food Safety A Perspective

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Synthesis and Crystal Structure of 7α-[(R)-1-Hydroxyl-1-methyl-3-(thien-2-yl)- propyl]-6,14-endoethanotetrahydrothebaine

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Chinese Journal of Structural Chemistry 2005年第9期24卷 1021-1024页

作者：刘河刘春河吴波陈兰福仲伯华 No. 7 department Beijing Institute of Pharmacology and Toxicology Beijing 100850 China

The crystal structure of 7α-[（R）-1-hydroxyl-1-methyl-3-（thien-2-yl）propyl]-6,14-endoethanotetrahydrothebaine （C29H37NO4S, Mr=495.66） has been determined by single-crystal X-ray diffraction analysis. The crystal belongs orthorhombic, space group P212121 with α=10.063（4）, b=12.571（5）, c=19.626（8）A°, V=2482.9（17）A°^3, Z=4, Dc=1.326 g/cm^3,μ=0.167 mm^-1, F（000）=1064, the final R=0.0537 and wR=0.0888. The C（7） substituent is l-hy-droxyl-1-methyl-3-（thienyl-2-）propyl group adopting R-configuration. The N-methyl group is located at the equatorial position as expected. The crystal structure shows the presence of intra- molecular hydrogen bonds, O（1）-H（1）…O（2）.

关键词： thebaine crystal structure grignard reaction

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Cadmium in soybeans and the relevance to human exposure

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Journal of environmental Sciences 2015年第11期27卷 157-162页

作者： Ashley M.Newbigging Xiaowen Yan X.Chris Le Division of Analytical and environmental toxicology Department of Laboratory Medicine and Pathology University of Alberta

Introduction Cadmium is considered a human carcinogen by the International Agency for Research on Cancer（IARC,1993）and the US National toxicology Program（NTP,1997）.Cadmium contamination of food crops is a persistent issue for both the agricultural industry as well as *** is an issue for agriculture because cadmium can be present in soils naturally or as a result of industrial processes and can contaminate foods that are consumed by ***

关键词： Cadmium Metals Food safety Dietary exposure Agricultural products Uptake of cadmium from soil

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