scholarly journals Intraventricular T3 reverses chronic restraint stress-induced depressive-like behaviors: Inhibition of NF-κB/ NLRP3 inflammasome pathway in the hippocampus

2021 ◽  
Author(s):  
Tahmineh Mokhtari ◽  
AymanEl-Meghawry El-Kenawy ◽  
Li Hu
Keyword(s):  
Nlrp3 Inflammasome ◽  
Restraint Stress ◽  
Male Rats ◽  
Control Group ◽  
Therapeutic Effects ◽  
Chronic Restraint Stress ◽  
Model Group ◽  
Nissl Staining ◽  
Caspase 1 ◽  
Ca1 Region

Abstract In this study, the effects of triiodothyronine (T3) were evaluated on the NLR family pyrin domain containing 3 (NLRP3) inflammasome complex formation in the rat's hippocampus with restraint stress-induced depressive-like behaviors.Thirty-six Wistar male rats were randomly allocated to following groups: Control, Model, and Model + T3. In the Model or Model+T3 group, a single dose of PBS or T3 was administered into the lateral ventricle. Depressive-like behaviors were induced by chronic restraint stress. The forced swimming (FST), tail suspension (TST), and open field (OFT) tests were used to investigate the depression. The rats were sacrificed, and brain tissues were stored for molecular and pathological evaluations. Chronic stress increased the immobility of rats in the Model group according to FST, TST, and OFT (P < 0.05). T3 significantly improved depressive-like behaviors (P < 0.05). The gene expression and protein level of hippocampal nuclear factor kappa B (NF-κB), NLRP3, apoptosis-associated speck-like protein (ASC), and Caspase-1 significantly increased in the Model group compared to the control group (P < 0.05). The reduced hippocampal levels of NF-κB, NLRP3, ASC, and Caspase-1 were observed in the T3 group compared to the Model group (P < 0.05). The Nissl staining of the CA1 region showed an increased number of dark neurons (P < 0.05) and reduced pyramidal layer thickness (P < 0.05) in the Model group. These histopathological alterations were changed by T3 administration compared to the Model group (P < 0.05). The findings confirmed the therapeutic effects of intraventricularly T3 on depressive-like behaviors induced by restraint stress via surviving pyramidal neurons of the CA1 region and inhibition of NF-κB/NLRP3 inflammasome pathway.

scholarly journals Intraventricular T3 Reverses Chronic Restraint Stress-Induced Depressive-Like Behaviors: Inhibition of NF-κB/ NLRP3 Inflammasome Pathway in the Hippocampus

2021 ◽  
Author(s):  
Tahmineh Mokhtari ◽  
AymanEl-Meghawry El-Kenawy ◽  
Li Hu
Keyword(s):  
Nlrp3 Inflammasome ◽  
Restraint Stress ◽  
Male Rats ◽  
Control Group ◽  
Therapeutic Effects ◽  
Chronic Restraint Stress ◽  
Model Group ◽  
Nissl Staining ◽  
Caspase 1 ◽  
Ca1 Region

Abstract In this study, the effects of triiodothyronine (T3) were evaluated on the NLRP3 inflammasome complex formation in the hippocampus of the rat with restraint stress-induced depressive-like behaviors.Thirty-six Wistar male rats were randomly allocated to the following groups: Control, Model, and Model + T3. In Model or Model + T3 group, a single dose of PBS or T3 () was administered into the lateral ventricle. Depressive-like behaviors were induced by chronic restraint stress. The forced swimming (FST), tail suspension (TST), and open field (OFT) tests were used to investigate depression. The rats were sacrificed, and brain tissues were stored for molecular and pathological evaluations. Chronic stress increased the immobility of rats in the Model group according to FST, TST, and OFT (P < 0.05). T3 significantly improved depressive-like behaviors (P < 0.05). The gene expression and protein level of hippocampal NF-κB, NLRP3, ASC, and Caspase-1 significantly increased in the Model group compared to the control group (P < 0.05). The reduced hippocampal levels of NF-κB, NLRP3, ASC, and Caspase-1 were seen in the T3 group compared to the Model group (P < 0.05). Also, the Nissl staining of the CA1 region showed an increased number of dark neurons (P < 0.05) and reduced pyramidal layer thickness (P < 0.05) in the Model group. These histopathological alterations were changed by T3 administration compared to the Model group (P < 0.05). The findings of confirmed the therapeutic effects of intraventricularly T3 on depressive-like behaviors induced by restraint stress via surviving pyramidal neurons of the CA1 region and inhibition of NF-κB/NLRP3 inflammasome pathway.

scholarly journals Toxicological evaluation of the nicotine on CA1 and protective effects of curcuma longa: An experimental study

2019 ◽  
Vol 6 (9) ◽  
pp. 3368-3378
Author(s):  
Mohammad Reza Salahshoor ◽  
Shiva Roshankhah ◽  
Babak Arji Roudsari ◽  
Cyrus Jalili
Keyword(s):  
Antioxidant Capacity ◽  
Dendritic Spines ◽  
Total Antioxidant Capacity ◽  
Curcuma Longa ◽  
Male Rats ◽  
Control Group ◽  
Therapeutic Effects ◽  
Nitrite Oxide ◽  
Ca1 Region ◽  
Total Antioxidant

Introduction: Nicotine is the most important alkaloid compound in tobacco and is a major risk factor in the development of functional disorders of several organ systems. Some plants produce Curcuma longa (curcumin), which has antioxidant and neuro-protective properties. Methods: This study was designed to evaluate the therapeutic effects of curcumin against nicotine injury on the hippocampus CA1 region of rats. In this study, 48 male rats were randomly assigned to eight groups: Normal control (saline) group, Nicotine control group (0.5 mg/kg); Curcumin groups (10, 30, and 60 mg/kg) and Nicotine + Curcumin groups (10, 30, and 60 mg/kg). Treatments were administered intra-peritoneally daily for 28 days. Golgi staining technique investigated the number of dendritic spines. Cresyl violet staining method was used to determine the number of neurons in the hippocampal region CA1. Griess technique was assessed to determine serum nitrite oxide levels. Also, the ferric reducing/antioxidant power (FRAP) method was applied to determine the total antioxidant capacity. Results: Nicotine administration significantly increased the nitrite oxide level and decreased total antioxidant capacity. The number of neuronal dendritic spines, as well as neurons per se, also decreased, compared to the control group (p < 0.01). In all the members of the Curcumin and Nicotine + Curcumin groups, the number of neurons, neuronal dendritic spines and total antioxidant capacity increased significantly compared to the nicotine control group, while nitrite oxide level decreased significantly compared to the nicotine control group (p < 0.01). Conclusions: It seems that Curcumin administration improved hippocampal CA1 region injury in rats caused by Nicotine.  

scholarly journals Xiaoyaosan Exerts Therapeutic Effects on the Colon of Chronic Restraint Stress Model Rats via the Regulation of Immunoinflammatory Activation Induced by the TLR4/NLRP3 Inflammasome Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Hui-Zheng Zhu ◽  
Yu-Dan Liang ◽  
Wen-Zhi Hao ◽  
Qing-Yu Ma ◽  
Xiao-Juan Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Restraint Stress ◽  
Gastrointestinal Diseases ◽  
Chronic Restraint Stress ◽  
Colonic Inflammation ◽  
Depressive Behavior ◽  
Expression Levels ◽  
Caspase 1 ◽  
Tnf Α

Depression is the neurological manifestation most commonly associated with gastrointestinal diseases. The release of inflammatory cytokines mediated by TLR4/NLRP3 inflammasome signaling-induced immunoinflammatory activation may represent a common pathogenic process underlying the development of gastrointestinal diseases and depression. Clinical studies have indicated that Xiaoyaosan (XYS) can relieve depressive behavior by improving gastrointestinal symptoms. We previously demonstrated that XYS can reduce colonic inflammation in a rat model of chronic unpredictable mild stress; however, the precise anti-inflammatory mechanisms involved remain unclear. Here, we investigated whether XYS can ameliorate depressive behavior through regulating the TLR4/NLRP3 inflammasome signaling pathway, thereby inhibiting immunoinflammatory activation and reducing colonic proinflammatory cytokine levels. Fifty-two healthy male Sprague–Dawley rats were randomly divided into four groups (control, model, XYS, and fluoxetine). The latter three groups were subjected to 21 days of chronic restraint stress to generate a model of stress-induced depression. XYS and fluoxetine were administered intragastrically. Behavioral changes in the rats were assessed after 21 days. Serum and colon samples were collected, and the relative levels of the inflammation indicators IL-6, IL-1β, and TNF-α were determined by ELISA. Pathological changes in colon tissue were assessed by hematoxylin and eosin staining. The levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, and TRAF6 were detected by immunohistochemistry, while the gene and protein expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The results indicated that XYS could improve the depressive-like behavior and the weight loss of rats with stress-induced depression. Furthermore, depressed rats treated with XYS exhibited decreased expression levels of TLR4, MyD88, NF-κB-p65, TAK1, IRAK1, TRAF6, NLRP3, ASC, and caspase-1 in colonic tissue; reduced colon and serum concentrations of the inflammatory factors IL-6, IL-1β, and TNF-α; and lowered levels of colonic inflammation.

scholarly journals Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Li-Yao Duan ◽  
Yan Liang ◽  
Wen-Ping Gong ◽  
Yong Xue ◽  
Jie Mi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chinese Medicine ◽  
Treatment Group ◽  
Mechanism Of Action ◽  
Cell Damage ◽  
Control Group ◽  
Therapeutic Effects ◽  
Model Group ◽  
Lung Histopathology ◽  
Th17 Cytokines

Abstract Background The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. Methods BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. Results After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. Conclusions NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.

Effects of chronic restraint stress on social behaviors and the number of hypothalamic oxytocin neurons in male rats

Neuropeptides ◽  
2016 ◽  
Vol 60 ◽  
pp. 21-28 ◽  
Author(s):  
Jin Li ◽  
Han-Xia Li ◽  
Xiao-Jing Shou ◽  
Xin-Jie Xu ◽  
Tian-Jia Song ◽  
...  
Keyword(s):  
Restraint Stress ◽  
Social Behaviors ◽  
Male Rats ◽  
Chronic Restraint Stress

Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  
Keyword(s):  
Male Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Plantaginis Semen ◽  
Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

The Effects of Moxibustion on Serum Interleukins and T Cell Subset in H.polyri Infected Rats

2015 ◽  
Vol 3 (1) ◽  
pp. 38-45
Author(s):  
Jing Shen ◽  
Yan Peng ◽  
Dong-Mei Shi ◽  
Yin-Shuai Feng ◽  
Yan-Ling Hou ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Control Group ◽  
Intragastric Administration ◽  
Therapeutic Effects ◽  
Model Group ◽  
Tnf Α ◽  
Group A ◽  
Histomorphological Changes ◽  
Group B ◽  
Group D

Abstract Objective: to observe the effects of moxibustion on histomorphological changes of gastric mucosa, as well as on serum IL-6、IL-8、TNF-α，Hp IgG、CD3+、CD4+、CD8+ in helicobacter pylori (Hp) infected rats, so that to better understand how the moxibustion repairs the Hp- induced gastric mucosal injury. Methods: 40 SD rats were randomly assigned to four groups: group A (blank control), group B (Hp infection model), group C (moxibustion plus model), group D (electro-acupuncture plus model), 10 for each group. The “NaHCO3 plus Indometacin and Hp intragastric administration” method was employed to make gastritis model. Acupoints selected for “repair” purpose were Zu San Li (ST36), Zhong Wan (CV12), Guan Yuan (RN4), Pi Shu (BL20), Wei Shu(BL21). The histomorphological changes of gastric mucosa in rats were observed under light microscope after HE stain; IL-6, IL-8, TNF-α, Hp IgG values were evaluated by ELISA method; values of CD3+、CD4+、CD8+、CD4+/CD8+ were measured by flow cytometry method. Results: compared with group A, the values of IL-6, IL-8, TNF-α, Hp IgG and CD8+ in group B were increased（P＜0.01）, whereas the values of CD3+、CD4+、CD4+/CD8+ were decreased（P＜0.01）. Compared with group B, the values of IL-8（P＜0.05）,TNF-α（P＜0.05）, IL-6（P＜0.01）, Hp IgG（P＜0.01） and CD8+ （P＜0.05） in group C were decreased, whereas the values of CD3+（P＜0.05）,CD4+（P＜0.05）,CD4+/CD8+ （P＜0.05） were increased, meanwhile such values in group D had no significant changes. Compared with group D, the values of IL-6（P＜0.05）,IL-8 （P＜0.05）and Hp IgG （P＜0.01）in group C were decreased, whereas CD4+/CD8+（P＜0.05）were increased, all those changes had statistical significance. Conclusion: the preventive and therapeutic effects of moxibustion on Hp related gastritis might be realized by two ways- to inhibit the secretion of proinflammatory cytokines such as IL-6, IL-8 and TNF-α, or to regulate the production of immune factors (such as up-regulation of CD3+, CD4+ and down-regulation of CD8+).

Effect of Electro-acupuncture on Ultrastructure in Diabetic Gastroparesis Model Rats

2015 ◽  
Vol 3 (1) ◽  
pp. 70-76
Author(s):  
Feng-E He ◽  
Quan-Quan Wan ◽  
Yan Peng ◽  
Ya-Ping Lin ◽  
Jing Shen
Keyword(s):  
Smooth Muscle ◽  
Point Group ◽  
Diabetic Gastroparesis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Phenol Red ◽  
Model Group ◽  
Sprague Dawley ◽  
Blank Control Group ◽  
Gastric Emptying Rate

Abstract Objective: To observe the effects of electro-acupuncture (EA) on ultrastructure of gastric antrum smooth muscle cells (GASMCs) in diabetic gastroparesis (DGP) model rats, and to explore the possible mechanism underlying the therapeutic effects of EA. Methods: Sixty Sprague Dawley rats were randomly divided into 5 groups: blank control (group A), DGP model (group B), EA point (group C), EA non-point (group D), Metoclopramide control (group E). DGP rat model was established by 2% STZ intraperitoneal injection at once, and then being fed with high-sugar-high-fat (HSHF) for 8wks. Phenol red lavage method was employed to measure gastric emptying rate (GER) and intestinal migration rate (IMR). The ultrastructure of GASMCs was observed under the electronic microscope. Results: Compared with the blank control group, the GER and IMR in model group were decreased significantly (P＜0.05 or P＜0.01). Compared with the model group, the GER and IMR in EA point group were increased significantly(P＜0.05 or P＜0.01). Electro-acupuncture on “Zu San Li”(ST36) point, etc. has been observed improving the ultrastructure of GASMCs, as well as increasing the number of interstitial cells of Cajal (ICCs). Conclusion: Electro-acupuncture can improve the GI motility promisingly, based on a potential underlying mechanism that the electro-acupuncture can improve the ultrastructure of gastric smooth muscle, and increase the number of ICCs.

scholarly journals Manual Acupuncture Suppresses the Expression of Proinflammatory Proteins Associated with the NLRP3 Inflammasome in the Hippocampus of SAMP8 Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ning Ding ◽  
Jing Jiang ◽  
Menghan Lu ◽  
Jiatong Hu ◽  
Yiyuan Xu ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Nlrp3 Inflammasome ◽  
Control Group ◽  
Spatial Learning And Memory ◽  
Manual Acupuncture ◽  
Caspase 1 ◽  
Donepezil Hydrochloride ◽  
Related Proteins ◽  
Samp8 Mice

Objective. To investigate the effect of manual acupuncture (MA) on NLRP3 inflammasome-related proteins. Methods. SAMP8 mice were randomly divided into Alzheimer’s disease (AD) group, the MA group, and the medicine (M) group. Mice in the M group were treated with donepezil hydrochloride at 0.65 μg/g. In the MA group, MA was applied on Baihui (GV20) and Yintang (GV29) for 20 min and then pricked at Shuigou (GV26). The Morris water maze was applied to assess spatial learning and memory. Immunohistochemical staining and western blot analysis were used to observe the expression of NLRP3 inflammasome-related proteins. Results. Compared with the normal (N) control group, spatial learning and the memory capabilities of the AD group significantly decreased (p<0.01). The number of NLRP3, ASC, Caspase-1, and IL-1β positively stained cells in the AD group was higher than the N group, and the relative expression levels of the above proteins were significantly higher than those in the N group (p<0.01). These changes were reversed by both MA and donepezil (p<0.01). Conclusion. MA can improve the learning and memory capabilities of SAMP8 mice. The negative regulation of the NLRP3/Caspase-1 pathway in the hippocampus may be a possible mechanism of MA in the treatment of AD.

scholarly journals HEMATOLOGICAL TOXICITY IN RATS;

2017 ◽  
Vol 24 (02) ◽  
pp. 342-346
Author(s):  
Noor ul Ain ◽  
Nusrat Bano ◽  
Anwar Ejaz Beg ◽  
Kamran Hameed ◽  
Talha Bin Fayyaz ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Treated Group ◽  
Saline Group ◽  
Andrographis Paniculata ◽  
Male Rats ◽  
Hematological Toxicity ◽  
Control Group ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Normal Saline Group

Objectives: Oxaliplatin causes hematological toxicities in clinical setting whichlimits its efficacy. The aim of this study is to investigate the therapeutic effects of Andrographispaniculata against hematological toxicity caused by oxaliplatin. Study design: Experimentalanimal study. Period: Study takes 8 month from March 2015 to Oct 2015. Setting: Dow universityanimal house. Method: Wistar albino male rats, divided into 3 equals groups (n=6): GroupN* was a control group (0.9% normal saline), Group NP0 was Oxaliplatin treated group andGroup NP1 was prophylactically treated with Andrographis paniculata followed by Oxaliplatinin order to assess the protective effects of Andrographis paniculata against the hematologictoxicity caused by Oxaliplatin. Results: Prophylactic treatment with Andrographis paniculata(NP1) significantly increases the levels of platelets and neutrophile count compared with thestandard (NP0) (p<0.01) and increases the RBCs count and levels of hemoglobin comparedwith the standard (NP0). Conclusion: Prophylactic treatment with Andrographis paniculata(NP1) was effective in reducing risk of thrombocytopenia, anemia and neutropenia associatedwith Oxaliplatin.

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