المؤلفون: Chengliang Luo, Xue-Ying Feng, Zheng-Hong Qin, Luyang Tao, Tao Wang, Rui Yang, Yu-Xia Sun, Xiping Chen, Ding-Kun Dai, Hai-Jun Bao, Ran Liu

المصدر: Neurological Sciences. 34:345-355

مصطلحات موضوعية: Male, Programmed cell death, Time Factors, Morris water navigation task, Inflammation, Dermatology, Pharmacology, Biology, Neuroprotection, Cathepsin B, Mice, chemistry.chemical_compound, Cytosol, medicine, Animals, Enzyme Inhibitors, Maze Learning, Neurons, Memory Disorders, Movement Disorders, Caspase 3, Intrinsic apoptosis, NF-kappa B, Brain, Cytochromes c, NF-κB, General Medicine, Mitochondria, Disease Models, Animal, Psychiatry and Mental health, Gene Expression Regulation, chemistry, Apoptosis, Brain Injuries, Immunology, Neurology (clinical), medicine.symptom, Peptides, BH3 Interacting Domain Death Agonist Protein, Propidium, Signal Transduction

الوصف: NF-κB upregulation has been demonstrated in neurons and glial cells in response to experimental injury and neuropathological disorders, where it has been related to both neurodegenerative and neuroprotective activities. It has been generally recognized that NF-κB plays important roles in the regulation of apoptosis and inflammation as well as innate and adaptive immunity. However, the regulatory mechanism of NF-κB in apoptosis remained to be determined. The present study sought to first investigate the effect of a NF-κB inhibitor SN50, which inhibits NF-κB nuclear translocation, on cell death and behavioral deficits in our mice traumatic brain injury (TBI) models. Additionally, we tried to elucidate the possible mechanisms of the therapeutic effect of SN50 through NF-κB regulating apoptotic and inflammatory pathway in vivo. Encouragingly, the results showed that pretreatment with SN50 remarkably attenuated TBI-induced cell death (detected by PI labeling), cumulative loss of cells (detected by lesion volume), and motor and cognitive dysfunction (detected by motor test and Morris water maze). To analyze the mechanism of SN50 on cell apoptotic and inflammatory signaling pathway, we thus assessed expression levels of TNF-α, cathepsin B and caspase-3, Bid cleavage and cytochrome c release in SN50-pretreated groups compared with those in saline vehicle groups. The results imply that through NF-κB/TNF-α/cathepsin networks SN50 may contribute to TBI-induced extrinsic and intrinsic apoptosis, and inflammatory pathways, which partly determined the fate of injured cells in our TBI model.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe3e51e12381a6de92da9a40dddb2ca1Test
https://doi.org/10.1007/s10072-012-1007-zTest

المؤلفون: Xin Chen, Zheng-Hong Qin, Lu-yang Tao

المصدر: Acta Pharmacologica Sinica. 28:1859-1872

مصطلحات موضوعية: Pharmacology, Programmed cell death, Cell Survival, Neurodegeneration, NF-kappa B, NF-κB, General Medicine, Biology, medicine.disease, Neuroprotection, Pathogenesis, chemistry.chemical_compound, Neuroprotective Agents, Immune system, chemistry, Apoptosis, Immunology, Cancer research, medicine, Animals, Humans, Pharmacology (medical), Transcription factor

الوصف: NF-kappaB is a well-characterized transcription factor with multiple physiological and pathological functions. NF-kappaB plays important roles in the development and maturation of lymphoids, regulation of immune and inflammatory response, and cell death and survival. The influence of NF-kappaB on cell survival could be protective or destructive, depending on types, developmental stages of cells, and pathological conditions. The complexity of NF-kappaB in cell death and survival derives from its multiple roles in regulating the expression of a broad array of genes involved in promoting cell death and survival. The activation of NF-kappaB has been found in many neurological disorders, but its actual roles in pathogenesis are still being debated. Many compounds with neuroprotective actions are strongly associated with the inhibition of NF-kappaB, leading to speculation that blocking the pathological activation of NF-kappaB could offer neuroprotective effects in certain neurodegenerative conditions. This paper reviews the recent developments in understanding the dual roles of NF-kappaB in cell death and survival and explores its possible usefulness in treating neurological diseases. This paper will summarize the genes regulated by NF-kappaB that are involved in cell death and survival to elucidate why NF-kappaB promotes cell survival in some conditions while facilitating cell death in other conditions. This paper will also focus on the effects of various NF-kappaB inhibitors on neuroprotection in certain pathological conditions to speculate if NF-kappaB is a potential target for neuroprotective therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::093c46a349b27ce3ecb3ebfab0976395Test
https://doi.org/10.1111/j.1745-7254.2007.00741.xTest

المؤلفون: Guanghui Wang, Zheng-Hong Qin, Kui Cui, Rong Han, Xuechu Zhen, Jin-Hua Gu, Jian-Qun Kou

المصدر: BMC Complementary and Alternative Medicine

مصطلحات موضوعية: Male, Pulmonary Fibrosis, Interleukin-1beta, Anti-Inflammatory Agents, Inflammation, Pharmacology, Bleomycin, medicine.disease_cause, complex mixtures, NF-κB, Antioxidants, Rats, Sprague-Dawley, chemistry.chemical_compound, Mice, Fibrosis, Transforming Growth Factor beta, Pulmonary fibrosis, medicine, Animals, Elapidae, Lung, Elapid Venoms, business.industry, Tumor Necrosis Factor-alpha, NF-kappa B, TGF-βm, General Medicine, medicine.disease, NFKB1, Hydroxyproline, Oxidative Stress, chemistry, Complementary and alternative medicine, Immunology, Tumor necrosis factor alpha, Female, medicine.symptom, business, Naja naja atra venom, Oxidative stress, Research Article

الوصف: Background Naja naja atra venom (NNAV) displays diverse pharmacological actions including analgesia, anti-inflammation and immune regulation. In this study, we investigated the effects of NNAV on pulmonary fibrosis and its mechanisms of action. Methods To determine if Naja naja atra venom (NNAV) can produce beneficial effects on pulmonary fibrosis, two marine models of pulmonary fibrosis were produced with bleomycin (BLM) and lipopolysaccharide (LPS). NNAV (30, 90, 270 μg/kg) was orally administered once a day started five days before BLM and LPS until to the end of experiment. The effects of NNAV treatment on pulmonary injury were evaluated with arterial blood gas analysis, hydroxyproline (HYP) content assessment and HE/Masson staining. The effects of NNAV treatment on inflammatory related cytokines, fibrosis related TGF-β/Smad signaling pathway and oxidative stress were examined. Results The results showed that NNAV improved the lung gas-exchange function and attenuated the fibrotic lesions in lung. NNAV decreased IL-1β and TNF-α levels in serum in both pulmonary fibrosis models. NNAV inhibited the activation of NF-κB in LPS-induced and TGF-β/Smad pathway in BLM-induced pulmonary fibrosis. Additionally, NNAV also increased the levels of SOD and GSH and reduced the levels of MDA in BLM-induced pulmonary fibrosis model. Conclusions The present study indicates that NNAV attenuates LPS- and BLM-induced lung fibrosis. Its mechanisms of action are associated with inhibiting inflammatory response and oxidative stress. The study suggests that NNAV might be a potential therapeutic drug for treatment of pulmonary fibrosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0bce627ff7e875d191e4dd590220cd33Test
http://europepmc.org/articles/PMC4258260Test

المؤلفون: Zheng-Hong Qin, Xifeng Fei, Ling-yun Li, Zhongqin Liang, Xi-lin Zhao, Zhen-Lun Gu

المصدر: Acta pharmacologica Sinica. 29(5)

مصطلحات موضوعية: Male, medicine.medical_specialty, animal structures, Substantia nigra, Cyclopentanes, Neuroprotection, Rats, Sprague-Dawley, symbols.namesake, chemistry.chemical_compound, Bilobalide, Internal medicine, medicine, Animals, Pharmacology (medical), Furans, Oxidopamine, Pharmacology, Neurons, Tyrosine hydroxylase, Dose-Response Relationship, Drug, Dopaminergic, NF-kappa B, Parkinson Disease, General Medicine, Rats, Substantia Nigra, Disease Models, Animal, Endocrinology, Ginkgolides, Neuroprotective Agents, nervous system, chemistry, Apoptosis, Nissl body, symbols, Sympatholytics

الوصف: Aim: To investigate the effects of bilobalide on the activation of NF-κB, and apoptosis of dopaminergic neurons induced by 6-hydroxydopamine (6-OHDA). Methods: A rat model of Parkinson's disease was produced with a unilateral infusion of 6-OHDA (8 μg) into the substantia nigra par compact. Bilobalide was administered 5, 10, and 20 mg/kg (ip) once a day for 7 d, starting 6 d prior to the 6-OHDA infusion. The rats were subjected to locomotor activity and rotational behavior testing 2 or 3 weeks after the 6-OHDA infusion. The expressions of tyrosine hydroxylase (TH) and NF-κB p65 were examined by immunofluorescence. The loss of dopaminergic neurons was detected by Nissl's staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to identify apoptosis. Results: The behavioral changes due to 6-OHDA were significantly restored by bilobalide pretreatment. Bilobalide inhibited the 6-OHDA-induced loss of TH-positive neurons, decreased the activation of NF-κB, and protected dopaminergic neurons from apoptosis remarkably. Conclusion: NF-κB activation contributes to the 6-OHDA-induced loss of dopaminergic neurons, and the inhibition of the NF-κB pathway is likely to be involved in the neuroprotective effect of bilobalide.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0ceba378d7f40ac91446e4ba03d4fd6bTest
https://pubmed.ncbi.nlm.nih.gov/18430361Test

المؤلفون: Jun-Chao Wu, Shu-dong Yu, Hong-jun Zhu, Zheng-Hong Qin, Jing-kang He

المصدر: Acta pharmacologica Sinica. 28(12)

مصطلحات موضوعية: Lipopolysaccharide, medicine.medical_treatment, Ischemia, Enzyme-Linked Immunosorbent Assay, Pharmacology, Lung injury, chemistry.chemical_compound, Medicine, Lung transplantation, Animals, Pharmacology (medical), Lung, biology, business.industry, NF-kappa B, General Medicine, respiratory system, Triptolide, Phenanthrenes, medicine.disease, medicine.anatomical_structure, chemistry, Myeloperoxidase, Reperfusion Injury, Immunology, Models, Animal, biology.protein, Immunohistochemistry, Epoxy Compounds, Rabbits, Diterpenes, business, Lung Transplantation

الوصف: To investigate the protective effect of triptolide (TRI) on ischemia/reperfusion-induced injury of transplanted rabbit lungs and to investigate the mechanisms underlying the actions of TRI.We established the rabbit lung transplantation model and studied lung injury induced by ischemia/reperfusion and the inhibitory effect of TRI on NF-kappaB. The severity of lung injury was determined by a gradual decline in PvO2, the degree of lung edema, the increase in the myeloperoxidase (MPO) activity, and the ultrastructural changes of transplanted lungs. The activation of NF-kappaB was measured by immunohistochemistry. The increase in intercellular adhesion molecule-1 (ICAM-1), which is the target gene of NF-kappaB, was evaluated by ELISA.After reperfusion, there was a gradual decline in the PvO2 level in the control group (group I). The level of PvO2 in the group treated with lipopolysaccharide (group II) was significantly decreased, whereas that of the group treated with TRI (group III) was markedly improved (P0.01). In group III, the activity of MPO was downregulated, and the pulmonary edema did not become severe and the ultrastructure of the donor lung remained normal. The activity of NF-kappaB and the expression of ICAM-1 was significantly increased in the donor lungs. TRI blocked NF-kappaB activation and ICAM-1 expression.The effects of TRI on reducing injury to donor lungs induced by ischemia/reperfusion may possibly be mediated by inhibiting the activity of NF-kappaB and the expression of the NF-kappaB target gene ICAM-1. Thus, TRI could be used in lung transplantations for improving the function of donor lungs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::640dd972a6e9b46a89a9b7997463b15dTest
https://pubmed.ncbi.nlm.nih.gov/18031605Test