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Celastrol

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https://www.readbyqxmd.com/read/28239352/celastrol-attenuates-multiple-sclerosis-and-optic-neuritis-in-an-experimental-autoimmune-encephalomyelitis-model
#1
Hongbin Yang, Chang Liu, Jie Jiang, Yuena Wang, Xiaoyu Zhang
This study was aimed to evaluate the effects of celastrol, a natural compound with multiple bioactivities, on multiple sclerosis and optic neuritis (ON) in rat experimental autoimmune encephalomyelitis (EAE). EAE was induced in Sprague Dawley rats using myelin basic protein, and the animals received daily intraperitoneal injections of celastrol or vehicle for 13 days. The EAE rats showed abnormal neurobehavior and inflammatory infiltration and demyelination in the spinal cord. Significantly upregulated mRNA expression of pro-inflammatory cytokines interferon-γ and interleukin-17 and downregulated anti-inflammatory cytokines interleukin-4 were found in the spinal cord of EAE rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28195223/celastrol-an-active-constituent-of-the-tcm-plant-tripterygium-wilfordii-hook-f-inhibits-prostate-cancer-bone-metastasis
#2
K Kuchta, Y Xiang, S Huang, Y Tang, X Peng, X Wang, Y Zhu, J Li, J Xu, Z Lin, T Pan
BACKGROUND: Treatment failure of prostate cancer (PCa) is often due to bone metastasis. Celastrol, an active constituent of Tripterygium wilfordii roots, has shown anti-tumor effects in previous studies in accordance with its indication in traditional Chinese medicine. METHODS: Using a PC-3 cell model, in vitro assays were performed to evaluate the effects of celastrol on proliferation, migration (wound healing assay), tissues invasion (Transwell-Matrigel penetration assay) and vascular endothelial growth factor (VEGF) secretion (enzyme-linked immunosorbent assay)...
February 14, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28189063/the-nf-%C3%AE%C2%BAb-inhibitor-celastrol-attenuates-acute-hepatic-dysfunction-induced-by-cecal-ligation-and-puncture-in-rats
#3
Ghada S El-Tanbouly, Mohammed S El-Awady, Nermeen A Megahed, Hatem A Salem, Hassan A El-Kashef
Acute hepatic dysfunction associating sepsis is mediated mainly by toll-like receptor-4 (TLR-4)/nuclear factor kappa-B (NF-κB) inflammatory pathway. This study explores potential hepatoprotective effect of the NF-κB inhibitor celastrol in cecal ligation and puncture (CLP) model in rats. Protective effect of celastrol (1mg/kg, i.p., 1h before CLP) was illustrated after 24h by preventing CLP-induced hepatic histopathological changes and elevation in serum hepatic biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB) and gamma aminotransferase (γ-GT)] without affecting mortality...
March 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28161417/celastrol-attenuates-mitochondrial-dysfunction-and-inflammation-in-palmitate-mediated-insulin-resistance-in-c3a-hepatocytes
#4
Mohamad Hafizi Abu Bakar, Mohamad Roji Sarmidi, Joo Shun Tan, Mohamad Norisham Mohamad Rosdi
Accumulating evidence indicates that mitochondrial dysfunction-induced inflammation is among the convergence points for the greatest hallmarks of hepatic insulin resistance. Celastrol, an anti-inflammatory compound from the root of Tripterygium Wilfordii has been reported to mitigate insulin resistance and inflammation in animal disease models. Nevertheless, the specific mechanistic actions of celastrol in modulating such improvements at the cellular level remain obscure. The present study sought to explore the mechanistic roles of celastrol upon insulin resistance induced by palmitate in C3A human hepatocytes...
February 1, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28129433/celastrol-ameliorates-cd-induced-neuronal-apoptosis-by-targeting-nox2-derived-ros-dependent-pp5-jnk-signaling-pathway
#5
Chong Xu, Xiaoxue Wang, Chenjian Gu, Hai Zhang, Ruijie Zhang, Xiaoqing Dong, Chunxiao Liu, Xiaoyu Hu, Xiang Ji, Shile Huang, Long Chen
Celastrol, a plant-derived triterpene, has neuroprotective benefit in the models of neurodegenerative disorders that are characterized by overproduction of reactive oxygen species (ROS). Recently, we have reported that cadmium (Cd) activates c-Jun N-terminal kinase (JNK) pathway leading to neuronal cell death by inducing ROS inactivation of protein phosphatase 5 (PP5), and celastrol prevents Cd-activated JNK pathway against neuronal apoptosis. Therefore, we hypothesized that celastrol could hinder Cd induction of ROS-dependent PP5-JNK signaling pathway from apoptosis in neuronal cells...
January 27, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28128232/functional-characterization-of-nes-and-ges-responsible-for-the-biosynthesis-of-e-nerolidol-and-e-e-geranyllinalool-in-tripterygium-wilfordii
#6
Ping Su, Tianyuan Hu, Yujia Liu, Yuru Tong, Hongyu Guan, Yifeng Zhang, Jiawei Zhou, Luqi Huang, Wei Gao
Triptolide and celastrol, two principal bioactive compounds in Tripterygium wilfordii, are produced from geranylgeranyl diphosphate (GGPP) and farnesyl diphosphate ((E,E)-FPP) through terpenoid biosynthesis pathway. However, little is known about T. wilfordii terpene synthases which could competitively utilize GGPP and (E,E)-FPP as substrates, producing C15 and C20 tertiary alcohols. Here we firstly cloned the genes encoding nerolidol synthase (NES) and geranyllinalool synthases (GES1, GES2), which are responsible for the biosynthesis of (E)-nerolidol and (E,E)-geranyllinalool...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28123944/celastrol-ameliorates-liver-metabolic-damage-caused-by-a-high-fat-diet-through-sirt1
#7
Yinliang Zhang, Chao Geng, Xiaoyan Liu, Meixia Li, Mingyue Gao, Xiaojun Liu, Fude Fang, Yongsheng Chang
OBJECTIVE: Celastrol was recently identified as a potential novel treatment for obesity. However, the effect of Celastrol on nonalcoholic fatty liver disease (NAFLD) remains elusive. The aim of this study is to evaluate the role of Celastrol in NAFLD. METHODS: Functional studies were performed using wild-type C57BL/6J (WT) mice and liver specific Sirt1-deficient (LKO) mice. The molecular mechanism was explored in primary mouse liver and primary hepatocytes. RESULTS: When WT mice receiving a high-fat diet (HFD) were treated with Celastrol, reductions in body weight, subcutaneous and visceral fat content, and liver lipid droplet formation were observed, along with reduced hepatic intracellular triglyceride and serum triglyceride, free fatty acid, and ALT concentrations...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28119074/celastrol-attenuates-angiotensin-ii-mediated-human-umbilical-vein-endothelial-cells-damage-through-activation-of-nrf2-erk1-2-nox2-signal-pathway
#8
Miao Li, Xin Liu, Yongpeng He, Qingyin Zheng, Min Wang, Yu Wu, Yuanpeng Zhang, Chaoyun Wang
Angiotensin II (Ang II), as a crucial factor of endothelial dysfunction, participates in endothelial oxidative damage and inflammation, which is present in all cardiovascular disease (CVD). Celastrol, extracted from Trypterygiun wilfordii Hook F. ("Thunder of God Vine"), is a natural compound with antioxidant and anti-inflammatory activities. In this study, the protective effects of celastrol on human umbilical vein endothelial cell (HUVEC) injury induced by Ang II were observed and its mechanisms were elucidated...
January 21, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28108421/tlr4-knockout-attenuated-high-fat-diet-induced-cardiac-dysfunction-via-nf-%C3%AE%C2%BAb-jnk-dependent-activation-of-autophagy
#9
Nan Hu, Yingmei Zhang
Obesity is commonly associated with a low grade systemic inflammation, which may contribute to the onset and development of myocardial remodeling and contractile dysfunction. Toll-like receptor 4 (TLR4) plays an important role in innate immunity and inflammation although its role in high fat diet-induced obesity cardiac dysfunction remains elusive. This study was designed to examine the effect of TLR4 ablation on high fat diet intake-induced cardiac anomalies, if any, and underlying mechanism(s) involved. Wild-type (WT) and TLR4 knockout mice were fed normal or high fat (60% calorie from fat) diet for 12weeks prior to assessment of mechanical and intracellular Ca(2+) properties...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28027722/celastrol-suppresses-expression-of-adhesion-molecules-and-chemokines-by-inhibiting-jnk-stat1-nf-%C3%AE%C2%BAb-activation-in-poly-i-c-stimulated-astrocytes
#10
Soo Yeon An, Gi Soo Youn, Hyejin Kim, Soo Young Choi, Jinseu Park
In the central nervous system, viral infection can induce inflammation by up-regulating pro-inflammatory mediators that contribute to enhanced infiltration of immune cells into the central nervous areas. Celastrol is known to exert various regulatory functions, including anti-microbial activities. In this study, we investigated the regulatory effects and the mechanisms of action of celastrol against astrocytes activated with polyinosinic-polycytidylic acid (poly(I:C)), a synthetic dsRNA, as a model of pro-inflammatory mediated responses...
September 2, 2016: BMB Reports
https://www.readbyqxmd.com/read/27931154/inhibition-of-ikk%C3%AE-by-celastrol-and-its-analogues-an-in-silico-and-in-vitro-approach
#11
Karpagam Veerappan, Sathishkumar Natarajan, Purushoth Ethiraj, Umashankar Vetrivel, Shila Samuel
CONTEXT: Alzheimer's disease (AD) is the most common form of dementia affecting the aged population and neuroinflammation is one of the most observed AD pathologies. NF-κB is the central regulator of inflammation and inhibitor κB kinase (IKK) is the converging point in NF-κB activation. Celastrol is a natural triterpene used as a treatment for inflammatory conditions. OBJECTIVE: This study determines the neuroprotective and inhibitory effect of celastrol on amyloid beta1-42 (Aβ1-42) induced cytotoxicity and IKKβ activity, respectively...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27920521/celastrol-nanomicelles-attenuate-cytokine-secretion-in-macrophages-and-inhibit-macrophage-induced-corneal-neovascularization-in-rats
#12
Zhanrong Li, Jingguo Li, Lei Zhu, Ying Zhang, Junjie Zhang, Lin Yao, Dan Liang, Liya Wang
The aim of the present study was to investigate the inhibitory effects of celastrol-loaded nanomicelles (CNMs) on activated macrophage-induced corneal neovascularization (CNV) in rats and cytokine secretion in macrophages. Using an angiogenesis assay in vitro, we detected the effects of CNMs on human umbilical vein endothelial cell (HUVEC) migration and invasion. In addition, the expression levels of cytokines secreted from hypoxia-induced macrophages were assessed through cytokine array analysis. The expression of hypoxia-inducible factors-1α (HIF-1α), nuclear factor-kappa B p65 (NF-κB p65), phospho-nuclear factor-kappa B p65 (phospho-NF-κB p65), p38 mitogen-activated protein kinase (p38 MAPK), phospho-p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and phospho-ERK1/2 was analyzed by western blotting...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27919190/investigation-of-the-influence-of-glycyrrhizin-on-the-pharmacokinetics-of-celastrol-in-rats-using-lc-ms-and-its-potential-mechanism
#13
Guangkui Yan, Hanhua Zhang, Wei Wang, Yuan Li, Chenghuang Mao, Mingqiao Fang, Xianhong Yi, Jingdong Zhang
1. The aim of this study was to investigate the effects of glycyrrhizin on the pharmacokinetics of celastrol in rats. 2. Twelve male Sprague-Dawley rats were randomly assigned to two groups: control group and test group. Test group was pretreated with glycyrrhizin at a dose of 100 mg/kg/day for 10 days, and then the two groups were orally administered with celastrol at a dose of 1 mg/kg. The concentration of celastrol was determined using a sensitive and reliable LC-MS method. 3. The results showed that glycyrrhizin could significantly decrease the plasma concentration (from 64...
December 5, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27910878/lipids-celastrol-protects-against-fatty-liver-through-sirt1
#14
Charlotte Ridler
No abstract text is available yet for this article.
December 2, 2016: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/27900015/celastrol-negatively-regulates-cell-invasion-and-migration-ability-of-human-osteosarcoma-via-downregulation-of-the-pi3k-akt-nf-%C3%AE%C2%BAb-signaling-pathway-in-vitro
#15
Xiaolong Yu, Qiang Wang, Xin Zhou, Changlin Fu, Ming Cheng, Runsheng Guo, Hucheng Liu, Bin Zhang, Min Dai
Osteosarcoma (OS) is a primary malignant tumor of the bone, with a tendency to metastasize early. Despite the advances in treatment options, more than 30% of patients develop distant metastases, and the prognosis of these patients with metastases is extremely poor. Celastrol has been demonstrated to manifest multiple pharmacological activities, including induction of apoptosis in numerous types of cancer cell lines. Our previous studies have also suggested that Celastrol is capable of inducing apoptosis of human osteosarcoma cells via the mitochondrial-dependent pathway...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27891586/celastrol-attenuates-cadmium-induced-neuronal-apoptosis-via-inhibiting-ca-2-camkii-dependent-akt-mtor-pathway
#16
Ruijie Zhang, Yu Zhu, Xiaoqing Dong, Beibei Liu, Nana Zhang, Xiaoxue Wang, Lei Liu, Chong Xu, Shile Huang, Long Chen
Cadmium (Cd), an environmental and industrial pollutant, affects the nervous system and consequential neurodegenerative disorders. Recently we have shown that celastrol prevents Cd-induced neuronal cell death partially by suppressing Akt/mTOR pathway. However, the underlying mechanism remains to be elucidated. Here we show that celastrol attenuated Cd-elevated intracellular free calcium ([Ca(2+) ]i ) level and apoptosis in neuronal cells. Celastrol prevented Cd-induced neuronal apoptosis by inhibiting Akt-mediated mTOR pathway, as inhibition of Akt with Akt inhibitor X or ectopic expression of dominant negative Akt reinforced celastrol's prevention of Cd-induced phosphorylation of S6K1/4E-BP1 and cell apoptosis...
November 27, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27881165/comparative-analysis-of-four-terpenoids-in-root-and-cortex-of-tripterygium-wilfordii-radix-by-different-drying-methods
#17
COMPARATIVE STUDY
Tuanjie Wang, Fei Shen, Shulan Su, Yongliang Bai, Sheng Guo, Hui Yan, Tao Ji, Yanyan Wang, Dawei Qian, Jin-Ao Duan
BACKGROUND: Tripterygium wilfordii Radix, a well-known traditional medicine in china which is used for treatment of inflammation, pain, tumor and immune regulation for centuries in china, accompany with the serious toxic side effects. This study was carried out for simultaneously analyzing the four main components (triptolide, triptophenolide, demethylzeylasteral and celastrol) in Tripterygium wilfordii Radix under different drying processes, which was important for reducing the toxicity and quality control of Tripterygium wilfordii Radix in future...
November 23, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27864779/activity-of-novel-inhibitors-of-staphylococcus-aureus-biofilms
#18
Seung-Gyun Woo, So-Yeon Lee, So-Min Lee, Kyoung-Hee Lim, Eun-Ju Ha, Yong-Bin Eom
Staphylococcus aureus is one of the most important pathogens causing chronic biofilm infections. These are becoming more difficult to treat owing to drug resistance, particularly because S. aureus biofilms limit the efficacy of antimicrobial agents, leading to high morbidity and mortality. In the present study, we screened for inhibitors of S. aureus biofilm formation using a natural product library from the Korea Chemical Bank (KCB). Screening by crystal violet-based biomass staining assay identified hit compounds...
November 18, 2016: Folia Microbiologica
https://www.readbyqxmd.com/read/27847245/celastrol-inhibits-dengue-virus-replication-via-up-regulating-type-i-interferon-and-downstream-interferon-stimulated-responses
#19
Jung-Sheng Yu, Chin-Kai Tseng, Chun-Kuang Lin, Yao-Chin Hsu, Yu-Hsuan Wu, Ching-Liang Hsieh, Jin-Ching Lee
ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY: Tripterygium wilfordii (lei gong teng; Thunder of God Vine), a member of the Celastraceae family, is a medicinal plant used to treat a range of illnesses. Celastrol is a quinone methide triterpene and the most abundant bioactive constituent isolated from the root extracts of T. wilfordii. Previous studies have shown that celastrol exhibits antiviral activity against HIV and SARS-CoV. To date, no investigations of the anti-DENV activity of celastrol have been reported...
January 2017: Antiviral Research
https://www.readbyqxmd.com/read/27823626/plant-derived-triterpene-celastrol-ameliorates-oxygen-glucose-deprivation-induced-disruption-of-endothelial-barrier-assembly-via-inducing-tight-junction-proteins
#20
Dan Luo, Jia Zhao, Jianhui Rong
BACKGROUND: The integrity and functions of blood-brain barrier (BBB) are regulated by the expression and organization of tight junction proteins. OBJECTIVE: The present study was designed to explore whether plant-derived triterpenoid celastrol could regulate tight junction integrity in murine brain endothelial bEnd3 cells. METHODS: We disrupted the tight junctions between endothelial bEnd3 cells by oxygen glucose deprivation (OGD). We investigated the effects of celastrol on the permeability of endothelial monolayers by measuring transepithelial electrical resistance (TEER)...
December 1, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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