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Celastrol

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https://www.readbyqxmd.com/read/29667734/celastrol-reverses-palmitic-acid-pa-caused-tlr4-md2-activation-dependent-insulin-resistance-via-disrupting-md2-related-cellular-binding-to-pa
#1
Xue Zhang, Ying Wang, Hui-Ya Ge, Yi-Jun Gu, Fan-Fan Cao, Chun-Xin Yang, Georges Uzan, Bin Peng, Deng-Hai Zhang
Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for celastrol is still unclear. As celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for celastrol to inhibit FFAs-caused inflammation and insulin resistance...
April 18, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29651912/effects-of-diclofenac-on-the-pharmacokinetics-of-celastrol-in-rats-and-its-transport
#2
Zengfu Wang, Dali Chen, Zhongwei Wang
CONTEXT: Diclofenac and celastrol are always used together for the treatment of rheumatoid arthritis; the herb-drug interaction potential between diclofenac and celastrol is still unknown. OBJECTIVE: This study investigates the effects of diclofenac on the pharmacokinetics of celastrol in rats. MATERIALS AND METHODS: Twelve male Sprague-Dawley rats were divided into two groups and received celastrol (1 mg/kg) or both celastrol (1 mg/kg) and diclofenac (10 mg/kg) by oral gavage, and blood samples were collected via the oculi chorioideae vein and determined using the LC-MS method developed in this study...
December 2018: Pharmaceutical Biology
https://www.readbyqxmd.com/read/29644847/preparation-of-microkernel-based-mesoporous-sio2-cdte-sio2-sio2-fluorescent-nanoparticles-for-imaging-screening-and-enrichment-of-heat-shock-protein-90-inhibitors-from-tripterygium-wilfordii
#3
Yue Hu, Zhao Yi Miao, Xiaojing Zhang, Xiaotong Yang, Yingying Tang, Sheng Yu, ChenXiao Shan, Hongmei Wen, Dong Zhu
The currently utilized ligand fishing for bioactive molecular screening from complex matrixes cannot perform imaging screening. Here, we developed a new solid-phase ligand fishing coupled with in situ imaging protocol for the specific enrichment and identification of heat shock protein 90 (Hsp 90) inhibitors from Tripterygium wilfordii, utilizing a multiple-layer and microkernel-based mesoporous nanostructure composed of a protective silica coating CdTe quantum dots (QDs) core and a mesoporous silica shell, i...
April 12, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29614269/celastrol-inhibits-cancer-metastasis-by-suppressing-m2-like-polarization-of-macrophages
#4
Yuening Yang, Shuyuan Cheng, Guikai Liang, Lou Honggang, Honghai Wu
In recent years, a large amount of clinical and experimental data has shown that M2-like polarized tumor-associated macrophages (TAMs) play an important role in cancer metastasis. Therefore, TAMs, especially M2-like TAMs is a promising target for anti-tumor metastasis therapy. Here, we found that celastrol dose-dependently suppressed IL-13 induced CD206 expression both in RAW264.7 and in primary macrophages. Consistently, celastrol also inhibited the expression of M2-like specific genes, including MRC1, Arg1, Fizz1, Mgl2 and CD11c...
March 31, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29593812/the-effect-of-celastrol-on-learning-and-memory-in-diabetic-rats-after-sevoflurane-inhalation
#5
Wei-Tao Liao, Xiao-Yu Xiao, Yinaxian Zhu, Shao-Peng Zhou
Introduction: The aim was to devise an animal model showing some of the neuropathological changes seen in senile dementia, and to investigate the effect of celastrol on cognition neuropathology in this model. Material and methods: Forty male Sprague Dawley rats weighing 300-350 g were randomly divided into 5 groups ( n = 8 each): control (Con); inhaled sevoflurane (Sev); diabetes mellitus (DM); diabetes mellitus + inhaled sevoflurane (DM/Sev); diabetes + inhaled sevoflurane + celastrol (Cel)...
March 2018: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29553945/celastrol-inhibits-colorectal-cancer-cell-proliferation-and-migration-through-suppression-of-mmp3-and-mmp7-by-the-pi3k-akt-signaling-pathway
#6
Tang Bufu, Xu Di, Zhao Yilin, Liang Gege, Chen Xi, Wang Ling
Colorectal cancer (CRC) is one of the most frequent malignant tumors. Signaling by the PI3K/AKT pathway is crucial for CRC development and progression, including proliferation and migration. Celastrol has an anticancer effect, but its mechanism needs to be determined. Here, we showed that celastrol suppressed CRC cell proliferation and migration. Celastrol treatment also decreased the PI3K/AKT pathway components, and MMP3 and MMP7 expression levels. In addition, knockdown of AKT, not mTOR, inhibited MMP3 and MMP7 expression levels and AKT silencing promoted the celastrol-induced effects on CRC cell proliferation and migration...
March 16, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29540209/celastrol-treatment-protects-against-acute-ischemic-stroke-induced-brain-injury-by-promoting-an-il-33-st2-axis-mediated-microglia-macrophage-m2-polarization
#7
Mei Jiang, Xinghui Liu, Denghai Zhang, Ying Wang, Xiaoxia Hu, Fengxia Xu, Mingming Jin, Fanfan Cao, Limin Xu
BACKGROUND: Acute ischemic stroke (AIS) is the most common type of cerebrovascular disease and is a leading cause of disability and death worldwide. Recently, a study suggested that transformation of microglia from the pro-inflammatory M1 state to the anti-inflammatory and tissue-reparative M2 phenotype may be an effective therapeutic strategy for ischemic stroke. Celastrol, a traditional oriental medicine, may have anti-inflammatory and neuroprotective effects. However, the underlying mechanisms remain unknown...
March 14, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29534015/targeting-hodgkin-and-reed-sternberg-cells-with-an-inhibitor-of-heat-shock-protein-90-molecular-pathways-of-response-and-potential-mechanisms-of-resistance
#8
Priscilla Segges, Stephany Corrêa, Bárbara Du Rocher, Gabriela Vera-Lozada, Flavia Krsticevic, Debora Arce, Cinthya Sternberg, Eliana Abdelhay, Rocio Hassan
Classical Hodgkin lymphoma (cHL) cells overexpress heat-shock protein 90 (HSP90), an important intracellular signaling hub regulating cell survival, which is emerging as a promising therapeutic target. Here, we report the antitumor effect of celastrol, an anti-inflammatory compound and a recognized HSP90 inhibitor, in Hodgkin and Reed-Sternberg cell lines. Two disparate responses were recorded. In KM-H2 cells, celastrol inhibited cell proliferation, induced G0/G1 arrest, and triggered apoptosis through the activation of caspase-3/7...
March 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29512444/pharmacokinetic-and-toxicological-characteristics-of-tripterigium-glycosides-and-their-derivatives
#9
Xi Du, Makafui Nyagblordzro, Lijun An, Xue Gao, Lemei Du, Yangyang Wang, Gregory Ondieki, Siambi Kikete, Xin He
Tripterigium wilfordii glycosides (TWG) demonstrate paramount bioactive effectiveness in the management of many autoimmune diseases, such as rheumatoid arthritis, psoriasis, and nephrotic syndrome. However, its side effects on the hepatic, nephrotic, reproductive, and cardiovascular systems have limited its immense therapeutic potentials. Triptolide (TP) and Celastrol (CL), the leading bioactive as well as toxic constituents of TWG, have been widely studied. These studies have documented the key mechanisms that trigger the toxic reactions and the precautionary measures that could prevent and reduce such reactions...
March 2, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29493374/in-vitro-immunomodulatory-activity-of-celastrol-against-influenza-a-virus-infection
#10
Niloofar Khalili, Ali Karimi, Mohammad-Taghi Moradi, Hedayatollah Shirzad
CONTEXT: The influenza A virus (IAV) causes severe respiratory disease that remains a leading reason for morbidity and mortality. Previous studies have indicated that influenza complications in addition to viral replication are due to overproduction of pro-inflammatory cytokines. Therefore, a new compound is needed to be used with current antiviral drugs to modulate overproduction of pro-inflammatory cytokines in IAV infection. OBJECTIVE: This study investigated the effect of celastrol on mRNA expression and concentration levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-6 (IL6) that are induced by influenza A/Puerto Rico/8/34 (H1N1; PR8) in Madin-Darby Canine Kidney (MDCK) cells...
March 1, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29491837/a-mechanistic-overview-of-triptolide-and-celastrol-natural-products-from-tripterygium-wilfordii-hook-f
#11
REVIEW
Shao-Ru Chen, Yan Dai, Jing Zhao, Ligen Lin, Yitao Wang, Ying Wang
Triptolide and celastrol are predominantly active natural products isolated from the medicinal plant Tripterygium wilfordii Hook F. These compounds exhibit similar pharmacological activities, including anti-cancer, anti-inflammation, anti-obesity, and anti-diabetic activities. Triptolide and celastrol also provide neuroprotection and prevent cardiovascular and metabolic diseases. However, toxicity restricts the further development of triptolide and celastrol. In this review, we comprehensively review therapeutic targets and mechanisms of action, and translational study of triptolide and celastrol...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29484434/mir-33a-5p-enhances-the-sensitivity-of-lung-adenocarcinoma-cells-to-celastrol-by-regulating-mtor-signaling
#12
You-Jie Li, Yun-Xiao Sun, Rui-Min Hao, Pin Wu, Li-Jun Zhang, Xu Ma, Ying Ma, Ping-Yu Wang, Ning Xie, Shu-Yang Xie, Wei Chen
MicroRNAs (miRNAs or miRs) have recently become a popular focus of cancer research due to their ability to act as oncogenes or tumor suppressors. In the present study, miR‑33a‑5p expression was identified to be downregulated in lung adenocarcinoma samples compared with normal, which suggested that miR‑33a‑5p may serve as a tumor suppressor gene. Transfection with miR‑33a‑5p mimics inhibited the proliferation and migration of A549 and LTEP‑a‑2 cells and increased cellular apoptosis. A luciferase reporter assay confirmed that miR‑33a‑5p targets the 3'‑untranslated region of the mechanistic target of rapamycin (mTOR) gene...
February 14, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29476742/celastrol-mediates-th17-and-treg-cell-generation-via-metabolic-signaling
#13
Jiabi Zhang, Juan Shan, Xuelu Chen, Shengfu Li, Dan Long, Youping Li
A T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance is involved in many immune disorders and diseases. Celastrol, a Chinese herbal compound that has anti-inflammatory and immunosuppressive properties, has been indicated to suppress T cell proliferation and Th17 cell induction, while facilitating Forkhead box P3 (Foxp3) expression and Treg cell generation. In this study, we explored the impact and mechanism of celastrol on Th17 cell/induced Treg (iTreg) cell induction. CD4+ CD25- T cells were purified, stimulated with anti-CD3 and anti-CD28 antibodies, and polarized in vitro to generate Th17 or iTreg cells in the presence or absence of celastrol...
February 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29475002/celastrol-pretreatment-attenuates-rat-myocardial-ischemia-reperfusion-injury-by-inhibiting-high-mobility-group-box-1-protein-expression-via-the-pi3k-akt-pathway
#14
Suiyang Tong, Liangliang Zhang, Jacob Joseph, Xue Jun Jiang
BACKGROUND/AIMS: Celastrol pretreatment has been shown to protect against myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism is poorly understood. This study aimed to investigate the cardioprotective effects of celastrol pretreatment on I/R injury and to further explore whether its mechanism of action was associated with the inhibition of high mobility group box 1 protein (HMGB1) expression via the phosphoinositide 3-kinase (PI3K)/Akt pathway. METHODS: In a fixed-dose study, hematoxylin and eosin staining and myocardial enzyme measurements were used to determine the optimal dose of celastrol that elicited the best cardioprotective effects against I/R injury...
February 20, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453086/pegylated-polyaminoacid-capped-mesoporous-silica-nanoparticles-for-mitochondria-targeted-delivery-of-celastrol-in-solid-tumors
#15
Ju Yeon Choi, Biki Gupta, Thiruganesh Ramasamy, Jee-Heon Jeong, Sung Giu Jin, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim
The major goal of cancer chemotherapy is to maximize the therapeutic efficacy of anticancer drugs, while minimizing their associated side effects. Celastrol (CST), which is extracted from the traditional Chinese medicinal plant Tripterygium wilfordii, has been reported to exhibit significant anticancer effects in various in vitro and in vivo cancer models. Nanoparticulate drug delivery systems could be employed to preserve and enhance the pharmacological effects of CST in cancer cells. Among these, mesoporous silica nanoparticles (MSNs) are one of the most promising drug delivery systems...
February 11, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29446727/natural-terpenoids-against-female-breast-cancer-a-5-year-recent-research
#16
Sylvin Benjamin Ateba, Sadrine Tchoukouegno Ngeu, Marie Alfrede Mvondo, Job Tchoumtchoua, Charline Florence Awounfack, Liselotte Krenn, Dieudonne Njamen
BACKGROUND: The approval of Taxol® in 1993 marked the great entrance of terpenoids in the anti-cancer area and this drug is still highly important in the treatment of refractory ovarian, breast and other cancers. Over decades, other prominent natural terpenoids have become indispensable for the modern pharmacotherapy of breast cancer. However, given the rapid evolution of drug resistance, effective treatments for advanced breast cancers requiring cytotoxic chemotherapy represent a major unmet clinical need...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29445341/celastrol-alleviates-airway-hyperresponsiveness-and-inhibits-th17-responses-in-obese-asthmatic-mice
#17
Zeyu Zeng, Xixi Lin, Rongying Zheng, Hui Zhang, Weixi Zhang
Severe airway hyperresponsiveness (AHR) is a clinical feature of asthma, which has been associated with obesity and has shown a poor response to standard asthma treatments such as glucocorticoids. Numerous studies have shown that Interleukin (IL)-17 producing CD4 + T cells (Th17 cells), which could be inhibited by celastrol, is essential in mediating steroid-resistant AHR. The following study investigates the impact of celastrol and its mechanism on the regulation of AHR in murine model of obesity and asthma...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29436996/herbal-products-for-common-auto-inflammatory-disorders-novel-approaches
#18
Fawzi Mahomoodally, Shanoo Suroowan
Common auto-inflammatory disorders (CAIDs) induce considerable suffering over the world. A panoply of synthetic medications areis available for theirits management. Nonetheless, available drug classes are limited by adverse effects, low systemic absorption, and high costs. In addition, no cure exists for most CAIDs. Interestingly, herbal products present a tremendous potential for development as anti-inflammatory agents. In this endeavor, major scientific databases; Google Scholar, Pubmed, ScienceDirect, and Scopus were explored to highlight novel therapeutic approaches using herbal products for CAIDs prophylaxis, management, treatment, and prevention of relapse...
February 12, 2018: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/29434967/celastrol-suppresses-the-proliferation-of-lung-adenocarcinoma-cells-by-regulating-microrna-24-and-microrna-181b
#19
Yun-Fei Yan, Han-Han Zhang, Qing Lv, Yue-Mei Liu, You-Jie Li, Bao-Sheng Li, Ping-Yu Wang, Wen-Jing Shang, Zhen Yue, Shu-Yang Xie
Cumulative evidence has indicated that celastrol may suppress cancer growth; however, the underlying mechanism requires further investigation. In the present study, A549 cells were treated with various concentrations of celastrol. Lung cancer cell proliferation was evaluated using an MTT assay and observed under a microscope. Cell apoptosis was detected by Annexin V fluorescein isothiocyanate/propidium iodide double-labeled flow cytometry. The results demonstrated that celastrol suppressed proliferation and induced apoptosis in a dose-independent manner...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29429468/-research-advances-in-necrotizing-enterocolitis-in-neonates
#20
Xin Gan, Juan Li
Necrotizing enterocolitis (NEC) is a catastrophic disease caused by a variety of factors in neonates, especially preterm infants. Severe NEC has a high fatality rate, and most survivors may face short- and long-term adverse prognosis. Risk factors for NEC include preterm birth, non-breastfeeding, microbial abnormalities in the digestive tract, and ischemia-reperfusion injury. High-resolution abdominal ultrasound helps with the early diagnosis of NEC. The preventive measures for NEC include protecting the intestinal mucosa through nutritional intervention, interfering with intestinal injury signals, changing intestinal microflora, and performing early minimal enteral nutrition...
February 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
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