Celastrol

[This retracts the article DOI: 10.1155/2022/1948657.].

Glioblastoma, a highly aggressive and lethal brain cancer, lacks effective treatment options and has a poor prognosis. In our study, we explored the potential anti-cancer effects of sodium butyrate (SB) and celastrol (CEL) in two glioblastoma cell lines. SB, a histone deacetylase inhibitor, and CEL, derived from the tripterygium wilfordii plant, act as mTOR and proteasome inhibitors. Both can cross the blood-brain barrier, and they exhibit chemo- and radiosensitive properties in various cancer models. GB cell lines LN-405 and T98G were treated with SB and CEL...

The object of this study was to trace TwHf-derived toxins in raw honey and clarify their acute toxic effect related to the addition of honey or sugars. TwHf flowers, raw honey from TwHf planting base and from beekeepers in high-risk area were detected using LC-MS/MS. The results revealed five target toxins were detected in TwHf flowers; only celastrol was detected in one raw honey sample, as a food safety risk factor, celastrol had been traced back to TwHf flowers from raw honey. In a series of acute toxic tests on zebrafish, toxification effects were observed when honey, mimic honey or sugar was mixed with toxins...

BACKGROUND: Spinal cord injury (SCI) is a traumatic injury to the central nervous system and can cause lipid peroxidation in the spinal cord. Ferroptosis, an iron-dependent programmed cell death, plays a key role in the pathophysiology progression of SCI. Celastrol, a widely used antioxidant drug, has potential therapeutic value for nervous system. PURPOSE: To investigate whether celastrol can be a reliable candidate for ferroptosis inhibitor and the molecular mechanism of celastrol in repairing SCI by inhibiting ferroptosis...

Previous study has indicated that Celastrol (Cel) has various physiological and pharmacological effects, including antibacterial, antioxidant, pro-apoptotic, anticancer and anti-rheumatoid arthritis (RA) effects. However, low water solubility, low oral bioavailability, narrow treatment window, and high incidence of systemic adverse reactions still limit the further clinical application of Cel. Here, aiming at effectively overcome those shortcomings of Cel to boost its beneficial effects for treating RA, we developed the leukosome (LEUKO) coated biomimetic nanoparticles (NPs) for the targeted delivery of Cel to arthritis injury area in RA...

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem was developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor were combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles were internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibited the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protected SH-SY5Y cells from the toxicity of H2 O2 ...

Mitochondrial dysfunction contributes to the development of secondary brain injury (SBI) following intracerebral hemorrhage (ICH) and represents a promising therapeutic target. Celastrol, the primary active component of Tripterygium wilfordii, is a natural product that exhibits mitochondrial and neuronal protection in various cell types. This study aims to investigate the neuroprotective effects of celastrol against ICH-induced SBI and explore its underlying mechanisms. Celastrol improves neurobehavioral and cognitive abilities in mice with autologous blood-induced ICH, reduces neuronal death in vivo and in vitro, and promotes mitochondrial function recovery in neurons...

OBJECTIVE: Celastrol is a bioactive constituent extracted from Tripterygium wilfordii (thunder god vine). It has been demonstrated to have a therapeutic effect on experimental disease models for chronic inflammatory and immune disorders. In the present study, we investigated whether and how celastrol exerts a regulatory effect on the autoimmune response in MRL/lpr mice. METHODS: We performed an in vivo study to determine the therapeutic effects of celastrol in MRL/lpr mice and then further investigated the underlying mechanism of celastrol in the regulation of the autoimmune response in MRL/lpr mice...

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Abnormal proliferation of aggressive fibroblast-like synoviocytes (FLS) and perpetuate synovial inflammation can inevitably accelerate the progression of rheumatoid arthritis (RA). Herein, a strategy of simultaneously promoting FLS apoptosis and inhibiting inflammation as mediated by macrophages is proposed to restore synovial homeostasis for effective RA therapy. A hyaluronic acid-based dissolvable microneedle (MN) is fabricated for transdermal delivery of dual human serum albumin (HSA)-contained biomimetic nanocomplexes to regulate RA FLS and macrophages...

Celastrol is a quinone methyl triterpenoid monomeric ingredient extracted from the root of Tripterygium wilfordii . Celastrol shows potential pharmacological activities in various diseases, which include inflammatory, obesity, cancer, and bacterial diseases. However, the application prospect of celastrol is largely limited by its low bioavailability, poor water solubility, and undesired off-target cytotoxicity. To address these problems, a number of drug delivery methods and technologies have been reported to enhance the efficiency and reduce the toxicity of celastrol...

Clear cell renal cell carcinoma (ccRCC) incidence has risen steadily over the last decade. Elevated lipid uptake and storage is required for ccRCC cell viability. As stored cholesterol is the most abundant component in ccRCC intracellular lipid droplets, it may also play an important role in ccRCC cellular homeostasis. In support of this hypothesis, ccRCC cells acquire exogenous cholesterol through the HDL receptor SCARB1, inhibition or suppression of which induces apoptosis. Here, we showed that elevated expression of 3 beta-hydroxy steroid dehydrogenase type 7 (HSD3B7), which metabolizes cholesterol-derived oxysterols in the bile acid biosynthetic pathway, is also essential for ccRCC cell survival...

PURPOSE: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. However, the effect of current treatment strategies by inducing tumor cell apoptosis alone is not satisfactory. The growth, metastasis and treatment sensitivity of tumors can be strongly influenced by cancer-associated fibroblasts (CAFs) in the microenvironment. Effective cancer therapies may need to target not only the tumor cells directly but also the CAFs that protect them. METHODS: Celastrol and small-sized micelles containing betulinic acid were co-encapsulated into liposomes using the thin-film hydration method (CL@BM)...

BACKGROUND: Tripterygium wilfordii Hook. f. (TW) shows anticancer activity, and no study has comprehensively investigated the effects of TW in treating cholangiocarcinoma (CHOL). This study was designed to identify the therapeutic role and the mechanism of TW against CHOL to obtain anti-CHOL candidate components and targets. METHODS: Ingredients of TW were collected from the Traditional Chinese Medicine System Pharmacology Database and literature. Limma package and weighted gene co-expression network analysis were used to identify the genes related to CHOL...

BACKGROUND: Malaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive. METHODS: We first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum...

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although treatment options have improved, a large proportion of patients show low survival rates, highlighting an urgent need for novel therapeutic strategies. The aim of this study was to investigate the efficacy of the new small-molecule compound dihydrocelastrol (DHCE), acquired through the structural modification of celastrol (CE), in the treatment of DLBCL. DHCE showed potent anti-lymphoma efficacy and synergistic effects with doxorubicin...

Anti-IL-17A antibodies, such as secukinumab and ixekizumab, are effective proinflammatory cytokine inhibitors for autoimmune disorders, including psoriasis. However, anti-IL-17A small molecule treatments are yet to be commercialized. Celastrol, a natural compound extracted from the roots of traditional Chinese medicinal plants, has anti-inflammatory and antioxidant properties. However, the binding of celastrol to IL-17A and the associated anti-inflammatory mechanisms remain unclear. This study investigated whether celastrol could directly bind to IL-17A and regulate inflammation in psoriatic in vitro and in vivo models...

OBJECTIVE: To determine whether celastrol, an inhibitor of the mechanosensitive transcriptional cofactor yes-associated protein-1 (YAP1), impairs the ability of TGFβ1 to stimulate fibrogenic activity in human gingival fibroblast cell line. DESIGN: Human gingival fibroblasts were pre-treated with celastrol or DMSO followed by stimulation with or without TGFβ1 (4 ng/ml). We then utilized bulk RNA sequencing (RNAseq), real-time polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, cell proliferation assays to determine if celastrol impaired TGFβ1-induced responses in a human gingival fibroblast cell line...

Triggering ferroptosis is a potential therapeutic pathway and strategy for the prospective treatment of lethal hepatocellular carcinoma (HCC). The asialo-glycoprotein receptor (ASGPR) is an over-expressed receptor on the membranes of hepatocellular carcinoma cells (HCCs) and binds specifically to galactose (Gal) ligand. Celastrol (CE) is a potent anticancer natural product, but its poor water solubility and severe toxicity restrict its clinical application. In this study, a carrier-free self-assembled nanoparticles, CE-Gal-NPs, were designed and prepared by nanoprecipitation method, which could recognize ASGPR receptor by active targeting (Gal ligand) and passive targeting (EPR effect), access to the cell through the clathrin pathway and finally internalize to lysosomes...

Matrix metalloproteinase 9 (MMP9) plays a pivotal role in mammary ductal morphogenesis, angiogenesis and glandular tissue architecture remodeling. However, the molecular mechanism of MMP9 expression in mammary epithelial cells of dairy cows remains unclear. This study aimed to explore the underlying mechanism of MMP9 expression. In this study, to determine whether the PI3K/AKT/mTORC1/NF-κB signalling pathway participates in the regulation of MMP9 expression, we treated mammary epithelial cells with specific pharmacological inhibitors of PI3K (LY294002), mTORC1 (Rapamycin) or NF-κB (Celastrol), respectively...