CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Li Zhu,Yue Zheng,Mengjuan Yu,Shan Yu,Yiyun Luo,Ravin Narain,Kaihui Nan,Yangjun Chen
Corneal neovascularization (CNV), a major cause of vision impairment, requires improved therapeutic strategies. While Celastrol (Cel), a natural product extracted from traditional Chinese herbs, demonstrates anti-angiogenic potential for CNV treatment, its clinical application can be hindered by poor aqueous solubility and ocular bioavailability. To address this, we developed mucoadhesive micelles using phenylboronic acid (PBA)- and stearic acid (SA)-modified chitosan oligosaccharides (COS) for encapsulation and enhanced ocular delivery of Cel. The Cel-loaded micelles (COSA-PBA@Cel) exhibited a positive Zeta potential of approximately +27 mV, facilitating electrostatic interaction with negatively charged ocular mucin. PBA integration further enabled dynamic covalent bonding with sialic acid residues, synergistically prolonging corneal retention. Therefore, COSA-PBA@Cel nanomicelles exhibited remarkably prolonged ocular surface retention time. In vitro experiments demonstrated that COSA-PBA@Cel micelles effectively inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs), showcasing potent anti-neovascular activity. In a mouse model of alkali burn-induced CNV, COSA-PBA@Cel micelles significantly suppressed pathological angiogenesis, primarily through enhanced Cel delivery that modulates the HIF-1α/VEGF signaling pathway. This nanoplatform overcomes key ocular drug delivery challenges while leveraging Cel's therapeutic potential, offering a promising topical solution for CNV management.
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高影响因子
JOURNAL OF DRUG TARGETING
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2024
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IF 4.3
Chenglong Li,Yan Li,Qing Zeng,Yang Zhou,Huaiyu Su,Yangyun Han,Chen Li
Rheumatoid arthritis (RA) is a chronic autoimmune inflammation. Excessive proliferation and inadequate apoptosis of synovial macrophages are the crucial events of RA. Therefore, delivering therapeutic molecules to synovial macrophages specifically to tackle apoptotic insufficiency probably be an efficient way to reduce joint inflammation and bone erosion. Based on the characteristics of dextran sulfate (DS) specifically binding scavenger receptor A (SR-A) on macrophage and celastrol (CLT) inducing apoptosis, we designed synovial macrophage-targeted nano-emulsions encapsulated with CLT (SR-CLTNEs) and explored their anti-RA effect. After intravenous injection, fluorescence-labeled SR-CLTNEs successfully targeted inflammatory joints and synovial macrophages in a mouse model of RA, with the macrophage targeting efficiency of SR-CLTNEs, CLTNEs, and Free DID was 20.53%, 13.93%, and 9.8%, respectively. In vivo and in vitro studies showed that SR-CLTNEs effectively promoted the apoptosis of macrophages, reshaped the balance between apoptosis and proliferation, and ultimately treated RA in a high efficiency and low toxicity manner. Overall, our work demonstrates the efficacy of using SR-CLTNEs as a novel nanotherapeutic approach for RA therapy and the great translational potential of SR-CLTNEs.
研究领域:
药理学
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免疫学
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纳米技术
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风湿病学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2026
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IF 5.2
Ke Tang,Ni Huang,Rui Xue,Lu-lu Jia,Qin-you Tan
Objective Investigate the inhibitory effect of iron oxide nanoparticles (Fe 3 O 4 @Cel) containing rhein from Celastrol (Cel) on glioblastoma multiforme (GBM) and the underlying mechanism. Method Fe 3 O 4 @Cel was synthesized, and its characteristics were evaluated through chemical and physical analysis and observed directly under a transmission electron microscope. The inhibitory effect of Fe 3 O 4 @Cel on GBM was monitored by constructing in situ GBM cell tumors and axillary transplantation tumor animal models, and the in vivo safety of Fe 3 O 4 @Cel was evaluated by measuring the body weight, liver and kidney serum indicators, and Hematoxylin-eosin staining (HE) indices of important organs such as heart, liver, spleen, lung, and kidney. After C6, U251, and U87-MG cells were intervened with Fe 3 O 4 Cel, the cell survival ability was detected using the Cell Counting Kit-8. The cell proliferation, invasion, and migration abilities were verified through plate cloning and transwell migration and invasion experiments. The morphological changes of cell ferroptosis were detected by transmission electron microscopy. Western blotting proved the expression levels of cell ferroptosis markers. The changes in IL-18 and IL-1β contents in the culture medium after Fe 3 O 4 @Cel intervention were detected by Elisa experiments. The construction of stable overexpressed and low-expressed GSDME gene GBM cell lines further verified the certainty of the mechanism of Fe 3 O 4 @Cel in inhibiting GBM. Result The successfully synthesized Fe 3 O 4 @Cel has a hydrated particle diameter of approximately 120 nanometers and a Zeta potential of -50.99. Fe 3 O 4 @Cel has inhibitory effects on both in situ GBM and axillary transplanted tumor models of tumors, and no significant changes in liver and kidney indicators or substantial damage to important organs were observed. In vitro, Fe 3 O 4 @Cel has inhibitory effects on C6, U251, and U87-MG cells. Compared with the control group, the transmission electron microscopy results of the Fe 3 O 4 @Ce group indicate that the pyroptosis phenomenon of C6 and U87-MG cells is significantly increased, and their migration and invasion abilities are significantly weakened. In addition, the expression of pyroptosis-related proteins Cleaved-Caspase-3 and GSDME-N, as well as the contents of IL-18 and IL-1β in the cell culture medium, have all increased. The transfection results indicate that the GSDME gene is one of the key effector genes for pyroptosis in C6 and U87-MG cells. Conclusion The Fe 3 O 4 @Cel nanomaterials possess stable characterization properties and exhibit certain anti-GBM cell activity both in vitro and in vivo. This process is dependent on the activation of Caspase-3/GSDME cell pyroptosis signaling by Fe 3 O 4 @Cel. Moreover, no substantial damage to important organs and functions was observed in the body due to Fe 3 O 4 @Cel. Graphical Abstrac: Fe 3 O 4 @Cel synthesis and the mechanism by which Fe 3 O 4 @Cel promotes pyroptosis and activates immune cell populations among GBM cells . We synthesized Fe 3 O 4 @Cel by high-temperature pyrolysis and a phase-transfer method, which enabled Cel to be loaded into Fe 3 O 4 nanocarriers. Fe 3 O 4 @Cel activated caspase-3 in GBM cells, and activated caspase-3 cleaves full-length GSDME, which separates its N-terminus from its C-terminus. This process promotes pyroptosis in GBM cells and the release of IL-18 and IL-1β into the TME, which activates immune cell populations, such as NK and T cells, in the TME. The promotion of pyroptosis in GBM cells enhances the anti-GBM effect of immune cells. Download: Download high-res image (305KB) Download: Download full-size image
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高影响因子
Frontiers in Oncology
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2025
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IF 3.3
Wei Zhang,Jiping Li,Xiuli Gao,Likun Liu,Hong Liang,Liling Yue
Background/Objectives Breast cancer treatment remains challenged by the non-specific distribution and systemic toxicity of conventional chemotherapeutics. Celastrol (CEL), a natural compound with antitumor efficacy, faces clinical limitations due to its toxicity and poor solubility. Glycyrrhizic acid (GA), known for tumor-suppressive and membrane-modifying properties, offers potential to enhance targeted drug delivery. This study aimed to develop GA-modified liposomes (GA/LIP-CEL) to synergistically improve CEL’s therapeutic specificity and safety. Methods GA/LIP-CEL nanoparticles were engineered via thin-film hydration, replacing cholesterol with GA. Physicochemical properties were characterized using TEM, DLS, and HPLC. In vitro evaluations included stability assays, cellular uptake (flow cytometry), cytotoxicity (MTT assay), mitochondrial membrane potential (JC-1 staining), apoptosis (Annexin V/PI), DNA damage (γ-H2AX immunofluorescence), and cell cycle analysis in BT549 breast cancer and MCF-10A normal cells. Results GA/LIP-CEL exhibited uniform spherical morphology (122.48 ± 5.37 nm), high drug loading (87.75 ± 2.61%), sustained release (70.13% cumulative release at 24 h), and colloidal stability (negligible size variation over 14 days). Compared to LIP-CEL, GA/LIP-CEL reduced IC50 in BT549 cells while lowering cytotoxicity in MCF-10A cells. Compared with the LIP-CEL group, GA/LIP-CEL treatment demonstrated a statistically significant increase in apoptotic cell proportion (P < 0.05). Enhanced mitochondrial dysfunction (P < 0.05) and DNA (P < 0.05) damage were observed. GA modification improved cellular uptake potentially via regulating membrane fluidity and receptor-mediated endocytosis effects, and induced S-phase arrest (31.66 ± 1.70% cells). Conclusions GA/LIP-CEL combines GA’s membrane-targeting capabilities with CEL’s therapeutic effects, improving stability, specificity, and safety. This platform represents a novel strategy for precision drug delivery, addressing limitations of conventional systems through natural component integration. Further validation of in vivo performance and pharmacokinetics is warranted to advance clinical translation.
研究领域:
药学
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肿瘤学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2024
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IF 7.6
Jie Chen,Yan Liu,Yanting You,Ruisi Zhou,Yanchun Li,Xinghong Zhou,Xiaohu Chen,Ying Yang,Jinxiang Chen,Hiu Yee Kwan,Xiaoshan Zhao,Yuyao Wu
Celastrol (CEL) has garnered significant interest for its anti-tumour properties and potential for colorectal cancer (CRC) treatment. However, its clinical use is constrained by its limited bioavailability and potential toxicity. Herein, a biotin-decorated CEL nano-drug delivery system using a zeolitic imidazolate framework (ZIF-8) as a carrier was synthesized, named CEL@ZIF-8@BIO. It exhibits excellent water solubility, efficient loading of CEL, and a high release rate in acidic environments. In vitro experiments demonstrated that CEL@ZIF-8@BIO inhibited proliferation, induced cell cycle arrest in G0/G1 phase, increased ROS production and reduced mitochondrial membrane potential in CRC cells. RNA-Seq analysis indicated that the anticancer mechanism of CEL@ZIF-8@BIO may be linked to ferroptosis as indicated by a significant increase in Fe 2 + levels, oxidative stress, lipid peroxidation, and mitochondrial dysfunction in CRC cells. Furthermore, these effects could be reversed by ferroptosis inhibitor. In vivo research revealed that CEL@ZIF-8@BIO significantly inhibited the growth of CRC tumours and reduced the toxicity associated with CEL treatment. Taken together, the CEL@ZIF-8@BIO nano-drug delivery system shows great promise for CRC therapy due to its improved efficacy and reduced toxicity.
研究领域:
癌症研究
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纳米技术
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药学
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分子生物学
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细胞生物学
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产品关联
DOI
高影响因子
Frontiers in Pharmacology
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2017
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IF 4.4
Yang Hongbin,Liu Chang,Jiang Jie,Wang Yuena,Zhang Xiaoyu
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. In the study of ON, severely inflammatory responses like in the spinal cord were also seen in the optic nerve, as well as obvious microgliosis. Furthermore, activation of nuclear factor kappa-B and upregulated inducible nitric oxide synthase was observed in the optic nerve. In addition, apoptosis of retinal ganglion cells and dysregulation of apoptotic-associated proteins in the optic nerve were found in EAE rats. Treatment of celastrol potently restored these changes. In most of the indexes, the effects of high dose of celastrol were better than the low dose. Our data conclude that administration of celastrol attenuates multiple sclerosis and ON in EAE via anti-inflammatory and anti-apoptotic effects. These findings provide new pre-clinical evidence for the use of celastrol in treatment of multiple sclerosis.
研究领域:
神经病学
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免疫学
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药理学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2023
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IF 5.6
Jiwen Fan,Meng Ren,Weiwei Chen,Haodong Wang,Yuquan He
Background Myocardial infarction (MI) triggers a strong inflammatory response mediating by NLRP3 inflammasome which is associated with cardiac fibrosis. The key players in this response are Interleukin (IL)-1 and IL-18, which are regulated by NLRP3 inflammasomes. Celastrol, a traditional Chinese medicine with strong anti-inflammatory activity, has recently reported as a cardioprotective agent. However, the mechanisms by which celastrol is cardioprotective in MI remain elusive. We hypothesized that Celastrol could reduce IL-1β and IL-18 expression and ameliorate myocardial fibrosis after myocardial infarction in rats, improve poor heart remodeling, and preserve heart function. Methods Myocardial infarction (MI) was caused by ligating the left anterior descending of male SD rats. Celastrol (1 mg/kg) or saline was administered every other day for 4 weeks. Heart function and fibrosis were assessed. Inflammatory and fibrotic markers in the myocardia were evaluated with immunohistochemistry, western blot, and ELISA. Molecular docking was employed to predict Celastrol's binding to NLRP3 protein. The effects of Celastrol on the expression of NLRP3 inflammasome and myocardial fibrosis genes were then examined in vitro . Results Celastrol maintained the left ventricular fractional shortening (FS) and ejection fraction (EF). Fibrosis was significantly reduced in animals treated with 1 mg/kg Celastrol (15.17 ± 1.82%) relative to controls (29.88 ± 4.28%). Celastrol also significantly reduced the NLRP3, IL-18, and IL-1β levels, together with macrophage and neutrophil infiltration in the myocardium. Molecular docking predicted that NLRP3 would bind tightly to Celastrol [Docking energy: −8.9 (kcal/mol)]. In vitro experiments showed reduced NLRP3 inflammasome and myocardial fibrosis-associated proteins expression in neonatal rat cardiac fibroblasts treated with Celastrol. Conclusions In post-MI rats, Celastrol, a naturally occurring active ingredient, was able to reduce myocardial fibrosis and improve cardiac function, according to our study. These effects may result from inhibiting the NLRP3 inflammasome and attenuating the early inflammatory storm after MI, suggesting that Celastrol may be useful in treating acute MI.
研究领域:
心脏病学
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药理学
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炎症
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Wanfen Liao,Aiwen Dong,Fatima Hafeez,Qinyong Ye,En Huang
Background Celastrol (CEL), a bioactive compound isolated from Tripterygium Wilfordii Hook. F, exerts neuroprotective effects through anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms in several neurodegenerative diseases, including Parkinson's disease (PD). CEL covalently binds to the thiol group of cysteine residues in cell division cycle 37 (CDC37), leading to redox-dependent modulation of CDC37 function. However, whether CEL redox regulates CDC37 and CEL-CDC37 interaction plays a role in pathogenesis of PD is still not be investigated yet. This study aids to demonstrate the role of CEL redox regulation of CDC37 in an MPTP-induced mouse model of PD. Methods Lentiviral vectors were used to overexpress or knock down CDC37 in MPTP-injected mice. CEL was administered to assess its effect on CDC37 redox status and related molecular pathways. Results CDC37 overexpression alleviated MPTP-induced motor deficits and dopaminergic neuron loss, whereas CDC37 knockdown exacerbated these impairments. Overexpression of CDC37 also suppressed activation of the NF-κB pathway and reduced phosphorylation of α-synuclein at serine 129 (p-S129-syn). MPTP insult decreased the reduced (active) form of CDC37 due to oxidative stress. CEL treatment restored CDC37 redox status, improved locomotor performance, preserved dopaminergic neurons, and inhibited both NF-κB activation and p-S129-synuclein levels. These effects were mediated by CEL's redox regulation of CDC37, which prevented its overoxidation, disrupted the Hsp90/CDC37 complex, and suppressed downstream pro-inflammatory and pro-pathogenic signaling. Conclusion Our study suggests that CEL restores the protective role of CDC37 in the MPTP-injected Parkinson's disease (PD) mouse model via redox regulation of CDC37, which prevents over-oxidation of CDC37 under high oxidative stress, and disrupts the Hsp90/CDC37 complex and subsequently blocks NF-κB pathway activation and p-S129-synuclein production. This study might provide a promising strategy for PD and further understanding of the therapeutic mechanism of CEL application.
研究领域:
神经退行性疾病
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药理学
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生物化学
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DOI
PubMed
高影响因子
Cells
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2024
·Vol. 13
·期 21
·1819
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IF 5.1
Peng He,Manshu Zou,Chanjuan Zhang,Yaning Shi,Li Qin
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and its prevention and treatment face severe challenges. It is crucial to improve the targeting of drugs on tumor cells and tissues. Celastrol (CeT), as an active ingredient of traditional Chinese medicine, possesses strong antitumor effects, especially in triggering apoptosis of HCC. However, due to its toxicity and lack of targeting, its application is greatly limited. HMCLPs, a nano-biomimetic platform carrying CeT with controllable drug release, enhanced targeting, and immunocompatibility, were developed for the first time, which can be used for the treatment of HCC. By utilizing homologous cell membranes and hyaluronic acid (HA), HMCLPs can precisely target tumor regions and release CeT in a controlled manner. Both in vitro and in vivo studies have demonstrated that HMCLPs loaded with CeT significantly increased the accumulation of reactive oxygen species (ROS), induced mitochondrial damage, and triggered apoptosis of HCC cells, resulting in effective treatment with minimal adverse reaction. The development of HMCLPs as a nanocarrier system for CeT delivery offers a promising therapeutic strategy for HCC. This innovative approach improves the targeted delivery and bioavailability of CeT, dramatically induces apoptosis in HCC cells, and exerts its powerful antitumor effects while minimizing systemic toxicity. The present study highlights the potential of combining innovative nanocarriers with powerful natural compounds such as CeT to enhance efficacy and reduce toxicity.
研究领域:
药理学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
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2021
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IF 5.051
Shaohua Xu,Ruolan Fan,Lu Wang,Weishen He,Haixia Ge,Hailan Chen,Wen Xu,Jian Zhang,Wei Xu,Yaqian Feng,Zhimin Fan
Using STAT3 inhibitors as a potential strategy in cancer therapy have attracted much attention. Recently, celastrol has been reported that it could directly bind to and suppress the activity of STAT3 in the cardiac dysfunction model. To explore more effective STAT3 inhibiting anti-tumour drug candidates, we synthesised a series of celastrol derivatives and biologically evaluated them with several human cancer cell lines. The western blotting analysis showed that compound 4 m, the most active derivative, could suppress the STAT3’s phosphorylation as well as its downstream genes. SPR analysis, molecular docking and dynamics simulations’ results indicated that the 4m could bind with STAT3 protein more tightly than celastrol. Then we found that the 4m could block cell-cycle and induce apoptosis on HCT-116 cells. Furthermore, the anti-tumour effect of 4m was verified on colorectal cancer organoid. This is the first research that discovered effective STAT3 inhibitors as potent anti-tumour agents from celastrol derivatives.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Theranostics
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2020
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IF 8.579
Xi Chen,Ying Zhao,Wu Luo,Sian Chen,Feng Lin,Xi Zhang,Shijie Fan,Xian Shen,Yi Wang,Guang Liang
Background: Oxidative stress from elevated reactive oxygen species (ROS) has been reported to induce cell apoptosis and may provide a means to target cancer cells. Celastrol is a natural bioactive compound that was recently shown to increase ROS levels and cause apoptosis in cancer cells. However, the underlying mechanism for this cytotoxic action remains unclear and direct molecular targets of Celastrol have not been identified. Methods: Proteome microarray, surface plasmon resonance, isothermal titration calorimetry and molecular simulation were used to identify the molecular target of Celastrol. Binding and activity assays were used to validate the interaction of Celastrol with target protein in cell-free and gastric cancer cell lysates. We then assessed target transcript levels in in biopsy specimens obtained from patients with gastric cancer. Gastric cancer growth-limiting and cytotoxic activity of Celastrol was evaluated in BALB/c nu/nu mice. Results: Our data show that Celastrol directly binds to an antioxidant enzyme, peroxiredoxin-2 (Prdx2), which then inhibits its enzyme activity at both molecular and cellular level. Inhibition of Prdx2 by Celastrol increased cellular ROS levels and led to ROS-dependent endoplasmic reticulum stress, mitochondrial dysfunction, and apoptosis in gastric cancer cells. Functional tests demonstrated that Celastrol limits gastric cancer cells, at least in part, through targeting Prdx2. Celastrol treatment of mice implanted with gastric cancer cells also inhibited tumor growth, associated with Prdx2 inhibition and increased ROS. Analysis of human gastric cancer also showed increased Prdx2 levels and correlation with survival. Conclusion: Our studies have uncovered a potential Celastrol-interacting protein Prdx2 and a ROS-dependent mechanism of its action. The findings also highlight Prdx2 as a potential target for the treatment of gastric cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
AAPS Journal
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2021
·Vol. 24
·期 1
·1-13
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IF 4.009
Zhao Xuan,Huang Chengyuan,Su Meiling,Ran Yu,Wang Ying,Yin Zongning
Celastrol (CLT) has shown anti-rheumatic activity against rheumatoid arthritis, while its poor water solubility and high organ toxicity restrict its further therapeutic applications. To mitigate these challenges, a reactive oxygen species (ROS)–responsive nanoparticle was developed for celastrol delivery based on the excessive ROS at the pathologic sites, which was synthesized by conjugating bilirubin to a polyethylene glycol (PEG) chain. The PEGylated bilirubin self-assembled into nanoparticle (BRNP) in aqueous solution had a hydrodynamic diameter of around 68.6 nm, and celastrol was loaded into BRNP (CLT/BRNP) with a drug encapsulation efficiency of 72.6% and a loading capacity of 6.6%. In vitro study revealed that CLT/BRNP exhibited the capacity of scavenging intracellular ROS and down-regulating the level of nitric oxide after it was effectively internalized by activated macrophages. Furthermore, in adjuvant-induced arthritis rats, BRNP was accumulated preferentially at inflamed joints, alleviating the joint swelling and bone erosion, which significantly decreased the secretion of pro-inflammatory cytokines to suppress the RA progression. Importantly, CLT/BRNP markedly enhanced its anti-arthritic effect and attenuated the toxic effect compared with free celastrol. Taken together, our results suggested that CLT/BRNP could be used for targeted drug delivery in rheumatoid arthritis. Graphical abstract
研究领域:
药学
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纳米技术
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炎症
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风湿病学
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产品关联
DOI
PubMed
高影响因子
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