Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats

Li, Zhanrong; Lin, Yu; Li, Jingguo; Zhang, Bo; Wu, Xianghua; Liu, Yi; Lin, Miaoli; Su, Wenru; Li, Yongping; Liang, Dan

doi:10.2147/ijn.s27860

Cited by 25 publications

(9 citation statements)

References 54 publications

(70 reference statements)

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“…This formula prolongs the blood circulation time of celastrol, increasing bioavailability and reducing the frequency of dosing ( Wolfram et al, 2014 ). Celastrol nanoparticles significantly inhibits suture-induced corneal neovascularization by reducing macrophage infiltration and decreasing the expression of vascular endothelial growth factor and matrix metalloproteinase 9 in rat cornea ( Li et al, 2012c ; Sanna et al, 2015 ). Mesoporous silica nanoparticle and axitinib in PEGylate lipid bilayers increases the inhibitory activity of celastrol on angiogenesis and mitochondrial function, and enhances its anticancer activity in SCC-7, BT-474, and SH-SY5Y cells ( Choi et al, 2016 ).…”

Section: Translational Development Of Triptolide and Celastrolmentioning

confidence: 99%

A Mechanistic Overview of Triptolide and Celastrol, Natural Products from Tripterygium wilfordii Hook F

et al. 2018

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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. We systemically discuss the structure-activity-relationship of triptolide, celastrol, and their derivatives. Furthermore, we propose the use of structural derivatives, targeted therapy, and combination treatment as possible solutions to reduce toxicity and increase therapeutic window of these potent natural products from T. wilfordii Hook F.

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Section: Translational Development Of Triptolide and Celastrolmentioning

confidence: 99%

A Mechanistic Overview of Triptolide and Celastrol, Natural Products from Tripterygium wilfordii Hook F

et al. 2018

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“…A study from Zhang et al ( 180 ) have demonstrated that oral administration of celastrol in rats results in ineffective absorption into the systemic circulation, with an absolute bioavailability of 17.06%. Li et al ( 194 ). suggest that besides low aqueous solubility in vivo metabolism and/or tissue distribution might also cause this poor bioavailability.…”

Section: Toxicity and Limitations Of Celastrol Formulationmentioning

confidence: 99%

“…To surpass the physicochemical and pharmacokinetic limitations of celastrol and to diminish the effective dose, several methodologies have been tested that can represent useful strategies, such as exosomes ( 200 ), lipid nanospheres ( 201 ), nanoencapsulation ( 202 ), polyamidoamine dendrimer nanocarriers ( 203 ), liposomes ( 204 – 206 ), polymeric micelles ( 207 , 208 ), cell-penetrating peptides-coated nanostructured lipid carriers ( 194 , 209 – 211 ), sugar-silica nanoparticles ( 212 ), and self-microemulsifying drug delivery system ( 193 ). For instance, recent data have shown that celastrol-loaded exosomes enhance free celastrol efficacy and reduce dose-related toxicity in lung cancer ( 200 ).…”

Section: New Strategies For the Use Of Celastrolmentioning

confidence: 99%

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

2017

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The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness.

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“…It has been shown to inhibit cell proliferation and promote cell death in breast [22], colon [23] and prostate cancers [24,25], oral squamous cell carcinoma [26], glioma [27], melanoma [28] and leukemia [29]. It also inhibits angiogenesis [27,30,31,32,33], possibly by inhibition of the AKT/mammalian target of rapamycin pathway [34] or by interference with the HIF-1α pathway [31], causing suppression of vascular endothelial growth factor (VEGF) [35]. …”

Section: Introductionmentioning

confidence: 99%

Celastrol Inhibits Lipopolysaccharide-Induced Angiogenesis by Suppressing TLR4-Triggered Nuclear Factor-Kappa B Activation

Zhao²,

Kong

et al. 2013

Acta Haematol

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Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. In this study, we investigated the effect of celastrol on lipopolysaccharide (LPS)-activated LP-1 human multiple myeloma cell-induced angiogenesis, and identified its molecular mechanism of action. Migration of human umbilical vein endothelial cells (HUVECs) was tested using a wound-healing assay. HUVEC invasion was assayed using a Transwell chamber. Cell surface expression of Toll-like receptor 4 (TLR4) was analyzed by flow cytometry. Angiogenic factor vascular endothelial growth factor (VEGF) level was quantified by LUMINEX and protein expression was analyzed by Western blot. Translocation of nuclear factor-kappa B (NF-κB) was observed by fluorescence microscopy. Celastrol inhibited LPS-stimulated LP-1 human multiple myeloma-induced HUVEC migration and invasion in a concentration-dependent manner. Wound diameters increased by 72.9, 165.4 and 246.2% at 0.025, 0.05 and 0.1 µM, respectively, compared to LPS alone. A 45-74% inhibition of LPS-dependent cell invasion was achieved in the presence of 0.025-0.1 µM celastrol. Celastrol significantly downregulated LPS-induced TLR4 expression and inhibited LPS-induced VEGF secretion in LP-1 cells. VEGF levels decreased by 64.8, 84.4 and 92.9% after coexposure to celastrol at 0.025, 0.05 and 0.1 µM, respectively, compared to LPS alone. Celastrol also inhibited the IκB kinase (IKK)/NF-κB pathway induced by LPS. Protein levels of NF-κB p65, IKKa and IκB-a decreased in a dose-dependent manner after coexposure to celastrol. Celastrol also blocked nuclear translocation of the p65 subunit. These results suggest that celastrol inhibits LPS-induced angiogenesis by suppressing TLR4-triggered NF-κB activation.

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Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats

Cited by 25 publications

References 54 publications

A Mechanistic Overview of Triptolide and Celastrol, Natural Products from Tripterygium wilfordii Hook F

A Mechanistic Overview of Triptolide and Celastrol, Natural Products from Tripterygium wilfordii Hook F

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

Celastrol Inhibits Lipopolysaccharide-Induced Angiogenesis by Suppressing TLR4-Triggered Nuclear Factor-Kappa B Activation

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