Oral bioavailability and gender-related pharmacokinetics of celastrol following administration of pure celastrol and its related tablets in rats

Jun, Zhang; Li, Chang-Yin; Xu, Meijuan; Wu, Ting; Chu, Jihong; Liu, Shijia; Ju, Wenzheng

doi:10.1016/j.jep.2012.09.005

Cited by 94 publications

(59 citation statements)

References 21 publications

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“…This might also indicate that this is not an effective dose or regimen. In fact, a study of celastrol pharmacokinetics has shown that its half-life is about 10 h in healthy rats (180). Contrarily, an in vitro study using RINm5F rat pancreatic β-cell line showed that celastrol regulates cytokine-induced cell death and proinflammatory responses by downregulating iNOS, COX-2, and chemokine (C-C motif) ligand 2 (CCL2) chemokine through NF-kB inhibition, exerting cytoprotective effects (181), which suggests that indeed it may be a therapeutic agent against type 1 diabetes.…”

Section: Therapeutic Properties Of Celastrol In Other Diseasesmentioning

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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Section: Therapeutic Properties Of Celastrol In Other Diseasesmentioning

confidence: 99%

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

2017

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“…An identical dose was given for the marketed domperidone tablet. The marketed domperidone tablet was grinded and dispersed in 1.5 ml of 0.5% (w/v) carboxymethylcellulose-sodium (CMC-Na) solution and tablet suspension was administered to rat by oral gavage 38 . After administration of the formulations, blood was withdrawn using the sparse withdrawal technique at suitable intervals of 0.5, 1, 2, 4, 6, 8, 10, 14, 15 and 24 h from the retro-orbital plexus of the rat eye.…”

Section: Ii) Drug Administration and Collection Of Plasmamentioning

confidence: 99%

Formulation and development of orodispersible sustained release tablet of domperidone

Patil

Tiwari

Repka

et al. 2015

Drug Development and Industrial Pharmacy

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Abstract:Commercially available domperidone orodispersible tablets (ODT) are intended for immediate release of the drug but none of them have been formulated for sustained action. The aim of the present research work was to develop and evaluate orodispersible sustained release tablet (ODT-SR) of domperidone, which has the convenience of ODT and benefits of controlled release product combined in one. The technology comprised of developing sustained release microspheres (MS) of domperidone, followed by direct compression of MS along with suitable excipients to yield ODT-SR which rapidly disperses within 30 seconds and yet the dispersed MS maintain their integrity to have a sustained drug release. The particle size of the MS was optimized to be less than 200 μm to avoid the grittiness in the mouth. The DSC thermograms of MS showed the absence of drug-polymer interaction within the microparticles, while SEM confirmed their spherical shape and porous nature. Angle of repose, compressibility and Hausner's ratio of the blend for compression showed good flowability and high percent compressibility. The optimised ODT-SR showed disintegration time of 21 seconds and matrix controlled drug release for 9 h. Invivo pharmacokinetic studies in Wistar rats showed that the ODT-SR had a prolonged MRT of 11.16 h as compared 3.86 h of conventional tablet. The developed technology is easily scalable and holds potential for commercial exploitation.

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“…The latter two compounds also have iron-chelating activity. The Nox1 inhibitors tested were selected based on their bioavailability in animals [15], [16], [17], [18], [19], [20]. The best small molecule inhibitors identified will be used as scaffolds for further modification to be developed into more specific Nox1 inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Deficiency in Duox2 activity alleviates ileitis in GPx1- and GPx2-knockout mice without affecting apoptosis incidence in the crypt epithelium

et al. 2017

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Mice deficient in glutathione peroxidase (GPx)-1 and -2 (GPx1-/-GPx2-/- double knockout or DKO mice) develop very-early-onset (VEO) ileocolitis, suggesting that lack of defense against reactive oxygen species (ROS) renders susceptibility to intestinal inflammation. Two members of ROS-generating NADPH oxidase family, NOX1 and DUOX2, are highly inducible in the intestinal epithelium. Previously, we reported that Nox1 deficiency ameliorated the pathology in DKO mice (Nox1-TKO). The role of Duox2 in ileocolitis of the DKO mice is evaluated here in Duoxa-TKO mice by breeding DKO mice with Duoxa-/- mice (Duoxa-TKO), which do not have Duox2 activity. Similar to Nox1-TKO mice, Duoxa-TKO mice no longer have growth retardation, shortened intestine, exfoliation of crypt epithelium, crypt abscesses and depletion of goblet cells manifested in DKO mice by 35 days of age. Unlike Nox1-TKO mice, Duoxa-TKO mice still have rampant crypt apoptosis, elevated proliferation, partial loss of Paneth cells and diminished crypt density. Treating DKO mice with NOX inhibitors (di-2-thienyliodonium/DTI and thioridazine/THZ) and an antioxidant (mitoquinone/MitoQ) significantly reduced gut pathology. Furthermore, in the inflamed human colon, DUOX protein expression is highly elevated in the apical, lateral and perinuclear membrane along the whole length of gland. Taken together, we conclude that exfoliation of crypt epithelium, but not crypt apoptosis, is a major contributor to inflammation. Both Nox1 and Duox2 induce exfoliation of crypt epithelium, but only Nox1 induces apoptosis. NOX1 and DUOX2 may be potential therapeutic targets for treating ileocolitis in human patients suffering inflammatory bowel disease (IBD).

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Oral bioavailability and gender-related pharmacokinetics of celastrol following administration of pure celastrol and its related tablets in rats

Cited by 94 publications

References 21 publications

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

Formulation and development of orodispersible sustained release tablet of domperidone

Deficiency in Duox2 activity alleviates ileitis in GPx1- and GPx2-knockout mice without affecting apoptosis incidence in the crypt epithelium

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