Anti-Inflammatory Effects of 4-Methylcyclopentadecanone on Edema Models in Mice

Ma, Yueming; Li, Yue; Li, Xiufeng; Wu, Yuankui

doi:10.3390/ijms141223980

Cited by 41 publications

(38 citation statements)

References 32 publications

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“…The mice were divided into five groups of six each, as described in Table I, and inflammation was induced on the right ear of each animal while maintaining the left ear as an internal control (25). Edema was quantified as the weight difference between earplugs obtained from the two ears of the same animal.…”

Section: Pharmacodynamic Evaluation: Anti-inflammatory Effectmentioning

confidence: 99%

Development and Evaluation of Curcumin-loaded Elastic Vesicles as an Effective Topical Anti-inflammatory Formulation

et al. 2014

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Abstract. Curcumin has diverse biological activities including antioxidant and anti-inflammatory activity. However, its clinical use for topical application is limited due to its poor aqueous solubility and thus, minimal cutaneous bioavailability. Elastic vesicles (EVs) of curcumin were prepared to improve its cutaneous bioavailability and to use it for topical anti-inflammatory effect. Ex vivo skin permeation and retention studies were performed to check if incorporation of curcumin into EVs could improve its permeation into and retention in the skin. Evaluation of acute and chronic anti-inflammatory effect was done using xylene-induced acute ear edema in mice and cotton pellet-induced chronic inflammation in rats, respectively. A significant improvement in flux (nine times) across murine skin was observed when aqueous dispersion of curcumin (flux−0.46±0.02 μg/h/cm 2 ) was compared with curcumin-loaded EVs (flux−4.14±0.04 μg/h/cm 2 ). Incorporation of these curcumin-loaded EVs into a hydrophilic ointment base resulted in higher skin retention (51.66%) in contrast to free curcumin ointment (1.64%) and a marketed formulation (VICCO® turmeric skin cream). The developed ointment showed an effect similar (p<0.05) to the marketed diclofenac sodium ointment (Omni-gel®) in suppression of acute inflammation in mouse; a significant inhibition (28.8% versus 3.91% for free curcumin) of cotton pellet-induced chronic inflammation was also observed. Thus, curcumin-loaded EVs incorporated in hydrophilic ointment is a promising topical anti-inflammatory formulation.

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Section: Pharmacodynamic Evaluation: Anti-inflammatory Effectmentioning

confidence: 99%

Development and Evaluation of Curcumin-loaded Elastic Vesicles as an Effective Topical Anti-inflammatory Formulation

et al. 2014

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“…However the neuroprotective activity of 4-MCPC was exhibited via activating the PI3K/Akt signal pathway. It is generally known that inflammation plays a crucial role in cerebral I/R injury, and our previous study testified that 4-MCPC has potent anti-inflammatory activity via decreasing the levels of IL-1b, TNF-a, PGE2, and MPO (17). So we speculate that the neuroprotective effects of 4-MCPC may also be related with the anti-inflammatory effects.…”

Section: Discussionmentioning

confidence: 54%

“…4-Methylcyclopentadecanone (4-MCPC) is a by-product of the synthesis process of muscone that was discarded in the past. Experimental studies have shown that 4-MCPC has similar effects on antiinflammation, antidementia, and antioxidation as muscone (16,17), and it was used to treat ischemic cerebrovascular disease in a patent in China. However, the neuroprotective effects and the associated mechanisms of 4-MCPC have not been explored in an I/R injury model.…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effect of 4-Methylcyclopentadecanone on Focal Cerebral Ischemia/Reperfusion Injury in Rats

Zhang³

et al. 2014

J Pharmacol Sci

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Abstract. The present study aimed to investigate the effect of 4-methylcyclopentadecanone (4-MCPC) on local cerebral ischemia-reperfusion and the possible mechanisms involved. For this purpose, the focal cerebral ischemia rat model was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats were treated with 4-MCPC (4 or 8 mg·kg −1 , p.o.) just 0.5 h before reperfusion. The neurological deficit scores and the ischemic infarct volume were recorded 24 h after the MCAO. In addition, the number of apoptotic cells was measured by TUNEL assay, and the expression of apoptosis-regulatory proteins and the PI3K/Akt neuroprotective signaling pathway were investigated by western blotting. Our results indicated that 4-MCPC (4 or 8 mg·kg −1 ) remarkably alleviated cerebral I/R injury by decreasing infarct volume and neurological deficit scores. 4-MCPC also decreased the number of apoptotic cells, regulated the expression of Bcl-2 and Bax, and increased the ratio of Bcl-2/Bax. Further study revealed that 4-MCPC treatment also increased the level of p-Akt and p-GSK-3b. Wortmannin (PI3K inhibitor) markedly abolished the effects of 4-MCPC. Taken together, our results suggest that 4-MCPC protects against cerebral I/R injury through the inhibition of apoptosis, and this neuroprotective effect may be partly related to the activation of the PI3K/Akt signal pathway.

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“…A dose range of 10, 50, and 100 mg/kg of muscone was used for the low-, middle-, and high-dose groups, respectively. The selection of the doses was based on preliminary experiments of acute oral toxicity as demonstrated by previous studies [18]. The mice were sacrificed 6 or 12 days after the end of the treatment period and tissues from liver and kidney organs were obtained for western blotting, real-time PCR, and immunohistochemistry experiments.…”

Section: Methodsmentioning

confidence: 99%

“…The cells were cultured in the DMEM solution containing 10% FBS in the presence of antibiotics (Pen/Strep 100 μg/mL) and 5% CO 2 as described previously [18]. The cells were passaged every 2-3 days.…”

Section: Methodsmentioning

confidence: 99%

Muscone Induces CYP1A2 and CYP3A4 Enzyme Expression in L02 Human Liver Cells and CYP1A2 and CYP3A11 Enzyme Expression in Kunming Mice

Cheng

Rao

et al. 2017

Pharmacology

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Aim: To examine the effect of synthetic muscone on the expression of CYP1A2 and CYP3A4 enzymes in human liver L02 cells and in the liver tissue of Kunming mice. Methods: The L02 hepatic cell line was used to study the effect of low (10^-4 μmol/L), middle (10^-3 μmol/L), and high concentrations (10^-2 μmol/L) of muscone on the expression of CYP1A2 and CYP3A4 enzymes. In addition, the cytochrome P450 (CYP) expression was investigated in Kunming mice after the administration of 10 mg/kg (low), 50 mg/kg (middle), and 100 mg/kg (high) dose of muscone for 6 days. A mixture of phenobarbital (30 mg/kg) and β-napthoflavone (80 mg/kg) was used as positive control and the effects of the compounds on CYP expression were investigated at the end of 6- and 12-day periods. Results: Muscone induced the expression of CYP1A2 (middle and low concentrations) and of CYP3A4 (high concentration) enzymes in L02 cells. In vivo, administration of muscone in Kunming mice revealed significant weight reduction at the end of 6- and 12-day periods (middle and high doses, respectively), compared to the control group (p < 0.05). Liver toxicity scores indicated that the liver injuries in the positive control and high doses of muscone group were significantly higher in the 6- and 12-day periods, compared to those in the blank control group (p < 0.05). Furthermore, muscone induced CYP1A2 and CYP3A11 expressions in Kunming mice at the middle dose and all doses during the 12-day period as demonstrated by immunoblotting experiments. A low dose of mucone induced the CYP enzyme expression more rapidly, whereas a high dose of muscone caused the longest inductive effect. The results were confirmed by immunohistochemistry experiments and real-time PCR studies, where similar patterns of muscone-mediated inductive effects were noted. Conclusions: Muscone induces CYP1A2 and CYP3A4 expression in liver cells in vitro and in vivo. In addition, it exhibits liver toxicity in Kunming mice at concentrations higher than 50 mg/kg. The CYP-inductive effect that is caused by muscone encompasses a 6- to 12-day period of activity after drug administration as demonstrated by follow-up in vivo studies.

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Anti-Inflammatory Effects of 4-Methylcyclopentadecanone on Edema Models in Mice

Cited by 41 publications

References 32 publications

Development and Evaluation of Curcumin-loaded Elastic Vesicles as an Effective Topical Anti-inflammatory Formulation

Development and Evaluation of Curcumin-loaded Elastic Vesicles as an Effective Topical Anti-inflammatory Formulation

Neuroprotective Effect of 4-Methylcyclopentadecanone on Focal Cerebral Ischemia/Reperfusion Injury in Rats

Muscone Induces CYP1A2 and CYP3A4 Enzyme Expression in L02 Human Liver Cells and CYP1A2 and CYP3A11 Enzyme Expression in Kunming Mice

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