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

Yukui Ma,Yue Li,Yingliang Wu,Xiufeng Li

doi:10.3390/ijms141223980

Abstract

The present study evaluated the anti-inflammatory effects of 4-methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and 5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced mouse paw edema. The animals were treated with 4-MCPC once every day for seven consecutive days. Edema index, % inhibition, IL-1β, TNF-α, PGE2 and MPO levels in paws were detected after the treatment with xylene or carrageenan. Our results indicated that the LD50 value of 4-MCPC in rats is greater than 5000 mg/kg. The ED50 of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg. 4-MCPC (8 or 16 mg/kg) remarkably inhibited carrageenan-induced mouse paw edema. Further study revealed that 4-MCPC treatment also decreased IL-1β, TNF-α, PGE2 and MPO levels in mice paws. Intragastric administration of 4-MCPC exhibited more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg. Taken together, our results suggest that 4-MCPC has potent anti-inflammatory activity and the mechanisms might be related to the decreases of the levels of IL-1β, TNF-α, PGE2 and MPO in inflamed paws.

Highlights

Inflammation is the first response of the immunological defense system to microbial infections, burns, allergens, mechanical injuries and other noxious stimuli [1]
Macrophages activated by stimuli produce inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), and various cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) [4,5]
4-MCPC at doses of 5–5000 mg/kg, p.o., given to rats showed no toxic symptoms during the monitoring period of 14 days after administration

Summary

Introduction

Inflammation is the first response of the immunological defense system to microbial infections, burns, allergens, mechanical injuries and other noxious stimuli [1]. Inflammation is a complex series of cascade reactions, including enzyme activation, release of chemical mediators, effusion of fluids, cell migration, and tissue damage and repair [3]. Macrophages activated by stimuli produce inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2), and various cytokines such as interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) [4,5]. Non-steroidal anti-inflammatory drugs (NSAIDs) are the main available potent synthetic drugs in the treatment of inflammatory diseases. The use of NSAIDs as anti-inflammatory agents has not been successful in their clinical use because of the serious adverse side effects such as gastric lesions and reappearance of symptoms after discontinuation [6]. There is a worldwide search for new anti-inflammatory drugs as an alternative to NSAIDs

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Conclusion