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Article

Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα

  • Authors:
    • Yanan Zhang
    • Chengwei Song
    • Haiou Li
    • Jingdong Hou
    • Dongliang Li
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Jining First People's Hospital, Jining, Shandong 272011, P.R. China, Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China
  • Pages: 5309-5316
    |
    Published online on: April 22, 2016
       https://doi.org/10.3892/mmr.2016.5172
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Abstract

Obesity is a risk factor for several pain syndromes and is associated with increased pain sensitivity. Evidence suggests that obesity causes the downregulation of peroxisome proliferator‑activated receptor (PPAR)α in the spinal cord, contributing to augmented peripheral edema and inflammatory hyperalgesia. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, has been shown to upregulate PPARα in the peripheral tissues of obese animals. The present study hypothesized that UA prevents augmented peripheral inflammation and inflammatory hyperalgesia in obesity by restoring downregulated spinal PPARα. The present study demonstrated that Sprague‑Dawley rats fed a high‑fat diet (HFD) for 12 weeks developed obesity and metabolic disorder. Following carrageenan injection, the HFD rats exhibited increased thermal hyperalgesia and paw edema, compared with the rats fed a low‑fat diet. Molecular investigations revealed that the HFD rats exhibited decreased PPARα activity, and exaggerated expression of inflammatory mediators and nuclear factor‑kB activity in the spinal cord in response to carrageenan. Oral administration of UA ameliorated obesity and metabolic disorder, and prevented increased thermal hyperalgesia and paw edema in the HFD rats. Additionally, UA normalized PPARα activity and inhibited the exaggerated spinal cord inflammatory response to carrageenan. Although the knockdown of spinal PPARα with small interfering RNA following the administration of UA did not alter obesity or metabolic parameters, it eradicated the beneficial effects of UA on thermal hyperalgesia and paw edema, and reversed the spinal cord inflammatory response. These results suggested that the systemic administration of UA inhibited the exaggerated spinal cord inflammatory response to peripheral inflammatory stimulation in HFD‑induced obesity by restoring downregulated spinal PPARα, preventing peripheral inflammation and inflammatory hyperalgesia. UA may be a potential therapeutic option for the prevention of increased inflammatory pain in obese patients.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Song C, Li H, Hou J and Li D: Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα. Mol Med Rep 13: 5309-5316, 2016.
APA
Zhang, Y., Song, C., Li, H., Hou, J., & Li, D. (2016). Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα. Molecular Medicine Reports, 13, 5309-5316. https://doi.org/10.3892/mmr.2016.5172
MLA
Zhang, Y., Song, C., Li, H., Hou, J., Li, D."Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα". Molecular Medicine Reports 13.6 (2016): 5309-5316.
Chicago
Zhang, Y., Song, C., Li, H., Hou, J., Li, D."Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα". Molecular Medicine Reports 13, no. 6 (2016): 5309-5316. https://doi.org/10.3892/mmr.2016.5172
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Song C, Li H, Hou J and Li D: Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα. Mol Med Rep 13: 5309-5316, 2016.
APA
Zhang, Y., Song, C., Li, H., Hou, J., & Li, D. (2016). Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα. Molecular Medicine Reports, 13, 5309-5316. https://doi.org/10.3892/mmr.2016.5172
MLA
Zhang, Y., Song, C., Li, H., Hou, J., Li, D."Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα". Molecular Medicine Reports 13.6 (2016): 5309-5316.
Chicago
Zhang, Y., Song, C., Li, H., Hou, J., Li, D."Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα". Molecular Medicine Reports 13, no. 6 (2016): 5309-5316. https://doi.org/10.3892/mmr.2016.5172
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