Anti-allergic activities of Umbelliferone against histamine- and Picryl chloride-induced ear edema by targeting Nrf2/iNOS signaling in mice

Younas, Ashrafullah Khan, Omer Shehzad, Eun Kyoung Seo, Alev Onder, Salman Khan

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: The current study was aimed to investigate the anti-allergic activities of the Umbelliferone (UMB) against the acute Histamine and chronic Picryl chloride (PiCl)-induced allergy in mice. UMB is a coumarin derivative (isolated from Angelica decursiva) found in various parts of the plants such as flowers, roots and, stems isolated from the plants of Umbelliferae family. Methods: The UMB (1, 10, 50 mg/kg) was administered intraperitoneally (i.p) half an h before or 2 h after the induction of allergic ear edema. The acute ear edema was induced by histamine (intradermally, i.d), while the chronic ear edema was induced by painting the PiCl (sensitized with the toluene) on the ear. The antioxidants and oxidative stress markers were assessed. The histological changes were assessed using Hematoxylin and eosin (H and E) and giemsa staining. The immunohistochemistry studies were performed to assess the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and inducible nitric oxide synthase (iNOS). The data was analyzed using one-way ANOVA tests followed by Tukey’s test with p < 0.05 was chosen as criteria for statistical significance. Results: UMB treatment markedly reduced the allergic ear edema and ear weight compared to the negative control. Furthermore, the UMB attenuated the oxidative stress markers, while induced the antioxidants enzymes. Similarly, the UMB treatment significantly attenuated the serum immunoglobulin E (IgE) level. The UMB treatment markedly improved the histological parameters using H and E staining and Giemsa staining. The UMB administration induced the Nrf2 expression, while attenuated the iNOS expression. Furthermore, the computational analysis was performed to assess the interaction of the UMB with the various protein targets and to determine the mechanism of interaction with the target proteins. Conclusion: In conclusion, the UMB treatment significantly alleviated the allergic symptoms, attenuating the oxidative stress, improved the histological features using in vivo and computational approaches.

Original languageEnglish
Article number215
JournalBMC Complementary Medicine and Therapies
Issue number1
StatePublished - 27 Aug 2021

Bibliographical note

Funding Information:
The current study was supported by the Higher education commission (HEC, Pakistan) Pakistan, under the SRGP project number (No. 357 SRGP/HEC/2014). The funding body provided the financial support only and no other assistance was provided.

Publisher Copyright:
© 2021, The Author(s).


  • Antioxidant
  • Inflammation
  • Oxidative stress
  • Picryl chloride
  • Umbelliferone


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