PMID- 34452623 OWN - NLM STAT- MEDLINE DCOM- 20211215 LR - 20211215 IS - 2662-7671 (Electronic) IS - 2662-7671 (Linking) VI - 21 IP - 1 DP - 2021 Aug 27 TI - Anti-allergic activities of Umbelliferone against histamine- and Picryl chloride-induced ear edema by targeting Nrf2/iNOS signaling in mice. PG - 215 LID - 10.1186/s12906-021-03384-1 [doi] LID - 215 AB - 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. CI - (c) 2021. The Author(s). FAU - Younas AU - Younas AD - Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan. FAU - Khan, Ashrafullah AU - Khan A AD - Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan. FAU - Shehzad, Omer AU - Shehzad O AD - Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan. FAU - Seo, Eun Kyoung AU - Seo EK AD - College of Pharmacy, Ewha Womans University, 52, Ewhayeodae-gil, Seodaemun-gu, Seoul, 03760, South Korea. FAU - Onder, Alev AU - Onder A AD - Department of Pharmacognosy, Faculty of Pharmacy, Ankara University, Ankara, Turkey. FAU - Khan, Salman AU - Khan S AUID- ORCID: 0000-0002-6226-8470 AD - Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Islamabad, Pakistan. skhan@qau.edu.pk. LA - eng PT - Journal Article DEP - 20210827 PL - England TA - BMC Complement Med Ther JT - BMC complementary medicine and therapies JID - 101761232 RN - 0 (Anti-Allergic Agents) RN - 0 (Antioxidants) RN - 0 (Plant Extracts) RN - 0 (Umbelliferones) SB - IM MH - Animals MH - Anti-Allergic Agents/*pharmacology MH - Antioxidants/*pharmacology MH - Dose-Response Relationship, Drug MH - Ear Auricle/drug effects MH - Edema/chemically induced/*drug therapy MH - Mice MH - Oxidative Stress/drug effects MH - Plant Extracts/*pharmacology MH - Umbelliferones/*pharmacology PMC - PMC8394045 OTO - NOTNLM OT - Antioxidant OT - Inflammation OT - Oxidative stress OT - Picryl chloride OT - Umbelliferone COIS- The author declares no conflict of interest. EDAT- 2021/08/29 06:00 MHDA- 2021/12/16 06:00 PMCR- 2021/08/27 CRDT- 2021/08/28 05:20 PHST- 2020/12/06 00:00 [received] PHST- 2021/07/29 00:00 [accepted] PHST- 2021/08/28 05:20 [entrez] PHST- 2021/08/29 06:00 [pubmed] PHST- 2021/12/16 06:00 [medline] PHST- 2021/08/27 00:00 [pmc-release] AID - 10.1186/s12906-021-03384-1 [pii] AID - 3384 [pii] AID - 10.1186/s12906-021-03384-1 [doi] PST - epublish SO - BMC Complement Med Ther. 2021 Aug 27;21(1):215. doi: 10.1186/s12906-021-03384-1.