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

Abstract

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.

Natural Coumarin Derivatives Activating Nrf2 Signaling Pathway as Lead Compounds for the Design and Synthesis of Intestinal Anti-Inflammatory Drugs

“…Additionally, known as 7-hydroxycoumarin, hydrangine, and skimmetine, this coumarin derivative displays several pharmacological activities. Among its actions, umbelliferone attenuates oxidative stress modulating the Nrf2 signaling pathway to control several disorders, mainly hepatotoxicity, diabetes, inflammation, allergy, and renal and cardiovascular disorders [116][117][118][119][120].…”

“…Additionally, known as 7-hydroxycoumarin, hydrangine, and skimmetine, this coumarin derivative displays several pharmacological activities. Among its actions, umbelliferone attenuates oxidative stress modulating the Nrf2 signaling pathway to control several disorders, mainly hepatotoxicity, diabetes, inflammation, allergy, and renal and cardiovascular disorders [116][117][118][119][120]. In vivo studies demonstrated umbelliferone protecting rats against tetrachloride-, cyclophosphamide-, methotrexate-, and N-nitrosodiethylamine-induced hepatotoxicity in rats, alleviating hepatic damage in db/db mice and hepatic ischemia/reperfusion-induced oxidative stress in rats via activation and upregulation of Nrf2 signaling pathway [116,117,[120][121][122][123].…”

Main Polar Metabolites from Leaves of the Native Andean Species Jungia rugosa Less (Asteraceae)

“…C 16 H 18 O 8 ; PM 338,31; sólido amorfo blanco. Los resultados de 1 H NMR (δ ppm, CD 3 OD, 500 MHz), 13 C NMR (δ ppm, CD 3 OD, 100 MHz) y DEPT-135 se detallan en la Tabla 2. Los resultados de HMQC y HMBC se muestran en la Figura 2.…”

“…La umbeliferona es una cumarina, cuya fórmula molecular es C 9 H 6 O 3 , también se le conoce como 7-hidroxicumarina, hidrangina, esquimetina y β-umbeliferona [13]. Generalmente, las cumarinas son metabolitos secundarios característicos de las familias Apiaceae, Rutaceae, Asteraceae y Fabaceae [14].…”

Influence of Umbelliferone on the Anticonvulsant and Neuroprotective Activity of Selected Antiepileptic Drugs: An In Vivo and In Vitro Study

“…Furthermore, anti-cancer and anti-apoptotic activity of UMB has also been documented in various models of carcinogenesis, i.e., colon, hepatic and renal cancer [ 22 , 23 , 24 ]. This coumarin is also known for its antiarthritic [ 25 ], hepatoprotective [ 26 ], anti-asthmatic [ 27 ], and anti-allergic activity (preclinical studies) [ 28 ]. UMB also has antinociceptive properties in different models of pain, such as acetic-acid-induced writhing, the formalin test, and complete Freund’s adjuvant-induced hyperalgesia [ 29 , 30 ].…”