Allergic reaction is the most common nasal conditions worldwide and it will remain throughout life. The symptoms of an allergic reaction include sneezing, itching, hives, swelling, difficulty breathing, and a runny nose. Hydroxysafflor yellow A (HYA) is a flavonoid compound which is the active phyto‐constituent of flower of Carthamus tinctorius L., and exhibited the various medicinal activities like antioxidant, anti‐inflammatory and cardiovascular protective effects. This study aimed to assess the efficacy and mode of action of HYA against the allergic rhinitis induced by ovalbumin in mice. HYA was given orally to the Swiss BALB/s mice once daily, 1 h before, they were challenged with ovalbumin (OVA) via intranasal administration, after that the mice were sensitized via intraperitoneal injection of OVA. Allergic nasal symptoms, body weight, spleen weight, OVA‐specific immunoglobulins, inflammatory cytokines, Th17 cytokines and Th17 transcription factors also estimated. HYA had a significant (p < .001) effect on body weight and reduced spleen weight. It effectively decreased the nasal symptoms of allergy such as sneezing, rubbing, and redness. HYA significantly reduced the level of malonaldehyde (MDA) and improved levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione (GSH). It also remarkably decreased the levels of Th2 cytokines and Th17 transcription factors like RAR‐related orphan receptor gamma (ROR‐γ), signal transducer and activator of transcription 3 (STAT3) and phosphor signal transducer and activator of transcription 3 (p‐STAT3), while increasing levels of nuclear factor erythroid 2‐related factor 2 (Nrf2) and heme oxygenase‐1 (HO‐1). The treatment with HYA improved the lung histology in mice with allergic rhinitis. The results suggest that HYA may have therapeutic potential against ovalbumin‐induced allergic rhinitis in mice, by altering the Th17/Treg balance and improving the Nrf2/HO‐1 signaling pathway.

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