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Clin Exp Allergy ; 48(11): 1494-1508, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30137697

RESUMO

BACKGROUND: Curcumin (Cur), derived from Curcuma species, exhibits anti-inflammatory, antioxidant, and anticancer effects. Although Cur has some beneficial effects on asthma, its clinical application is limited by its low bioavailability. Tetrahydrocurcumin (THC), the major active metabolite of Cur, has multiple biological functions, similarly to Cur, and importantly, it showed enhanced bioavailability in tissues and plasma. However, the effect of THC on asthma has not been reported. OBJECTIVE: The current study sought to investigate the efficacy of dietary THC on allergic asthma compared to that of Cur in an animal model. METHODS: The anti-inflammatory effects of Cur and THC were evaluated in an ovalbumin-induced asthmatic mouse model. The nasal symptoms, pathological alterations of the lung tissues, oxidants and antioxidants, cytokine production, T cell subsets, and Th2-related signalling pathway activity were assessed. RESULTS: Both THC and Cur had beneficial effects on asthmatic mice with regard to nasal symptoms, pathological changes (eosinophils and mucus hyper-production), oxidative stress (malondialdehyde), cytokine production (IL-13), Th17 and cytotoxic T cell subsets, and Th2 signalling pathway (IL-4Rα-Jak1-STAT6 and Jagged1/Jagged2-Notch1/Notch2 axis) activity. THC was more effective than Cur in suppressing tissue eosinophilia, mucus production, and IL-4Rα/Jak1/STAT6 pathway activity. Furthermore, only THC inhibited peripheral eosinophil levels, Th2 cytokines (IL-4 and IL-5), and Th2 cell subsets and enhanced an antioxidant enzyme (glutathione). CONCLUSION AND CLINICAL RELEVANCE: The above results demonstrated for the first time that THC was superior to Cur in modulating allergic asthmatic phenotypes, especially attenuating the Th2 response. THC might be a potentially effective agent for asthma treatment.


Assuntos
Asma/imunologia , Asma/metabolismo , Biomarcadores , Curcumina/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo , Alérgenos/imunologia , Animais , Asma/tratamento farmacológico , Curcumina/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Mediadores da Inflamação/metabolismo , Proteína Jagged-1/metabolismo , Proteína Jagged-2/metabolismo , Janus Quinase 1/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Camundongos , Estresse Oxidativo , Receptor Notch1/metabolismo , Receptor Notch2/metabolismo , Receptores de Superfície Celular/metabolismo , Fator de Transcrição STAT6/metabolismo
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