Tetrahydrocurcumin, a major metabolite of curcumin, ameliorates allergic airway inflammation by attenuating Th2 response and suppressing the IL‐4Rα‐Jak1‐STAT6 and Jagged1/Jagged2 ‐Notch1/Notch2 pathways in asthmatic mice

Chen, Bin Lin; Chen, Yan Qiu; Bai, Hui; Yu, Si Fei; Li, Li Yue; Zeng, Qing Xiang; Zhou, Yu; Wu, Yin Fan; Liu, Wen long; Wan, Jian‐Bo; Yang, Yan; Li, Chun Wei

doi:10.1111/cea.13258

Cited by 39 publications

(43 citation statements)

References 37 publications

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“…Our previous study demonstrated that the immune-modulating properties of THC against asthma were at least partly targeted to the inhibitory effects of the Th2 response by suppressing the IL-4Rα-Jak1-STAT6 and Jagged1/Jagged2-Notch1/Notch2 pathways [10]. Similarly, DEX treatment significantly decreased the number of eosinophils, Th2 cells, and Th2 cytokines [23].…”

Section: Discussionmentioning

confidence: 99%

“…Four-week-old BALB/c mice (female) were purchased from Sun Yat-sen University Animal Center (Guangzhou, China) and were housed in a specific pathogen-free facility. The murine model of allergic asthma was established as previously reported [9, 10]. First step: mice were sensitized via i.p.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, the beneficial effects of certain nutrients on asthma outcomes are of growing interest, such as vitamin D [6, 7], resveratrol [8], and anthocyanin [9]. Additionally, our previous study demonstrated that tetrahydrocurcumin (THC), a major curcumin metabolite, exhibited anti-asthma properties in a murine model, and its inhibitory effects on airway inflammation were stronger than those of curcumin [10].…”

Section: Introductionmentioning

confidence: 99%

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Supplementation with Tetrahydrocurcumin Enhances the Therapeutic Effects of Dexamethasone in a Murine Model of Allergic Asthma

Chen

Qin

et al. 2020

Int Arch Allergy Immunol

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Background: Tetrahydrocurcumin (THC) is the major active metabolite of curcumin, which is a dietary factor derived from Curcuma species. Our previous study demonstrated a significant beneficial effect of THC in mice with allergic asthma. Glucocorticosteroids (GCs) are commonly used drugs in asthma. Whether THC supplementation could promote the beneficial effects of GC therapy on asthma has not yet been reported. The current study aimed to investigate the combined efficacy of GC and THC treatment in a mouse model of allergic asthma. Methods: BALB/c mice were randomly divided into 5 groups: the control group, ovalbumin (OVA)-induced group, and OVA-induced mice treated with dietary THC only, intraperitoneal injection of dexamethasone (DEX) only, or THC combined with DEX. The nasal symptoms, histopathological alterations of lung tissues, lung cytokine production, and Th cell subsets were assessed. Results: THC or DEX had beneficial effects on nasal symptoms and pathological lung changes, and the therapeutic effects between THC and DEX treatment were comparable. Importantly, compared to the monotherapy groups (THC or DEX only), the combination of THC and DEX showed a significantly reduced nasal rubbing frequency, lower mucus hyperproduction, lower Th2 and Th17 cell numbers as well as lower related cytokine levels (IL-4, IL-5, and IL-17A). Conclusions: Supplementation with THC can enhance the therapeutic effects of DEX to alleviate airway symptoms, lung inflammation, and the Th2 response. Our findings suggest that dietary administration of THC could act as an add-on therapy for asthma treated with GCs.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Supplementation with Tetrahydrocurcumin Enhances the Therapeutic Effects of Dexamethasone in a Murine Model of Allergic Asthma

Chen

Qin

et al. 2020

Int Arch Allergy Immunol

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“…2 Curcumin is a phenolic pigment that is extracted from the rhizome of Curcuma longa, and it is a main active ingredient with strong antiinflammatory and antioxidant effects. [2][3] The Notch signaling pathway exists widely in vertebrates and non-vertebrates, and it is highly conserved in evolution. Both humans and rats have four Notch receptors.…”

Section: Introductionmentioning

confidence: 99%

Post-treatment curcumin reduced ischemia–reperfusion-induced pulmonary injury via the Notch2/Hes-1 pathway

Feng

2019

J Int Med Res

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Objective To investigate the influence of curcumin on the Notch2/Hes-1 pathway after pulmonary injury induction via limb ischemia–reperfusion (I/R). Methods Adult male Sprague–Dawley rats were randomly divided into four groups (n = 30 each): sham, I/R, curcumin post-treatment (I/R+Cur), and inhibitor (I/R+DAPT). Hind-limb ischemia was induced for 4 hours, followed by reperfusion for 4 hours. After ischemia, curcumin (200 mg/kg) or DAPT (0.5 µm) was injected intraperitoneally in the I/R+Cur or I/R+DAPT group, respectively. PaO2 was examined after 4 hours of reperfusion. Pathological changes in the lung and the apoptotic index (AI) were examined. Lung malondialdehyde (MDA), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β levels, the wet/dry (W/D) ratio, semi-quantitative score of lung injury (SSLI), and Notch2 protein and Hes-1 mRNA expression were also examined. Results In the I/R group, inflammatory changes were observed, AI increased, and MDA, SSLI, W/D, TNF-α, IL-1β, Notch2, and Hes1-mRNA expression increased, while PaO2 decreased compared with the Sham group. Pathological changes in the I/R+Cur group were reversed. All indexes in the I/R+DAPT and I/R+Cur group were similar. Conclusion Curcumin post-treatment reduced I/R-induced lung injury in rats. Its mechanism may be related to the inhibition of Notch2/Hes-1 signaling pathway and the release of inflammatory factors.

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“…IL-4 production in mast cells has been studied in relation to IgE-mediated activation [8,9]. IL-4 is a multifunctional cytokine that plays an important role in inducing allergic Th2-type immune responses [10]. IL-4 activates signal transducers and activators of transcription 6 (STAT6) and induces the expression of IL-4-inducible genes, including class II major histocompatibility molecules, low-a nity IgE receptor, and IL-13 [9,11] [7].…”

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confidence: 99%

Tespa1 plays a role in the modulation of airway hyperreactivity through the IL-4/STAT6 pathway

Yang

Wang

et al. 2020

Preprint

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Background: Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a critical signaling molecule in thymocyte development. This study aimed to investigate the regulatory effect of Tespa1 on mast cells in the pathogenesis of asthma and its relationship with the interleukin (IL)-4 /signal transducers and activators of transcription 6 (STAT6) signaling pathway.Methods: Tespa1 mRNA expression analysis and IgE levels were carried out using the induced sputum of 33 adults with stable asthma and 36 healthy controls. Tespa1- knockout mice ( Tespa1 -/- , KO) and C57BL/6 background (wild-type, WT) mice were sensitized and treated with ovalbumin (OVA) to establish an asthma model. Pathological changes, number and activity of mast cells, and changes in activation of the IL-4 /STAT6 pathway in lung tissue were detected. The changes of tryptase expression and STAT6 activation after mast cell gene knockout were analyzed in vitro . The changes of enzyme activation and STAT6 activation after mast cell gene knockout were analyzed in vitro . The association between the Tespa1 and p-STAT6 was analyzed by co-immunoprecipitation method.Results: Compared with the healthy controls, Tespa1 expression was decreased, and IgE levels were elevated in the sputum of asthmatic patients. Animal experiments showed that Tespa1 -/- mice exhibited more severe inflammation, higher quantity of goblet cells and mast cells in the bronchium, and greater activity of mast cell tryptase, which is induced by ovalbumin, than WT mice. And IL-4, IL-13, phospho-Janus kinase 1, and p-STAT6 expressions presented a higher increase in the Tespa1 -/- mouse model than in the WT mouse model. Further in vitro studies confirmed that IL-4 could more significantly promote tryptase and p-STAT6 activities in Tespa1 -/- mast cells than their WT counterparts. Correlation analysis results showed a negative correlation between Tespa1 and p-STAT6. Co-immunoprecipitation results demonstrated an association between Tespa1 and p-STAT6.Conclusions: Altogether, our results indicate that Tespa1 can negatively regulate mast cell activity, and this event is related to the mast cell IL-4/STAT6 signaling pathway and could be therapeutically exploited to treat asthma attacks.

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Tetrahydrocurcumin, a major metabolite of curcumin, ameliorates allergic airway inflammation by attenuating Th2 response and suppressing the IL‐4Rα‐Jak1‐STAT6 and Jagged1/Jagged2 ‐Notch1/Notch2 pathways in asthmatic mice

Abstract: 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.

Cited by 39 publications

References 37 publications

Supplementation with Tetrahydrocurcumin Enhances the Therapeutic Effects of Dexamethasone in a Murine Model of Allergic Asthma

Supplementation with Tetrahydrocurcumin Enhances the Therapeutic Effects of Dexamethasone in a Murine Model of Allergic Asthma

Post-treatment curcumin reduced ischemia–reperfusion-induced pulmonary injury via the Notch2/Hes-1 pathway

Tespa1 plays a role in the modulation of airway hyperreactivity through the IL-4/STAT6 pathway

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