Alpinetin prevents inflammatory responses in OVA-induced allergic asthma through modulating PI3K/AKT/NF-κB and HO-1 signaling pathways in mice

Wu, Di; Li, Shuangqiu; Liu, Xiao; Xu, Jingnan; Jiang, Aimin; Zhang, Yong; Liu, Ziyi; Wang, Jingjing; Zhou, Ershun; Wei, Zhengkai; Yang, Zhengtao; Guo, Changmin

doi:10.1016/j.intimp.2020.107073

Cited by 35 publications

(27 citation statements)

References 79 publications

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“…Numerous studies have demonstrated that the PI3K/AKT/ NF-kB pathway participates in the occurrence of asthma and is related to allergic airway inflammation and Th cell differentiation, especially airway remodeling (41)(42)(43)(44). Lin et al found that enhanced PI3K/AKT/NF-kB signaling occurred in mast cell activation, which further promoted allergic airway inflammation (45).…”

Section: Discussionmentioning

confidence: 99%

Small Proline-Rich Protein 3 Regulates IL-33/ILC2 Axis to Promote Allergic Airway Inflammation

Zhu

Cai

et al. 2022

Front. Immunol.

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Small proline-rich proteins (SPRRs), components of cornified cell envelope precursors, have recently been found to participate in airway diseases. However, their role in allergic airway inflammatory conditions remains unknown. Here, we explored the expression of SPRR3 in house dust mite (HDM)-sensitized/challenged mice and attempted to elucidate the regulatory role of SPRR3 in allergic airway inflammation. SPRR3 was identified via bioinformatics analysis of Gene Expression Omnibus (GEO) databases and further confirmed to be upregulated in the lungs of asthmatic mice. Knockdown of SPRR3 via the intratracheal route significantly inhibited eosinophils in bronchoalveolar lavage fluid (BALF) and suppressed the expressions of type 2 cytokines (IL-4, IL-5, and IL-13) in BALF and lung tissues. Further, SPRR3 knockdown reduced the expression of IL-33 and further attenuated the activation of the PI3K/AKT/NF-κB signaling pathway in the recruitment of group 2 innate lymphoid cells (ILC2s) to inhibit allergic airway inflammation. In vitro, SPRR3 siRNA could alleviate HDM-induced inflammatory responses in BEAS-2B cells. This study reveals the regulatory role of SPRR3 in allergic airway inflammation, identifying this protein as a potential novel therapeutic target for asthma.

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Section: Discussionmentioning

confidence: 99%

Small Proline-Rich Protein 3 Regulates IL-33/ILC2 Axis to Promote Allergic Airway Inflammation

Zhu

Cai

et al. 2022

Front. Immunol.

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“…Finally, the activated AKT was able to phosphorylate plenty of downstream effectors, which regulated the cell growth, cell survival, angiogenesis, and migration, or invasion. In the previous research, Wu et al found through experiments that alpinetin had good anti-inflammatory activity against allergic asthma by regulating PI3K/AKT/NF-κB and HO-1 signaling pathways ( Wu D. et al, 2020 ). Ma et al mentioned in the study that allergic asthma would activate the mTOR signaling pathway, which led to the upregulation of p-PI3K, p-AKT, and p-mTOR.…”

Section: Discussionmentioning

confidence: 99%

“…IL-4 produced by Th2 cells played a central role in the development of asthma, in that it increased the expression level of inflammatory cytokines in the lung and ultimately stimulated the production of IgE. Inspired by the fact that IgE can mediate an allergic immune response, it was the main regulator of Th2 cytokines that controlled the progression of asthma ( Aghajani et al, 2019 ; Wu D. et al, 2020 ). The results of ELISA showed that DCM could effectively reduce the expression levels of IgE, IL-17, and IL-4 in serum.…”

Section: Discussionmentioning

confidence: 99%

Screening of Bioactive Fraction of Radix Paeoniae Alba and Enhancing Anti-Allergic Asthma by Stir-Frying Through Regulating PI3K/AKT Signaling Pathway

et al. 2022

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Allergic asthma is a common respiratory inflammation disease. The crude Radix Paeoniae Alba (RPA) and its processed products have been used frequently as antipyretic and anti-inflammatory agents in traditional medicine. To evaluate the effect of honey and bran processing, different fractions of RPA were used for treating anti-allergic asthma in the ovalbumin (OVA)-induced mice model, and then, the most effective fraction of RPA and stir-frying Radix Paeoniae Alba with honey and bran (FRPA) for treating anti-allergic asthma were compared mutually for pharmacological effects. The results showed that the treatment of the dichloromethane fraction of RPA significantly improved the pathological condition of lung tissues, decreased the number of eosinophils and other cells in bronchoalveolar lavage fluid (BALF), and the increased the expression of various inflammatory factors. Furthermore, the study discovered that the lung pathological conditions, compared with the high dose of dichloromethane RPA fraction, could be ameliorated by high dose of dichloromethane FRPA fraction treatment. Moreover, the expression of inflammatory factors and the phosphorylation of the PI3K/AKT signaling pathway could be diminished by FRPA. Finally, the contents of compounds with a significant difference in the FRPA dichloromethane fraction were paeoniflorin, ethyl gallate, pentagalloylglucose, galloylpaeoniflorin, and others by UPLC/Q-TOF-MS analysis. These findings suggest that the dichloromethane fraction of FRPA has an enhancement effect on anti-allergic asthma and provide the experimental basis for exploring the processed mechanism of RPA.

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“…TNF-α plays multiple roles in disease pathology by inducing an accumulation of in ammatory cells, stimulating the generation of in ammatory mediators, and causing oxidative and nitrosative stress, airway hyperresponsiveness, and tissue remodeling [48]. AKT regulates many processes, including metabolism, proliferation, cell survival, growth, and angiogenesis [59],and targeting the PI3K/AKT signal pathway is effective in treating asthma and IPF [59,60]. In the present study, we found that IL-6 was anchored by 6 potential ingredients of BSYQ Despite the profound signi cance of this study, several limitations should be noted.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Comorbidity Mechanisms Between Asthma and Idiopathic Pulmonary Fibrosis and the Pharmacological Mechanisms of Bu-Shen-Yi-Qi Decoction Therapy via Network Pharmacology

Zhong

Chen

et al. 2021

Preprint

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Backgrounds. Asthma and idiopathic pulmonary fibrosis (IPF) are common chronic diseases of the respiratory system in clinical practice. However, the relationship and molecular links between them remain unclear, and the current treatment's efficacy is disappointing. Bu-Shen-Yi-Qi (BSYQ) decoction has clinically proved to be effective in treating various chronic airway inflammatory diseases, including asthma and IPF. But the underlying pharmacological mechanisms are still to be elucidated. Methods. This study searched the proteins related to asthma and IPF via TTD, CTD, and DisGeNET database. We then submitted them to the STRING database to establish the protein-protein interaction (PPI) network. The co-bioinformatics analysis was conducted by Metascape. The active ingredients of BSYQ decoction were screened from TCMSP，ETCM，BATMAN-TCM database and HPLC/MS experiment. Then we predicted the corresponding targets based on TCMSP，ETCM, and BATMAN-TCM database. The common targets for asthma and IPF treatment were recognized, and further GO and KEGG analyses were conducted with the DAVID platform. Finally, molecule docking via Autodock Vina was employed to predict the potential binding mode between core potential compounds and targets.Results. One thousand three hundred thirty-three asthma-related targets and 404 IPF-related proteins were retrieved, 120 were overlapped between them, and much of the asthma-related proteins fall into the same statistically significant GO terms with IPF. One hundred sixteen active ingredients of BSYQ decoction were acquired, and 1535 corresponding targets were retrieved. Eighty-three potential compounds and 56 potential targets were recognized for both asthma and IPF treatment. GO and KEGG analysis indicated that the inflammation response, cytokine production, leukocyte differentiation, oxygen level response, etc., were the common pathological processes in asthma and IPF, which were regulated by BSYQ decoction. Molecule docking further predicted the potential binding modes between the core potential compounds and targets.Conclusion. The current study successfully clarified the complex molecule links between asthma and IPF and found the potential common targets between them. Then we demonstrated the efficacy of BSYQ decoction for asthma and IPF treatment from the angle of network pharmacology, which may provide valuable references for further studies and clinical use.

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Alpinetin prevents inflammatory responses in OVA-induced allergic asthma through modulating PI3K/AKT/NF-κB and HO-1 signaling pathways in mice

Cited by 35 publications

References 79 publications

Small Proline-Rich Protein 3 Regulates IL-33/ILC2 Axis to Promote Allergic Airway Inflammation

Small Proline-Rich Protein 3 Regulates IL-33/ILC2 Axis to Promote Allergic Airway Inflammation

Screening of Bioactive Fraction of Radix Paeoniae Alba and Enhancing Anti-Allergic Asthma by Stir-Frying Through Regulating PI3K/AKT Signaling Pathway

Exploring the Comorbidity Mechanisms Between Asthma and Idiopathic Pulmonary Fibrosis and the Pharmacological Mechanisms of Bu-Shen-Yi-Qi Decoction Therapy via Network Pharmacology

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