Chrysophanol attenuates airway inflammation and remodeling through nuclear factor‐kappa B signaling pathway in asthma

• Published in: Phytotherapy research 2019-10, Vol.33 (10), p.2702-2713
• Main Authors: Song, Guihua, Zhang, Yan, Yu, Suping, Lv, Weigang, Guan, Zhiwei, Sun, Mengmeng, Wang, Jing
• Format: Article
• Language: English
• Subjects: Actin; airway remodeling; Airway Remodeling - drug effects; Animals; Anthraquinones - pharmacology; Anthraquinones - therapeutic use; Asthma; Asthma - drug therapy; Autophagy; Chrysophanic acid; chrysophanol; Inflammation; Inflammation - drug therapy; Interleukins; Lungs; Male; Mice; Mice, Inbred BALB C; Muscles; NF-kappa B - physiology; NF‐κB pathway; Nitric oxide; Nitric-oxide synthase; Nuclear transport; Ovalbumin; Phagocytosis; Respiratory tract; Respiratory tract diseases; Signal transduction; Signal Transduction - drug effects; Signaling; Smooth muscle; Translocation; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.6444

Chrysophanol (CHR), a purified active constituent extracted from Rheum palmatum L., possesses anti‐inflammatory activity. This study aimed to evaluate its effects on asthma‐associated airway inflammation and remodeling. BALB/c mice were sensitized and challenged by ovalbumin (OVA) and administrated with different doses of CHR. We found that CHR decreased OVA‐induced pulmonary inflammation: the levels of interleukin (IL)‐4, IL‐5, and IL‐13, tumor necrosis factor (TNF)‐α, and inducible nitric oxide synthase were downregulated. CHR also attenuated airway remodeling induced by OVA challenge—CHR inhibited pulmonary α‐smooth muscle actin expression. Moreover, both the nuclear translocation and activity of NF‐κB p65 were inhibited by CHR in the asthmatic lung. Enhanced autophagy was initiated in the lung by OVA challenge as evidenced by upregulated light chain 3 beta, autophagy‐related protein 5, and Beclin 1. CHR suppressed OVA‐induced alterations in these autophagy‐related molecules. In vitro, CHR (2 or 20 μM) was used to treat human pulmonary epithelial BEAS‐2B cells in the presence of 10 ng/ml recombinant TNF‐α. CHR not only exhibited the antiproliferation effect but also inhibited the activation of nuclear factor‐kappa B (NF‐kB) signaling pathway in TNF‐α‐treated BEAS‐2B cells. In conclusion, our study indicates that CHR has the potential to ameliorate asthma.