Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway.

BACKGROUND: Obese asthma is one of the important asthma phenotypes that have received wide attention in recent years. Excessive oxidative stress and different inflammatory endotypes may be important reasons for the complex symptoms, frequent aggravation, and resistance to traditional treatments of obese asthma. Apigenin (API), is a flavonoid natural small molecule compound with good anti-inflammatory and antioxidant activity in various diseases and proved to have the potential efficacy to combat obese asthma. METHODS: In vivo, this study fed C57BL/6 J mice with high-fat diets(HFD)for 12 weeks and then stimulated them with OVA for 6 weeks to establish a model of chronic obese asthma, while different doses of oral API or dexamethasone were used for therapeutic interventions. In vitro, this study used HDM to stimulate human bronchial cells (HBEs) to establish the model and intervened with API or Selonsertib (SEL). RESULTS: This study clarified that OVAinduced a type of mixed granulocytic asthma with elevated neutrophils and eosinophils in obese male mice fed with long-term HFD, which also exhibited mixed TH17/TH1/TH2 inflammation. Apigenin effectively suppressed this complex inflammation and acted as a regulator of immune homeostasis. Meanwhile, apigenin reduced AHR, inflammatory cell infiltration, airway epithelial cell apoptosis, airway collagen deposition, and lung oxidative stress via the ROS-ASK1-MAPK pathway in an obese asthma mouse model. In vitro, this study found that apigenin altered the binding status of TRAF6 to ASK1, inhibited ASK1 phosphorylation, and protected against ubiquitin-dependent degradation of ASK1, suggesting that ROS-activated ASK1 may be an important target for apigenin to exert anti-inflammatory and anti-apoptotic effects. To further verify the intervention mechanism, this study clarified that apigenin improved cell viability and mitochondrial function and inhibited apoptosis by interfering with the ROS-ASK1-MAPK pathway. CONCLUSIONS: This study demonstrates for the first time the therapeutic effect of apigenin in chronic obese asthma and further clarifies its potential therapeutic targets. In addition, this study clarifies the specificity of chronic obese asthma and provides new options for its treatment.

The Anticancer Properties of Herba Epimedii and Its Main Bioactive Componentsicariin and Icariside II.

Cancer is one of the leading causes of deaths worldwide. Compounds derived from traditional Chinese medicines have been an important source of anticancer drugs and adjuvant agents to potentiate the efficacy of chemotherapeutic drugs and improve the side effects of chemotherapy. Herba Epimedii is one of most popular herbs used in China traditionally for the treatment of multiple diseases, including osteoporosis, sexual dysfunction, hypertension and common inflammatory diseases. Studies show Herba Epimedii also possesses anticancer activity. Flavonol glycosides icariin and icariside II are the main bioactive components of Herba Epimedii. They have been found to possess anticancer activities against various human cancer cell lines in vitro and mouse tumor models in vivo via their effects on multiple biological pathways, including cell cycle regulation, apoptosis, angiogenesis, and metastasis, and a variety of signaling pathways including JAK2-STAT3, MAPK-ERK, and PI3k-Akt-mTOR. The review is aimed to provide an overview of the current research results supporting their therapeutic effects and to highlight the molecular targets and action mechanisms.

Comparison of effect of granules and herbs of Bu-Shen-Yi-Qi-Tang on airway inflammation in asthmatic mice.

BACKGROUND: Bu-Shen-Yi-Qi-Tang (BSYQT), which is prescribed on the basis of clinical experience, is commonly used in clinics of traditional Chinese medicine (TCM) for asthma treatment. The components of BSYQT include Radix Astragali (RA), Herba Epimedii (HE) and Radix Rehmanniae (RR). The aim of this study was to compare the effect of granules and herbs of BSYQT on airway inflammation in asthmatic mice. METHODS: Sixty female BALB/c mice were randomly divided into the normal control (NC) group, asthmatic group (A), decoction of granules of BSYQT treatment group (GD), decoction of herbs of BSYQT treatment group (HD), and dexamethasone treatment group (DEX). The mouse asthmatic model was induced by ovalbumin (OVA) sensitization and challenge. GD and HD of BSYQT as well as DEX were prepared and administered by intragastric infusion. Airway hyperresponsiveness (AHR) to methacholine (Mch), lung histopathology analysis, inflammatory mediators in serum (IL-4, IL-5, IL-17A, IFN-γ, and eotaxin) and in lung (IL-4, IL-5, IFN-γ, and eotaxin) were selected for investigation and comparison. RESULTS: Both GD and HD treatment could decrease airway resistance (RL) and increase dynamic compliance (Cdyn) to Mch compared with the A group (P < 0.05). HD treatment was more effective in RL reduction than Mch at doses of 3.125 and 6.25 mg/ml (P < 0.05) and in Cdyn increase at Mch doses of 6.25 and 12.5 mg/ml (P < 0.05). There were no marked differences in RL reduction and Cdyn improvement between mice in HD and DEX groups (P > 0.05). Both GD and HD treatment markedly attenuated lung inflammation (P < 0.05), and HD treatment demonstrated more significant therapeutic function in alleviating lung inflammation than that of GD and DEX treatment (P < 0.05). Both GD and HD treatment resulted in a significant reduction in IL-4 and IL-17A levels and an increase in the IFN-γ level in serum compared with the A group (P < 0.05). The effect of HD in lowering the IL-4 and IL-17A level was significantly greater than that of GD (P < 0.05), and was not significantly different from DEX (P > 0.05). HD treatment significantly reduced the serum level of IL-5 and eotaxin compared with the A group (P < 0.05), however, mice in the GD treatment group did not demonstrate this effect. GD and HD treatment significantly reduced IL-4 and eotaxin mRNA expression compared with the A group (P < 0.05). HD treatment significantly reduced IL-5 mRNA expression compared with the A group (P < 0.05). There was a significant difference between the GD and HD treatment groups in reducing IL-5 and eotaxin mRNA expression (P < 0.05). HD treatment was more effective in down-regulation of IL-5 in serum and eotaxin level both in serum and lung than DEX (P < 0.05). Compared with the A group, an obvious increase in mRNA expression of IFN-γ was observed in both the GD and HD treatment groups (P < 0.05). However, the effect of HD treatment on increase of IFN-γ mRNA expression was more apparent than GD and DEX treatment (P < 0.05). CONCLUSIONS: Both GD and HD treatment could decrease AHR, attenuate lung inflammation, reduce IL-4, IL-5, IL-17A, and eotaxin levels and increase IFN-γ levels in asthmatic mice. HD treatment manifests more remarkable inhibitory effects on asthmatic inflammation than GD treatment, which could provide a guide for further research on the screening of the material basis of the best anti-inflammatory effect of BSYQT.