Active Ingredients of Epimedii Folium and Ligustri Lucidi Fructus Balanced GR/HSP90 to Improve the Sensitivity of Asthmatic Rats to Budesonide

Xiufeng Tang,Xinwei Yang,Yan Yang,Renhui Liu,Xiaoxi Li,Liping Xu,Xiujuan Wang,Honglei Nian,Yuheng Chen

doi:10.1155/2017/7961231

Xiufeng Tang, Xinwei Yang + Show 7 more

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https://doi.org/10.1155/2017/7961231

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Abstract

This study aimed to investigate the possible molecular mechanisms of active ingredients of Epimedii Folium (EF) and Ligustri Lucidi Fructus (LLF) combined with Budesonide (Bun) in asthmatic rats. Rats were divided into 5 groups, including normal group, asthma model group, Bun group, group of active ingredients of EL and LLF (EL), and group of coadministration of Bun with EL (Bun&EL). The asthmatic model was prepared by ovalbumin sensitizing and challenging. Lymphocyte apoptosis, GR protein and binding, and the protein and mRNA of GRα, GRβ, and HSP90 were tested. The results showed that Bun&EL ① markedly increased lymphocyte apoptosis, GR and HSP90 protein, and GR binding in BALF and ② enhanced the expressions of GRα and HSP90 and the ratio of GRα to GRβ or to HSP90 both in protein and in mRNA levels in lung, ③ while decrease occurred in GRβ mRNA and the mRNA ratio of GRβ to HSP90 compared with asthma or Bun group. Moreover, there was a significant correlation between GRα and GRβ in protein level, or between GRα and HSP90 both in protein and in mRNA levels. EL may effectively enhance the sensitivity of asthmatic rats to Bun via balancing GR/HSP90. And these findings will be beneficial for the treatment of asthma in the future.

Highlights

Asthma is one of the most serious worldwide public health problems that affects all age groups [1] and is characterized by chronic airway inflammation [2]
We demonstrated that the decoction of combined Epimedii Folium (EF) and Ligustri Lucidi Fructus (LLF) (EL) in combination with dexamethasone (Dex) had a better anti-inflammatory effect on the ovalbumin(OVA-) induced asthmatic rats and could prevent the inhibition of HPA axis and loss of bone mass compared with only using Dex [13, 14]
The level of lymphocyte apoptosis in bronchoalveolar lavage fluid (BALF), which was significantly lower in the asthma model group than in the control group, was shown in Figure 1(a) (P = 0.032)

Summary

Introduction

Asthma is one of the most serious worldwide public health problems that affects all age groups [1] and is characterized by chronic airway inflammation [2]. Glucocorticoids (GCs), which have powerful anti-inflammatory effects, are thought to be the first choice for the prevention and treatment of asthma, especially the application of inhaled GCs, playing anti-inflammatory effects and reducing the systemic side effects of GCs in a certain extent [3, 4]. Some asthma patients with treatment of inhaled GCs at conventional doses may experience no curative effects. When inhaled GCs are administered at high doses, or in long-term using, a series of side effects will be produced, such as growth stunting in children, hormone dependence, hormone resistance, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction [5,6,7]. How to increase the sensitivity of GC actions in the airway of asthma patients and reduce its adverse reactions has a great significance for the treatment of asthma. The expression of GR and HSP90 is closely related to the pharmacological effects of GCs

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