Semen cassiae Extract Inhibits Contraction of Airway Smooth Muscle.

Yu‐Shan She ,Shanshan Chen,Chenyou Shen,Lei Cao,Qian Wang,Jiapei Dai,Jingyu Chen,Xiaowei Nie,Hao Xu,Ping Zhao,Weiwei Chen,Shu Chen,Gangjian Qin,Ximing Luo ,Li‐Qun Ma ,Wenjing Zhang ,Junying Qiu ,Xue Lü ,Yuanyuan Chen ,Dun‐An Zang ,Beibei Liu ,Meng‐Fei Yu ,Xiaozhen Zhao ,Yongbo Peng ,Mengyue Li ,Qinghua Liu

doi:10.3389/fphar.2018.01389

Abstract

β2-adrenoceptor agonists are commonly used as bronchodilators to treat obstructive lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), however, they induce severe side effects. Therefore, developing new bronchodilators is essential. Herbal plants were extracted and the extracts’ effect on airway smooth muscle (ASM) precontraction was assessed. The ethyl alcohol extract of semen cassiae (EESC) was extracted from Semen cassia. The effects of EESC on the ACh- and 80 mM K+-induced sustained precontraction in mouse and human ASM were evaluated. Ca2+ permeant ion channel currents and intracellular Ca2+ concentration were measured. HPLC analysis was employed to determine which compound was responsible for the EESC-induced relaxation. The EESC reversibly inhibited the ACh- and 80 mM K+-induced precontraction. The sustained precontraction depends on Ca2+ influx, and it was mediated by voltage-dependent L-type Ca2+ channels (LVDCCs), store-operated channels (SOCs), TRPC3/STIM/Orai channels. These channels were inhibited by aurantio-obtusin, one component of EESC. When aurantio-obtusin removed, EESC’s action disappeared. In addition, aurantio-obtusin inhibited the precontraction of mouse and human ASM and intracellular Ca2+ increases. These results indicate that Semen cassia-contained aurantio-obtusin inhibits sustained precontraction of ASM via inhibiting Ca2+-permeant ion channels, thereby, which could be used to develop new bronchodilators.

Highlights

300 million and 328.6 million people suffer from asthma and chronic obstructive pulmonary disease (COPD) worldwide (Braman, 2006; Vos et al, 2012)
The IC50 was 0.37 ± 0.04 mg/mL, and the maximal inhibition was 104.24 ± 3.12% (n = 8). These data indicate that ethyl alcohol extract of Semen cassia (EESC) almost completely blocks acetylcholine chloride (ACh)- and high K+-induced airway smooth muscle (ASM) contraction
We found that the ingredients (i.e., EESC and aurantio-obtusin) of Semen cassia reversibly reduced both ACh- and high K+-induced precontractions in mouse tracheal rings (TRs) and lung slices

Summary

Introduction

300 million and 328.6 million people suffer from asthma and COPD worldwide (Braman, 2006; Vos et al, 2012). Bronchodilators are a major group of medications for the treatment of these obstructive lung diseases (Dekhuijzen, 2015), they cause various side effects such as palpitations, tremor, headache, cardiovascular death (Kajioka et al, 2012), ischemic heart disease, cardiac failure, death due to lifethreatening asthma attacks (Abramson et al, 2003; Cazzola et al, 2005; Hasford and Virchow, 2006; Wijesinghe et al, 2009), and desensitization (Nino et al, 2009). According to Chinese records, “Shennong Ben Cao Jing” (published in approximately 1602∼1616, during the Ming Dynasty), Semen cassiae has been used as folkloric medicine to treat various diseases/disorders such as sore red swollen eyes, poor vision, headache, dizziness, diuresis, constipation, and swollen, tinea, and hepatic irrhosis ascites. We found that the ethyl alcohol extract of Semen cassia (EESC) inhibits ASM contraction via inhibiting Ca2+ permeant ion channels

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