Han Jing, Zhang Siwang, Jiang Baoping, Wang Jingwen, Ge Xiaojing, Wu Bingrong, Zhang Sen, Wang Dongsheng
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China.
Phytomedicine. 2022 May;99:154032. doi: 10.1016/j.phymed.2022.154032. Epub 2022 Mar 3.
Asthma is a complex airway disease involving a variety of cells and cytokines. Xanthium sibiricum Patrin ex Widder (X. sibiricum) is a traditional Chinese medicine for various immune diseases, especially allergic rhinitis and asthma. Sesquiterpene lactones are the main bioactive and most abundant constituent, and are characteristic component of the plant. We explore whether sesquiterpene lactones from X. sibiricum (SL-XS) is the main active constitute for its anti-asthma activity.
In the present study, SL-XS was isolated, the major compounds were isolated and identified in extract of SL-XS, and the anti-asthma activity of SL-XS was validated in vivo.
SL-XS was isolated by a standard phytochemical method. The structures of major sesquiterpene lactones were identified by NMR and LC-MS spectra. The contents of major SL-XS were analyzed by HPLC. The anti-asthma effect of SL-XS was evaluated in a house dust mite (HDM)-induced mouse model.
The sesquiterpene lactones were isolated from X. sibiricum, and five major constituents i.e., 8‑epi-xanthatin-1β, 5β-epoxide (1), tomentosin (2), 8‑epi-xanthatin (3), 2‑epi-xanthumin (4) and sibiriolide B (5) were identified from SL-XS. Oral administration of SL-XS dose-dependently ameliorated airway inflammation and remodeling in HDM-challenged asthma mouse model. Furthermore, SL-XS treatment inhibited the upregulation of proinflammatory and Th2 cytokines, while reversed the downregulation of Th1 related cytokines. In addition, SL-XS regulated the balance between T-bet and GATA-3. Moreover, SL-XS inhibited the upregulation of JAK1, p-JAK1, JAK2, p-JAK2, JAK3, p-JAK3 and p-STAT6 in HDM-challenged mice.
The sesquiterpene lactones including five major constituents may be the main anti-asthma active constituent of X. sibiricum. SL-XS exerted its anti-asthma effect by modulating the Th1/Th2 balance via the JAK/STAT signaling pathway.
哮喘是一种涉及多种细胞和细胞因子的复杂气道疾病。苍耳（Xanthium sibiricum Patrin ex Widder，苍耳）是一种用于治疗多种免疫疾病，尤其是过敏性鼻炎和哮喘的传统中药。倍半萜内酯是其主要的生物活性成分且含量最为丰富，是该植物的特征性成分。我们探究来自苍耳的倍半萜内酯（SL-XS）是否是其抗哮喘活性的主要活性成分。
在本研究中，分离出SL-XS，鉴定出其提取物中的主要化合物，并在体内验证了SL-XS的抗哮喘活性。
采用标准植物化学方法分离SL-XS。通过核磁共振（NMR）和液相色谱-质谱（LC-MS）光谱鉴定主要倍半萜内酯的结构。采用高效液相色谱法（HPLC）分析主要SL-XS的含量。在屋尘螨（HDM）诱导的小鼠模型中评估SL-XS的抗哮喘作用。
从苍耳中分离出倍半萜内酯，并从SL-XS中鉴定出五种主要成分，即8-表-苍耳亭-1β,5β-环氧化物（1）、绵毛苍耳素（2）、8-表-苍耳亭（3）、2-表-苍耳明（4）和苍耳内酯B（5）。口服SL-XS可剂量依赖性地改善HDM激发的哮喘小鼠模型中的气道炎症和重塑。此外，SL-XS治疗抑制促炎细胞因子和Th2细胞因子的上调，同时逆转Th1相关细胞因子的下调。此外，SL-XS调节T-bet和GATA-3之间的平衡。此外，SL-XS抑制HDM激发小鼠中JAK1、p-JAK1、JAK2、p-JAK2、JAK3、p-JAK3和p-STAT6的上调。
包括五种主要成分的倍半萜内酯可能是苍耳抗哮喘的主要活性成分。SL-XS通过JAK/STAT信号通路调节Th1/Th2平衡发挥其抗哮喘作用。
