Ilex asprella aqueous extracts exert in vivo anti-inflammatory effects by regulating the NF-κB, JAK2/STAT3, and MAPK signaling pathways

• Published in: Journal of ethnopharmacology 2018-10, Vol.225, p.234-243
• Main Authors: Yang, Xinyao, Gao, Xiaoli, Du, Bingzhao, Zhao, Feng, Feng, Xiao, Zhang, Hexinge, Zhu, Zhixiang, Xing, Jianyong, Han, Zhengzhou, Tu, Pengfei, Chai, Xingyun
• Format: Article
• Language: English
• Subjects: Anti-inflammation; Ilex asprella; JAK2/STAT3; MAPK; NF-κB
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2018.06.037

Ilex asprella (Hook. et Arn.) Champ. ex Benth. (IA) is a representative medicinal plant from the South of the Five Ridges of China. Its roots (RIA) and stems (SIA) have been traditionally used for the inflammation-related diseases, such as acute and chronic pharyngitis, cough, and sore throats. To evaluate the in vivo anti-inflammatory effects of IA extracts to provide evidence for its traditional use and to enhance the knowledge of the medicinal properties of IA. Models of xylene-induced ear edema in mice and carrageenan-induced paw edema in rats were used for the pharmacological evaluations. The mice were randomly divided into eight groups (n = 10 per group): a model group, a positive control group [dexamethasone (Dex), 10 mg/kg, intragastrically (i.g.)], RIA aqueous extract groups with three dosages (30, 15, and 7.5 mg/kg, i.g.), and SIA aqueous extract groups with three dosages (60, 30, and 15 mg/kg, i.g.). The rats were randomly divided into eight groups (n = 6 per group): a model group, a positive control group [acetylsalicylic acid (ASA), 300 mg/kg, i.g.], RIA groups with three dosages (80, 40, and 20 mg/kg, i.g.) and SIA aqueous extract groups with three dosages (160, 80, and 40 mg/kg, i.g.). Histological examinations of the ear and paw tissues were observed by hematoxylin-eosin (HE) staining, and neutrophil elastase levels were assessed in ear tissues by immunohistochemical analysis. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured by ELISAs, and expression levels of TNF-α, IL-6, and IL-1β in rat paw tissues were measured by RT-PCR. The signal transduction proteins p65, IκBα, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), p38 mitogen-activated protein kinases (p38), extracellular regulated protein kinases (ERK1/2), and c-Jun N-terminal kinase (JNK) in the rat paw tissues were investigated by western blot analyses. RIA and SIA were characterized by HPLC and LC-MS analyses, and the components were confirmed by comparison with isolated compounds. Intragastric administration with RIA (30 mg/kg) and SIA (60, 30 mg/kg) significantly mitigated ear edema in mice. RIA administration at 80 and 40 mg/kg reduced paw edema in rats 2‒3 h after injection. SIA administration with 160 mg/kg inhibited paw edema in rats after the injection of carrageenan for 1‒4 h, and SIA administration at 80 mg/kg inhibited paw edema after the injection of carrageenan for 2‒4 h. Mean