This study aimed to investigate the interventional effect and potential mechanism of a lignan compound, (7S, 8R, 8'R)-eplignan C (EPC), from Ephedra intermedia, on ovalbumin (OVA)-sensitized asthmatic mice. Specific pathogen-free (SPF) male BALB/c mice were randomly assigned to normal control (CON), model (M), positive control (montelukast sodium, 1.3 mg·kg-1), EPC low-dose (EPC-L, 10 mg·kg-1), and EPC high-dose (EPC-H, 20 mg·kg-1) groups. An allergic asthma model was established through intraperitoneal injection of OVA with aluminum hydroxide adjuvant followed by OVA aerosol challenge. After 7 consecutive days of administration, cough and asthma indicators, lung function, serum immunoglobulin E (IgE) levels, and lung tissue pathology were assessed 24 h post-final dose. Enzyme-linked immunosorbent assay (ELISA) was employed to measure serum levels of mast cell degranulation products and inflammatory factors; flow cytometry was utilized to detect immune cells (dendritic cells, mast cells, Tregs) and Ca2+ levels; immunofluorescence was applied to evaluate tryptase alpha/beta 1 (TPSAB1) and septin 11 (Septin11) protein expression in lung tissue; Western blot analysis was conducted to examine protein expression and activation levels of key molecules in the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in lung tissue samples. Furthermore, a co-culture system comprising mouse lung epithelial cells (MLE-12) and primary mouse splenocytes, combined with the JAK2/STAT3-specific inhibitor tyrphostin AG490, was employed to elucidate the mechanism underlying EPC's intervention in OVA-sensitized asthma. Results demonstrated that EPC alleviated asthma-related cough, inhibited airway hyperresponsiveness, improved lung pathological damage, modulated immune cell levels, suppressed inflammatory responses and mast cell degranulation, exhibiting significant anti-asthmatic effects, and reduced key protein expression in the JAK2/STAT3 signaling pathway. Further mechanistic investigation revealed that EPC regulated Th17/Treg immune imbalance and attenuated inflammatory responses in the co-culture system, effects that were blocked by AG490. Thus, it is speculated that EPC may exert its anti-asthmatic effects by regulating the JAK2/STAT3 signaling pathway to inhibit mast cell degranulation and modulate immune-inflammatory responses. This animal experiment gas been approved by the Animal Ethics Committe of Henan University of Chinese Medicine (approval number DWLL2018080003).
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |