Demethylzeylasteral (T-96) Alleviates Allergic Asthma via Inhibiting MAPK/ERK and NF-κB Pathway

Demethylzeylasteral (T-96), a new extract of Tripterygium wilfordii Hook F, exerted immunomodulatory properties in autoimmune diseases, but its effect on airway inflammatory diseases remains unclear. Our study aims to explore the protective effect and underlying mechanism of T-96 in allergic asthma.

The OVA-induced asthmatic mice were administered by gavage with T-96 (0.1 mg/10 g, 0.3 mg/10 g, or 0.6 mg/10 g) 1 h before each challenge. The airway hyperresponsiveness was assessed, pathological changes were evaluated by HE and PAS staining, and expressions of Th2 cytokines were determined by PCR and ELISA. The activation of MAPK/ERK and NF-κB pathway was assessed by western blot.

T-96 significantly relieved airway hyperresponsiveness in asthmatic mice, evidenced by reduced airway resistance (Raw) and increased lung compliance dynamic compliance (Cdyn). Also, enhanced inflammatory infiltration and mucus hypersecretion were ameliorated in lungs of asthmatic mice following increasing doses of T-96 treatment, accompanied by decreased eosinophils in bronchoalveolar lavage fluid (BALF), IgE and OVA-specific IgE levels in serum, and downregulated IL-5 and IL-13 expressions in BALF and lung tissues as well. Notably, phosphorylation levels of p38 MAPK, ERK, and p65 NF-κB were obviously increased in asthmatic mice compared with the control group, which were then abrogated upon T-96 treatment.

This study first revealed that T-96 alleviated allergic airway inflammation and airway hyperresponsiveness via inhibiting MAPK/ERK and NF-κB pathway. Thus, T-96 could potentially act as a new anti-inflammatory agent in allergic asthma.