Zhichuanling oral liquid attenuates airway inflammation in asthma by targeting the STIM1/CHOP/JNK axis.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Zhichuanling oral liquid (ZCLOL) is a multi-component traditional Chinese medicine formulation that has been widely used in the clinical management of asthma. However, the molecular mechanisms underlying its clinical efficacy remain largely undefined, particularly regarding calcium homeostasis and endoplasmic reticulum stress (ERS) regulation. AIM OF THE STUDY: This study aimed to elucidate the mechanisms by which ZCLOL mitigates asthma-related airway inflammation through the integration of in vivo and in vitro models with proteomic profiling. METHODS: In this study, an OVA-induced asthma model was established to evaluate the therapeutic effects of ZCLOL by assessing pulmonary function, serum Th2 cytokine levels, and macrophage polarization. To further elucidate the underlying mechanisms of ZCLOL in asthma treatment, we conducted proteomic analysis, measured calcium levels in lung tissue, and performed Western blotting. Additionally, an inflammatory BEAS-2B cell model induced by LPS and IL-13, combined with BAPTA-AM treatment, was used to explore the molecular pathways involved. RESULTS: ZCLOL effectively alleviated airway hyperresponsiveness, reduced lung tissue injury, inhibited M1 macrophage polarization and Th2 cytokine secretion, decreased intracellular calcium ion levels, mitigated endoplasmic reticulum stress, and downregulated the expression of STIM1, Bip, Ero1-Lα, PDI, CHOP, and phosphorylated JNK (p-JNK). CONCLUSION: ZCLOL alleviates airway inflammation and hyperresponsiveness in asthma by restoring Cahomeostasis and suppressing ERS through inhibition of the STIM1/CHOP/JNK axis. These findings provide mechanistic evidence supporting ZCLOL as a potential multi-target therapeutic strategy for asthma.