Mechanism of Ginkgolide B regulating Th1/Th2 balance to improving airway inflammatory response and hyperresponsiveness in asthma model mice: TLR4/NF-κB pathway.

The objective of the study is to investigate the protective effect of Ginkgolide B on house dust mite (HDM)-sensitized asthmatic mice and its potential mechanism involving the TLR4/NF-κB pathway. In HDM-induced asthmatic mice, we administered varying doses of Ginkgolide B. We evaluated airway hyperresponsiveness and the expectorant properties of Ginkgolide B. Changes in inflammatory infiltration, goblet cell proliferation, and airway fibrosis were detected with HE, PAS, and Masson staining. We analyzed the Th1 and Th2 cell numbers and their secreted cytokine levels. In a more in-depth study, we administered lentiviruses that overexpressed and knocked down TLR4, while also treating with Ginkgolide B. Subsequently, we conducted experiments on airway hyperresponsiveness, HE and PAS staining, and flow cytometry for detecting the Th1 and Th2 cell numbers. HDM-sensitized asthmatic mice exhibited high airway reactivity and severe inflammatory response. After treatment with Ginkgolide B, airway hyperresponsiveness significantly improved; inflammation, airway tissue fibrosis, and goblet cell proliferation were reduced, while airway secretions decreased and expectorant ability was enhanced. In addition, Ginkgolide B effectively inhibited the shift of Th1/Th2 immune balance to Th2 in asthmatic mice. In-depth mechanistic research has found that the aforementioned effects of Ginkgolide B were related to the TLR4/NF-κB pathway. Ginkgolide B inactivated the TLR4/NF-κB pathway, restored the Th2/Th1 immune balance, and alleviated airway hyperresponsiveness and the inflammatory response. Our research showed that Ginkgolide B effectively treated HDM-sensitized asthma in mice by inhibiting the TLR4/NF-κB pathway, restoring Th1/Th2 balance, and alleviating airway inflammation and hyperresponsiveness.