Bian, T.; Lynch, A. C.; Ballas, K.; Mamallapalli, J.; Freeman, B.; Scala, A.; Wang, Y.; Trabouls, H.; Chellian, R. k.; Fagan, A.; Tang, Z.; Ding, H.; De, U.; Fredenburg, K. M.; Huo, Z.; Baglole, C. J.; Zhang, W.; Reznikov, L.; Bruijnzeel, A.; Xing, C.

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onsets of numerous preventive diseases, and imposing significant financial burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB free kava has the potential to reduce tobacco smoke induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB free kava on a panel of health indicators in mice exposed to 2 to 4 weeks of daily tobacco smoke exposure. Our comprehensive assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal PKA signaling pathway. As expected, Tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke induced deficits at the molecular and functional levels with promising safety profiles, offering a unique promise to mitigate tobacco smoke related health damages. Further preclinical evaluation and clinical translation are warranted to fully harness the potential of AB free kava in combating tobacco smoke-related harms.