Flavokavains A-\nand B‑Free Kava Enhances Resilience\nagainst the Adverse Health Effects of Tobacco Smoke in Mice

Tobacco\nsmoke remains a serious global issue, resulting\nin serious\nhealth complications, contributing to the onset of numerous preventive\ndiseases and imposing significant health burdens. Despite regulatory\npolicies and cessation measures aimed at curbing its usage, novel\ninterventions are urgently needed for effective damage reduction.\nOur preclinical and pilot clinical studies showed that AB-free kava\nhas the potential to reduce tobacco-smoking-induced lung cancer risk,\nmitigate tobacco dependence, and reduce tobacco use. To understand\nthe scope of its benefits in damage reduction and potential limitations,\nthis study evaluated the effects of AB-free kava on a panel of health\nindicators in mice exposed to 2–4 weeks of daily tobacco smoke\nexposure. Our assessments included global transcriptional profiling\nof the lung and liver tissues, analysis of lung inflammation, evaluation\nof lung function, exploration of tobacco nicotine withdrawal, and\ncharacterization of the causal protein kinase A (PKA) signaling pathway.\nAs expected, tobacco smoke exposure perturbed a wide range of biological\nprocesses and compromised multiple functions in mice. Remarkably,\nAB-free kava demonstrated the ability to globally mitigate tobacco\nsmoke-induced deficits at the molecular and functional levels with\npromising safety profiles, offering AB-free kava unique promise to\nmitigate tobacco smoke-related health damages. Further preclinical\nevaluations are warranted to fully harness the potential of AB-free\nkava in combating tobacco smoke-related harms in the preparation of\nits clinical translation.