Cordyceps extract and withaferin A (Wi-A) are natural compounds that have therapeutic effects on non-alcoholic fatty liver disease (NAFLD). However, their efficacy is limited and a long treatment duration is usually required. To enhance their efficiency, the synergistic effects of nanobubble water (NBW) derived from nitrogen, hydrogen, and oxygen gases were investigated. Results showed that the physical properties of all three NBWs, including nanobubble density (108 particles/mL) and zeta potential (below −22 mV), were stable during 48 h of storage. Hydrogen and nitrogen NBWs did not reduce, but instead promoted, free fatty acid-induced lipid accumulation in HepG2 cells. In contrast, oxygen NBW synergistically enhanced the effects of cordyceps extract and Wi-A. The lipid content decreased by 29% and 33% in the oxygen NBW + cordyceps extract and oxygen NBW + Wi-A groups, respectively, compared to reductions of 22% and 16% by aqueous extracts without NB. This study found that NBW may enhance the lipid-reducing effects of natural compounds, such as cordyceps extract and withaferin A, in hepatic cells. Further studies in animal experiments are needed to determine whether NBW has a potential application in NAFLD.
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