Exploring the effective materials of flavonoids-enriched extract from Scutellaria baicalensis roots based on the metabolic activation in influenza A virus induced acute lung injury

Flavonoids-enriched extract from Scutellaria baicalensis roots (FESR) ameliorated influenza A virus (IAV) induced acute lung injury (ALI) in mice by inhibiting the excessive activation of complement system in vivo. However, FESR had no anti-complementary activity in vitro. In order to reveal the effective materials of FESR for the treatment of IAV-induced ALI, the present research explored the metabolic process of FESR both in nomal and IAV infected mice by the method of UHPLC-ESI-LTQ/MS, as well as the metabolic activating mechanism. The results showed that the inactive flavonoid glycosides of FESR were partly metabolized into anti-complementary aglycones in vivo, mainly including 5,7,4'-trihydroxy-8-methoxy-flavone, norwogonin, baicalein, wogonin, oroxylin A and chrysin. Moreover, compared with the normal mice, IAV-induced ALI mice exhibited more efficient on producing and absorbing these active metabolites, with AUC0-t and Cmax in plasma and concentrations in lungs and intestines markedly elevated in the IAV treated groups (P < 0.05). Interestingly, the intestinal bacteria from IAV-induced ALI mice showed stronger β-glucuronidase activity and also had higher efficiency on transforming FESR to the flavonoid aglycones. These findings suggested that the anti-complementary aglycones produced by metabolic activation in vivo should be the potential effective materials of FESR against IAV infections, and intestinal bacteria might play an important role on the higher bioavailability of FESR in IAV infected mice. Additionally, the animals under the pathological state are more suitable for the metabolic study of traditional Chinese medicine.