Therapeutic effects on H1N1-induced pneumonia in mice and intestinal bacteria biotransformation of four main flavonoids from Houttuynia cordata Thunb.

Flavonoids widely exist in a large number of Chinese herbal medicines with antiviral and anti-inflammatory properties. Houttuynia cordata Thunb. is a traditional Chinese herbal medicine for heat-clearing and detoxification. In our previous research, total flavonoids from H. cordata (HCTF) effectively alleviated H1N1-induced acute lung injury (ALI) in mice. In this study, 8 flavonoids were recognized from HCTF (containing 63.06 % ± 0.26 % of total flavonoids, as quercitrin equivalents) by UPLC-LTQ-MS/MS. Four main flavonoid glycosides in HCTF (rutin, hyperoside, isoquercitrin and quercitrin) and their common aglycone quercetin (100 mg/kg) all showed therapeutic effects on H1N1-induced ALI in mice. The two flavonoids (hyperoside and quercitrin) with higher contents and quercetin showed stronger therapeutic effects on H1N1-induced ALI in mice. Hyperoside, quercitrin and quercetin significantly reduced the levels of pro-inflammatory factors, chemokines, or neuraminidase activity compared with the same dose of HCTF (p < 0.05). The results of mice intestinal bacteria biotransformation in vitro showed that quercetin was the main metabolite. The conversion rates of hyperoside and quercitrin were significantly higher by the intestinal bacteria under the pathological state (0.81 ± 0.02 and 0.91 ± 0.01, respectively) than normal state (0.18 ± 0.01 and 0.18 ± 0.12, respectively, p < 0.001). Our findings showed that hyperoside and quercitrin were the main efficacious components of HCTF for treating H1N1-induced ALI in mice and could be metabolized to quercetin by intestinal bacteria in pathological state to exert their effects.