Metabolism and Tissue Distribution of Chelerythrine and Effects of Macleaya Cordata Extracts on Liver NAD(P)H Quinone Oxidoreductase

Abstract

Background:Macleaya cordata (Willd.) (Papaveraceae) is listed as a feed additive in animal production by the European Food Authority.Methods: The metabolites of chelerythrine in rats were measured in vitro and in vivo by rapid and accurate high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (HPLC/QqTOF-MS). The structures of CHE metabolites were elucidated by comparing their changes in accurate molecular masses and fragment ions with those of parent ion or metabolite. The metabolic enzymes that were involved in chelerythrine reduction were investigated using an inhibition method. The tissue distribution of chelerythrine and the effects on NQO1 following intragastric administration with M. cordata extracts in rats were examined.Results: A total of twelve metabolites of chelerythrine were characterized by this approach in rat liver S9 and in vivo. The reduction of the iminium bond of chelerythrine and subsequent O-demethylation was the main metabolic pathway of chelerythrine in rat liver S9 while the reduction of the iminium bond of chelerythrine was the main metabolic pathway of chelerythrine in rats in vivo. After the rats were given intragastric administration, the low concentration residues of sanguinarine and chelerythrine in different rat tissues were found at 48 h after the last dose, suggesting that both compounds could be widely distributed in tissues. The results also indicated that XO, NQO1, NQO2, and carbonyl reductase are involved in chelerythrine reduction. Macleaya cordata extracts treated female and male rats, respectively, showed different responses, inhibiting NQO1 activity in males, but inducing NQO1 activity in females. Chelerythrine had a weak impact on NQO1 activity, but sanguinarine inhibited NQO1 activityConclusion: Through studying the effects of cytosolic reductase inhibitors on chelerythrine reduction and the impact of chelerythrine and sanguinarine on the activity of NQO1 in vitro and in vivo, we clarified the potential drug interaction of Macleaya cordata extract in clinical application, so as to provide theoretical guidance for clinically safe medication. In addition, it provided a reference basis for the metabolic mechanism of chelerythrinein rats.

Sanguinarine Exhibits Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus via Multisite Inhibition Mechanisms

“…Sanguinarine along with chelerythrine are known as main effective alkaloids of Macleaya cordata [ 26 ]. Sangrovit ® is a low-cost, safe, and effective feed additive derived from Macleaya cordata , with sanguinarine and chelerythrine as the major bioactive compounds [ 27 ].…”

Effects of Dietary Macleaya cordata Extract on Growth Performance, Biochemical Indices, and Intestinal Microbiota of Yellow-Feathered Broilers Subjected to Chronic Heat Stress

“…Consistently, the current study showed that treatment with MCE reduced the AST, ALT, and LDH activity and increased the ALP activity in HS-induced broilers, suggesting that MCE seems to protect the broilers from liver injury. The protective effect of MCE on the liver may be due to the inhibition of hepatic NAD(P)H quinone oxidoreductase activity [ 62 ] and the hepatic lipid peroxidation and inflammatory response [ 63 ] by chelerythrine. Moreover, HS also significantly decreased the levels of serum GLU and significantly increased the levels of TC and LDL-C.…”

Effects of Macleaya cordata Extract on Blood Biochemical Indices and Intestinal Flora in Heat-Stressed Mice

“…As expected, MCE administration attenuated HS-mediated liver damage, evidenced by serum’s reduction in AST and ALT activities. The protective effect of MCE on the liver may be due to the inhibition of hepatic NAD(P)H quinone oxidoreductase activity [ 52 ] and the hepatic lipid peroxidation and inflammatory response [ 53 ] by chelerythrine.…”