The Toxicity and Metabolism Properties ofHerba EpimediiFlavonoids on Laval and Adult Zebrafish

Abstract

Zebrafish is being increasingly used for metabolism and toxicity assessment. The drugs consumed in zebrafish metabolism studies are far less than those used in rat studies. In our study, zebrafish embryos were exposed to icariin, Baohuoside I (BI), Epimedin A (EA), Epimedin B (EB), Epimedin C (EC), Sagittatoside A (SA), Sagittatoside B (SB), and 2′′-O-rhamnosylicariside II (SC), respectively, to examine the toxicity and metabolic profiles of these flavonoids. The order of toxicity was SC, SB > EC, SA > BI, icariin, EA, EB. After 24 h exposure to SB and SC, the mortality of zebrafish larvae reached 100% and yolk sac swollen was obvious. Both SC and SB caused severe hepatocellular vacuolization and liver cells degeneration in adult zebrafish after 15 consecutive days’ treatment. The metabolic profiles of these flavonoids with trace amount were also monitored in larvae. BI was the common metabolite shared by icariin, EA, EB, SA, and SB, via deglycosylation. Both BI and SC remained as the prototype in the medium, suggesting that it is hard for BI and SC to cleave the rhamnose residue. EC was metabolized into SC and BI in zebrafish, inferring that SC might be responsible for the toxicity observed in EC group. The metabolites of icariin, EA, EB, EC, and BI in zebrafish larvae coincided with results from rats and intestinal flora. These data support the use of this system as a surrogate in predicting metabolites and hepatotoxicity risk, especially for TCM compound with trace amount.

Flavonoids from Epimedium pubescens: extraction and mechanism, antioxidant capacity and effects on CAT and GSH-Px of Drosophila melanogaster

“…Meanwhile, Epimedium flavonoids exhibit anti-osteoporosis, anti-tumor (e.g., blood cancer), anti-aging and anti-inflammatory activities (Zhang & Yang, 2010;Yang et al, 2018;Yang, Xi & Li, 2019;Wang et al, 2018). Besides, the major flavonoids of Epimedium (e.g., epimedin A, epimedin B and icariin) have no acute toxicity and long-term adverse health effects (Li et al, 2008;Hwang et al, 2017;Zhong et al, 2019;Ling et al, 2018). As a result, there is an increasing interest in Epimedium flavonoids for developing phytomedicines and/or functional foods (Zhang et al, 2014;Yang et al, 2018).…”

Characterization and biological properties of sulfated polysaccharides of Corallina officinalis and Pterocladia capillacea

“…The antioxidant efficiency of SP2 appeared higher TAC than SP1; this might be related to its sulfate concentration. Whereas there is a positive correlation between the antioxidant ability of algal polysaccharides and their sulfate content (Zhong et al 2019).…”

Icarisid I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity

“…Nevertheless, with numerous reports about liver injury related to EF, more attention has been paid to the clinical safety of EF. Thus, it is urgent to elucidate the characteristics and mechanisms of EF-induced liver injury [22,23]. Our previous studies con rmed that EF could induce liver injury in an LPS-mediated susceptible mouse model of IDILI.…”