Objective

2

To evaluate the

in vivo

and

in vitro

toxicity of Evodia Fructus water extraction and its index components， and provide a basis for basic research on the toxic substances of Evodia Fructus.

Method

2

Institute of Cancer Research（ICR） mice were divided into high， medium and low dose groups of water extraction of Evodia Fructus and a blank control group. The administration groups were respectively given 80，60，40 g·kg

-1

water extraction of Evodia Fructus， the blank control group was given distilled water in equal volume， blood was taken 24 hours later to determine the serum alanine aminotransferase（ALT）and aspartate aminotransferase（AST）values， the liver was weighed and histopathological examination was performed. Evodia Fructus water extract， evodiamine， rutaecarpine and limonin were respectively acted on HepG2 cells for 24 h， and cell counting kit-8（CCK-8） method was used to investigate the cytotoxicity. The ICR Mice were divided into two groups， one group was given by oral gavage and the other group was given intraperitoneal injection. The two routes of administration were separately given 3 index components of Evodia Fructus， and the dosage was 200 mg·kg

-1

. Take blood 24 hours after administration to determine the activity of ALT and AST in serum， and take liver to calculate liver index.

Result

2

Compared with the blank group， the high and medium dose groups of Evodia Fructus water extract were depressed 24 hours after administration， and the behavior of the low dose group was not significantly abnormal. The serum biochemical results showed that the activities of serum ALT and AST in the high and medium dose groups were significantly increased （

P

<

0.01）， the activities of serum ALT and AST in the low dose group were significantly increased， and the histopathological results showed that the high and medium dose groups were significantly increased Punctate necrosis and vacuolar degeneration appeared in the liver of the medium dose group， and there was no obvious abnormality in the low dose group. Compared with the blank group， evodiamine and rutaecarpine had a certain inhibitory effect on the proliferation of HepG2 cells， but the inhibitory effect was not strong. Limonin had no significant inhibitory effect on the proliferation of HepG2 cells. Compared with the control group， the 3 index components of Evodia Fructus have no effect after oral administration. There was no significant difference in the activity of ALT and AST in serum of mice， and there was no significant difference in liver index. Intraperitoneal injection of evodiamine and rutaecarpine can cause the activity of serum ALT and AST to increase， and limonin can cause ALT activity was significantly increased （

P

<

0.01）， and the liver index was significantly increased （

P

<

0.05）.

Conclusion

2

Evodia Fructus water extract can cause acute liver injury in mice， Oral administration of evodiamine， rutaecarpine and limonin had no damage to the liver of mice. Intraperitoneal administration of evodiamine and rutaecarpine had no effect on liver injury in mice， and intraperitoneal administration of limonin could cause acute liver injury in mice.