Study on Liver Injury of Different Components of Evodia Fructus <italic style="font-style: italic">in Vivo</italic> and <italic style="font-style: italic">in Vitro</italic>

Shu-ting WEI; Yun-hua SHENG; Jian HUANG; Li-ming TANG

doi:10.13422/j.cnki.syfjx.20220121

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Study on Liver Injury of Different Components of Evodia Fructus in Vivo and in Vitro

更新时间：2021-12-14

- Study on Liver Injury of Different Components of Evodia Fructus in Vivo and in Vitro
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 28, Issue 2, Pages: 87-92(2022)
- 作者机构：
  
  1.中国医药工业研究总院，上海 201203
  2.上海市食品药品检验研究院，上海 201203
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20220121
  CLC： R22;R242;R2-031;R285.5
- Published：20 January 2022，
  
  Published Online：04 November 2021，
  
  Received：09 August 2021，
- 稿件说明：
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魏舒婷,盛云华,黄坚等.吴茱萸指标成分体内外的肝损伤作用[J].中国实验方剂学杂志,2022,28(02):87-92.

WEI Shu-ting,SHENG Yun-hua,HUANG Jian,et al.Study on Liver Injury of Different Components of Evodia Fructus in Vivo and in Vitro[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(02):87-92.
魏舒婷,盛云华,黄坚等.吴茱萸指标成分体内外的肝损伤作用[J].中国实验方剂学杂志,2022,28(02):87-92. DOI： 10.13422/j.cnki.syfjx.20220121.

WEI Shu-ting,SHENG Yun-hua,HUANG Jian,et al.Study on Liver Injury of Different Components of Evodia Fructus in Vivo and in Vitro[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(02):87-92. DOI： 10.13422/j.cnki.syfjx.20220121.

摘要

目的

评价吴茱萸中吴茱萸碱、吴茱萸次碱、柠檬苦素体内外作用的肝损伤，为吴茱萸毒性物质基础研究提供依据。

方法

吴茱萸水提物小鼠肝损伤实验，将美国癌症研究所（ICR）小鼠分为吴茱萸水提物高、中、低剂量组（80，60，40 g·kg

-1

）和空白组，给药24 h后取血测定血清丙氨酸氨基转移酶（ALT），天门冬氨酸氨基转移酶（AST）活性，取肝脏进行组织病理学检查。吴茱萸碱，吴茱萸次碱，柠檬苦素体外毒性实验，将不同单体成分分别作用于HepG2细胞24 h，采用细胞增殖与活性检测（CCK-8）法考察细胞毒性。将雄性ICR小鼠分为吴茱萸碱组、吴茱萸次碱组、柠檬苦素组和空白组，每组分别采取灌胃给药和腹腔注射给药，给药剂量为200 mg·kg

-1

，24 h后对小鼠进行大体观察，取血测血清ALT，AST活性，取肝脏称质量并计算肝体比。

结果

与空白组比较，吴茱萸水提物高、中剂量组小鼠给药24 h后精神萎靡，眼部分泌物增多，低剂量组小鼠行为无明显异常，血清生化学结果显示，与空白组比较，吴茱萸水提物高、中剂量组小鼠血清ALT，AST活性显著升高（

0.01），低剂量组小鼠血清ALT，AST活性有升高趋势，组织病理学检查结果显示，吴茱萸水提物高、中剂量组肝脏出现点状坏死，空泡变性，吴茱萸水提物低剂量组无明显异常。与空白组比较，吴茱萸碱、吴茱萸次碱对HepG2细胞的增殖具有一定抑制作用，抑制作用不强；柠檬苦素对HepG2细胞的增殖无明显抑制作用。与空白组比较，各组小鼠行为均无明显异常，灌胃给药的各给药组小鼠血清中ALT，AST活性及肝体比均无明显变化，腹腔注射给药的柠檬苦素组小鼠血清ALT活性显著升高（

0.01），肝体比明显升高（

0.05），吴茱萸次碱组小鼠血清AST活力明显升高（

0.05），肝体比无明显变化，吴茱萸碱组则均无明显变化。

结论

口服给予吴茱萸水提物能造成小鼠急性肝损伤；口服给予吴茱萸碱、吴茱萸次碱、柠檬苦素对小鼠肝脏无损伤作用；腹腔给予吴茱萸碱、吴茱萸次碱对小鼠肝脏无损伤作用，腹腔给予柠檬苦素能造成小鼠急性肝损伤。

Abstract

Objective

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

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

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 （

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 （

0.01）， and the liver index was significantly increased （

0.05）.

Conclusion

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.

关键词

吴茱萸碱吴茱萸次碱柠檬苦素肝损伤

Keywords

evodiaminerutaecarpinelimoninliver injury

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Study on Liver Injury of Different Components of Evodia Fructus in Vivo and in Vitro

DOI：10.13422/j.cnki.syfjx.20220121

摘要

Abstract

关键词

Keywords

references