鲜/干蒲公英提取物对过量APAP所致急性肝损伤的保护作用

Yao ZHENG; Lei LEI; Shuai LIANG; Jiao AI; Xin DENG; Yan-qiu LI; Tian-pei ZHANG; Shi-biao PU; Yong-shen REN

doi:10.1007/s11655-021-3295-8

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鲜/干蒲公英提取物对过量APAP所致急性肝损伤的保护作用

Original Article | Updated：2022-07-20

- 鲜/干蒲公英提取物对过量APAP所致急性肝损伤的保护作用
- Protective Effect of Fresh/Dry Dandelion Extracts on APAP-Overdose-Induced Acute Liver Injury
- Chinese Journal of Integrative Medicine 2022年28卷第8期页码：683-692
- Affiliations：
  
  1.School of Pharmaceutical Science, South-Central University for Nationalities, Wuhan (430074), China
  2.College of Chinese Materia Medica, Yunnan University of Chinese Medicine,Kunming (650500), China
- Author bio：
  
  Prof. REN Yong-shen, E-mail: godreny@mail.scuec.edu.cn
- Funds：
  
  the National Natural Science Foundation of China(81773893;81760812);National Major Scientific and Technological Special Project for "Significant New Drugs Development"(2017ZX09301060-001);Jiangxi Province"Thousand Talents Plan" of Scientific and Technological Innovation(JXSQ2019201105);Yunnan Province"Ten Thousand Talents" Special Support Plan(YNWR-QNBJ-2018-190)
- DOI：10.1007/s11655-021-3295-8
  中图分类号：
- 纸质出版日期：2022-08，
  
  网络出版日期：2021-11-24，
  
  录用日期：2020-04-23
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Yao ZHENG, Lei LEI, Shuai LIANG, 等. 鲜/干蒲公英提取物对过量APAP所致急性肝损伤的保护作用[J]. Chinese Journal of Integrative Medicine, 2022,28(8):683-692.

Yao ZHENG, Lei LEI, Shuai LIANG, et al. Protective Effect of Fresh/Dry Dandelion Extracts on APAP-Overdose-Induced Acute Liver Injury[J]. Chinese Journal of Integrative Medicine, 2022,28(8):683-692.
Yao ZHENG, Lei LEI, Shuai LIANG, 等. 鲜/干蒲公英提取物对过量APAP所致急性肝损伤的保护作用[J]. Chinese Journal of Integrative Medicine, 2022,28(8):683-692. DOI： 10.1007/s11655-021-3295-8.

Yao ZHENG, Lei LEI, Shuai LIANG, et al. Protective Effect of Fresh/Dry Dandelion Extracts on APAP-Overdose-Induced Acute Liver Injury[J]. Chinese Journal of Integrative Medicine, 2022,28(8):683-692. DOI： 10.1007/s11655-021-3295-8.

摘要

目的:

比较新鲜/干蒲公英提取物对对乙酰氨基酚 (APAP) 诱导的肝毒性的保护作用.

方法:

将90只昆明种小鼠按体重随机分为10组 (每组9只) . 正常对照组和模型 (溶媒对照) 组小鼠仅给予羧甲基纤维素钠 (CMC-Na

0.5%) . 给药组包括: 高剂量和低剂量的干蒲公英提取物预处理组 (1000或500 g新鲜草药

经干燥后煎煮成120 mL溶液

DDE-H和DDE-L) ; 低剂量、中剂量和高剂量蒲公英汁组 (250 g、500 g、1000 g鲜蒲公英榨汁后分别浓缩至120 mL

DJ-L、DJ-M和DJ-H) ; 新鲜蒲公英汁旋蒸水组 (120 mL

DEJW) ; 用纯水溶解的干蒲公英提取物组 (相当于1000 g鲜蒲公英干燥后提取物用纯水溶解至120 mL

DDED-PW) 及DEJW溶解的干蒲公英提取物组 (相当于1000 g鲜蒲公英干燥后提取物用DEJW溶解至120 mL

DDED-DEJW) . 上述药物以0.5 mL溶液/10 g体重的剂量经口灌胃溶解的干蒲公英提取物7天. 除正常对照组外

其余各组均腹腔注射APAP 350mg/kg诱导肝损伤. APAP给药后20 h

收集血清和肝组织

用生化试剂盒定量测定血清丙氨酸氨基转移酶 (AST) 、天冬氨酸转氨酶 (ALT) 、碱性磷酸酶 (AKP) 、丙二醛 (MDA) 、谷胱甘肽 (GSH) 、超氧化物歧化酶 (SOD) 活性; 采用酶联免疫吸附测定试剂盒测定肝组织肿瘤坏死因子 (TNF-α) 、白细胞介素 (IL-2) 和白细胞介素-1β含量. 苏木精-伊红 (H&E) 染色观察肝组织病理变化; TUNEL法和Hoechst 33258染色用于细胞凋亡评估. Western blot法分析检测血红素加氧酶-1 (HO-1) 、核因子红系-2相关因子2 (Nrf-2) 、半胱天冬酶-9、B细胞白血病/淋巴瘤2 (Bcl-2) 、Bax和p-JNK表达.

结果:

与溶媒对照组比较

新鲜蒲公英汁 (FDJ

包括DJ-L、DJ-M、DJ-H、DEJW和DDED-DEJW) 预处理明显降低血清ALT、AST、AKP、TNF-α和IL-1β水平 (

0.05或

0.01) . 此外

与溶媒对照组比较

FDJ可降低肝脏MDA水平

恢复了肝脏GSH水平和SOD活性 (

0.05或

0.01) . FDJ抑制包括环氧合酶-2和诱导型一氧化氮合酶在内的促炎因子在肝组织中的过度表达 (

0.05或

0.01) . 此外

Western-blot分析显示

FDJ预处理通过降低Bax、caspase-9和JNK蛋白表达来抑制凋亡信号通路激活

并抑制JNK通路激活 (

0.05或

0.01) . 肝脏组织病理学观察进一步证明FDJ预处理可明显抑制APAP诱导的肝细胞坏死、炎性细胞浸润和充血.

结论:

FDJ预处理可通过激活Nrf-2/HO-1通路和抑制内源性凋亡通路来保护APAP诱导的小鼠急性肝损伤

且新鲜蒲公英提取物的作用优于干燥蒲公英提取物.

Abstract

Objecitvie:

To compare the liver protective activity of fresh/dried dandelion extracts against acetaminophen (APAP)-induced hepatotoxicity.

Methods:

Totally 90 Kunming mice were randomly divided into 10 groups according to body weight (9 mice for each group). The mice in the normal control and model (vehicle control) groups were administered sodium carboxymethyl cellulose (CMC-Na

0.5%) only. Administration groups were pretreated with high and low-dose dry dandelion extract (1

000 or 500 g fresh herb dried and then decocted into 120 mL solution

DDE-H and DDE-L); low-

medium- and high-dose dandelion juice (250

500

000 g/120 mL

DJ-L

DJ-M

and DJ-H); fresh dandelions evaporation juice water (120 mL

DEJW); dry dandelion extract dissolved by pure water (1 kg/120 mL

DDED-PW); dry dandelion extract dissolved by DEJW (120 g/120 mL

DDED-DEJW) by oral gavage for 7 days at the dosage of 0.5 mL solution/10 g body weight; after that

except normal control group

all other groups were intraperitonealy injected with 350 mg/kg APAP to induce liver injury. Twenty hours after APAP administration

serum and liver tissue were collected and serum alanine aminotransferase (AST)

aspartate transaminase (ALT)

alkaline phosphatase (AKP)

malondialdehyde (MDA)

glutathione (GSH)

superoxide dismutase (SOD) activities were quantified by biochemical kits; tumor necrosis factor (TNF-α)

interleukin (IL)-2

and IL-1β contents in liver tissue were determined by enzyme linked immunosorbent assay kits. Histopathological changes in liver tissues were observed by hematoxylin and eosin staining; TUNEL Assay and Hoechst 33258 staining were applied for cell apoptosis evaluation. The expressions of heme oxygenase-1 (HO-1)

nuclear factor erythroid- 2-related factor 2 (Nrf-2)

caspase-9

B-cell leukemia/lymphoma 2 (Bcl-2)

Bax and p-JNK were determined by Western blot analysis.

Results:

Pretreatment with fresh dandelion juice (FDJ

including DJ-L

DJ-M

DJ-H

DEJW and DDED-DEJW) significantly decreased the levels of serum ALT

AST

AKP

TNF-α and IL-1β compared with vehicle control group (

0.05 or

0.01). Additionally

compared with the vehicle control group

FDJ decreased the levels of hepatic MDA and restored GSH levels and SOD activity in livers (

0.05 or

0.01). FDJ inhibited the overexpression of pro-inflammatory factors including cyclooxygenase-2 and inducible nitric oxide synthase in the liver tissues (

0.05 or

0.01). Furthermore

Western blot analysis revealed that FDJ pretreatment inhibited activation of apoptotic signaling pathways via decreasing of Bax

and caspase-9 and JNK protein expression

and inhibited activation of JNK pathway (

0.05 or

0.01). Liver histopathological observation provided further evidence that FDJ pretreatment significantly inhibited APAP-induced hepatocyte necrosis

inflammatory cell infiltration and congestion.

Conclusions:

FDJ pretreatment protects against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway

and the effect of fresh dandelion extracts was superior to dried dandelion extracts in APAP hepatotoxicity model mice.

关键词

Keywords

fresh dandelion juiceacetaminopheninduced liver injuryoxidative stressanti-inflammationanti-apoptosis

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