Ursolic acid in <i>Hippophae rhamnoides L</i>. inhibits hepatocyte apoptosis in rats with alcoholic liver disease by regulating mitochondria-cytochrome c

Yanhong BAO; Qiang WANG; Wenlong ZHANG; Na GE; Nan LI; Jun SU; Kexin LI

doi:10.3969/j.issn.1001-5256.2023.07.016

Volume 39 Issue 7

Jul. 2023

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Article Navigation > Journal of Clinical Hepatology > 2023 > 39(7): 1617-1626

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Ursolic acid in Hippophae rhamnoides L. inhibits hepatocyte apoptosis in rats with alcoholic liver disease by regulating mitochondria-cytochrome c

DOI: 10.3969/j.issn.1001-5256.2023.07.016

Yanhong BAO^1a,
Qiang WANG^1b,
Wenlong ZHANG²,
Na GE^{3
,
,
,},
Nan LI^{3
,
,
,},
Jun SU⁴,
Kexin LI³

1a.
Institute of Health, Baotou Medical College, Baotou, Inner Mongolia 014040, China
1b.
Institute of Basis and Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, China
2.
The First Affiliated Hospital, Baotou Medical College, Baotou, Inner Mongolia 014010, China
3.
Institute of Nutrition and Food Health, Baotou Medical College, Baotou, Inner Mongolia 014040, China
4.
System Reform's Office, Inner Mongolia Health Committee, Hohhot 010030, China

Research funding:

National Natural Science Foundation of China (81550044);

National Natural Science Foundation of China (81760586);

Natural Science Foundation of Inner Mongolia Autonomous Region (2014MS0303);

The Program for Young Talents of Science and Technology in Universities of the Inner Mongolia Autonomous Region (NJTY-15-B11);

Scientific Research Project on Health and Family Planning in Inner Mongolia Autonomous Region (201701084);

The Doctoral Research Foundation Project of Baotou Medical College (BSJJ201630);

Young Innovative Talents Training Program of Grassland Talents Project in Inner Mongolia Autonomous Region (Q2017089);

Baotou Youth Innovative Talent Project (2017-284);

Innovation Team Development Plan of Baotou Medical College (BTMCTD202205)

More Information

Corresponding author: GE Na, genanihao80@163.com (ORCID: 0000-0002-1512-1185); LI Nan, 383541607@qq.com (ORCID: 0000-0001-6635-7393)
Received Date: 2022-11-01
Accepted Date: 2022-12-26
Published Date: 2023-07-20

Abstract

Abstract

Objective To investigate the inhibitory effect of ursolic acid in Hippophae rhamnoides L. on hepatocyte apoptosis in rats with alcoholic liver disease based on the mitochondria-cytochrome c pathway. Methods A total of 50 specific pathogen-free male Wistar rats were divided into normal control group, alcohol model group, and low-, middle-, and high-dose ursolic acid groups using a random number table, with 10 rats in each group. The rats in the normal control group were given normal saline by gavage once a day for 8 weeks; the rats in the alcohol model group were given alcohol at increasing concentrations by gavage for 8 consecutive weeks; the rats in the low-, middle-, and high-dose ursolic acid groups were given ursolic acid at a dose of 50, 100, and 150 mg/kg, respectively, followed by an equal volume of alcohol as the model group 1 hour later. Serum liver function parameters were measured for each group; HE staining was used to observe liver histopathology; an electron microscope was used to observe hepatocyte ultrastructure; the TUNEL method was used to measure hepatocyte apoptosis; Western Blotting was used to measure the protein expression levels of cytochrome c and activated caspase-3 in hepatocyte mitochondria and cytoplasm. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significant reductions in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase (all P < 0.05). The rats in the alcohol model group had disordered arrangement of hepatic cords with marked hepatocyte edema and fatty degeneration, while those in the middle- and high- dose ursolic acid groups had basically normal arrangement of hepatic cords and a significant improvement in hepatocyte fatty degeneration, as well as a significant increase in the number of hepatocyte mitochondria and a significant improvement in morphology. Compared with the alcohol model group, the middle- and high-dose ursolic acid groups had significantly lower hepatocyte apoptosis rate and protein expression levels of cytochrome c and caspase-3 in cytoplasm (all P < 0.05). Conclusion Ursolic acid in Hippophae rhamnoides L. can improve the liver function and histomorphology of rats with alcoholic liver disease, possibly by inhibiting the release of cytochrome c in hepatocyte mitochondria, the activation of caspase-3, and the apoptosis of hepatocytes via the mitochondria-cytochrome c pathway.
- Liver Diseases, Alcoholic,
- Hippophae Fructus,
- Apoptosis,
- Mitochondria,
- Cytochromes c

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References(45)

References

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Ursolic acid in Hippophae rhamnoides L. inhibits hepatocyte apoptosis in rats with alcoholic liver disease by regulating mitochondria-cytochrome c

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Ursolic acid in Hippophae rhamnoides L. inhibits hepatocyte apoptosis in rats with alcoholic liver disease by regulating mitochondria-cytochrome c

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