The protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damage
BackgroundStress-induced liver injury, resulting from acute or chronic stress, is associated with oxidative stress and inflammation. The endocannabinoid system, particularly cannabinoid receptor 2 (CB2R), plays a crucial role in liver damage. However, there are currently no clinical drugs targeting...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-03-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1567210/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850222030844067840 |
|---|---|
| author | Chengyu Huang Chengyu Huang Huichao Liang Huichao Liang Xiaohua Liang Yueyi Liu Jiaoling Wang Haoran Jiang Xinhui Kou Xinhui Kou Jun Chen Jun Chen Lili Huang Lili Huang |
| author_facet | Chengyu Huang Chengyu Huang Huichao Liang Huichao Liang Xiaohua Liang Yueyi Liu Jiaoling Wang Haoran Jiang Xinhui Kou Xinhui Kou Jun Chen Jun Chen Lili Huang Lili Huang |
| author_sort | Chengyu Huang |
| collection | DOAJ |
| description | BackgroundStress-induced liver injury, resulting from acute or chronic stress, is associated with oxidative stress and inflammation. The endocannabinoid system, particularly cannabinoid receptor 2 (CB2R), plays a crucial role in liver damage. However, there are currently no clinical drugs targeting CB2R for liver diseases. Cannabidiol (CBD), a CB2R agonist, possesses anti-inflammatory and antioxidant properties. This study aims to investigate the pharmacological effects of CBD in a mouse model of stress-induced liver injury.MethodsWe employed a mouse model of stress-induced liver injury to evaluate the protective effects of CBD. Assessments included histopathological analysis, cytokine detection via ELISA, protein expression analysis using immunohistochemistry and Western blot, and gene transcription differential analysis. Transmission electron microscopy was utilized to observe mitochondrial morphology. Additionally, we examined the expression levels of CB2R, SLC7A11, α-SMA, and ACSL4 proteins to elucidate the mechanisms underlying CBD’s effects.ResultsCBD exhibited significant protective effects against stress-induced liver injury in mice. Decreases in liver function indicators (including Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) and inflammatory cytokines (such as IL-1β and Tumor Necrosis Factor-alpha (TNF-α)) were observed. CBD enhanced CB2R expression and reduced α-SMA levels, mitigating liver fibrosis. It also decreased ACSL4 levels, increased SOD and GSH-Px activities, and upregulated SLC7A11 protein expression. Furthermore, CBD improved mitochondrial morphology, indicating a reduction in oxidative cell death.ConclusionCBD activates the CB2R/α-SMA pathway to modulate liver inflammation and fibrosis. Through the SLC7A11/ACSL4 signaling pathway, CBD alleviates oxidative stress in stress-induced liver injury, enhances mitochondrial morphology, and reduces liver damage. These findings provide a theoretical basis for the potential application of CBD in the prevention and treatment of stress-induced liver injury. |
| format | Article |
| id | doaj-art-e847c56817464c92a8cbeb6ce16dcd50 |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-e847c56817464c92a8cbeb6ce16dcd502025-08-20T02:06:30ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15672101567210The protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damageChengyu Huang0Chengyu Huang1Huichao Liang2Huichao Liang3Xiaohua Liang4Yueyi Liu5Jiaoling Wang6Haoran Jiang7Xinhui Kou8Xinhui Kou9Jun Chen10Jun Chen11Lili Huang12Lili Huang13Department of Pharmacy, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Pharmacy, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, ChinaThe Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, ChinaSchool of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Pharmacy, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, ChinaThe Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Pharmacy, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, ChinaThe Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Pharmacy, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, ChinaThe Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaBackgroundStress-induced liver injury, resulting from acute or chronic stress, is associated with oxidative stress and inflammation. The endocannabinoid system, particularly cannabinoid receptor 2 (CB2R), plays a crucial role in liver damage. However, there are currently no clinical drugs targeting CB2R for liver diseases. Cannabidiol (CBD), a CB2R agonist, possesses anti-inflammatory and antioxidant properties. This study aims to investigate the pharmacological effects of CBD in a mouse model of stress-induced liver injury.MethodsWe employed a mouse model of stress-induced liver injury to evaluate the protective effects of CBD. Assessments included histopathological analysis, cytokine detection via ELISA, protein expression analysis using immunohistochemistry and Western blot, and gene transcription differential analysis. Transmission electron microscopy was utilized to observe mitochondrial morphology. Additionally, we examined the expression levels of CB2R, SLC7A11, α-SMA, and ACSL4 proteins to elucidate the mechanisms underlying CBD’s effects.ResultsCBD exhibited significant protective effects against stress-induced liver injury in mice. Decreases in liver function indicators (including Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) and inflammatory cytokines (such as IL-1β and Tumor Necrosis Factor-alpha (TNF-α)) were observed. CBD enhanced CB2R expression and reduced α-SMA levels, mitigating liver fibrosis. It also decreased ACSL4 levels, increased SOD and GSH-Px activities, and upregulated SLC7A11 protein expression. Furthermore, CBD improved mitochondrial morphology, indicating a reduction in oxidative cell death.ConclusionCBD activates the CB2R/α-SMA pathway to modulate liver inflammation and fibrosis. Through the SLC7A11/ACSL4 signaling pathway, CBD alleviates oxidative stress in stress-induced liver injury, enhances mitochondrial morphology, and reduces liver damage. These findings provide a theoretical basis for the potential application of CBD in the prevention and treatment of stress-induced liver injury.https://www.frontiersin.org/articles/10.3389/fphar.2025.1567210/fullstress-induced liver injurydifferential gene expression analysismitochondriacannabidioloxidative stress |
| spellingShingle | Chengyu Huang Chengyu Huang Huichao Liang Huichao Liang Xiaohua Liang Yueyi Liu Jiaoling Wang Haoran Jiang Xinhui Kou Xinhui Kou Jun Chen Jun Chen Lili Huang Lili Huang The protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damage Frontiers in Pharmacology stress-induced liver injury differential gene expression analysis mitochondria cannabidiol oxidative stress |
| title | The protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damage |
| title_full | The protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damage |
| title_fullStr | The protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damage |
| title_full_unstemmed | The protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damage |
| title_short | The protective role of cannabidiol in stress-induced liver injury: modulating oxidative stress and mitochondrial damage |
| title_sort | protective role of cannabidiol in stress induced liver injury modulating oxidative stress and mitochondrial damage |
| topic | stress-induced liver injury differential gene expression analysis mitochondria cannabidiol oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1567210/full |
| work_keys_str_mv | AT chengyuhuang theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT chengyuhuang theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT huichaoliang theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT huichaoliang theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT xiaohualiang theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT yueyiliu theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT jiaolingwang theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT haoranjiang theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT xinhuikou theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT xinhuikou theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT junchen theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT junchen theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT lilihuang theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT lilihuang theprotectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT chengyuhuang protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT chengyuhuang protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT huichaoliang protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT huichaoliang protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT xiaohualiang protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT yueyiliu protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT jiaolingwang protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT haoranjiang protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT xinhuikou protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT xinhuikou protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT junchen protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT junchen protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT lilihuang protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage AT lilihuang protectiveroleofcannabidiolinstressinducedliverinjurymodulatingoxidativestressandmitochondrialdamage |