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Cannabigerol Alleviates Liver Damage in Metabolic Dysfunction-Associated Steatohepatitis Female Mice via Inhibition of Transforming Growth Factor Beta 1.

作者信息

Joly Raznin, Tasnim Fariha, Krutsinger Kelsey, Li Zhuorui, Pullen Nicholas A, Han Yuyan

机构信息

College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.

Department of Biological Sciences, University of Northern Colorado, Greeley, CO 80639, USA.

出版信息

Nutrients. 2025 Apr 30;17(9):1524. doi: 10.3390/nu17091524.


DOI:10.3390/nu17091524
PMID:40362835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12073672/
Abstract

Metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), involves inflammation, fibrosis, steatosis, and oxidative stress. Previous research from our lab shows that cannabigerol (CBG) reduces inflammation and fibrosis in male MASH mice, but its effects in females remain unknown. Given immune cell population changes in MASLD patients, this study examines CBG's impact on methionine-choline deficient (MCD) diet-induced MASH in female mice. MCD-fed female mice are supplemented with two different doses for three weeks. Liver fibrosis, steatosis, oxidative stress, ductular reaction, and inflammation are assessed via Sirius Red, Oil Red O, immunohistochemistry, and immunofluorescence staining. Immune cell changes in non-parenchymal cells (NPCs) are analyzed via flow cytometry. CBG treatment improves liver health by reducing leukocyte infiltration. Both CBG doses significantly decrease fibrosis, oxidative stress, ductular proliferation, and inflammation in MCD-fed mice, including monocyte and T lymphocyte reductions. Additionally, CBG downregulates mast cell activation, inhibiting transforming growth factor (TGF)-β1 release, thereby suppressing hepatic stellate cell activation. This reduces collagen deposition, fibrosis, and ductular proliferation. Our findings provide insights for pre-clinical and clinical research, highlighting CBG's potential therapeutic role and dosage considerations in mitigating liver fibrosis and inflammation in female patients.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/14d763f7c534/nutrients-17-01524-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/17a6152cf060/nutrients-17-01524-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/558405edd9ee/nutrients-17-01524-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/6297c62a4497/nutrients-17-01524-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/6146f1097a2d/nutrients-17-01524-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/14d763f7c534/nutrients-17-01524-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/17a6152cf060/nutrients-17-01524-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/558405edd9ee/nutrients-17-01524-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/6297c62a4497/nutrients-17-01524-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/6146f1097a2d/nutrients-17-01524-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9554/12073672/14d763f7c534/nutrients-17-01524-g005.jpg

相似文献

[1]
Cannabigerol Alleviates Liver Damage in Metabolic Dysfunction-Associated Steatohepatitis Female Mice via Inhibition of Transforming Growth Factor Beta 1.

Nutrients. 2025-4-30

[2]
Low-Dose Administration of Cannabigerol Attenuates Inflammation and Fibrosis Associated with Methionine/Choline Deficient Diet-Induced NASH Model via Modulation of Cannabinoid Receptor.

Nutrients. 2022-12-30

[3]
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[4]
Sodium butyrate ameliorates liver fibrosis in metabolic dysfunction-associated steatohepatitis rats via miR-155-5p/SOCS1/PDGF signaling pathway.

Hepatobiliary Pancreat Dis Int. 2025-8

[5]
Hepatocellular CMPK2 promotes the development of metabolic dysfunction-associated steatohepatitis.

J Hepatol. 2025-1-22

[6]
Multi-modal analysis of human hepatic stellate cells identifies novel therapeutic targets for metabolic dysfunction-associated steatotic liver disease.

J Hepatol. 2025-5

[7]
Development of SOCS1 mimetics as novel approach to harmonize inflammation, oxidative stress, and fibrogenesis in metabolic dysfunction-associated steatotic liver disease.

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[8]
Cinnabarinic acid protects against metabolic dysfunction-associated steatohepatitis by activating aryl hydrocarbon receptor-dependent AMPK signaling.

Am J Physiol Gastrointest Liver Physiol. 2025-4-1

[9]
Novel Choline-Deficient and 0.1%-Methionine-Added High-Fat Diet Induces Burned-Out Metabolic-Dysfunction-Associated Steatohepatitis with Inflammation by Rapid Immune Cell Infiltration on Male Mice.

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[10]
Synergistic effects of C-C chemokine receptor 2 inhibitor and transforming growth factor-β type I receptor kinase inhibitor combination in metabolic dysfunction-associated steatohepatitis.

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本文引用的文献

[1]
A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis.

N Engl J Med. 2024-2-8

[2]
Low-Dose Administration of Cannabigerol Attenuates Inflammation and Fibrosis Associated with Methionine/Choline Deficient Diet-Induced NASH Model via Modulation of Cannabinoid Receptor.

Nutrients. 2022-12-30

[3]
The immune response as a therapeutic target in non-alcoholic fatty liver disease.

Front Immunol. 2022

[4]
The epidemiology of non-alcoholic steatohepatitis (NASH) in the United States between 2010-2020: a population-based study.

Ann Hepatol. 2022

[5]
Nobiletin mitigates hepatocytes death, liver inflammation, and fibrosis in a murine model of NASH through modulating hepatic oxidative stress and mitochondrial dysfunction.

J Nutr Biochem. 2022-2

[6]
A phase 1b randomised, placebo-controlled trial of nabiximols cannabinoid oromucosal spray with temozolomide in patients with recurrent glioblastoma.

Br J Cancer. 2021-4

[7]
Mast Cells Promote Nonalcoholic Fatty Liver Disease Phenotypes and Microvesicular Steatosis in Mice Fed a Western Diet.

Hepatology. 2021-7

[8]
In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa.

Sci Rep. 2020-11-23

[9]
Protocol for Primary Mouse Hepatocyte Isolation.

STAR Protoc. 2020-9-18

[10]
Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGF-β/Smad and YAP signaling.

Phytomedicine. 2020-7-28

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