Le Carbone prevents liver damage in non-alcoholic steatohepatitis-hepatocellular carcinoma mouse model via AMPKα-SIRT1 signaling pathway activation

Mst Rejina Afrin; Somasundaram Arumugam; Vigneshwaran Pitchaimani; Vengadeshprabhu Karuppagounder; Rajarajan Amirthalingam Thandavarayan; Meilei Harima; Chowdhury Faiz Hossain; Kenji Suzuki; Hirohito Sone; Yasuhiro Matsubayashi; Kenichi Watanabe

doi:10.1016/j.heliyon.2020.e05888

Le Carbone prevents liver damage in non-alcoholic steatohepatitis-hepatocellular carcinoma mouse model via AMPKα-SIRT1 signaling pathway activation

Heliyon. 2021 Jan 5;7(1):e05888. doi: 10.1016/j.heliyon.2020.e05888. eCollection 2021 Jan.

Authors

Mst Rejina Afrin^{1

2}, Somasundaram Arumugam^{2

3}, Vigneshwaran Pitchaimani², Vengadeshprabhu Karuppagounder^{2

4}, Rajarajan Amirthalingam Thandavarayan^{2

5}, Meilei Harima^{2

6}, Chowdhury Faiz Hossain¹, Kenji Suzuki⁷, Hirohito Sone⁸, Yasuhiro Matsubayashi⁸, Kenichi Watanabe^{2

8}

Affiliations

¹ Department of Pharmacy, Faculty of Sciences and Engineering, East West University, Dhaka 1212, Bangladesh.
² Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
³ Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, 168 Manicktala Main Road, Kolkata 700 054, West Bengal, India.
⁴ Department of Orthopedics and Rehabilitation, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
⁵ Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX 77030, USA.
⁶ Niigata University of Rehabilitation, Faculty of Allied Health Sciences, 2-16, Kaminoyama, Murakami, Niigata 958-8292, Japan.
⁷ Department of Clinical Engineering and Medical Technology, Niigata University of Health and Welfare, Niigata 950-3198, Japan.
⁸ Department of Hematology, Endocrinology and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.

Abstract

Le Carbone (LC), a fiber-enriched activated charcoal dietary supplement, claimed to be effective against inflammation associated with colitis, trimethylaminuria, and sclerosis. The study aimed to investigate the underlying mechanisms of LC to protect liver damage and its progression in non-alcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mice. To induce this model, C57BL/6J male baby mice were injected with a low-dose of streptozotocin and fed with a high-fat diet (HFD) 32 during 4 weeks-16 weeks of age. The LC suspension was administered orally at a dose of 5 mg/mouse/day started at the age of 6 weeks and continued until 16 weeks of age along with HFD32 feeding. At the end of the experiment, serum and liver tissues were collected for the biochemical, histological, and molecular analysis. We found that LC suspension improved the histopathological changes, serum aminotransferases in NASH mice. The hepatic expression of metabolic proteins, p-AMPKα and sirtuin 1, and proteins responsible for β-oxidation of fatty acids, peroxisome proliferator-activated receptor (PPAR) γ coactivator-α, PPARα were significantly repressed in NASH mice. LC treatment markedly restored these expressions. LC treatment significantly reduced the hepatic proteins expressions of PPARγ, tissue inhibitor of metalloproteinases 4, p47phox, p-JNK, p-ERK1/2, glypican-3, and prothrombin in NASH mice. Our findings demonstrate that LC prevents the liver damage and progression of NASH, possibly by enhancing the AMPK-SIRT1 signaling pathway.

Keywords: AMPKα; Le carbone; Non-alcoholic steatohepatitis; PPARα; SIRT1.