Seed oil of Rosa roxburghii Tratt against non-alcoholic fatty liver disease in vivo and in vitro through PPARα/PGC-1α-mediated mitochondrial oxidative metabolism

Hai-Yan Ni; Liang Yu; Xue-Lian Zhao; Li-Tao Wang; Chun-Jian Zhao; Han Huang; Han-Lin Zhu; Thomas Efferth; Cheng-Bo Gu; Yu-Jie Fu

doi:10.1016/j.phymed.2021.153919

Seed oil of Rosa roxburghii Tratt against non-alcoholic fatty liver disease in vivo and in vitro through PPARα/PGC-1α-mediated mitochondrial oxidative metabolism

Phytomedicine. 2022 Apr:98:153919. doi: 10.1016/j.phymed.2021.153919. Epub 2022 Jan 1.

Authors

Hai-Yan Ni¹, Liang Yu¹, Xue-Lian Zhao¹, Li-Tao Wang², Chun-Jian Zhao¹, Han Huang¹, Han-Lin Zhu¹, Thomas Efferth³, Cheng-Bo Gu⁴, Yu-Jie Fu⁵

Affiliations

¹ College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, China.
² College of Forestry, Beijing Forestry University, Beijing 100083, China.
³ Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, 55128 Mainz, Germany.
⁴ College of Chemistry, Chemical Engineering and Resource Utilization, Northeast Forestry University, Harbin 150040, China; Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, China. Electronic address: dilisatis@163.com.
⁵ Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin 150040, China; College of Forestry, Beijing Forestry University, Beijing 100083, China. Electronic address: yujie_fu@163.com.

PMID: 35104757
DOI: 10.1016/j.phymed.2021.153919

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic steatosis and hepatocyte injury, is an obesity-induced metabolic dysregulation with few available therapeutic options. Enhancement of the mitochondrial function was considered as an effective treatment for NALFD. Unsaturated fatty acids (UFAs) have been shown to have beneficial effects on metabolic syndrome disease such as hyperlipidemia, coronary artery disease and cardiovascular diseases. The seed oil of Rosa roxburghii Tratt (ORRT) was of high quality in terms of its high amount of unsaturated fatty acids. However, the effects of ORRT on NALFD have not been reported so far.

Purpose: The study aimed to evaluate the protective effects and molecular mechanism of ORRT for the treatment of NAFLD in vivo and in vitro.

Methods: The beneficial effects, especially improving the mitochondrial function, and the potential mechanism of ORRT on NAFLD were studied both in vivo and in vitro. Lipid levels were determined by triglyceride (TG), total cholesterol (TC), and Oil Red O staining. Oxidative stress and inflammation were assessed by detecting antioxidant enzyme activity, MDA content, and ELISA assay. Blood TG, TC, HDL-c and LDL-c levels were measured in HFD mice. Western blot analyses were used to determine the levels of the protein involved in fatty acid oxidation, oxidative metabolism, and mitochondria biogenesis and function. The mitochondrial membrane potential level was measured by JC-1 staining to teste the effect of ORRT on mitochondrial function in vitro. GW6471 (inhibitor of PPARα) was used to confirm the relationship between PPARα and PGC-1α.

Results: ORRT significantly restrained NAFLD progression by attenuating lipid accumulation, oxidative stress and inflammatory response. Furthermore, ORRT upregulated thermogenesis-related gene expressions, such as uncoupling protein 1 (UCP1) and p38 mitogen-activated protein kinase (p38 MAPK). The results showed that the expression of key genes involved in fatty acid oxidation (e.g., CPT-1α, ACADL, PPARα) and in mitochondrial biogenesis and function (e.g., TFAM, NRF1, PGC-1α, and COX IV) was significantly increased. Together with the observed MMP improvement, these findings suggested that ORRT activated the mitochondrial oxidative pathway. Additionally, GW6471 inhibited the ORRT on promoting the expression of PGC-1α, CPT-1α, and ACADL. In conclusion, ORRT possessed the potential to prevent lipid accumulation via the PPARα/PGC-1α signaling pathway, which could be developed as a natural health-promoting oil against NAFLD.

Keywords: Hepatology; Mitochondrial dysfunction; NALFD; Oxidative stress; PBS, phosphate buffer saline; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1α; PPARα, peroxisome proliferator activated receptor α; PPARα/PGC-1α signaling; Phytotherapy; TFAM, Mitochondrial transcription factor A; TGF-β, transforming growth factor-beta; TNF-α, Tumor Necrosis Factor alpha; TNF-α, Tumor necrosis factor-α; UCP1, uncoupling protein 1; p38 MAPK, p38 mitogen-activated protein kinase.