Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Atractylodes Lancea and Its Constituent, Atractylodin, Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease via AMPK Activation

  • Ga Yeon Song (Department of Pharmacy, Kangwon National University) ;
  • Sun Myoung Kim (Department of Pharmacy, Kangwon National University) ;
  • Seungil Back (Department of Pharmacy, Kangwon National University) ;
  • Seung-Bo Yang (Department of Korean Internal Medicine, College of Korean Medicine, Gachon University) ;
  • Yoon Mee Yang (Department of Pharmacy, Kangwon National University)
  • Received : 2024.05.22
  • Accepted : 2024.07.24
  • Published : 2024.11.01
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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD), which encompasses a spectrum of conditions ranging from simple steatosis to hepatocellular carcinoma, is a growing global health concern associated with insulin resistance. Since there are limited treatment options for MASLD, this study investigated the therapeutic potential of Atractylodes lancea, a traditional herbal remedy for digestive disorders in East Asia, and its principal component, atractylodin, in treating MASLD. Following 8 weeks of high-fat diet (HFD) feeding, mice received oral doses of 30, 60, or 120 mg/kg of Atractylodes lancea. In HFD-fed mice, Atractylodes lancea treatment reduced the body weight; serum triglyceride, total cholesterol, and alanine aminotransferase levels; and hepatic lipid content. Furthermore, Atractylodes lancea significantly ameliorated fasting serum glucose, fasting serum insulin, and homeostatic model assessment of insulin resistance levels in response to HFD. Additionally, a glucose tolerance test demonstrated improved glucose homeostasis. Treatment with 5 or 10 mg/kg atractylodin also resulted in anti-obesity, anti-steatosis, and glucose-lowering effects. Atractylodin treatment resulted in the downregulation of key lipogenic genes (Srebf1, Fasn, Scd2, and Dgat2) and the upregulation of genes regulated by peroxisome proliferator-activated receptor-α. Notably, the molecular docking model suggested a robust binding affinity between atractylodin and AMP-activated protein kinase (AMPK). Atractylodin activated AMPK, which contributed to SREBP1c regulation. In conclusion, our results revealed that Atractylodes lancea and atractylodin activated the AMPK signaling pathway, leading to improvements in HFD-induced obesity, fatty liver, and glucose intolerance. This study suggests that the phytochemical, atractylodin, can be a treatment option for MASLD.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (No. 2022R1G1A1003601 to S.B.Y. and RS-2023-00210489, RS-2023-00301850 to Y.M.Y.). This research was supported by Korean Fund for Regenerative Medicine (KFRM) funded by Ministry of Science and ICT, and Ministry of Health & Welfare (RS-2022-00070363 to Y.M.Y.). This research was supported by Korea Basic Science Institute (National Research Facilities and Equipment Center) grant funded by the Ministry of Education (No. 2022R1A6C101A739).

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