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  3. Senkyunolide A mitigates lipid deposition in hyperlipidemic hepatocytes through SIRT6-mediated suppression of oxidative stress and fetuin-A

Senkyunolide A mitigates lipid deposition in hyperlipidemic hepatocytes through SIRT6-mediated suppression of oxidative stress and fetuin-A

  • Biochem Biophys Res Commun. 2025 Jul 22:771:152046. doi: 10.1016/j.bbrc.2025.152046.
Jun Hwi Ko 1,  Tae Woo Jung 2,  Min Kyung Pyo 1,  Do Su Lim 1,  Hyeon Ji Gwon 1,  A M Abd El-Aty 3,  Rıdvan Yağan 4,  Jong Wook Shin 5,  Moo Yeol Lee 6,  Jin-Ho Song 7,  Ji Hoon Jeong 8
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea.
  • 2 Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
  • 3 Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt; Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, 25240, Turkey. Electronic address: abdelaty44@hotmail.com.
  • 4 Dr. Filiz Dolunay Family Health Center Unit Number:61 Erzurum, Turkey.
  • 5 Department of Internal Medicine, Division of Allergy and Respiratory Medicine, Chung-Ang University, Seoul, Republic of Korea.
  • 6 Department of Physiology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
  • 7 Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea. Electronic address: jinhos@cau.ac.kr.
  • 8 Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, Republic of Korea. Electronic address: jhjeong3@cau.ac.kr.
PMID: 40403679 DOI: 10.1016/j.bbrc.2025.152046
Abstract

Senkyunolide A (SenA), a phthalide compound isolated from celery seed essential oil, is known for its anti-inflammatory and antioxidant properties in various disease models. However, its impact on hepatic lipid metabolism and associated molecular mechanisms remain unclear. This study investigated the protective effects of SenA against lipotoxicity-induced hepatic steatosis and explored its underlying pathways. Lipid accumulation was assessed via Oil Red O staining, whereas protein expression was analyzed via Western blotting. Apoptosis was evaluated through TUNEL staining, Caspase-3 activity, and cell viability assays. Oxidative stress was measured via DCFDA-based ROS detection and assays for MDA and H2O2. The role of SIRT6 was examined through siRNA-mediated knockdown. SenA treatment significantly reduced lipid deposition, Apoptosis, oxidative stress, and fetuin-A expression in palmitate-treated hepatocytes. It also increased the expression of SIRT6 and Nrf2, two key regulators of metabolic and redox homeostasis. Silencing SIRT6 diminished these protective effects, indicating its essential role in mediating SenA activity. These findings suggest that SenA mitigates hepatic steatosis by modulating oxidative stress and metabolic dysfunction via SIRT6/Nrf2 signaling. As a natural bioactive compound, SenA offers promise for the development of safer therapeutic strategies for managing nonalcoholic fatty liver disease (NAFLD), which has broader relevance to metabolic health.

Keywords

Apoptosis; Fetuin-A; Oxidative stress; SIRT6; Senkyunolide A; Steatosis.

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