2. Academic Validation
  3. Corydalis saxicola Bunting total alkaloids improve NAFLD by suppressing de novo lipogenesis through the AMPK-SREBP1 axis

Corydalis saxicola Bunting total alkaloids improve NAFLD by suppressing de novo lipogenesis through the AMPK-SREBP1 axis

  • J Ethnopharmacol. 2023 Sep 8;117162. doi: 10.1016/j.jep.2023.117162.
Yating Guo 1,  Qiushuang Sun 2,  Shijiao Wang 3,  Mengdi Zhang 4,  Yuanyuan Lei 5,  Jiejie Wu 6,  Xinhong Wang 7,  Wenjun Hu 8,  Haitao Meng 9,  Zhiyu Li 10,  Luzhou Xu 11,  Fang Huang 12,  Zhixia Qiu 13
Affiliations

Affiliations

  • 1 Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 2 Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 3 Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 4 School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 5 Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 6 Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 7 Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 8 Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 9 Shimadzu (China) Co., LTD., Nanjing Branch, Nanjing, China. Electronic address: [email protected].
  • 10 Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 11 Gastroenterology Department, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China. Electronic address: [email protected].
  • 12 Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
  • 13 Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, China. Electronic address: [email protected].
PMID: 37690477 DOI: 10.1016/j.jep.2023.117162
Abstract

Ethnopharmacological relevance: Along with the gradually increasing incidence, nonalcoholic fatty liver disease (NAFLD) has already been influencing the health of more and more people in the world. Corydalis saxicola Bunting (CSB), a valuable folk medicine, is the dried whole grass of a perennial herb, Yanhuanglian (Papaveraceae), which has significant effects on various hepatitis, liver fibrosis, cirrhosis and other liver diseases. Corydalis saxicola Bunting total Alkaloids (CSBTA), a mixture of Alkaloids extracted from CSB, exhibit widely-accepted hepatoprotective effects.

Aim of the study: This study aimed to explore the therapeutic potential of CSBTA on NAFLD and the underlying mechanism.

Materials and methods: A mice model was established by high fat and high Cholesterol diet (HFHCD) to study the benefits of CSBTA on the progression of NAFLD. The efficacy of CSBTA on NAFLD was revealed systematically via RNA-sequencing analysis. Further efficacy and molecular mechanism study were explored in mouse primary hepatocytes and HepG2 cells stimulated with high energy with or without pharmacological inhibition or gene silencing.

Results: CSBTA effectively improved the major hallmarks of NAFLD including liver lipid accumulation, liver injury, inflammation and fibrosis in HFHCD-fed mice. RNA sequencing and targeted qPCR analysis jointly evidenced CSBTA significantly suppressed the expression of Srebf1, Acc1 and Fasn which are the genes responsible for fatty acid biosynthesis. Moreover, stable isotope tracer test denoted CSBTA reduced lipid accumulation via interrupting fatty acid biosynthesis in hepatocytes or the liver. Mechanistically, CSBTA could impede SREBP1 maturation via AMPK activation, thereby reducing DNL-derived lipid accumulation in hepatocytes.

Conclusions: CSBTA protected against hepatic steatosis and other hallmarks of NAFLD induced by HFHCD via suppressing DNL, through modulating the AMPK-SREBP1 axis. CSBTA may therefore have a therapeutic potential for NAFLD treatment.

Keywords

AMPK-SREBP1 axis; Corydalis saxicola bunting total alkaloids; Lipid accumulation; Nonalcoholic fatty liver disease; de novo lipogenesis.

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