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Gastrodin attenuates hypercholesterolaemia through regulating the PCSK9/LDLR signalling pathway by suppressing HNF-1α

Yaowen Zhang1, Lan Han2, Qiyuan Ning1

  • 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230011, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|April 25, 2025
PubMed

Insights

Gastrodin (Gas) effectively treats hypercholesterolaemia by regulating cholesterol metabolism. It inhibits PCSK9 expression and increases LDLR transcription, offering new therapeutic insights for hyperlipidaemia.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Cardiovascular Research

Background:

  • Hypercholesterolaemia is a major risk factor for cardiovascular diseases (CVDs).
  • Gastrodin (Gas), from Gastrodia elata Bl., possesses lipid-lowering properties, but its mechanism in CVD treatment is unclear.
  • The PCSK9/LDLR pathway is crucial for cholesterol metabolism regulation.

Purpose of the Study:

  • To investigate the inhibitory effect of Gastrodin on hypercholesterolaemia.
  • To determine if Gastrodin's hypolipidemic effects are linked to the PCSK9/LDLR signalling pathway.

Main Methods:

  • Hypercholesterolaemia induced in mice via high-fat diet (HFD) for 12 weeks.
  • In vivo analysis of therapeutic effects and pathways.
  • In vitro verification using western blotting, qRT-PCR, molecular docking, and transfection.

Main Results:

  • Gastrodin demonstrated significant therapeutic effects against hypercholesterolaemia in HFD mice.
  • Gastrodin attenuated HFD-induced hepatic lipid accumulation and liver damage.
  • Mechanistically, Gas inhibited JAK2/STAT3 signalling, suppressing HNF-1α and promoting FoxO3a to decrease PCSK9 expression, while activating SREBP2 to increase LDLR transcription.

Conclusions:

  • Gastrodin effectively treats hyperlipidaemia by modulating the PCSK9/LDLR pathway.
  • These findings offer novel insights into hyperlipidaemia prevention and treatment strategies.
Abstract

Keywords:
GastrodinHypercholesterolemiaJAK2/STAT3PCSK9/LDLR

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