Andrographolide and pterostilbene inhibit adipocyte differentiation by downregulating PPARγ through different

Saurabh D Kalamkar1, Ganesh Suraj Bose2, Saroj Ghaskadbi1

  • 1Department of Zoology, Savitribai Phule Pune University, Pune, India.

Natural Product Research
|November 14, 2022
PubMed

Insights

Two natural compounds, andrographolide (AN) and pterostilbene (PT), inhibit fat cell formation (adipogenesis) by blocking key molecular pathways and reducing reactive oxygen species (ROS). This research clarifies their anti-adipogenic mechanisms.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Adipogenesis is the process of stem cell differentiation into adipocytes, regulated by hormones and nutrients.
  • Natural compounds are explored for anti-adipogenic effects via apoptosis, blocked differentiation, or inhibited triglyceride synthesis.
  • Understanding the molecular mechanisms of these compounds is crucial for developing anti-obesity strategies.

Purpose of the Study:

  • To elucidate the molecular mechanisms of andrographolide (AN) and pterostilbene (PT) in inhibiting human mesenchymal stem cell (MSC) differentiation into adipocytes.
  • To investigate the role of AN and PT in regulating key adipogenic transcription factors and signaling pathways.

Main Methods:

  • Human MSCs were induced to differentiate into adipocytes.
  • The expression levels of microRNAs (e.g., miR27a) and proteins (e.g., SIRT1, PPARγ, SREBP1c) were analyzed.
  • Reactive oxygen species (ROS) production during differentiation was measured.

Main Results:

  • Andrographolide (AN) upregulated miR27a, while pterostilbene (PT) upregulated SIRT1.
  • Both AN and PT inhibited the expression of key adipogenic transcription factors, including PPARγ (peroxisome proliferator-activated receptor gamma) and SREBP1c (sterol regulatory element-binding protein 1c).
  • AN and PT effectively blocked the surge of reactive oxygen species (ROS) during adipocyte differentiation.

Conclusions:

  • Andrographolide and pterostilbene demonstrate significant anti-adipogenic activity through distinct molecular pathways.
  • These phytocompounds inhibit adipogenesis by modulating miR27a, SIRT1, and crucial transcription factors (PPARγ, SREBP1c), and by reducing ROS.
  • The findings provide a molecular basis for the potential therapeutic use of AN and PT in managing obesity and related metabolic disorders.

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