Antiplatelet and Antithrombotic Effects of Isaridin E Isolated from the Marine-Derived Fungus via Downregulating the

Ni Pan1,2, Zi-Cheng Li1, Zhi-Hong Li1

  • 1Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

Marine Drugs
|January 20, 2022
PubMed

Insights

Isaridin E, a marine compound, effectively prevents blood clots in mice by inhibiting adenosine diphosphate (ADP)-induced platelet aggregation. This antithrombotic effect occurs without increasing bleeding risk, suggesting a potential new therapeutic avenue.

Area of Science:

  • Marine natural products
  • Pharmacology
  • Biochemistry

Background:

  • Isaridin E, a cyclodepsipeptide from marine fungus Amphichorda felina, exhibits anti-inflammatory and insecticidal properties.
  • Platelet aggregation plays a critical role in thrombosis and hemostasis.

Purpose of the Study:

  • To investigate the antithrombotic effects of Isaridin E.
  • To elucidate the underlying molecular mechanisms of Isaridin E's action on platelets.

Main Methods:

  • In vitro studies on ADP-, collagen-, and thrombin-induced platelet aggregation, activation, and secretion.
  • In vivo thrombosis model using FeCl3-induced carotid artery injury in mice.
  • Western blot analysis to assess PI3K and Akt phosphorylation.

Main Results:

  • Isaridin E inhibited ADP-induced platelet aggregation, activation, and secretion in a concentration-dependent manner.
  • Isaridin E dose-dependently reduced thrombosis in a mouse model without affecting bleeding time.
  • Isaridin E decreased ADP-mediated phosphorylation of PI3K and Akt.

Conclusions:

  • Isaridin E demonstrates significant antithrombotic activity in vivo.
  • The mechanism involves the inhibition of ADP-induced platelet activation and aggregation via the PI3K/Akt signaling pathway.
  • Isaridin E represents a promising antithrombotic agent with a favorable safety profile regarding bleeding risk.

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