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Rewiring the regulated cell death network in diabetic retinopathy: natural products as system-level modulators

Qun Huang1, Tingru Chen2, Fang Wang3

  • 1Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|February 8, 2026
PubMed
Abstract

Insights

Natural products can modulate the network of cell death pathways involved in diabetic retinopathy (DR). These agents offer a promising therapeutic strategy to address the root causes of retinal degeneration by rewiring the regulated cell death network.

Area of Science:

  • Ophthalmology
  • Pharmacology
  • Cell Biology

Background:

  • Diabetic retinopathy (DR) pathogenesis involves dysregulated cell death pathways like apoptosis, pyroptosis, and ferroptosis.
  • Current DR therapies often fail to address upstream cellular damage.
  • Natural products (NPs) offer polypharmacology to modulate complex cell death networks.

Purpose of the Study:

  • Conceptualize DR as a collapse of the regulated cell death (RCD) network.
  • Position NPs as RCD network modulators for restoring homeostasis.
  • Overcome limitations of existing mono-target DR therapies.

Main Methods:

  • Systematic literature search using Web of Science and PubMed.
  • Keywords: natural products, diabetic retinopathy, regulated cell death modalities.
  • Adherence to ethical guidelines for animal experiments.

Main Results:

  • NPs target mitochondrial dysfunction, inflammasome activation, and oxidative stress.
  • NPs modulate Bcl-2 rheostat, autophagic flux, NLRP3, and Nrf2/SIRT1 pathways.
  • Pharmacokinetic challenges (bioavailability, ocular penetration) limit clinical translation.

Conclusions:

  • DR pathology arises from network-level RCD dysregulation.
  • NPs act as RCD network modulators, addressing root causes of retinal degeneration.
  • NPs represent a therapeutic shift for treating DR.
Keywords:
ApoptosisAutophagy-dependent cell deathDiabetic retinopathyFerroptosisNatural productsNetwork pharmacologyPyroptosis

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