# Diversity Supplement to “Mechanistic study of Small-molecular Therapy in diabetic Wound Healing”

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2024 · $73,635

## Abstract

Project summary
Diabetic foot ulcers that lead to amputations are a major health problem affecting ~20% of the 30
million diabetic patients in the US. The current regimen has limited success, and the amputation
rates remain high. Therefore, understanding molecular mechanisms for compounds with
translational potential is a crucial step toward making a breakthrough in wound care protocols.
Endothelial cells (ECs) are indispensable cellular components for wound angiogenesis. However,
EC functions are impaired in patients with diabetes. The coformulation of two dietary compounds
- Trans-resveratrol (tRES) and hesperetin (HESP) - improves glucose metabolic profile and
arterial function in overweight and obese subjects through inducing the gene expression of
glyoxalase 1 (GLO1), an enzyme that detoxifies reactive metabolites during glycolysis and
protects cells against glycation stress. Our pilot data indicated that tRES+HESP improved wound
healing in diabetic animals with an increase in GLO1 expression. However, its effects are likely
far beyond inducing GLO1 expression because tRES+HESP treated ECs produced many pro-
angiogenic factors, including angiopoietin-1 (ANGPT1) that plays an essential role in
angiogenesis. Therefore, it is critical to determine proteins that are regulated by tRES+HESP in
angiogenesis and tissue repair. The objective of this project is to fill the knowledge gap of the role
of tRES+HESP in rescuing the disrupted angiogenesis in diabetes, and our long-term goal is to
develop therapeutic strategies for diabetic wound repair. We hypothesize that tRES+HESP
augments angiogenesis and improves diabetic wound healing through enhancing the expression
of GLO1 and a potent pro-angiogenic factor, ANGPT1, and through novel changes in additional
proteins in pathways critical to diabetic wound repair. We will test this hypothesis by completing
two aims. Aim 1: Identification of molecular pathways and protein changes induced by
tRES+HESP in human dermal microvascular ECs in vitro. Aim 2: Determine the therapeutic
potential of tRES+HESP and its underlying molecular mechanisms in chronic diabetic wounds in
vivo. The outcome of the proposed research will determine the efficacy of topical application of
this formula, tRES+HESP, in diabetic wound healing, and will unveil underlying molecular
mechanisms for its beneficial effect. Since tRES+HESP has not been approved by the FDA to
treat diabetic wound healing yet, these results may facilitate the FDA approval of this
coformulation in diabetic wound treatment.

## Key facts

- **NIH application ID:** 10837420
- **Project number:** 3R01DK128937-04S1
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Jiemei Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $73,635
- **Award type:** 3
- **Project period:** 2021-04-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10837420

## Citation

> US National Institutes of Health, RePORTER application 10837420, Diversity Supplement to “Mechanistic study of Small-molecular Therapy in diabetic Wound Healing” (3R01DK128937-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10837420. Licensed CC0.

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