# Pentagalloyl glucose as an inhibitor of monosodium urate induced inflammation

> **NIH NIH F31** · WASHINGTON STATE UNIVERSITY · 2024 · $14,539

## Abstract

Project Summary
Monosodium urate-induced inflammation begins with hyperuricemia leading to monosodium urate (MSU) crystal
deposition in the joints and periarticular tissues. These deposits can cause inflammation, pain, and tissue
destruction through either acute inflammatory flares or chronic disease. In MSU-induced inflammation, activated
macrophages produce the pleiotropic cytokine Interleukin-1β (IL-1β) which is recognized as the major driver of
pathogenesis and a key inducer of other pro-inflammatory molecules. The inflammatory signaling cascade
begins with activation of Toll-like/IL-1β receptors (TIRs) in macrophages, which triggers production of pro-IL-1β
and other inflammasome components. Pro-IL-1β is then activated by cleaved caspase from the NOD-Like
Receptor Protein 3 (NLRP3) inflammasome before being exported and initiating further inflammation. Several
treatment options exist for gout patients, mostly falling into two categories – reduction of circulating levels of
soluble urate, or the suppression of pain and inflammation. These therapies, however, leave much to be desired
as they have significant adverse effects, deleterious drug-drug interactions, high cost and low/non-responder
groups. This project investigates a potential novel therapeutic agent for MSU-induced inflammation –
pentagalloyl glucose (PGG) – that is known to have strong antioxidant and anti-inflammatory effects. Additionally,
our preliminary data shows that this compound inhibits xanthine oxidase which produces soluble urate. We also
demonstrate that PGG inhibits TGFβ-activated kinase which plays a role in the upregulation of proinflammatory
mediators critical to MSU-induced inflammation. Finally, we have demonstrated that PGG inhibits both a critical
downstream kinase and proinflammatory cytokines. In Aim one we will investigate the mechanism by which PGG
reduces MSU-induced inflammation in vitro using THP-1 macrophages, investigate the atomistic interactions of
PGG with MSU in-silico, then use phosphoproteomics to identify global changes induced by MSU and PGG. In
Aim two we will determine the effects of PGG treatment in vivo using mouse models of gout previously published
by our group. Taken together, these findings will provide a more complete knowledge of MSU-induced
inflammatory signaling while exploring a potential novel therapeutic and providing a training mechanism for this
student.

## Key facts

- **NIH application ID:** 10761696
- **Project number:** 5F31AR081679-02
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Paul Panipinto
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $14,539
- **Award type:** 5
- **Project period:** 2023-01-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10761696

## Citation

> US National Institutes of Health, RePORTER application 10761696, Pentagalloyl glucose as an inhibitor of monosodium urate induced inflammation (5F31AR081679-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10761696. Licensed CC0.

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