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Abstract Number: 19

Pentagalloyl Glucose (PGG) Exhibits Anti-Rheumatic Activity in Human RA Synovial Fibroblasts and Rat Adjuvant-Induced Arthritis

Sadiq Umar1, Gates Roe1, Sabrina Fechtner1 and Salahuddin Ahmed2, 1Department of Pharmaceutical Science, Washington State University College of Pharmacy, Spokane, WA, 2Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, WA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: alternative medicine, Animal models, Cytokines and fibroblasts, IL-1

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Session Information

Date: Sunday, November 8, 2015

Session Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Pentagalloyl glucose (PGG) is a natural polyphenolic and water-soluble gallotannin that exhibits anti-cancer and anti-inflammatory activities. In the present study, we evaluated the efficacy of PGG in regulating interleukin-1β (IL-1β) stimulated human rheumatoid arthritis synovial fibroblasts (RA-FLS) and rat adjuvant-induced arthritis (AIA) model of inflammatory arthritis. 

Methods: The effect of PGG on RA-FLS viability was tested using MTT assay. Human RA-FLS were pretreated with PGG (0.1–10 µM) for 2 hours followed by IL-1β (10 ng/ml) stimulation 24 hours (for IL-6 and IL-8 production) and 30 mins to study cell signaling mechanisms. Conditioned medium was used for the quantification of IL-6 and IL-8 by ELISA and cell lysates were prepared for the analysis of IL-1β signaling network proteins like Myd88, IRAK1, p-TAK1, and TRAF6. To test in vivo efficacy of PGG, we performed studies in a rat AIA model. PGG was administered at doses of 12.5 and 25 mg/kg body weight once daily (starting on day 8 of AIA induction). The severity of the arthritis was quantified by ankle circumferences  measurement. 

Results: PGG (0.1–10 µM) had no adverse effect on the viability of RA-FLS. Pretreatment of PGG inhibited IL-1β-induced IL-6 (55 and 91% at 1 and 5 µM) and IL-8 (61 and 94 % at 1 and 5 µM) production in human RA-FLS in a dose-dependent manner (p<0.01; n=4). Evaluation of the signaling pathways using Western immunoblotting showed that PGG had no inhibitory effect on MyD88 expression, an adaptor protein in IL-1 receptor signaling pathway that mediates the innate immune responses. Similarly, among the downstream proteins proximal to IL-1β receptor such as IRAK1/TAK1/TRAF6, PGG was unable to inhibit IL-1β induced TRAF6 expression or rapid degradation of IRAK-1. However, PGG selectively inhibited the phosphorylation of TAK1 at Thr184/187, a site critical for its kinase activity and downstream activation of MAPK and NF-κB pathways in RA-FLS. In our rat AIA studies, arthritis peaked around day 19 and therapeutic administration of PGG at the daily doses of 12.5 and 25 mg/kg p.o. from day 8 markedly inhibited the severity of arthritis as evident from the reduction in ankle circumferences by ~30 and 45%, respectively, when compared to the untreated arthritic rats. In addition, there was no body weight loss observed with PGG treatment.

Conclusion: Our study provides novel evidence that PGG interferes with IL-1β signaling in RA-FLS by selectively inhibiting TAK1 activation and ameliorates rat AIA. These findings suggest PGG or its synthetic analogs may be developed for the comprehensive pre-clinical testing for their anti-rheumatic activity.


Disclosure: S. Umar, None; G. Roe, None; S. Fechtner, None; S. Ahmed, None.

To cite this abstract in AMA style:

Umar S, Roe G, Fechtner S, Ahmed S. Pentagalloyl Glucose (PGG) Exhibits Anti-Rheumatic Activity in Human RA Synovial Fibroblasts and Rat Adjuvant-Induced Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/pentagalloyl-glucose-pgg-exhibits-anti-rheumatic-activity-in-human-ra-synovial-fibroblasts-and-rat-adjuvant-induced-arthritis/. Accessed March 28, 2023.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pentagalloyl-glucose-pgg-exhibits-anti-rheumatic-activity-in-human-ra-synovial-fibroblasts-and-rat-adjuvant-induced-arthritis/

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