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Islam, Purba (2019) Effects of resveratrol, piceatannol and quercetin in an equine cartilage explant model for potential use in treating osteoarthritis. PhD thesis, University of Nottingham.

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Abstract

Currently there are no disease-modifying osteoarthritis drugs (DMOADs) available and the treatment for osteoarthritis (OA) is still based on minimising symptoms. Commonly used drugs for OA have health hazards from long and short term use and has led to patients using alternatives therapies such as nutraceuticals.

In this study, three natural phenols (resveratrol, piceatannol and quercetin) were compared with commonly used drugs used for treating OA; phenylbutazone (NSAID) and prednisolone (corticosteroid) and a nitric oxide inhibitor marker (S-ethylisothiourea) in an IL-1β stimulated explant culture. The treatments at 100 µg/ml were assessed for their ability to inhibit inflammatory markers of OA (nitric oxide, PGE2, glycosaminoglycan, cell viability). Resveratrol, piceatannol and quercetin showed 100% nitric oxide inhibition similar to S-ethylisothiourea. Piceatannol was the only treatment which showed significant GAG inhibition. Cell viability for fresh, control, piceatannol (in the presence of IL-1β) and resveratrol (in the presence of IL-1β) treated cartilage were 83.9 ± 0.98 %, 76.8 ± 2.59 %, 78.8 ±3.57 % and 63.1 ± 4.35 % respectively.

In a dose-response stimulated cartilage explant study, piceatannol and quercetin significantly inhibited nitric oxide at a concentration range of 1-300 µg/ml, whereas for resveratrol it was 10-300 µg/ml. Effective inhibition of GAG breakdown for resveratrol and quercetin was in a range of 10-30 µg/ml in the stimulated cartilage explant. The IC50 for inhibition by piceatannol of GAG breakdown was 2 µg/ml. Inhibition of PGE2 production appears to be obscured by the vehicle (1% DMSO) used to dissolve the treatments.

This study suggests that nitric oxide is not playing a major role in GAG breakdown and cell death in the stimulated equine cartilage explant. Moreover, in this study, it was observed that GAG breakdown does not appear to initiate cell death at least at the early stages of an OA-like condition.

Resveratrol, piceatannol and quercetin may be potential DMOAD candidates to treat OA. Further studies on their beneficial effects especially in vivo should be compared against novel OA-modulators (such as GLPG1972) which are currently in clinical trials as they may offer a far cheaper therapeutic alternative.

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Paine, Stuart Freeman, Sarah Tötemeyer, Sabine
Keywords:	osteoarthritis, nutraceuticals, equine cartilage explant
Subjects:	Q Science > QP Physiology
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Item ID:	59374
Depositing User:	ISLAM, PURBA
Date Deposited:	06 Oct 2023 12:50
Last Modified:	06 Oct 2023 12:50
URI:	https://eprints.nottingham.ac.uk/id/eprint/59374

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