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. 2012 Jun 13;60(23):5755-62.
doi: 10.1021/jf203456w. Epub 2011 Dec 1.

Anti-inflammatory effects of polyphenolic-enriched red raspberry extract in an antigen-induced arthritis rat model

Dinorah Jean-Gilles  1 , Liya Li, Hang Ma, Tao Yuan, Clinton O Chichester 3rd, Navindra P Seeram
Affiliations

Anti-inflammatory effects of polyphenolic-enriched red raspberry extract in an antigen-induced arthritis rat model

Dinorah Jean-Gilles et al. J Agric Food Chem. .

Abstract

The red raspberry ( Rubus idaeus ) fruit contains bioactive polyphenols including anthocyanins and ellagitannins with reported anti-inflammatory properties. This study sought to investigate the cartilage-protecting and anti-inflammatory effects of a polyphenolic-enriched red raspberry extract (RRE; standardized to total polyphenol, anthocyanin, and ellagitannin contents) using (1) an in vitro bovine nasal explant cell culture model and (2) an in vivo adjuvant-induced arthritis rat model. RRE contained 20% total polyphenols (as gallic acid equivalents), 5% anthocyanins (as cyanidin-3-glucoside equivalents), and 9.25% ellagitannins (as ellagic acid equivalents). In the in vitro studies, bovine nasal explants were stimulated with 10 ng/mL IL-1β to induce the release of proteoglycan and type II collagen. On treatment with RRE (50 μg/mL), there was a decrease in the rate of degradation of both proteoglycan and type II collagen. In the in vivo antigen-induced arthritis rat model, animals were gavaged daily with RRE (at doses of 30 and 120 mg/kg, respectively) for 30 days after adjuvant injection (750 μg of Mycobacterium tuberculosis suspension in squalene). At the higher dose, animals treated with RRE had a lower incidence and severity of arthritis compared to control animals. Also, histological analyses revealed significant inhibition of inflammation, pannus formation, cartilage damage, and bone resorption by RRE. This study suggests that red raspberry polyphenols may afford cartilage protection and/or modulate the onset and severity of arthritis.

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Figures

Figure 1
Figure 1
HPLC-UV chromatogram of the polyphenolic-enriched red raspberry extract (RRE). Fig 1A: 280 nm (characteristic of phenolics including ellagitannins); Fig. 1B: 360 nm (characteristic of phenolics including flavonols and ellagic acid glycosides); Fig. 1C: 520 nm (characteristic of anthocyanins). Compounds were identified based on comparison to published reports and LC-MS/MS data as follows: Peak 1 = cyanidin-3-O-sophoroside, Peak 2 = cyanidin-3-O-glucoside, Peak 3 = quercetin glycoside, Peak 4 = ellagic acid. Based on literature, unlabelled/unknown peaks correspond to flavonols, ellagic acid glycosides and ellagitannins which are known to be present in the red raspberry fruit.
Figure 2
Figure 2
In vitro effects of the polyphenol-enriched red raspberry extract (RRE) on nasal bovine cartilage degradation. Fig. 2A: Cumulative release of the GAG; Fig. 2B: Cumulative release of CII epitopes; Fig. 2C: Gelatynolitic activity of culture media collected at day 28. Lane 1, un-stimulated; lane 2 IL-1β alone, lane 3, IL-1β + RRE. *represent un-identified MMP bands; Fig. 2D: Picture showing the appearance of the cartilage plugs at the end of the culture period with and without treatment with RRE. Values as shown in Figs. 2A and 2B are reported as the mean ± SD (n = 4).
Figure 3
Figure 3
In vivo effects of the polyphenol-enriched red raspberry extract (RRE) in the antigen-induced arthritis (AIA) rat model. Fig. 3A: Effects of RRE on body weight; Fig. 3B: Effects of RRE on left paw volume; Fig. 3C: Representative toluidine blue-stained histology sections (16 X magnification) showing the ability of RRE to decrease inflammation (S), pannus formation (large arrow), cartilage damage (arrow head), and bone resorption (large arrow); Fig. 3D: Mean histology scores. Data is expressed as the mean ± SEM (n = 6).
Figure 3
Figure 3
In vivo effects of the polyphenol-enriched red raspberry extract (RRE) in the antigen-induced arthritis (AIA) rat model. Fig. 3A: Effects of RRE on body weight; Fig. 3B: Effects of RRE on left paw volume; Fig. 3C: Representative toluidine blue-stained histology sections (16 X magnification) showing the ability of RRE to decrease inflammation (S), pannus formation (large arrow), cartilage damage (arrow head), and bone resorption (large arrow); Fig. 3D: Mean histology scores. Data is expressed as the mean ± SEM (n = 6).
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