The potential of coloured-rice derived polyphenols in alleviating obesity-related oxidative stress and inflammation

This thesis investigates the role of pigmented rice polyphenols and their ability to modulate obesity-related oxidative stress and inflammation. This study aims to conduct polyphenol profiling across Australian-grown pigmented rice varieties, identify anti-adipogenic potential and explore the anti-inflammatory and antioxidant properties of pigmented rice in in-vitro, ex-vivo and in-vivo biological systems. Australian-grown rice varieties, were profiled for their polyphenol content and antioxidant activity. Pigmented rice varieties contained higher total antioxidant activity compared to brown varieties. Yunlu29 (red) had the highest total antioxidant activity. UHPLC profiling determined Yunlu29 to contain phenolic acids and proanthocyanidins. Polyphenol profiling facilitated the selection of Yunlu29 (red), Purple (purple/black) and Reiziq (brown) to be used for in-vitro, ex-vivo and in-vivo biological testing. In-vitro studies investigated the effect of pigmented rice-derived polyphenol extracts (PE) on adipocyte differentiation using C3H10T1/2 cells. Lipid accumulation and peroxisome proliferator-activated receptor gamma (PPAR) expression were quantified. PE derived from Purple rice significantly reduced (p < 0.001) lipid accumulation by 56.0% and PPAR expression in adipocytes by 35.6%. To investigate antioxidant and anti-inflammatory potential, human umbilical vein endothelial cells (HUVECs) were treated with PE. Purple PE significantly decreased reactive oxygen species by 46.0%. Yunlu29 (red) PE reduced interleukin-8 (IL-8) (84.0%) and interleukin-6 (IL-6) (63.0%). To explore anti-inflammatory and antioxidant potential of pigmented rice PE an ex-vivo study was conducted. Fasting blood samples were treated with PE. PE treatment demonstrated a dose-dependent reduction in malondialdehyde (MDA) and tumour necrosis factor-α (TNF-) levels. Purple PE reduced plasma MDA concentration by 59.0%. Brown rice PE at 50 g mL-1 reduced TNF- levels by 98.0%. A cross-over dietary intervention human clinical trial was conducted on a pre-screened healthy population (n = 24) investigating the antioxidant and anti-inflammatory potential of pigmented rice varieties. Blood samples were collected 30-minutes, 1, 2 and 4-hours post rice consumption. Antioxidant activity, MDA and pro-inflammatory cytokines were analysed on the blood samples collected. Post purple rice consumption, antioxidant activity increased (p < 0.0001) by 70.5%. The red rice variety Yunlu29, (p < 0.005) reduced MDA levels by 9.2% 30-minutes post-consumption . Purple rice decreased TNF- levels at the 1-hour (p < 0.05) and 4-hour (p < 0.005) time points by 21.9% and 25.4% respectively. To investigate the antioxidant and anti-inflammatory potential of pigmented rice in the obese population a dietary intervention study was conducted of the same experimental design as previously described, on an obese (BMI > 30) cohort (n = 22). Antioxidant activity increased (p < 0.001) at the 1-hour time point by 40.3% post purple rice consumption. MDA decreased (p < 0.05) at the 30-minute time point by 6.8% post purple rice consumption. At the 4-hour time point MDA levels was reduced (p < 0.001) by Yunlu29 (red) by 9.6%. Yunlu29 (red) reduced interleukin-6 levels by 13.6% at the 30-minutes post consumption. Both the purple (p < 0.01) and red (p < 0.001) varieties reduced interleukin-12p70 concentrations at 30-minutes by 8.7% and 10.3% respectively. The outcomes highlighted in this thesis, demonstrate that polyphenols found in pigmented rice may play a key role in targeting specific therapeutic pathways in obesity-related oxidative stress and inflammation.