Indicaxanthin from Opuntia ficus-indica Fruit Ameliorates Glucose Dysmetabolism and Counteracts Insulin Resistance in High-Fat-Diet-Fed Mice

Abstract

Obesity-related dysmetabolic conditions are amongst the most common causes of death globally. Indicaxanthin, a bioavailable betalain pigment from Opuntia ficus-indica fruit, has been demonstrated to modulate redox-dependent signalling pathways, exerting significant anti-oxidative and anti-inflammatory effects in vitro and in vivo. In light of the strict interconnections between inflammation, oxidative stress and insulin resistance (IR), a nutritionally relevant dose of indicaxanthin has been evaluated in a high-fat diet (HFD) model of obesity-related IR. To this end, biochemical and histological analysis, oxidative stress and inflammation evaluations in liver and adipose tissue were carried out. Our results showed that indicaxanthin treatment significantly reduced body weight, daily food intake and visceral fat mass. Moreover, indicaxanthin administration induced remarkable, beneficial effects on HFD-induced glucose dysmetabolism, reducing fasting glycaemia and insulinaemia, improving glucose and insulin tolerance and restoring the HOMA index to physiological values. These effects were associated with a reduction in hepatic and adipose tissue oxidative stress and inflammation. A decrease in RONS, malondialdehyde and NO levels, in TNF-α, CCL-2 and F4-80 gene expression, in p65, p-JNK, COX-2 and i-NOS protein levels, in crown-like structures and hepatic inflammatory foci was, indeed, observed. The current findings encourage further clinical studies to confirm the effectiveness of indicaxanthin to prevent and treat obesity-related dysmetabolic conditions.

Structural Effects on the Antioxidant Properties of Amino Acid Betaxanthins

“…The fact that all experiments have been performed using compounds prepared, purified, and studied in the same way increase the confidence for comparing the results obtained. Our results on Pro-Bx (indicaxanthin) agree with reports showing that, despite being a well-known antioxidant and anti-inflammatory agent in vivo [ 73 , 74 , 75 ], Pro-Bx does not have an exceptional antioxidant capacity [ 55 , 72 ], and is lower than that of vulgaxanthin I (Gln-Bx) [ 72 ], which is abundant in Golden beetroots [ 76 ]. These results have been rationalized by considering that the presence of a positively charged iminium group in indicaxanthin decreases its antioxidant capacity [ 53 , 72 ], but this interpretation implies that other more negatively charged betaxanthins may have even better antioxidant properties and/or that the iminium portion of Pro-Bx is important for its biological properties.…”

Redox Properties, Bioactivity and Health Effects of Indicaxanthin, a Bioavailable Phytochemical from Opuntia ficus indica, L.: A Critical Review of Accumulated Evidence and Perspectives

“…Relevantly, data from investigations in Caenorhabditis elegans [ 47 , 48 ] showed modulation of pathways that control health and longevity. Finally, findings in animal models of inflammation [ 49 ], cancer [ 44 ], obesity-related dysmetabolic conditions [ 50 ] and neuronal excitability [ 36 ], propose Indicaxanthin as a nutraceutical. Data and experimental results summarized in this review highlight key points while at the same time raising questions that open prospects for further research.…”

“…While Western-style eating habits are considered the main culprits in promoting obesity, dietary patterns, foods, and individual bioactive components, including phytochemicals, are now being evaluated to prevent, counteract, or treat obesity-associated disorders. Beneficial effects of Indicaxanthin have recently been observed in a mouse model of high-fat diet (HFD)-induced obesity [ 50 ], where the animals progressively develop a pathology similar to human metabolic syndrome, including high increase of body weight and fat mass, hyperglycemia, IR and hepatic steatosis. As an overall impact, a nutritionally relevant dose of Indicaxanthin (1.3 μmol/kg) twice daily for four weeks significantly reduced the food intake, body weight, visceral fat and subcutaneous adipose tissue mass of HFD mice.…”

“…It was also clearly evident that, unlike other phytochemicals [ 252 , 253 , 254 ], Indicaxanthin did not directly affect lipid metabolism. Other measurements showed that Indicaxanthin prevented HFD-induced oxidative stress, restoring RONS, MDA and NO levels in liver and adipose tissue, and decreased macrophage infiltration in visceral fat tissue as well as several inflammatory parameters, from TNF-α, CCL-2 and F4-80 gene expression, to p65, p-JNK, COX-2, and i-NOS protein levels in both tissues [ 50 ].…”

Engineering and Evaluation of Forcespun Gelatin Nanofibers as an Isorhamnetin Glycosides Delivery System

“…Opuntia ficus-indica (L.) Mill (OFI), known as nopal, has proven health benefits attributed to its dietary fiber and phytochemicals such as isorhamnetin glycosides (di and tri-glycosides) [49]. The isorhamnetin and its glycosides have shown their potential for medical applications through their involvement in different biological mechanisms such as apoptosis, adipogenesis inhibition, insulin resistance modulation, and inflammatory response [49][50][51][52][53][54]. An important challenge to incorporate these bioactive compounds into pharmaceutic or cosmetic products is their chemical stability under storage and biological conditions which directly impact their biological activity.…”