Indicaxanthin, a multi-target natural compound from Opuntia ficus-indica fruit: From its poly-pharmacological effects to biochemical mechanisms and molecular modelling studies

Allegra, Mario; Tutone, Marco; Tesoriere, Luisa; Almerico, Anna Maria; Culletta, Giulia; Livrea, Maria Antonia; Attanzio, Alessandro

doi:10.1016/j.ejmech.2019.07.006

Cited by 26 publications

(23 citation statements)

References 59 publications

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“…Indicaxanthin content in pulps was comparable to yellow Sicilian prickly pears (12.32 mg/100 g fresh pulp) [21]. Indicaxanthin is an interesting molecule as suggested by the overview on the therapeutic effects ranging from the anti-inflammatory to the neuro-modulatory and anti-tumoral ones [29]. Furthermore, Colorada also contained significant amounts of other betaxanthins such as portulacaxanthin, vulgaxanthin III, vulgaxanthin I, and vulgaxanthin II, among others.…”

Section: Quantification Of Betalainsmentioning

confidence: 83%

Digestive Stability and Bioaccessibility of Antioxidants in Prickly Pear Fruits from the Canary Islands: Healthy Foods and Ingredients

et al. 2020

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Although prickly pear fruits have become an important part of the Canary diet, their native varieties are yet to be characterized in terms of betalains and phenolic compounds. To exert potential health benefits, these antioxidants must be released from the food matrix and be stable in the gastrointestinal tract. Our aim was to characterize the betalain and phenolic profile of four prickly pear varieties from the Canary Islands (Spain) and determine their digestive stability and bioaccessibility via in vitro gastrointestinal digestion. Digestive studies were performed considering the (i) importance of the edible fraction (pulps) and (ii) potential of fruit peels as by-products to obtain healthy ingredients. Betalains and phenolic profiles were analyzed by HPLC-DAD-ESI/MS and HPLC-DAD-MS/QTOF. Pulps in Colorada and Fresa varieties presented high indicaxanthin and betanin content, respectively. Despite low pH in the gastric phase, betalains were stable to reach the intestinal phase, although indicaxanthin presented a higher bioaccessibility. Blanco Buenavista peels contained a distinct flavonoid profile including a new isorhamnetin-hexosyl-rhamnoside. Phenolic compounds were abundant and highly bioaccessible in fruit peels. These findings suggest that prickly pear pulps are rich in bioaccessible betalains; and that their peels could be proposed as potential by-products to obtain sustainable healthy ingredients.

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Section: Quantification Of Betalainsmentioning

confidence: 83%

Digestive Stability and Bioaccessibility of Antioxidants in Prickly Pear Fruits from the Canary Islands: Healthy Foods and Ingredients

et al. 2020

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“…Their capacity of enhancing anticancer activity or minimizing the resistance of cancer cells to a number chemotherapeutics has been explored [7,9]. Ind, the characteristic pigment of cactus pear fruits, is a redox-active compound able to exert important poly-pharmacological effects included antiproliferative and tumor suppressor effects both in vivo and in vitro [15][16][17]28] and may have a chemopreventive potential. In this study, we show that Ind individually exhibits growth inhibitory activity on HeLa cervical cancer cells and when combined with CDDP cooperates in producing an enhanced anti-tumor effect against these cells.…”

Section: Discussionmentioning

confidence: 99%

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis

et al. 2020

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Combining phytochemicals with chemotherapics is an emerging strategy to treat cancer to overcome drug toxicity and resistance with natural compounds. We assessed the effects of indicaxanthin (Ind), a pigment obtained from Opuntia ficus-indica (L. Mill) fruit, combined with cisplatin (CDDP) against cervical cancer cells (HeLa). Measured cell viability via Trypan blue assay; cell morphology via fluorescence microscopy; apoptosis, cell cycle, mitochondrial membrane potential (MMP) and cell redox balance via flow-cytometry; expression levels of apoptosis-related proteins via western blot. Cell viability assays and Chou-Talalay plot demonstrated that the combination of CDDP and Ind had synergistic cytotoxic effects. Combined treatment had significant effects (p < 0.05) on phosphatidylserine externalization, cell morphological changes, cell cycle arrest, fall in MMP, ROS production and GSH decay compared with the individual treatment groups. Bax, cytochrome c, p53 and p21waf1 were over-expressed, while Bcl-2 was downregulated. Pre-treatment with N-acetyl-l-cysteine abolished the observed synergistic effects. We also demonstrated potentiation of CDDP anticancer activity by nutritionally relevant concentrations of Ind. Oxidative stress-dependent mitochondrial cell death is the basis of the chemosensitizing effect of Ind combined with CDDP against HeLa cancer cells. ROS act as upstream signaling molecules to initiate apoptosis via p53/p21waf1 axis. Ind can be a phytochemical of interest in combo-therapy.

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“…It has been reported that hippocampal neurons are more responsive to Indicaxanthin [39]. In particular, it has an important role in several metabolic functions both in vitro and in vivo, reducing in ammation and enhancing immune response [22,23,40].…”

Section: Discussionmentioning

confidence: 99%

Amyloid-Beta induces different expression pattern of tissue transglutaminase and its isoforms on Olfactory Ensheathing Cells: modulatory effect of Indicaxanthin

Campisi

Raciti

Sposito

et al. 2021

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Alzhèimer Disease (AD) is characterized by protein aggregates in the brain, including amyloid-beta (Aβ), a substrate for tissue transglutaminase (TG2). We assessed the effect of full native peptide of Aβ (1–42), the fragments (25–35 and 35–25) on TG2 expression and its isoforms (Long and Short) on mouse Olfactory Ensheathing Cells (OECs). The levels of cytoskeletal proteins, Vimentin and Glial Fibrillary Acid Protein, were also studied. The effect of the pre-treatment with Indicaxanthin on cell viability, total Reactive Oxygen Species, superoxide anion and apoptotic pathway activation was assessed. Since Nestin is co-expressed in pluripotent stem cells with cyclin D1, their levels were also evaluated. Our findings highlight that Aβ (1–42) and its fragments induced an increase of TG2 levels and the different expression pattern of its isoforms on OECs. Indicaxanthin pre-treatment was able to reduce TG2 over-expression upregulated by Aβ exposure of cells differently modulating its isoforms. In addition, it prevented total Reactive Oxygen Species and superoxide anion production, it reduced Glial Fibrillary Acid Protein and Vimentin levels and inhibited apoptotic pathway activation. It also leaded to an increase of Nestin and cyclin D1 expression, stimulating stem cells renewal through the reparative activity played by TG2. Our results suggest that Aβ in OECs, both in the absence and in the presence of Indicaxanthin, might differently induce the transition of TG2 between “closed” and “open” conformation, providing a new mechanism involved in the signal pathways activated by the protein in Aβ injury important for neural regeneration of AD.

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Indicaxanthin, a multi-target natural compound from Opuntia ficus-indica fruit: From its poly-pharmacological effects to biochemical mechanisms and molecular modelling studies

Cited by 26 publications

References 59 publications

Digestive Stability and Bioaccessibility of Antioxidants in Prickly Pear Fruits from the Canary Islands: Healthy Foods and Ingredients

Digestive Stability and Bioaccessibility of Antioxidants in Prickly Pear Fruits from the Canary Islands: Healthy Foods and Ingredients

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis

Amyloid-Beta induces different expression pattern of tissue transglutaminase and its isoforms on Olfactory Ensheathing Cells: modulatory effect of Indicaxanthin

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