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Review

Phenolic Compounds’ Occurrence in Opuntia Species and Their Role in the Inflammatory Process: A Review

by
Walid Zeghbib
1,2,
Fares Boudjouan
3,4,
Vitor Vasconcelos
2,5 and
Graciliana Lopes
2,*
1
Laboratoire de Biochimie Appliquée, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia 06000, Algeria
2
CIIMAR—Interdisciplinary Centre of Marine and Environmental Research, Terminal de Cruzeiros do Porto de Leixões, Avenida General Norton de Matos s/n, 4450-208 Matosinhos, Portugal
3
Laboratoire de Génie de l’Environnement, Faculté de Technologie, Université de Bejaia, Bejaia 06000, Algeria
4
Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, Bejaia 06000, Algeria
5
FCUP—Faculty of Sciences, University of Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
*
Author to whom correspondence should be addressed.
Molecules 2022, 27(15), 4763; https://doi.org/10.3390/molecules27154763
Submission received: 5 July 2022 / Revised: 18 July 2022 / Accepted: 18 July 2022 / Published: 25 July 2022
(This article belongs to the Special Issue Natural Polyphenols in Human Health)
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Abstract

:
Within the Cactaceae family, Opuntia comprises the most widespread species, with a recognized importance in human life, including feeding, domestic use as home natural barriers, and as a traditional remedy for diverse diseases and conditions such asthma, edema, and burns. Indeed, scientific reports have stated that these health benefits may be due to various active compounds, particularly polyphenols, which are ubiquitously found in plants and have proven their pharmacological efficiency by displaying antimicrobial, anti-cancer, and anti-inflammatory activities, among others. Opuntia species contain different classes of phenolic compounds that are recognized for their anti-inflammatory potential. Among them, quercetin, isorhamnetin, and kaempferol derivates were reported to greatly contribute to modulate cells’ infiltration and secretion of soluble inflammatory mediators, with key implications in the inflammatory process. In this review, we make a summary of the different classes of phenolic compounds reported in Opuntia species so far and explore their implications in the inflammatory process, reported by in vitro and in vivo bioassays, supporting the use of cactus in folk medicine and valorizing them from the socio-economic point of view.

Graphical Abstract

1. Introduction

Cacti belong to the plant family Cactaceae, which includes around 1500 species with recognized and very high phenotypic variations. Although the taxonomical characterization of the species is not always easy [1,2], the main subfamilies are currently well classified (Figure 1). Among them, the genus Opuntia, from the Opuntioideae subfamily, is the most recognized, being widely distributed across the globe [3,4]. Opuntia cacti (prickly pear) are among the plants with greater recognition in quotidian life, with archeological evidence encompassing the analysis of human coprolites dating back between 6500 to 10,000 years ago and suggesting its use as foodstuff [5,6]. The first discovery of cacti dates back to the times of the conquest of the new world by Spanish conquistadors who, besides being amazed by its attractive and delicious fruits, also noticed its granted economic and cultural importance in the daily life of the ancient Mesoamerican population [7,8] (Figure 2). After this, the plant became widely spread worldwide through cultivation and trade, nowadays being abundant in many arid and semi-arid regions of America, Africa, Asia, Europe, and Oceania [9,10].
The fast growth of cactus species and their good adaptation to poor soil make them very important plants for these populations, being part of their nourishment, livestock feed, and as a home natural barrier [11,12]. In addition, cacti became important in folk medicine for their capacity to alleviate diverse health conditions, such as diarrhea, asthma, hemorrhoids, ulcers, burns, and edema [2,13,14]. These beneficial properties to human health led to an increase in scientific research focused in cacti plants, particularly on species of the genus Opuntia, due to their recognized pharmacological properties [6]. Indeed, it was revealed that all parts of cacti (flowers, fruits, cladodes, and peels) constitute undeniable sources of valuable nutritional elements and biologically active primary and secondary metabolites, such as vitamins, carotenoids, betalains, polyunsaturated fatty acids, and polyphenols, leading people to consider them as important functional foods, with interesting nutraceutical and pharmacological properties [15,16,17].
Phenolic compounds, including flavonoids and phenolic acids, are ubiquitous molecules found in nature, particularly in plants, with more than 8000 compounds described so far, and divided into different classes [18]. Among other factors, the phenolics’ qualitative and quantitative profiles vary with plants’ genus, species, ripeness, cultivar, growth region, and kind of plant tissue [19,20,21]. The literature has reported a multitude of phenolic compounds in all Opuntia species [6,22], with a particular prevalence of phenolic acids and flavonoids, such as dihydroquercetin, quercetin, isorhamnetin, and kaempferol, known for their efficient antioxidant activity and ability to protect human organisms from the deleterious effects of free radicals through diverse mechanisms of action. It is widely known that oxidative stress appears as a consequence of tilting the balance in favor of free radicals compared to the antioxidant system. This imbalance stands at the base of many diseases, including different types of cancer, arteriosclerosis, myocardial infarction, diabetes, inflammatory diseases, central nervous system disorders, and cells’ aging [23,24]. In addition to the antioxidant power of polyphenols, recent investigations also recognized their antimicrobial, hepatoprotective, anti-carcinogenic, and anti-inflammatory properties [22,25]. As a matter of fact, research devoted to phenolic compounds’ valorization is ever present in the majority of natural matrices, from the optimization of the extraction processes to their biotechnological exploitation in food and cosmetic industries and elucidation of mechanisms of action in a wide array of pharmacological targets. Following the traditional use of cacti in acute health conditions where inflammation plays a central role, inflammatory mediators and enzymes appear among the main targets. Inflammation is a body’s natural response to a pathogen invasion, toxin, or physical damage (chemical or traumatic), which involves the generation of a wide array of inflammatory mediators, such as reactive oxygen species (ROS), by inflammatory and immune cells. When the inflammatory process is uncontrolled or when the endogenous defense systems fail to establish homeostasis, inflammation can become chronic, leading to tissue damage and often preceding the establishment of chronic diseases [26,27]. There are many pharmacological treatments for inflammation based on steroidal and non-steroidal compounds; however, they present significant undesirable side effects and resistances, leading to an increasing interest in the search for bioactive compounds from natural sources as a potential effective and alternative non-pharmacological approach [28]. In this regard, the present work provides a general review on the different classes of phenolic compounds found in Opuntia sp. and on the anti-inflammatory activity reported for the genus so far.

2. Phenolic Compounds

2.1. General Overview

After cellulose, phenolic compounds represent the most abundant group of secondary metabolites of the plant kingdom. This large family ranges from simple compounds with low molecular weight to large and complex polyphenols mainly found conjugated with sugars and organic acids [29]. In plants, phenolic compounds are biosynthesized by the shikimate pathway, which is localized in the chloroplasts. These aromatic molecules have important roles in plants, being implicated in the regulation of their growth, signaling, defense, and in conferring color to their fruits, leaves, and flowers [24,30,31]. Their chemical structure is characterized by the presence of at least one aromatic ring containing one or more hydroxyl groups [32]. From the chemical point of view, phenolic compounds are characterized by an acidic behavior, since the oxygen of the hydroxyl function is strongly linked to the ring, while the connection to the hydrogen atom is weak, allowing the proton dissociation into the medium and giving origin to a negatively charged phenolate ion [33].
The medicinal properties reported for polyphenols over the years aroused scientists’ interest in improving their extraction methodologies by using different solvents and extraction methods, the most widely explored being infusion, decoction, and maceration as well as Soxhlet, ultrasound, and microwave-assisted extraction [34]. There are more than 8000 phenolic compounds described in plants, with a high structural variability [18,35]. According to the classification system followed by De la Rosa et al. [30], phenolic compounds can be divided according to their chemical structure into two main classes: flavonoids and non-flavonoids. The first category is characterized by its structure complexity and known for its efficient bioactivity, accounting for nearly two-thirds of dietary polyphenols [30]. Its basic structure consists of a 15-carbon structure with two phenyl rings (A and B) connected by a three-carbon bridge, forming a heterocyclic pyran ring (ring C) skeleton (Figure 3a). The differences in the pyran ring substituents and the extent of hydrogenation allows defining six subcategories: flavones, flavonols, flavanols, isoflavones, flavanones, and anthocyanidins [29,31].
The non-flavonoids’ category includes smaller and simpler compounds. The principal molecules in this category are phenolic acids, particularly present in fruits and vegetables, accounting for one-third of dietary phenolic compounds. Phenolic acids are structurally composed by a single benzene unit, substituted by one carboxylic group and at least one hydroxyl group. Thus, many compounds can be considered simple phenols, and they are generally classified according to the number of carbons they have, the most common being hydroxybenzoic acids with a basic skeleton C6–C1 (Figure 3b) [30,33]. However, the non-flavonoids’ category also includes other compounds with a complex structure and with a high molecular weight, which are characteristic and major components of some plants, such as lignans, chalcones, and stilbenes [30].
Furthermore, the significant differences between species reported in the literature make it difficult to establish the qualitative and quantitative phenolic profiles of Opuntia sp. These differences are mostly devoted to the different extraction methods followed by the authors, which include both the use of solvents of different polarities, different extraction times, temperatures, and equipment. Differences in the Opuntia raw material used for extraction are also worth considering: phenolics’ extractions can be performed using dry or fresh material, of different maturation states, and from different geographic locations, which modifies the abiotic factors to which species are exposed and, consequently, their phenolic profile. For instance, Chahdoura et al. [60] found that ferulic acid derivatives were the most abundant compounds in Opuntia sp. seeds, reaching about 0.36 and 0.95 mg/g for Opuntia microdasys (Lehm.) N.E. Pfeiffer and Opuntia macrorhiza Engelm., respectively, while Amrane-Abider et al. [46] found a higher chlorogenic acid content, with 0.89 mg/g in Opuntia ficus-indica L. (Mill) seeds. The most abundant phenolic acid from the pulp of different varieties of O. ficus-indica found by the authors was piscidic acid, with 8.70–22.31 mg/g, and quercetin was the most abundant flavonoid with 0.08–0.26 mg/g (dry weight, DW). Contrarily, Zenteno-Ramírez et al. [17] reported gallic acid and epicatechin as the most abundant compounds in the pulp of different Opuntia species. In the peel of different O. ficus-indica varieties, García-Cayuela et al. [57] found that piscidic acid was the most abundant phenolic acid with 27.53–44.62 mg/g DW and isorhamnetin derivates were the most representative flavonoids (1.48–2.54 mg/g DW). For the cladodes, some reports indicated that quinic acid and myricetin were the most common in Opuntia dillenii (Ker Gawl.) Haw. cladodes [39,56], while Missaoui et al. [41] reported for O. ficus-indica a higher abundance for piscidic acid and isorhamnetin derivates, with 9.67 mg/g and 3.93 mg/g, respectively. Regarding the flowers, a study by Chahdoura et al. [59] on the flowering stage of O. microdasys demonstrated that ferulic acid and isorhamnetin derivates were the most frequent, ranging from 1.24–2.95 mg/g and 4.68–23.04 mg/g, respectively, while Ammar et al. [65] found a higher content in quinic acid and quercetin derivates, with 1.32 and 8.50 mg/g, respectively, for O. ficus-indica flowers. Moreover, Ouerghemmi et al. [54] reported that ferulic acid and quercetin were in higher amounts when compared to other phenolic compounds in O. ficus-indica flowers. It seems evident, based on the available studies, that besides the abiotic factors, the species-specific ones have a significant role in phenolics’ concentration and distribution throughout the different plant tissues. It seems difficult to establish a tissue fingerprint for Opuntia sp. since both flavonoids and phenolic acids present a wide distribution throughout all the studied plant parts. Based on the available studies, it seems that seeds present the widest variety of phenolic compounds, while the lowest variability has been observed for flowers. It was also observed that anthocyanidins and hydroxycinnamic acid were almost exclusive of cladodes; however, the fact that this was reported in only one study is not enough to state it as a tissue fingerprint or a species-specific characteristic. The same line of thought can be followed for phloretin, psoralen, and pinoresinol, which were only reported in the seeds of Opuntia stricta (Haw.) Haw.

2.2. Phenolic Compounds’ Occurrence in Opuntia sp.

Different classes of phenolic compounds can be found in cactus plants, with different qualitative and quantitative profiles, which mainly depends on environmental factors, plant origin, species, developmental stage, and age [2]. From the literature, there are no records about a specific extraction method or the most suitable solvent for polyphenols’ recovery from Opuntia sp. samples; hence, researchers tend to choose the procedure that suits them according to their objectives and equipment availability. Accordingly, due to the polarity of polyphenols, some high polar solvents have been generally used, such as methanol, acetone, ethanol, water, or even mixtures between them [36,37]; several extraction methods have been followed, including conventional ones, such as maceration, infusion, and decoction [10,38,39], and non-conventional ones, such as microwave-assisted extraction and ultrasonic-assisted extraction [40,41].
The occurrence of phenolic compounds in cactus has been described in seeds, flowers, cladodes, pulp, and peel, as detailed in Table 1. According to Santos-Díaz et al. [6], the phenolic profile in Opuntia genera is complex, with more than 40 compounds described in both pulp and cladodes and more than 20 in seeds of different species. It seems important to highlight that the majority of the available reports do not specify the phenolic composition of each vegetative tissue of Opuntia sp., which makes it difficult to establish a defined qualitative profile. However, some compounds such as delphinidin, petunidin, and malvidin seem to be exclusively found in Opuntia sp. cladodes, while phloretin, psoralen, pinoresinol, and epigallocatechin are found in seeds.

3. Opuntia sp. in Inflammation

Inflammation is a physiological, self-limiting process occurring in mammalian tissues as a response to harmful situations such as microorganism invasion, physical damage, or exposition to toxic chemicals. The inflammatory process tends to eliminate primary triggers and contributes to initiating the regeneration of injured tissues by mediating an organized immune response, involving particularly macrophages and mast cells [66,67]. However, in some situations, the mechanisms involved in restoring tissues’ homeostasis fail, generating a deregulated response that often results in a chronic inflammatory response, which is ever present in a wide variety of diseases and metabolic disorders such as diabetes, obesity, cancer, arthritis, and neurodegenerative and cardiovascular diseases [66,68].
The inflammatory framework involves a complex cascade of events with a coordinated action between pro- and anti-inflammatory mediators and biological systems including different cell lines (macrophages, neutrophils) and signaling molecules [69,70]. The NF-κB transcription factors have been long recognized for constituting a prototypical pro-inflammatory signaling pathway. In fact, these proteins are normally retained in the cytoplasm, being bound to a class of inhibitory proteins known as the IκB family. However, after stimulation, the activation of specific enzymes, known as IκB kinases (IKK), may phosphorylate the inhibitory protein, leading to the dissociation of the IκB/NF-κB complex. This results in a proteasomal degradation of IκB protein, while NF-κB can then translocate to the nucleus, binding DNA and activating the transcription of some targeted genes for cytokines, such as tumor necrosis factor-α (TNF-α) and interleukins (IL) (IL-1β and IL-6), as well as the production of several enzymes including cyclooxygenase (COX) and lipoxygenase (LOX) (Figure 4) [71,72,73]. These latter enzymes have a key role in the inflammatory process through the transformation of the arachidonic acid released from the phospholipid membrane into a spectrum of pro-inflammatory bioactive mediators including prostanoids and leukotrienes, which act by enhancing edema formation, increasing vascular permeability and leukocytes’ infiltration into the injured tissue [74,75,76].
Over the years, many studies have been conducted in order to explore the potential targets of Opuntia sp. extracts and isolated phenols regarding the inflammatory process. From the anti-inflammatory investigations of Opuntia sp. reported in the literature, some species were the subject of greater scrutiny: O. stricta, Opuntia humifusa (Raf.) Raf., Opuntia elatior Mill., O. dillenii, and, mostly, O. ficus-indica [65,77,78,79,80,81]. Different parts of the plant (flowers, cladodes, seeds, and fruits) were explored, and different extraction methods and solvents were used according to the desired purpose. However, most of the works exploring the anti-inflammatory potential of Opuntia sp. were conducted using crude extracts, and only a few of them provided information on the anti-inflammatory potential of isolated phenolic molecules, especially flavonoids from Opuntia sp., such as isorhamnetin and kaempferol derivates [77,82,83].

3.1. Modulation of Inflammatory Mediators and Enzymes

Most of the available studies exploring the anti-inflammatory activity of Opuntia sp. extracts and isolated compounds were undertaken in vitro and explored specific mediators and enzymes involved in the inflammatory process (Table 2). Among them, nitric oxide (NO), produced by the inducible nitric oxide synthase (iNOS) upon inflammatory stimuli, is among the most explored. Gómez-Maqueo and co-workers [84] reported that the pulps and peels of two varieties of prickly pears presented anti-inflammatory potential by scavenging NO radicals. Indeed, besides being implicated in many physiological processes, the high levels of NO also play a key role in the pathogenesis of inflammation, by upregulating iNOS and pro-inflammatory cytokines’ production (TNF-α and IL-8), leading at the end to serious tissue damage [78,85]. Following this train of thought, the reduction in the inflammatory response can benefit from the well-known free radical scavenging ability of phenolic compounds. The same authors followed their study and found that the different prickly pears’ parts were also able to inhibit hyaluronidase activity. This enzyme is implicated in both physiological and pathological processes by hydrolyzing hyaluronic acid (HA), one of the most important compounds in the extracellular matrix, with more than 50% found in human skin [86]. The degradation of HA leads to the breakdown of tissues’ structural integrity and, consequently, to an increase in their permeability, favoring the progression of inflammatory mediators. Thus, a balanced regulation of hyaluronic acid metabolism is important to maintain normal tissue organization and structure of the extracellular matrix. On the other hand, an over-activation of hyaluronidase may contribute to degenerative changes in connective tissues; therefore, enzyme inhibitors may play a beneficial role during the inflammatory process, presenting potential beneficial health effects such as hindering the exacerbation of the inflammatory response [86,87,88]. Similarly, another study of Gómez-Maqueo et al. [89], using other varieties of prickly pears, explored the same bioactivities in vitro, with a notably higher efficiency for peels when compared to pulps. The authors attributed this behavior to some compounds found in the species under study, particularly to indicaxanthin and to the phenolic compounds isorhamnetin glycosides, kaempferol glycoside, and quercetin, which mainly contributed to the observed anti-inflammatory potential by presenting a higher hyaluronidase inhibitory activity when compared to other purified standards.
A study conducted by Chaalal et al. [90] demonstrated that polyphenols extracted from different parts of O. ficus-indica fruits (seeds, pulp, and entire fruit) presented an anti-inflammatory potential and could exert a neuroprotective effect by decreasing the transcriptional expression of pro-inflammatory mediators such as TNF-α, IL-1β, and iNOS in N13-microglial cells after lipopolysaccharide (LPS) stimulation, pointing out the potential health benefit of these compounds in case of neuronal damage. In another study, Cho et al. [78] reported that chloroform and ethyl acetate fractions of O. humifusa cladodes were able to decrease NO production in LPS-stimulated RAW 264.7 macrophages, pointing to quercetin as one of the main compounds responsible for this behavior. Moreover, they also noticed that both fractions differently modulated cytokines’ gene expression, especially for iNOS, IL-6, and IL-1β, suggesting the implication of other bioactive components from the species in the anti-inflammatory potential, while Yeo et al. [91] showed that methanolic extracts obtained from the seeds of the same species reduced NO production from LPS-stimulated macrophages’ RAW 264.7. The isolated compound americanin A was found to be responsible for reducing iNOS and pro-inflammatory cytokines’ (TNF-α and IL-6) expression levels, which resulted principally by preventing NF-κB translocation into the nucleus.
In a study conducted with the intestinal Caco-2/TC7 cell line, Filannino and co-workers [92] reported that raw material and fermented extracts from O. ficus-indica cladodes presented an anti-inflammatory effect by significantly reducing NO and chemokines’ (IL-8 and TNF-α) production, which are important effectors in the inflammatory process contributing to the recruitment and activation of different inflammatory cells. In addition to decreasing the intracellular ROS generated during cells’ stimulation, flavonoids (especially kaempferol and isorhamnetin), were considered to be the main responsible for this anti-inflammatory modulation. They displayed a significant decrease in prostaglandin E2 accumulation, which is a pro-inflammatory product from COX-2 and prostaglandin synthase metabolism, generally implicated in promoting local vasodilatation, and attraction and regulation of different immune cells’ functions. Similarly, a study conducted by Matias et al. [82] found that flavonoid-rich concentrate from O. ficus-indica fruits prevented oxidative stress through the neutralization of H2O2-induced free radicals and also prevented protein oxidation in inflamed Caco-2 cells. Otherwise, the extract allowed protecting the intestinal barrier dysfunction, which was correlated with the ability of some flavonoids to decrease TNF-α secretion. They also found that the incubation of inflamed Caco-2 cells with the extract significantly modulated cytokines’ secretion, leading particularly to a decrease in IL-8 and NO production, which are linked to the activation of the NF-κB pathway. Indeed, it was proven that the extract reduced the degradation of IκBα, an important inhibitor of NF-κB, preventing its migration from cytosol to the nucleus, where it could promote the transcription of pro-inflammatory genes.

3.2. Anti-Inflammatory Activity In Vivo

Most of the in vivo works exploring the anti-inflammatory activity of Opuntia species were conducted using rats as animal models, following the carrageenan-induced inflammation method, which is frequently used to evaluate the anti-edematous effect of natural products (Table 2) [79].
A study by Ahmed et al. [77] reported the in vivo anti-inflammatory potential of different parts of O. dillenii with a high efficiency verified for the flowers, from which three isolated compounds, namely, kaempferol 3-O-α-arabinoside, isorhamnetin-3-O-β-d-glucopyranoside, and isorhamnetin-3-O-β-d-rutinoside, were characterized as the active principles contributing significantly to reducing paw edema in albino rats. Ammar et al. [65] also reported the anti-inflammatory potential for Opuntia sp. flowers; the authors found that the methanolic extracts of O. ficus-indica flowers exhibited an anti-inflammatory potential by reducing the paw edema size in Wistar rats, with the same efficiency as the non-steroidal anti-inflammatory drug indomethacin. This effect was confirmed by a significant decrease in the number of inflammatory cells, including leukocytes and lymphocytes, a decrease in malondialdehyde (MDA) levels, which is correlated with the decrease in the lipid peroxidation process occurring at inflammatory sites, and a restoration of some antioxidant enzymes’ activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), which contribute to neutralize free radicals’ overproduction. According to the phytochemical analysis, the authors suggested the implication of phenolic compounds, particularly quercetin, isorhamnetin, and kaempferol, which could scavenge free radicals and decrease inflammation. Moreover, Antunes-Ricardo et al. [83] found that O. ficus-indica cladodes’ extract and its isolated isorhamnetin derivatives (isorhamnetin-3-O-glucosyl-rhamnosyl-rhamnoside and isorhamnetin-3-O-glucosyl-rhamnoside) decreased the amount of neutrophils’ infiltration into the inflammatory site (carrageenan-induced air-pouch inflammation in rats) with a decrease in NO production more efficient than that obtained with the standard drug used, indomethacin. The authors also found that cladodes’ extract and isolated compounds were able to inhibit COX-2 activity and cytokines’ production, particularly TNF-α and IL-6, with a better efficiency for the crude sample, probably due to a synergistic effect of its different phytochemicals.

4. Conclusions

The present review shows the richness of Opuntia species as producers of a wide variety of phenolic compounds, with an important role in the inflammatory process. The anti-inflammatory studies conducted until now demonstrated the benefit of different species to reduce the oxidative stress occurring at the site of an injury, decreasing the amount of neutrophils’ infiltration, as well as pro-inflammatory mediators’ production, such as NO, TNF-α, and interleukins. These effects were correlated with the presence of flavonoids in the different tissues of cactus, namely, quercetin, isorhamnetin, and kaempferol derivates, as the important bioactive components. Even though the Opuntia genus regroups a lot of species throughout the world, the available studies are limited to a few of them, with O. ficus-indica being by far the most explored. Nevertheless, reports on cactus plants reveal their potential anti-inflammatory application in the pharmaceutical industry, supporting the traditional use of these species in folk medicine and enhancing their economic value worldwide and for local communities.

Author Contributions

Conceptualization, G.L.; methodology, G.L. and W.Z.; investigation, W.Z.; writing—original draft preparation, W.Z.; writing—review and editing, F.B., V.V., and G.L.; supervision, F.B. and G.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research was partially funded by the strategic funding from UIDB/04423/2020 and UIDP/04423/2020 of CIIMAR.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

Graciliana Lopes thanks the Portuguese Foundation for Science and Technology (FCT) for the financial support for her work contract through the Scientific Employment Stimulus-Individual Call (CEECIND/01768/2021).

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Sáenz, C. Opuntias as a natural resource. In Agro-Industrial Utilization of Cactus Pear; Sáenz, C., Berger, H., Rodríguez-Félix, A., Galletti, L., García, J.C., Sepúlveda, E., Varnero, M.T., García de Cortázar, V., García, R.C., Arias, E., et al., Eds.; Rural Infrastructure and Agro-Industries Division: Rome, Italy, 2013; pp. 17–21. [Google Scholar]
  2. El-Mostafa, K.; El-Kharrassi, Y.; Badreddine, A.; Andreoletti, P.; Vamecq, J.; El-Kebbaj, M.S.; Latruffe, N.; Lizard, G.; Nasser, B.; Cherkaoui-Malki, M. Nopal Cactus (Opuntia ficus-indica) as a Source of Bioactive Compounds for Nutrition, Health and Disease. Molecules 2014, 19, 14879–14901. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Labra, M.; Grassi, F.; Bardini, M.; Imazio, S.; Guiggi, A.; Citterio, S.; Banfi, E.; Sgorbati, S. Genetic Relationships in Opuntia Mill. Genus (Cactaceae) Detected by Molecular Marker. Plant Sci. 2003, 165, 1129–1136. [Google Scholar] [CrossRef]
  4. Hahm, S.-W.; Park, J.; Oh, S.-Y.; Lee, C.-W.; Park, K.-Y.; Kim, H.; Son, Y.-S. Anticancer Properties of Extracts from Opuntia humifusa against Human Cervical Carcinoma Cells. J. Med. Food 2015, 18, 31–44. [Google Scholar] [CrossRef] [PubMed]
  5. Callen, E.O. Analysis of the Tehuacan coprolites. In The Prehistory of the Tehuacan Valley; Byers, D.S., Ed.; University of Texas Press: London, UK, 1967; Volume 1, pp. 261–289. [Google Scholar]
  6. Santos-Díaz, M.S.; Balch, E.P.M.; Ramírez-Malagón, R.; Nuñez-Palenius, H.G.; Ochoa-Alejo, N. Mexican threatened cacti: Current status and strategies for their conservation. In Species Diversity and Extinction; Nova Science Publishers: Hauppauge, NY, USA, 2011; pp. 1–59. [Google Scholar]
  7. Kamble, S.M.; Debaje, P.P.; Ranveer, R.C.; Sahoo, A. Nutritional Importance of Cactus: A Review. Trends Biosci. 2017, 10, 7668–7677. [Google Scholar]
  8. Ochoa, M.J.; Barbera, G. History and economic and agro-ecological importance. In Crop Ecology, Cultivation and Uses of Cactus Pear; Inglese, P., Mondragon, C., Nefzaoui, A., Sáenz, C., Eds.; Food and Agriculture Organization of the United Nations (FAO): Rome, Italy, 2017; pp. 1–11. [Google Scholar]
  9. Ganopoulos, I.; Kalivas, A.; Kavroulakis, N.; Xanthopoulou, A.; Mastrogianni, A.; Koubouris, G.; Madesis, P. Genetic Diversity of Barbary Fig (Opuntia ficus-indica) Collection in Greece with ISSR Molecular Markers. Plant Gene 2015, 2, 29–33. [Google Scholar] [CrossRef] [Green Version]
  10. Zeghbib, W.; Boudjouan, F.; Bachir-bey, M. Optimization of Phenolic Compounds Recovery and Antioxidant Activity Evaluation from Opuntia ficus indica Using Response Surface Methodology. J. Food Meas. Charact. 2022, 16, 1354–1366. [Google Scholar] [CrossRef]
  11. Gurrieri, S.; Miceli, L.; Lanza, C.M.; Tomaselli, F.; Bonomo, R.P.; Rizzarelli, E. Chemical Characterization of Sicilian Prickly Pear (Opuntia ficus indica) and Perspectives for the Storage of Its Juice. J. Agric. Food Chem. 2000, 48, 5424–5431. [Google Scholar] [CrossRef]
  12. Benayad, Z.; Martinez-Villaluenga, C.; Frias, J.; Gomez-Cordoves, C.; Es-Safi, N.E. Phenolic Composition, Antioxidant and Anti-Inflammatory Activities of Extracts from Moroccan Opuntia ficus-indica Flowers Obtained by Different Extraction Methods. Ind. Crops Prod. 2014, 62, 412–420. [Google Scholar] [CrossRef] [Green Version]
  13. Kaur, M.; Kaur, A.; Sharma, R. Pharmacological Actions of Opuntia ficus indica: A Review. J. App. Pharm. Sci. 2012, 2, 15–18. [Google Scholar] [CrossRef] [Green Version]
  14. Leem, K.-H.; Kim, M.-G.; Hahm, Y.-T.; Kim, H.K. Hypoglycemic Effect of Opuntia Ficus-Indica Var. Saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/P38 MAPK Pathway. Nutrients 2016, 8, 800. [Google Scholar] [CrossRef] [Green Version]
  15. Hernández-Urbiola, M.I.; Pérez-Torrero, E.; Rodríguez-García, M.E. Chemical Analysis of Nutritional Content of Prickly Pads (Opuntia ficus indica) at Varied Ages in an Organic Harvest. Int. J. Environ. Res. Public Health 2011, 8, 1287–1295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Slimen, I.B.; Mabrouk, M.; Hanène, C.; Najar, T.; Abderrabba, M. LC-MS Analysis of Phenolic Acids, Flavonoids and Betanin from Spineless Opuntia ficus-indica Fruits. Cell Biol. 2017, 5, 17–28. [Google Scholar] [CrossRef]
  17. Zenteno-Ramírez, G.; Juárez-Flores, B.I.; Aguirre-Rivera, J.R.; Monreal-Montes, M.; García, J.M.; Serratosa, M.P.; Santos, M.Á.V.; Pérez, M.D.O.; Rendón-Huerta, J.A. Juices of Prickly Pear Fruits (Opuntia spp.) As Functional Foods. Ital. J. Food Sci. 2018, 30, 614–627. [Google Scholar] [CrossRef]
  18. Ćavar Zeljković, S.; Šišková, J.; Komzáková, K.; de Diego, N.; Kaffková, K.; Tarkowski, P. Phenolic Compounds and Biological Activity of Selected Mentha Species. Plants 2021, 10, 550. [Google Scholar] [CrossRef]
  19. Yeddes, N.; Chérif, J.K.; Guyot, S.; Sotin, H.; Ayadi, M.T. Comparative Study of Antioxidant Power, Polyphenols, Flavonoids and Betacyanins of the Peel and Pulp of Three Tunisian Opuntia Forms. Antioxidants 2013, 2, 37–51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  20. Pérez-Loredo, M.G.; García-Ochoa, F.; Barragán-Huerta, B.E. Comparative Analysis of Betalain Content in Stenocereus Stellatus Fruits and Other Cactus Fruits Using Principal Component Analysis. Int. J. Food Prop. 2016, 19, 326–338. [Google Scholar] [CrossRef] [Green Version]
  21. Murevanhema, Y.Y.; Jideani, V.A.; Oguntibeju, O.O. Review on potential of seeds and value-added products of bambara groundnut (Vigna Subterranea): Antioxidant, anti-inflammatory, and anti-oxidative stress. In Bioactive Compounds of Medicinal Plants; Goyal, M.R., Ayeleso, A.O., Eds.; Apple Academic Press: New York, NY, USA, 2018; pp. 102–141. ISBN 978-1-315-14747-5. [Google Scholar]
  22. De Santiago, E.; Gill, C.I.R.; Carafa, I.; Tuohy, K.M.; de Peña, M.-P.; Cid, C. Digestion and Colonic Fermentation of Raw and Cooked Opuntia ficus-indica Cladodes Impacts Bioaccessibility and Bioactivity. J. Agric. Food Chem. 2019, 67, 2490–2499. [Google Scholar] [CrossRef]
  23. Osuna-Martínez, L.; Reyes Esparza, J.; Rodríguez-Fragoso, L. Cactus (Opuntia ficus-indica): A Review on Its Antioxidants Properties and Potential Pharmacological Use in Chronic Diseases. Stud. Nat. Prod. Chem. 2014, 2, 153–160. [Google Scholar] [CrossRef] [Green Version]
  24. Santos-Sánchez, N.F.; Salas-Coronado, R.; Villanueva-Cañongo, C.; Hernández-Carlos, B. Antioxidant compounds and their antioxidant mechanism. In Antioxidants; Shalaby, E., Ed.; IntechOpen: London, UK, 2019; ISBN 978-1-78923-920-1. [Google Scholar]
  25. Shan, S.; Huang, X.; Shah, M.H.; Abbasi, A.M. Evaluation of Polyphenolics Content and Antioxidant Activity in Edible Wild Fruits. Biomed. Res. Int. 2019, 2019, e1381989. [Google Scholar] [CrossRef] [Green Version]
  26. Biswas, S.K. Does the Interdependence between Oxidative Stress and Inflammation Explain the Antioxidant Paradox? Oxid. Med. Cell Longev. 2016, 2016, 5698931. [Google Scholar] [CrossRef] [Green Version]
  27. Chatterjee, S. Chapter two—Oxidative stress, inflammation, and disease. In Oxidative Stress and Biomaterials; Dziubla, T., Butterfield, D.A., Eds.; Academic Press: Cambridge, MA, USA, 2016; pp. 35–58. ISBN 978-0-12-803269-5. [Google Scholar]
  28. Maroon, J.C.; Bost, J.W.; Maroon, A. Natural Anti-Inflammatory Agents for Pain Relief. Surg. Neurol. Int. 2010, 1, 80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  29. Crozier, A.; Jaganath, I.B.; Clifford, M.N. Phenols, polyphenols and tannins: An overview. In Plant Secondary Metabolites; Crozier, A., Clifford, M.N., Ashihara, H., Eds.; John Wiley & Sons, Ltd.: Hoboken, NJ, USA, 2006; pp. 1–24. ISBN 978-0-470-98855-8. [Google Scholar]
  30. De la Rosa, L.A.; Alvarez-Parrilla, E.; Shahidi, F. Phenolic Compounds and Antioxidant Activity of Kernels and Shells of Mexican Pecan (Carya Illinoinensis). J. Agric. Food Chem. 2011, 59, 152–162. [Google Scholar] [CrossRef] [PubMed]
  31. Chu, K.O.; Chan, S.-O.; Pang, C.P.; Wang, C.C. Pro-Oxidative and Antioxidative Controls and Signaling Modification of Polyphenolic Phytochemicals: Contribution to Health Promotion and Disease Prevention? J. Agric. Food Chem. 2014, 62, 4026–4038. [Google Scholar] [CrossRef] [PubMed]
  32. Soto-Vaca, A.; Gutierrez, A.; Losso, J.N.; Xu, Z.; Finley, J.W. Evolution of Phenolic Compounds from Color and Flavor Problems to Health Benefits. J. Agric. Food Chem. 2012, 60, 6658–6677. [Google Scholar] [CrossRef]
  33. Pabón-Baquero, L.C.; Otálvaro-Álvarez, Á.M.; Fernández, M.R.R.; Chaparro-González, M.P. Plant extracts as antioxidant additives for food industry. In Antioxidants in Foods and Its Applications; Shalaby, E., Azzam, G.M., Eds.; IntechOpen: London, UK, 2018; pp. 87–116. ISBN 978-1-78923-379-7. [Google Scholar]
  34. Ali Redha, A. Review on Extraction of Phenolic Compounds from Natural Sources Using Green Deep Eutectic Solvents. J. Agric. Food Chem. 2021, 69, 878–912. [Google Scholar] [CrossRef]
  35. Wang, Z.; Li, S.; Ge, S.; Lin, S. Review of Distribution, Extraction Methods, and Health Benefits of Bound Phenolics in Food Plants. J. Agric. Food Chem. 2020, 68, 3330–3343. [Google Scholar] [CrossRef]
  36. Haminiuk, C.W.I.; Plata-Oviedo, M.S.V.; de Mattos, G.; Carpes, S.T.; Branco, I.G. Extraction and Quantification of Phenolic Acids and Flavonols from Eugenia Pyriformis Using Different Solvents. J. Food Sci. Technol. 2014, 51, 2862–2866. [Google Scholar] [CrossRef] [Green Version]
  37. Alara, O.R.; Abdurahman, N.H.; Ukaegbu, C.I. Extraction of Phenolic Compounds: A Review. Curr. Res. Nutr. Food Sci. 2021, 4, 200–214. [Google Scholar] [CrossRef]
  38. Ammar, I.; Ennouri, M.; Bouaziz, M.; Ben Amira, A.; Attia, H. Phenolic Profiles, Phytchemicals and Mineral Content of Decoction and Infusion of Opuntia ficus-indica Flowers. Plant Foods Hum. Nutr. 2015, 70, 388–394. [Google Scholar] [CrossRef]
  39. Ben Lataief, S.; Zourgui, M.-N.; Rahmani, R.; Najjaa, H.; Gharsallah, N.; Zourgui, L. Chemical Composition, Antioxidant, Antimicrobial and Cytotoxic Activities of Bioactive Compounds Extracted from Opuntia dillenii Cladodes. J. Food Meas. Charact. 2021, 15, 782–794. [Google Scholar] [CrossRef]
  40. Melgar, B.; Dias, M.I.; Barros, L.; Ferreira, I.C.F.R.; Rodriguez-Lopez, A.D.; Garcia-Castello, E.M. Ultrasound and Microwave Assisted Extraction of Opuntia Fruit Peels Biocompounds: Optimization and Comparison Using RSM-CCD. Molecules 2019, 24, 3618. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  41. Missaoui, M.; D’Antuono, I.; D’Imperio, M.; Linsalata, V.; Boukhchina, S.; Logrieco, A.F.; Cardinali, A. Characterization of Micronutrients, Bioaccessibility and Antioxidant Activity of Prickly Pear Cladodes as Functional Ingredient. Molecules 2020, 25, 2176. [Google Scholar] [CrossRef] [PubMed]
  42. Tounsi, M.S.; Ouerghemmi, I.; Ksouri, R.; Wannes, W.A.; Hammrouni, I.; Marzouk, B. HPLC-Determination of Phenolic Composition and Antioxidant Capacity of Cactus Prickly Pears Seeds. Asian J. Chem. 2011, 23, 1006–1010. [Google Scholar]
  43. Koubaa, M.; Mhemdi, H.; Barba, F.J.; Angelotti, A.; Bouaziz, F.; Chaabouni, S.E.; Vorobiev, E. Seed Oil Extraction from Red Prickly Pear Using Hexane and Supercritical CO2: Assessment of Phenolic Compound Composition, Antioxidant and Antibacterial Activities. J. Sci. Food Agric. 2017, 97, 613–620. [Google Scholar] [CrossRef]
  44. López-Palacios, C.; Peña-Valdivia, C.B. Screening of Secondary Metabolites in Cladodes to Further Decode the Domestication Process in the Genus Opuntia (Cactaceae). Planta 2020, 251, 74. [Google Scholar] [CrossRef]
  45. Kıvrak, Ş.; Kıvrak, İ.; Karababa, E. Analytical Evaluation of Phenolic Compounds and Minerals of Opuntia robusta J.C. Wendl. and Opuntia ficus-barbarica A. Berger. Int. J. Food Prop. 2018, 21, 229–241. [Google Scholar] [CrossRef] [Green Version]
  46. Amrane-Abider, M.; Nerin, C.; Canellas, E.; Benkerrou, F.; Louaileche, H. Modeling and Optimization of Phenolic Compounds Extraction from Prickly Pear (Opuntia ficus-indica) Seeds via Ultrasound-Assisted Technique. Ann. Univ. Dunarea Jos Galati. Fascicle VI Food Technol. 2018, 42, 109–121. [Google Scholar]
  47. Rocchetti, G.; Pellizzoni, M.; Montesano, D.; Lucini, L. Italian Opuntia ficus-indica Cladodes as Rich Source of Bioactive Compounds with Health-Promoting Properties. Foods 2018, 7, 24. [Google Scholar] [CrossRef] [Green Version]
  48. Aruwa, C.E.; Amoo, S.; Kudanga, T. Phenolic Compound Profile and Biological Activities of Southern African Opuntia ficus-indica Fruit Pulp and Peels. LWT 2019, 111, 337–344. [Google Scholar] [CrossRef]
  49. Ortega-Hernández, E.; Nair, V.; Welti-Chanes, J.; Cisneros-Zevallos, L.; Jacobo-Velázquez, D.A. Wounding and UVB Light Synergistically Induce the Biosynthesis of Phenolic Compounds and Ascorbic Acid in Red Prickly Pears (Opuntia ficus-indica Cv. Rojo Vigor). Int. J. Mol. Sci. 2019, 20, 5327. [Google Scholar] [CrossRef] [Green Version]
  50. Astello-García, M.G.; Cervantes, I.; Nair, V.; del Santos-Díaz, M.S.; Reyes-Agüero, A.; Guéraud, F.; Negre-Salvayre, A.; Rossignol, M.; Cisneros-Zevallos, L.; Barba de la Rosa, A.P. Chemical Composition and Phenolic Compounds Profile of Cladodes from Opuntia spp. Cultivars with Different Domestication Gradient. J. Food Compos. Anal. 2015, 43, 119–130. [Google Scholar] [CrossRef]
  51. Mata, A.; Ferreira, J.P.; Semedo, C.; Serra, T.; Duarte, C.M.M.; Bronze, M.R. Contribution to the Characterization of Opuntia spp. Juices by LC-DAD-ESI-MS/MS. Food Chem. 2016, 210, 558–565. [Google Scholar] [CrossRef] [PubMed]
  52. Lanuzza, F.; Occhiuto, F.; Monforte, M.T.; Tripodo, M.M.; D’Angelo, V.; Galati, E.M. Antioxidant Phytochemicals of Opuntia ficus-indica (L.) Mill. Cladodes with Potential Anti-Spasmodic Activity. Pharmacogn. Mag. 2017, 13, S424–S429. [Google Scholar] [CrossRef] [PubMed]
  53. Melgar, B.; Dias, M.I.; Ciric, A.; Sokovic, M.; Garcia-Castello, E.M.; Rodriguez-Lopez, A.D.; Barros, L.; Ferreira, I. By-Product Recovery of Opuntia spp. Peels: Betalainic and Phenolic Profiles and Bioactive Properties. Ind. Crops Prod. 2017, 107, 353–359. [Google Scholar] [CrossRef] [Green Version]
  54. Ouerghemmi, I.; Harbeoui, H.; Aidi Wannes, W.; Bettaieb Rebey, I.; Hammami, M.; Marzouk, B.; Saidani Tounsi, M. Phytochemical Composition and Antioxidant Activity of Tunisian Cactus Pear (Opuntia ficus indica L.) Flower. J. Food Biochem. 2017, 41, 1–10. [Google Scholar] [CrossRef]
  55. De Santiago, E.; Pereira-Caro, G.; Moreno-Rojas, J.M.; Cid, C.; de Peña, M.-P. Digestibility of (Poly)phenols and Antioxidant Activity in Raw and Cooked Cactus Cladodes (Opuntia ficus-indica). J. Agric. Food Chem. 2018, 66, 5832–5844. [Google Scholar] [CrossRef]
  56. Mena, P.; Tassotti, M.; Andreu, L.; Nuncio-Jáuregui, N.; Legua, P.; del Rio, D.; Hernández, F. Phytochemical Characterization of Different Prickly Pear (Opuntia ficus-indica (L.) Mill.) Cultivars and Botanical Parts: UHPLC-ESI-MSn Metabolomics Profiles and Their Chemometric Analysis. Food Res. Int. 2018, 108, 301–308. [Google Scholar] [CrossRef]
  57. García-Cayuela, T.; Gómez-Maqueo, A.; Guajardo-Flores, D.; Welti-Chanes, J.; Cano, M.P. Characterization and Quantification of Individual Betalain and Phenolic Compounds in Mexican and Spanish Prickly Pear (Opuntia ficus-indica L. Mill) Tissues: A Comparative Study. J. Food Compos. Anal. 2019, 76, 1–13. [Google Scholar] [CrossRef]
  58. Kolniak-Ostek, J.; Kita, A.; Miedzianka, J.; Andreu-Coll, L.; Legua, P.; Hernandez, F. Characterization of Bioactive Compounds of Opuntia ficus-indica (L.) Mill. Seeds from Spanish Cultivars. Molecules 2020, 25, 5734. [Google Scholar] [CrossRef]
  59. Chahdoura, H.; Barreira, J.C.M.; Barros, L.; Santos-Buelga, C.; Ferreira, I.C.F.R.; Achour, L. Phytochemical Characterization and Antioxidant Activity of Opuntia microdasys (Lehm.) Pfeiff Flowers in Different Stages of Maturity. J. Funct. Foods. 2014, 9, 27–37. [Google Scholar] [CrossRef]
  60. Chahdoura, H.; Barreira, J.C.M.; Barros, L.; Santos-Buelga, C.; Ferreira, I.C.F.R.; Achour, L. Seeds of Opuntia spp. as a Novel High Potential by-Product: Phytochemical Characterization and Antioxidant Activity. Ind Crops Prod. 2015, 65, 383–389. [Google Scholar] [CrossRef] [Green Version]
  61. Anwar, M.M.; Sallam, E.M. Utilization of Prickly Pear Peels to Improve Quality of Pan Bread. Arab. J. Nucl. Sci. Appl. 2016, 49, 151–163. [Google Scholar]
  62. Cruz-Bravo, R.K.; Guzmán-Maldonado, S.H.; Araiza-Herrera, H.A.; Zegbe, J.A. Storage Alters Physicochemical Characteristics, Bioactive Compounds and Antioxidant Capacity of Cactus Pear Fruit. Postharvest Biol. Technol. 2019, 150, 105–111. [Google Scholar] [CrossRef]
  63. Gómez-López, I.; Lobo-Rodrigo, G.; Portillo, M.P.; Cano, M.P. Characterization, Stability, and Bioaccessibility of Betalain and Phenolic Compounds from Opuntia stricta var dillenii Fruits and Products of Their Industrialization. Foods 2021, 10, 1593. [Google Scholar] [CrossRef]
  64. Chougui, N.; Tamendjari, A.; Hamidj, W.; Hallal, S.; Barras, A.; Richard, T.; Larbat, R. Oil Composition and Characterisation of Phenolic Compounds of Opuntia ficus-indica Seeds. Food Chem. 2013, 139, 796–803. [Google Scholar] [CrossRef]
  65. Ammar, I.; Ben Salem, M.; Harrabi, B.; Mzid, M.; Bardaa, S.; Sahnoun, Z.; Attia, H.; Ennouri, M. Anti-Inflammatory Activity and Phenolic Composition of Prickly Pear (Opuntia ficus-indica) Flowers. Ind. Crops Prod. 2018, 112, 313–319. [Google Scholar] [CrossRef]
  66. Geronikaki, A.A.; Gavalas, A.M. Antioxidants and Inflammatory Disease: Synthetic and Natural Antioxidants with Anti-Inflammatory Activity. Comb. Chem. High Throughput Screen 2006, 9, 425–442. [Google Scholar] [CrossRef]
  67. Linus, L.O.; Hanson, C.; Alolga, R.N.; Zhou, W.; Qi, L. Targeting the Key Factors of Inflammation in Cancer: Plant Intervention. Int. J. Clin. Exp. Med. 2017, 10, 15834–15865. [Google Scholar]
  68. Yahfoufi, N.; Alsadi, N.; Jambi, M.; Matar, C. The Immunomodulatory and Anti-Inflammatory Role of Polyphenols. Nutrients 2018, 10, 1618. [Google Scholar] [CrossRef] [Green Version]
  69. Jones, S.L.; Blikslager, A. The Future of Anti-inflammatory Therapy. Vet. Clin. N. Am. 2001, 17, 245–262. [Google Scholar]
  70. Joseph, S.V.; Edirisinghe, I.; Burton-Freeman, B.M. Berries: Anti-Inflammatory Effects in Humans. J. Agric. Food Chem. 2014, 62, 3886–3903. [Google Scholar] [CrossRef] [PubMed]
  71. Lawrence, T. The Nuclear Factor NF-κB Pathway in Inflammation. Cold Spring Harb. Perspect. Biol. 2009, 1, a001651. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  72. Hoesel, B.; Schmid, J.A. The Complexity of NF-κB Signaling in Inflammation and Cancer. Mol. Cancer 2013, 12, 86. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Liu, T.; Zhang, L.; Joo, D.; Sun, S.-C. NF-κB Signaling in Inflammation. Signal Transduct. Target Ther. 2017, 2, 17023. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Li, C.; Chen, R.; Jiang, C.; Chen, L.; Cheng, Z. Correlation of LOX-5 and COX-2 Expression with Inflammatory Pathology and Clinical Features of Adenomyosis. Mol. Med. Rep. 2019, 19, 727–733. [Google Scholar] [CrossRef] [Green Version]
  75. Wang, B.; Wu, L.; Chen, J.; Dong, L.; Chen, C.; Wen, Z.; Hu, J.; Fleming, I.; Wang, D.W. Metabolism Pathways of Arachidonic Acids: Mechanisms and Potential Therapeutic Targets. Sig. Transduct. Target Ther. 2021, 6, 1–30. [Google Scholar] [CrossRef]
  76. Cuzzo, B.; Lappin, S.L. Physiology, leukotrienes. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022. [Google Scholar]
  77. Ahmed, M.S.; El Tanbouly, N.D.; Islam, W.T.; Sleem, A.A.; El Senousy, A.S. Antiinflammatory Flavonoids from Opuntia dillenii (Ker-Gawl) Haw. Flowers Growing in Egypt. Phytother. Res. 2005, 19, 807–809. [Google Scholar] [CrossRef]
  78. Cho, J.Y.; Park, S.C.; Kim, T.W.; Kim, K.S.; Song, J.-C.; Kim, S.K.; Lee, H.M.; Sung, H.J.; Park, H.J.; Song, Y.B.; et al. Radical Scavenging and Anti-Inflammatory Activity of Extracts from Opuntia humifusa Raf. J. Pharm. Pharmacol. 2006, 58, 113–119. [Google Scholar] [CrossRef]
  79. Chauhan, S.P.; Sheth, N.R.; Suhagia, B.N. Analgesic and Anti-Inflammatory Action of Opuntia elatior Mill Fruits. J. Ayurveda Integr. Med. 2015, 6, 75–81. [Google Scholar] [CrossRef] [Green Version]
  80. Benattia, F.K.; Arrar, Z.; Khabbal, Y. Evaluation of the Anti-Inflammatory Activity of the Seeds Extracts of Prickly Pear (Opuntia ficus-indica L.). Der Pharma Chem. 2017, 9, 14–17. [Google Scholar]
  81. Izuegbuna, O.; Otunola, G.; Bradley, G. Chemical Composition, Antioxidant, Anti-Inflammatory, and Cytotoxic Activities of Opuntia stricta Cladodes. PLoS ONE 2019, 14, e0209682. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  82. Matias, A.; Nunes, S.L.; Poejo, J.; Mecha, E.; Serra, A.T.; Madeira, P.J.A.; Bronze, M.R.; Duarte, C.M.M. Antioxidant and Anti-Inflammatory Activity of a Flavonoid-Rich Concentrate Recovered from Opuntia ficus-indica Juice. Food Funct. 2014, 5, 3269–3280. [Google Scholar] [CrossRef] [PubMed]
  83. Antunes-Ricardo, M.; Gutiérrez-Uribe, J.A.; López-Pacheco, F.; Alvarez, M.M.; Serna-Saldívar, S.O. In Vivo Anti-Inflammatory Effects of Isorhamnetin Glycosides Isolated from Opuntia ficus-indica (L.) Mill Cladodes. Ind. Crops Prod. 2015, 76, 803–808. [Google Scholar] [CrossRef]
  84. Gómez-Maqueo, A.; García-Cayuela, T.; Fernández-López, R.; Welti-Chanes, J.; Cano, M.P. Inhibitory Potential of Prickly Pears and Their Isolated Bioactives against Digestive Enzymes Linked to Type 2 Diabetes and Inflammatory Response. J. Sci. Food Agric. 2019, 99, 6380–6391. [Google Scholar] [CrossRef]
  85. Sharma, J.N.; Al-Omran, A.; Parvathy, S.S. Role of Nitric Oxide in Inflammatory Diseases. Inflammopharmacology 2007, 15, 252–259. [Google Scholar] [CrossRef] [PubMed]
  86. McCook, J.P.; Dorogi, P.L.; Vasily, D.B.; Cefalo, D.R. In Vitro Inhibition of Hyaluronidase by Sodium Copper Chlorophyllin Complex and Chlorophyllin Analogs. Clin. Cosmet. Investig. Dermatol. 2015, 8, 443. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  87. Bralley, E.; Greenspan, P.; Hargrove, J.L.; Hartle, D.K. Inhibition of Hyaluronidase Activity by Vitis rotundifolia. (Muscadine) Berry Seeds and Skins. Pharm. Biol. 2007, 45, 667–673. [Google Scholar] [CrossRef]
  88. González-Peña, D.; Colina-Coca, C.; Char, C.D.; Cano, M.P.; de Ancos, B.; Sánchez-Moreno, C. Hyaluronidase Inhibiting Activity and Radical Scavenging Potential of Flavonols in Processed Onion. J. Agric. Food Chem. 2013, 61, 4862–4872. [Google Scholar] [CrossRef]
  89. Gómez-Maqueo, A.; García-Cayuela, T.; Welti-Chanes, J.; Cano, M.P. Enhancement of Anti-Inflammatory and Antioxidant Activities of Prickly Pear Fruits by High Hydrostatic Pressure: A Chemical and Microstructural Approach. Innov. Food Sci. Emerg. Technol. 2019, 54, 132–142. [Google Scholar] [CrossRef]
  90. Chaalal, M.; Gavilán, E.; Louaileche, H.; Ruano, D.; Parrado, J.; Castaño, A. Anti-Inflammatory Activity of Phenolic Extracts from Different Parts of Prickly Pear on Lipopolysaccharide-Stimulated N13 Microglial Cells. Int. J. Phytomed. 2016, 7, 411–419. [Google Scholar]
  91. Yeo, J.Y.; Hwang, K.W.; Park, S.-Y. Anti-Inflammatory Effect of Neo-Lignan Isoamericanin A via Suppression of NF-κB in Liposaccharide-Stimulated RAW 264.7 Cells. Trop. J. Pharm. Res. 2020, 19, 1857–1862. [Google Scholar] [CrossRef]
  92. Filannino, P.; Cavoski, I.; Thlien, N.; Vincentini, O.; Angelis, M.D.; Silano, M.; Gobbetti, M.; Cagno, R.D. Lactic Acid Fermentation of Cactus Cladodes (Opuntia ficus-indica L.) Generates Flavonoid Derivatives with Antioxidant and Anti-Inflammatory Properties. PLoS ONE 2016, 11, e0152575. [Google Scholar] [CrossRef] [Green Version]
Molecules 27 04763 g001 550
Figure 1. Taxonomic classification of Opuntia species (photograph from the author (W.Z.): wild Opuntia sp., Bejaia, Algeria).
Figure 1. Taxonomic classification of Opuntia species (photograph from the author (W.Z.): wild Opuntia sp., Bejaia, Algeria).
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Molecules 27 04763 g002 550
Figure 2. Representation of the emblem of Tenochtitlan from the Codex Mendoza, with the prickly pear as the center of the universe. Photo: © Bodleian Libraries, University of Oxford; Shelfmark: Bodleian Library MS. Arch. Selden. A. 1; Holding Institution: Bodleian Libraries, University of Oxford; Terms of use: CC-BY-NC 4.0.
Figure 2. Representation of the emblem of Tenochtitlan from the Codex Mendoza, with the prickly pear as the center of the universe. Photo: © Bodleian Libraries, University of Oxford; Shelfmark: Bodleian Library MS. Arch. Selden. A. 1; Holding Institution: Bodleian Libraries, University of Oxford; Terms of use: CC-BY-NC 4.0.
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Figure 3. Basic structures of flavonoids (a) and phenolic acids (b).
Figure 3. Basic structures of flavonoids (a) and phenolic acids (b).
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Figure 4. The implication of NF-κB signaling pathway in inflammation. The inflammatory stimulation of a cell may lead to IKK phosphorylation and activation which, in turn, may lead to the phosphorylation of the IκB/NF-κB complex retained in the cytoplasm. The IκB is degraded by the proteasome, while the NF-κB transcription factor can enter into the nucleus and bind DNA to initiate the transcription of some targeted genes implicated in the inflammatory response.
Figure 4. The implication of NF-κB signaling pathway in inflammation. The inflammatory stimulation of a cell may lead to IKK phosphorylation and activation which, in turn, may lead to the phosphorylation of the IκB/NF-κB complex retained in the cytoplasm. The IκB is degraded by the proteasome, while the NF-κB transcription factor can enter into the nucleus and bind DNA to initiate the transcription of some targeted genes implicated in the inflammatory response.
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Table
Table 1. Phenolic compounds reported in the different vegetative parts of the genus Opuntia 1.
Table 1. Phenolic compounds reported in the different vegetative parts of the genus Opuntia 1.
Phenolic CompoundsPlant TissueConcentration (µg/g)Opuntia SpeciesReferences
Flavonoids
Flavones
ApigeninSeeds
Cladodes
Flowers		NS
0.19–0.65
NS		O. stricta
O. ficus-indica
O. hyptiacantha
O. streptacantha
O. megacantha
O. albicarpa		[38,42,43,44]
LuteolinPulp
Peel		NS
NS		O. ficus-barbarica
O. robusta		[45]
Flavonols
MyricetinSeeds
Pulp
Peel
Cladodes		198.19–428.14
NS
NS
8.52		O. ficus-indica
O. ficus-barbarica
O. robusta		[45,46,47]
RutinSeeds
Pulp
Peel
Cladodes		8.00–100.00
9.70–12.50
65.70–103.40
2.11–4.95		O. ficus-indica
O. ficus-barbarica
O. hyptiacantha
O. streptacantha
O. megacantha
O. albicarpa		[42,44,45,48,49]
Quercetin and derivatesSeeds
Pulp
Peel
Cladodes
Flowers		4.37–18.77
84.20–599.20
715.70–1316.20
8.97–75.13
NS		O. ficus-indica
O. ficus-barbarica
O. robusta
O. engelmannii
O. streptacantha
O. hyptiacantha
O. megacantha
O. albicarpa		[12,38,42,44,45,47,49,50,51,52,53,54,55,56,57,58]
Kaempferol and derivatesPulp
Peel
Cladodes
Flowers		207.10–529.10
52.90–675.50
72.97–241.68
321.00–708.00		O. ficus-indica
O. engelmannii
O. streptacantha
O. hyptiacantha
O. megacantha
O. albicarpa
O. microdasys		[38,47,48,49,50,52,53,54,55,57,59]
Isorhamnetin and derivatesSeeds
Pulp
Peel
Cladodes
Flowers		67.14–288.58
29.30–58.40
1484.70–2213.70
1250.00–4140.00
NS		O. ficus-indica
O. microdasys
O. stricta
O. streptacantha
O. hyptiacantha
O. megacantha
O. albicarpa		[12,19,38,44,46,47,48,50,51,52,53,54,55,56,57,59,60]
Flavanones
NaringeninPulp
Peel		210.00
20.00–180.00		O. ficus-indica
O. ficus-barbarica
O. robusta		[45,56]
Flavanols
CatechinSeeds
Pulp
Peel
Cladodes
Flowers		NS
14.44–27.89
NS
180.00
NS		O. stricta
O. ficus-indica
O. megacantha
O. streptacantha
O. robusta		[17,38,43,49,52,54,61]
EpicatechinSeeds
Pulp
Peel		NS
19.16–90.81
NS		O. ficus-indica
O. albicarpa
O. megacantha
O. streptacantha
O. robusta		[17,42,61]
GallocatechinSeeds
Pulp
Peel		NS
116.60–178.20
120.40–334.70		O. stricta
O. ficus-indica		[43,49]
EpigallocatechinSeedsNSO. stricta
O. ficus-indica		[42,43]
Anthocyanidins
PelargonidinSeeds
Cladodes		NS
187.97		O. stricta
O. ficus-indica		[43,47]
CyanidinSeeds
Cladodes		NS
1058.57		O. stricta
O. ficus-indica		[43,47]
DelphinidinCladodes2.81O. ficus-indica[47]
PetunidinCladodes186.55O. ficus-indica[47]
MalvidinCladodes4.31O. ficus-indica[47]
Phenolic Acids
Gallic acid and derivatesSeeds
Pulp
Peel
Cladodes
Flowers		NS
32.60–81.20
NS
20.53–38.96
NS		O. ficus-indica
O. stricta
O. ficus-barbarica
O. robusta
O. albicarpa
O. megacantha
O. streptacantha
O. hyptiacantha		[17,42,43,44,45,49,54,61,62,63]
Ferulic acid and derivatesSeeds
Pulp
Peel
Cladodes
Flowers		96.33–1366.24
80.00
150.00–390.00
130.00–370.00
291.00–786.00		O. ficus-indica
O. stricta
O. ficus-barbarica
O. microdasys
O. hyptiacantha
O. streptacantha
O. megacantha
O. albicarpa		[12,43,44,45,46,48,49,51,52,55,56,59,61,64]
Caffeic acid and derivatesSeeds
Pulp
Peels
Cladodes
Flowers		NS
NS
NS
NS
255.00–469.00		O. ficus-indica
O. ficus-barbarica
O. robusta
O. microdasys
O. hyptiacantha
O. streptacantha
O. megacantha
O. albicarpa		[12,38,42,44,45,48,49,51,54,59,61]
Sinapic acidSeeds
Pulp
Peel
Cladodes		NS
100.00–4100.00
820.00–2350.00
40.00–750.00		O. stricta
O. ficus-indica		[43,49,56]
p-Coumaric acidSeeds
Pulp
Peel
Cladodes
Flowers		NS
NS
NS
20.91
65.00–178.00		O. ficus-indica
O. ficus-barbarica
O. robusta
O. microdasys
O. hyptiacantha
O. streptacantha
O. megacantha
O. albicarpa		[42,44,45,48,49,52,59]
Hydroxycinnamic acidCladodes8.45–1248.24O. ficus-indica
O. hyptiacantha
O. streptacantha
O. megacantha
O. albicarpa		[44,47]
Chlorogenic acidSeeds
Cladodes		885.31–1148.41
5.00–26.49		O. ficus-indica
O. streptacantha
O. hyptiacantha
O. megacantha
O. albicarpa		[42,44,46,50,52]
Ellagic acidSeeds
Pulp
Peel		73.74–74.38
25.00–73.20
NS		O. ficus-indica
O. megacantha
O. streptacantha
O. robusta
O. ficus-indica		[17,46,61]
Vanillic acidSeeds
Pulp
Peel
Cladodes
Flowers		NS
NS
NS
0.11–24.30
NS		O. stricta
O. ficus-barbarica
O. robusta
O. ficus-indica
O. hyptiacantha
O. streptacantha
O. megacantha
O. albicarpa		[43,44,45,49,54,61]
Syringic acidSeeds
Pulp
Peel
Cladodes
Flowers		NS
13.60–66.50
NS
2.34–13.99
NS		O. ficus-indica
O. robusta
O. albicarpa
O. megacantha
O. streptacantha
O. hyptiacantha
O. stricta		[12,17,42,43,44,45,54,61]
Protocatechuic acidSeeds
Pulp
Peel		4.57–22.36
NS
NS		O. ficus-indica
O. ficus-barbarica
O. robusta
O. stricta		[45,46,49,58,61,62,63]
Hydroxybenzoic acidPulp
Peel
Cladodes		200.90–816.80
964.00–1718.20
114.01		O. ficus-indica
O. hyptiacantha
O. streptacantha
O. megacantha
O. albicarpa		[44,47,49,57,62]
Piscidic acidSeeds
Pulp
Peel
Cladodes		NS
NS
NS
NS		O. ficus-indica
O. stricta		[48,51,53,55,57,58,63]
Eucomic acidSeeds
Pulp
Peel
Cladodes		NS
NS
NS
NS		O. ficus-indica
O. streptacantha
O. hyptiacantha
O. megacantha
O. albicarpa
O. stricta		[48,50,51,53,55,58,63]
Gentisic acidPulp
Peel		NS
NS		O. ficus-barbarica
O. robusta		[45]
Rosmarinic acidPeel
Flowers		NS
NS		O. ficus-indica[49,54]
CatecholSeeds
Pulp
Peel		NS
NS
NS		O. stricta
O. ficus-barbarica
O. robusta
O. ficus-indica		[43,45,61]
Other Phenolics
Phloretin
Psoralen
Pinoresinol		SeedsNSO. stricta[43]
1 NS, not specified.
Table
Table 2. Anti-inflammatory potential and mechanism of action of phenolic compounds extracted from Opuntia species 1.
Table 2. Anti-inflammatory potential and mechanism of action of phenolic compounds extracted from Opuntia species 1.
Species (Tissue) Compounds Dose Model Mechanism of Action Ref.
In Vitro Studies Opuntia ficus-indica
(seeds, pulp, fruits) 		Phenolic compounds from crude extracts 10 mg/mL LPS-stimulated murine
N13 microglial cells
-
Downregulation of TNF-α, IL-1β, and iNOS expression
[90]
Opuntia humifusa
(cladodes) 		Phenolic compound
from crude extracts 		0.05/0.1
mg/mL 		LPS-stimulated
Macrophages’ RAW 264.7
-
↓ NO production
-
Downregulation of iNOS, IL-1β, and IL-6 genes’ expression
[78]
Opuntia humifusa
(seeds) 		Isoamericanin A 1.0–4.0
µg/mL 		LPS-stimulated
Macrophages’ RAW 264.7
-
↓ TNF-α, IL-6, and iNOS expression levels
-
↓ NF-Κb levels in the nucleus by inhibition of IκB phosphorylation
[91]
Opuntia ficus-indica
(cladodes) 		Crude extract 10 mg/mL Human intestinal
Caco-2/TC7 cells
-
↓ NO, TNF-α, and IL-8 production
-
Intracellular reduction in reactive species
-
↓ Prostaglandin synthesis
[92]
Opuntia ficus-indica
(fruits) 		Polyphenols from
crude extract 		0.05 mg/mL Human colon
carcinoma Caco-2 cells
-
↓ H2O2-induced reactive species
-
Prevention of H2O2–induced protein oxidation
-
Cell protection from barrier dysfunction
-
↓ NO, TNF-α, and IL-8 secretion
-
↓ IκBα depletion
[82]
In Vivo Studies Opuntia dillenii
(stems, flowers, fruits) 		Kaempferol 3-O-α-arabinoside
Isorhamnetin-3-O-β-d-glucopyranoside
Isorhamnetin-3-O-β-d-rutinoside		 50 mg/kg
BW 		Carrageenan-induced
paw edema in Albino rats
-
↓ Edema formation
[77]
Opuntia ficus-indica
(flowers) 		Phenolic compounds from crude extract 400 mg/kg
BW 		Carrageenan-induced
paw edema in Wistar rats
-
↓ Edema formation
-
↓ Amount of immune cells
-
Neutralization of lipid peroxidation induced by reactive species
-
↑ CAT, SOD, and GSH activities
[65]
Opuntia ficus-indica
(cladodes) 		Isorhamnetin-3-O-
glucosyl-rhamnoside
Isorhamnetin-3-O-
glucosyl-rhamnosyl-rhamnoside 		5 mg/kg
BW 		Carrageenan-induced
air-pouch inflammation
in Wistar rats
-
↓ Edema formation
-
↓ Total leukocytes’ amount
-
Inhibition of COX-2 activity
-
↓ NO, TNF-α, and IL-6 production
[83]
1 BW, body weight; CAT, catalase; COX, cyclooxygenase; GSH, glutathione; H2O2, hydrogen peroxide; IL, interleukin; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; NO, nitric oxide; SOD, superoxide dismutase; TNF, tumor necrosis factor.
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Zeghbib, W.; Boudjouan, F.; Vasconcelos, V.; Lopes, G. Phenolic Compounds’ Occurrence in Opuntia Species and Their Role in the Inflammatory Process: A Review. Molecules 2022, 27, 4763. https://doi.org/10.3390/molecules27154763

AMA Style

Zeghbib W, Boudjouan F, Vasconcelos V, Lopes G. Phenolic Compounds’ Occurrence in Opuntia Species and Their Role in the Inflammatory Process: A Review. Molecules. 2022; 27(15):4763. https://doi.org/10.3390/molecules27154763

Chicago/Turabian Style

Zeghbib, Walid, Fares Boudjouan, Vitor Vasconcelos, and Graciliana Lopes. 2022. "Phenolic Compounds’ Occurrence in Opuntia Species and Their Role in the Inflammatory Process: A Review" Molecules 27, no. 15: 4763. https://doi.org/10.3390/molecules27154763

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