Mairá-Potato (Casimirella sp.): Botanical, Food, Pharmacological, and Phytochemical Aspects

Millions of people in the world live in food insecurity, so identifying a tuber with characteristics capable of meeting the demand for food and also identifying active compounds that can be used to minimize harm to human health is of great value. The aim was to carry out a review based on systematic review tools and the main objective was to seek information on botanical, food, pharmacological, and phytochemical aspects of Casimirella sp. and propose possible applications. This review showed papers that addressed botanical, food, pharmacological, and phytochemical aspects of the Mairá-potato and presented suggestions for using this tuber allied to the information described in the works found in the Google Academic, Scielo, Science Direct, Scopus, PubMed, and Web of Science databases. This review synthesized knowledge about the Mairá-potato that can contribute to the direction of further research on the suggested technological applications, both on the use of this tuber as a polymeric material and its use as biomaterial, encapsulation, bioactive use, and 3D printing, because this work collected information about this non-conventional food plant (PANC) that shows great potential for use in various areas of study.


Introduction
One person out of nine does not have enough food for a healthy life. Around 805 million people worldwide are food insecure according to the Food and Agriculture Organization of the United Nations (FAO). This insecurity is due to the poorer classes being unable to obtain enough food to meet an adequate diet [1]. But, in 2022, the FAO reported that in 2021 about 828 million people in the world, approximately 10.5% of the world's population, faced hunger and estimated that by 2030 almost 670 million people are expected to remain undernourished [2]. The discussion around the inability to meet human food demand is increasingly present due to population projections that indicate increased consumption, growth of cities, and restrictions on land exploitation [3].
Root and tuber crops are tropical countries' second largest cultivated species after cereals. They occupy a privileged position in food security because of their high carbohydrate content and calorific value [4]. They can contain various medicinally important bioactive principles found in different parts such as tubers, stems, and leaves; furthermore, tubers serve as different carbohydrate depots [5].
Identifying a plant with constituents that promote health benefits is of great interest. Foods of plant origin have a wide variety of non-nutritive phytochemical compounds. They are synthesized as secondary metabolites and serve various ecological functions in plants [6]. Tubers are significant sources of several compounds, such as saponins, Table 1. Systematization of the 19 papers on food, botanical, pharmacological, and phytochemical aspects of Casimirella sp. resulting from searches in the Google Academic, Scielo, Science Direct, Scopus, PubMed, and Web of Science databases.

No Title
Principal Findings Publication Ref.

Acta
Amazonica [14] 03 The presence of toxic inorganic substances in the genus Humirianthera (Icacinaceae) The isolation of thiocyanate crystals, sodium and potassium nitrate, and nitrite in the tuber and stem of Humirianthera ampla has been reported. The nitrate and nitrite contents in the leaves of H. ampla and H. rupestris at young and adult ages were also determined. The entire contents of N-NO 3 observed for H. ampla and H. rupestris were 8.83 mg % and 6.42 mg %.

04
Seasonal variation of macro-and microelements in the genus Humirianthera (Icacinaceae) as a function of age Twenty-six specimens of H. ampla and nine of H. rupestris at young and adult ages collected during the dry and rainy seasons were analyzed for the total content of N, F, K, Ca, Mg, Mo, Cu, Zn, Mn, Fe, B, Al, Co, Cr, Na, Pb, Si, and Sr in the different vegetative parts of the plants. The concentration of macro-elements in the leaves, stems, and tubers of H. ampla and H. rupestris obeys the relationship N > Ca > Mg > F > K. The average concentration of these elements indicates no significant variability in the organs analyzed nor in relation to the ages, except for N, which presents a higher content in the leaves and in relation to the other elements. The micro-elements are uniformly distributed in the various organs, with Fe, Al, and Na having the highest concentration.

Revista
Brasileira de Farmacog nosia [20] 09 Antitumour screening of Brazilian plants Organic and aqueous extracts of 145 Brazilian plants (538) from 34 families were evaluated for antitumor activity against the human tumor cell lines HT29 and NCIH460. Of the extracts tested, 117 (22%) demonstrated cytotoxicity against one or both cell lines at a 100 mg/mL concentration. These results also confirm the continuing importance of natural product screening models, alongside targeted drug development, in discovering new anti-neoplastic pharmacophores.

Pharmaceutical
Biology [21] 10 The acetyl derivative of humirianthol The title compound, 15alpha-acetate-3beta,20:14beta,16-diepoxy-3alpha-hydroxy-9-epi-7pimaren-19,6beta-olide, C22H28O7, formed from the acetylation of humirianthol, isolated from the tubers of Humirianthera ampla, crystallized in the chiral space group P2(1)2(1)2(1). The structure comprised a pimarane ring system with a methylene ether bridge over ring A, a double bond in ring B, and two five-membered furanyl rings, one fused to rings A and B and the other to ring C. The absolute configuration was set using the absolute configuration of C15, as determined by the Horeau method.
The phytochemical investigation of the roots of Humiranthera ampla (Icacinaceae) resulted in the isolation and identification of a mixture of beta-sitosterol and stigmasterol, annonalide, lupeol, and the 3-beta-O-beta-D-glucopyranosyl sitosterol. The structures of these compounds were established by spectrometric analysis (IR, MS, NMR 1H, and 13C), including bidimensional NRM techniques (COSY, HMQC, HMBC, and NOESY) and for comparison with data described in the literature. All extracts were tested using the Ellman assay. Only ethyl acetate extracts and their fractions showed acetylcholinesterase inhibition. The ethanolic extract was the most active. The ethyl acetate extract showed xanthine oxidase inhibition.
Dissertation [26] 15 Anti-nociceptive action of ethanolic extract obtained from roots of Humirianthera ampla Miers The anti-nociceptive actions of ethanolic extract (EE) of roots of Humirianthera ampla in chemical and thermal models of pain in mice were investigated. Oral treatment with ethanolic extract inhibited, in a dose-dependent manner, glutamate-, capsaicin-and formalin-induced licking. However, it did not prevent nociception caused by radiant heat in the tail jerking test. The ethanolic extract (30 mg/kg) caused marked inhibition of the nociceptive bite response induced by glutamate, (±) -1-aminocyclopentane-trans -1,3-dicarboxylic acid (trans-ACPD), N-methyl-d-aspartate (NMDA), and substance P. The anti-nociception caused by the ethanolic extract was significantly attenuated by naloxone, L-arginine, WAY100635, ondansetron, or ketanserin, but not by caffeine or naloxone methiodide. The ethanolic extract of Humirianthera ampla roots produced anti-nociception against neurogenic and inflammatory models of nociception.
Journal of ethnopharmacology [27] 16 Anti-ophidic activity of the extract of the Amazon plant Humirianthera ampla and constituents Although serotherapy against snakebites was discovered more than one hundred years ago, anti-venom is not available all over Brazil. The use of plants from folk medicine is common mainly in the Brazilian Amazon area. One of these plants is named Humirianthera ampla (HA).
Journal of ethnopharmacology [28] 17 Annonalide and derivatives: semi-synthesis, cytotoxic activities, and studies on interaction of annonalide with DNA The cytotoxic activity of the pimarane diterpene annonalide (1) and nine of its semisynthetic derivatives (2-10) was investigated against the human tumor cell lines HL-60 (leukemia), PC-3 (prostate adenocarcinoma), HepG2 (hepatocellular carcinoma), SF-295 (glioblastoma), and HCT-116 (colon cancer) and normal mouse fibroblast (L929) cells. The preparation of 2-10 involved derivatization of the side chain of 1 at C-13. Except for 2, all derivatives were reported for the first time. Most of the tested compounds presented IC50s below 4.0 µM, being considered potential anti-tumor agents. The interaction of annonalide (1) with ctDNA was evaluated using spectroscopic techniques; the formation of a supramolecular complex with the macromolecule was confirmed. Competition assays with fluorescent probes (Hoechst and ethidium bromide) and theoretical studies confirmed that 1 interacted preferentially via DNA intercalation with stoichiometric ratio of 1:1 (1:ctDNA).

Origin and Distribution of the Mairá-Potato
The Mairá-potato belongs to a genus known as Neotropical because of its distribution in South and Central America; it is composed of seven species [18]. These species' distribution and endemic occurrence in the Brazilian Amazon Forest (in the Amazonas and Pará) has been recorded [18,31]. Two species have been found in the Amazon Forest (Casimirella ampla and Casimirella rupestris), while the others are restricted to Brazil in the Cerrado and Pantanal [31]. According to Howard [18] and Amorim [31], four species occur in Brazilian territory.
The genus Humirianthera comprises only two feculent species [32], H. ampla (Miers) Baehni and H. rupestris Ducke, which are easily distinguished from all other species of the Icacinaceae family by having an enormously enlarged connective, which resembles the tip of a spear, extends like a limb in the shape of a triangle, and has at the base two wing-like anther sacs [33]. Howard [18] cited that the genus Humirianthera is accepted as a synonym of Casimirella, which will be adopted henceforth.

Taxonomic Classification and Botanical Characterisation of the Mairá-Potato
According to the Global Biodiversity Information Facility (GBIF) [34], the taxonomy of the Mairá-potato follows the classification described in Table 2. Common name Mairá-potato Source: [34].

Food Use of the Mairá-Potato
The Mairá-potato was collected and identified by the British naturalist Richard Spruce during his trip to the Amazon in 1849. He found it among the Tapuyas indigenous peoples who lived on the Janauari River on the lower Negro River. According to Spruce (1851), they knew it by the name maniaca-açu ("big cassava") and used it in the same way as cassava, obtaining flour and tapioca from it. The botanist also noted that the plant was first used by the Purupuru indigenous peoples who lived on the Purus River [38].
The fruits, roots, and tubers were used to produce gum, which, according to the Arawa language, was used as biha (or bija), which designates tuberous plants, roots, and tubers translated as wild tubers of terra firme corroborating with the information provided by the botanist Richard Spruce regarding Casimirella rupestris being compatible with information regarding the bija of the Suruwaha. The Mairá-potato occurs in sloping forests and capoeira on sandy and clay soils. In dry land environments, this plant produces a sizeable tuberous plant that can reach a mass of more than 200 kg, from which native peoples extract the starch for the production of grolado and beiju [12].
Tubers are considered significant food sources for Amazonian gathering groups that also practice the cultivation of some plant species. In 1948, the ethnologist Paul Ehrenreich observed that an indigenous group called Paumari from the Purus basin exploited a large native tuber-the Mairá-potato (Casimirella rupestris)-from which they extracted the starch for the production of flour [39]. Historically, travelers recorded the presence of the Mairápotato in several Amazonian rivers used by indigenous groups to produce gum [12].
The plant species of this genus have starchy tubers and are edible (after successive washing with water as they contain toxic substances) [40]. Rizzini and Mors [11] stated that C. ampla and C. rupestris are starchy sources used for food, that these plant species are popularly known as the Mairá-potato, and that they can reach weights over 100 kg.
In the work of Leitão-Barboza et al. [41], it was reported that the Katukina indigenous peoples still have several specimens of Casimirella sp. in their gardens. However, despite having consumed this tuber for a long time, they currently opt for cassava flour; the Indians consider cassava more productive and it requires less work to process.
Ribeiro [8] carried out an ethnobotanical study of Casimirella rupestris. Firstly, he surveyed the indigenous peoples of the Paumari, Apurinã, Jamamadi, and Jarawara ethnic groups located in the region of the middle Purus/Amazonas/Brazil. All the ethnic groups reported the use of the tuber as food, with a similar technique for extracting the starch contained in the tuber with rudimentary techniques. They grated it on thorny roots and squeezed in tipiti, an instrument formed by vegetable fibers in which all the material is compressed and the liquid residue is expelled. The study showed that the Paumari indigenous peoples have several specimens of Casimirella ampla in their lands. However, several of the indigenous people who lived there reported that they did not know the species.
Ribeiro [8] evaluated various parameters of interest for food use such as, starch yield ranging from 5.7 to 15.7%; starch yield around 84.31%; amylose content 38.17%; starch morphology, which showed predominant granules in circular, oval, and ellipsoid shapes with an average diameter of 24.48 µm; swelling power at temperatures of 65, 75, 85, and 95 • C was low, being 3.13, 17.71, 21.58, and 24.67 g of water/g of starch, respectively; solubility was low at the same temperatures, being 2.77, 14.53, 14.85 and 16.36%, respectively; paste properties (peak viscosity 256 RVU-rapid viscosity analyzer unit, breakdown 125 RVU, final viscosity 207 RVU, retrogradation tendency 76 RVU, paste temperature 76.4, and peak time 7.4 min); thermal properties (initial temperature 65.51 • C, peak 69.99 • C, and conclusion 75.93 • C; enthalpy variation 17.13 J/g; temperature variation 10.42 • C. In the toxicity test, it was possible to detect toxicity in the samples that went through up to five washes; after the sixth wash of the extracts, toxicity was not detected. This study evidenced the high concentration of starch and amylose, demonstrating this tuber's technological and functional potentiality with respect to toxicity studies. In work by dos Santos et al. [42], the diagnosis of starch grains from bread found in the southern region of the Amazonas state was performed. In the publication, the authors surveyed several findings of "Indian bread" (as they called the material) and it was possible to identify the presence of the Mairá-potato. Traces of mechanical impact related to Casimirella sp. grains were observed, suggesting its processing in grinders or graters. However, due to such a high quantity of transitory starches, the authors inferred that they could be from various plant parts, such as the leaves. For example, Watling et al. [43] stated that there were several records of bread being wrapped in leaves of different species before being buried; still, dos Santos et al. [42] indicated this process.

Pharmacological Properties of the Mairá-Potato
Empirically, Amazonian communities usually use Casimirella ampla extract as an antiophidic and even administer therapeutic preparations of this tuber orally [20]. Some authors have claimed that plants of the genus Casimirella possess chemical compounds that work against snake venom [44] and have an anti-inflammatory action [45,46].
Raw ethanolic extract of C. ampla or its isolated constituents were evaluated for possible anti-ophidic activity in the study of Strauch [28]. The experiments showed a concentration dependent inhibition of Bothrops atrox, Bothrops jararaca, and Bothrops jararacussu venoms by Humirianthera ampla extract and inhibition of Bothrops jararacussu and Bothrops atrox by sitosterol and lupeol, respectively. These data suggested that the decrease in myotoxicity of Bothrops venoms is related to the inhibition of phospholipase A2 activity and proteolytic activities of the venom. The study further suggested that some effects in vivo can depend on these enzymatic activities.
Monks et al. [21] conducted studies identifying Brazilian plant species that demonstrated in vitro activity against human tumor cell lines. When they evaluated C. rupestris, they observed cytotoxic activity in one or both cell lines tested. Cytotoxicity was observed when the reduction in SRB absorbance was <10% for HT29 and <5% for NCI-H460 from the control. These values equaled the zero-control absorbance time for each cell line, i.e., the initial cell number.
Boakye et al. [56] showed that lupeol has been shown to inhibit NF-κB and increase FGF-2, TGF-β1, and collagen III levels, followed by negative regulation of IL-6 and subsequent positive regulation of IL-10 levels in a wound healing model in diabetic patients. Saha et al. [57] confirmed the anti-inflammatory activity of lupeol against 7KC in M (IFN-γ/LPS) macrophages by suppression of the inflammasome and activation of autophagy, suggesting further studies of lupeol regarding therapeutic strategies for plaque regression and further detailing of the therapeutic anti-inflammatory effect for future human applications. However, they reinforced previous findings on the immuno-modulatory system effects of lupeol on innate immune cells. They referred to the utility of this triterpene as an adjuvant drug to counteract the proatherogenic signaling of oxysterol within atherosclerotic plaque by activating autophagy and inhibiting pro-inflammatory cytokines.
Sharma et al. [58] stated that lupeol and some analogs were shown to possess several popular and recognized biological activities and, in addition, possessed the potential to be consumed as a nutritional supplement to prevent cancer, inflammation, and coronary and liver diseases. This compound also exhibited low cytotoxicity in healthy cells. It acted synergistically when used in combination therapies, enabling it to be applied alone or as an adjuvant to clinically used anti-neoplastic and anti-inflammatory drugs.
The cytotoxic activity of all compounds was investigated against five tumor cell lines and normal cells. Annonalide and derivatives were the most active compounds when tested against the leukemic cell line HL-60. Nine annonalide derivatives were prepared by the semi-synthesis method. Most compounds showed IC50 of 4.0 µM or less, suggesting their potential as anti-tumor agents. The chemical modifications in the natural product were mainly done on the side chain linked at C-13. The interaction was verified and it can be inferred that annonalide interacts with ctDNA by intercalation. The cytotoxic activity of annonalide against human tumor cell lines may be associated with its interaction with DNA [29].
Jiménez-Escrig et al. [61] established the calculation of the index of dietary sterol status as the ratio of plant sterol/cholesterol, i.e., ((β-sitosterol + stigmasterol)/cholesterol). They evaluated four groups of people (composed of Seventh-Day Adventists; vegetarians; ovo-lacto-vegetarians, and the general population). A ratio ranging from 0.49 to 16 was observed, which the authors attributed to different individual diets. Regarding β-sitosterol, [62] stated that the daily intake of β-sitosterol was about 79.7% of the total phytosterol per person. Furthermore, they stated that β-sitosterol exhibited a protective influence on experimentally induced colon cancer. Moreover, it also possessed anti-cancer, anti-atherosclerosis, anti-inflammatory, and anti-oxidant properties.
Gupta et al. [63] administered β-sitosterol 10, 15, and 20 mg/kg for 21 days to streptozotocin-induced diabetic rats; all doses administered decreased serum glucose, nitric oxide, and glycated hemoglobin and increased serum insulin and pancreatic anti-oxidant levels, with a significant decrease in thiobarbituric acid reactive substances, demonstrating that β-sitosterol is a promising anti-diabetic and anti-oxidant agent.
Shi et al. [64] noted that incorporating β-sitosterol into mitochondria increased mitochondrial inner membrane fluidity without affecting mitochondrial outer membrane fluidity and consequently increased mitochondrial membrane potential (∆Ψm) and mitochondrial ATP content. This effect may be beneficial for neurodegenerative diseases such as Alzheimer's disease. Ayaz et al. [65] also studied the effect of β-sitosterol on neurodegenerative disorders; they observed strong anti-cholinesterase and anti-oxidant potential and double efficiency (inhibition of enzymes and elimination of free radical capacity) and concluded that the use of β-sitosterol can improve cognitive deficits, short-term memory, and locomotor deficits.
Zhao et al. [66] mentioned that natural supplies of Casimirella sp. molecules and derivatives can be further investigated because, unlike other compounds that are formed from stress-induced metabolites with limited amounts such as momilactone, Casimirella rupestris presents high structural diversity and high content, providing opportunities for the discovery of promising compounds, as well as precursors for the semi-synthesis method. In addition, it has the potential for developing herbicidal crops and anti-fungal, anti-bacterial, and anti-tumor agents.

Anti-Parasitic and Anti-Fungal Potential of Mairá-Potato Compounds
The study by Ramos et al. [67] evaluated the in vitro leishmanicidal activity of extracts and substances isolated from Casimirella ampla. It was observed that the ethanolic extract presented results against Leishmania amazonenses and Leishmania braziliensis, the concentration of 50 mg/mL promoted the death of 97.2% of L. braziliensis parasites after 48 h of treatment and 99.2% of inhibition for L. amazonenses parasites.
Gonçalves et al. [68] also studied the in vitro leishmanicidal activity of the extract of C. ampla roots. It was observed that the ethanolic extract at a concentration of 100 µg/mL completely inhibited the growth of Leishmania braziliensis parasites, showing the possibility of application of compounds present in C. ampla as an anti-leishmanial drug.

Phytochemicals Present in Parts of the Mairá-Potato Plant
Some scientists have studied the chemical compounds in the plant species C. ampla and C. rupestris. In the study by Zoghbi et al. [13], C. rupestris tubers were isolated and identified and several secondary metabolites were classified as degraded γ-lactonic diterpenoids, with structures containing between seventeen and nineteen carbon atoms. Afterward, Zoghbi et al. [14], using tubers and stems of C. ampla and C. rupestris, isolated sodium and potassium thiocyanate and sodium and potassium nitrite and nitrate and obtained concentrations of 1 g from the tuber and 2.75 g from the stem, respectively.
The average content of these elements indicated no significant variability dependent on seasonality or physiological age. A study by Varejão et al. [17] evaluated the same organs of the same species, physiological ages, and seasons. They observed that sulfate (SO 4− ) uptake by C. ampla and C. rupestris individually did not depend on seasonality or physiological age. They also noted that sulfur (S) content followed the different relationship between species in the rainy season, regardless of physiological age.
Based on the methodology used by Graebner et al. [19], in which humirianthol and acrenol were isolated and purified from C. ampla, Burrow et al. [22,23] were able to synthesize the compound acetylated humirianthol and subsequently synthesized diacetylated acrenol. In addition, the identification of the compound icacinol was reported, which had not been described in the works surveyed previously for this species.
Adou et al. [25], from ethyl acetate and methanol extracts of C. ampla, isolated the following compounds: humirianthol, annonalide, acrenol, the oxidized compound of annonalide, and icacinol, as well as five other compounds, to which they assigned the nomenclatures humirianthone, 1 hydroxy-humirianthone, 15R-humirianthol 15 R-humirianthol, patogonol, and patogonal. The tubers of C. ampla species were also studied by Marques [26], who isolated and identified mixtures of the steroids β-sitosterol and stigmasterol, annonalide, lupeol, and 3-β-O-β-D-glucopyranose sitosterol. Ribeiro [8] evaluated the mineral content in C. rupestris starch. In addition to other minerals, the author observed contents of 90, 20.9, and 4.1 mg/100 g of calcium (Ca), iron (Fe), and zinc (Zn), respectively. However, according to him, the bioavailability of minerals should be evaluated because little is known about this PANC. Table 4 shows the structural formulas of phytochemical compounds isolated and identified from parts of the Mairá-potato plant.

Toxicity of Mairá-Potato and Indications for Evaluation to Ensure Application as a New Product or Ingredient
There is a scarcity of scientific data systematically compiled on the Mairá-potato, either C. ampla or C. rupestris. Although it has been used as food, little is known about the effect of the consumption of this PANC in the case of habitual consumption, so it is necessary to cite studies on toxicity since the safety of the material for human consumption needs to be ensured regarding the applications that are suggested in this work. This scarcity may be closely related to the little known level of toxicity in this tuber;, the most recent work of Molecules 2023, 28, 6069 11 of 28 2018 was the dissertation by Ribeiro [8], who sought to address the issue of toxicity and how to minimize it in the Mairá-potato. respectively. However, according to him, the bioavailability of minerals should be evaluated because little is known about this PANC. Table 4 shows the structural formulas of phytochemical compounds isolated and identified from parts of the Mairá-potato plant. Humiriantenolides A

C. rupestris
Thin layer chromatography and nuclear magnetic resonance spectroscopy [13] Humiriantenolides C

C. rupestris
Thin layer chromatography and nuclear magnetic resonance spectroscopy [13] [13] C. ampla Liquid chromatography [14] Humiriantenolides B C. rupestris Thin layer chromatography and nuclear magnetic resonance spectroscopy respectively. However, according to him, the bioavailability of minerals should be evaluated because little is known about this PANC. Table 4 shows the structural formulas of phytochemical compounds isolated and identified from parts of the Mairá-potato plant. Humiriantenolides A

C. rupestris
Thin layer chromatography and nuclear magnetic resonance spectroscopy [13] Humiriantenolides C

C. rupestris
Thin layer chromatography and nuclear magnetic resonance spectroscopy respectively. However, according to him, the bioavailability of minerals should be evaluated because little is known about this PANC. Table 4 shows the structural formulas of phytochemical compounds isolated and identified from parts of the Mairá-potato plant. Humiriantenolides A

C. rupestris
Thin layer chromatography and nuclear magnetic resonance spectroscopy [13] Humiriantenolides C

C. rupestris
Thin layer chromatography and nuclear magnetic resonance spectroscopy C. ampla Liquid chromatography [14] Humiriantenolides E C. rupestris Thin layer chromatography and nuclear magnetic resonance spectroscopy [13] Humiriantenolides F C. rupestris Thin layer chromatography and nuclear magnetic resonance spectroscopy [13] β-sitosterol

C. ampla
Column chromatography and nuclear magnetic resonance spectroscopy [20] C. ampla Thin layer chromatography and nuclear magnetic resonance spectroscopy Liquid chromatography and atomic absorption spectroscopy [15] Sodium nitrite C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Potassium nitrite C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Sodium nitrate C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Potassium nitrate C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Lupeol

C. ampla
Column chromatography and nuclear magnetic resonance spectroscopy [20] C. ampla Thin layer chromatography and nuclear magnetic resonance spectroscopy Liquid chromatography and atomic absorption spectroscopy [15] Sodium nitrite C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Potassium nitrite C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Sodium nitrate C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Potassium nitrate C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Lupeol

C. ampla
Column chromatography and nuclear magnetic resonance spectroscopy [20] C. ampla Thin layer chromatography and nuclear magnetic resonance spectroscopy Liquid chromatography and atomic absorption spectroscopy [15] Sodium nitrite C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Potassium nitrite C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Sodium nitrate C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Potassium nitrate C. ampla Liquid chromatography and atomic absorption spectroscopy [15] Lupeol

Gas chromatography coupled with a flame ionization detector
Molecules 2023, 28, x FOR PEER REVIEW 14 of 29 β-sitosterol glycosylate

C. ampla
Column chromatography and nuclear magnetic resonance spectroscopy [20]  Gas chromatography coupled with a flame ionization detector [19] C. ampla Column chromatography and nuclear magnetic resonance spectroscopy [20] Annonalide

C. ampla
Gas chromatography coupled with a flame ionization detector [19] C. ampla Thin layer chromatography, nuclear magnetic resonance spectroscopy and infrared spectroscopy [24] C. ampla Column chromatography and nuclear magnetic resonance spectroscopy [20] C. ampla High efficiency liquid chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [25] C. ampla Thin layer chromatography and nuclear magnetic resonance spectroscopy [26] Acrenol

Gas chromatography coupled with a flame ionization detector
Molecules 2023, 28, x FOR PEER REVIEW 14 of 29 β-sitosterol glycosylate

C. ampla
Gas chromatography coupled with a flame ionization detector [19] C. ampla Thin layer chromatography, nuclear magnetic resonance spectroscopy and infrared spectroscopy [24] C. ampla Column chromatography and nuclear magnetic resonance spectroscopy [20] C. ampla High efficiency liquid chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [25] C. ampla Thin layer chromatography and nuclear magnetic resonance spectroscopy [26] Acrenol

C. ampla
Column chromatography and nuclear magnetic resonance spectroscopy [20] C. ampla Thin layer chromatography, nuclear magnetic resonance spectroscopy and infrared spectroscopy [24] C. ampla High efficiency liquid chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [25]  and infrared spectroscopy Humirianthol

C. ampla
Gas chromatography coupled with a flame ionization detector [19] C. ampla Column chromatography and nuclear magnetic resonance spectroscopy [20] C. ampla Thin layer chromatography, nuclear magnetic resonance spectroscopy and infrared spectroscopy [24] C. ampla High efficiency liquid chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [25] Phthalate

Column chromatography and nuclear magnetic resonance spectroscopy
Molecules 2023, 28, x FOR PEER REVIEW 15 of 29 and infrared spectroscopy Humirianthol

C. ampla
Gas chromatography coupled with a flame ionization detector [19] C. ampla Column chromatography and nuclear magnetic resonance spectroscopy [20] C. ampla Thin layer chromatography, nuclear magnetic resonance spectroscopy and infrared spectroscopy [24] C. ampla High efficiency liquid chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [25] Phthalate

C. ampla
Gas chromatography coupled with a flame ionization detector [19] C. ampla Column chromatography and nuclear magnetic resonance spectroscopy [20] C. ampla Thin layer chromatography, nuclear magnetic resonance spectroscopy and infrared spectroscopy [24] C. ampla High efficiency liquid chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [25] Phthalate

C. ampla
Thin layer chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [24] Acetylated Humirianthol C. ampla Gas chromatography coupled with a flame ionization detector and solvation with chloroform [22] Acrenol diacetylate C. ampla Gas chromatography coupled with a flame ionization detector and thin layer chromatography [23] Icacinol C. ampla Gas chromatography coupled with a flame [22] [24] Acetylated Humirianthol C. ampla Gas chromatography coupled with a flame ionization detector and solvation with chloroform Thin layer chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [24] 1βOβ-D glycopyranosyl plumeric

C. ampla
Thin layer chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [24] Acetylated Humirianthol C. ampla Gas chromatography coupled with a flame ionization detector and solvation with chloroform [22] Acrenol diacetylate C. ampla Gas chromatography coupled with a flame ionization detector and thin layer chromatography [23] Icacinol C. ampla Gas chromatography coupled with a flame [22] [22] Acrenol diacetylate C. ampla Gas chromatography coupled with a flame ionization detector and thin layer chromatography Thin layer chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy [24] 1βOβ-D glycopyranosyl plumeric

Gas chromatography coupled with a flame ionization detector and solvation with chloroform
Molecules 2023, 28, x FOR PEER REVIEW 17 of 29 ionization detector and solvation with chloroform

C. ampla
High efficiency liquid chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy ionization detector and solvation with chloroform

Technique of Analysis Structural Formula of Compound
Ref.

C. ampla
High efficiency liquid chromatography, nuclear magnetic resonance spectroscopy, and infrared spectroscopy

C. ampla
Thin layer chromatography and nuclear magnetic resonance spectroscopy [26] Toxicity of Mairá-Potato and Indications for Evaluation to Ensure Application as a New Product or Ingredient [25] Stigmasterol

C. ampla
Thin layer chromatography and nuclear magnetic resonance spectroscopy

C. ampla
Thin layer chromatography and nuclear magnetic resonance spectroscopy [26] Toxicity of Mairá-Potato and Indications for Evaluation to Ensure Application as a New Product or Ingredient [26] 3-βOβ-D glycopyranosyl sitosterol

C. ampla
Thin layer chromatography and nuclear magnetic resonance spectroscopy

C. ampla
Thin layer chromatography and nuclear magnetic resonance spectroscopy [26] Toxicity of Mairá-Potato and Indications for Evaluation to Ensure Application as a New Product or Ingredient [26] Spruce [38] reported that the Mairá-potato is a food species that needs treatment to remove flour and starch toxicity, corroborating the study of Ribeiro [8] regarding the presence of toxicity in this species. According to him, after successive washings of the starch and the bark, the material showed no toxicity after the fifth wash. In the study by Zoghbi et al. [13], the toxicity of this species was mentioned regarding the tubers of C. rupestris. The authors stated that, in a study from Uabatuba, which was not published in the consulted databases, such toxicity has yet to be wholly clarified.
However, according to Paschoal and Souza [10], it is essential to search for knowledge regarding the possible presence of toxic phytochemicals and anti-nutritional factors in the case of inappropriate consumption of non-conventional food plants. Considering that the Mairá-potato has already been used for food, as mentioned during the work, and that some authors have cited the presence of toxicity, it is suggested that safety tests should be carried out for pharmaceutical and food purposes.
Huggett and Verschuren [69] stated that, when it comes to the launch of a novel food or ingredient, a safety evaluation is necessary, including information on name, origin, source, production or preparation methods, previous history, specification (water content, nitrogen, lipid, carbohydrate, and ash composition), the purpose as well as its uses, and toxicological studies for its application, such as toxicokinetic, genotoxicity, and allergenic potential.
Several guidelines for toxicological assessments are described by the Organization for Economic Co-operation and Development (OECD) [70].

What Advances Can Contribute to the Development of New Technologies on the Basis of What Has Been Learned?
The biomolecules present in vegetables are essential for the technological advancements in the food and pharmaceutical areas because they allow the discovery of new products and ingredients, as much for food consumption as for medicine production. However, even though many activities of plants have already been tested empirically by native communities, it is not enough to prove their safety, as already mentioned. This way, by respecting the safety evaluations, several suggestions will be presented for the application of the Mairá-potato for the use of some of the compounds already identified and isolated from this tuber, as well as the use of starch for food use, polymeric matrix, and encapsulation of natural actives, other than use in the 3D printing of food.
Developing a relevant product, be it a drug, vaccine, or even a biomaterial, is a complex process that requires financial and human resources. From the beginning of the idea to the final stage, these products demand considerable time, high cost, and strict process control. Although the development of new technologies can be expensive, the final product will undoubtedly contribute to humanity's scientific and social advancement [71].
From now on, we will look at possible applications for the Mairá-potato. The lessons learned will be used to discuss more clearly the possible applications of this tuber and to propose ways to contribute to developing new technologies.

Application of Starch for the Development of Biodegradable Films
The environmental concern of consumers regarding plastic disposal has produced an interest in biodegradable films in the industrial environment, since such films make it possible to control factors such as oxygen, humidity, and carbonic gas associated with the possible incorporation of anti-microbial and functional bio-compounds into the polymeric matrix [72,73]. This matrix can be lipidic, proteinic, or polysaccharide, such as starch. Starch is widely used because it has several characteristics such as film-forming capacity, neutral sensorial aspects, low cost, and abundance [74][75][76].
In addition to its importance in the food industry, starch has wide applications in the paper, chemical, textile, pharmaceutical, and biotechnological industries, making it a very versatile raw material [77]. The type of starch for specific industrial purposes is selected based on its availability and physicochemical properties, which are influenced by the source from which the starch is extracted [78,79]. In addition, there is immediate availability in nature, biodegradability, renewable character, and possibilities of modifications due to the abundance of chemical -OH [80].
Polysaccharides are employed as ice cream stabilizers, food emulsions, micro-encapsulation of flavors and dyes, clarifiers, and beverage stabilizers. Therefore, information about the molecular structure, thermal stability, interaction with water, and rheological behavior is essential knowledge to prospect and develop applications for each type of polysaccharide, either isolated or in mixtures. Another point to consider is the constant search for new sources of polysaccharides that may have similar or better effects than those already known. This is important because it also shows regional appreciation, source of income, and new business opportunities [81].
Studies on the technological potential of starch from alternative sources can provide an alternative to the traditional primary sources of starch feedstock [82]. Unlike conventional starches that are widely produced around the world, new botanical sources are generally consumed as a staple food by local populations and indigenous cultures in rural areas of emerging countries, where diets are rich in vegetables and family farming is common [83][84][85].
Knowing starch's functionalities is paramount to determining its possible use. Amylose is an essential characteristic in terms of optimum film-forming properties; the shape and size of granules are also relevant and all these properties depend on the botanical origin [49,86]. The Mairá-potato emerges as a non-conventional source of starch, which can be significantly explored from the point of view of the functionalities sought for a starch-based polymeric matrix, because, as mentioned in the study of Ribeiro [8], this tuber has several properties.
The Mairá-potato starch is a promising polymer for the development of films. Liporacci et al. [87] attributed this capacity to the starch with high amylose content studied by them (Dioscorea alata starch), with values of 37.46 g/100 g, a value near to that found by Ribeiro [8], which was 38.17% amylose. The lower the number of other constituents and the higher the amount of amylose, the better the film and coating formation because amylose is directly linked to the chemical and physical characteristics of the film [88][89][90].
Other essential features for film formation are paste properties and thermal properties. According to Ribeiro [8], the initial paste temperature (76.4 • C) presented by the Mairápotato is associated with internal inter-molecular forces of starch granules, which is closely linked to the amylose. The paste formed by starch from this tuber showed mechanical and thermal stability; it took 7.39 min to reach the peak of viscosity (256 RVU) and showed a low value of breakdown (125 RVU) and a low tendency to retrogradation (76 RVU). As for the gelatinization temperature, it was between 69.99 and 75.93 • C, which favored application in processes that demand high temperatures, as happens in the formation of biodegradable films of cassava starch between 75 and 95 • C [91] and potato starch at 80 • C [92].
Film-forming material can be applied in encapsulation and grouped according to particle size, micro-encapsulation, and nano-encapsulation. Micro-emulsions have a diameter between 3 and 800 µm, while nano-emulsions have a particle size ranging from 10 to 1000 nm (1 µm) [93]. Ribeiro [8], in the study with the Mairá-potato, observed a starch grain size of 24.48 µm, i.e., the starch grains of Mairá-potato are within the classification of micro-emulsions. Micro-emulsions are indicated for use in the encapsulation of veterinary drugs, taken as an efficient approach to delivery. In other terms, it is a more efficient way for the active compound to be released in a controlled manner, in the veterinary case, to prevent animals from being affected with another substance other than the bioactive substance of interest [94]. In addition, micro-encapsulation technology can be applied to regenerative medicine, in which hydrogels are produced to encapsulate stem cells [95].

Application of Bioactive Ingredients Contained in the Mairá-Potato
Throughout history, bioactive compounds have been used for treatment because of their therapeutic effects. The new trend is to recover bioactive compounds that have physiological effects on living organisms [96]. Bioactive compounds can be recovered from food processing by-products, medicinal plants, and other natural resources [97].
The quality and yield of bioactive compounds depend on two crucial factors, the extraction method and the extraction parameters, including the plan matrix type, the solvent used, time, and temperature [98]. The initial steps for using active compounds from plant matrices are extraction followed by pharmacological testing, isolation, characterization, and clinical evaluation. It should be kept in mind that choosing the delivery system of a bioactive compound depends on some factors such as solubility, stability of the bioactive compound, and its product applications [99].
Considering the proposal to use the encapsulation technique, a compound such as lupeol has been discussed by several authors [57,58]. Other encapsulated compounds discussed were annonalide [29] and β-sitosterol [64,65]. The latter is already known to be used in the production of pharmaceuticals. The proposal is to apply these activities in the Mairá-potato in possible products. We then suggest encapsulation.
Encapsulation is a method in which a component is surrounded by another material and produces particles with diameters of nano-, micro-, or millimeter sizes. The encapsulated components can be in different forms, such as an active agent, base material, filler, internal phase, or payload phase [99]. The nutraceutical and pharmaceutical sectors use active extracts to develop functional foods and herbal medicines, which have the potential to heal and provide health benefits [98].
Encapsulation technology can be grouped into two broad groups. The first is proper encapsulation, in which a liquid or solid core is trapped in a gelatinous capsule. The other includes contemporary techniques, in which active ingredients are trapped in the encapsulating matrix or wall material made of various carriers [100]. The success of an effective encapsulation process depends on the selection of three target bioactive factors: molecules, wall materials, and a suitable encapsulation method [101].
Encapsulation technology has been prominent for decades for solving the limitations encountered in delivering active pharmaceutical ingredients (APIs), food ingredients, and cosmetics and veterinary, hygiene, and cleaning products. Among the technologies most commonly used in producing delivery systems for APIs are coacervation, solvent evaporation, solvent emulsion, ionic gelation, extrusion, high-pressure homogenization, spray drying, and spray cooling or spray cooling/spray freezing [102].
Therefore, the active molecules of the Mairá-potato have potential for various applications, whether pharmaceutical, cosmetic, or food, because there is a range of ways to encapsulate bio-compounds, being necessary to deepen the knowledge specifically about the target molecule.

Material for Printing 3D
Three-dimensional (3D) printing, or additive manufacturing, uses digital data to create a three-dimensional physical object, usually by laying down layers of material in succession. Three-dimensional printing is a unique technique that allows users to create highly complex materials that are difficult to create otherwise using traditional mechanical manufacturing techniques. In addition, 3D-printed objects are immensely customizable through design parameters and different types of printing materials [103]. Three-dimensional printing has already been adopted in several areas, such as the military [104], medicine, pharmaceuticals and biomedicine [105], chemistry [106], and food [107,108].
Three-dimensional printing of food, or additive manufacturing of food, has long been touted as a method for on-demand production and complex customization of food products, with the ability to produce products with unique shapes, combinations of food types, customized flavors, textures, and nutrition. Three-dimensional printing offers the potential for localized on-demand production and is proposed to create personalized nutritional profiles of meals [109].
Depending on their design, 3D printers can print various materials, metals, and plastics [110]. Three-dimensional printing techniques include extrusion-based printing, selective laser sintering, and binder jet and inkjet printing. Of these, extrusion-based printing is the most commonly used method for 3D food printing, which involves a liquid or semi-solid material being extruded through a nozzle, moving in the x-, y-and z-directions, to build a food product layer by layer, usually followed by post-printing processing such as baking or frying [111].
Formulating food inks with the required physicochemical and functional properties is one of the most critical factors in any successful 3D food printing application [111]. Food inks, which may contain one or more ingredients, are typically added to an extruder, pushed out applying an external force, and then printed into pre-designed shapes using spatial data stored in the instrument's software [112]. The force required to extrude food ink through a nozzle is typically provided by connecting the printer to an air pressure unit.
The researchers identified several important parameters affecting the success of 3D food printing, including hardness, elasticity, plasticity, and visco-elasticity [112][113][114][115]. To successfully print food, essential material properties such as rheology, surface tension, and phase behavior of the food ink need to be considered. In addition, the operating parameters of the 3D printer used, such as nozzle height, nozzle diameter, flow rate, and printing speed, are also crucial as they affect the structure and stability of the printed food.
Ensuring the extrusion capability of food materials is essential for 3D printing capabilities, such as shape fidelity and retention over time [116,117]. Three-dimensional structures require precise extrusion of individual line filaments (1D structures), also known as extrudability. Extrudability is assessed by extrusion and filament uniformity [118].
Liu et al. [119] investigated the impact of rheological properties of 3D-printed mashed potatoes with the addition of different concentrations of potato starch and concluded that the most desirable materials for 3D food printing should not only possess adequate yield strength and modulus of elasticity to be able to hold the printed shapes, but also should have low consistency index and flow behavior index to be easily extruded out of the nozzle onto a printer-type extrusion base. They observed that the mashed potato, with 2% potato starch added, showed excellent extrudability and printability.
Liu et al. [120] suggested that yield stress and pseudo plasticity were closely related to the extrudability of food hydro-colloids. Furthermore, printing parameters, including printing pressure, nozzle speed, and nozzle height, were identified as factors that codetermined the extrusion capacity and printability of alginate/gelatin hydrogels [116].
Although the paste-forming ability of Mairá-potato starch has been tested by Ribeiro [8], its flowing and pseudo-plasticity behavior is not known, nor is it known whether the printing nozzle can extrude it. However, it is suggested to use this starch as an emulsifying ingredient or even to add texture to 3D-printed products for food (subject to safety and adaptability tests).

Materials and Methods
This review followed the statement of preferred reporting items for systematic reviews and meta-analyses (PRISMA) [121]. On 9 June 2021, information on the Casimirella sp. species (botanical, food, pharmacological, and phytochemical aspects and isolates) were searched in the Google Academic, Scielo, Science Direct, Scopus, PubMed, and Web of Science databases. After searching the databases with the terms Casimirella rupestris and Casimirella ampla, only one article was found that related to the subject, thus it was decided to search for the terms Humirianthera rupestris and Humirianthera ampla. No restriction was applied. In other words, publications in any language that were published until 9 June 2021 (the date of the research) in the databases mentioned above that were related to botanical, food, pharmacological, and phytochemical aspects were included. Table 5 shows the descriptor terms and Boolean operators used for the search in the Google Academic, Scielo, Science Direct, Scopus, PubMed, and Web of Science databases. Table 5. Descriptor terms and Boolean operators used for searching the Google Academic, Scielo, Science Direct, Scopus, PubMed, and Web of Science databases.

Science Direct
Humirianthera ampla AND Humirianthera rupestris Humirianthera ampla OR Humirianthera rupestris Scopus ALL FIELDS = (Humirianthera ampla AND Humirianthera rupestris) ALL FIELDS = (Humirianthera ampla OR Humirianthera rupestris) PubMed Humirianthera Web of Science ALL = (Humirianthera ampla AND Humirianthera rupestris) ALL = (Humirianthera ampla OR Humirianthera rupestris) Duplicate articles were excluded and, after reading the title and abstract, articles that did not meet the inclusion criteria were excluded. In addition to the selected articles, theses and dissertations that addressed the searched terms were included.

PubMed Humirianthera
Web of Science ALL = (Humirianthera ampla AND Humirianthera rupestris) ALL = (Humirianthera ampla OR Humirianthera rupestris) Duplicate articles were excluded and, after reading the title and abstract, articles that did not meet the inclusion criteria were excluded. In addition to the selected articles, theses and dissertations that addressed the searched terms were included. Figure 2 shows the flowchart of the evaluation of the articles resulting from the bibliographic survey.

Conclusions
The Mairá-potato (Casimirella sp.) appears as a species that, despite being cited by some authors as edible by indigenous peoples, has been little studied for food purposes. However, knowledge of its medicinal use is also an excellent research alternative on the population's use in food and its possible application in products from various areas such as pharmaceuticals, cosmetics, and food.
This review synthesized knowledge about the Mairá-potato, which can contribute to the direction of new research on the technological applications suggested as a polymeric material, biomaterial encapsulation, and bioactive and 3D printing. As such, this work gathered information about this PANC that shows great potential for use in various areas of study.
Several characteristics of the Mairá-potato have not yet been studied. There is a wide field of research on possible enzymes, extraction, and isolation of other food products, such as bread, that are produced technologically, application as an emulsifier or stabilizer, in the formulation of breaded products, creams, soups, and several other uses, where conventional starches are applied and the Mairá-potato can be inserted.