{'fraction_non_alphanumeric': 0.04112737389621386, 'fraction_numerical': 0.017217047699689528, 'mean_word_length': 5.226964599548079, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Current Situation and Perspectives of Fruit Annonaceae in Mexico: Biological and Agronomic Importance and Bioactive Properties

The Annonaceae family is one of the oldest angiosperms. The genus Annona is the one with the most species and, together with Asimina, the only ones that contain edible fruits. In the last 10 years, interest in these fruit species has increased, mainly due to their nutritional properties and their application in the treatment of human diseases. Mexico is the center of origin for most of them. However, at present much of the basic agronomic information, postharvest handling of the fruits, and their potential as new crops for areas with poor soils in organic matter or semi-dry climates is unknown. It is considered that these custard apple species may be an option to change towards instead of crops that have lost profitability and sustainability. A review of the current state of knowledge in different areas of the species A. muricata, A. macroprophyllata, A. reticulata, A. squamosa, and A. cherimola was carried out and to focus research efforts on the topics of greatest interest and on those where is required to achieve a sustainable production and use of these resources in Mexico. However, knowledge about the cultivation and potential uses of these species is needed to increase their commercialization; the integration of interdisciplinary and interinstitutional groups is required.


Introduction
The Annonaceae family is one of the oldest angiosperms. In the analysis of fossils of leaves, seeds, fruits, and pollen, it is estimated that it had its origin in the late Cretaceous period [1]. The Annonaceae family is significant for ecological, evolutionary, and economic reasons [2]. Worldwide, the Global Biodiversity Information Facility (GBIF) database lists 162 genera, and 3049 species of the Annonaceae family, distributed mainly in the tropical and subtropical region of Central and South America, Africa, Asia, and Australia [3]. On the other hand, the World Checklist of Vascular Plants (WCVP) lists 111 genera with 2444 accepted species [4]. The most representative genera of the family are Annona with 215 species, Goniothalamus with 147 species, Guatteria with 314 species, Polyalthia with and applications in the fields of medicine (various pathologies), nutraceuticals (antioxidants, minerals, and fiber), metabolomics (acetogenins and other insecticidal, fungicidal, and bactericidal compounds), and agriculture (alternative crops, molecular characterization, germplasm collection, characterization, plant breeding, and obtaining new varieties), among others [23].
Due to their genetic characteristics and biotechnological potential, interdisciplinary research groups have been formed in countries such as Spain, France, the United States, Japan, Brazil, Argentina, Colombia, and Mexico [24], and recently India and Bangladesh, as highlighted by numerous publications. In Mexico, the National Network of Anonaceas (NNA) was formed in 2002, made up of researchers from different institutions and disciplines of knowledge, with an emphasis on the study of the species A. muricata, A. cherimola, A. squamosa, A. diversifolia, A. reticulate, A. purpurea, and related wild genera that, faced with the increasing threat of environmental deterioration, are at risk of genetic erosion and gradual loss. The main objectives are the generation of knowledge for in situ and ex situ conservation, use and enhancement, and capacity building in these species [25]. Although some activities have been carried out in the NNA, the lack of budget support has limited the monitoring and fulfillment of these objectives. Currently, this network is part of the subcommittee on genetic resources, which in turn is coordinated by the Sectoral Committee on Genetic Resources for Food and Agriculture, whose legal basis is on the Agreement by which the Sectoral Committee on Genetic Resources for Food and Agriculture is created. The objective of this Committee is to promote the conservation, management, fair and equitable distribution of benefits, and sustainable use of genetic resources, through inter-institutional and interdisciplinary coordination in the sector [26]. Similarly, specialist meetings have been held with presentations of research results in different areas of knowledge in the Annonaceae group [24,25].
Considering the above, the objective of this review is to gather the current information generated in these Annona species, delimit the frontier of knowledge, and propose actions in the short, medium, and long term for the NNA. The JSTOR, ResearchGate, Google Scholar, Scopus databases and national production statistics, as well as technical publications from research institutes and centers were reviewed.
It is interesting to observe how the development of research in these Annona species has been, on the one hand, the basic agronomic knowledge for their commercial production, and postharvest management technologies and obtaining derived products is still limited. They have made progress only in some areas of the production process and postharvest handling. However, in topics such as phytochemistry, nutraceutical uses, and applications in different pharmacological areas, important research contributions have been constructed in several countries.

Agronomic Knowledge
Of the species of fruit custard apples or soursop, A. muricata is the one with the greatest development in its agronomic knowledge in Mexico. It has the largest cultivated area and production [12]. In Mexico, clonal varieties of A. muricata (breeder titles: Guanay-1, Guanay-2, and Guanay-3) have been characterized and registered [27]. However, most of the current agronomic knowledge is generalized. More specific studies are required, such as adaptation in different environments, generation of varieties with higher yields and tolerance to pests and diseases, studies of phenology and nutritional requirements, planting density and formation pruning, collection, morphological and genetic characterization, and genotype conservation. Currently, there is greater knowledge in different areas of biology, agronomy, and biotechnology in this species. Its agronomic management can be consulted in [18,[28][29][30][31][32]. Some specific work has been carried out which contributes to optimal production. The management of the main pests and disease problems can be consulted in [28,[33][34][35][36]. Similarly, important advances have been made in the collection, description, and selection of genotypes [32,[37][38][39], with which improvement activities could begin.
The species A. cherimola is second in economic importance in Mexico. However, the cultivation area and production are smaller, with an establishment potential in central and southern Mexico [40]. Currently, it is only cultivated in Michoacán and Morelos [12]. It is found naturally in temperate and subtropical zones in the states of Morelos, Oaxaca, Michoacán, Hidalgo, Veracruz, Chiapas, Puebla, Jalisco, Guanajuato, and the State of Mexico [41]. In this context, some genotypes of A. cherimola have been characterized and registered, including Tonaltzintl, Metztli 34, Selección 94-33, Álvaro, Urhuata, and Lamtl 256 [27]. As with A. muricata, its agronomic knowledge in Mexico is limited, and the recommended management is generalized [42,43]. Research has been carried out in specific areas such as pollination [44], selection and characterization [45,46], and pests and pathogens [47][48][49][50]. The knowledge of the crop is more advanced in Spain, technology has been developed, along with a selection of varieties for their best use [51][52][53][54][55].
On the other hand, the species A. macroprophyllata, A. reticulata, and A. squamosa have less development and knowledge in Mexico. These species do not have a breeder's title and registration in National System of Genetic Resources (SNICS-acronym in Spanish), and there is less agronomic knowledge about them. However, they have a potential for cultivation as an alternative or complementary option to the production of tropical fruit trees that have lost profitability. A. macroprophyllata, commonly known as ilama, is found naturally from Colima in Mexico to El Salvador [14]. At present, there is no knowledge of any cultivated area, as its trade is local, and all of the fruit comes from the collection of trees that are found naturally on the edge of pastures or orchards and in backyards. The first studies for its knowledge in Mexico were carried out by members of the National Network Anonaceae (NNA). In the communities of Tierra Caliente, in the Balsas region of southern Mexico, this fruit is most widely known. Its production is rustic; it presents tolerance to high temperatures, drought, and soils poor in nutrients and organic matter [16]. A research group from the Technological Institute of Ciudad Altamirano, Guerrero, as members of the NNA, has managed to identify and describe the physical-chemical characteristics of 24 types of ilama, of which 146 accessions were collected for propagating and promoting its conservation and cultivation. It is estimated that there are approximately 100 types of ilama in this region [16]. The morphological description and genomic identification of the most representative types of ilama can be consulted in the catalog Diversity in the ilamas of Tierra Caliente del Balsas, Mexico [56]. In addition to the above, more specific studies have been carried out to identify its chemical composition and antioxidant activity [57]. This species represents an interesting option due to its adaptation and pleasant flavor, with development potential for the semi-dry climate regions in the states of Colima, Guerrero, Michoacán, and Oaxaca.
A. reticulata is known as sugar apple, custard apple, or ox heart custard apple; native to India and Central America, there are no reports about the large of cultivated areas. It is mainly found naturally in tropical and subtropical regions, and only a few small areas are cultivated in south Florida, Bahamas, Bangladesh, Pakistan, and some parts of India [58,59]. In Mexico, there are no reports of its cultivation. It is found in its natural state in the Pacific region, from southern Sinaloa to Chiapas; it is not cultivated commercially, and its consumption is local in the production season. It has been observed in Nayarit, Jalisco, and Colima that the fruits are collected in the months of March to May; their consumption is fresh, and presents a great phenotypic variety, which would imply greater selection, characterization, and possible use as a crop in these areas. Its potential for use and research in medicine has great potential; numerous studies have been carried out on its chemical constitution and pharmacology, finding satisfactory results [60][61][62][63][64]. Regarding A. squamosa, known as saramuyo, it has a cultivated area of 50.5 hectares in Mexico, with a production of 431 tons. Its cultivation is recent, and it is located mainly in the south of the country, in the state of Yucatán. [12]. It is distributed naturally from the tropics in Mexico to Bolivia [21,65], with Brazil being the main producer [13]. Until a few years ago, in Mexico, the saramuyo was only found to be naturally occurring; however, recent research has contributed to a better understanding of this species. Similar to other Annona species, in saramuyo, there are numerous studies on chemical composition, evaluation, and use of its pharmacological properties [66][67][68], and little research on the selection, characterization, improvement, and agronomic management. General recommendations for its knowledge and agronomic management can be consulted in the Manual of Propagation and production of saramuyo (Annona squamosa L.) [69]. However, its potential for alternative cultivation as the main activity in areas with warm and semi-dry climates and soils poor in the organic matter makes the saramuyo a species that requires more attention and research. Table 1 shows the nutritional composition and energy value of the edible part of A. muricata, A. cherimola, A. squamosa, and A. macroprophyllata. A. cherimola and A. squamosa fruits are sweeter than A. muricata, A. reticulata, and A. macroprophyllata. They have a low content of lipids and proteins [70][71][72][73][74][75][76][77][78][79]. Furthermore, the pulp exhibits a good quantity of dietary fiber, although A. muricata and A. cherimola fruits are more fibrous. The pulps are prominent in some vitamins (C, E, thiamin, riboflavin, and niacin) and minerals (Ca, P, Mg, K, and Fe). In addition, they are very low in calories. In this context, the regular consumption of these fruits provides essential nutrients for the recommended daily intake.

Tradicional Medicine Use
In addition to the nutritional importance of the Annona fruits, different reports have demonstrated the use of all parts from the trees of A. muricata, A. cherimola, A. squamosa, A. reticulata, and A. macroprophyllata in traditional medicine. Since many years ago, the native people of various cultures have consumed beverages produced from Annonaceae stem bark, roots, leaves, fruit pulp, peel, and seed for a wide range of illnesses. The preparation of beverages has been by maceration, decoction, or infusion [80]. People have consumed these products for the treatment of illnesses such as parasitic infections, dysentery, fever, urethritis, hematuria, and asthma, liver diseases, diarrhea, and for their anticold, antispasmodic, antisudorific, anti-depressive, and antiemetic properties [81]. Nonetheless, most biological properties of members of the Annonaceae family are attributed to the presence of diverse secondary metabolites/bioactive compounds [82]. Tables 2 and 3 show some phytochemicals (quantitative or qualitative) identified in pulp, leaf, peel, seeds, roots, and stem bark of fruit Annona species: A. muricata, A. cherimola, A. squamosa, A. reticulata, and A. macroprophyllata [83][84][85][86][87][88][89]. These compounds include phenolic compounds, alkaloids, fatty acids, cyclopeptides, alkaloids, and acetogenins.

Cyclopeptides
Cyclopeptides or cyclic peptides are polypeptides formed from amino acids organized in a cyclic ring structure [101,102]. In the seeds of some Annona species bioactive compounds named cyclopeptides have been reported that in recent years have been of much pharmaceutical interest. Annomuricin A-C has been extracted and identified from A. muricata seeds (Table 3) [89,101,102]. Two other cyclopeptides (cherimolacyclopeptide E and F) were obtained from A. cherimola seeds [103,104]. Moreover, seven cyclopeptides (cyclosquamosin A-G and met-cherimolacyclopeptide B) were reported in seeds, and two cyclopeptides (fanlizhicyclopeptide A and B) were found in the peel of A. squamosa [105][106][107][108]. The Annona cyclopeptides show a remarkable variety of derivatives and a wide array of bioactivities, including antiproliferative, antimicrobial, anthelmintic, and anti-inflammatory, and cytotoxicity [104].

Acetogenins (ACGs)
ACGs are molecules characterized by a long aliphatic chain of 35 to 37 carbon atoms with one, two, or three tetrahydrofuran or tetrahydropyran rings in their central region [124]. Annonaceae acetogenins are secondary metabolites with the highest therapeutic interest, due to their cytotoxic capacity on cancer cell lines and their in vivo antitumoral activity [82]. The acetogenins are found in the seeds (A. muricata, A. cherimola" A. diversifolia, A. squamosa, and A. reticulata), leaves (A. muricata, A. cherimola, and A. squamosa), edible pulp (A. muricata and A. squamosa), roots (A. muricata), and stem bark (A. muricata, A. cherimola, and A. squamosa). Although there are more than five hundred identified acetogenins, annonacin and bullatacin are considered the acetogenins with the highest concentration in Annona species. Moreover, they have excellent cytotoxicity at low doses, but they can be highly toxic if consumed in high concentrations [82,145]. They can be found in the pulp, leaves, seeds, and roots of A. muricata [83,124,125,127,134]. In the same way, annonacin and bullatacin have been identified in the pulp and stem bark of A. squamosa [135,138]. In A. macroprophyllata, the principal reported acetogenins from seeds are rolliniastatin-2, laherradurin, and cherimolin-2 [88,89].

Biological Activities from Extracts or Isolated Compounds from Annona Species
There are many biological activities attributed to extracts (aqueous, ethanolic, methanolic, and ethyl acetate) or isolated compounds from Annona species such as anti-angiogenic, analgesic, thrombolytic, anti-ulcer, anti-platelet, vasorelaxant, anti-pyretic, anti-convulsant, anti-depressive, neuroprotective, anxiolytic, antitumoral or cytotoxic, hypoglycemic, and anti-inflammatory [146]. Table 4 shows several studies on the biological effects of extracts or isolated compounds from principal fruit Annonas.

Technologies for Postharvest Handling
The fruit belonging to the genus Annona are climacteric, with respiration rates of up to 350 mL of CO 2 kg −1 h −1 , in addition to having ethylene production values of 46.2 and 68.5 µL kg −1 h −1 at a storage temperature of 25 to 30 • C [171]. Due to the above, the production capacity of Annona is wasted, since the production of these fruit in the country presents various management problems [172]. Moreover, a 60% post-harvest loss has been reported, which causes the producer to choose to move their fruit in transport with high cost (air) and use expensive post-harvest technologies to delay the ripening of the fruit, mainly refrigeration (13 • C) [173].
During the handling of the fruit, it is essential to preserve the physical, chemical, and organoleptic characteristics that are ideal for the consumer [174], which is why the essential result is to carry out an adequate postharvest handling. However, there are no postharvest technologies registered or issued by organizations for the handling of fruit belonging to the genus Annona [175]. The considerations for the post-harvest handling of soursop (Annona muricata L.) that are applied are those described by Morton, where it is mentioned that the fruit needs to be kept under conditions of room temperature and relative humidity of 85 and 90%. In addition, it is necessary to be cautious when handling the fruit, since they are susceptible to physical, chemical, and microbiological damage [176]. The common operations in the post-harvest handling of soursop are harvesting, selection, cleaning of organic residues, classification, antifungal treatment, weighing, pre-cooling (12 to 15 • C), drying of residual humidity, post-harvest treatment (waxing), storage, and transport [177].
As mentioned above, high rates of respiration and ethylene production play an important role in the postharvest handling of the genus Annona. Ethylene is responsible for regulating the maturation and senescence of various agricultural products [178]; therefore, it is responsible for the fruit to acquire optimal organoleptic characteristics for consumption, as well as for the senescence of the fruit [179]. Eventually, having identified the mechanisms of action of ethylene on the fruit, it has been possible to develop technologies and procedures to control the different negative effects that this hormone can cause (Table 1). In research carried out by Wijesinghe et al., the effect of 1-methylcyclopropene (1-MCP) at 0.3, 0.6, and 0.9 µL/L was evaluated in four different Annona fruit: A. atemoya, A. reticulata, A. muricata, and A. squamosa. As response variables, the days of storage, physiological weight loss (PWL), firmness, color, total soluble solids (TSS), and titratable acidity (TA) were measured. At the end of the investigation, it was concluded that the application of 1-MCP increased the shelf life to three extra days for all the fruit compared to the control fruit without treatment. The 0.6 µL/L concentration reduced PWL, the enzyme activity responsible for the loss of firmness and control of chlorophyll degradation in addition to regular TSS and TA [180].
Other technologies used to extend the shelf life of perishable fruit are coatings or so-called "waxes". Montalvo-González et al. [181] used candelilla and beeswax emulsions as postharvest technology applied to soursop fruit (A. muricata). Respiration rate, ethylene production, PWL, firmness, TSS, TA, pH, and color ( • hue) were considered as response variables. The authors describe a favorable effect on respiration rate, since it decreased in the fruit treated with wax and managed to delay the appearance of the climacteric peak one day after the control fruit. A similar effect was found in the rate of ethylene production since the levels of the treated fruit were lower compared to the control fruit. Finally, for TSS, TA, pH, and color, a moderating effect was noted in the generation of these parameters since the metabolic processes of the fruit were not inhibited or modified [181].
By showing an interesting effect on the genus Annona, 1-MCP and waxes were studied in combination due to their high performance and potential applications.
The research of Tovar et al. [173] was based on applying to soursop fruit 1000 nL/L of 1-MCP in combination with three different wax formulations: first, carnauba wax type III Emulwax 3060; second, carnauba wax type III, and food-grade silicone oils Emulwax 3061; and third, refined candelilla wax Emulwax 3070 (all formulations were applied after 1-MCP). The determinations that were used as response variables were PWL, TSS, TA, pH, color ( • hue), and firmness. In general, the combination of 1-MCP and the three types of coatings managed to lengthen the shelf life of the fruit by an extra six days, as compared to the control (18 days in total). In the PWL analyses, it was discovered that the combination of these technologies managed to significantly reduce this parameter; however, no difference was found between the treatments. Regarding the content of TSS, TA and pH were observed a major delay in the normal evolution of the variables. The values of Hue for the control fruit and combination 1 and 2 did not show significant differences; however, for combination 3, a decrease in color development was noted. The author attributed this phenomenon to the synergistic effect of formulations 1 and 3. Finally, in the firmness data, was reported significant differences between the treated and control fruit, but no differences were found between treatments [173]. Table 5 shows some technologies to extend the shelf life of Annona fruits.
Control of physicochemical, microbiological, and sensory characteristics [188] Cold storage Annona muricata L. Increase the days of shelf life of the fruit (2 extra days) [189] Bacillus atrophaeus strain B5 Annona muricata L. Biocontrol of postharvest anthracnose [190]

Perspectives
Since the agronomic knowledge of these fruit species of Annona in Mexico is still limited, it is necessary to exploit the conditions of the center of origin of most of these and the optimal climatic conditions for their cultivation. Therefore, the Red Nacional de Annonaceae should initially focus its activities on the generation of knowledge of best agronomic practices that allow for obtaining the highest yields and the least environmental impact of these crops to achieve their sustainable development. There is a lack of selected varieties and characterization of the great gene pool that is still found in natural conditions, backyard, or underutilized on the verges of harvesting roads or grazing areas. It is necessary to carry out an exhaustive search, characterize and begin an improvement program with the most outstanding productive genotypes or with some characteristics of interest. The potential for commercial use of these species is underutilized, given the great acceptance of the fruits for fresh consumption, and obtaining products and applications in areas such as medicine or therapeutic treatments. Currently, it is still important to look for extraction alternatives to increase the yield and demonstrate the distribution and contents of compounds in the different Annona species. Although these species are rich in secondary metabolites, it is not fully clear if they can be a source of nutraceutical metabolites for the pharmaceutical industry. According to the review, various extracts of A. muricata, A. cherimola, A. squamosa, A. macroprophyllata, and A. reticulata species contain metabolites capable of exerting different biological activities that are beneficial to health; however, further studies on the precise mechanisms of action and expanding the knowledge of Annona species less investigated such as A. reticulata are required.