Lesser-Consumed Tropical Fruits and Their by-Products: Phytochemical Content and Their Antioxidant and Anti-Inflammatory Potential

Açaí, lychee, mamey, passion fruit and jackfruit are some lesser-consumed tropical fruits due to their low commercial production. In 2018, approximately 6.8 million tons of these fruits were harvested, representing about 6.35% of the total world production of tropical fruits. The present work reviews the nutritional content, profile of bioactive compounds, antioxidant and anti-inflammatory capacity of these fruits and their by-products, and their ability to modulate oxidative stress due to the content of phenolic compounds, carotenoids and dietary fiber. Açaí pulp is an excellent source of anthocyanins (587 mg cyanidin-3-glucoside equivalents/100 g dry weight, dw), mamey pulp is rich in carotenoids (36.12 mg β-carotene/100 g fresh weight, fw), passion fruit peel is rich in dietary fiber (61.16 g/100 dw). At the same time, jackfruit contains unique compounds such as moracin C, artocarpesin, norartocarpetin and oxyresveratrol. These molecules play an important role in the regulation of inflammation via activation of mitogen-activated protein kinases (including p38, ERK and JNK) and nuclear factor κB pathways. The properties of the bioactive compounds found in these fruits make them a good source for use as food ingredients for nutritional purposes or alternative therapies. Research is needed to confirm their health benefits that can increase their marketability, which can benefit the primary producers, processing industries (particularly smaller ones) and the final consumer, while an integral use of their by-products will allow their incorporation into the circular bioeconomy.


Introduction
The search for a healthier lifestyle has led to increased consumption of fruits, vegetables, and functional foods. Several studies indicate that diets rich in fruits and vegetables positively correlate with improved health, due to a reduced risk of cancer, obesity, inflammatory conditions, and cardiovascular diseases, in addition to their high nutritional value [1][2][3][4]. Fruits and vegetables are rich sources of fiber, vitamins, minerals, and bioactive compounds such as phenolic compounds, carotenoids, and betalains. Recently, these Using different by-products from lesser-known tropical fruits as food ingredients is an area of interest for further research. In this sense, passion fruit peel (PFP) supplementation is considered an important source of dietary fiber. Studies in humans demonstrated that a diet supplemented with passion fruit peel (PFP) flour could improve metabolic parameters, such as reducing fasting glycemia and glycated hemoglobin in type 2 diabetic individuals, as well as reducing fasting glycemia and triglyceride levels in hypercholesteremic women [29]. It was recently found that mamey is a potential source of pro-vitamin A carotenoids (pulp) and dietary fiber (peel).Still, their use as a food ingredient is distant from being commercially available, since there are no reports of actual research because of their small cultivation area [30,31]. In this sense, some commercially available products have been developed from different by-products, but they are not widely accessible worldwide, such as the case of PFP flour developed in Brazil, jackfruit peel and pulp flour in India, lychee seed oil in China, mamey seed oil in several local markets in Mexico, and newly developed açaí seed powder in the United States.
Therefore, the present review analyses the nutritional composition and content of bioactive compounds in lesser-consumed tropical fruits, their by-products (peel and seed), and their antioxidant and anti-inflammatory potentials. The information discussed herein will be useful to understand their possible health benefits. It will serve to increase their consumption, as well as to promote the use of their by-products, which are currently underutilized.

Methods and Data Collection
Science Direct, Google Scholar, Scopus and Springer databases were used to find information on the composition and bioactivities of lesser-consumed tropical fruits and their by-products. Keywords such as "common and scientific name of the fruit" + peel, pulp, flesh, pomace, seed and by-products, phenolic compounds and bioactivities were used for the data search. Alternatively, the most characteristic bioactive compound present in a fruit were searched with the terms "antioxidant" and "anti-inflammatory". The data search also included the words "exotic fruits" and "Amazonian fruits" because several sources include these fruits without listing their names in the title or key words. Figure 1 shows each tropical fruit's percentage of pulp, peel, and seed, while Table 1 shows their nutritional composition. Açaí seed is approximately 85 to 90% of the fruit's weight, with its pulp (10%) and peel (2%) comprising the rest. Its pulp contains a high percentage of dietary fiber, carbohydrates, and lipids, while also being a good source of minerals such as calcium, iron, magnesium, and phosphorus. This fruit is also characterized by phenolic compounds, particularly anthocyanins, and some carotenoids, such as α-carotene, β-carotene, lutein, and zeaxanthin (Tables 1 and 2) [32][33][34][35].

Chemical Composition of Peel, Seed, and Pulp of Lesser-Consumed Tropical Fruits
Mamey contains mostly pulp (approximately 70%), with its peel and seed making up a minor percentage of its composition. Its peel is rich in dietary fiber (61.43 g/100 g dw), as compared to the pulp (21.50 g/100 g dw). Its pulp has an energy content of 1287 KJ/100 g dw [31], while the seed is rich in monounsaturated and polyunsaturated fatty acids.
Peel is the major component of passion fruit (approximately 64%), followed by pulp and seed. Its seed is rich in dietary fiber, with a 2:1 ratio of insoluble-to-soluble fiber, followed by protein and lipids. Its fatty acid profile is high in polyunsaturated fatty acids. Its pulp and peel contain mostly carbohydrates, while some of its most representative bioactive compounds include vitamin E and some carotenoids such as lycopene and β-carotene [11,[36][37][38].
Lychee seed and peel have similar caloric densities, while the peel is also noteworthy for its high dietary fiber content. Minerals such as calcium, iron, magnesium, phosphorus, and potassium are also found in lychee. Its profile of bioactive compounds is characterized by vitamin C in all tissues, with the highest concentration in the peel. Its content of β-carotene in pulp and peel also stands out with 291. 4 and 195.09 µg of β-carotene equivalents/100 g dw, respectively [39,40].  Figure 1. Percentage of pulp, seed, and peel in lesser-consumed tropical fruits (lychee [39], mamey [43], passion fruit [36], jackfruit [41] and açaí [32]).

Phytochemical Content
Phytochemicals are secondary plant metabolites that protect plant tissues against various biotic and abiotic stresses. Some of them play important roles in human health, for example, edible plants contain phenolic compounds, carotenoids, and tocopherols, which are associated with beneficial effects on the prevention of cardiovascular disease risk factors, inhibition of inflammation, reducing oxidative stress and preventing or delaying oxidation by scavenging free radicals [51,52]. Recognizing the presence of phytochemicals in lesser-consumed tropical fruits and their by-products requires knowing their quantities and diversity to investigate their possible effects on human health, and this is described in this section. Table 2 describes the content of several bioactive compounds present in lesser-consumed tropical fruits and their by-products. It should be noted that flavonoids are the predominant phenolic species present in these fruits and the ones that this review focuses on the most; however, other minor components may also be present (such as non-flavonoids), but have been less studied in these fruits. Percentage of pulp, seed, and peel in lesser-consumed tropical fruits (lychee [39], mamey [43], passion fruit [36], jackfruit [41] and açaí [32]).

Phytochemical Content
Phytochemicals are secondary plant metabolites that protect plant tissues against various biotic and abiotic stresses. Some of them play important roles in human health, for example, edible plants contain phenolic compounds, carotenoids, and tocopherols, which are associated with beneficial effects on the prevention of cardiovascular disease risk factors, inhibition of inflammation, reducing oxidative stress and preventing or delaying oxidation by scavenging free radicals [51,52]. Recognizing the presence of phytochemicals in lesser-consumed tropical fruits and their by-products requires knowing their quantities and diversity to investigate their possible effects on human health, and this is described in this section. Table 2 describes the content of several bioactive compounds present in lesser-consumed tropical fruits and their by-products. It should be noted that flavonoids are the predominant phenolic species present in these fruits and the ones that this review focuses on the most; however, other minor components may also be present (such as non-flavonoids), but have been less studied in these fruits.

Phenolic Compounds
Phenolic compounds have a common basic structure with significant diversity, which is precisely why their physicochemical properties are diverse. Complex glycosylation and polymerization patterns complicate their extraction, purification, and identification and, therefore, different methods are required for these purposes [53]. Table 3 shows the content of phenolic compounds found in lesser-consumed tropical fruits and their by-products, as obtained by different extraction methods.
Açaí pulp also has a high phenolic content, but it has been observed that its highest concentration is found in unripe fruits (12,317 mg GAE/100 g dw), which gradually decreases until fully ripe (3437 mg GAE/100 g dw). It has been observed that, in general, unripe fruit had the highest phenolic content. Passion fruit (1297.31 mg GAE/100 g dw) and jackfruit pulp (1034-1157 mg GAE/100 g dw) contain lower concentrations, followed by lychee (20.30 mg GAE/100 g dw) [22,26,36]. Phenolic compounds in mamey have also been reported to vary by up to 10-fold from unripe (256.3 mg GAE/100 g fw) to ripe (23.4 mg GAE/100 g fw) fruit, while senescent mamey fruit shows further decreases (6.6 mg GAE/100 g dw) [55,56].

Flavanols
Catechin and epicatechin can be found in mamey, açaí and lychee pulps as representative compounds. Reported values of catechin in mamey and lychee are 11.31 and 0.486 mg/100 g fw, respectively. In açaí pulp, catechin values of 5.07 mg/100 g dw have been reported. For epicatechin, values of 0.58 mg/100 g fw in mamey pulp and 0.498 mg/100 g fw in lychee pulp have been reported. In açaí pulp, 2.09 mg/100 g dw of epicatechin was reported. Gallocatechin-3-gallate is found in mamey and açaí pulp, while gallocatechin and catechin-3-O-gallate is found in mamey pulp. A total flavanol content of 50.65 mg/100 g dw have been reported in açaí pulp [56][57][58]60,63,64].

Flavones
Flavones have been identified in açaí pulp, where orientin and isovitexin stand out, with 15.0 and 12.0 mg/100 g dw, respectively. Passion fruit peel also contains isoorientin, with 19.63 mg/100 g dw and its pulp has 16.226 mg/L fw [10,11,62]. This phenolic species is widely spread in the plant kingdom and has been reported in several fruits, vegetables, cereals, legumes, and wines [65]. Nevertheless, no studies have been addressed to identify and quantify them in lesser-consumed tropical fruits such as lychee, mamey, jackfruit or their by-products.

Carotenoids
Carotenoids are an important and widespread type of phytochemicals found in plants and plant-derived food, bacteria, fungi, and animals, with several health-promoting properties attributed to them. They are tetraterpene pigments, of which more than 700 have been identified in nature [70,71]. Carotenoids are commonly found in lesser-consumed tropical fruits and their by-products.
Mamey is distinguished for its carotenoid composition, since sixty-two carotenoids and carotenoid esters in saponified and non-saponified mamey pulp extracts have been identified. Likewise, twenty-three compounds that belong to seventeen different chemical classes of carotenoids have been identified. The most representative molecules include neoxanthin, cryptocapsin, luteoxanthin and capsoneoxanthin [19,70].
Mamey is also notable for its carotenoid content with a kappa terminal group, which are not very common; the kappa ring is usually hydroxylated, such as in capsanthin, capsorubin, and cryptocapsin. Studies suggest that mamey contains two enzymes that carry out the biosynthesis of kappa-carotenoids, one that catalyzes the epoxidation of the non-hydroxylated β-ring and another that reorganizes the epoxides [30,74]. As noted, lesser-consumed tropical fruits are a significant source of carotenoids, which is of interest because of the bioactivities these compounds can perform. Evidences indicate that these phytochemicals contribute to the decrease in the incidence of diseases and protect against the recurrence of pathological events [63,71]. Table 2. Phytochemical content in the pulp, seed, and peel of mamey, açaí, passion fruit, lychee, and jackfruit.

Antioxidant Activity (AOXA)
As can be noticed in Table 3, lesser-consumed tropical fruits have shown significant AOXA. The AOXA of jackfruit, as determined with the 2,2 -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS • ) assay, is reported as IC 50 = 570, 23 and 762 mg dw/100 mL extract in pulp, peel, and seed, respectively. The results of DPPH • are reported as 16 µM Trolox equivalents (TE)/100 g fw, 1.25 mg dw/mL and >10 mg dw/mL in pulp, peel, and seed, respectively. In the same way, an in vitro assay of α-glucosidase inhibition was developed and indicated that peel extract inhibited about 11.8-fold, as compared to acarbose [22,69]. AOXA values have been reported to positively correlate with the total phenolic compounds content in jackfruit when using the ABTS • (R = 0.94, p ≤ 0.001) and DPPH • (R = 0.88, p≤ 0.001) assays, higher values than the correlation with ascorbic acid (R = 0.38 and R = 0.50, respectively) and anthocyanins (R = 0.36 and R = 0.19, respectively), suggesting that phenolic compounds other than anthocyanins, such as phenolic acids, tannic acid and proanthocyanidins, may be the most important contributors to the AOXA of this fruit [69]. Therefore, the results reveal the potential of jackfruit peel as a source of natural antioxidants and hypoglycemic agents.
In vitro assays have shown that extracts from jackfruit pulp have ABTS • radical scavenging capacity, with an inhibition of 11.7%. Jackfruit extracts have also shown a greater capacity to inhibit nitric oxide (NO • ) (75.3% inhibition) and superoxide anion (O •− ) (46% inhibition) than other fruits that are commonly known as good inhibitors of NO • and O 2 •− , such as blueberries (44.2 and 10%), black raspberry (13.1 and 8.7%), grapes (66.9 and 43%) and red raspberry (37 and 43%). The capacity of jackfruit pulp extracts to stabilize DPPH • , ABTS • , NO • and O 2 •− has shown positive correlation with total phenolic content (R = 0.967, 0.621, 0.380 and 0.532), flavonoids (R = 0.30, 0.995, 0.685 and 0.802) and proanthocyanidins (R = 0.902, 0.755, 0.201 and 0.371). This suggests that the stabilization of the DPPH • radical is mainly due to the presence of total phenolic compounds, including proanthocyanidins and the stabilization of the ABTS • radical is due to the presence of the flavonoids and proanthocyanidins, while the inhibition of NO . and O 2 •− is due to the presence of flavonoids [79].
AOXA of açaí pulp has been reported as 5795 and 93,682 µM Trolox/100 g dw according to the ABTS • and DPPH • assays, respectively. Fruit ripening has been shown to directly influence AOXA of açaí, where AOXA of unripe (green), intermediate maturity (reddish-brown) and ripe (dark purple) has been reported as 17.0, 4.04 and 2.78 µM TE/100 g dw, respectively [35]. DPPH • radical scavenging capacity of passion fruit shows that seed extracts had the lowest IC 50 value (49.71 µg/mL), indicating a stronger AOXA than in the peel and pulp, which had values of 347.6 and 869.05 µg/mL, respectively. According to the ferric reducing antioxidant power (FRAP) assay, AOXA varied between 27.50 and 119.32 µM of FeSO 4 /g, with seed extracts showing the highest values [11].
Polyphenolic compounds have been intensely studied for their anti-inflammatory potential during the past century, since during severe inflammation, cells produce several pro-inflammatory reactive oxygen species (ROS), such as singlet oxygen and NO, while also activating cyclooxygenases (COX) that produce additional molecules [80][81][82]. The anti-inflammatory activities of lesser-consumed tropical fruits and their by-products are discussed in the following section.  PL: peel; PP: pulp; SD: seed; dw: dry weight; fw: wet weight; rpm: revolutions per minute; h: hours; AAE: ascorbic acid equivalents; TE: Trolox equivalents; NR: not reported. Units are shown unmodified from the original sources.

Anti-Inflammatory Activity
Different mechanisms of action might be related to the anti-inflammatory effects of phenolic compounds. Among them, up/downregulation of transcription factors (e.g., NF-κB), inhibition of pro-inflammatory mediators (e.g., interleukin 6, IL-6), of activated immune cells (e.g., macrophages) and inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), are considered in the present work and can be seen in Table 4 [80,81]. Figure 2 shows how several antioxidants, all found in lesser-consumed tropical fruits, can mitigate or even stop several pathways that lead to inflammation. The possible mechanisms of this action are not yet clear; however, they can inhibit the cascade of pro-inflammatory signals, such as caspases, COX-2, iNOS, IL-6, TNF-α, among others [86][87][88]. Figure 3 summarizes the main bioactive compounds in lesser-consumed tropical fruits, which are known to have significant anti-inflammatory activity.

Changes Exerted by Altering Gene Expression
Moracin C is a phenolic compound found in jackfruit, which can significantly inhibit the release of ROS and lipopolysaccharide (LPS)-induced nitric oxide in RAW 264.7 cells, at doses of 25 and 50 µM without apparent cytotoxicity after treatment for 48 or 72 h. Regulation of the expression of iNOS, COX-2 and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) was observed in response to these treatments. The anti-inflammatory action of moracin C was associated with the activation of some MAPK, including p38, ERK, and JNK, and NF-κB pathways [87]. Anti-inflammatory activity of phenolic compounds artocarpesin, norartocarpetine and oxyresveratrol isolated from jackfruit was reported. Artocarpesin suppressed LPS-induced nitric oxide and prostaglandin E2 (PGE 2) by downregulating the expression of iNOS and COX-2 [86].
Açaí pulp extract has anti-inflammatory properties that strongly inhibit COX-1 and COX-2 in vitro. It has also been shown to protect umbilical vein endothelial cells (HUVEC) against glucose-mediated inflammation by reducing the expression of IL-6 and IL-8 [89,90]. Velutin is a flavone in açaí pulp that inhibits NF-κB activation induced by oxidized LDL (oxLDL) in RAW-Blue cells. Its inhibitory effect was better than luteolin, another flavone with high anti-inflammatory activity [91]. The chemical structures of both compounds are similar, differing only in two substituents, where velutin bears two methoxyl groups at 7-and 3 -positions, whereas luteolin has two hydroxyl groups. Substitution of methoxyl groups appears to be a significant factor that regulates some bioactivities of the molecules, as determined by the evidence described. Velutin has also been shown to reduce the production of TNF-α and IL-6 in peripheral murine macrophages andactivate NF-kB [89,90].  A flavanol-rich lychee fruit extract (FRLFE) has been reported to contain a mixture of oligomerized phenolic compounds rich in monomers, dimers, and trimers of flavanol. Supplementation with FRLFE has been shown to suppress inflammation and tissue damage, both caused by high-intensity physical training of young long-distance runners for two months. Treatment with FRLFE reduced the serum concentration of IL-6 and significantly increased the transforming growth factor-β level between pre-and post-training [92]. Additionally, its effects on the expression of inflammatory genes were observed in rat hepatocytes treated with IL-1b and decreased mRNA and protein expression of iNOS, leading to an inhibition of nitric oxide and IL-1β. FRLFE also inhibited phosphorylation of the NF-κB inhibitor (IκB-a) and reduced the mRNA expression of NF-κB and TNF-α [93].
Flavonoids and ferulic acid found in passion fruit flour have been shown to improve obesity-related inflammation, according to a decrease of TNF-α and IL-1β and inactivation of JNK. Results were found in male Sprague Dawley rats fed with a high-fat diet, with 50% of the cellulose replaced by Passiflora edulis peel flour. This suggests that these compounds protect from obesity-related inflammation; thus, passion fruit flour containing 60.9% of total fiber (19.94 soluble fiber and 40.15% insoluble fiber), 137 mg/100 g dw of total carotenoids, 116 mg catechin equivalents (CE)/100 g dw of total flavonoids and 14 mg/100 g dw of ferulic acid could mitigate this condition in obese subjects [88].

Changes Exerted by Targeting Different Metabolites
Other compounds from jackfruit significantly inhibited the release of β-glucuronidase and histamine from P-methoxy-N-methylphenylethylamine (dihydroisocycloartomunin), inhibited lysozyme release (artocarpanone), and the formation of superoxide anion (cycloheterohyll, artonins B and artocarpanone) in rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP), as well as the inhibition of nitric oxide production and iNOS expression in RAW 264.7 cells (artocarpanone) [95].  Passion fruit peel flour treatment (8 mg/mL in the drinking water) has shown an antiinflammatory effect on the intestine of female C57BL/6J mice by attenuating colitis-induced damage. Biochemical and molecular analyses revealed the inhibition of the expression of pro-inflammatory cytokines and an improved intestinal protective barrier. In addition to these effects, increases in the formation of short-chain fatty acids were observed, which are known to play an important role in the maintenance of colonic homeostasis; any imbalance in the microbiota homeostasis can up-regulate the immune response leading to mucosal damage and intestinal inflammation, thus supporting a prebiotic effect of passion fruit peel flour [20]. Different treatments can reduce or inhibit several inflammation cascades based on the bioactive compounds found in the lesser-consumed tropical fruits and their by-products.
Nevertheless, further research is still needed to identify, isolate, and quantify their phytochemical content and determine their efficacy on human health.

Conclusions
The present review brings attention to the phytochemical content of lesser-consumed tropical fruits such as passion fruit, lychee, mamey, açaí and jackfruit, as well as their by-products. Their phytochemical composition is associated with some biological activities, such as antioxidant and anti-inflammatory activities. Particular compounds such as velutin, moracin, malvidin, pelargonidin, naringerin, ferulic acid, chlorogenic acid, caffeic acid, catechin, epicatechin, quercetin and rutin found in these fruits are promising candidates for developing novel functional foods and/or nutraceuticals. However, their safety must be validated, while additional in vivo trials are required as a precedent to their pharmacological capitalization in contemporary medicine. Detailed studies on their pharmacokinetic behavior are also lacking, and these are required to associate their consumption with specific biological activities conclusively and indisputably be at the heart of upcoming research. Additional data generated on the lesser-consumed tropical fruits will serve to increase their production and consumption in diverse markets. At the same time, research into their by-products will allow their incorporation into the circular bioeconomy. Funding: This research was funded by CONACYT, through the project "De los subproductos alimenticios de vegetales a nuevos productos de valor agregado, el papel de la tecnología en la bioeconomía" (320351).

Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.