de Oliveira et al. [54] have concentrated on the antioxidant capacity of pineapples. They studied the total phenolic content and antioxidant activities of methanolic extracts of pineapple residues (including pulp, seeds, and peels from a local juice factory) using DPPH and superoxide anion scavenging activity. Hossain et al. [37] extracted total polyphenols of pineapple with different solvents, and the results showed that the polyphenolic contents of the extracts were found to be highest in methanol corresponding to the highest antioxidant properties. Gallic acid, catechin, epicatechin, and ferulic acid were found to be the main polyphenolics in pineapple peels. Results of polyphenolics’ interactions indicated no synergistic effects. In the combinations of ferulic acid-epicatechin and ferulic acid-gallic acid, additive effects were found using both antioxidant activity assays [55]. However, some researchers have reported that pineapple peel is a potential source of bioactive compounds, such as vitamin C, carotenoid, phenolic compounds, flavonoids [38] [39] [40] [41], and these compounds have been reported to have antioxidant activity and various biological activities [21] [56] [57]. However, these bioactive compounds are varied depending on many factors, including cultivar, pre-and postharvest treatment and particularly method for raw material and extract preparation [58] [59] [60] [61] [62]. Also, some studies confirmed the antioxidant activity of pineapple peel extract [31] [63] [64] [65]. Chlorogenic acid and ferulic acid in aqueous pineapple extract is considered having an important role as reducing agent or antioxidant [44].

Ferulic acid is a hydroxycinnamic acid, a type of organic compound. It is an abundant phenolic photochemical found in extracted from pineapple peel. It is related to trans-cinnamic acid and contributes to the antibacterial, anticancer activity and antioxidant properties of the plant [66]. The antioxidant potential for extracted and standard ferulic acid was calculated by DPPH assay of 87.3% and 81.92% respectively and the total antioxidant capacity was calculated by FRAP assay which is expressed as 2315 μM and 3985 μM. The anticancer activity of extracted ferulic acid was evaluated based on viability of cells using MTT assay. The optimum cell viability was 48.04% at a concentration 125 μg/ml and the maximum cell viability was 91.63% obtained at the concentration of 7.8 μg/ml using MTT assay. So, pineapple is a potent source of ferulic acid that can be extracted and used as anticancer and antioxidant [66]. Bromelain also showed significant anticancer activity against breast cancer cells, melanoma cells, human epidermoid carcinoma cells, malignant peritoneal mesothelioma cells and mammary carcinoma cells. The major anticancer mechanism of bromelain is by inhibiting cancer cell proliferation and inducing differentiation of leukemic cells [31].

Recycling pineapple wastes by using pineapple waste as potential lead to discover new drugs to control some food poisoning and other infectious bacteria is a promising aim. Lubaina et al. [67] showed that the antibacterial potential exhibited by ethyl acetate extract of pineapple peel was effective against gram-positive and gram-negative bacterial strains such as Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Vibrio cholera (MCV09) and Klebsiella pneumoniae (ATCC 700603). From the results it can be concluded that pineapple peel could be a useful source for antibiotic production and has the potential of medicinal and industrial application. Antimicrobial properties of various extracts from pineapple peel have recently been of great interest because of their possible use as natural additives emerged from a growing tendency to replace synthetic antimicrobials with natural ones [67]. Das et al. [68] reported antioxidant, antibacterial, antidiabetic, and cytotoxicity of pineapple peel.

The antibacterial activity revealed by the pineapple extracts might be due to presence of polyphenols, flavonoids, saponins and other secondary metabolites present in the extract. Flavonoids and polyphenols are more potent in inhibiting gram-positive bacteria. Both are phenolic compounds which have polar properties mostly work in the peptidoglycan layer in gram-positive bacteria rather than the non-polar lipid layer. Most plant phenolic compounds are non-toxic for human consumption therefore they could be used to prevent growth of many food-borne and food spoilage microorganisms. These phenols have the ability to denatures the protein and its lipophilic nature helps them to attract the lipid molecules contained in the cell membranes and damage the bacterial cell membrane [69]. Both bromelain and saponins act on bacterial cell wall and membranes. The active compound working against gram-negative bacteria is mainly bromelain. Bromelain is a proteolytic enzyme play a role in the breakdown of proteins, one of the essential components in bacterial membrane causing injury and cell death. It also disintegrates protein in surface membrane which eventually weakens the cell wall, leads to cell leakage and damages the cell. The numbers of amino acids in the bacterial cell wall are thought to determine the antibacterial activity of proteolytic enzymes. Saponins increases the permeability of the bacterial cell membrane, causing alteration in the structure and function of the membrane thereby disrupting the surface tension of the cell wall and allowing antibacterial substances to easily enter the cells and interfere the cell metabolism which in turn leads to the lysis of membrane. Saponins selectively interact with cholesterols on cell membrane leaving a hole in the membrane [70]. Phenols alter the permeability of the membrane that could result in the uncoupling of oxidative phosphorylation, inhibition of active transport, and loss of metabolites due to membrane damage. Polyphenols inhibit bacterial DNA gyrase by binding to the ATP binding site [71]. Gallic acid has proven antifungal and antibacterial properties [72]. Similarly, tannins exert antimicrobial activities by iron deprivation, hydrogen binding or specific interactions with vital proteins, such as enzymes in microbial cells, bind to adhesions, complex with cell wall, other membranes and metal ion complexes. Flavonoids are also possessing antimicrobial potential by link to adhesions or complexes with the cell wall, inactivation of enzymes and inhibition of HIV reverse transcriptase [73].

Bromelain is an extract isolated from pineapple mainly containing proteinase. It is a crude, aqueous extract showed significant antibacterial activity against gram negative and gram-positive bacteria such as Bacillus subtilis, Streptococcus pyogenes, Corynebacterium spp, Streptococcus sanguis (10556 ATCC), Enterococcus faecalis, Escherichia coli, Proteus spp and Pseudomonas aeruginosa. The anti-bacterial mechanism of bromelain is not well known but, it may inhibit the growth of bacteria through hydrolysis of some peptide bonds present in the bacterial cell wall [31]. Bromelain was extracted from all parts of pineapple. Bromelain was tested for antibacterial activity against bacterial pathogens. Among them, Pulp bromelain had maximum inhibition effect on Bacillus subtilis, Klebsiella pneumonia and Core bromelain had maximum inhibitory effect on Bacillus subtilis, Proteus vulgaris, Schigella flexneri and Escherichia coli and there was no inhibitory activity for the other tested pathogens [74]. Das et al. [68] investigated the antimicrobial activity of pineapple peel (PP) extract (PPE) to observe possibility of using it as a natural antimicrobial agent in food. The antimicrobial activity of the PPE was performed against some food pathogens (Bacillus cereus, Staphylococcus aureus, Salmonella typhimurium and Escherichia coli). In addition, the gram-positive bacteria tended to be more susceptible to the PPE than the gram negative one. B. cereus exhibited the most sensitive strain with minimum inhibition concentration (MIC) of 0.0675 g/mL, followed by S. aureus and E. coli (0.1349 g/mL) and S. typhimurium (0.2699 g/mL), respectively. In addition, the minimum bactericidal concentration (MBC) against all the tested bacteria in broth dilution assay was 0.0675 g/mL, except B. cereus, in which the lethally effect was not detected. The results suggested that the pineapple peel extract is a potent natural antimicrobial agent for food application. IUPAC name for Bromelain is N-[(2S,3R,4R,5S,6R) 2-[(2R,3S,4R,5R)-5-acetamido-6-hydroxy-2-(hydroxymethyl)-4-[(2S,3S,4R,5S,6S) 3,4,5trihydroxy-6-methyloxan-2-yl]oxyoxan-3-yl]oxy-5-[(2S,3S,4S,5S,6R)-4,5-dihydroxy 6[[(2S,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]-3 [(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl] oxyoxan-2-yl]oxy-4-hydroxy-6 (hydroxymethyl)oxan-3-yl]acetamide. The chemical structure has been drawn by ChemDraw Professional software (Figure 5).

Pineapple peel extract demonstrates antibacterial properties because it contains chemical compounds. In addition to flavonoids as the highest concentration of chemical compounds in pineapple peel extract, there are other active compounds, namely: saponins, tannins, and enzymes bromelain. Each of these chemical compounds has a specific role in inhibiting the growth of Enterococcus faecalis [42] [75]. Flavonoid compounds have the ability to form complex bonds with extracellular protein through hydrogen bonding. Hydrogen bonds with extracellular proteins cause bacterial cell membrane structures containing proteins to become unstable. Consequently, the permeability of bacterial cell wall will be disrupted, resulting in bacterial cell death [76]. Tannin compounds can damage bacterial cell membranes and result in reduced permeability, so the growth and activities at bacterial cells is inhibited [77]. In other chemical compounds, saponin, as an antibacterial agent, can reduce the surface tension leading to the increasing

permeability of cell membranes. Changes in cell membrane permeability cause release of intracellular compounds from the cell that leads to bacterial lysis [77]. The action mechanism of the bromelain enzyme as an antimicrobial lies in altering or damaging the wall structure of bacteria-containing protein. The bromelain enzyme will break down and denature the protein constituent of bacterial cell walls. As the cell weakens it can allow small molecule to leak out [70]. Okoh et al. [44] performed the antibacterial activity of the peel extract and showed a greater inhibition for Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi. The data obtained show that the pineapple peel contains potential antimicrobial component that may be of great use for the development of pharmaceutical based therapies against various diseases. Drinking the juice or its peel eating can help to hydrate the body and restore the immune system.

Olakunle et al. [78] investigated the antifungal activity and phytochemical analysis of selected fruit peels (orange, pineapple cashew and banana fruits). Extracts were prepared from each powder using water and ethanol as solvents. The antimicrobial activity of each of the aqueous extracts (100 mg/ml) against Aspergillus niger and Alternaria alternata. Results obtained showed that Aspergillus niger had its respective inhibition zones with orange, cashew, pineapple, and banana peel extracts as 0.33 ± 0.33, 0.40 ± 0.30, 0.60 ± 0.20 and 0.87 ± 0.33 cm while inhibition zones of Alternaria alternata with the peels in the same order were 0.50 ± 0.50, 0.60 ± 0.35, 0.87 ± 0.43 and 1.37 ± 0.67 cm. Hence, the order of antifungal activity of the peel extracts against Aspergillus niger and Alternaria alternata was banana > pineapple > cashew > orange. The antifungal activity of these peel extracts could be due to different classes of compounds such as alkaloid, flavonoid, tannin, cardiac glycoside, saponin and phlobatannin found in them. The phytochemical constituents of ethanolic extracts of pineapple peels were alkaloid, tannin and cardiac glycoside [78]. Antimicrobial properties of plants extracts had been attributed to the presence of alkaloids and flavonoids [79] [80] [81]. Phytochemicals with bitter taste such as alkaloids and flavonoids have been found to possess microbial properties and the presence of cardiac glycosides, flavonoids and alkaloids suggest that the possible antimicrobial activity was due to the presence of these phytochemicals in the peels. These bioactive groups of natural products have been reported for their inhibition roles against pathogens in ethnobotany, drug application and plant health management [82] [83]. These results have opened up the possibility of the use of peels in the treatment of fruits against spoilage microorganisms. The peels are novel, natural and economic sources of antimicrobics, which can be used in the control of post-harvest diseases [78].

Along the pineapple processing chain, waste products such as peels, crowns, stems and cores result, and these parts are usually containing significant amounts of the enzyme bromelain [84] [85]. Bromelain, a protease found in pineapples, is of high demand in the pharmaceutical, cosmetic and in the food industries, which use as a meat tenderiser, anti-browning agent and in the production of infant formulas [86]. As a protease, it hydrolyses proteins in these formulas, thus making amino acids more readily available to infants. Cosmetic and pharmaceutical usage of bromelain, as well as usage in the textile industry, has also been reported [87] [88] [89] [90].

Pineapple peel has the potential to being used as a nonpharmacological treatment in the form of processed food and instant drinks. One of the causes of hypertension is reduction of intracellular potassium concentrations in the body. Increased potassium intake could be done by consuming pineapple, because it is one of the superior fruits which have a high content of potassium [91]. Safriani et al. [91] showed that potassium levels in pineapple peel were 938.48 mg/kg. The potassium content is greater than flesh and core which are 485.28 mg/kg and 12.98 mg/kg, respectively. From the result, it was appeared that, the peel contains more potassium than flesh and core. Also, producing vinegar from fermented pineapple by-products (peels). The vinegar was produced after fermenting the peels of pineapple using three selected strains of acetic acid bacteria. such as propionic bacterium acidipropionici, panteo agglomerans, and pantea dispersa. The results of Chalchisa et al. [92] work have revealed that it is possible to produce vinegar from pineapple peels. This was done via the use of yeast (Saccharomyces cerevisae) as an aerobic degradation of sugar to ethanol and Acetobacter aceti oxidizers ethanol to acetic acid (vinegar) by using different strain of acetic acid bacterias. The study also revealed that while cleaning the environment, an added value can be achieved through recycle or conversion of supposed wastes into useful products [93]. In addition to pineapples consumption as fresh, cooked, juiced, and preserved and are found in a wide array of cuisines., the pineapple leaves are used to produce the textile fibre pina employed as a component of wallpaper and furnishings, among other uses. Pineapple peel, is normally used as animal feed [94], development of new products such as cereal bars [95] [96], cakes [97] and jellies [31] [98], citric acid extraction [31], phenolic compounds production [31], bromelain from stem and rind [31], hydrogel from peel cellulose [31], nanocellulose from leaf fibres [32].

Generally, Pineapple peel waste (PPW) has been used for animal feed or land fertilizer [99], and substrate for production of bio-ethanol [41]. Antioxidant or reducing agent plays an important role both in health sector and chemical industry. Therefore, explored PPW as a potential of natural antioxidant is one of interesting pineapple applications as reducing agent is in biosynthesis of metal nanoparticles. It is found that biosynthesis of metal nanoparticles can be carried out by aqueous pineapple extract [45], and had successfully produced silver and cooper nanoparticles. Although fruit is the most used part of plant, other parts (root, rhizome, leaf, cortex, and stem) also have various nutritional and medicinal properties. Leaves, stem, and pineapple fruit have an important role in traditional medicine as good antioxidants, antidiabetics, vermicides, emmenagogues, and hypolipemic agents. They are also used in different stadiums of wound healing and as an anti-edematous and anti-inflammatory agents in healing of soft tissue injuries, as well as in the treatment of arthritis, hematoma, and necrotic tissue [100] [101] [102] [103] [104]. The root and fruit are either eaten or applied topically as an anti-inflammatory and as a proteolytic agent. It is traditionally used as an anti-helminthic agent in the Philippine. A root decoction is used to treat diarrhea [2] [3]; however, this fruit also has anti-inflammatory and digestive properties. The fruit can also be used to aid in digestion. It can clear bronchial passages in those suffering with pneumonia and bronchitis [2] [3].

Pineapple has been used as a medicinal plant in numerous cultures, both Lawal [105] and Dabesor et al. [106] reported that the solvent extracts of the various parts of A. comosus exhibit antibacterial, antiviral, antifungal, antiparasitic and anti-inflammatory properties. Moreover, pineapple juice, can be taken to alleviate sore throat and seasickness. The functional bioactivity of a plant extract, in general, depends upon the presence of compounds such as polyphenols, carotenoids and chlorophyll [14] [107], due to the antioxidant activity of polyphenolic compounds [108]. Flavonoids, mainly present as colouring pigments in plants also function as potent antioxidants at various levels. Some studies showed that flavonoids could protect membrane lipids from oxidation [109]. The anti-inflammatory properties in the fruit help reduce the symptoms of arthritis, and help reduce pain after surgery and sport injuries. A. comosus juice is taken as a diuretic and to expediate labour, also as a gargle in cases of sore throat and as an antidote for sea sickness, also to expel intestinal worms; and as a drastic treatment for venereal diseases. In Africa the dried, powdered root is a remedy for edema. The crushed rind is applied on fractures and the rind decoction with rosemary is applied on hemorrhoids. Indians in Panama use the leaf juice as a purgative, emmenagogue and vermifuge [2] [3]. Figure 6 shows the health benefits of pineapple waste (Ali et al., 2020) [110].