Pharmacological Actions of Ananas comosus L. Merril: Revision of the Works Published from 1966 to 2020

Juliana Azevedo da Paixão1,2,*, José Fernando de Araújo Neto1, Bruna Oliveira do Nascimento1, Diego Mota da Costa2, Hugo Neves Brandão2, Fernanda Vidigal Duarte Souza3, Everton Hilo de Souza4, Quiara Lovatti Alves5, Samile Barreto Lima Erling6, Juceni Pereira de Lima David1 1Universidade Federal da Bahia, Instituto de Química, Salvador, BRAZIL. 2UEFS, Km 03, Br 116, s/n, Feira de Santana, BRAZIL. 3EMBRAPA, Rua Embrapa, s/n, Chapadinha, Cruz das Almas, BRAZIL. 4Universidade Federal do Recôncavo da Bahia (UFRB), Rua Rui Barbosa, 710, Centro, Cruz das Almas, BRAZIL. 5FIOCRUZ. Rua Waldemar Falcão, Candeal, Salvador-Bahia, BRAZIL. 6UNIJORGE, Av. Luis Viana Filho, São Marcos, Salvador-Bahia, BRAZIL.


INTRODUCTION
The use of medicinal plants and phytotherapics has occurred since ancient times, it is essential in the discovery of new medicines and have been contributed significantly to humanity. They are capable of treating several pathologies acting as antibacterial, antiparasitic, immunosuppressive and anticancer. [3] The huge potential for the development of medicines produced directly from biologically active natural or synthetic products that use the chemical structure of the natural product as a base, given that the main entities currently developed are chemotherapeutic and antimicrobial. [1,2] Considering the variety of existing plants, phytochemical studies associated with biological assays represent a promising approach in the discovery of new drugs and for the rational use of biodiversity elements. In addition, it is possible verify the use of plants as a therapeutic resource from ancient times to the current day. [4,5] Brazil has an invaluable source of natural resources to obtain drugs, although the pharmacological potential of our native species have been poorly studied. [6] In Brazilian territory, Bromeliaceae's family is very common. It's include approximately 78 genera and about 3663 species, which are divided into subfamilies: Pitcairnioideae, Bromelioideae, Tillandsioideae, Brocchinioideae, Hechtioideae, Lindmanioideae, Navioideae and Puyoideae About 38% of the total Bromeliaceae species are in Brazil, with 56 genera registered in the national territory. Ananas comosus (L.) Merr. is the most studied species among them, also known as pineapple, its one of the most consumed tropical fruits in the world. [7] Commonly, some of the plants in this family are used to treat several pathologies in traditional medicine, presenting different pharmacological activities, such as diuretic, antimicrobial, anthelmintic, antitussive, antidiabetic and others. In addition to reports of bromelain enzyme and cysteine proteases, various special secondary metabolites as triterpenes, steroids, flavonoids, glycerols, cinnamic acid derivatives, among others, were reported. [7,[8][9][10] Thus, knowing the richness of the Bromeliaceae, due to the presence of the mentioned metabolites and studies that report the various medicinal properties, it's essential to carry out research identifying the main biological or pharmacological activities in A.comosus and its varieties, correlating with the substances responsible for the activity. This study aimed to conduct a review to summarize the main pharmacological or biological actions of varieties of this species, indicating, when possible, the identified components of each varieties, described in the literature. It has expected that this review may provide a starting point for future research focusing on chemistry composition and biological activities of this genera.

MATERIALS AND METHODS
An integrative review of the biological activities of A. comosus and its varieties in publications cataloged in PubMed, SciELO, Science Direct, Lilacs, using as keywords: Ananas, Ananas comosus, biological activities, pharmacology and phytotherapy was carried out from August 2017 to November 2020. Articles citing Ananas comosus or pineapple and its varieties, uses for therapeutic purposes in the treatment against different pathologies that were cited in more than one work, bibliographic surveys that addressed the pharmacological use of A. comosus were used as inclusion criteria. Exclusion criteria were non-scientific texts, only a work that cited a certain biological / pharmacological activity. For evaluation and adequacy to the inclusion or exclusion criteria, critical reading of the selected material was performed. After that, 100 articles were selected to compose the results.

RESULTS AND DISCUSSION
We found 100 studies dating from 1966 to 2020, which reported the use of A. comosus for the following activities: abortion; anticholinesterase; anticancer, anticoagulant; antidepressant, antihelmintic; antimicrobial; antioxidant; antiplasmodic; antirheumatic; cardioprotective; hypoglycemic, hypolipidemic, hepatoprotective, burns treatment and respiratory tract diseases. Among the selected research, the main ones were in vitro and in vivo studies and some ethnobotanical surveys. Regarding the substances responsible for the activities, there are mainly bromelain, phenolic compounds and some triterpenes and steroids. The species and varieties found were: A. comosus and A. comosus var. bracteatus. The main parts of the plant used were the leaves and fruits, followed by the peel. Table 1 presents the main information found in A. comosus.

Abortive effects, antilutetrophic and antiovulatory
Studies assessing the ability of A. comosus to terminate pregnancy are old, evaluated the isolated substances ergosterol peroxide, β-sitosterol, 5-estigmastene-3β,7alpha-diol, 5α-stigmastane-3β, 5,6β-triol, 3 monobenzoate from pineapple leaf extracts and also they identified that when administered in rats it showed abortifacient activity. [11,12] The compounds: ergosterol peroxide, β-sitosterol, 5-stigmastene-3p-7a-diol, 5 stigmastene-3p-7p-diol, 7-Oxo-5-stigmastene-3p-ol, 5α Stigmastane-3 β, 5, 6 β-triol extracted with petroleum ether and benzene from A. comosus leaves exerted abortive activity. Since the first day of administration it can be detected, but ergosterol peroxide showed the maximum abortifacient effect between 6 and 7 days of pregnancy, and action postponed from 13-16, after implementation. [13] A more recent work performed, using 16 pregnant albino rats, which evaluates the abortive activity of the pineapple juice in two repeated tests, showed that, although the abortion was not provoked, it has potential. The animals presented contractions similar to oxytocin, thus it is possible the abortion act as well as the drug. [14] Some mechanisms pointed these steroids as the main substances responsible for A. comosus abortive action. According to the author, A. comosus crude fruit extract has dose dependent effect with the content of serotonin present in A. comosus, this substance is responsible for uterine motility in different species. [15] According to studies conducted in rats and rabbits [11,12,[16][17][18][19] steroid 5α-stigmastane-3β, 5,6β-triol 3-monobenzoate also exhibit antilutetrophic and antiovulatory activity. In order to investigate the tocolytic properties of Ananas comosus extract, many researchers use mice and human uterine tissue in vitro assays. It was observed that ethyl acetate extract produced a non-selective inhibitory response on oxytocin, prostaglandin F2α, acetylcholine and KCl. Furthermore, the authors concluded that the extract acted by multiple mechanisms as antagonism of Ca 2+ type L channels, interfering in intracellular Ca 2+ release mechanism, and releasing nitric oxide, characterize the extract as a promising candidate to be developed as a tocolytic agent. [17] Several ethnobotanical studies realized showed the use of A. comosus leaves and fruits by the India's population, being used as leaf tea or fruit juices, accompanied or not by other ingredients for birth and fertility control. [20][21][22] Anti acetylcholinesterase Different studies report that plant extracts have inhibitory activity of the acetylcholinesterase enzyme (AChE). [23,24] An in vitro study using extracts of fruits from A. comosus, showed that only the aqueous extract showed 4.3% inhibition, [25] it is considered low activity if evaluated according to Vinhuta et al. [23] However, as a controversial result compared to this previous one, the neuroprotection was evaluated using bromelain in an in vivo study in mice. The enzyme provided neuroprotection by decreasing oxidative stress and increasing cholinesterase. [26] It is remarkable that this work was carried out in vivo, using only the enzyme bromelain, which may present different results from A. comosus extract from previous in vitro studies.

Hepatoprotective activity
The hepatoprotective activity of ethanolic and aqueous extracts from A. comosus fruits in an animal model, which hepatotoxicity was alcohol-induced. According to the authors, the antioxidant property of A. comosus, due to the presence of terpenoids, polyketides, amino acids, peptides, proteins, carbohydrates, lipids and polyphenolic compounds found in ethanolic and aqueous extracts, is responsible to hepatoprotective activity of this species. Despite this, more studies are necessary to clarify which phytochemicals are responsible for this organo-protective activity. [27] According to the literature, pineapple protects the liver by promoting a reconstructive effect on the hepatic metabolism, but not the kidneys intoxicated by damage induced by paracetamol in rats. [28,29] Oral administration of pineapple vinegar can reduce the levels of serum enzyme biomarkers, such as alanine transaminase (ALT), aspartate transaminase (AST) and triglycerides (TG) after 7 days of treatment with paracetamol. Its also restored the levels of liver antioxidants, reduced the expression of inflammatory factors and the expression of cytochrome P450 protein in the liver in liver damage induced by paracetamol in mice. [30] Corroborating these data, ethanolic and aqueous extracts from Ananas comosus fruits can decrease ALT and AST levels in rats poisoned by isoniazid after four weeks of treatment. The authors conclude that pineapple juice has hepatoprotective activity by inhibiting the widening of the central venous diameter, although analysis of the data has shown that liver function in these rats was not as good as in positive controls. [31] These studies are relevant since they assess the pineapple's potential as a possible adjunct to treatment with drugs such as isoniazid and paracetamol, possibly minimizing its hepatotoxic side effects.

Antitumor
According to Table 1, it is possible to verify that this Bromeliacea's species presents studies that relate its use as an antitumor, and indicate that the bromelain presence in A. comosus as the main agent of such activity. [32][33][34][35][36] Bromelain stimulates the body's defense mechanism against cancer by increasing the cytotoxic activity of monocytes and macrophages, its inhibit cancer growth, acting as an immunomodulator, it is also used to treat leukemia and pulmonary metastasis. [32,36] The cytotoxic activity of A. comosus pulp and peel was verified with Artemia salina, its showed LC 50 25 μg.mL -1 and 29,6 μg.mL -1 respectively. [37] Thus, it is possible to corroborate the cytotoxic activity of A. comosus with possible antineoplastic activities, considering the toxicity low to LC 50 above 500 μg.mL -1 ; moderate to 100 to 500 μg.mL -1 and high to LC 50 below 100 μg.mL -1 . [38] Anticoagulant The availability of A. comosus and the various activities of bromelain had led to the evaluation of this enzyme as anticoagulant. [35,39] Among four extraction methods used, 95% ethanol extraction by maceration, Soxhlet using Analytical Grade Petroleum Ether, Expression with Spiral Twist and Decoction, first extract showed the ability to prevent blood clotting. This activity was obtained using different volumes of extract in the sample with human blood that was observed for 1-3 using and its ability to prevent blood clotting was evaluated. The results obtained were comparable to EDTA, the positive control; however, further studies are necessary relating to the subject. [39] Several studies have provided useful information for the development of new pharmacotherapies using medicinal plants to treat depression. Some species as Hypericum perforatum, Vicia sojakii and Hibiscus esculentus can act as important sources of new antidepressant drugs, furthermore A. comosus has an interesting potential as antidepressant agent. [40][41][42]
Leaves and fruits Peel and leaves Leaves Ananas comosus Italy,

India Peel
Bromelain, flavonoids and tannins [63,64] Cardioprotective  [84,85,86] test (TST) and reserpine-induced hypothermia, compared to antidepressants fluoxetine (20 mg kg -1 ) and imipramine (15 mg kg -1 ). The authors concluded that A. comosus juice presented results comparable to antidepressants, showed reduction of immobility time, reversing hypothermia, as well as inhibition of brain monoamine activity. [43] The antidepressant activity in mice of the methanolic extract of A. comosus peels using three different doses compared to imipramine, FWT and TST were also performed. The extract has excellent low-dose antidepressant potential, but its effect on long-term administration and the safety profile in acute and chronic administration should be evaluated. Moreover, according to the same study, the presence of quercitrin, narigenin, rutin, saponins, and the numerous brain monoamines, such as serotonin, norepinephrine and dopamine, may contribute positively to their antidepressant effect. [44] Antiparasitic Ananas comosus species has different uses in folk medicine, but also has uses in veterinary medicine, mainly as anthelmintic, being one of the causes of reduced productivity in livestock. [45,47] The scientific validation of antiparasitic effects and possible side effects of plant products in ruminants were evaluated by different in vitro and in vivo methods of the activity of various plants, including A. comosus. [45,48,49,50,46,47] In vivo studies showed that treatments using plant, in most cases, resulted in reductions in parasitism level, however, its not compared with anthelmintic drugs. [45] On the other hand, the species in question evaluated against, the Rhicephalus microplus parasite and the Haemonclus contortus helminth, regarding the parasite, showed activity and with respect to helminth the activity in vitro was high and despite having in vivo activity, it was less significant. Further studies are necessary to prove the antiparasitic activities of the species. [46,47] Antimicrobial activity Several papers present the antimicrobial activity of plant extracts, including fruits such as lemon, orange and pineapple. [51] Studies using pineapple peels, the activities against pathogenic bacterial strains were verified, by the agar diffusion test against pathogenic bacterial strains (Klebsiella pneumoniae K2044, Pseudomonas aeruginosa MTCC4676, Bacillus subtillis Py79 and Xanthomonas axonopodis pv. Malvacearum LMG859). It showed that methanolic extract of A. comosus peels can act as antimicrobial agent, but appropriate studies with adequate safety information should be performed. [52] Another study showed that the aqueous extract of A. comosus crown leaves showed proteolytic, gelatinolytic, collagenase, fibrinolytic activity, considerable antibacterial and antifungal activities. Collectively, these properties have revealed their application for treatment of microbial infection and as a healing agent. [53] Nanoparticles obtained with A. comosus extract and pineapple leaf extract proved to demonstrate antimicrobial properties. [54] Antioxidant activity

Ananas comosus
Ananas comosus is the most processed tropical fruit generating large amounts of residues, 25-35% are residues with high content of compounds with antioxidant activity, which gives them a huge industrial potential (WU, 2012). The total phenolics, flavonoids and antioxidant activity of A. comosus fruits, identified the presence of phenolic compounds, and the antioxidant activity of the extract according to the amount present in the fruit extract, rich in phenolic compounds that provides a good source of antioxidant. [55] In order to verify the antioxidant capacity of various tropical fruits using the DPPH method, it was observed that the A. comosus extract showed moderate action between 60-70% scavenged of the DPPH radical. [56] The β-carotene oxidation technique reveals a modest value for pineapple residue (47.66%). [98] The concentration of phenolic compounds from pineapple fruit pulp residues showed values of 0.0860 ±0.0145 g de AGE. 100 g -1 in aqueous extract and 0.0911 ± 0.0099 g of AGE 100 g -1 in hydroalcoholic extract. [57] On the other hand, performing the same study on three cultivars of A. comosus, others researchers observed much higher values around 0.30 ± 0.003 to 0.492 ± 0.4 g of AGE. 100 g -1 for 70 % methanolic extract. [58] In the quantification of flavonoids in pineapple fruit puree, values for the total flavonoid content of 0.0867 g QE 100 g -1 . Studying three extracts (ethyl acetate, methanol and water) of the pineapple fruit observed that flavonoid contents ranged from 0.394 to 0.552 g QE g -1 of weight, while for phenolic content were from 0.026 to 0.561g QE g -1 of weight. [59] In the same study, the authors evaluated the total phenolics, flavonoids and antioxidant activity of pineapple fruits, and found that the extent of the antioxidant activity of the extract is in accordance with the amounts of phenolic compounds present in the rich pineapple fruit extract in these compounds, which provides a good source of antioxidant. [55] Other ethnobotanical studies report the use of A. comosus as antioxidant, thus correlating the presence of phenolics and flavonoids as the main substances that can express this activity. The antioxidant capacity of aqueous and hydroalcoholic extracts of pineapple pulp residues, using the DPPH free radical was evaluated. It was found EC 50 of 7486.5 μg mL -1 and 3293.92 μg mL -1 , respectively. [57] In the analysis of leaves of different Bromeliaceae's species, found EC 50 of 64.24 μg mL -1 to the methanolic extract of A. comosus var. bracteatus. [97] Different studies have evaluated the presence of antimalarial activity of natural substances from plants and A. comosus is indicated. [60,61] However, research indicates that A. comosus presented weak activities because its IC 50 (> 100 μg mL -1 ). The report of antimalarial activities was supported by the in vivo study of this plant against Plasmodium berghei in mice. This same study suggests that A. comosus may be an immune stimulant, thus relieving the symptoms of the disease. [62] Activity against rheumatoid arthritis Studies indicate bromelain activity against rheumatoid arthritis (RA), with specific inhibitory activities on Cox-2 and PGE2. [63] The methanolic extract from A. comosus peel exhibited antirheumatic activity increasing the levels of SOD, CAT, and GPx enzymes in the liver, kidney, and spleen, thus decreasing CRP and prostaglandin PGE2 levels in the serum of arthritic rats. In addition, that paw histopathology also showed a reduction in necrosis when treated with the extract, flavonoids and tannins present in the extract may be responsible for the observed activity. The same author reports that the production of PGE2 by the rheumatoid synovial tissue causes cartilage erosion and the decrease of PGE2 levels when administered with the tested extract indicates the anti-inflammatory potential of A. comosus. In addition, it also suggests the possible use of A. comosus to protect cartilage from damage caused during RA. [64] Cardiovascular protective effects Research also links the use of A. comosus with cardiovascular protective effects. A study using rats to assess the protective effect on isoproterenolinduced structural and myocardial damage found that A. comosus hydroalcoholic extract protected the myocardium from damage, maintaining cell membrane integrity and improving cardiac systolic / diastolic dysfunction induced by isoproterenol. Pretreatment with 200 mg kg -1 extract showed decreased area of infarction with coagulative necrosis and inflammatory cells with moderate myocardial edema, there was mild edema. However, there was no infarction and inflammatory cells and cardiac fibers were within normal limits in the myocardium of A. comosus may improve insulin sensitivity in type 2 diabetes and be developed as a potential new natural product for the treatment of insulin resistance in diabetic patients. [69] To diabetic complications, the leaf extract of A. comosus attenuated the increase of triacylglycerol in mice with acute fructose administration indicating inhibition of endogenous triacylglycerol synthesis. [68] However, in another model that induces hypercholesterolemia, mice treated with the plant had no plasma lipid increase in 24h. Its indicate that A. comosus activates the lipase enzyme, besides inhibiting HMG-CoA reductase inhibiting endogenous cholesterol synthesis, being related to hypolipidemic action. [77] Anti-hyperlipidemic The first investigation of anti-hyperlipidemic activity in rats was carried out due to the traditional use. To evaluate the anti hyperlipidemic potential of the hydroalcoholic extract of the A. comosus leaves, rats with hyperlipidemic induced by high fat diet was treated with different concentrations of extracts. The amount of fiber present in A. comosus is directly responsible to the improvement in insulin and cholesterol levels, through the action of lipids and carbohydrates. As results of the treatment with extract the rats had significant reduction in blood glucose levels and LDL cholesterol, it was found a lipid-lowering effect in cholesterol of 32% and triglycerides of 49% after 56 days of administration. [79] However, studies that assess the true potential of the species and indicate which substances are responsible for such activities are necessary.
Ananas comosus is widely used in diseases that affect the respiratory system, such as mucolytic and fluidizing secretions and upper airways in home preparations. [80] Bromelain is a set of enzymes present in A. comosus, which have different pharmacological activities, including mucolytic action and there respiratory tract present in several studies. [81][82][83] The use in the treatment of burns Bromelain, known as an efficient debridement agent in the treatment of burns and tissue regeneration. [84] If applied topically (35% on a lipid basis) is able to promote complete debridement in experimental burns in rats in about 2 days, in comparison with collagenase, which took about 10 days, with no side effects or damage to the adjacent burnt tissue. [85] A recent study evaluated the healing potential of chitosan nanofibers containing bromelain (2% and 4% w / v) in burns induced in rats for 21 days and the results demonstrated that chitosan nanofibers with bromelain (2%) had better physical-chemicals and release profile, in addition to lower cytotoxicity than chitosan nanofibers with 4% bromelain. Compared to pure chitosan nanofiber, chitosan nanofibers with 2% bromelain were more efficient in healing burns, evidencing their wound healing activity and as an effective natural topical treatment for burn healing. [86]

Treatment of infections
Pineapples are used to help in cure of infections such as bronchitis and sore throat, due to the benefits of bromelain to the respiratory tract are bronchitis, sinusitis, mucus shrinkage, allowing the mucus to drain and relieve facial pressure and headache commonly caused by sinusitis. [87] Bromelain is a proteolytic and mucolytic enzyme, significant in the dissolution of bronchial secretion, widely used in the treatment of young children diagnosed with acute sinusitis, and safe for use in children. [82] The potential of bromelain when associated with others medicines It is well described that bromelain is capable of increasing the tissue permeability of penicillins and tetracyclines after oral administration.
rats pretreated with the extract. The protection may have been mediated by A. comosus-induced increase of antioxidant activities in myocardial enzyme, concluding that A. comosus has strong activity due to the presence of bromelain and other antioxidant substances. [65] To evaluate cadioprotection, the potency of pineapple anti-inflammatory activity in the necrotic myocardium in combination with the losartan angiotensin blocker. Sprague-Dawley rats were tested using losartan (LTN) (30mg kg -1 , 10 days, VO), and pineapple doses (100, 250 and 500 mg kg -1 , 30 days, VO) and subsequently subjected to isoprenaline administration (150 mg kg -1 ). Subsequently, histopathological observations and biochemical tests were performed to evaluate antioxidant activity. The elevated LDH and CK-MB in cardiac tissue and the enzymes SOD and catalase increased significantly, thus proving the efficacy of cardiac protection of A. comosus. The authors attributed the efficacy to the presence of bromelain, which is responsible for the increase of biomarkers and the association with the drug. [66] Hypolipidemic and hypoglycemic activity Among the plant species that present hypolipidemic and hypoglycemic activity, there are several ethnobotanical reports and research showing that A. comosus presents the pharmacological activities mentioned. According to Table 1, the following papers present research related to hypolipidemic and glycemic activity and mostly report the presence of phenolic compounds as the main agents of such activities. [67][68][69]71,72,70,[73][74][75][76][77][78] Different cereals made using the aqueous extract of A. comosus fruits were studied, showing that with the use of such cereals in vivo hypolipidemic effects were observed, however further research should be conducted with greater numbers of participants. [72] The hypolipidemic activity was investigated in fructose-fed rats. The study showed that using a dose of 0.40 g kg -1 Ananas comosus the serum triglycerides significantly reduced by 40% in rats. Since the animals' diet was increased, serum cholesterol levels increased and remained high within 7 days after the removal of high fat diets, by the administration of A. comosus, demonstrating the hypolipidemic activity of the species in question. [73] Ananas comosus could be a new alternative drug of plant origin for the treatment of hyperlipidemia, and its activity occurs by inhibition of HMG-CoA reductase and activation of LPL. The mechanism for hypolipidemic action of A. comosus, where it reports that the phenolic compounds present in A. comosus leaves act on hepatic fat metabolism, his results showed that the phenolic compounds called PLP, by the author, significantly decreased the abdominal load and the liposide accumulation in the diet. Its mechanism is different from fibrates, but somewhat similar to statins, being a good adjunct to fibrates in the treatment of hyperlipidemia. Due to the protein level, PLP increased the expression of carnitine palmitoyltransferase 1. Regarding mRNA expression, PLP mainly promoted CPT-1, PGC1a, UCP-1 and AMPK expression in mitochondria, PLP appeared to increase fat metabolism in mitochondria. Since the p-coumaric acid, a major component of the PLP, collaborated with their activity. In addition, phenolic compounds and p-coumaric acid have strong antioxidant properties, enhancing safety at preliminary values. However, further research is still important to investigate the effects of phenolic compounds and the p-coumaric acid precursor. [77] Hypoglycemic activity The hypoglycemic activity of A. comosus ethanolic extracts of leaves was investigated. The insulin sensitivity in streptozotozine-treated wistar rats fed low-fat high-dose diets and challenged with exogenous human insulin, treatment was used with A. comosus at an oral dose of 0.40 g kg -1 and A. comosus application was found to inhibit the development of insulin resistance in HepG2 cells. In addition, the authors suggest that This promotes increased absorption and leads to improved diffusion after subcutaneous and intramuscular application of antibiotics, culminating in increased serum and tissue levels and reduced side effects. [88,89] The association of bromelain and antibiotic therapy of 53 hospitalized patients with pneumonia, bronchitis, staph infections, thrombophlebitis, pyelonephritis and rectal abscesses. In all disease states, there was a significant reduction in morbidity compared to antibiotics alone. In addition, among the 53 patients, 23 were unsuccessful on antibiotics, however, 22 of them responded favorably to the combined treatment of bromelain and antibiotics. [90] In a double-blind clinical study on acute sinusitis of the patients who received bromelain, 83% had complete resolution of nasal mucosa inflammation versus 52% in the placebo group. [91] This review of the works published from 1966 to 2019 involving pharmacological actions of A. comosus relates the medicinal potential of the species and showed that A. comosus is used in popular practice in different countries, mainly Asian and African continents, in South America. Brazil has the largest number of publications. This study demonstrated that the species in question is the focus of in vitro and in vivo scientific research for several pharmacological actions, besides presenting pharmacologically important substances and secondary metabolites, especially phenolic compounds, mainly phenolic acids and flavonoids, as well as steroids and bromelain. Such compounds have different potential biological activities was already been investigated in studies. However, there is a need for work to confirm its pharmacological potential, establishing the safe use as well as the identification of other active substances. In addition, the fruit and vegetable industry generate a large number of wastes, which can serve as a basis for the extraction of these commercially important substances.
The results of this work should stimulate the continuity of studies with this species and its varieties, since the popular use of vegetables directs scientific research to search for new therapies. The multidisciplinary studies involving phytochemicals and pharmacologists are becoming increasingly important in defining the therapeutic and toxic potentials of A. comosus.

CONCLUSION
Several research groups have been working with plant species due to the interest in the scientific confirmation and validation of the effect of medicinal plants used in folk medicine. Ananas comosus presents satisfactory results in several researches involving biological / pharmacological activities, making this species attractive for future research, requiring further studies that prove mechanism of action and establish safe conditions for use.