pineapple

What is pineapple good for

The pineapple (Ananas comosus) is a tropical plant with an edible multiple fruit consisting of coalesced berries, also called pineapples and the most economically significant plant in the Bromeliaceae family 1). Pineapple crop is cultivated in all tropical and subtropical regions and ranks third in production among noncitrus tropical fruits, following banana (including plantain) and mango. The annual worldwide production reached 21.9 million metric tons in 2012 and the top seven producers (Brazil, Philippines, Thailand, Costa Rica, Indonesia, India, and China) jointly accounted for 90% of the global production (FAO, 2014) 2). The pineapple plant is indigenous to South America 3). The putative center of origin is located in the Paraná–Paraguay River drainages between southern Brazil and Paraguay, based on the diversity distribution of related species and botanical varieties of pineapple in this region 4).

The flesh and juice of the pineapple are used in cuisines around the world. In many tropical countries, pineapple is prepared and sold on roadsides as a snack. It is sold whole or in halves with a stick inserted. Whole, cored slices with a cherry in the middle are a common garnish on hams in the West. Chunks of pineapple are used in desserts such as fruit salad, as well as in some savory dishes, including pizza toppings, or as a grilled ring on a hamburger. Crushed pineapple is used in yogurt, jam, sweets, and ice cream. The juice of the pineapple is served as a beverage, and it is also the main ingredient in cocktails such as the piña colada and in the drink tepache.

Pineapples can be consumed fresh, cooked, juiced, or preserved. They are found in a wide array of cuisines. In addition to consumption, the pineapple leaves are used to produce the textile fiber piña in the Philippines, commonly used as the material for the men’s barong and women’s baro’t saya formal wear in the country 5). The fiber is also used as a component for wallpaper and other furnishings.

Figure 1. Pineapples

pineapples

Pineapple nutrition facts

In a 100-gram reference amount, raw pineapple is a rich source of manganese (44% Daily Value, DV) and vitamin C (58% DV), but otherwise contains no essential nutrients in significant quantities. Also in 100 gram of pineapple has 13.12 gram of carbs and only 50 calories. Sugar/acid ratio and ascorbic acid content vary considerably with the cultivar. The sugar content may change from 4% to 15% during the final 2 weeks before full ripening.

Table 1. Pineapple, raw, all varieties nutrition facts

NutrientUnitValue per 100 g
Approximates
Waterg86
Energykcal50
EnergykJ209
Proteing0.54
Total lipid (fat)g0.12
Ashg0.22
Carbohydrate, by differenceg13.12
Fiber, total dietaryg1.4
Sugars, totalg9.85
Sucroseg5.99
Glucose (dextrose)g1.73
Fructoseg2.12
Lactoseg0
Maltoseg0
Galactoseg0
Starchg0
Minerals
Calcium, Camg13
Iron, Femg0.29
Magnesium, Mgmg12
Phosphorus, Pmg8
Potassium, Kmg109
Sodium, Namg1
Zinc, Znmg0.12
Copper, Cumg0.11
Manganese, Mnmg0.927
Selenium, Seµg0.1
Vitamins
Vitamin C, total ascorbic acidmg47.8
Thiaminmg0.079
Riboflavinmg0.032
Niacinmg0.5
Pantothenic acidmg0.213
Vitamin B-6mg0.112
Folate, totalµg18
Folic acidµg0
Folate, foodµg18
Folate, DFEµg18
Choline, totalmg5.5
Betainemg0.1
Vitamin B-12µg0
Vitamin B-12, addedµg0
Vitamin A, RAEµg3
Retinolµg0
Carotene, betaµg35
Carotene, alphaµg0
Cryptoxanthin, betaµg0
Vitamin A, IUIU58
Lycopeneµg0
Lutein + zeaxanthinµg0
Vitamin E (alpha-tocopherol)mg0.02
Vitamin E, addedmg0
Tocopherol, betamg0
Tocopherol, gammamg0
Tocopherol, deltamg0
Vitamin D (D2 + D3)µg0
Vitamin DIU0
Vitamin K (phylloquinone)µg0.7
Lipids
Fatty acids, total saturatedg0.009
04:00:00g0
06:00:00g0
08:00:00g0
10:00:00g0
12:00:00g0
14:00:00g0
16:00:00g0.005
18:00:00g0.003
Fatty acids, total monounsaturatedg0.013
16:1 undifferentiatedg0.001
18:1 undifferentiatedg0.012
20:01:00g0
22:1 undifferentiatedg0
Fatty acids, total polyunsaturatedg0.04
18:2 undifferentiatedg0.023
18:3 undifferentiatedg0.017
18:04:00g0
20:4 undifferentiatedg0
20:5 n-3 (EPA)g0
22:5 n-3 (DPA)g0
22:6 n-3 (DHA)g0
Fatty acids, total transg0
Cholesterolmg0
Phytosterolsmg6
Amino Acids
Tryptophang0.005
Threonineg0.019
Isoleucineg0.019
Leucineg0.024
Lysineg0.026
Methionineg0.012
Cystineg0.014
Phenylalanineg0.021
Tyrosineg0.019
Valineg0.024
Arginineg0.019
Histidineg0.01
Alanineg0.033
Aspartic acidg0.121
Glutamic acidg0.079
Glycineg0.024
Prolineg0.017
Serineg0.035
Other
Alcohol, ethylg0
Caffeinemg0
Theobrominemg0
Anthocyanidins
Cyanidinmg0
Petunidinmg0
Delphinidinmg0
Malvidinmg0
Pelargonidinmg0
Peonidinmg0
Flavan-3-ols
(+)-Catechinmg0
(-)-Epigallocatechinmg0
(-)-Epicatechinmg0
(-)-Epicatechin 3-gallatemg0
(-)-Epigallocatechin 3-gallatemg0
(+)-Gallocatechinmg0
Flavanones
Hesperetinmg0
Naringeninmg0
Flavones
Apigeninmg0
Luteolinmg0
Flavonols
Kaempferolmg0
Myricetinmg0
Quercetinmg0.1
Isoflavones
Daidzeinmg0
Genisteinmg0
Total isoflavonesmg0
Proanthocyanidin
Proanthocyanidin dimersmg0
Proanthocyanidin trimersmg0
Proanthocyanidin 4-6mersmg0
Proanthocyanidin 7-10mersmg0
Proanthocyanidin polymers (>10mers)mg0
[Source 6)]

Table 2. Pineapple juice canned or bottled, unsweetened, without added ascorbic acid nutrition facts

NutrientUnitValue per 100 g
Approximates
Waterg86.37
Energykcal53
Proteing0.36
Total lipid (fat)g0.12
Carbohydrate, by differenceg12.87
Fiber, total dietaryg0.2
Sugars, totalg9.98
Minerals
Calcium, Camg13
Iron, Femg0.31
Magnesium, Mgmg12
Phosphorus, Pmg8
Potassium, Kmg130
Sodium, Namg2
Zinc, Znmg0.11
Vitamins
Vitamin C, total ascorbic acidmg10
Thiaminmg0.058
Riboflavinmg0.021
Niacinmg0.199
Vitamin B-6mg0.1
Folate, DFEµg18
Vitamin B-12µg0
Vitamin A, RAEµg0
Vitamin A, IUIU5
Vitamin E (alpha-tocopherol)mg0.02
Vitamin D (D2 + D3)µg0
Vitamin DIU0
Vitamin K (phylloquinone)µg0.3
Lipids
Fatty acids, total saturatedg0.008
Fatty acids, total monounsaturatedg0.014
Fatty acids, total polyunsaturatedg0.042
Fatty acids, total transg0
Cholesterolmg0
Other
Caffeinemg0
[Source 7)]

Pineapple health benefits

Present in all parts of the pineapple plant, bromelain is a mixture of proteolytic enzymes 8).

Bromelain belongs to a group of protein digesting enzymes obtained commercially from the fruit or stem of pineapple 9). However, bromelain is usually referred to the pineapple stem bromelain. Pineapple is the common name of Ananas comosus (Ananas sativus, Ananassa sativa, Bromelia ananas, Bromelia comosa). Pineapple is the leading edible member of the family Bromeliaceae, grown in several tropical and subtropical countries including Philippines, Thailand, Indonesia, Malaysia, Kenya, India, and China. Pineapple has been used as a medicinal plant in several native cultures 10) and these medicinal qualities of pineapple are attributed to bromelain, which is a crude extract from pineapple.

Bromelain concentration is high in pineapple stem, thus necessitating its extraction because, unlike the pineapple fruit which is normally used as food, the stem is a waste byproduct and thus inexpensive 11).

Bromelain is a mixture of different thiol endopeptidases and other components like phosphatase, glucosidase, peroxidase, cellulase, escharase and several protease inhibitors. In vitro (test tubes) and in vivo (animal) studies demonstrate that bromelain exhibits various fibrinolytic, antiedematous, antithrombotic and anti-inflammatory activities. Bromelain is considerably absorbable in the body without losing its proteolytic activity and without producing any major side effects. Bromelain accounts for many therapeutic benefits like the treatment of angina pectoris, bronchitis, sinusitis, surgical trauma, and thrombophlebitis, debridement of wounds, and enhanced absorption of drugs, particularly antibiotics. Bromelain also relieves osteoarthritis, diarrhea, and various cardiovascular disorders. Bromelain also possesses some anticancerous activities and promotes apoptotic cell death.

Pineapple Side Effects and Toxicity

When unripe, the pineapple is not only inedible but poisonous, irritating the throat and acting as a strong laxative 12).

The bromelain content of raw pineapple is responsible for the sore mouth feeling often experienced when eating it, due to the enzymes breaking down the proteins of sensitive tissues in the mouth. Also, raphides, needle-shaped crystals of calcium oxalate that occur in pineapple fruits and leaves, likely cause microabrasions, contributing to mouth discomfort 13).

Excessive consumption of pineapple cores has caused the formation of fiber balls (bezoars) in the digestive tract 14).

Bromelain enzyme

Bromelainis a mixture of different thiol endopeptidases and other components like phosphatases, glucosidase, peroxidases, cellulases, glycoproteins, carbohydrates, and several protease inhibitors 15). Stem bromelain is different from fruit bromelain 16). Proteinases are considered to be the most active fraction, which comprise ~2% of the total proteins 17). Bromelain enzymatic activities comprise a wide spectrum with pH range of 4.5 to 9.5 18). Nowadays, bromelain is prepared from cooled pineapple juice by centrifugation, ultrafiltration, and lyophilization 19). The process yields a yellowish powder, the enzyme activity of which is determined with different substrates such as casein, gelatin (gelatin digestion units), or chromogenic tripeptides 20).

The composition of bromelain varies based on the method of purification and the source; stem bromelain contains high quantities of protease content when compared with bromelain derived from the fruit 21). It was demonstrated that the majority of the physiological activity of bromelain may not be due to single proteolytic fraction and it is likely that the beneficial effects of bromelain are due to multiple factors 22). Bromelain has not only been used to treat various health problems, it is also popular as a nutritional supplement to promote health. Bromelain is absorbed into the human intestines and remains biologically active with a half-life of ~6–9 hours 23). The highest concentration of bromelain was identified in the blood one hour after administration 24). Bromelain increases bioavailability and reduces the side effects that are associated with various antibiotics 25). Furthermore, bromelain acts as an immunomodulator, is anti-metastatic, anti-edematous, anti-thrombotic and anti-inflammatory 26). These findings indicate that bromelain may present as a promising candidate for the development of future anticancer therapeutic strategies. Notably, although numerous studies have been conducted regarding bromelain there are limited reviews that document the complete anticancer activity of bromelain.

Absorption and Bioavailability of Bromelain

The body can absorb significant amount of bromelain; about 12 gm/day of bromelain can be consumed without any major side effects 27). Bromelain is absorbed from the gastrointestinal tract in a functionally intact form; approximately 40% of labeled bromelain is absorbed from intestine in high molecular form 28). In a study carried out by Castell et al. 29) bromelain was detected to retain its proteolytic activity in plasma and was also found linked with alpha 2-macroglobulin and alpha1-antichymotrypsin, the two antiproteinases of blood. In a recent study, it was demonstrated that 3.66 mg/mL of bromelain was stable in artificial stomach juice after 4 hrs of reaction and also 2.44 mg/mL of bromelain remained in artificial blood after 4 hrs of reaction 30).

Bromelain benefits

A wide range of therapeutic benefits have been claimed for bromelain, such as reversible inhibition of platelet aggregation, sinusitis, surgical traumas 31), thrombophlebitis [inflammation of the wall of a vein with associated blood clot], pyelonephritis [inflammation of the kidney as a result of bacterial infection], angina pectoris [condition marked by severe pain in the chest due to blocked artery to the heart muscle], bronchitis [inflammation of the mucous membrane in the bronchial tubes] 32), and enhanced absorption of drugs, particularly of antibiotics 33). Several studies have been carried out indicating that bromelain has useful phytomedical application. However, these results are yet to be amalgamated and critically compared so as to make out whether bromelain will gain wide acceptance as a phytomedical supplement 34). Bromelain acts on fibrinogen giving products that are similar, at least in effect, to those formed by plasmin 35). Experiment in mice showed that antacids such as sodium bicarbonate preserve the proteolytic activity of bromelain in the gastrointestinal tract 36). Bromelain is considered as a food supplement and is freely available to the general public in health food stores and pharmacies in the USA and Europe 37). Existing evidence indicates that bromelain can be a promising candidate for the development of future oral enzyme therapies for cancer patients 38). Bromelain can be absorbed in human intestines without degradation and without losing its biological activity 39).

Bromelain on Rhinosinusitis

Chronic rhinosinusitis in adults is defined as sinonasal inflammation persisting for >12 weeks. Chronic rhinosinusitis in adults is characterized by nasal obstruction/congestion/blockage, anterior or posterior nasal mucopurulent, facial pain/pressure/fullness, and decreased/loss of sense of smell. Symptoms must be accompanied by objective findings including positive nasal endoscopy (purulence, edema) or positive imaging findings such as inflammation or mucosal changes within the sinuses. A systematic review 40) of the evidence indicates that bromelain is helpful in relieving symptoms of acute nasal and sinus inflammation when used in combination with standard medications. In a study 41) to quantity bromelain in rhinosinusal mucosa of patients with chronic rhinosinusitis and individuals without nasal and paranasal pathology. It was found that patients taking Bromelain 500 mg tablet twice daily was administered for 30 days has significant distribution of bromelain in the ethmoid sinus and nasal turbinates mucus of patients with chronic rhinosinusitis, indicating that Bromelain could be exploited for use as an anti-inflammatory agent in nasal and sinusal pathologies.

Anti-inflammatory activity of bromelain

Inflammation is pivotal in the development of cancer during cellular transformation, proliferation, angiogenesis, invasion and metastasis. It has been demonstrated that suppression of chronic inflammation may reduce the cancer incidence and also inhibit cancer progression 42). Cyclooxigenase-2 (COX-2) is an important component of cancer-associated inflammation that is involved in the synthesis of prostaglandin E2 (PGE-2). PGE-2 is a pro-inflammatory lipid that also acts as an immunosuppressant, as well as a promoter of tumor progression 43). COX-2 converts arachidonic acid into PGE-2 and promotes tumor angiogenesis and cancer progression 44). It has been shown that bromelain downregulates COX-2 and PGE-2 expression levels in murine microglial cells and human monocytic leukemia cell lines 45). Bromelain activates the inflammatory mediators, including interleukin (IL)-1β, IL-6, interferon (INF)-γ and tumor necrosis factor (TNF)-α in mouse macrophage and human peripheral blood mononuclear cells 46). These results indicated that bromelain potentially activates the healthy immune system in association with the rapid response to cellular stress. Conversely, bromelain reduces IL-1β, IL-6 and TNF-α secretion when immune cells are already stimulated in the condition of inflammation-induced over production of cytokines 47). Studies have shown that bromelain reduced the expression of INF-γ and TNF-α in inflammatory bowel disease 48). A study demonstrated that bromelain diminished the cell damaging effect of advanced glycation end products by proteolytic degradation of receptor of advanced glycation end products 49) and controlled the inflammation 50). The cell surface marker, cluster of differentiation (CD)44 is expressed by cancer and immune cells directly involved in cancer growth and metastasis. Furthermore, CD44 regulates lymphocyte requirement at the site of inflammation 51). Bromelain was shown to reduce the level of CD44 expression on the surface of mouse and human tumor cells, and regulate lymphocyte homing and migration to the sites of inflammation 52). Furthermore, bromelain modulates the expression of transforming growth factor (TGF)-β, one of the major regulators of inflammation in patients affected by osteomyelofibrosis and rheumatoid arthritis 53). There are various studies that report the immunomodulatory effect of bromelain 54). Bromelain activates natural killer cells and augments the production of granulocyte-macrophage-colony stimulating factor, IL-2, IL-6 and decreases the activation of T-helper cells 55). Thus, bromelain decreases the majority of inflammatory mediators and has demonstrated a significant role as an anti-inflammatory agent in various conditions 56).

Anticancer activity of bromelain

Recent studies have shown that bromelain has the capacity to modify key pathways that support malignancy. Presumably, the anticancerous activity of bromelain is due to its direct impact on cancer cells and their micro-environment, as well as on the modulation of immune, inflammatory, and hemostatic systems 57). Most of the in vitro (test tubes) and in vivo (animals) studies on anticancer activity of bromelain are concentrated on mouse and human cells, both cancerous and normal, treated with bromelain preparations. In an experiment conducted by Beez et al 58) chemically induced mouse skin papillomas were treated with bromelain and they observed that it reduced tumor formation, tumor volume and caused apoptotic cell death. In one study related to bromelain treatment of gastric carcinoma Kato III cell lines, significant reduction of cell growth was observed 59) while in another study bromelain reduced the invasive capacity of glioblastoma cells and reduced de novo protein synthesis 60). Bromelain is found to increase the expression of p53 and Bax in mouse skin, the well-known activators of apoptosis 61). Bromelain also decreases the activity of cell survival regulators such as Akt and Erk, thus promoting apoptotic cell death in tumours. Different studies have demonstrated the role of NF-κB, Cox-2, and PGE2 as promoters of cancer progression. Evidence shows that the signaling and overexpression of NF-κB plays an important part in many types of cancers 62). Cox-2, a multiple target gene of NF-κB, facilitates the conversion of arachidonic acid into PGE2 and thus promotes tumour angiogenesis and progression 63). It is considered that inhibiting NF-κB, Cox-2, and PGE2 activity has potential as a treatment of cancer. Bromelain was found to downregulate NF-κB and Cox-2 expression in mouse papillomas 64) and in models of skin tumourigenesis 65). Bromelain was also shown to inhibit bacterial endotoxin (LPS)-induced NF-κB activity as well as the expression of PGE2 and Cox-2 in human monocytic leukemia and murine microglial cell lines 66). Bromelain markedly has in vivo antitumoural activity for the following cell lines: P-388 leukemia, sarcoma (S-37), Ehrlich ascetic tumour, Lewis lung carcinoma, and ADC-755 mammary adenocarcinoma. In these studies, intraperitoneal administration of bromelain after 24 hours of tumour cell inoculation resulted in tumour regression 67).

Antimicrobial activity

Bromelain supplementation protects animals against diarrhea caused by bacterial enterotoxins from Escherichia coli and Vibrio cholerae 68). Bromelain acts as anti-adhesion agent by modifying the receptor attachment sites and influences the intestinal secretory signaling pathways 69). In addition to its ability to counter certain effects of particular intestinal pathogens and its synergism with antibiotics, these two mechanisms are indicative of the benefits of bromelain against specific infections. In vitro evidence also suggests that bromelain exerts antihelminthic activity against the gastrointestinal nematodes, Trichuris muris and Heligmosomoides polygyrus 70). Conversely, bromelain acts as an anti-fungal agent by stimulating phagocytosis and respiratory burst killing of Candida albicans when incubated with trypsin in vitro 71). Pityriasis lichenoides chronica is an infectious skin disease and bromelain reportedly caused complete resolution of this condition 72). Bromelain has been documented to increase blood and urine levels of certain antibiotics in humans 73). Combined bromelain and antibiotic therapy was shown to be more effective than antibiotics alone in pneumonia, bronchitis, cutaneous Staphylococcus infection, thrombophlebitis, cellulitis, pyelonephritis, and in perirectal and rectal abscesses 74), sinusitis 75) and urinary tract infections 76). A combination of bromelain, trypsin, and rutin has been administered as an adjuvant therapy in combination with antibiotics for children with sepsis 77). A combination of bromelain with enzymes derived from Aspergillus niger improved protein utilization in elderly nursing home patients 78). Another study demonstrated that bromelain, in combination with sodium alginate, sodium bicarbonate and essential oils, significantly improved dyspeptic symptoms 79). In addition, bromelain has been administered successfully as a digestive enzyme to treat intestinal disorders, pancreatectomy and exocrine pancreas insufficiency 80). Finally, the combination of ox bile, pancreatin, and bromelain is effective in lowering stool fat excretion in patients with pancreatic steatorrhea, resulting in symptomatic improvements in pain, flatulence and stool frequency 81).

Bromelain on Cardiovascular and Circulation System

Bromelain prevents or minimizes the severity of angina pectoris and transient ischemic attack (TIA). It is useful in the prevention and treatment of thrombophlebitis. It may also break down cholesterol plaques and exerts a potent fibrinolytic activity. A combination of bromelain and other nutrients protect against ischemia/reperfusion injury in skeletal muscle 82). Cardiovascular diseases (CVDs) include disorders of the blood vessels and heart, coronary heart disease (heart attacks), cerebrovascular disease (stroke), raised blood pressure (hypertension), peripheral artery disease, rheumatic heart disease, heart failure, and congenital heart disease 83). Stroke and heart disease are the main cause of death, about 65% of people with diabetes die from stroke or heart disease. Bromelain has been effective in the treatment of cardiovascular diseases as it is an inhibitor of blood platelet aggregation, thus minimizing the risk of arterial thrombosis and embolism 84). King et al. 85) reported that administration of medication use to control the symptoms of diabetes, hypertension, and hypercholesteromia increased by 121% from 1988–1994 to 2001–2006 and was greater for patients with fewer healthy lifestyle habits. Bromelain supplement could reduce any of risk factors that contribute to the development of cardiovascular disease. In a recent research, Bromelain was found to attenuate development of allergic airway disease, while altering CD4+ to CD8+T lymphocyte populations. From this reduction in allergic airway disease outcomes it was suggested that bromelain may have similar effects in the treatment of human asthma and hypersensitivity disorders 86). In another study, carried out by Juhasz et al., Bromelain was proved to exhibit the ability of inducing cardioprotection against ischemia-reperfusion injury through Akt/Foxo pathway in rat myocardium 87).

Bromelain on Osteoarthritis

Osteoarthritis is the most common form of arthritis in Western countries; in USA prevalence of osteoarthritis ranges from 3.2 to 33% dependent on the joint 88). A combination of bromelain, trypsin, and rutin was compared to diclofenac in 103 patients with osteoarthritis of the knee. After six weeks, both treatments resulted in significant and similar reduction in the pain and inflammation 89). Bromelain is a food supplement that may provide an alternative treatment to nonsteroidal anti-inflammatory drug (NSAIDs) 90). It plays an important role in the pathogenesis of arthritis 91). Bromelain has analgesic properties which are thought to be the result of its direct influence on pain mediators such as bradykinin 92). The earliest reported studies investigating bromelain were a series of case reports on 28 patients, with moderate or severe rheumatoid or osteoarthritis 93).

In conclusion, bromelain appears to have potential for the treatment of knee osteoarthritis. However it is important to note that there are a number of methodological issues that are common to the studies reported, including the possibility of inadequate power, inadequate treatment periods, inadequate or non-existent follow-up to monitor possible adverse drug reactions. Furthermore, the optimum dosage for this condition remains unclear. A phase II clinical trial would be beneficial to identify the optimal dosage and to systematically monitor safety issues before a definitive efficacy study could be completed.

Bromelain on Immune System

Bromelain has been recommended as an adjuvant therapeutic approach in the treatment of chronic inflammatory, malignant, and autoimmune diseases 94). In vitro experiments have shown that Bromelain has the ability to modulate surface adhesion molecules on T cells, macrophages, and natural killer cells and also induce the secretion of IL-1β, IL-6, and tumour necrosis factor α (TNFα) by peripheral blood mononuclear cells 95). Tumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory cytokine and increased TNF-α production is found in serum, stools, and bowel mucosa in both inflammatory bowel disease (IBD) patients and inflammatory bowel disease (IBD) models 96). Anti-TNF therapy has been confirmed to alleviate symptoms, heal mucosal ulcers, spare corticosteroid treatment, and decrease hospitalization costs. TNF-α leads to the activation of nuclear factor kappa B (NF-κB), which can transmigrate into the nucleus, and it binds to DNA response elements in gene promoter regions to control transcription of genes, such as inducible NO synthase (iNOS), cyclo-oxygenase-2 (COX2), and myosin light chain kinase 97). Both iNOS and COX2 are pro-inflammatory mediators which play crucial roles in inflammatory responses 98). The expression and activity of myosin light chain kinase is increased in human inflammatory bowel disease (IBD) and associated with histological evidence of disease activity 99). Myosin light chain kinase-induced phosphorylation of perijunctional actomyosin mediates tight junction loss, which triggers the initiation and development of inflammatory bowel disease (IBD) 100). TNF-α exerts its biological function by binding to two kinds of TNF-α receptors (TNFRs), including TNFR1 and TNFR2. Epithelial TNFR1 and TNFR2 are relatively under-examined, but they have been implicated in epithelial apoptosis, proliferation, migration, and tight junction regulation 101). Oral administration of bromelain relieved IBD symptoms 102); however, the effect of bromelain on intestinal inflammation induced by chemical damage and its underlying mechanisms are still not fully understood.

Bromelain can block the Raf-1/extracellular-regulated-kinase- (ERK-) 2 pathways by inhibiting the T cell signal transduction 103). Treatment of cells with bromelain decreases the activation of CD4 (+) T cells and reduce the expression of CD25 104). Moreover, there is evidence that oral therapy with bromelain produces certain analgesic and anti-inflammatory effects in patients with rheumatoid arthritis, which is one of the most common autoimmune diseases 105).

Bromelain on Blood Coagulation and Fibrinolysis

Bromelain influences blood coagulation by increasing the serum fibrinolytic ability and by inhibiting the synthesis of fibrin, a protein involved in blood clotting 106). In rats, the reduction of serum fibrinogen level by bromelain is dose dependent. At a higher concentration of bromelain, both prothrombin time (PT) and activated partial thromboplastin time (APTT) are markedly prolonged 107). In vitro and in vivo studies have suggested that bromelain is an effective fibrinolytic agent as it stimulates the conversion of plasminogen to plasmin, resulting in increased fibrinolysis by degrading fibrin 108).

Bromelain on Diarrhea

Evidence has suggested that bromelain counteracts some of the effects of certain intestinal pathogens like Vibrio cholera and Escherichia coli, whose enterotoxin causes diarrhoea in animals. Bromelain appears to exhibit this effect by interacting with intestinal secretory signaling pathways, including adenosine 3′ : 5′-cyclic monophosphatase, guanosine 3′ : 5′-cyclic monophosphatase, and calcium-dependent signaling cascades 109). Other studies suggest a different mechanism of action. In E. coli infection, an active supplementation with bromelain leads to some antiadhesion effects which prevent the bacteria from attaching to specific glycoprotein receptors located on the intestinal mucosa by proteolytically modifying the receptor attachment sites 110).

Bromelain in Surgery

Administration of bromelain before a surgery can reduce the average number of days for complete disappearance of pain and postsurgery inflammation 111). Trials indicate that bromelain might be effective in reducing swelling, bruising, and pain in women having episiotomy 112). Nowadays, bromelain is used for treating acute inflammation and sports injuries 113).

Bromelain in Debridement Burns

The removal of damaged tissue from wounds or second/third degree burns is termed as debridement. Bromelain applied as a cream (35% bromelain in a lipid base) can be beneficial for debridement of necrotic tissue and acceleration of healing. Bromelain contains escharase which is responsible for this effect. Escharase is nonproteolytic and has no hydrolytic enzyme activity against normal protein substrate or various glycosaminoglycan substrates. Its activity varies greatly with different preparations 114). In two different enzymatic debridement studies carried out in pig model, using different bromelain-based agents, namely, Debriding Gel Dressing (DGD) and Debrase Gel Dressing showed rapid removal of the necrotic layer of the dermis with preservation of the unburned tissues 115), 116). In another study on Chinese landrace pigs, enzymatic debridement using topical bromelain in incised wound tracks accelerated the recovery of blood perfusion, pO2 in wound tissue, controlled the expression of TNF-α, and raised the expression of TGT-β 117). Enzymatic debridement using bromelain is better than surgical debridement as surgical incision is painful, nonselective and exposes the patients to the risk of repeated anaesthesia and significant bleeding 118), 119).

Bromelain side effects

Studies that have used a higher daily dose of bromelain to treat osteoarthritis [945 mg/day 120); 1890 mg/day 121)] appear to be conflicting. The authors employing the highest dose reported that the medication was well tolerated; the dose of 945 mg/day, however, showed a higher incidence of adverse drug reactions and drop-outs. Adverse events that have been reported are mainly gastrointestinal (i.e. diarrhoea, nausea and flatulence), but have also included headache, tiredness, dry mouth, skin rash and allergic reactions (not specified) 122).

There have been some reports of gastrointestinal problems, increased heart rate, and menstrual problems in people who have taken bromelain orally.

Allergic reactions may occur in individuals who are sensitive or allergic to pineapples or who may have other allergies.

According to Taussig et al. 123) bromelain has very low toxicity with an LD50 (lethal doses) greater than 10 g/kg in mice, rates, and rabbits. Toxicity tests on dogs, with increasing level of bromelain up to 750 mg/kg administered daily, showed no toxic effects after six months. Dosages of 1500 mg/kg per day when administered to rats showed no carcinogenic or teratogenic effects and did not provoke any alteration in food intake, histology of heart, growth, spleen, kidney, or hematological parameters 124). Eckert et al. 125) after giving bromelain (3000 FIP unit/day [FIP is an enzyme unit that produces a certain amount of enzymatic activity]) to human over a period of ten days found no significant changes in blood coagulation parameters.

References   [ + ]