Use Of Bromelain Research Articles

ASO Author Reflections: Innovative HIPEC Organoid Models and Mucolytics: Targeted Therapeutic Use of Bromelain for Appendiceal Cancer.

ASO Author Reflections: Innovative HIPEC Organoid Models and Mucolytics: Targeted Therapeutic Use of Bromelain for Appendiceal Cancer.

Current Uses of Bromelain in Children: A Narrative Review.

Bromelain is a complex natural mixture of sulfhydryl-containing proteolytic enzymes that can be extracted from the stem or fruit of the pineapple. This compound is considered a safe nutraceutical, has been used to treat various health problems, and is also popular as a health-promoting dietary supplement. There is continued interest in bromelain due to its remarkable therapeutic properties. The mechanism of action of bromelain appears to extend beyond its proteolytic activity as a digestive enzyme, encompassing a range of effects (mucolytic, anti-inflammatory, anticoagulant, and antiedematous effects). Little is known about the clinical use of bromelain in pediatrics, as most of the available data come from in vitro and animal studies, as well as a few RCTs in adults. This narrative review was aimed at highlighting the main aspects of the use of bromelain in children, which still appears to be limited compared to its potential. Relevant articles were identified through searches in MEDLINE, PubMed, and EMBASE. There is no conclusive evidence to support the use of bromelain in children, but the limited literature data suggest that its addition to standard therapy may be beneficial in treating conditions such as upper respiratory tract infections, specific dental conditions, and burns. Further studies, including RCTs in pediatric settings, are needed to better elucidate the mechanism of action and properties of bromelain in various therapeutic areas.

Effect of the use of bromelain associated with bioactive glass-ceramic on dentin/adhesive interface.

To evaluate the effect of bromelain associated with Biosilicate on the bond strength (BS) of a universal adhesive system to sound (SD) and caries-affected dentin (CAD), and on the proteolytic activity. Cavities were prepared in 360 molars, half submitted to cariogenic challenge. Teeth were separated into groups (n=20): Control-No treatment; CHX-0.12% chlorhexidine; NaOCl-5% sodium hypochlorite; Br5%-5% bromelain; Br10%-10% bromelain; Bio-10% Biosilicate; NaOClBio-NaOCl+Bio; Br5%Bio-Br5%+Bio; Br10%Bio-Br10%+Bio. Following treatments, the adhesive system was applied, and cavities were restored. Samples were sectioned into sticks and stored at 37 °C for 24 h, 6 months, and 1 year. Microtensile BS (2-way ANOVA, Bonferroni's test, α=0.05), fracture patterns (SEM), and adhesive interfaces (TEM) were evaluated. Bacterial collagenase assay and in situ zymography were performed. In CAD, Br10% presented higher BS (p=0.0208) than Br5%Bio. Br5% presented higher BS (p=0.0033) after 6 months than after 24 h; and association of treatments, higher BS (p<0.05) after aging than after 24 h. Mixed fractures were the most prevalent. Association of treatments promoted a more uniform hybrid layer with embedded Bio particles. Experimental groups presented lower (p<0.0001) relative fluorescence units than Control. Bromelain, associated or not with Bio, showed collagenolytic degradation. Bromelain associated with Biosilicate did not affect the BS to SD. In CAD, Br5%Bio decreased immediate BS but had no long-term influence. This association decreased the proteolytic activity. Bromelain and Biosilicatemay enhance the longevity of adhesive restorations by inhibiting endogenous proteases.

Tetrasiklin Antibiyotikleri ve Bromelain Enzimi Arasındaki Etkileşimlerin Kenetleme Araçları Kullanılarak İncelenmesi

Bromelain, extracted from the stem of the pineapple, is a complex enzyme used for different purposes. Bromelain supplements are often used to facilitate digestion, improve the circulatory system and relieve arthritis symptoms due to its pain relief. However, in some cases where there is a risk of antibiotic use or bleeding, the use of bromelain or direct consumption of pineapple should be limited. For this purpose, this study was carried out to show the mechanism by which the antibiotic bromelain interaction occurs. Firstly, the bromelain molecule and demeclocycline, minocycline, and tetracycline antibiotics were prepared in the UCSF Chimera visualizing program. The interactions were monitored in the Auto Dock Molecular Modelling Toolkit molecular modeling program. The free binding energies of these interactions were also calculated in Auto Dock. According the molecular modelling results, bromelain and demeclocycline, minocycline, tetracycline antibiotics were interact with hydrogen bonds and hydrophobic interactions. These interactions between bromelain and antibiotics were energetically favorable based on free binding energy calculations.

Mucoadhesive Cationic Bromelain Laden Nanocarriers Restore Patency of Airway Hyperresponsive Remodeling via Nasal Route

AbstractBromelain, a complex mixture of proteolytic cysteine proteases has shown positive attributes in management of allergen induced inflammatory conditions. However, efficient use of bromelain in clinics is restricted by bromelain instability at storage conditions and on oral use. Therefore, the goal of present investigation is to encapsulate bromelain in rationally tailored mucoadhesive polymeric nanocarriers for nasal delivery to refurbish its anti‐asthmatic activity and improve bioavailability. Bromelain laden Eudragid RL 100 nanocarriers (Br‐EuNCs) are engineered via double emulsion solvent evaporation method and optimized to amplify bromelain encapsulation within nanosize range (259.73 ± 16.51 nm). Dissolution study reveals prolonged bromelain release behavior (24 h) whereas higher mucin binding strength confirms mucoadhesive nature of Br‐EuNCs. Pharmacokinetic study in rats indicates 2.89‐fold increase in bromelain bioavailability after its encapsulation. Subsequently, pharmacodynamic studies reveal that optimized formulation significantly (p &lt;0.05) reduces spasm, bronchial hyper‐responsiveness and inhibits convulsions in the ovalbumin induced asthma model. In addition, Br‐EuNCs significantly regulate hematological, biochemical, and immunological parameters disturbed during ovalbumin exposure. Histological studies of lung show significant protectionoffered by formulation against tissue damage during asthma. The results suggest that therapeutic performance of bromelain can be improved utilizing Br‐EuNCs as a platform via nasal route for asthma management.

Extracorporeal shock wave therapy in association with bromelain and escin for the management of patients affected by chronic prostatitis/chronic pelvic pain syndrome.

Extracorporeal shock wave therapy (ESWT) has been purposed for the management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with encouraging results. Phytotherapeutic compounds have been used in everyday clinical practice for patients with CP/CPSS due to their anti-inflammatory properties. The present study aimed to investigate the effects of ESWT in association with the use of bromelain and escin extracts in patients with CP/CPSS. For this purpose, 95 patients with a clinical diagnosis of CP/CPSS were enrolled in the study. The patients were randomly allocated to either the ESWT plus bromelain and escin group (group A; n=48) or the ESWT only group (group B; n=47). A total of five weekly ESWT treatment sessions were administered alone or in combination with bromelain and escin. Each session consisted of 3,000 focused shock waves. Doses of 160 and 500 mg/day bromelain and escin were administered respectively for 5 weeks. The changes in urinary symptoms, pain and quality of life were considered the main outcome measures and were assessed at baseline, and at 4, 12 and 24 weeks of follow-up. Urinary symptoms, pain and quality of life were evaluated using the international prostatic symptoms score (IPSS), visual analog scale (VAS) and the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). After 4 weeks, the mean VAS score, mean IPSS and mean satisfaction rate score had significantly improved in patients receiving ESWT plus bromelain and escin. After 12 weeks, the mean IPSS and mean satisfaction rate score were stable in the ESWT plus bromelain and escin group, while the mean VAS score was significantly lower when compared with the baseline values in both groups. On the whole, the present study demonstrates that in patients affected by CP/CPPS, treatment with ESWT plus bromelain and escin leads to pain resolution, and both treatments improve the IPSS, VAS and NIH-CPSI results.

Therapeutic Efficacy of Bromelain in Alveolar Ridge Preservation.

Most of research in regenerative oral surgery describes materials or techniques for increasing volumetric results for implant-supported prosthesis. The use of bio-materials in alveolar ridge preservation after tooth extraction commonly leads to a delayed recovery. Bromelain is an enzyme that belongs to a family of proteolytic enzymes derived from the stem of the pineapple plant (Ananas comosus) with effectiveness in decreasing the inflammation development and swelling. The present paper reports a prospective comparative study performed in order to test the possible use of oral bromelain 40 mg in alveolar ridge preservation. Evaluations were performed at three time points after the surgery: after 2 days (t1), after 7 days (t2) and after 14 days (t3). A statistically significant difference among patients that used bromelain and patients that used placebo resulted among the use of bromelain and lower Visual Analogue Scale (VAS) at t1 (r = -0.75, p = 0.0067), t2 (r = -0.90, p = 0.0001) and t3 (r = -0.8566, p = 0.0008). Bromelain therapy reported a statistically significant difference among patients that used bromelain and patients that used placebo even with regards to the use of bromelain and postoperative swelling at t1 (r = -0.79, p = 0.0034), t2 (r = -0.81, p = 0.0020) but not at t3 (r = -0.34, p = 0.2967). With the result of the present paper, and the poorness of contraindication of the investigated drug, bromelain may be suggested to be used for patients that undergo to alveolar ridge preservation after tooth extraction.

Efficiency of Bromelain-Enriched Enzyme Mixture (NexoBrid™) in the Treatment of Burn Wounds

Background: The use of bromelain for the removal of eschar in deep burns is considered to be effective because it does not affect the unaffected skin and leaves a clean dermis after use. The main objective of this study is to find out whether bromelain is a good alternative to surgical debridement. In order to achieve that, we aim to evaluate its indications, limitations, and safety measures. Methods: The current study was conducted on a group of 30 patients with deep burn lesions, aged 20 to 56 years, from which 15 underwent enzymatic debridement and 15 patients acted as a control group in which primary surgical debridement was used. The mixture of enzymes enriched in bromelain, meant to dissolve burn eschar, was provided by NexoBrid™. The inclusion criteria were in agreement with the manufacturer’s protocols, but the application protocol was slightly modified in order to implement a better intern protocol and to assess its efficiency. Results: Complete eschar debridement was obtained in 13 of the 15 cases, from which 10 patients went through spontaneous healing and 3 needed to be covered with a skin graft. In the other 2 cases, partial eschar debridement was associated with surgical debridement and coverage with split-thickness skin graft in the same operation. The results obtained in the two groups were assessed with the Vancouver Scar Scale. Conclusions: Even though early excision followed by coverage with split-thickness skin graft remains the gold standard for the treatment of deep burns, enzymatic debridement can provide a series of advantages when the inclusion and exclusion criteria are respected. Bromelain is an alternative to surgical debridement that provides speed, tissue selectivity, safety, and less blood loss.

REVIEW: APPLICATION OF BROMELAIN ENZYMES IN ANIMAL FOOD PRODUCTS

This review focuses on the use of bromelain in various applications in animal products with the latest literature so that it can provide information on what parts of this enzyme can be applied. Bromelain is a protease enzyme found in stems (EC 3.4.22.32), leaves, crowns, fruit skins, fruit flesh (EC 3.4.22.33) and fruit tubers in pineapple. Bromelain has been exploited commercially in many applications in the food industry (baking industry), drinks industry (stabilizers in beer), tenders (meat), and pharmaceuticals (anti-tumorigenic agents). However, not all types of proteins can be hydrolyzed by bromelain, such as keratin which can only be hydrolyzed by keratinase, this is because the enzymes work specifically. In animal food products, bromelain is applied as a meat tenderizer, making of protein hydrolyzate products, cheese and also fish sauce product. The application of bromelain to animal food products has proven that hydrolyzed products using this enzyme can increase umami taste, which means that bromelain has great potential when applied to animal food products. Bromelain is useful in the processing of some animal food products because bromelain works specifically and is very active in animal protein such as milk, meat and collagen.

Use of bromelain in cutaneous wound healing in streptozocin-induced diabetic rats: an experimental model.

To assess the effect of bromelain on different aspects of the wound healing process in type 1 diabetic rats. In this study, 112 streptozocin-diabetic (type 1) male Wistar rats were euthanised; 28 each on days three, five, seven and 15, after a wound incision had been made. To estimate changes in a number of different cellular and tissue elements, histological sections were provided from all wound areas and stained with haematoxylin and eosin. Some 1.056mm2 of total wound area from all specimens were evaluated, by assessment of 4200 microscope photos provided from all histological sections, by stereological methods. A biomechanical test of each wound area was performed with an extensometer to evaluate the work-up to maximum force and maximum stress of the healed wound on day 15. In the experimental groups, bromleain caused significant wound contraction and reduced granulation tissue formation by day 7 (p=0.003); increased neovasculars (new small vessels that appear in the wound area during wound healing) on days three, five and seven (p=0.001); significantly increased fibroblasts on day five but decreased by day seven (p=0.002); and significantly decreased macrophage numbers and epithelium thickness on all days of study (p=0.005). Wound strength significantly increased in experimental groups by day 15. Bromelain has a wide range of therapeutic benefits, but in most studies the mode of its action is not properly understood. It has been proved that bromelain has no major side effects, even after prolonged use. According to the results of this study, bromelain can be used as an effective health supplement to promote and accelerate wound healing indices, reduce inflammation and improve biomechanical parameters in diabetic wounds.

Effective enzymatic debridement of burn wounds depends on the denaturation status of collagen.

The treatment of burn wounds by enzymatic debridement using bromelain has shown promising results in our burn center. However, inadequate debridement occurred in a few cases in which the etiology of the burn was attributed to relatively low temperature burns. We hypothesized that bromelain is ineffective in burns in which collagen denaturation, which occurs approximately at 65°C, has not taken place. Our objective was to assess whether there is a relationship between the denaturation of collagen and the ability of bromelain to debride acute scald burn wounds of different temperatures. Ex vivo human skin from four different donors was cut into 1x1 cm samples, and scald burns were produced by immersion in water at temperatures of 40°C, 50°C, 60°C, 70°C, and 100°C for 20 minutes. Denaturation of collagen was assessed with histology, using hematoxylin and eosin (H&E) staining and a fluorescently labeled collagen hybridizing peptide (CHP), and with second harmonic generation (SHG) microscopy. Burned samples and one control sample (room temperature) were weighed before and after application of enzymatic debridement to assess the efficacy of enzymatic debridement. After enzymatic debridement, a weight reduction of 80% was seen in the samples heated to 70°C and 100°C, whereas the other samples showed a reduction of 20%. Unfolding of collagen, loss of basket-weave arrangement, and necrosis was seen in samples heated to 60°C or higher. Evident CHP fluorescence, indicative of collagen denaturation, was seen in samples of 60°C, 70°C and 100°C. SHG intensity, signifying intact collagen, was significantly lower in the 70°C and 100°C group (P <.05) compared to the lower temperatures. In conclusion, denaturation of collagen in skin samples occurred between 60°C and 70°C and strongly correlated with the efficacy of enzymatic debridement. Therefore, enzymatic debridement with the use of bromelain is ineffective in scald burns lower than 60°C.

Microtensile Bond Strength of Composite Resin Following the Use of Bromelain and Papain as Deproteinizing Agents on Etched Dentin: An In Vitro Study.

ABSTRACTAim and objectivesThe aim of this study was to evaluate and compare the deproteinizing effect of sodium hypochlorite, bromelain, and papain on microtensile bond strength of composite resin to etched dentin.Materials and methodsEighty freshly extracted permanent molars were wet grounded into a flat surface using a diamond disk to expose the superficial dentinal surface. Teeth were etched with 37% phosphoric acid for 15 seconds and rinsed with water and blot dried. Teeth were divided into four groups (n = 20) based on the method of dentin deproteinization. Group I: only etching; group II: deproteinized with 5.25% sodium hypochlorite for 1 minute; group III: deproteinized with 8% bromelain enzyme for 1 minute; and group IV: deproteinized with 8% papain enzyme for 1 minute. All the samples were washed off with distilled water to remove deproteinizing agents. Sample surfaces were blot dried and bonding of the dentin surface was performed and restored with light cure bulk fill composite. Samples were stored in distilled water (37°C/24 hours) and thermocycled. Then, the teeth were longitudinally sectioned and individually fixed to a sectioning block using acrylic resin. The block was mounted on hard tissue microtome and sectioned to get one to three slabs of 1 mm thick sections. The beam was then attached to a custom-made jig using screws subjected to the Instron universal testing machine. A tensile load was applied at a crosshead speed of 0.5 mm/minute until the beam fractured.ResultsHigher mean bond strength was recorded in group IV followed by group III, group II, and group I, respectively. Group III presented a statistically significant highest mean score compared to other study groups with group I and group II (p < 0.001), followed by group IV having significantly higher mean score compared to group I and group II (p < 0.001) and finally a significant difference was observed between group II and group I (p < 0.001). However, the mean microtensile bond strength score did not differ significantly between group III and group IV (p = 0.20).ConclusionWithin the limitations of this present in vitro study, the following conclusions were drawn. The microtensile bond strength of dentine tested in various deproteinizing agents is as follows: 8% bromelain > 8% papain > 5.25% NaOCl > control group. Naturally occurring deproteinizing agents, such as bromelain and papain, used in this study have resulted in greater bond strength values when compared to that of traditionally used chemical agent such as NaOCl.How to cite this articleKhatib MS, Devarasanahalli SV, Aswathanarayana RM, et al. Microtensile Bond Strength of Composite Resin Following the Use of Bromelain and Papain as Deproteinizing Agents on Etched Dentin: An In Vitro Study. Int J Clin Pediatr Dent 2020;13(1):43–47.

Novel use of bromelain in the management of infected prosthetic surgical mesh after ventral hernia repair

Surgical mesh infections from ventral hernia repairs are common in obese patients. Definitive management includes the surgical removal of mesh; however, obese patients are often poor surgical candidates with limited therapeutic options. We report the case of a 64-year-old male with an abdominal wall seroma secondary to an infected surgical mesh. This was on a background of multiple abdominal wall reconstructions for previous strangulated ventral hernias. A nonoperative novel approach utilizing bromelain percutaneously in conjunction with antibiotics successfully resolved the infected seroma. The purpose of this case is to detail the potential clinical application of bromelain in surgical site infections involving surgical prosthesis. We illustrate the successful use of bromelain as a nonoperative alternative for abdominal infections or when all other surgical and conservative therapies have been exhausted.

REVIEW: PEMANFAATAN BROMELAIN PADA BEBERAPA PANGAN LOKAL INDONESIA

Bromelain is one of the protease that can be produced from all of parts of the pineapple plants (Ananas comosus). It has potential to improve quality of local Indonesian food such as tempeh gembus, virgin coconut oil (VCO), and dumbo catfish based fish sauce (DCBFS). Tempeh gembus is a traditional food that has unique characteristics especially in its taste because it contains amino acids. VCO attracts consumers because of its health aspect. Its raw materials are available in Indonesia. DCBS is a product of fermented fish with salt that has a distinctive taste and is produced in Indonesia. This study aimed to analyze the effect of bromelain on local Indonesian food and its applications. The result showed that the use of bromelain in local Indonesian food could improve the quality and nutritional value of local food. Bromelain can be used in local food like tempeh gembus, virgin coconut oil, and fish sauce from dumbo catfish. The use of bromelain in tempeh gembus could increase both of the water-soluble nitrogen level and the pH value. However, the addition of bromelain in the production of virgin coconut oil and fish sauce from dumbo catfish could increase the yield of theirs. .

The use of bromelain as a feed additive in fish diets: Growth performance, intestinal morphology, digestive enzyme and immune response of juvenile Sterlet (Acipenser ruthenus)

Bromelain is a proteolytic enzyme extracted from Ananas comosus and has great potential to affect several physiological functions. The current study examined the effect of bromelain added to commercial feed at concentrations of 0 g (control), 10 g (B1) and 20 g (B2) per kg diet on growth, feed utilization, intestinal morphology, digestive enzyme and immune response of juvenile Sterlet (Acipenser ruthenus) for 56 days. At the end of this experiment, the highest final body weight was detected in fish fed diet of B2 compared to control. The protein content of whole fish was higher in fish fed diet of B1 and B2, but the content of calcium, iron, copper and zinc was noted lower in fillets of fish fed diet of B1 and B2. Supplementation with bromelain significantly increased the height of mucosal folds, enterocytes and the supranuclear zone of the epithelial cells compared to control diet. The enzymatic activity of lipase and pepsin was significantly (p 0.05) difference was found in ceruloplasmin, metabolic activity of spleen macrophages and potential killing activity of spleen phagocytes between different treatments.

In Vitro Effect of Bromelain on the Regenerative Properties of Mesenchymal Stem Cells.

Bromelain belongs to a group of protein-digesting enzymes obtained commercially from the fruit or stem of pineapple. Several studies demonstrated that bromelain exhibits various fibrinolytic, anti-edematous, antithrombotic, and anti-inflammatory activities supporting its application for many therapeutic benefits. The aim of this study was to analyze the effects of bromelain on the pro-wound healing activities and the regenerative properties of mesenchymal stem cells. Mesenchymal stem cells were treated in vitro with bromelain alone or combined with dexamethasone sodium phosphate. Real-time polymerase chain reaction was performed to profile the expression of extracellular matrix components and remodeling enzymes, and cytokines. The combination of bromelain and dexamethasone sodium phosphate induced a great activation of mesenchymal stem cells with an increase in hyaluronan and collagen production and anti-inflammatory cytokines release. Based on the results of this in vitro study, the combined use of bromelain and dexamethasone sodium phosphate stimulated the pro-wound healing activities and the regenerative properties of mesenchymal stem cells better than bromelain and dexamethasone alone.

The potential use of bromelain as a natural oral medicine having anticarcinogenic activities.

Bromelain (BR), a protease extracted from Ananas comosus, reportedly possesses pharmacological activities including the reduction of thrombogenesis, and antihypertensive, and antimicrobial effects. This study aimed to investigate the potential effects of BR on oral cancer cells. The effect of BR on the viability of Ca9‐22 and SCC25 cells was determined using the MTT assay. These cells were also treated with different doses of BR, and Western blotting was conducted to monitor apoptosis. Finally, flow cytometry analysis was performed to identify sub‐G1 populations of oral cancer cells. After treatment, the viability of both Ca9‐22 and SCC25 cells was markedly reduced, in a dose‐dependent manner. BR induced poly (ADP‐ribose) polymerase (PARP) and lamin A/C degradation, and generated cleavage products. Flow cytometry analysis showed that BR treatment significantly increased the sub‐G1 population. Our findings therefore indicate that BR has potential as a novel, natural anticarcinogenic medicine.

Is bromelain effective in controlling the inflammatory parameters of pain, edema, and trismus after lower third molar surgery? A systematic review and meta-analysis.

The aim of this systematic review was to evaluate the clinical evidences of the bromelain in minimizing inflammatory parameters such as pain, edema, and trismus after lower third molar surgeries. An electronic search was conducted in six databases through November 2017. The eligibility criteria included randomized and non-randomized clinical trials and/or comparative studies that used bromelain after lower third molar surgeries. The search strategy resulted in 117 articles. Following the selection process, seven studies were included in the systematic review and four in the meta-analysis. In terms of the risk of bias analysis, all the evaluated studies were classified as low or unclear risk of bias in the following criteria: selection bias, detection bias, and reporting bias. The final quantitative analysis of the variables showed that the use of bromelain resulted in greater reduction of pain levels (mean difference [MD]: -0.38; 95% confidence interval [CI; -0.66 to -0.09]), edema (MD: -0.34; 95% CI [ -0.68 to -0.01]), and trismus (MD: -2.01; 95% CI [ -3.99 to -0.02]) among the analyzed groups. The results suggest that the bromelain appears to be effective in the control of pain, edema, and trismus after lower third molar surgeries; however, further high-quality studies are needed to confirm this finding.

Bromelain's penetration into the blood and sinonasal mucosa in patients with chronic rhinosinusitis.

The aim of this research is to investigate penetration of Bromelain into sinonasal mucosa in patients with chronic rhinosinusitis (CRS) versus a control group. Bromelain is derived from pineapple (Ananas comosus) and has various pharmacological effects. 40 patients (20 patients and 20 controls) were enrolled in the study. Bromelain 500 mg tablet twice daily was administered for 30 days. We scored bromelain presence in turbinate and ethmoid mucosas and in the serum of both the groups. Bromelain has an excellent distribution from blood to rhinosinusal mucosa. Its diffusion ability may allow the use of bromelain as an anti-inflammatory agent in paranasal sinus pathologies.

In Silico and In Vitro Study of the Bromelain-Phytochemical Complex Inhibition of Phospholipase A2 (Pla2).

Phospholipase A2 (Pla2) is an enzyme that induces inflammation, making Pla2 activity an effective approach to reduce inflammation. Therefore, investigating natural compounds for this Pla2 inhibitory activity has important therapeutic potential. The objective of this study was to investigate the potential in bromelain-phytochemical complex inhibitors via a combination of in silico and in vitro methods. Bromelain-amenthoflavone displays antagonistic effects on Pla2. Bromelian-asiaticoside and bromelain-diosgenin displayed synergistic effects at high concentrations of the combined compounds, with inhibition percentages of more than 70% and 90%, respectively, and antagonistic effects at low concentrations. The synergistic effect of the bromelain-asiaticoside and bromelain-diosgenin combinations represents a new application in treating inflammation. These findings not only provide significant quantitative data, but also provide an insight on valuable implications for the combined use of bromelain with asiaticoside and diosgenin in treating inflammation, and may help researchers develop more natural bioactive compounds in daily foods as anti-inflammatory agent.