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Bromelain is a proteolytic enzyme found in pineapple fruit. This study was conducted to evaluate the effects of bromelain supplementation on disease activity and quality of life (QoL) in patients with ulcerative colitis (UC). Seventy individuals with mild-to-moderate UC participated in a randomized, triple-blind clinical trial. Participants were randomly assigned to receive either maltodextrin as a placebo or 400 mg of bromelain daily for eight weeks. QoL and Simple Clinical Colitis Activity Index (SCCAI) scores were assessed. All results were analyzed using both intention-to-treat (ITT) and per-protocol (PP) approaches. The only demographic factor that differed between the two groups statistically significantly was gender (p = 0.01). Additionally, the mean difference in vitamin B6 consumption variations between the bromelain and placebo groups was significant (0.39 ± 0.86 vs. -0.44 ± 1.43; p < 0.001). There was no considerable difference detected for the other nutrients. The bromelain group had considerably higher changes in their SCCAI score in comparison with the placebo group (-3.29 ± 2.17 vs. -1.11 ± 1.71; p < 0.001). There was no considerable difference in changes in QoL questionnaire scores between the intervention and control groups (3.76 ± 6.18 vs. 3.91 ± 4.30; p = 0.90). After correcting for baseline, the findings remained significant for the SCCAI variable but not for the QoL variable (p < 0.001 and p = 0.99). In UC patients, the severity of the disease is reduced by bromelain supplementation, which is an alternative therapy.Trial registration: The study protocol received approval from the Ethics Committee at Iran University of Medical Sciences "IR.IUMS.REC.1402.125" and was registered with the Iranian Clinical Trials Registry "IRCT20191105045340N2" on 09/07/2023. © 2025. The Author(s).

This randomized, double-blind, placebo- and active-controlled clinical trial evaluated the efficacy and safety of EnMax tablets in managing postoperative inflammation and supporting wound healing following orthopedic surgery. A total of 105 patients were randomized to receive EnMax, a comparator enzyme formulation (trypsin-bromelain-rutoside), or placebo alongside standard care for 7 days. Baseline characteristics were statistically comparable across all groups. EnMax demonstrated significant clinical benefits, including substantial reductions in pain (93.10%), inflammation (89.77%), and key inflammatory biomarkers-C-reactive protein (CRP, 57% reduction) and erythrocyte sedimentation rate (ESR, 61.32% reduction) by the final visit. EnMax also outperformed both placebo and the comparator in reducing erythema, local irritation, discharge, and tenderness. Notably, EnMax patients required less analgesic use and reported no adverse events, with full study compliance. In contrast, the placebo group exhibited minimal improvement across all measured parameters. These results suggest that EnMax is a promising, safe, and effective therapeutic option for enhancing postoperative recovery. Additional larger, long-term studies are recommended to further establish its clinical benefits. © 2025. The Author(s).

BACKGROUND: Acute bronchitis (AB) is a lower respiratory tract infection manifested by cough, which is challenging to manage at the moment. Therefore, this study aimed to evaluate the efficacy and safety of a food supplement (Atusin® CAP) combining 4 types of purified essential oils, bromelain, and green Brazilian propolis in adults. METHODS: A post-surveillance, multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical study was conducted over 6 months. Participants with acute uncomplicated bronchitis were administered the combination preparation (verum group) or placebo for 10 days in total. The primary outcome was clinical cure, defined as a ≥ 75% reduction in baseline Bronchitis Severity Scale (BSS) score after 10 days. RESULTS: In total, 310 participants were randomized 1:1, of which 155 and 150 participants in the verum and placebo group, respectively, were included in the efficacy and safety analysis sets. A statistically significantly higher number of clinically cured participants was observed in the verum group compared to the placebo group on all reporting days until the end of study intervention administration (Day 10: p = 0.029). The mean BSS score was statistically significantly different between the study intervention groups from Day 7 (p = 0.050) until Day 10 (p = 0.011). In addition, there were no differences in the incidence of adverse events between the verum and placebo group. CONCLUSIONS: The study shows that the studied combination preparation, containing scientifically proven active substances that bring together key mechanisms for cough relief, is effective in the treatment of acute uncomplicated bronchitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06142994. Registered on 22 November 2023. © 2025. The Author(s).

OBJECTIVES: Oral enzyme combination (OEC) therapy with bromelain, trypsin and rutoside reduces pain and improves function in patients with knee osteoarthritis (OA). Here, we investigated several potential biological mechanisms underlying the clinical effects of OEC therapy in patients with established knee OA with respect to innate immunity, systemic inflammation and cartilage turnover (EudraCT 2020-003154-80, NCT05038410). METHODS: Patients (age ≥40 years, body mass index (BMI) ≤35 kg/m2) with symptomatic knee OA were randomised to either placebo or OEC, administered 2×3 tablets/day, for 8 weeks before crossing over after a 4-week washout period. Different markers exploring innate immunity, inflammation and cartilage matrix degradation have been measured in the blood using immunoassays or cytometric methods. Data from the modified intention-to-treat population (mITT) were analysed using a generalised linear mixed model. No correction for multiple comparisons was made due to the exploratory nature of the study. RESULTS: Altogether, 45 patients were randomised; 43 completed both treatment sequences (mITT; mean age: 63.3 years; mean BMI: 27.4 kg/m2; mean global Knee injury and Osteoarthritis Outcome Score (KOOS): 48.7). OEC significantly increased levels of α2-macroglobulin (p=0.038) and interleukin-10 (p<0.0001) while decreasing urinary carboxyl-terminal cross-linked telopeptide of type II collagen (p=0.038). Patients administered OEC exhibited significant improvements in KOOS Pain (p=0.0464) and Symptoms (p=0.026) subdomains but not globally. OEC was well tolerated, with no serious related adverse events reported in either group. CONCLUSIONS: One of the key findings of this proof-of-mechanism study is that OEC modulates IL-10 production, suggesting an anti-inflammatory effect in patients with knee OA. This main finding contributes to explaining the effects of OEC on pain and function in these patients. TRIAL REGISTRATION NUMBER: NCT05038410. © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.

OBJECTIVE: This post hoc analysis determined the correlation between wound bed preparation (WBP), defined as complete debridement of nonviable tissue and complete granulation tissue coverage, and wound closure, using data from a published, Consolidated Standards of Reporting Trials (CONSORT)-compliant randomized controlled trial that evaluated bromelain-based enzymatic debridement (BBD) compared with a placebo gel vehicle (GV) or nonsurgical standard of care (NSSOC) in patients with chronic venous leg ulcers (VLUs). APPROACH: Patients with chronic VLUs were randomized (3:3:2 ratio) to daily treatment with BBD, GV, or NSSOC for up to 2 weeks and followed up weekly with NSSOC for 12 weeks. Wound closure incidence was compared between those who did and did not achieve WBP by 14 days or anytime during the study. RESULTS: Data were analyzed from 119 VLUs. Among 80 wounds that achieved WBP anytime during the study, 42% healed; among 39 wounds without WBP, only 10.3% healed (relative risk [RR] = 4.1, p = 0.0004, negative predictive value [NPV] = 90%). Among 37 wounds that achieved WBP by 14 days, 54% healed; among 78 wounds that did not achieve WBP by 14 days, only 22% healed (NPV = 78%). Wounds were 2.4 times more likely to achieve closure anytime during the study, if they achieved WBP by 14 days (RR = 2.4, p = 0.0005). INNOVATION: This landmark analysis confirms that WBP status is an early predictive variable of wound closure. CONCLUSION: WBP of chronic VLUs significantly increased the likelihood of wound closure and is a critical, though not sufficient, condition for healing.

A freeze-dried pineapple extract-Brome-Inf, from pineapple by-products of industrial rings production, was enriched in bioactive polypeptides and bromelain by membrane ultrafiltration. Orchiepididymitis (OE), a painful pediatric pathology, was treated with this extract. A pilot, double-blind, randomized study involving 60 pediatric OE patients compared the effects of Brome-Inf to a placebo over a 15-day period, in conjunction with antibiotic treatment. In the present study, the primary objective was to assess the disparity in NSAIDs usage and pain intensity between the Brome-Inf group and the placebo group, utilizing the Wong-Becker, Numerical Rating Scale (NRS), and Visual Analogue Scale (VAS) pain rating scales. Results revealed a significant reduction in VAS and NRS within the Brome-Inf group from Days 1 to 15 compared with placebo. A rapid regression of edema was observed in the active group after 1 week and at the end of the study. We can conclude that oral supplementation with Brome-Inf emerges as a promising co-management option for OE for its action on pain and edema, potentially enhancing the quality of life for affected children. Importantly, due to its well-balanced fruity flavor, the palatability of Brome-Inf was appreciated, ensuring optimal patient compliance and treatment safety. © 2025 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.

BACKGROUND: A randomized controlled trial reported that bromelain-based enzymatic debridement (BBD) more effectively debrided and granulated venous leg ulcers (VLUs) compared with placebo (gel vehicle, hydrogel) and nonsurgical standard of care (including collagenase ointment [CO]). OBJECTIVE: To assess the efficacy of BBD vs CO-based enzymatic debridement in VLUs during the ChronEx trial. MATERIALS AND METHODS: The Wilcoxon exact test was used to compare the proportion of wounds in each group that achieved complete debridement and granulation at 2 weeks. Kaplan-Meier analysis was used to compare median times to complete debridement and granulation between groups. RESULTS: Forty-six patients with 46 wounds were treated with BBD, and 8 were treated with CO. Twenty-nine wounds treated with BBD (63%; 95% CI, 48-77) were completely debrided within 2 weeks compared with none treated with CO (P = .001). Twenty-three wounds treated with BBD (50%; 95% CI, 35-65) achieved complete granulation by 2 weeks compared with none with CO (P = .015). The estimated median time to complete debridement and complete granulation, respectively, in the BBD group vs the CO group, respectively, were 9 days vs not achieved (P = .023), and 11 days vs not achieved (P = .014). The groups had comparable safety and pain profiles. CONCLUSION: BBD appears to be more effective and faster than CO in achieving complete debridement and granulation of VLUs as part of wound bed preparation.

OBJECTIVES: This study aimed to compare the analgesic efficacy of Bromelain, Ibuprofen, and Bromelain plus turmeric for pain control after orthodontic separator placement. MATERIAL AND METHODS: This triple-blind randomized clinical trial included 135 patients over the age of 15 who required orthodontic treatment. The patients were randomly assigned to three groups: 400 mg Ibuprofen (Group A), 200 mg Bromelain (ANAHEAL; Group B), and 150 mg Bromelain + 300 mg Turmeric (ANAHEAL PLUS; Group C). The patients took one tablet immediately after the separator was placed. Four separators were placed at the mesial and distal regions of both maxillary first molars. The degree of pain and discomfort was measured using a visual analog scale (VAS) at the following time points: Immediately after the separator placement (T0), 2 h posttreatment (T1), 6 h posttreatment (T2), 24 h posttreatment (T3), and 48 h after separator placement (T4). The data were analyzed using SPSS (version 15.0). Different statistical tests including ANOVA, Tukey's test, and paired t-test were utilized. p < 0.05 was considered statistically significant. RESULTS: Pain scores at 2 h (T1) and 6 h (T2) after separator placement differed significantly among the three groups (p = 0.006 and p = 0.025, respectively), with the Ibuprofen group experiencing significantly higher pain levels than the Bromelain and Bromelain Plus Turmeric groups. At 48 h (T4), a significant difference was observed only in chewing function (p = 0.024), where patients in the Bromelain group reported higher pain scores than those in the Ibuprofen group. Sex had no significant effect on pain perception (P < 0.05). CONCLUSIONS: Bromelain with or without turmeric might be a useful alternative to Ibuprofen for pain control following orthodontic separator placement. © 2025 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.

OBJECTIVES: This study evaluated the safety and efficacy of an enzymatic bromelain-based debridement (BBD) agent (NexoBrid®) in children with deep thermal burns. METHODS: We conducted a multicenter, open-label, parallel design, randomized controlled trial at 36 burn centers in Europe, US, Israel and India. Main eligibility criteria included children 0-18 years old, suffering from deep thermal burns covering 1-30 % of their total body surface area. Patients were randomized to either BBD or standard of care (SOC) eschar removal methods. Primary endpoints included time to complete eschar removal (superiority), percentage of wound area surgically excised (superiority) and blinded 12 months follow-up assessment of cosmesis and function using the Modified Vancouver Scar Scale (MVSS, non-inferiority). RESULTS: One hundred and forty-five children were enrolled between 2015 and 2020 (last patient completed 12-month follow-up on April 2021); 72 were randomized to BBD and 73 to SOC. All three primary endpoints of the study were met. The median time to complete eschar removal was significantly lower in the BBD arm (1 vs. 6 days, P < 0.001). The mean [SD] percentage of wound area surgically excised was also significantly lower in the BBD arm (1.5 % [12.1 %] vs. 48.1 % [46.6 %], P < 0.001). Mean [SD] 12-month MVSS scores were 3.8 [2.9] and 4.9 [3.3] in the BBD and SOC arms, respectively (non-inferiority demonstrated at P < 0.001). The incidence of adverse events was similar between the groups, and there were no significant safety issues or deaths during the trial. CONCLUSIONS: BBD was demonstrated to be safe and effective in children. Its use lead to a shorter time to complete eschar removal, a reduction in excisional surgery and non-inferior cosmesis and function results as compared to SOC eschar removal methods.

PURPOSE: To compare intravitreal aflibercept alone versus aflibercept combined with oral anti-inflammatory supplementation in patients with diabetic macular edema. METHODS: A prospective, randomized study included 134 treatment-naive eyes with central-involving diabetic macular edema. Participants were assigned to receive either intravitreal aflibercept (Group A) or aflibercept with oral Lenidase supplementation (Group B, containing baicalin, bromelain, and escin). Both groups followed a treat-and-extend regimen. The primary outcome was the number of injections over 24 months. Secondary outcomes included changes in best-corrected visual acuity, central macular thickness, and safety assessments. RESULTS: At 24 months, Group A required a mean of 14.34 ± 0.51 injections, while Group B required 12.96 ± 0.44 ( P < 0.0001). Both groups showed significant improvement in best-corrected visual acuity: from 0.62 ± 0.12 logMAR (20/83 Snellen) to 0.43 ± 0.13 logMAR (20/54 Snellen) in Group A and from 0.64 ± 0.13 logMAR (20/87 Snellen) to 0.42 ± 0.15 logMAR (20/53 Snellen) in Group B ( P < 0.0001 for both). Central macular thickness also significantly decreased in both groups ( P < 0.0001). No significant differences were found between the groups for vision improvement ( P = 0.918) or central macular thickness reduction ( P = 0.777). No ocular complications were reported. CONCLUSION: Oral supplementation with Lenidase showed similar efficacy to aflibercept monotherapy in diabetic macular edema, with fewer injections, potentially reducing treatment burden.

Colorectal cancer (CRC) is one of the most prevalent and lethal cancers worldwide, with few effective treatment options and substantial associated side effects. As a result, there is growing interest in therapeutic alternatives that reduce toxicity. Natural compounds such as sodium butyrate (NaB), a microbial metabolite of dietary fiber, and bromelain, a proteolytic enzyme from pineapple, have shown individual anticancer properties. However, their combined effect in CRC remains underexplored. This study investigates the synergistic potential of NaB and bromelain in colorectal cancer cell lines, focusing on their ability to inhibit proliferation, induce apoptosis, and modulate key molecular pathways. Findings reveal that co-treatment enhances antitumor activity in vitro, suggesting a promising and safer therapeutic strategy for CRC.

Breast cancer is the most common tumor in women. Chemotherapy is the gold standard for cancer treatment; however, severe side effects and tumor resistance are the major obstacles to chemotherapy success. Numerous dietary components and phytochemicals have been found to inhibit the molecular and signaling pathways associated with different stages of breast cancer development. In particular, this review is focused on the antitumor effects of PUFAs, dietary enzymes, and glucosinolates against breast cancer. The major databases were consulted to search in vitro and preclinical studies; only those with solid scientific evidence and reporting protective effects on breast cancer treatment were included. A consistent number of studies highlighted that dietary components and phytochemicals can have remarkable therapeutic effects as single agents or in combination with other anticancer agents, administered at different concentrations and via different routes of administration. These provide a natural strategy for chemoprevention, reduce the risk of breast cancer recurrence, impair cell proliferation and viability, and induce apoptosis. Some of these bioactive compounds of dietary origin, however, show poor solubility and low bioavailability; hence, encapsulation in nanoformulations are promising tools able to increase clinical efficiency.

CONTEXT: Since the outbreak of SARS-CoV-2, researchers have been working on finding ways to prevent viral entry and pathogenesis. Drug development from naturally-sourced pharmacological constituents may be a fruitful approach to COVID-19 therapy. OBJECTIVE: Most of the published literature has focussed on medicinal plants, while less attention has been given to biodiverse sources such as animal, marine, and microbial products. This review focuses on highlighting natural products and their derivatives that have been evaluated for antiviral, anti-inflammatory, and immunomodulatory properties. METHODS: We searched electronic databases such as PubMed, Scopus, Science Direct and Springer Link to gather raw data from publications up to March 2021, using terms such as 'natural products', marine, micro-organism, and animal, COVID-19. We extracted a number of documented clinical trials of products that were tested in silico, in vitro, and in vivo which paid specific attention to chemical profiles and mechanisms of action. RESULTS: Various classes of flavonoids, 2 polyphenols, peptides and tannins were found, which exhibit inhibitory properties against viral and host proteins, including 3CLpro, PLpro, S, hACE2, and NF-κB, many of which are in different phases of clinical trials. DISCUSSION AND CONCLUSIONS: The synergistic effects of logical combinations with different mechanisms of action emphasizes their value in COVID19 management, such as iota carrageenan nasal spray, ermectin oral drops, omega-3 supplementation, and a quadruple treatment of zinc, quercetin, bromelain, and vitamin C. Though in vivo efficacy of these compounds has yet to be established, these bioproducts are potentially useful in counteracting the effects of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds. We sought to determine the effect of BromAc on the spike and envelope proteins and its potential to reduce infectivity in host cells. Recombinant spike and envelope SARS-CoV-2 proteins were disrupted by BromAc. Spike and envelope protein disulfide bonds were reduced by Acetylcysteine. In in vitro whole virus culture of both wild-type and spike mutants, SARS-CoV-2 demonstrated a concentration-dependent inactivation from BromAc treatment but not from single agents. Clinical testing through nasal administration in patients with early SARS-CoV-2 infection is imminent.

Enzymatic gold nanoparticles (B-GNPs) have been synthesized using a natural anticancer agent bromelain (a cysteine protease) and these nanoparticles were used to bioconjugate Cisplatin (highly effective against osteosarcoma and lung cancer). Cisplatin bioconjugated bromelain encapsulated gold nanoparticles (B-C-GNPs) were found profoundly potent against same cancers at much lower concentration with minimum side effects due to the synergistic effect of bromelain. The B-C-GNPs have been observed to inhibit the proliferation of osteosarcoma cell lines Saos-2 and MG-63 with IC50 estimation of 4.51 µg/ml and 3.21 µg/ml, respectively, and against small lung cancer cell line A-549 with IC50 2.5 µg/ml which is lower than IC50 of cisplatin against same cell lines. The B-GNPs/B-C-GNPs were characterized by TEM, UV-Visible spectroscopy, Zeta potential and DLS to confirm the production, purity, crystalline nature, stability of nanoemulsion, size and shape distribution. The change in 2D and 3D conformation of bromelain after encapsulation was studied by Circular Dichroism and Fluorometry, respectively. It was found that after encapsulation, a 19.4% loss in secondary structure was observed, but tertiary structure was not altered significantly and this loss improved the anticancer activity. The confirmation of bioconjugation of cisplatin with B-GNPs was done by UV-Visible spectroscopy, TEM, FTIR, 2D 1H NMR DOSY and ICP-MS. Further, it was found that almost ~4 cisplatin molecules bound with each B-GNPs nanoparticle.

AIM: This study aimed to test biofilm inhibition activities of each of essential oils (EOs), main compounds of EOs and enzymes against pathogenic Klebsiella pneumoniae. METHODS AND RESULTS: The effect of seven EOs and three enzymes was tested on formation and eradication of K. pneumoniae biofilm. Peppermint oil showed a robust biofilm inhibitory effect, causing inhibition that ranged from 69·2 to 98·2% at 5 μl ml-1 . Thyme oil was found to have the best biofilm eradication ability, causing eradication that ranged from 80·1 to 98·0% at 10 μl ml-1 . The most effective EOs were analysed by GC/MS, to determine the major chemical constitutes of each oil. Pure menthol was found to cause 75·3-97·5% biofilm inhibition at 2·5 μg ml-1 , whereas thymol caused 85·1-97·8% biofilm eradication at 5 μg ml-1 . However, moderate inhibition activity was detected for α-amylase and bromelain, while poor activity was detected for β-amylase. Ciprofloxacin combination with thyme oil and thymol was found to enhance antibiotic activity, and affect biofilm cell viability. The observed inhibitory/eradication activity on K. pneumoniae biofilms was confirmed by scanning electron microscopy. CONCLUSIONS: Thyme and peppermint EOs, and their active components are promising antibiofilm agents alone and/or in combination with ciprofloxacin to inhibit/eradicate biofilms of K. pneumoniae. SIGNIFICANCE AND IMPACT OF THE STUDY: The presented results suggest the potential application of EOs against infections, caused by biofilm-producing K. pneumoniae, to prevent biofilm formation or decrease their resistance threshold. Moreover, the combination of EOs with ciprofloxacin minimizes the antibiotic concentration used and accordingly the potential accompanying toxic side effects. © 2018 The Society for Applied Microbiology.

Alicyclobacillus spp. are spore forming bacteria that are often related to the deterioration of acidic products such as beverages and citrus juices. After the process of industrial pasteurization, the spore produced by the bacteria can germinate and the microorganism can grow, causing sensory abnormalities in the product. Alternative biopreservatives, such as the antimicrobial compounds, are of considerable importance to the food industry. Papain and bromelain are proteolytic enzymes derived frompapaya and pineapple, respectively. These enzymes are widely used in medicine and in the pharmaceutical and food industries, but while some studies have described their antibacterial action, no studies of the Alicyclobacillus spp. exist. The aimof this studywas to analyze the antibacterial effect of papain and bromelain on Alicyclobacillus spp. through 1) determining minimum inhibitory and bactericidal concentration (MIC and MBC); 2) determining the death time curve of the micro-organism in the presence and absence of enzymes; and 3) investigating the enzymatic mechanism on the microorganism. The antibacterial activity of enzymes in combination with nisin was also evaluated. The results showed that for the Alicyclobacillus acidoterrestris strain, the MIC of papain was 0.98 μg/mL and the MBC was 3.91 μg/mL, while theMIC of bromelain was 62.5 μg/mL and the MBCwas 250 μg/mL. The concentration of 4 ×MIC for both the enzymes was sufficient to eliminate 4 logs of the micro-organism after 24 h of incubation. Through the use of enzyme inhibitors specific for cysteine proteases, it was found that the antibacterial activity of papain and bromelain is not related to its proteolytic activity, butmay be related to other activities, such as amidse and esterase. The synergistic activity of the enzymes revealed a fractional inhibitory concentration (FIC) level of 0.16. Combination with nisin revealed an FIC of 0.25 for papain and 0.19 for bromelain, indicating synergism between both compounds. The application of enzymes in reconstituted orange juice contaminated with A. acidoterrestris was found to be effective, as after 48 h of incubation, at three different temperatures, the initial m

BACKGROUND: Bromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored. METHODS: The growth-inhibitory effects of bromelain and N-acetylcysteine, on their own and in combination, on a panel of human gastrointestinal carcinoma cell lines, including MKN45, KATO-III, HT29-5F12, HT29-5M21 and LS174T, were assessed by sulforhodamine B assay. Moreover, the influence of the treatment on the expression of a range of proteins involved in the regulation of cell cycle and survival was investigated by Western blot. The presence of apoptosis was also examined by TUNEL assay. RESULTS: Bromelain and N-acetylcysteine significantly inhibited cell proliferation, more potently in combination therapy. Drug-drug interaction in combination therapy was found to be predominantly synergistic or additive. Mechanistically, apoptotic bodies were detected in treated cells by TUNEL assay. Furthermore, Western blot analysis revealed diminution of cyclins A, B and D, the emergence of immunoreactive subunits of caspase-3, caspase-7, caspase-8 and cleaved PARP, withering or cleavage of procaspase-9, overexpression of cytochrome c, reduced expression of anti-apoptotic Bcl-2 and pro-survival phospho-Akt, the emergence of the autophagosomal marker LC3-II and deregulation of other autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12 and Beclin 1. These results were more prominent in combination therapy. CONCLUSION: We report for the first time to our knowledge the growth-inhibitory and cytotoxic effects of bromelain and N-acetylcysteine, in particular in combination, on a panel of gastrointestinal cancer cell lines with different phenotypes and characteristics. These effects apparently resulted from

Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneum, causally related to asbestos exposure. Nonspecific symptoms with a late diagnosis results in poor survival (<1 year). Treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has improved survival in some patients (median 3-5 years). Hence, new therapies are urgently needed. MUC1 is a glycosylation-dependent protein that confers tumours with invasiveness, metastasis and chemoresistance. Bromelain (cysteine proteinase) hydrolyses glycosidic bonds. Therefore, we investigated the antitumour effect of bromelain on MUC1-expressing MPM cell lines. MUC1 expressions in cells were assessed using immunofluorescent probes with cells grown on cover slips and western blot analysis on cell lysates. The cell lines were treated with various concentrations of bromelain and after 4 and 72 h, their viability was assessed using standard sulforhodamine assays. The cells were also treated with combinations of bromelain and cytotoxic drugs (cisplatin or 5-FU) and their viability was assessed at 72 h. Finally, with western blotting, the effects of bromelain on cellular survival proteins were investigated. PET cells expressed more MUC1 compared with YOU cells. The cell viability of both PET and YOU cells was adversely affected by bromelain, with PET cells being slightly resistant. The addition of bromelain increased the cytotoxicity of cisplatin significantly in both cell lines. However, 5-FU with bromelain did not show any significant increase in cytotoxicity. Bromelain-induced cell death is by apoptosis and autophagy. Bromelain has the potential of being developed as a therapeutic agent in MPM.

5. Oncology (Williston Park). 2011 Feb;25(2):195. Complementary therapies, herbs, and other OTC agents. Bromelain. Cassileth B(1). Author information: (1)Memorial Sloan-Kettering Cancer Center, New York, New York, USA. PMID: 21456393 [Indexed for MEDLINE]

Background: NexoBrid® (NXB; MediWound Ltd., Yavne, Israel) (anacaulase-bcdb) is a bromelain-based enzymatic debriding agent approved for eschar removal in burn care. Despite widespread clinical use, histological evidence of tissue-level changes after enzymatic debridement remains limited. This systematic review aimed to evaluate preclinical and clinical studies describing histological findings following bromelain-based enzymatic debridement of thermal burns. Methods: Following PRISMA 2020 guidelines, we performed parallel systematic searches of preclinical (animal) and clinical (human) studies across PubMed, Embase, CENTRAL, Web of Science, and Scopus. Included studies reported thermal burns treated with bromelain-based enzymatic debridement and tissue biopsies with histological analysis. Quality was assessed using the SYRCLE Risk of Bias Tool (preclinical) and JBI Critical Appraisal Checklists (clinical). Results: Six preclinical studies (five porcine, one rat) met inclusion criteria. Findings included: selective eschar removal with dermal preservation; protection of the zone of stasis (67% partial- vs. 100% full-thickness necrosis; p = 0.05); viable dermal thickness of 1.1 ± 0.7 mm; and accelerated re-epithelialization (7.4 ± 0.8 vs. 9.1 ± 2.1 days; p < 0.05). Only two clinical studies (n = 9 patients) met the inclusion criteria: one case series (n = 8) and one case report. Clinical findings showed upper dermal homogenisation with preserved deep dermis, vascular congestion correlating with pinpoint bleeding, and pseudoeschar formation via transepidermal elimination. Conclusions: Preclinical evidence supports selective enzymatic debridement with dermal preservation. However, clinical histological data are limited to nine patients after over 13 years of use. This highlights a critical translational gap and underscores the need for prospective clinical histological studies.

Bromelain-based enzymatic debridement (BBD) may selectively remove devitalised tissue in chronic wounds, but randomised evidence is limited. Following PRISMA and a PROSPERO-registered protocol (CRD420251116455), we searched MEDLINE, CENTRAL and Embase from inception to 8 Aug 2025 for randomised controlled trials in adults with chronic wounds comparing topical BBD versus standard care/vehicle. Two reviewers screened, extracted and assessed risk of bias. Primary outcomes were incidence of complete debridement (efficacy) and ≥ 1 adverse event (safety). Of 24 records, 3 RCTs (n = 314) met inclusion; 2 contributed complete-debridement data and 3 contributed adverse-event data. BBD increased complete debridement versus control (RR 2.81, 95% CI 1.15-6.86; I2 = 58.7). Safety was comparable (RR 1.02, 95% CI 0.76-1.36; I2 = 0), and leave-one-out analyses for adverse events showed no influential study. BBD improves the likelihood of complete debridement without increasing adverse events, suggesting a possible role in its use as a selective, non-surgical adjunct alongside guideline-directed care. © 2026 The Wound Healing Society.

PURPOSE: To systematically evaluate evidence-based interventions aimed at reducing postoperative edema and ecchymosis in eyelid and periocular surgery, with the goal of improving patient outcomes and recovery. METHODS: A systematic review of 29 randomized controlled trials (RCTs), involving 2,287 patients undergoing eyelid and periocular surgery, was conducted. A comprehensive search was performed across Embase, MEDLINE, Cochrane Central, and Google Scholar up to April 2025. Studies assessing interventions for postoperative edema and ecchymosis were included. Study quality was evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool. RESULTS: Tranexamic acid was the most consistently effective intervention for reducing ecchymosis. Vessel-preserving surgical techniques significantly reduced edema and hematoma, while skin-only excision led to less swelling than combined skin and muscle excision. Carbon dioxide laser - assisted blepharoplasty improved hemostasis and reduced chemosis. Magnesium sulfate dressings were more effective for edema than ice packs, though cold compresses provided short-term relief. Anesthesia modifications (pre-cooling, buffered lidocaine) reduced injection pain but had variable effects on swelling. Herbal and adjunctive therapies, including Arnica montana and bromelain, showed no significant benefits. CONCLUSION: Tranexamic acid, vessel-preserving surgical methods, and magnesium sulfate dressings are among the most effective strategies for minimizing ecchymosis and edema in eyelid and periocular surgery. Further RCTs should explore optimized combinations of these interventions and assess long-term patient-reported outcomes.

BACKGROUND: The use of complementary and alternative medicine is becoming increasingly important in the prevention and management of complications related to diabetes. METHODS: A comprehensive literature search was conducted across major databases (EMBASE, Scopus, PubMed, Google Scholar, Web of Science, Cochrane Library) up to December 2024. The search focused on studies examining the effect of bromelain on glycemic control, lipid profiles, and related mediators in diabetes. KEY FINDINGS: Bromelain supplementation demonstrated positive effects on key metabolic markers. Bromelain may stimulate AMPK in muscle cells, enhancing glucose uptake and utilization, potentially lowering blood glucose levels, and benefiting individuals with diabetes. Although direct evidence of bromelain's impact on incretin levels is limited, its ability to modulate gastrointestinal function and improve nutrient absorption could indirectly influence incretin secretion. Moreover, Peptides or smaller amino acids resulting from bromelain's proteolytic activity enter the bloodstream and potentially enhance nutrient absorption, which plays an important role in evaluating the therapeutic potential of bromelain in diabetes management. CONCLUSION: Bromelain supplementation is effective in improving glycemic and lipid indices in diabetes. However, further research is needed to clarify the underlying mechanisms, including bromelain's potential interaction with the incretin system and its role in modulating insulin resistance through various pathways. © The Author(s) 2025. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

Systemic therapies for the treatment of cancer collaborate to reduce cancer progression and have been used for decades. However, despite the clinical benefits, its long-term use is associated with toxicity, promoting important side effects that can compromise the quality of life. Enzyme supplementation has been pointed out as a therapeutic potential in several diseases. Bromelain is an enzyme complex that regulates pathways associated with inflammation. This review aims to evaluate the use of bromelain-containing supplements to improve the side effects of cancer treatment. This systematic review was developed in PubMed, Web of Science, and Cochrane Library, using the terms: Cancer AND Bromelain. 239 studies were retrieved, and only three met our objective. In general, it was possible to observe that supplementation was able to reduce side effects of adjuvant hormone therapy and chemotherapy, such as mucosal dryness, arthralgia, and peripheral neuropathy induced by chemotherapy.

Chronic venous disease (CVD) is a prevalent condition leading to significant morbidity and affecting quality of life. Among conservative treatment strategies, venoactive drugs are often recommended by major guidelines for the management of CVD. Bromelain and vitamin C are now emerging as promising options in the management of several chronic diseases owing to their anti-inflammatory, immunoregulatory, and antioxidant properties, though evidence remains scarce in this setting. This systematic review of the literature, endorsed by the Italian Society of Angiology and Vascular Medicine (Societa Italiana di Angiologia e Patologia Vascolare, SIAPAV), aims to evaluate the efficacy and safety of these compounds in the treatment of CVD. A comprehensive search yielded nine studies, two on bromelain and seven on vitamin C. No studies have evaluated the effects of bromelain and vitamin C alone or in combination, whereas both molecules were administered in combination with other nutritional supplements. Overall, CVD-related symptoms and edema seem to improve with dietary supplement containing these two compounds, with no major safety issues reported. Bromelain and vitamin C may thus represent attractive options in the management of patients with symptomatic CVD and/or presence of venous edema, provided optimal conservative treatment is in place. Dedicated clinical studies are needed to clarify the efficacy and safety of a combination of these molecules in CVD management.

BACKGROUND: Liver diseases pose a significant challenge to the well-being of the public, given their high prevalence and the potential to escalate to liver failure and hepatocellular carcinoma. The efficacy of current therapies is rather limited, resulting in the manifestation of severe side effects. Bromelain, derived from the pineapple plant, exhibits promising prospects for the treatment of inflammatory disorders, cancer, and wound healing, although its impact on liver functionality remains largely unexplored. OBJECTIVE: To evaluate the efficiency of bromelain in liver injuries, we performed a systematic review of preclinical studies. METHOD: Our search was conducted in August 2020 on PubMed and Scopus, employing the search terms "Liver disease," "Liver injury," and "Bromelain," with subsequent updates in December 2023. RESULTS: Out of the 329 articles that were examined, only 7 fulfilled the criteria for inclusion. CONCLUSION: Our research suggests that bromelain possesses both prophylactic and curative qualities in terms of liver damage, as supported by its ability to decrease enzyme levels, enhance liver structure, reduce oxidative stress markers, and regulate lipid metabolism. In summary, bromelain demonstrates a capacity to enhance liver function across a range of injury types.

Deep burn injuries necessitate effective debridement to promote healing and reduce complications. Traditional surgical debridement is the standard of care; however, it can lead to significant tissue loss, excessive bleeding and delayed healing. Bromelain-based enzymatic debridement offers a potential less invasive alternative that aims to selectively remove necrotic tissue while preserving viable ones. Therefore, this systematic review and meta-analysis comprehensively compares bromelain debridement versus standard care in the management of partial and full thickness burns. Cochrane Library, Embase, and Medline were searched until May 30, 2024 for studies comparing bromelain debridement versus standard care. R version 4.4.0 was used to pooled risk ratio and mean difference in a random-effects model. We included 7 studies, comprising 484 participants, of whom 238 (49%) were treated with enzymatic debridement. Bromelain significantly reduced time to eschar removal (MD -7.60 days 95% CI [-9.76, -5.44]; I2 = 70%) in comparison with standard care. Additionally, bromelain group presented a significant reduction in the risk of surgical excision (RR 0.17; 95% CI [0.06, 0.47]; I2 = 79%) and need for autografts (RR 0.40; 95% CI [0.18, 0.93]; I2 = 76%) in comparison with standard group. No differences were found in behalf of time to wound closure (MD -7.64 days; 95% CI [-18.46]-[3.18]; I2 = 86%), nor in Modified Vancouver Scar Scale (MD -0.36 points; 95% CI [-0.96]-[0.23]; I2 = 0%). Bromelain-based enzymatic debridement may accelerate eschar removal and reduce the need for surgical excision and autografts, without adversely affecting wound closure time or long-term scar quality. © The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

Bromelain is a mixture of proteolytic enzymes primarily extracted from the fruit and stem of the pineapple plant (Ananas comosus). It has a long history of traditional medicinal use in various cultures, particularly in Central and South America, where pineapple is native. This systematic review will delve into the history, structure, chemical properties, and medical indications of bromelain. Bromelain was first isolated and described in the late 19th century by researchers in Europe, who identified its proteolytic properties. Since then, bromelain has gained recognition in both traditional and modern medicine for its potential therapeutic effects.

Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1β, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.