Pineapple bromelain — a natural remedy for inflammation?

Aim of the study: The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have been used to reduce the significant side effects of available anti-inflammatory drugs. Bromelain is an enzyme complex derived from Ananas comosus, known for its anti-inflammatory potential and good tolerance.

Results: 1375 studies were retrieved, of which 269 were duplicates. Seven (7) randomized controlled trials were eligible for the systematic review. In most studies, supplementation with bromelain, isolated or in combined therapy, reduced inflammatory parameters. Regarding the reduction of inflammatory parameters among studies with associated bromelain, two presented reduction of inflammatory parameters, while in the evaluation of bromelain treated alone, two studies also showed reduction. In relation to doses supplemented, the studies with associated bromelain ranged from 99.9 to 1200 mg/day and the supplementation time ranged from 3 to 16 weeks. Moreover, the inflammatory parameters evaluated were: IL-12, PGE-2, COX-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, CRP, NFγ B1, PPAR-α, TNF, TRAF, MCP-1 and adiponectin. In studies with isolated bromelain supplementation, it ranged from 200 to 1050 mg/day for 1 week to 16 weeks.

Aim of the study: 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.

Results: 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.

Aim of the study: The aim of this systematic review was to determine whether bromelain is an effective drug for the control of pain and inflammation associated with third molar surgery. Randomized, controlled clinical trials on the subject were identified through a systematic search of the literature using the PubMed/MEDLINE, Scopus, and Cochrane Library databases.

Results: A meta-analysis was performed for the outcomes pain and trismus and was based on the inverse variance method for continuous outcomes, considering the mean difference (MD) and corresponding 95% confidence interval (CI). A total of 186 articles were initially retrieved from the databases. After the different stages of the selection process, five articles reporting data for a total 252 patients remained and were included in the review. Bromelain proved to be effective at controlling postoperative pain at 48-72h after surgery (P=0.03; MD -0.89, 95% CI -1.70 to -0.09), but did not achieve a significant effect in comparison to the control group with regard to oedema or trismus.

Aim of the study: Traumatic brain injury (TBI) is the leading cause of death from injury. Many studies have shown that cytokines, chemokines, and oxidative stress play a crucial role in the pathophysiology of TBI.

Results: Bromelain supplementation significantly improved IL-6 levels, APACHE, SOFA, and NUTRIC scores, and reduced 60-day mortality in patients with traumatic brain injury. However, its effects on CRP, MDA and TAC levels were not statistically significant. These findings suggest that bromelain may serve as a promising adjunctive therapy to reduce inflammation and improve clinical outcomes in critically ill TBI patients. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these results.

Aim of the study: Diabetes mellitus (DM) is a chronic metabolic disorder that affects millions of people worldwide. A growing evidence suggests that hyperglycemia in DM causes a pre-aging and pro-inflammatory condition known as inflammaging, which increases periodontitis susceptibility. Bromelain has been demonstrated to have anti-inflammatory and anti-aging properties in variety of tissues, but its effects on diabetic periodontitis remain unclear.

Results: Bromelain concentrations ranging from 2.5 to 20 g/mL had no adverse effect on HGF cell proliferation. Bromelain improved wound healing in HGFs with AGEs stimulation. In addition, Bromelain suppressed the production of pro-inflammatory cytokines IL-6 and IL-8 in HGFs elicited by AGEs. Meanwhile, Bromelain treatment also inhibited the senescence activity and expression of p16 in AGEs-stimulated HGFs. Western blot analysis indicated that the upregulation of p-ERK, p-p38 and p65 induced by AGEs were inhibited by Bromelain in HGFs. These data suggest that excessive AGEs in the gingiva may lead to the accumulation of pro-inflammatory cytokines and marked senescence activity. Bromelain application may be helpful in enhancing wound healing by suppressing inflammaging via downregulation of NF-κB and MAPK/ERK signaling pathways in DM individuals with periodontal disease.

Aim of the study: Background and Objectives: Bromelain is a mixture of protease obtained from pineapple fruits or stems. Even though the biological mechanism of action of bromelain has not been completely understood, it is well known that bromelain possesses anticancer, anti-inflammatory and immunomodulatory effects.

Results: Bromelain also promoted ALP activity and mineralized nodule formation. Conclusions: Bromelain inhibits the expression of inflammatory cytokines in LPS-stimulated hDPCs. The inhibitory effect of bromelain on inflammatory mediators is related to decreased NF-κB and the MAPK pathway. Therefore, bromelain might have the potential to be used for regenerative endodontics, including vital pulp therapy.

Aim of the study: The aim of this study was to investigate the molecular, biochemical, and histopathological effects of bromelain, which has antioxidant and anti-inflammatory properties, against cisplatin-induced ocular toxicity. The groups were designed as (1) Control, (2) Cisplatin (7 mg/kg, intraperitoneally), (3) Cisplatin + Bromelain (50 mg/kg, orally for 14 consecutive days), (4) Cisplatin + Bromelain (100 mg/kg, orally for 14 consecutive days).

Results: The mRNA expression of NF-κB and Caspase-3 was also evaluated. Also, ocular sections were evaluated histopathologically. Bromelain demonstrated a dose-dependent protective effect in cisplatin-induced toxicity by regulating oxidative stress, inflammation, and tissue damage. Our results suggested that bromelain may be a potential adjuvant that can protect the eye from cisplatin-induced toxicity.

Aim of the study: This study aimed to investigate how bromelain protects glial cells from pentylenetetrazole (PTZ)-induced damage, focusing on its anti-inflammatory effects. C6 glioma cells were treated with PTZ, bromelain, or a combination of PTZ and bromelain.

Results: On the other hand, bromelain at 50 µg/mL reduced inflammation, as indicated by lower levels of NO, iNOS, and COX2 (p < 0.001). In-silico predictions suggest that bromelain can effectively target iNOS and COX2, key inflammatory proteins. These findings indicate that bromelain protects glial cells by exerting anti-inflammatory effects. However, further research is needed to understand the underlying mechanisms fully.

Aim of the study: The objective of this study is to evaluate the effects of bromelain on serum endocannabinoid levels and oxidative stress markers in a rat model of surgically induced endometriosis.

Results: Induction of endometriosis significantly reduced serum 2-arachidonoylglycerol, anandamide, superoxide dismutase, and glutathione levels while increasing malondialdehyde concentrations compared with the Sham group (p<0.05). Bromelain treatment significantly improved most endocannabinoid and oxidative stress parameters compared with the untreated endometriosis group (p<0.05). Bromelain ameliorated endocannabinoid deficiency and oxidative stress in experimental endometriosis. These findings suggest that bromelain may represent a promising non-hormonal therapeutic candidate targeting interconnected inflammatory and redox pathways in endometriosis.

Aim of the study: Inflammation and increased oxidative stress in testicular tissue are documented side effects of torsion of the testicles. The preventive role of Bromelain (Bro) against testicle torsion-induced ischemia/reperfusion (I/R) injury was investigated in this research.

Results: Sperm morphology, motility, and concentration notably improved in the bromelain-treated group, according to spermatological examination. Testicular samples treated with bromelain showed less tissue damage according to histological evaluations than the untreated I+R group. These findings imply that Bro has anti-inflammatory, anti-apoptotic, and antioxidant qualities. It effectively reduces oxidative stress and inflammation by modulating the PI3K/Akt/mTOR and NRF-2/HO-1 pathways, hence minimizing I/R injury.