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Journal of Dental Sciences Apr 2023Diabetes 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...
BACKGROUND/PURPOSE
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. Thus, the aim of this study is to investigate the its Bromelain's impact in diabetic periodontitis in terms of inflammation and senescence activity.
MATERIALS AND METHODS
We assessed the wound healing capacity, production of pro-inflammatory cytokines Interleukin (IL)-6 and IL-8 and senescence marker p16 in human gingival fibroblasts (HGFs) in response to Advanced glycation end-products (AGEs) stimulant, with or without Bromelain treatment. The expression of p65, p-ERK, and p-p38 were also examined to elucidate whether Bromelain's anti-inflammaging activity is mediated through NF-κB and MAPK/ERK signaling pathway.
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.
CONCLUSION
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.
PubMed: 37021274
DOI: 10.1016/j.jds.2022.09.018 -
PloS One 2023Colorectal cancer (CRC) is one of the most lethal cancers worldwide. Long-term survival is not achieved in metastatic CRC despite the current multidisciplinary...
BACKGROUND
Colorectal cancer (CRC) is one of the most lethal cancers worldwide. Long-term survival is not achieved in metastatic CRC despite the current multidisciplinary therapies. Bromelain, a compound extracted from the pineapple plant, has multiple functions and anticancer properties. Previously, bromelain has been chromatographically separated into four fractions. Fraction 3 (F3) exhibits the highest proteolytic activity. The anticancer effects of F3 bromelain in CRC cells is unknown.
METHODS
In vitro cytotoxicity was verified through a sulforhodamine B assay. Apoptosis in CRC cells induced by unfractionated or F3 bromelain was examined using Annexin V-FITC/PI staining and Western blot analysis. ROS status, autophagy and lysosome formation were determined by specific detection kit.
RESULTS
The cytotoxicity of F3 bromelain in CRC cells was found to be comparable to that of unfractionated bromelain. F3 bromelain induces caspase-dependent apoptosis in CRC cells. Treatment with unfractionated or F3 bromelain increased superoxide and oxidative stress levels and autophagy and lysosome formation. ATG5/12 and beclin-1 were upregulated, and the conversion of LC3B-I to LC3B-II was increased significantly by treatment with F3 bromelain. Treated CQ, autophagy inhibitor, with unfractionated or F3 bromelain enhances the cytotoxic effects. Finally, the combination of unfractionated and F3 bromelain with a routine chemotherapeutic agent (5-fluourouracil, irinotecan, or oxaliplatin) resulted in synergistically higher cytotoxic potency in CRC cells.
CONCLUSION
Unfractionated and F3 bromelain inhibits CRC cell proliferation in vitro, and the cytotoxic effects of unfractionated bromelain are equivalent to F3 bromelain. F3 bromelain may be a potential and potent drug for clinical use due to its anticancer efficacy and high synergistic cytotoxicity when combined with a routine chemotherapeutic agent for CRC.
Topics: Humans; Bromelains; Cell Line, Tumor; Antineoplastic Agents; Irinotecan; Colonic Neoplasms; Apoptosis; Cell Proliferation; Colorectal Neoplasms
PubMed: 37262048
DOI: 10.1371/journal.pone.0285970 -
Medicina (Kaunas, Lithuania) Feb 2023: Bromelain and ficin are aqueous extracts from fruits of and plants, used widely for medical applications. Angiotensin-converting enzyme 2 (ACE2) is a homolog of ACE,...
: Bromelain and ficin are aqueous extracts from fruits of and plants, used widely for medical applications. Angiotensin-converting enzyme 2 (ACE2) is a homolog of ACE, degrading Ang II to angiotensin 1-7 and decreasing the cellular concentration of Ang II. : In this study, we investigated the ACE2-inhibitory, antiproliferative, and apoptosis-inducing effects of ficin and bromelain on caco-2 cells. : We found that bromelain and ficin significantly reduced the viability of human colon cancer cells with IC value concentrations of 8.8 and 4.2 mg/mL for bromelain after 24 and 48 h treatments, and 8.8 and 4.2 mg/mL for ficin after 24 and 48 h treatments, respectively. The apoptosis of the caco-2 cell line treated with bromelain was 81.04% and 56.70%, observed after 24 and 48 h. Total apoptotic proportions in caco-2 cells treated with ficin after 24 and 48 h were 83.7% and 73.0%. An amount of 1.6 mg/mL of bromelain and ficin treatments on caco-2 cells after 24 h revealed a higher decrease than that of other concentrations in the expression of ACE2 protein. : In conclusion, bromelain and ficin can dose-dependently decrease the expression of ACE2 protein in caco-2 cells.
Topics: Humans; Angiotensin-Converting Enzyme 2; Bromelains; Ficain; Caco-2 Cells; Colonic Neoplasms
PubMed: 36837502
DOI: 10.3390/medicina59020301 -
American Journal of Translational... 2021Gemcitabine (GEM) is commonly chosen for treating pancreatic cancer. However, its use is limited by toxicity. Earlier studies with GEM in combination with Bromelain...
Gemcitabine (GEM) is commonly chosen for treating pancreatic cancer. However, its use is limited by toxicity. Earlier studies with GEM in combination with Bromelain (Brom) and Acetylcysteine (Ac) indicated a substantial reduction in IC. In this study, immunocytochemistry and Western blot were used to explore the mechanistic effects of Brom and Ac (BromAc) . Then, we explored the efficacy and safety of BromAc only and with GEM in a pancreatic cancer model . Immunocytochemistry results revealed a reduction in both MUC1 and MUC4 post-treatment. There was a decrease in VEGF, MMP-9, NF-κβ and cleavage of PARP. There was also a decrease in the cell cycle regulators Cyclin B and D as well as TGF-β and the anti-apoptotic Bcl-2. , the low and high doses of BromAc alone and with chemotherapy agents were safe. A very significant reduction in pancreatic tumour volume, weight, and ki67 were seen with BromAc therapy and was equal to treatment with GEM alone and better than treatment with 5-FU. In addition, tumour density was significantly reduced by BromAc. In conclusion, the anticancer effect of BromAc is probably related to its mucin depletion activity as well as its effect on proteins involved in cell cycle arrest, apoptosis and modulation of the tumour microenvironment. The results are encouraging and are considered the first evidence of the efficacy of BromAc in pancreatic cancer. These results also provide some mechanistic leads of BromAc.
PubMed: 35035694
DOI: No ID Found -
Journal of Dentistry (Tehran, Iran) Sep 2018Considering the optimal efficacy of bromelain for pain relief and wound healing, this study aimed to assess the effect of bromelain on wound healing, pain, and bleeding...
OBJECTIVES
Considering the optimal efficacy of bromelain for pain relief and wound healing, this study aimed to assess the effect of bromelain on wound healing, pain, and bleeding at the donor site following free gingival grafting (FGG).
MATERIALS AND METHODS
This randomized, controlled double-blind clinical trial was performed on 26 patients with gingival recession. The patients were randomly divided into two groups of bromelain and placebo (n=13). Treatment was started on the day of surgery and was continued for 10 days. Pain, bleeding, and epithelialization at the donor site were the variables evaluated in this study using a questionnaire. The level of pain was determined using a visual analog scale (VAS) considering the number of analgesic tablets taken within 7 days postoperatively. Bleeding was determined according to the patient's report, and epithelization was assessed by applying 3% hydrogen peroxide (HO) to the donor site. The donor site epithelialization was assessed at 7 and 10 days after surgery.
RESULTS
Bromelain caused a significant reduction in pain at the donor site (2.605±0.509) compared to the placebo (4.885±0.519; P<0.05). The number of donor sites with complete epithelialization was higher in the bromelain group compared to the placebo, but this difference was not statistically significant (P>0.05). The two groups were the same regarding postoperative bleeding (P>0.05).
CONCLUSIONS
The results showed that oral bromelain (500 mg/day) can be effective in the reduction of pain at the donor site after FGG and may also enhance wound healing. Oral bromelain does not increase the risk of postoperative bleeding.
PubMed: 30833977
DOI: No ID Found -
Antibiotics (Basel, Switzerland) Nov 2022Most of research in regenerative oral surgery describes materials or techniques for increasing volumetric results for implant-supported prosthesis. The use of...
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 () 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, = 0.0067), t2 (r = -0.90, = 0.0001) and t3 (r = -0.8566, = 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, = 0.0034), t2 (r = -0.81, = 0.0020) but not at t3 (r = -0.34, = 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.
PubMed: 36358197
DOI: 10.3390/antibiotics11111542 -
Metabolism Open Dec 2020The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, while no treatment has been proven effective. COVID-19 pathophysiology involves the activation of...
The coronavirus disease 2019 (COVID-19) pandemic is still ongoing, while no treatment has been proven effective. COVID-19 pathophysiology involves the activation of three main pathways: the inflammatory, the coagulation and the bradykinin cascades. Here, we highlight for the first time the joint potential therapeutic role of bromelain and curcumin, two well-known nutraceuticals, in the prevention of severe COVID-19. Bromelain (a cysteine protease isolated from the pineapple stem) and curcumin (a natural phenol found in turmeric) exert important immunomodulatory actions interfering in the crucial steps of COVID-19 pathophysiology. Their anti-inflammatory properties include inhibition of transcription factors and subsequent downregulation of proinflammatory mediators. They also present fibrinolytic and anticoagulant properties. Additionally, bromelain inhibits cyclooxygenase and modulates prostaglandins and thromboxane, affecting both inflammation and coagulation, and also hydrolyzes bradykinin. Interestingly, curcumin has been shown in studies to prevent entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into cells as well as viral replication, while a recent experimental study has demonstrated that bromelain may also inhibit viral entry into cells. Notably, bromelain substantially increases the absorption of curcumin after oral administration. To the best of our knowledge, this is the first report highlighting the significance of bromelain and, most importantly, the potential preventive value of the synergistic effects of bromelain and curcumin against severe COVID-19.
PubMed: 33205039
DOI: 10.1016/j.metop.2020.100066 -
American Journal of Translational... 2021Bromelain consisting of a number of proteolytic enzymes possess anticancer and thrombotic properties. Hence, four chromatically separated fractions were examined for...
Bromelain consisting of a number of proteolytic enzymes possess anticancer and thrombotic properties. Hence, four chromatically separated fractions were examined for their proteolytic, anticancer and antithrombotic activity. Bromelain fractions were separated using ion-exchange column chromatography. Proteolytic properties were assessed using standard azocasein assay. Anticancer properties were first assessed using four different cell lines PANC-1, HEP 2B, HEP 3G and OVCAR-3 on cells grown in 96 well plates. Subsequently, fraction 2 and fraction 3 combined with gemcitabine were tested in ASPC-1 cells. Then cytotoxicity of fraction 3 was compared to bromelain in combination with doxorubicin and N-acetylcysteine on HEP G2 and HEP 3B cells. Finally, the anticoagulation effect of fraction 3 or bromelain combined with N-acetylcysteine was evaluated using human blood. Fraction 3 showed the highest proteolytic activity (5% greater than standard bromelain) whilst others were less active. Cytotoxicity as assessed by IC50 indicated fraction 3 to be the most potent whilst the others did not follow their proteolytic potency order. OVCAR-3 was the most sensitive amongst the cell lines. Fraction 3 showed higher potency in combination with gemcitabine in ASPC-1 cells compared to fraction 2. Similarly, fraction 3 in combination with doxorubicin showed higher toxicity when compared to bromelain. Fraction 3 or bromelain only showed thrombolytic activity in combination with N-acetylcysteine. Fraction 3 may be developed for clinical use since it showed better cytotoxicity compared to bromelain.
PubMed: 34150016
DOI: No ID Found -
Polymers Nov 2022Enzyme immobilization on various carriers represents an effective approach to improve their stability, reusability, and even change their catalytic properties. Here, we...
Enzyme immobilization on various carriers represents an effective approach to improve their stability, reusability, and even change their catalytic properties. Here, we show the mechanism of interaction of cysteine protease bromelain with the water-soluble derivatives of chitosan-carboxymethylchitosan, -(2-hydroxypropyl)-3-trimethylammonium chitosan, chitosan sulfate, and chitosan acetate-during immobilization and characterize the structural features and catalytic properties of obtained complexes. Chitosan sulfate and carboxymethylchitosan form the highest number of hydrogen bonds with bromelain in comparison with chitosan acetate and -(2-hydroxypropyl)-3-trimethylammonium chitosan, leading to a higher yield of protein immobilization on chitosan sulfate and carboxymethylchitosan (up to 58 and 65%, respectively). In addition, all derivatives of chitosan studied in this work form hydrogen bonds with His158 located in the active site of bromelain (except -(2-hydroxypropyl)-3-trimethylammonium chitosan), apparently explaining a significant decrease in the activity of biocatalysts. The -(2-hydroxypropyl)-3-trimethylammonium chitosan displays only physical interactions with His158, thus possibly modulating the structure of the bromelain active site and leading to the hyperactivation of the enzyme, up to 208% of the total activity and 158% of the specific activity. The FTIR analysis revealed that interaction between -(2-hydroxypropyl)-3-trimethylammonium chitosan and bromelain did not significantly change the enzyme structure. Perhaps this is due to the slowing down of aggregation and the autolysis processes during the complex formation of bromelain with a carrier, with a minimal modification of enzyme structure and its active site orientation.
PubMed: 36501516
DOI: 10.3390/polym14235110 -
Journal of Dentistry (Shiraz, Iran) Sep 2022Squamous cell carcinoma (SCC) comprises over 90% of oral malignancies. Cisplatin, as a selective chemotherapy agent to treat SCC, has many side effects despite its high...
STATEMENT OF THE PROBLEM
Squamous cell carcinoma (SCC) comprises over 90% of oral malignancies. Cisplatin, as a selective chemotherapy agent to treat SCC, has many side effects despite its high effectiveness. There are some studies on the effects of bromelain derived from pineapple stems on different malignancies.
PURPOSE
The aim of this study was to investigate the effect of bromelain alone and in combination with Cisplatin on oral squamous cell carcinoma (OSCC) and fibroblast cell lines.
MATERIALS AND METHOD
In this interventional study, the HN5 cell line of OSCC and fibroblast cell line were treated with different concentrations of bromelain alone and in combination with cisplatin. Cell viability test was performed after 24, 48 and 72 hours using MTT (3-)4,5-dimethylthiazol-2-yl(-2,5 diphenyl tetrazolium bromide) assay. In the final stage, the drug-treated cells underwent flow cytometry to assess apoptosis patterns. Data were analyzed using SPSS 17, ANOVA (for general comparison of groups) and LSD post hoc tests (for comparison two groups). p< 0.05 was considered statistically significant.
RESULTS
The findings suggested that although bromelain showed toxic effects on HN5 cancer cells, its combination with Cisplatin resulted in little improvement in its effectiveness. Bromelain alone and in combination with Cisplatin presented cytotoxic effects against fibroblasts, which depended on the dosage and time exposure (p< 0.05). The flow cytometry results did not support the superior effect of the combination of two medications over Cisplatin alone (p> 0.05).
CONCLUSION
According to the findings, although adding bromelain to Cisplatin reduced toxicity on normal tissues, the combination of these two drugs did not increase the anticancer effect of Cisplatin. Thus, bromelain in combination with Cisplatin is not recommended as an adjuvant drug for OSCC.
PubMed: 36506883
DOI: 10.30476/DENTJODS.2021.89577.1478