PMID: 

Int J Appl Basic Med Res. 2019 Apr-Jun;9(2):100-106. PMID: 31041173

Abstract Title: 

Effect of Boswellia Serrata Extract on Acute Inflammatory Parameters and Tumor Necrosis Factor-α in Complete Freund's Adjuvant-Induced Animal Model of Rheumatoid Arthritis.

Abstract: 

Context: The worldwide prevalence of rheumatoid arthritis (RA) is about 1%, whereas in India, it is approximately 0.75%. The current therapy for RA includes nonsteroidal anti-inflammatory drugs corticosteroids, disease-modifying anti-rheumatic drugs and some recently developed biologic agents, but all of these are associated with adverse effects. Some herbal drugs, such as Boswellia serrata, have been reported to possess anti-inflammatory activity.Aims: The aim of this study is to evaluate the anti-arthritic activity of Boswellia serrata extract (BSE) in complete Freund's adjuvant (CFA)-induced arthritis in rats.Materials and Methods: Thirty-six Wistar rats were divided into six equal groups. RA was induced by intradermal injection of 0.1 ml CFA in hind paw. Body weight, ankle diameter, paw volume, arthritic index, tumor necrosis factor-α (TNF-α), and histopathological examination were assessed. The experimental data were statistically assessed by one-way analysis of variance (ANOVA).Statistical Analysis Used: The recorded data were analyzed using paired-test and ANOVA test using SPSS. The data were analyzed and represented as mean difference. Value of

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PMID: 

Avicenna J Phytomed. 2019 May-Jun;9(3):281-290. PMID: 31143695

Abstract Title: 

Effects ofresin extract on motor dysfunction and brain oxidative stress in an experimental model of Parkinson's disease.

Abstract: 

Objective: oleo-gum resin (frankincense) exerted antioxidant and anti-inflammatory effects against several diseases, such as; asthma, rheumatoid arthritis and irritable bowel syndrome. In the current study, the influences ofresin extract on motor dysfunction and oxidative stress markers were investigated in the intrastriatal 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD).Materials and Methods: The animals were randomly assigned to sham, lesion (6-OHDA), and three lesion groups treated with ethyl alcoholic extract ofat doses of 125, 250 and 500 mg/kg for 3 weeks. The neurotoxin 6-OHDA (12.5µg) was microinjected into the left striatum to induce PD in male rats. Motor behavior was assessed by rotational and elevated narrow beam tests. Oxidative stress markers were measured in striatal and midbrain homogenates.Results: There was a significant increase in contralateral rotations in 6-OHDA group versus sham group (p

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PMID: 

J Craniofac Surg. 2019 Jun ;30(4):1064-1067. PMID: 30358745

Abstract Title: 

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

Abstract: 

BACKGROUND: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.

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PMID: 

Anim Cells Syst (Seoul). 2018 ;22(5):334-340. Epub 2018 Aug 30. PMID: 30460115

Abstract Title: 

Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis.

Abstract: 

Here, we investigated the possible anti-cancer properties of bromelain in Kras mutant human colorectal carcinoma cell lines and a mouse model harboring a Kras mutation. Cell growth and proliferation were significantly reduced in the Kras mutant colorectal carcinoma cell lines following treatment with 50 μg/mL bromelain as assessed by crystal violet staining and a proliferation assay. To identify the molecules responsible for this action, the expression levels of genes involved in signaling pathways and miRNAs were analyzed by real-time PCR. Among the genes tested, down-regulation of ACSL-4 andup-regulation of miRNAs targeting ASCL-4 were observed in Cacocells. Compared to the Kras wild-type colorectal carcinoma cell lines, Kras mutant colorectal carcinoma cell lines exhibited a remarkably up-regulated expression of ACSL-4, which is responsible for ferroptosis sensitivity. Moreover, the knockdown of ACSL-4 by a specific shRNA inhibited erastin-induced ferroptosis in Kras mutant DLD-1 cells as assessed by propidium iodide staining and lipid reactive oxygen species measurement. Our findings indicate that bromelain effectively exerts cytotoxic effects in Kras mutant colorectal cancer cells compared to in Kras wild-type colorectal cancer cells. Differential expression of ACSL-4 is responsible for the differential action of bromelain in regulating ferroptotic cell death.

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PMID: 

PLoS One. 2019 ;14(1):e0210274. Epub 2019 Jan 18. PMID: 30657763

Abstract Title: 

Bromelain inhibits the ability of colorectal cancer cells to proliferate via activation of ROS production and autophagy.

Abstract: 

Advanced colorectal cancer (CRC) survival rates are still low despite advances in cytotoxic and targeted therapies. The development of new effective or alternative therapies is therefore urgently needed. Bromelain, an extract of pineapple, was shown to have anticancer effects, but its mechanisms in CRC have not been fully explored. Therefore, the roles of bromelain in CRC progression were investigated using different CRC cell lines, a zebrafish model, and a xenograft mouse model. The anticancer mechanisms were explored by assessing the role of bromelain in inducing reactive oxygen species (ROS), superoxide, autophagosomes, and lysosomes. The role of bromelain in the induction of apoptosis was also assessed. It was found that bromelain inhibited CRC cell growth in cell lines and tumor growth in the zebrafish and xenograft mouse models. It also induced high levels of ROS and superoxide, plus autophagosome and lysosome formation. High levels of apoptosis were also induced, which were associated with elevated amounts of apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8, and -9 according to a qPCR analysis. In a Western blot analysis, increases in levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This study explored the role of bromelain in CRC while giving insights into its mechanisms of action. This compound can offer a cheap alternative to current therapies.

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PMID: 

J Med Signals Sens. 2019 Jan-Mar;9(1):68-74. PMID: 30967992

Abstract Title: 

Evaluation of the Radiosensitizing Potency of Bromelain for Radiation Therapy of 4T1 Breast Cancer Cells.

Abstract: 

Breast cancer (BC) remains the leading cause of death in women worldwide, despite the improvements of cancer screening and treatment methods. Recently, development of novel anticancer drugs for the improved prevention and treatment of BC is in the center of research. The anticancer effects of bromelain, as enzyme extract derived from the pineapples, contains chemicals that interfere with the growth of tumor cells. The aim of this study was to evaluate the effect of radiosensitizing of bromelain in 4T1 BC cells. This investigation utilized the 3-(4,5-dimethylthiazol-2-yl)-2,5-dimethyltetrazolium bromide assay to characterize the cytotoxicity of bromelain. Colony formation method was used to establish the truth of the capability of bromelain to make sensitive to radiation therapy. Flowcytometry performed to define the contribution the apoptosis effect to bromelain mediated radiosensitization of 4T1 cells. Bromelain reduced growth and proliferation of 4T1 cell as a concentration-dependence manner significantly. The survival of 4T1 cancer cells was decreased after combined treatment in a number and size-dependent manner with regard to the control group (

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PMID: 

Food Sci Nutr. 2019 May ;7(5):1656-1667. Epub 2019 Apr 1. PMID: 31139378

Abstract Title: 

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

Abstract: 

Bromelain (BR), a protease extracted from, 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.

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PMID: 

Nutr Cancer. 2019 Oct 8:1-11. Epub 2019 Oct 8. PMID: 31591915

Abstract Title: 

Bromelain plus peroxidase reduces non-Hodgkin lymphoma progression invia up-regulation of antioxidant enzymes and modulating apoptotic protein expression.

Abstract: 

Pineapple ((L.) Merr.) is a good source of bromelain (B) and also contain peroxidase. The objective of this study is isoaltion of bromelain plus peroxidase (BP) from the pineapple fruit to evaluate the anticancer activity of BP from the pineapple fruit of Tripura, compared to commercial bromelain against ascitic Dalton's lymphoma cells (DLA) in mice.By acetone precipitation BP was isolated from the pineapple. Animals bearing DLA, receive B and BP orally for 15 alternative days. Apoptotic proteins are assayed using western blot.BP treated mice showed recover of hemoglobin and WBC count compared to control lymphoma animal. The animal showed significant reduction of body weight due to reduced tunor load and elevated reactive oxygen species (ROS) production, elevated levels of vitamin C and vitamin E and other antioxidants in blood after BP treatment. Histology of liver and kidney also shows restored architecture in BP treated animal compared to only B treated group. BP treatment upregulates the cytochrome C, BAD, and BAX protein and downregulates the Bcl-2 and NF-kβ occuring upon BP treatment in the DLA cells collected from lymphoma animal. This induce the apoptosis of DLA cells in lymphoma animal and reduce the tumor load.The present findings suggest that BP from pineapple improves the survival of the induced lymphoma animal compared to only B which may be used as therapeutic target.

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PMID: 

Naunyn Schmiedebergs Arch Pharmacol. 2019 Oct 26. Epub 2019 Oct 26. PMID: 31655851

Abstract Title: 

Bromelain reversed electrolyte imbalance in the chronically constricted sciatic nerve of Wistar rats.

Abstract: 

Derangement of electrolyte in the sensory nervous system has been attributed to the development and maintenance of hyperalgesic and allodynic symptoms in painful neuropathy. This study investigated the effect of bromelain on electrolyte imbalance in chronically constricted sciatic nerve of rats (a model of neuropathic pain). Forty Wistar rats, divided into five groups of eight animals each were used for this study. von Frey filaments, tail immersion and acetone spray tests were used to assessed allodynic and thermal hyperalgesic symptoms in the Wistar rats. Sodium ion (Na), potassium ion (K), calcium ion (Ca) and chloride ion (Cl) concentrations as well as sodium-potassium and calcium electrogenic pump (Na-K ATPase and Ca ATPase, respectively) activities were estimated using spectrophotometry techniques. Bromelain significantly (p

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PMID: 

J Altern Complement Med. 2019 Nov 1. Epub 2019 Nov 1. PMID: 31674795

Abstract Title: 

Benefits of a Food Supplement Containingand Bromelain for Improving the Quality of Life in Patients with Osteoarthritis: A Pilot Study.

Abstract: 

Osteoarthritis (OA) is a joint disease involving articular cartilage degeneration causing patients pain, joint stiffness, physical disability, and significantly reducing their quality of life (QoL).The aim of this study was to assess whether the daily consumption of a gastroresistant food supplement formulation containing a combination of Band bromelain could improve the QoL of patients suffering from various forms of OA.Forty-nine patients were enrolled in this pilot study conducted from June 2015 to October 2016. Patients took a Boswellia- and bromelain-based supplement for a period between 1 and 6 months. At baseline and at the end of the study, patients completed a self-assessment QoL questionnaire regarding their independence in performing daily activities. QoL scores were compared between baseline and follow-up by means of the Wilcoxon signed-rank test in all patients and in the subgroups of patients with knee, hip, or generalized OA.Forty-nine patients, 6 men and 43 women, aged between 23 and 92 years, (mean age 63.24) participated in the study. At follow-up (3.0 ± 0.7 months), a significant improvement was observed for 7 of 10 QoL questions and, overall, for the total QoL score. The most significant improvements were observed in the joints that were more strongly affected at baseline. A similar trend was observed when separately considering patients with knee, hip, or generalized OA. No patients experienced adverse events and no drug interactions were reported.From this pilot study, it emerges that the use of the gastroresistant formulation containing the combination of Boswellia and bromelain supplements can represent a valuable nonpharmacological tool for improving the QoL of patients suffering from different forms of OA. Further studies should be conducted to confirm this first evidence.

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