Abstract
Proteases or proteinases are enzymes that catalyze cleavage of proteins at peptide bonds generating smaller peptides. Some of them are very specific in their choice of target site while others act rather nonspecifically and hydrolyze the protein substrate if conditions allow into short peptides. They must have appeared early in evolution along with proteins, to keep a balance between synthesis and protein degradation. Their early emergence is confirmed by their ubiquitous presence in most living forms including viruses, plants, and animals.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Abdul Khalek A, Elkateb MA, Abdel Aziz WE, El Tantawi M (2017) Effect of papacarie and alternative restorative treatment on pain reaction during caries removal among children: a randomized controlled clinical trial. J Clin Pediatr Dent 41:219–224. https://doi.org/10.17796/1053-4628-41.3.219
Agoro R, Piotet-Morin J, Palomo J, Michaudel C, Vigne S, Maillet I, Chenuet P, Guillou N, Le Bérichel J, Kisielow M, Flodby P, Borok Z, Crandall ED, Le Bert M, Quesniaux V, Muller M, Di Padova F, Ryffel B, Gabay C, Couturier-Maillard A (2016) IL-1R1-MyD88 axis elicits papain-induced lung inflammation. Eur J Immunol 46:2531–2541. https://doi.org/10.1002/eji.201646366
Agostinis C, Zorzet S, De Leo R, Zauli G, De Seta F, Bulla R (2015) The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis. Mediat Inflamm 2015:918089. https://doi.org/10.1155/2015/918089
Aichele K, Bubel M, Deubel G, Pohlemann T, Oberringer M (2013) Bromelain down-regulates myofibroblast differentiation in an in vitro wound healing assay. Naunyn Schmiedeberg’s Arch Pharmacol 386(10):853–863
Aiyegbusi AI, Duru FI, Awelimobor D, Noronha CC, Okanlawon AO (2010) The role of aqueous extract of pineapple fruit parts on the healing of acute crush tendon injury. Nig Q J Hosp Med 20:223–227
Amini A, Ehteda A, Masoumi S, Moghaddam AJ, Pillai K, Morris DL (2013) Cytotoxic effects of bromelain in human gastrointestinal carcinoma cell lines (MKN45, KATO-III, HT29-5F12, and HT29-5M21). Onco Targets Ther 6:403–409. https://doi.org/10.2147/OTT.S43072
Araujo e Silva AC, de Oliveira Lemos F, Gomes MTR, Salas CE, Lopes MTP (2015) Role of gastric acid inhibition, prostaglandins and endogenous-free thiol groups on the gastroprotective effect of a proteolytic fraction from Vasconcellea cundinamarcensis latex. J Pharm Pharmacol 67:133–141. https://doi.org/10.1111/jphp.12318
Arruda MS, Silva FO, Egito AS, Silva TMS, Lima-Filho JL, Porto ALF, Moreira KA (2012) New peptides obtained by hydrolysis of caseins from bovine milk by protease extracted from the latex Jacaratia corumbensis. LWT - Food Sci Technol 49:73–79. https://doi.org/10.1016/J.LWT.2012.04.001
Atacan K, Özacar M, Özacar M (2018) Investigation of antibacterial properties of novel papain immobilized on tannic acid modified Ag/CuFe2O4magnetic nanoparticles. Int J Biol Macromol 109:720–731. https://doi.org/10.1016/j.ijbiomac.2017.12.066
Auwal S, Zarei M, Tan C, Basri M, Saari N (2017) Improved in vivo efficacy of anti-hypertensive biopeptides encapsulated in chitosan nanoparticles fabricated by ionotropic gelation on spontaneously hypertensive rats. Nanomaterials 7:421. https://doi.org/10.3390/nano7120421
Bagga P, Ansari TM, Siddiqui HH, Syed A, Bahkali AH, Rahman MA, Khan MS (2016) Bromelain capped gold nanoparticles as the novel drug delivery carriers to aggrandize effect of the antibiotic levofloxacin. EXCLI J 15:772–780. https://doi.org/10.17179/excli2016-710
Balakireva AV, Kuznetsova NV, Petushkova AI, Savvateeva L, Zamyatnin AA (2017) Trends and prospects of plant proteases in therapeutics. Curr Med Chem. https://doi.org/10.2174/0929867325666171123204403
Barrett AJ, Fred Woessner J (2013) Handbook of proteolytic enzymes. Academic, London, pp li–liv
Baur X, Fruhmann G (1979) Allergic reactions, including asthma, to the pineapple protease bromelain following occupational exposure. Clin Allergy 9:443–450
Bernela M, Ahuja M, Thakur R (2016) Enhancement of anti-inflammatory activity of bromelain by its encapsulation in katira gum nanoparticles. Carbohydr Polym 143:18–24. https://doi.org/10.1016/j.carbpol.2016.01.055
Beuth J (2008) Proteolytic enzyme therapy in evidence-based complementary oncology: fact or fiction? Integr Cancer Ther 7:311–316. https://doi.org/10.1177/1534735408327251
Bhatnagar P, Patnaik S, Srivastava AK, Mudiam MKR, Shukla Y, Panda AK, Pant AB, Kumar P, Gupta KC (2014) Anti-cancer activity of bromelain nanoparticles by oral administration. J Biomed Nanotechnol 10:3558–3575
Bhatnagar P, Pant AB, Shukla Y, Chaudhari B, Kumar P, Gupta KC (2015) Bromelain nanoparticles protect against 7,12-dimethylbenz[a]anthracene induced skin carcinogenesis in mouse model. Eur J Pharm Biopharm 91:35–46. https://doi.org/10.1016/j.ejpb.2015.01.015
Bhatnagar P, Pant AB, Shukla Y, Panda A, Gupta KC (2016) Hyaluronic acid grafted PLGA copolymer nanoparticles enhance the targeted delivery of bromelain in Ehrlich’s ascites carcinoma. Eur J Pharm Biopharm 105:176–192. https://doi.org/10.1016/j.ejpb.2016.06.002
Bhui K, Tyagi S, Prakash B, Shukla Y (2010) Pineapple bromelain induces autophagy, facilitating apoptotic response in mammary carcinoma cells. Biofactors 36:474–482. https://doi.org/10.1002/biof.121
Bilheiro RP, Braga AD, Filho ML, Carvalho-Tavares J, Agero U, Carvalho M Das G, Sanchez EF, Salas CE, Lopes MTP (2013) The thrombolytic action of a proteolytic fraction (P1G10) from Carica candamarcensis. Thromb Res 131:e175–e182. https://doi.org/10.1016/j.thromres.2013.01.028
Brien S, Lewith G, Walker AF, Middleton R, Prescott P, Bundy R (2006) Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study. QJM 99:841–850. https://doi.org/10.1093/qjmed/hcl118
Burney RO, Giudice LC (2012) Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98:511–519. https://doi.org/10.1016/j.fertnstert.2012.06.029
Bussadori SK, Castro LC, Galvão AC (2005) Papain gel: a new chemo-mechanical caries removal agent. J Clin Pediatr Dent 30:115–119
Büttner L, Achilles N, Böhm M, Shah-Hosseini K, Mösges R (2013) Efficacy and tolerability of bromelain in patients with chronic rhinosinusitis - a pilot study. B-ENT 9:217–225
Carrilho DM, Duarte IC, Francisco R, Ricardo CPP, Duque-Magalhães MC (2009) Discovery of novel plant peptides as strong inhibitors of metalloproteinases. Protein Pept Lett 16:543–551
Chay SY, Tan WK, Saari N (2015) Preparation and characterisation of nanoliposomes containing winged bean seeds bioactive peptides. J Microencapsul 32:488–495. https://doi.org/10.3109/02652048.2015.1057250
Chen Y-Y, Lu Y-H, Ma C-H, Tao W-W, Zhu J-J, Zhang X (2017) A novel elastic liposome for skin delivery of papain and its application on hypertrophic scar. Biomed Pharmacother 87:82–91. https://doi.org/10.1016/j.biopha.2016.12.076
Choi J-H, Kim D-W, Park S-E, Choi B-S, Sapkota K, Kim S, Kim S-J (2014) Novel thrombolytic protease from edible and medicinal plant Aster yomena (Kitam.) Honda with anticoagulant activity: purification and partial characterization. J Biosci Bioeng 118:372–377. https://doi.org/10.1016/j.jbiosc.2014.03.004
Cordts T, Horter J, Vogelpohl J, Kremer T, Kneser U, Hernekamp J-F (2016) Enzymatic debridement for the treatment of severely burned upper extremities – early single center experiences. BMC Dermatol 16:8. https://doi.org/10.1186/s12895-016-0045-2
de Menezes Y, Félix-Silva J, da Silva-Júnior A, Rebecchi I, de Oliveira A, Uchoa A, Fernandes-Pedrosa M (2014) Protein-Rich Fraction of Cnidoscolus urens (L.) Arthur Leaves: Enzymatic Characterization and Procoagulant and Fibrinogenolytic Activities. Molecules 19:3552–3569. https://doi.org/10.3390/molecules19033552
Dąbrowska A, Szołtysik M, Babij K, Pokora M, Zambrowicz A, Chrzanowska J (2013) Application of Asian pumpkin (Cucurbita ficifolia) serine proteinase for production of biologically active peptides from casein. Acta Biochim Pol 60:117–122
DeClerck MP, Bailey Y, Craig D, Lin M, Auerbach LJ, Linney O, Morrison DE, Patry W, Auerbach PS (2016) Efficacy of topical treatments for Chrysaora Chinensis species: a human model in comparison with an in vitro model. Wilderness Environ Med 27:25–38. https://doi.org/10.1016/j.wem.2015.10.008
Déry O, Corvera CU, Steinhoff M, Bunnett NW (1998) Proteinase-activated receptors: novel mechanisms of signaling by serine proteases. Am J Phys 274:C1429–C1452
Dhandayuthapani S, Perez HD, Paroulek A, Chinnakkannu P, Kandalam U, Jaffe M, Rathinavelu A (2012) Bromelain-induced apoptosis in GI-101A breast cancer cells. J Med Food 15:344–349. https://doi.org/10.1089/jmf.2011.0145
Dittz D, Figueiredo C, Lemos FO, Viana CTR, Andrade SP, Souza-Fagundes EM, Fujiwara RT, Salas CE, Lopes MTP (2015) Antiangiogenesis, loss of cell adhesion and apoptosis are involved in the antitumoral activity of proteases from v. Cundinamarcensis (C. candamarcensis) in murine melanoma B16F1. Int J Mol Sci 16:7027–7044. https://doi.org/10.3390/ijms16047027
Divya G, Prasad MG, Vasa AAK, Vasanthi D, Ramanarayana B, Mynampati P (2015) Evaluation of the efficacy of caries removal using polymer bur, stainless steel bur, carisolv, papacarie - an in vitro comparative study. J Clin Diagn Res 9:ZC42–ZC46. https://doi.org/10.7860/JCDR/2015/12705.6202
Domsalla A, Melzig MF (2008) Occurrence and properties of proteases in plant latices. Planta Med 74:699–711. https://doi.org/10.1055/s-2008-1074530
Dutta S, Bhattacharyya D (2013) Enzymatic, antimicrobial and toxicity studies of the aqueous extract of Ananas comosus (pineapple) crown leaf. J Ethnopharmacol 150:451–457. https://doi.org/10.1016/j.jep.2013.08.024
Errasti M, Caffini N, Pelzer L, Rotelli A (2013) Anti-inflammatory activity of bromelia hieronymi: comparison with bromelain. Planta Med 79:207–213. https://doi.org/10.1055/s-0032-1328201
Errasti ME, Prospitti A, Viana CA, Gonzalez MM, Ramos MV, Rotelli AE, Caffini NO (2016) Effects on fibrinogen, fibrin, and blood coagulation of proteolytic extracts from fruits of Pseudananas macrodontes, Bromelia balansae, and B. hieronymi (Bromeliaceae) in comparison with bromelain. Blood Coagul Fibrinolysis 27:441–449. https://doi.org/10.1097/MBC.0000000000000531
Eskenazi B, Warner ML (1997) Epidemiology of endometriosis. Obstet Gynecol Clin N Am 24:235–258
Fitzhugh DJ, Shan S, Dewhirst MW, Hale LP (2008) Bromelain treatment decreases neutrophil migration to sites of inflammation. Clin Immunol 128:66–74. https://doi.org/10.1016/j.clim.2008.02.015
Fortelny N, Cox JH, Kappelhoff R, Starr AE, Lange PF, Pavlidis P, Overall CM (2014) Network analyses reveal pervasive functional regulation between proteases in the human protease web. PLoS Biol 12:e1001869. https://doi.org/10.1371/journal.pbio.1001869
Freitas KM, Barcelos LS, Caliari MV, Salas CE, Lopes MTP (2017) Healing activity of proteolytic fraction (P1G10) from Vasconcellea cundinamarcensis in a cutaneous wound excision model. Biomed Pharmacother 96:269–278. https://doi.org/10.1016/j.biopha.2017.09.109
Gajanan PG, Elavarasan K, Shamasundar BA (2016) Bioactive and functional properties of protein hydrolysates from fish frame processing waste using plant proteases. Environ Sci Pollut Res Int 23:24901–24911. https://doi.org/10.1007/s11356-016-7618-9
Golezar S (2016) Ananas comosus effect on perineal pain and wound healing after episiotomy: a randomized double-blind placebo-controlled clinical trial. Iran Red Crescent Med J 18:e21019. https://doi.org/10.5812/ircmj.21019
Gomes MTRTR, Mello VJ, Rodrigues KC, Bemquerer MP, Lopes MTP, Faça VM, Salas CE (2005) Isolation of two plant proteinases in latex from Carica candamarcensis acting as mitogens for mammalian cells. Planta Med 71:244–248. https://doi.org/10.1055/s-2005-837824
Gomes MTR, Turchetti AP, Lopes MTP, Salas CE (2009) Stimulation of fibroblast proliferation by the plant cysteine protease CMS2MS2 is independent of its proteolytic activity and requires ERK activation. Biol Chem 390:1285–1291. https://doi.org/10.1515/BC.2009.137
Gomes FSL, Spínola CDV, Ribeiro HA, Lopes MTP, Cassali GD, Salas CE (2010) Wound-healing activity of a proteolytic fraction from Carica candamarcensis on experimentally induced burn. Burns 36:277–283. https://doi.org/10.1016/j.burns.2009.04.007
Guimarães-Ferreira C, Rodrigues E, Mortara R, Cabral H, Serrano F, Ribeiro-dos-Santos R, Travassos L (2007) Antitumor effects in vitro and in vivo and mechanisms of protection against melanoma B16F10-Nex2 cells by fastuosain, a cysteine proteinase from Bromelia fastuosa. Neoplasia 9:723–733. https://doi.org/10.1593/neo.07427
Hafez MA, Elkateb M, El Shabrawy S, Mahmoud A, El Meligy O (2017) Microleakage evaluation of composite restorations following papain-based chemo-mechanical caries removal in primary teeth. J Clin Pediatr Dent 41:53–61. https://doi.org/10.17796/1053-4628-41.1.53
Hale LP, Greer PK, Trinh CT, Gottfried MR (2005) Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease. Clin Immunol 116:135–142. https://doi.org/10.1016/j.clim.2005.04.011
Hale LP, Chichlowski M, Trinh CT, Greer PK (2010) Dietary supplementation with fresh pineapple juice decreases inflammation and colonic neoplasia in IL-10-deficient mice with colitis. Inflamm Bowel Dis 16:2012–2021. https://doi.org/10.1002/ibd.21320
Harada T, Yoshioka H, Yoshida S, Iwabe T, Onohara Y, Tanikawa M, Terakawa N (1997) Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis. Am J Obstet Gynecol 176:593–597. https://doi.org/10.1016/S0002-9378(97)70553-2
Heinicke RM, Gortner WA (1957) Stem bromelain---a new protease preparation from pineapple plants. Econ Bot 11:225–234. https://doi.org/10.1007/BF02860437
Ho D, Jagdeo J, Waldorf HA (2016) Is there a Role for Arnica and Bromelain in prevention of post-procedure ecchymosis or Edema? A systematic review of the literature. Dermatol Surg 42(4):445–463
Huffaker RC (1990) Proteolytic activity during senescence of plants. New Phytol 116:199–231. https://doi.org/10.1111/j.1469-8137.1990.tb04710.x
Iida H, Takai T, Hirasawa Y, Kamijo S, Shimura S, Ochi H, Nishioka I, Maruyama N, Ogawa H, Okumura K, Ikeda S (2014) Epicutaneous administration of papain induces IgE and IgG responses in a cysteine protease activity-dependent manner. Allergol Int 63:219–226. https://doi.org/10.2332/allergolint.13-OA-0621
Iram S, Zahera M, Khan S, Khan I, Syed A, Ansary AA, Ameen F, Shair OHM, Khan MS (2017) Gold nanoconjugates reinforce the potency of conjugated cisplatin and doxorubicin. Colloids Surf B Biointerfaces 160:254–264. https://doi.org/10.1016/j.colsurfb.2017.09.017
Kim D-W, Choi J-H, Park S-E, Kim SS-J, Sapkota K, Kim SS-J (2015) Purification and characterization of a fibrinolytic enzyme from Petasites japonicus. Int J Biol Macromol 72:1159–1167. https://doi.org/10.1016/j.ijbiomac.2014.09.046
Kong X, Guo M, Hua Y, Cao D, Zhang C (2008) Enzymatic preparation of immunomodulating hydrolysates from soy proteins. Bioresour Technol 99:8873–8879
Kush A, Thakur R, Patil SDS, Paul ST, Kakanur M (2015) Evaluation of antimicrobial action of Carie CareTM and Papacarie DuoTM on Aggregatibacter actinomycetemcomitans a major periodontal pathogen using polymerase chain reaction. Contemp Clin Dent 6:534–538. https://doi.org/10.4103/0976-237X.169860
Lacroix IME, Li-Chan ECY (2012) Dipeptidyl peptidase-IV inhibitory activity of dairy protein hydrolysates. Int Dairy J 25:97–102. https://doi.org/10.1016/J.IDAIRYJ.2012.01.003
Lemos FO, Ferreira LAM, Cardoso VN, Cassali GD, Salas CE, Lopes MTP (2011) Skin-healing activity and toxicological evaluation of a proteinase fraction from Carica candamarcensis. Eur J Dermatol 21:722–730. https://doi.org/10.1684/ejd.2011.1466
Levecke B, Buttle DJ, Behnke JM, Duce IR, Vercruysse J (2014) Cysteine proteinases from papaya (Carica papaya) in the treatment of experimental Trichuris suis infection in pigs: two randomized controlled trials. Parasit Vectors 7:255. https://doi.org/10.1186/1756-3305-7-255
Lewinsohn TM (1991) The geographical distribution of plant latex. Chemoecology 2:64–68. https://doi.org/10.1007/BF01240668
Li-Chan ECY, Hunag S-L, Jao C-L, Ho K-P, Hsu K-C (2012) Peptides derived from Atlantic salmon skin gelatin as dipeptidyl-peptidase IV inhibitors. J Agric Food Chem 60:973–978. https://doi.org/10.1021/jf204720q
Luoga W, Mansur F, Lowe A, Duce IR, Buttle DJ, Behnke JM (2015) Factors affecting the anthelmintic efficacy of papaya latex in vivo: host sex and intensity of infection. Parasitol Res 114:2535–2541. https://doi.org/10.1007/s00436-015-4456-5
Majid OW, Al-Mashhadani BA (2014) Perioperative Bromelain reduces pain and swelling and improves quality of life measures after mandibular third molar surgery: a randomized, double-blind, placebo-controlled clinical trial. J Oral Maxillofac Surg 72(6):1043–1048
Manosroi A, Chankhampan C, Manosroi W, Manosroi J (2012) Toxicity reduction and MMP-2 stimulation of papain and Bromelain loaded in elastic Niosomes. J Biomed Nanotechnol 8(5):720–729
Mansur F, Luoga W, Buttle DJ, Duce IR, Lowe A, Behnke JM (2014) The anthelmintic efficacy of natural plant cysteine proteinases against two rodent cestodes Hymenolepis diminuta and Hymenolepis microstoma in vitro. Vet Parasitol 201:48–58. https://doi.org/10.1016/j.vetpar.2013.12.018
Mazorra-Manzano MA, Ramírez-Suarez JC, Yada RY (2017) Plant proteases for bioactive peptides release: a review. Crit Rev Food Sci Nutr 10:1–17. https://doi.org/10.1080/10408398.2017.1308312
Medeiros AF, Costa IS, Carvalho FMC, Kiyota S, Souza BBP, Sifuentes DN, Serquiz RP, Maciel BLL, Uchôa AF, Santos EA, Morais AHA (2018) Biochemical characterisation of a Kunitz-type inhibitor from Tamarindus indica L. seeds and its efficacy in reducing plasma leptin in an experimental model of obesity. J Enzyme Inhib Med Chem 33:334–348. https://doi.org/10.1080/14756366.2017.1419220
Mello VJ, Gomes MTR, Lemos FO, Delfino JL, Andrade SP, Lopes MTP, Salas CE (2008) The gastric ulcer protective and healing role of cysteine proteinases from Carica candamarcensis. Phytomedicine 15:237–244. https://doi.org/10.1016/j.phymed.2007.06.004
Mendonça RJ, Maurício VB, Teixeira LB, Lachat JJ, Coutinho-Netto J (2010) Increased vascular permeability, angiogenesis and wound healing induced by the serum of natural latex of the rubber tree Hevea brasiliensis. Phytother Res 24:764–768. https://doi.org/10.1002/ptr.3043
Menzel C, Bernkop-Schnürch A (2018) Enzyme decorated drug carriers: targeted swords to cleave and overcome the mucus barrier. Adv Drug Deliv Rev 124:164–174. https://doi.org/10.1016/j.addr.2017.10.004
Miranda ÍKSPB, Miranda AFS, Souza FVD, Vannier-Santos MA, Pirovani CP, Pepe IM, Rodowanski IJ, Ferreira KTSE, Vaz LMS, de Assis SA (2017) The biochemical characterization, stabilization studies and the antiproliferative effect of bromelain against B16F10 murine melanoma cells. Int J Food Sci Nutr 68:442–454. https://doi.org/10.1080/09637486.2016.1254599
Morimatsu F, Ito M, Budijanto S, Watanabe I, Furukawa Y, Kimura S (1996) Plasma cholesterol-suppressing effect of papain-hydrolyzed pork meat in rats fed hypercholesterolemic diet. J Nutr Sci Vitaminol 42:145–153
Motta LJ, Bussadori SK, Campanelli AP, Silva AL, Alfaya TA, Godoy CHL, Navarro MFL (2014) Randomized controlled clinical trial of long-term chemo-mechanical caries removal using PapacarieTM gel. J Appl Oral Sci 22:307–313. https://doi.org/10.1590/1678-775720130488
Mugita N, Nambu T, Takahashi K, Wang P-L, Komasa Y (2017) Proteases, actinidin, papain and trypsin reduce oral biofilm on the tongue in elderly subjects and in vitro. Arch Oral Biol 82:233–240. https://doi.org/10.1016/j.archoralbio.2017.04.035
Muhammad ZA, Ahmad T (2017) Therapeutic uses of pineapple-extracted bromelain in surgical care - a review. J Pak Med Assoc 67:121–125
Müller A, Barat S, Chen X, Bui KC, Bozko P, Malek NP, Plentz RR (2016) Comparative study of antitumor effects of bromelain and papain in human cholangiocarcinoma cell lines. Int J Oncol 48:2025–2034. https://doi.org/10.3892/ijo.2016.3411
Nongonierma AB, FitzGerald RJ (2014) Susceptibility of milk protein-derived peptides to dipeptidyl peptidase IV (DPP-IV) hydrolysis. Food Chem 145:845–852. https://doi.org/10.1016/j.foodchem.2013.08.097
Ochsner A, Storck A (1936) The prevention of peritoneal adhesions by papain: a clinical study. Ann Surg 104:736–747
Oliveira de Lima VC, de Araújo Machado RJ, Vieira Monteiro NK, de Lyra IL, da Silva Camillo C, Coelho Serquiz A, Silva de Oliveira A, da Silva Rufino FP, Leal Lima Maciel B, Ferreira Uchôa A, Antunes Dos Santos E, de Araújo Morais AH (2017) Gastroprotective and antielastase effects of protein inhibitors from Erythrina velutina seeds in an experimental ulcer model. Biochem Cell Biol 95:243–250. https://doi.org/10.1139/bcb-2016-0034
Oliveira CP, Prado WA, Lavayen V, Büttenbender SL, Beckenkamp A, Martins BS, Lüdtke DS, Campo LF, Rodembusch FS, Buffon A, Pessoa A, Guterres SS, Pohlmann AR (2017) Bromelain-functionalized multiple-wall lipid-core nanocapsules: formulation, chemical structure and antiproliferative effect against human breast cancer cells (MCF-7). Pharm Res 34:438–452. https://doi.org/10.1007/s11095-016-2074-2
Onken JE, Greer PK, Calingaert B, Hale LP (2008) Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro. Clin Immunol 126:345–352. https://doi.org/10.1016/j.clim.2007.11.002
Ordesi P, Pisoni L, Nannei P, Macchi M, Borloni R, Siervo S (2014) Therapeutic efficacy of bromelain in impacted third molar surgery: a randomized controlled clinical study. Quintessence Int 45(8):679–684. https://doi.org/10.3290/j.qi.a32237
Parodi A, Haddix SG, Taghipour N, Scaria S, Taraballi F, Cevenini A, Yazdi IK, Corbo C, Palomba R, Khaled SZ, Martinez JO, Brown BS, Isenhart L, Tasciotti E (2014) Bromelain surface modification increases the diffusion of silica nanoparticles in the tumor extracellular matrix. ACS Nano 8:9874–9883. https://doi.org/10.1021/nn502807n
Patel DV, Sawant MG, Kaur G (2015) Evaluation of anti-osteoarthritic activity of Vigna mungo in papain induced osteoarthritis model. Indian J Pharm 47:59–64. https://doi.org/10.4103/0253-7613.150340
Patil PA, Ankola AV, Hebbal MI, Patil AC (2015) Comparison of effectiveness of abrasive and enzymatic action of whitening toothpastes in removal of extrinsic stains - a clinical trial. Int J Dent Hyg 13(1):25–29
Pepe A, Frey ME, Muñoz F, Fernández MB, Pedraza A, Galbán G, García DN, Daleo GR, Guevara MG (2016) Fibrin(ogen)olytic and antiplatelet activities of a subtilisin-like protease from Solanum tuberosum (StSBTc-3). Biochimie 125:163–170. https://doi.org/10.1016/j.biochi.2016.03.015
Phares K, Kubik J (1996) The growth factor from plerocercoids of Spirometra mansonoides is both a growth hormone agonist and a cysteine proteinase. J Parasitol 82:210–215
Pillai K, Akhter J, Chua TC, Morris DL (2013) Anticancer property of bromelain with therapeutic potential in malignant peritoneal mesothelioma. Cancer Investig 31:241–250
Pu C, Tang W (2017) The antibacterial and antibiofilm efficacies of a liposomal peptide originating from rice bran protein against Listeria monocytogenes. Food Funct 8:4159–4169. https://doi.org/10.1039/C7FO00994A
Rakashanda S, Qazi AK, Majeed R, Andrabi SM, Hamid A, Sharma PR, Amin S (2015) Plant-derived protease inhibitors LC-pi (Lavatera cashmeriana) inhibit human lung cancer cell proliferation in vitro. Nutr Cancer 67:156–166. https://doi.org/10.1080/01635581.2015.967876
Rakhimov MR (2001) Anti-inflammatory activity of domestic papain. Eksp Klin Farmakol 64:48–49
Romano B, Fasolino I, Pagano E, Capasso R, Pace S, De Rosa G, Milic N, Orlando P, Izzo AA, Borrelli F (2014) The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects. Mol Nutr Food Res 58:457–465. https://doi.org/10.1002/mnfr.201300345
Rosenberg L, Krieger Y, Silberstein E, Arnon O, Sinelnikov IA, Bogdanov-Berezovsky A, Singer AJ (2012) Selectivity of a bromelain based enzymatic debridement agent: a porcine study. Burns 38:1035–1040. https://doi.org/10.1016/j.burns.2012.02.011
Rosenberg L, Krieger Y, Bogdanov-Berezovski A, Silberstein E, Shoham Y, Singer AJ (2014) A novel rapid and selective enzymatic debridement agent for burn wound management: a multi-center RCT. Burns 40:466–474. https://doi.org/10.1016/j.burns.2013.08.013
Sahana S, Vasa AAK, Geddam D, Reddy VK, Nalluri S, Velagapudi N (2016) Effectiveness of chemomechanical caries removal agents Papacarie(®) and Carie-CareTM in primary molars: an in vitro study. J Int Soc Prev Community Dent 6:S17–S22. https://doi.org/10.4103/2231-0762.181162
Sahbaz A, Aynioglu O, Isik H, Ozmen U, Cengil O, Gun BD, Gungorduk K (2015) Bromelain: a natural proteolytic for intra-abdominal adhesion prevention. Int J Surg 14:7–11. https://doi.org/10.1016/j.ijsu.2014.12.024
Sahu K, Kaurav M, Pandey RS (2017) Protease loaded permeation enhancer liposomes for treatment of skin fibrosis arisen from second degree burn. Biomed Pharmacother 94:747–757. https://doi.org/10.1016/j.biopha.2017.07.141
Salampessy J, Phillips M, Seneweera S, Kailasapathy K (2010) Release of antimicrobial peptides through bromelain hydrolysis of leatherjacket (Meuchenia sp.) insoluble proteins. Food Chem 120:556–560. https://doi.org/10.1016/J.FOODCHEM.2009.10.054
Salas CE, Gomes MTR, Hernandez M, Lopes MTP (2008) Plant cysteine proteinases: evaluation of the pharmacological activity. Phytochemistry 69:2263–2269. https://doi.org/10.1016/j.phytochem.2008.05.016
Salu BR, Pando SC, Brito MV, Medina AF, Odei-Addo F, Frost C, Naude R, Sampaio MU, Emsley J, Maffei FHA, Oliva MLV (2018) Improving the understanding of plasma kallikrein contribution to arterial thrombus formation using two plant protease inhibitors. Platelets 14:1–9. https://doi.org/10.1080/09537104.2018.1428738
Schulz A, Shoham Y, Rosenberg L, Rothermund I, Perbix W, Christian Fuchs P, Lipensky A, Schiefer JL (2017) Enzymatic versus traditional surgical debridement of severely burned hands: a comparison of selectivity, efficacy, healing time, and three-month scar quality. J Burn Care Res 38:e745–e755. https://doi.org/10.1097/BCR.0000000000000478
Seaf M, Ben-Zimra M, Mankuta D, Dayan N, Levi-Schaffer F (2016) Papain activates human mast cells to release proinflammatory mediators via its enzymatic activity. J Invest Dermatol 136:1523–1525. https://doi.org/10.1016/j.jid.2016.03.030
Secor ER, Shah SJ, Guernsey LA, Schramm CM, Thrall RS (2012) Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma. Altern Ther Health Med 18:9–17
Shimizu M, Sawashita N, Morimatsu F, Ichikawa J, Taguchi Y, Ijiri Y, Yamamoto J (2009) Antithrombotic papain-hydrolyzed peptides isolated from pork meat. Thromb Res 123:753–757. https://doi.org/10.1016/j.thromres.2008.07.005
Shing CM, Chong S, Driller MW, Fell JW (2015) Acute protease supplementation effects on muscle damage and recovery across consecutive days of cycle racing. European Journal of Sport Science 16(2):206–212
Shivalingu BR, Vivek HK, Priya BS, Soujanya KN, Swamy SN (2016) Purification and characterization of novel fibrin(ogen)olytic protease from Curcuma aromatica Salisb.: role in hemostasis. Phytomedicine 23:1691–1698. https://doi.org/10.1016/j.phymed.2016.09.007
Shivaprasad HV, Rajesh R, Nanda BL, Dharmappa KK, Vishwanath BS (2009) Thrombin like activity of Asclepias curassavica L. latex: action of cysteine proteases. J Ethnopharmacol 123:106–109. https://doi.org/10.1016/j.jep.2009.02.016
Shoba E, Lakra R, Syamala Kiran M, Korrapati PS (2017) Fabrication of core-shell nanofibers for controlled delivery of bromelain and salvianolic acid B for skin regeneration in wound therapeutics. Biomed Mater 12:35005. https://doi.org/10.1088/1748-605X/aa6684
Singer AJ, Taira BR, Anderson R, McClain SA, Rosenberg L (2010) The Effects of rapid enzymatic debridement of deep partial-thickness burns with Debrase® on wound reepithelialization in swine. J Burn Care Res 31:795–802. https://doi.org/10.1097/BCR.0b013e3181eed48e
Siritapetawee J, Sojikul P, Klaynongsruang S (2015) Biochemical characterization of a new glycosylated protease from Euphorbia cf. lactea latex. Plant Physiol Biochem 92:30–38. https://doi.org/10.1016/j.plaphy.2015.04.012
Soplin SP, Millones EA, Campos JLA, Deza LG, Ríos EJ, Sánchez IB, Benítez MR, Pando LG, Panizo RS, Merino C del C, Rivera JC (1995) Perú: Informe nacional para la conferencia técnica internacional de la FAO sobre los recursos fitogenéticos (Leipzig, 1996). Peru, p 253
Stevens LE (1968) A reassessment of papain in preventing peritoneal adhesions. Am J Surg 115:535–539
Tadikonda A, Pentapati K-C, Urala A-S, Acharya S (2017) Anti-plaque and anti-gingivitis effect of Papain, Bromelain, Miswak and Neem containing dentifrice: a randomized controlled trial. J Clin Exp Dent 9:e649–e653. https://doi.org/10.4317/jced.53593
Tavares T, Contreras MDM, Amorim M, Pintado M, Recio I, Malcata FX (2011) Novel whey-derived peptides with inhibitory effect against angiotensin-converting enzyme: in vitro effect and stability to gastrointestinal enzymes. Peptides 32:1013–1019. https://doi.org/10.1016/j.peptides.2011.02.005
Tharakan A, Dobzanski A, London NR, Khalil SM, Surya N, Lane AP, Ramanathan M (2018) Characterization of a novel, papain-inducible murine model of eosinophilic rhinosinusitis. Int Forum Allergy Rhinol 8(4):513–521. https://doi.org/10.1002/alr.22072
Uday P, Maheshwari M, Sharanappa P, Nafeesa Z, Kameshwar VH, Priya BS, Nanjunda Swamy S (2017) Exploring hemostatic and thrombolytic potential of heynein - a cysteine protease from Ervatamia heyneana latex. J Ethnopharmacol 199:316–322. https://doi.org/10.1016/j.jep.2016.12.047
van der Hoorn RAL (2008) Plant proteases: from phenotypes to molecular mechanisms. Annu Rev Plant Biol 59:191–223. https://doi.org/10.1146/annurev.arplant.59.032607.092835
van Wijk KJ (2015) Protein maturation and proteolysis in plant plastids, mitochondria, and peroxisomes. Annu Rev Plant Biol 66:75–111. https://doi.org/10.1146/annurev-arplant-043014-115547
Wang B, Li Z-R, Chi C-F, Zhang Q-H, Luo H-Y (2012) Preparation and evaluation of antioxidant peptides from ethanol-soluble proteins hydrolysate of Sphyrna lewini muscle. Peptides 36:240–250. https://doi.org/10.1016/j.peptides.2012.05.013
Wei B, He L, Wang X, Yan GQ, Wang J, Tang R (2017) Bromelain-decorated hybrid nanoparticles based on lactobionic acid-conjugated chitosan for in vitro anti-tumor study. J Biomater Appl 32:206–218. https://doi.org/10.1177/0885328217715537
Wu S-Y, Hu W, Zhang B, Liu S, Wang J-M, Wang A-M (2012) Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds. J Surg Res 176:503–509. https://doi.org/10.1016/j.jss.2011.11.1027
Yariswamy M, Shivaprasad HV, Joshi V, Nanjaraj URSAN, Nataraju A, Vishwanath BS (2013) Topical application of serine proteases from Wrightia tinctoria R. Br. (Apocyanaceae) latex augments healing of experimentally induced excision wound in mice. J Ethnopharmacol 149:377–383. https://doi.org/10.1016/j.jep.2013.06.056
Zetter BR, Chen LB, Buchanan JM (1976) Effects of protease treatment on growth, morphology, adhesion, and cell surface proteins of secondary chick embryo fibroblasts. Cell 7:407–412. https://doi.org/10.1016/0092-8674(76)90170-7
Zhou Z, Wang L, Feng P, Yin L, Wang C, Zhi S, Dong J, Wang J, Lin Y, Chen D, Xiong Y, Peng J (2017) Inhibition of epithelial TNF-α receptors by purified fruit bromelain ameliorates intestinal inflammation and barrier dysfunction in colitis. Front Immunol 8:1468. https://doi.org/10.3389/fimmu.2017.01468
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Salas, C.E., Dittz, D., Torres, MJ. (2018). Plant Proteolytic Enzymes: Their Role as Natural Pharmacophores. In: Guevara, M., Daleo, G. (eds) Biotechnological Applications of Plant Proteolytic Enzymes. Springer, Cham. https://doi.org/10.1007/978-3-319-97132-2_5
Download citation
DOI: https://doi.org/10.1007/978-3-319-97132-2_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-97131-5
Online ISBN: 978-3-319-97132-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)