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Serratiopeptidase as an adjunct in burn care: a critical review and testable hypothesis for reducing NSAID exposure
Authors
1 Director and Medical Advisor, Eutherva Medicament Pvt. Ltd., Mumbai, India. 2 Senior Consultant Projects and Operations, Xplora Clinical Research Services Pvt. Ltd., Bangalore, Karnataka, India. 3 PhD Scholar, Chitkara University, Punjab, India.
Article Information
- DOI
- No Doi
- Published In
- Year 2026 · Volume 1 · Issue 3
- Published Online
- September-December 2026
- Pages
- 01-11
- Article Type
- Review Article
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References
1. Jeschke MG, van Baar ME, Choudhry MA, Chung KK, Gibran NS, Logsetty S. Burn injury. Nat Rev Dis Primers. 2020;6:11. doi: 10.1038/s41572-020-0145-5.
2. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999;341(10):738–46. doi: 10.1056/NEJM199909023411006.
3. Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014;6(265):265sr6. doi: 10.1126/scitranslmed.3009337.
4. You Z, Jain S, Shen S, Mao J, Martyn JAJ. Pathophysiology and management of burn injury-induced pain. Burns Open. 2025;10:100396. doi: 10.1016/j.burnso.2025.100396.
5. Romanowski KS, Carson J, Pape K, Bernal E, Sharar S, Wiechman S, et al. American Burn Association guidelines on the management of acute pain in the adult burn patient: a review of the literature, a compilation of expert opinion, and next steps. J Burn Care Res. 2020;41(6):1129–51. doi: 10.1093/jbcr/iraa119.
6. Bhagat S, Agarwal M, Roy V. Serratiopeptidase: a systematic review of the existing evidence. Int J Surg. 2013;11(3):209–17. doi: 10.1016/j.ijsu.2013.01.010.
7. Burgess M, Valdera F, Varon D, Kankuri E, Nuutila K. The immune and regenerative response to burn injury. Cells. 2022;11(19):3073. doi: 10.3390/cells11193073.
8. Keyloun JW, Campbell R, Carney BC, Yang R, Miller SA, Detwiler L, et al. Early Transcriptomic Response to Burn Injury: Severe Burns Are Associated With Immune Pathway Shutdown. J Burn Care Res. 2022;43(2):306–314. doi: 10.1093/jbcr/irab217.
9. Dobson GP, Morris JL, Letson HL. Pathophysiology of Severe Burn Injuries: New Therapeutic Opportunities From a Systems Perspective. J Burn Care Res. 2024;45(4):1041–1050. doi: 10.1093/jbcr/irae049.10. Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, et al. Burn wound healing and treatment: review and advancements. Crit Care. 2015;19:243. doi: 10.1186/s13054-015-0961-2.
11. Ryan MJ, Raby E, Whiley L, Masuda R, Lodge S, Nitschke P, et al. Nonsevere burn induces a prolonged systemic metabolic phenotype indicative of a persistent inflammatory response postinjury. J Proteome Res. 2024;23(8):2893–2907. doi: 10.1021/acs.jproteome.3c00516.
12. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986–1000. doi: 10.1161/ATVBAHA.110.207449.
13. Rao R, Redha R, Macias-Perez I, Su Y, Hao C, Zent R, et al. Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo. J Biol Chem. 2007;282(23):16959–68. doi: 10.1074/jbc.M701214200.
14. Goren I, Lee SY, Maucher D, Nüsing R, Schlich T, Pfeilschifter J, et al. Inhibition of cyclooxygenase-1 and -2 activity in keratinocytes inhibits PGE2 formation and impairs vascular endothelial growth factor release and neovascularisation in skin wounds. Int Wound J. 2017;14(1):53–63. doi: 10.1111/iwj.12550.
15. Kämpfer H, Bräutigam L, Geisslinger G, Pfeilschifter J, Frank S. Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair. J Invest Dermatol. 2003;120(5):880–890. doi: 10.1046/j.1523-1747.2003.12140.x.
16. Futagami A, Ishizaki M, Fukuda Y, Kawana S, Yamanaka N. Wound healing involves induction of cyclooxygenase-2 expression in rat skin. Lab Invest. 2002;82(11):1503–1513. doi: 10.1097/01.lab.0000035024.75914.39.
17. Liu M, Saeki K, Matsunobu T, Okuno T, Koga T, Sugimoto Y, et al. 12-Hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor. J Exp Med. 2014;211(6):1063–78. doi: 10.1084/jem.20132063.
18. Fairweather M, Heit YI, Buie J, Rosenberg LM, Briggs A, Orgill DP, et al. Celecoxib inhibits early cutaneous wound healing. J Surg Res. 2015;194(2):717–24. doi: 10.1016/j.jss.2014.12.026.
19. Jadhav SB, Shah N, Rathi A, Rathi V, Rathi A. Serratiopeptidase: Insights into the therapeutic applications. Biotechnol Rep (Amst). 2020;28:e00544. doi: 10.1016/j.btre.2020.e00544.
20. Moriya N, Nakata M, Nakamura M, Takaoka M, Iwasa S, Kato K, et al. Intestinal absorption of serrapeptase (TSP) in rats. Biotechnol Appl Biochem. 1994;20(Pt 1):101–8. doi: 10.1111/j.1470-8744.1994.tb00308.x.
21. Meng Y, Yang M, Liu W, Li J. Cell-Free Expression of a Therapeutic Protein Serratiopeptidase. Molecules. 2023;28(7):3132. doi: 10.3390/molecules28073132.
22. Kakinuma A, Moriya N, Kawahara K, Sugino H. Repression of fibrinolysis in scalded rats by administration of Serratia protease. Biochem Pharmacol. 1982;31(18):2861–6. doi: 10.1016/0006-2952(82)90255-6.
23. Mazzone A, Catalani M, Costanzo M, Drusian A, Mandoli A, Russo S, et al. Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. J Int Med Res. 1990;18(5):379–88. doi: 10.1177/030006059001800506.
24. Kee WH, Tan SL, Lee V, Salmon YM. The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trial. Singapore Med J. 1989;30(1):48–54. PubMed record.
25. Chopra D, Rehan HS, Mehra P, Kakkar AK. A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model. Int J Oral Maxillofac Surg. 2009;38(4):350–5. doi: 10.1016/j.ijom.2008.12.013.
26. Tamimi Z, Al Habashneh R, Hamad I, Al-Ghazawi M, Roqa’a AA, Kharashgeh H. Efficacy of serratiopeptidase after impacted third molar surgery: a randomized controlled clinical trial. BMC Oral Health. 2021;21:91. doi: 10.1186/s12903-021-01451-0.
27. Al-Khateeb TH, Nusair Y. Effect of the proteolytic enzyme serrapeptase on swelling, pain and trismus after surgical extraction of mandibular third molars. Int J Oral Maxillofac Surg. 2008;37(3):264–268. doi: 10.1016/j.ijom.2007.11.011.
28. Murugesan K, Sreekumar K, Sabapathy B. Comparison of the roles of serratiopeptidase and dexamethasone in the control of inflammation and trismus following impacted third molar surgery. Indian J Dent Res. 2012;23(6):709–713. doi: 10.4103/0970-9290.111243.
29. Chappi D M, Suresh KV, Patil MR, Desai R, Tauro DP, Bharani K N S S, et al. Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery. J Clin Exp Dent. 2015;7(2):e197–202. doi: 10.4317/jced.51868.
30. Al-Moraissi EA, Al-Zendani EA, Al-Selwi AM. Efficacy of Submucosal Injection of Chymotrypsin, Oral Serratiopeptidase or Oral Dexamethasone in Reducing Postoperative Complications Following Impacted Lower Third Molar Surgery: A Prospective, Randomized, Double-Blind, Controlled Clinical Trial. Front Oral Health. 2020;1:575176. doi: 10.3389/froh.2020.575176.
31. Arbildo-Vega H, Rendón-Alvarado A, Castillo-Cornock T, Cruzado-Oliva F, Vidal-Mosquera A, Vásquez-Rodrigo H. Efficacy of serratiopeptidase in third molar surgery. A systematic review and meta-analysis. J Oral Res. 2023;12(1):348–361. doi: 10.17126/joralres.2023.030.
32. Moitra S, Sen S, Banerjee I, Das P, Tripathi SK. Diclofenac-serratiopeptidase combination induced Stevens–Johnson syndrome: a rare case report with review of literature. J Clin Diagn Res. 2014;8(7):YD08–11. doi: 10.7860/JCDR/2014/9509.4610.
33. Rajaram P, Bhattacharjee A, Ticku S. Serratiopeptidase - A Cause for Spread of Infection. J Clin Diagn Res. 2016;10(8):ZD31-2. doi: 10.7860/jcdr/2016/21388.8302.
34. Hirahara K, Saitoh T, Terada I, Uno K, Nagai A, Kioi S, et al. [A case of pneumonitis due to serrapeptase]. Nihon Kyobu Shikkan Gakkai Zasshi. 1989;27(10):1231–1236. Japanese. PubMed record.
35. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239. doi: 10.1136/bmj.i5239.
36. Chan AW, Boutron I, Hopewell S, Moher D, Schulz KF, Collins GS, et al. SPIRIT 2025 statement: updated guideline for protocols of randomised trials. BMJ. 2025;389:e081477. doi: 10.1136/bmj-2024-081477.
37. Hopewell S, Chan AW, Collins GS, Hróbjartsson A, Moher D, Schulz KF, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025;389:e081123. doi: 10.1136/bmj-2024-081123.
38. Chipp E, Charles L, Thomas C, Whiting K, Moiemen N, Wilson Y. A prospective study of time to healing and hypertrophic scarring in paediatric burns: every day counts. Burns Trauma. 2017;5:3. doi: 10.1186/s41038-016-0068-2.
39. Draaijers LJ, Tempelman FR, Botman YA, Tuinebreijer WE, Middelkoop E, Kreis RW, et al. The patient and observer scar assessment scale: a reliable and feasible tool for scar evaluation. Plast Reconstr Surg. 2004;113(7):1960–5. doi: 10.1097/01.prs.0000122207.28773.56.
40. Carrière ME, Mokkink LB, Tyack Z, Westerman MJ, Pijpe A, Pleat J, et al. Development of the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS) 3.0: a qualitative study. Qual Life Res. 2023;32(2):583–592. doi: 10.1007/s11136-022-03244-6.
2. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999;341(10):738–46. doi: 10.1056/NEJM199909023411006.
3. Eming SA, Martin P, Tomic-Canic M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci Transl Med. 2014;6(265):265sr6. doi: 10.1126/scitranslmed.3009337.
4. You Z, Jain S, Shen S, Mao J, Martyn JAJ. Pathophysiology and management of burn injury-induced pain. Burns Open. 2025;10:100396. doi: 10.1016/j.burnso.2025.100396.
5. Romanowski KS, Carson J, Pape K, Bernal E, Sharar S, Wiechman S, et al. American Burn Association guidelines on the management of acute pain in the adult burn patient: a review of the literature, a compilation of expert opinion, and next steps. J Burn Care Res. 2020;41(6):1129–51. doi: 10.1093/jbcr/iraa119.
6. Bhagat S, Agarwal M, Roy V. Serratiopeptidase: a systematic review of the existing evidence. Int J Surg. 2013;11(3):209–17. doi: 10.1016/j.ijsu.2013.01.010.
7. Burgess M, Valdera F, Varon D, Kankuri E, Nuutila K. The immune and regenerative response to burn injury. Cells. 2022;11(19):3073. doi: 10.3390/cells11193073.
8. Keyloun JW, Campbell R, Carney BC, Yang R, Miller SA, Detwiler L, et al. Early Transcriptomic Response to Burn Injury: Severe Burns Are Associated With Immune Pathway Shutdown. J Burn Care Res. 2022;43(2):306–314. doi: 10.1093/jbcr/irab217.
9. Dobson GP, Morris JL, Letson HL. Pathophysiology of Severe Burn Injuries: New Therapeutic Opportunities From a Systems Perspective. J Burn Care Res. 2024;45(4):1041–1050. doi: 10.1093/jbcr/irae049.10. Rowan MP, Cancio LC, Elster EA, Burmeister DM, Rose LF, Natesan S, et al. Burn wound healing and treatment: review and advancements. Crit Care. 2015;19:243. doi: 10.1186/s13054-015-0961-2.
11. Ryan MJ, Raby E, Whiley L, Masuda R, Lodge S, Nitschke P, et al. Nonsevere burn induces a prolonged systemic metabolic phenotype indicative of a persistent inflammatory response postinjury. J Proteome Res. 2024;23(8):2893–2907. doi: 10.1021/acs.jproteome.3c00516.
12. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):986–1000. doi: 10.1161/ATVBAHA.110.207449.
13. Rao R, Redha R, Macias-Perez I, Su Y, Hao C, Zent R, et al. Prostaglandin E2-EP4 receptor promotes endothelial cell migration via ERK activation and angiogenesis in vivo. J Biol Chem. 2007;282(23):16959–68. doi: 10.1074/jbc.M701214200.
14. Goren I, Lee SY, Maucher D, Nüsing R, Schlich T, Pfeilschifter J, et al. Inhibition of cyclooxygenase-1 and -2 activity in keratinocytes inhibits PGE2 formation and impairs vascular endothelial growth factor release and neovascularisation in skin wounds. Int Wound J. 2017;14(1):53–63. doi: 10.1111/iwj.12550.
15. Kämpfer H, Bräutigam L, Geisslinger G, Pfeilschifter J, Frank S. Cyclooxygenase-1-coupled prostaglandin biosynthesis constitutes an essential prerequisite for skin repair. J Invest Dermatol. 2003;120(5):880–890. doi: 10.1046/j.1523-1747.2003.12140.x.
16. Futagami A, Ishizaki M, Fukuda Y, Kawana S, Yamanaka N. Wound healing involves induction of cyclooxygenase-2 expression in rat skin. Lab Invest. 2002;82(11):1503–1513. doi: 10.1097/01.lab.0000035024.75914.39.
17. Liu M, Saeki K, Matsunobu T, Okuno T, Koga T, Sugimoto Y, et al. 12-Hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor. J Exp Med. 2014;211(6):1063–78. doi: 10.1084/jem.20132063.
18. Fairweather M, Heit YI, Buie J, Rosenberg LM, Briggs A, Orgill DP, et al. Celecoxib inhibits early cutaneous wound healing. J Surg Res. 2015;194(2):717–24. doi: 10.1016/j.jss.2014.12.026.
19. Jadhav SB, Shah N, Rathi A, Rathi V, Rathi A. Serratiopeptidase: Insights into the therapeutic applications. Biotechnol Rep (Amst). 2020;28:e00544. doi: 10.1016/j.btre.2020.e00544.
20. Moriya N, Nakata M, Nakamura M, Takaoka M, Iwasa S, Kato K, et al. Intestinal absorption of serrapeptase (TSP) in rats. Biotechnol Appl Biochem. 1994;20(Pt 1):101–8. doi: 10.1111/j.1470-8744.1994.tb00308.x.
21. Meng Y, Yang M, Liu W, Li J. Cell-Free Expression of a Therapeutic Protein Serratiopeptidase. Molecules. 2023;28(7):3132. doi: 10.3390/molecules28073132.
22. Kakinuma A, Moriya N, Kawahara K, Sugino H. Repression of fibrinolysis in scalded rats by administration of Serratia protease. Biochem Pharmacol. 1982;31(18):2861–6. doi: 10.1016/0006-2952(82)90255-6.
23. Mazzone A, Catalani M, Costanzo M, Drusian A, Mandoli A, Russo S, et al. Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo. J Int Med Res. 1990;18(5):379–88. doi: 10.1177/030006059001800506.
24. Kee WH, Tan SL, Lee V, Salmon YM. The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trial. Singapore Med J. 1989;30(1):48–54. PubMed record.
25. Chopra D, Rehan HS, Mehra P, Kakkar AK. A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model. Int J Oral Maxillofac Surg. 2009;38(4):350–5. doi: 10.1016/j.ijom.2008.12.013.
26. Tamimi Z, Al Habashneh R, Hamad I, Al-Ghazawi M, Roqa’a AA, Kharashgeh H. Efficacy of serratiopeptidase after impacted third molar surgery: a randomized controlled clinical trial. BMC Oral Health. 2021;21:91. doi: 10.1186/s12903-021-01451-0.
27. Al-Khateeb TH, Nusair Y. Effect of the proteolytic enzyme serrapeptase on swelling, pain and trismus after surgical extraction of mandibular third molars. Int J Oral Maxillofac Surg. 2008;37(3):264–268. doi: 10.1016/j.ijom.2007.11.011.
28. Murugesan K, Sreekumar K, Sabapathy B. Comparison of the roles of serratiopeptidase and dexamethasone in the control of inflammation and trismus following impacted third molar surgery. Indian J Dent Res. 2012;23(6):709–713. doi: 10.4103/0970-9290.111243.
29. Chappi D M, Suresh KV, Patil MR, Desai R, Tauro DP, Bharani K N S S, et al. Comparison of clinical efficacy of methylprednisolone and serratiopeptidase for reduction of postoperative sequelae after lower third molar surgery. J Clin Exp Dent. 2015;7(2):e197–202. doi: 10.4317/jced.51868.
30. Al-Moraissi EA, Al-Zendani EA, Al-Selwi AM. Efficacy of Submucosal Injection of Chymotrypsin, Oral Serratiopeptidase or Oral Dexamethasone in Reducing Postoperative Complications Following Impacted Lower Third Molar Surgery: A Prospective, Randomized, Double-Blind, Controlled Clinical Trial. Front Oral Health. 2020;1:575176. doi: 10.3389/froh.2020.575176.
31. Arbildo-Vega H, Rendón-Alvarado A, Castillo-Cornock T, Cruzado-Oliva F, Vidal-Mosquera A, Vásquez-Rodrigo H. Efficacy of serratiopeptidase in third molar surgery. A systematic review and meta-analysis. J Oral Res. 2023;12(1):348–361. doi: 10.17126/joralres.2023.030.
32. Moitra S, Sen S, Banerjee I, Das P, Tripathi SK. Diclofenac-serratiopeptidase combination induced Stevens–Johnson syndrome: a rare case report with review of literature. J Clin Diagn Res. 2014;8(7):YD08–11. doi: 10.7860/JCDR/2014/9509.4610.
33. Rajaram P, Bhattacharjee A, Ticku S. Serratiopeptidase - A Cause for Spread of Infection. J Clin Diagn Res. 2016;10(8):ZD31-2. doi: 10.7860/jcdr/2016/21388.8302.
34. Hirahara K, Saitoh T, Terada I, Uno K, Nagai A, Kioi S, et al. [A case of pneumonitis due to serrapeptase]. Nihon Kyobu Shikkan Gakkai Zasshi. 1989;27(10):1231–1236. Japanese. PubMed record.
35. Eldridge SM, Chan CL, Campbell MJ, Bond CM, Hopewell S, Thabane L, et al. CONSORT 2010 statement: extension to randomised pilot and feasibility trials. BMJ. 2016;355:i5239. doi: 10.1136/bmj.i5239.
36. Chan AW, Boutron I, Hopewell S, Moher D, Schulz KF, Collins GS, et al. SPIRIT 2025 statement: updated guideline for protocols of randomised trials. BMJ. 2025;389:e081477. doi: 10.1136/bmj-2024-081477.
37. Hopewell S, Chan AW, Collins GS, Hróbjartsson A, Moher D, Schulz KF, et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025;389:e081123. doi: 10.1136/bmj-2024-081123.
38. Chipp E, Charles L, Thomas C, Whiting K, Moiemen N, Wilson Y. A prospective study of time to healing and hypertrophic scarring in paediatric burns: every day counts. Burns Trauma. 2017;5:3. doi: 10.1186/s41038-016-0068-2.
39. Draaijers LJ, Tempelman FR, Botman YA, Tuinebreijer WE, Middelkoop E, Kreis RW, et al. The patient and observer scar assessment scale: a reliable and feasible tool for scar evaluation. Plast Reconstr Surg. 2004;113(7):1960–5. doi: 10.1097/01.prs.0000122207.28773.56.
40. Carrière ME, Mokkink LB, Tyack Z, Westerman MJ, Pijpe A, Pleat J, et al. Development of the Patient Scale of the Patient and Observer Scar Assessment Scale (POSAS) 3.0: a qualitative study. Qual Life Res. 2023;32(2):583–592. doi: 10.1007/s11136-022-03244-6.
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