Therapeutic promise of Calotropis procera (Aiton) W.T. Aiton latex for wound healing and keloid prevention: A narrative review

Authors

  • Vibhu Khanna
  • Saurabh Singh
  • Ankit Kumar
  • Sheetu wadhwa
  • Dileep Singh Baghel
  • Narendra Kumar Panday
  • Bimlesh Kumar
  • Tirthanu Ghosh
  • Gurinder Singh
  • Mehul Mehta

DOI:

https://doi.org/10.70066/jahm.v13i12.2329

Keywords:

Arka, Calotropis procera (Aiton) W.T. Aiton, keloid prevention, narrative review, wound healing.

Abstract

Background: A scar represents an alteration in skin architecture that occurs during the wound-healing process when the regenerated tissue does not fully resemble the original structure. Optimal healing requires a harmonious balance between the deposition and degradation of the extracellular matrix (ECM). Conditions such as keloids and hypertrophic scars (HTS) arise due to excessive collagen accumulation and dysregulated fibroblast activity, primarily influenced by growth factors like PDGF and TGF-β within the ECM. Disturbed maturation of granulation tissue further contributes to abnormal scar formation. Calotropis procera (Aiton) W.T. Aiton, a traditionally recognized medicinal plant in Ayurveda, possesses bioactive latex constituents with significant wound-healing potential. Its soluble latex proteins exhibit hemostatic, pro-inflammatory, and anti-inflammatory actions that support sequential phases of healing. These properties highlight the therapeutic relevance of Calatropis. procera in managing pathological scar formation within holistic and integrative wound-care approaches. Objectives: This review compiles in vitro and in vivo studies on raw and processed latex of Calotropis procera, (Ait.), emphasizing its hemostatic and anti-inflammatory effects. It focuses on gallic acid, quercetin, and kaempferol as secondary metabolites in the lyophilized non-protein fraction, proposing their repurposing as bio-rational agents for anti-scar therapeutic and cosmetic applications. Results: Research supports the latex’s hemostatic, pro-inflammatory, and anti-inflammatory activities in various animal models. Latex cysteine peptidases exhibit thrombin- and plasmin-like activities. It synergistically inhibits inflammatory cytokines such as COX-2, TNF-α, iNOS, and TGF-β, protecting against acute infections. Gallic acid modulates inflammatory mediators, while quercetin and kaempferol provide protective effects against scar formation. Conclusion: Current evidence supports the use of Calotropis procera latex as a hemostatic and anti-inflammatory agent with potential for further development as an anti-scar therapeutic and cosmetic drug. This review suggests its theoretical use in scar management warrants additional investigation.

Author Biographies

Vibhu Khanna

School of Pharmaceutical Sciences, Lovely Professional University, Punjab

Saurabh Singh

Ayurvedic Pharmacy School of Pharmaceutical Sciences ,Lovely Professional University, Punjab

Ankit Kumar

School of Pharmaceutical Sciences, Lovely Professional University, Punjab

Sheetu wadhwa

School of Pharmaceutical Sciences, Lovely Professional University, Punjab

Dileep Singh Baghel

Professor School of Pharmaceutical Sciences, Lovely Professional University, Punjab 

Narendra Kumar Panday

School of Pharmaceutical Sciences, Lovely Professional University, Punjab

Bimlesh Kumar

School of Pharmaceutical Sciences, Lovely Professional University, Punjab

Tirthanu Ghosh

School of Pharmaceutical Sciences, Lovely Professional University, Punjab

Gurinder Singh

School of Allied Medical Sciences , Lovely Professional University

Mehul Mehta

Institute of Teaching and Research in Ayurveda- Pharmacy

References

Sarvade D, Kamini B, Jaiswal M . Arka Calotropis procera.): A potent drug of indian materia medica. World Journal of Pharmacy and Pharmaceutical Sciences. 2017;6(5):471–487. https://doi.org/10.20959/wjpps20175-9138

Chundattu SJ, Agrawal VK, Ganesh N. Phytochemical investigation of Calotropis procera. (Ait.) .): Arabian Journal of Chemistry. 2016;9(S1):S230–S234. https://doi.org/10.1016/j.arabjc.2011.03.011.

Singh S, Sachin S K, B. Kumar Effect of Co-Administration of Herbal Extracts with Copper Nanoparticles: A Novel Two-Pronged Approach in Treating Type 2 Diabetes, Recent Innovations in Chemical Engineering. 2020;13(5):366-378. 10.2174/2405520413999200719140819

Venkatesha SH, Rajaiah R, Vishwanath BS. Hemostatic Interference of Plant Latex Proteases. SM Journal of Clinical Pathology. 2016;1(1):1002. https://www.jsmcentral.org/article-info/Hemostatic-Interference-of-Plant-Latex-Proteases

Ramos M V., Viana CA, Silva AFB, Freitas CDT, Figueiredo IST, Oliveira RSB, et al. Proteins derived from latex of C. procera maintain coagulation homeostasis in septic mice and exhibit thrombin- and plasmin-like activities. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2012;385(5):455–463. https://doi.org/10.1007/s00210-012-0733-3.

Parihar G, Balekar N. Calotropis procera: A phytochemical and pharmacological review. Thai Journal of Pharmaceutical Sciences. 2016;40(2):115–131. https://thaiscience.info/Journals/Article/TJPS/10984244.pdf

Rasik AM, Raghubir R, Gupta A, Shukla A, Dubey MP, Srivastava S, et al. Healing potential of Calotropis procera on dermal wounds in Guinea pigs. Journal of Ethnopharmacology. 1999;68(1-3):261–266. https://doi.org/10.1016/S0378-8741(99)00118-X.

Kumar MA, Rana AC, Dixit VK. Calotropis species (Asclepiadaceae): A comprehensive review. Pharmacognosy Magazine. 2005;1(2):48–52. https://phcog.com/article/view/2005/1/2/48-52

Ramos MV, Aguiar VC, Melo VMM, Mesquita RO, Silvestre PP, Oliveira JS, et al. Immunological and allergenic responses induced by latex fractions of Calotropis procera. Journal of Ethnopharmacology 2007;111(1):115–122. https://doi.org/10.1016/j.jep.2006.10.034.

Tomar VP, Agarwal PK, Agarwal BL. Toxic iridocyclitis caused by calotropis. Indian Journal of Ophthalmology. 1970;18(1):15–16. https://pubmed.ncbi.nlm.nih.gov/5529936/

Bezerra CF, Mota ÉF, Silva ACM, Tomé AR, Silva MZR, de Brito D, et al. Latex proteins from Calotropis procera: Toxicity and immunological tolerance revisited. Chemical-Biological Interactions. 2017;27(4):138–149. https://doi.org/10.1016/j.cbi.2017.07.007.

Cavalcante GS, Morais SM de, André WPP, Araújo-Filho JV de, Muniz CR, Rocha LO da, et al. Chemical constituents of Calotropis procera latex and ultrastructural effects on Haemonchus contortus. Revista Brasileira de Parasitologia Veterinária 2020;29(3):e004520. https://doi.org/10.1590/s1984-29612020045.

Chan EWC, Sweidan NI, Wong SK, Chan HT. Cytotoxic Cardenolides from Calotropis Species: A Short Review. Records of Natural Products. 2017;11(4):334–344. https://doi.org/10.25135/rnp.2017.1701.002.

Al-Snafi AE. The Constituents and Pharmacological Properties of Calotropis procera—An Overview. International Journal of Pharmacy Review & Research 2015;5(3):259–275. https://www.scirp.org/reference/referencespapers?referenceid=3203667

Farooq U, Nisar S, Merzaia AB, Azeem MW. Isolation of Bioactive components from Calotropis procera Plant Latex- A Review. International Journal of Chemical and Biochemical Sciences 2017;11:95–101. https://www.iscientific.org/wp-content/uploads/2020/05/11-IJCBS-17-11-11.pdf

Madan Ranjit P, Rao EG. An overview of phytochemical and pharmacological activities of calotropis procera. FS J Pharm Res | 2012;1(1):18–25. https://doi.org/10.5530/PJ.2019.11.181

Freitas CDT, Oliveira JS, Miranda MRA, Macedo NMR, Sales MP, Villas-Boas LA, et al. Enzymatic activities and protein profile of latex from Calotropis procera. Plant Physiology and Biochemistry. 2007;45(10-11):781–789. https://doi.org/10.1016/j.plaphy.2007.07.020.

Dubey VK, Jagannadham MV. Procerain, a stable cysteine protease from the latex of Calotropis procera. Phytochemistry. 2003;62(7):1057-1071 https://doi.org/10.1016/S0031-9422(02)00676-3.

Singh AN, Shukla AK, Jagannadham MV, Dubey VK. Purification of a novel cysteine protease, procerain B, from Calotropis procera with distinct characteristics compared to procerain. Process Biochemistry 2010;45(3):399–406. https://doi.org/10.1016/j.procbio.2009.10.014.

Ramos MV, Araújo ES, Jucá TL, Monteiro-Moreira ACO, Vasconcelos IM, Moreira RA, et al. New insights into the complex mixture of latex cysteine peptidases in Calotropis procera. International Journal of Biological Macromolecules. 2013;58:211–219. https://doi.org/10.1016/j.ijbiomac.2013.04.001.

Alencar NMN, Oliveira JS, Mesquita RO, Lima MW, Vale MR, Etchells JP, et al. Pro- and anti-inflammatory activities of the latex from Calotropis procera. are triggered by compounds fractionated by dialysis. Inflammation Research .2006;55(12):559–564. https://doi.org/10.1007/s00011-006-6025-y

Ramos M V., Oliveira JS, Figueiredo JG, Figueiredo IST, Kumar VL, Bitencourt FS, et al. Involvement of NO in the inhibitory effect of Calotropis procera latex protein fractions on leukocyte rolling, adhesion and infiltration in rat peritonitis model. Journal of Ethnopharmacology. 2009;125(3):387–392. https://doi.org/10.1016/j.jep.2009.07.030.

Tripathi S, Soni K, Agrawal P, Gour V, Mondal R, Soni V. Hypertrophic scars and keloids: a review and current treatment modalities. Biomedical Dermatology. 2020;4(1):11. https://doi.org/10.1186/s41702-020-00063-8.

Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies. Molecula Medicine.2011;17(1-2):113–125. https://doi.org/10.2119/molmed.2009.00153.

Deitch EA, Wheelahan TM, Rose MP, Clothier J, Cotter J. Hypertrophic burn scars: analysis of variables. Journal of Trauma. 1983;23(10):895–898.

Lewis WHP, Sun KKY. Hypertrophic scar: a genetic hypothesis. Burns .1990;16(3):176–178. https://doi.org/10.1016/0305-4179(90)90033-S.

Kumar VL, Basu N. Anti-inflammatory activity of the latex of Calotropis procera. Journl of Ethnopharmacology. 1994;44(2):123–125. https://doi.org/10.1016/0378-8741(94)90078-7.

Kahkeshani N, Farzaei F, Fotouhi M, Alavi SS, Bahramsoltani R, Naseri R, et al. Pharmacological effects of gallic acid in health and diseases: A mechanistic review. Iranian Journal of Basic Medical Sciences. 2019;22(3):225–237. https://doi.org/10.22038/ijbms.2019.32806.7897.

Alencar NM, Figueiredo IS, Vale MR, Bitencurt FS, Oliveira JS, Ribeiro RA, et al. Anti-Inflammatory Effect of the Latex from Calotropis procera in Three Different Experimental Models: Peritonitis, Paw Edema and Hemorrhagic Cystitis. Planta Med 2004;70(12):1144–1149. https://doi.org/10.1055/s-2004-835842.

Toriseva M, Kähäri V-M. Proteinases in cutaneous wound healing. Cellular and Molecular Life Sciences. 2009;66(2):203–224. https://doi.org/10.1007/s00018-008-8388-4.

Sousa BF, Silva AFB da, Lima-Filho JV, Agostinho AG, Oliveira DN, de Alencar NMN, et al. Latex proteins downregulate inflammation and restores blood-coagulation homeostasis in acute Salmonella infection. Memorias do Instituto Oswaldo Cruz. 2020;115:e200458. https://doi.org/10.1590/0074-02760200458.

Ren K, Torres R. Role of interleukin-1β during pain and inflammation. Brain Research Reviews. 2009;60(1):57–64. https://doi.org/10.1016/j.brainresrev.2008.12.020.

Müller G, Müller A, Tüting T, Steinbrink K, Saloga J, Szalma C, et al. Interleukin-10-Treated Dendritic Cells Modulate Immune Responses of Naive and Sensitized T Cells In Vivo. Journal of Investigative Dermatology. 2002;119(4):836–841. https://doi.org/10.1046/j.1523-1747.2002.00496.x.

Peñaloza HF, Schultz BM, Nieto PA, Salazar GA, Suazo I, Gonzalez PA, et al. Opposing roles of IL-10 in acute bacterial infection. Cytokine & Growth Factor Reviews. 2016;32:17–30. https://doi.org/10.1016/j.cytogfr.2016.07.003.

Burton NA, Schürmann N, Casse O, Steeb AK, Claudi B, Zankl J, et al. Disparate Impact of Oxidative Host Defenses Determines the Fate of Salmonella during Systemic Infection in Mice. Cell Host & Microbe 2014;15(1):72–83. https://doi.org/10.1016/j.chom.2013.12.006.

Schultz GS, Chin GA, Moldawer L, Diegelmann RF. Principles of wound healing. In: Mechanisms of Vascular Disease, University of Adelaide Press; 2011, p. 423–450. https://doi.org/10.1017/UPO9781922064004.024.

Ravanti L, Kähäri VM. Matrix metalloproteinases in wound repair (review). International Journal of Molecular Medicine. 2000;6(4):391–407. https://pubmed.ncbi.nlm.nih.gov/10998429/

Freitas APF, Bitencourt FS, Brito GAC, de Alencar NMN, Ribeiro RA, Lima-Júnior RCP, et al. Protein fraction of Calotropis procera latex protects against 5-fluorouracil-induced oral mucositis associated with downregulation of pivotal pro-inflammatory mediators. Naunyn-Schmiedeberg's Archives of Pharmacology. 2012;385(10):981–990. https://doi.org/10.1007/s00210-012-0778-3.

Lijnen HR. Matrix Metalloproteinases and Cellular Fibrinolytic Activity. Biochemistry (Moscow). 2002;67(1):92–98. https://doi.org/10.1023/A:1013908332232.

Szulgit G, Rudolph R, Wandel A, Tenenhaus M, Panos R, Gardner H. Alterations in Fibroblast α1β1 Integrin Collagen Receptor Expression in Keloids and Hypertrophic Scars. Journal of Investigative Dermatology. 2002;118(3):409–415. https://doi.org/10.1046/j.0022-202x.2001.01680.x.

Slemp AE, Kirschner RE. Keloids and scars: a review of keloids and scars, their pathogenesis, risk factors, and management. Current Opinion in Pediatrics 2006;18(4):396–402. https://doi.org/10.1097/01.mop.0000236389.41462.ef.

Lee TY, Chin GS, Kim WJH, Chau D, Gittes GK, Longaker MT. Expression of Transforming Growth Factor Beta 1, 2, and 3 Proteins in Keloids. Annals of Plastic Surgery 1999;43(2):179–184. https://doi.org/10.1097/00000637-199943020-00013.

Xia W, Phan T, Lim IJ, Longaker MT, Yang GP. Complex epithelial–mesenchymal interactions modulate transforming growth factor‐β expression in keloid‐derived cells. Wound Repair and Regeneration. 2004;12(5):546–556. https://doi.org/10.1111/j.1067-1927.2004.012507.x.

Sephel G, Stephen C W. Repair , Regeneration , and Fibrosis. In: Rubin’s Pathology, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2006. https://downloads.lww.com/wolterskluwer_vitalstream_com/sample-content/9780781795166_Rubin/samples/91731_ch03.pdf

Phan T-T, Lim IJ, Chan S-Y, Tan E-K, Lee S-T, Longaker MT. Suppression of Transforming Growth Factor Beta/Smad Signaling in Keloid-Derived Fibroblasts by Quercetin. Journal of Trauma. 2004;57(5):1032–1037. https://doi.org/10.1097/01.TA.0000114087.46566.EB.

Shivaprasad H V., Riyaz M, Venkatesh Kumar R, Dharmappa KK, Tarannum S, Siddesha JM, et al. Cysteine proteases from the Asclepiadaceae plants latex exhibited thrombin and plasmin like activities. Journal of Thrombosis and Thrombolysis. 2009;28(3):304–308. https://doi.org/10.1007/s11239-008-0290-2.

Arya S, Kumar VL. Antiinflammatory Efficacy of Extracts of Latex of Calotropis procera Against Different Mediators of Inflammation. Mediators of Inflammation. 2005;2005(4):228–232. https://doi.org/10.1155/MI.2005.228.

Shivkar YM, Kumar VL. Histamine mediates the pro‐inflammatory effect of latex of Calotropis procera in rats. Mediators of Inflammation. 2003;12(5):299–302. https://doi.org/10.1080/096293503310001619708.

Dewan S, Sangraula H, Kumar VL. Preliminary studies on the analgesic activity of latex of Calotropris procera. Journal of Ethnopharmacology. 2000;73(1-2):307–311. https://doi.org/10.1016/S0378-8741(00)00272-5.

Roy S, Sehgal R, Padhy BM, Kumar VL. Antioxidant and protective effect of latex of Calotropis procera against alloxan-induced diabetes in rats. Journal of Ethnopharmacology. 2005;102(3):470–473. https://doi.org/10.1016/j.jep.2005.06.026.

Lima-Filho J V., Patriota JM, Silva AFB, Filho NT, Oliveira RSB, Alencar NMN, et al. Proteins from latex of Calotropis procera prevent septic shock due to lethal infection by Salmonella enterica serovar Typhimurium. Journal of Ethnopharmacology. 2010;129(3):327–334. https://doi.org/10.1016/j.jep.2010.03.038.

Seddek A latif S, Mahmoud ME, Shiina T, Hirayama H, Iwami M, Miyazawa S, et al. Extract from Calotropis procera latex activates murine macrophages. Journal of Natural Medicines. 2009;63(3):297–303. https://doi.org/10.1007/s11418-009-0335-7.

Oliveira RSB, Figueiredo IST, Freitas LBN, Pinheiro RSP, Brito GAC, Alencar NMN, et al. Inflammation induced by phytomodulatory proteins from the latex of Calotropis procera (Asclepiadaceae) protects against Salmonella infection in a murine model of typhoid fever. Inflammation Research. 2012;61(7):689–698. https://doi.org/10.1007/s00011-012-0460-8.

Viana CA, Ramos M V., Filho JDBM, Lotufo LVC, Figueiredo IST, de Oliveira JS, et al. Cytotoxicity against tumor cell lines and anti-inflammatory properties of chitinases from Calotropis procera latex. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2017;390(10):1005–1013. https://doi.org/10.1007/s00210-017-1397-9.

Ramos M V., Freitas APF, Leitão RFC, Costa DVS, Cerqueira GS, Martins DS, et al. Anti-inflammatory latex proteins of the medicinal plant Calotropis procera: a promising alternative for oral mucositis treatment. Inflammation Research. 2020;69(9):951–966. https://doi.org/10.1007/s00011-020-01365-7.

Nascimento DC de O, Ralph MT, Batista JEC, Silva DMF, Gomes-Filho MA, Alencar NM, et al. Latex protein extracts from Calotropis procera with immunomodulatory properties protect against experimental infections with Listeria monocytogenes. Phytomedicine. 2016;23(8):745–753. https://doi.org/10.1016/j.phymed.2016.03.012

Additional Files

Published

2026-01-17

How to Cite

Khanna, V. ., Singh, S. ., Kumar, A. ., wadhwa, S. ., Baghel, D. S. ., Panday, N. K. ., Kumar, B. ., Ghosh, T. ., Singh, G. ., & Mehta, M. . (2026). Therapeutic promise of Calotropis procera (Aiton) W.T. Aiton latex for wound healing and keloid prevention: A narrative review. Journal of Ayurveda and Holistic Medicine (JAHM), 13(12). https://doi.org/10.70066/jahm.v13i12.2329