Aim: The aim of this research was to determine the angiogenesis activity of Jatropha curcas latex in cream formulation on CD34 immune expression during wound healing phase in mice skin.

Materials and Methods: Amount of 36 2-month-old male mice were used between 30 and 40 g. To surgical procedures, wound skin incision was performed 2.0 cm in length until subcutaneous on the paravertebral of each animal. The treatment was carried under locally anesthetized with procaine cream. All mice were divided into four groups, namely the base cream as control group (A), sulfadiazine 0.1% cream (B), Jatropha curcas latex cream 10% (C), and J. curcas latex cream 15% (D). All groups were treated entire surface of wound. All experiments were performed twice a day for 10 days. Experiments were terminated on days 3, 7, and 10, respectively. The wound healing was assayed in stained histological section in immunohistochemical of the wounds. The CD34 expression was investigated under a microscope.

Results: The results showed that the cream from 10% and 15% latex J. curcas revealed moderate immune reaction to CD34 on days 3 and 7 in wound healing of mice skin.

Conclusion: We concluded that the cream from 10% and 15% latex J. curcas has potential as angiogenesis activity in wound healing of mice skin.

Keywords: angiogenesis, CD34, Jatropha curcas latex cream, wound healing.

1. Prasetyono, T.O.H. (2009) General concept of wound healing, revisited. Med. J. Indones., 18(3): 208-216. [Crossref]

2. Agyare, C., Boakye, Y.D., Bekoe, E.O., Hensel, A., Dapaah, S.O. and Appiah T. (2016) Review: African medicinal plants with wound healing properties. J. Ethnopharmacol., 177: 85-100. [Crossref] [PubMed]

3. Velnar, T., Bailey, T. and Smrkolj, V. (2009) The wound healing process: An overview of cellular and molecular mechanism. J. Int. Med. Res., 37: 1528-1542. [Crossref] [PubMed]

4. Guo, S. and DiPietro, L.A. (2010) Factor affecting wound healing. J. Den. Res., 89(3): 219-229. [Crossref] [PubMed] [PMC]

5. Honnegowda, T.M., Kumar, P., Udupa, E.G., Kumar, S., Kumar, U. and Rao, P. (2015) Role of angiogenesis and angiogenic factors in acute and chronic wound healing. Plast. Aesthet. Res., 2: 243-249. [Crossref]

6. Masir, O., Manjas, M., Putra, A.E. and Agus, S. (2012) Effect of fibroblast filtrate culture fluid (CFF) on wound healing: Experimental study on wistar norvegicus rats. J. Kes. Andal., 1(3): 112-117.

7. Guo, X., Liu, L., Zhang, M., Bergeron, A., Cui, Z., Dong. J. and Zhang, J. (2009) Correlation of CD34+ cells with tissue angiogenesis after traumatic brain injury in a rat model. J. Neurotrauma, 26(8): 1337-1344. [Crossref] [PubMed] [PMC]

8. Nielsen, J.S. and McNagny, K.M. (2008) Novel function of the CD34 family. ?J. Cell Sci., 121: 3683-3692. [Crossref] [PubMed]

9. Sidney, L.A., Branch, M.J., Dunphy, S.E., Dua, H.S. and Hopkinson, A. (2014) Concise review: Evidence for CD34 as a common marker for diverse progenitors. Stem Cells, 32: 1380-1389. [Crossref] [PubMed] [PMC]

10. Ruswanti, E.O., Cholil., and Sukmana, B.I. (2014). The effectiveness of papaya leaf ethanol extract (Carica papaya) 100% on wound healing. Dentino. J. Kedokteran Gigi., 2(2): 162-166.

11. Yuniarti, W.M. and Lukiswanto, B.S. (2017) Effects of herbal ointment containing the leaf extracts of Madeira vine (Anredera cordifolia (Ten.) Steenis) for burn wound healing process on albino rats. Vet. World, 10(7): 808-813. [Crossref] [PubMed] [PMC]

12. Krishnaiah, D., Devi, T., Bono, A. and Sarbatly, R. (2009) Studies on phytochemical constituents of six Malaysian medicinal plants. J. Med. Plants Res., 3(2): 67-72.

13. Abdelgadir, H.A. and Staden, J.V. (2013) Ethnobotany, ethnopharmacology and toxicity of Jatropha curcas L. (Euphorbiaceae): A review. South Afr. J. Bot., 88: 204-218. [Crossref]

14. Setyaningsih, D., Panji, C. and Perwatasari, D.D. (2014) Study of antioxidant and antimicrobial activity of leaves and twigs extracts and fraction of Jatropha curcas L.and its utilization in personal hygiene products. Agritech, 34(2): 126-137.

15. Nayak, B.S. and Patel, K.N. (2010) Pharmacognostic studies of the Jatropha curcas leaves. Int. J. Pharm. Tech. Res., 2(1): 140-143.

16. Kamal, S., Manmohan, S. and Birendra, S. (2011) A review on chemical and medicobiological applications of Jatropha curcas. Int. Res. J. Pharm., 2(4): 61-66.

17. Prasad, D.M.R., Izam, A. and Khan, M.R. (2012) Jatropha curcas: Plant of medical benefits. J. Med. Plants Res., 6(14): 2691-2699.

18. Esimone, C.O, Nworu, C.S. and Jackson, C.L. (2008) Cutaneous wound healing activity of a herbal ointment containing the leaf extract of Jatropha curcas L. (Euphorbiaceae). Int. J. Appl. Res. Nat. Prod., 1: 1-4.

19. Sharma, A.K., Gangwar, M., Tilak, R., Nath, G., Sinha, A.S.K., Tripathi, Y.B. and Kumar, D. (2012) Comparative in vitro antimicrobial and phytochemical evaluation of methanolic extract of root, stem and leaf of Jatropha curcas Linn. Phcog. J., 4(30): 34-40. [Crossref]

20. Oskoueian, E., Abdullah, N., Saad, W.Z., Omar, A.R., Ahmad, S., Kuan, W.B., Zolkifli, N.A., Hendra, R. and Ho, Y.W. (2011) Antioxidant, anti-inflammatory and anticancer activities of methanolic extracts from Jatropha curcas Linn. J. Med. Plants Res., 5(1): 49-57.

21. Patil, R.N., Patil, R.Y., Ahirwar, B. and Ahirwar, D. (2011) Evaluation of antidiabetic and related actions of some Indian medicinal plants in diabetic rats. Asian Pac. J. Trop. Med., 4(1): 20-23. [Crossref]

22. Sachdeva, K., Garg, P., Singhal, M. and Srivastava, B. (2011) Wound healing potential of extract of Jatropha curcas L. (stem bark) in rats. Phcog. J., 3(25): 67-72. [Crossref]

23. Muntiaha, M.C., Yamlean, P.V.Y. and Lolo, WA. (2014) Test effectivity Jatropha multifida L. to heal wound infection cause by Staphylococcus aureus in rabbit (Orytolagus cuniculus). Pharmacon, 3(3): 294-302.

24. Salim, M.N., Masyitha, D., Harris, A., Balqis, U., Iskandar, C.D., Hambal, M. and Darmawi (2018) Anti-inflammatory activity of Jatropha curcas Linn. latex in cream formulation on CD68 expression in mice skin wound. Vet. World, 11(2): 99-103. [Crossref] [PubMed] [PMC]

25. Darmawi, D., Balqis, U., Hambal, M., Tiuria, R., Frengki . and Priosoeryanto, B.P. (2013) Mucosal mast cell response in jejunum of Ascaridia galli-infected laying hens. Media Peternak., 36(2): 113-119. [Crossref]

26. Balqis, U., Hambal, M., Rinidar , Athaillah, F., Ismail, Azhar , Vanda, H. and Darmawi, D. (2017) Cuticular surface damage of Ascaridia galli adult worms treated with Veitchia merrillii betel nuts extract in vitro. Vet. World, 10(7): 732-737. [Crossref] [PubMed] [PMC]

27. Darmawi, D., Balqis, U., Hambal, M., Tiuria, R., Priosoeryanto, B.P. and Handharyani, E. (2012) The ability of immunoglobulin yolk recognized the antigen in the tissue of Ascaridia galli. Media Peternak., 35(3): 190-195. [Crossref]

28. Yoshida, C.K., Ichimura, T., Kawamura, N., Nakano A., Kasai, M., Sumi, T. and Ishiko, O. (2009) A scoring system for histopathologic and immunohistochemical evaluation of uterine leiomyosarcomas. Oncol. Rep., 22: 725-731. [Crossref] [PubMed]

29. Goel, M.M., Agrawal, D., Natu, S.M. and Goel, A. (2011) Hepsin immunohistochemical expression in prostate cancer in relation to Gleason's grade and serum prostate-specific antigen. Indian J. Pathol. Microbiol., 54(3): 476-481. [Crossref] [PubMed]

30. Nucera, S., Biziato, D. and Palma, M.D. (2011) The interplay between macrophages and angiogenesis in development of tissue injury and regeneration. Int. J. Dev. Biol., 55: 495-503. [Crossref] [PubMed]

31. Thom, S.R., Hampton, M., Troiano, M., Mirza, Z., Malay, D.S., Shannon, S., Jennato, N.B., Donohue, C.M., Hoffstad, O., Woltereck, D., Yang, M., Yu, K., Bhopale, V.M., Kovtun, S. and Margolis, D.J. (2016) Measurements of CD34+/CD45-dim stem cells predict healing of diabetic neuropathic wounds. Diabetes, 65: 486-497. [Crossref] [PubMed] [PMC]

32. Velazquez, O.C. (2007) Angiogenesis and vasculogenesis: Including the growth of blood vessels and wound healing by stimulation of bone marrow-derived progenitor cells mobilization and homing. J. Vasc. Surg., 45: 39A-47A. [Crossref] [PubMed] [PMC]

33. Ieronimakis, N., Balasundaram, G., Rainey, S., Srirangam, K., Yablonka-Reuveni, Z. and Reyes, M. (2010) Absence of CD34 on murine skeletal muscle satellite cells marks a reversible state of activation during acute injury. PLoS One, 5(6): e10920. [Crossref]

34. Kirby, G.T.S., Mills, S.T., Cowin, A.J. and Smith, L.S. (2015) Stem cells for cutaneous wound healing. Biomed. Res. Int., Article ID: 285869, 11 Pages.

35. Ribatti, D. and Crivellato, E. (2012) Sprouting angiogenesis, a reappraisal. Dev. Biol., 372: 157-165. [Crossref] [PubMed]

36. Jasmadi, R., Salim, M.N., Harris, A., Aisyah, S., Armansyah, T. and Amiruddin, A. (2016) Effectiveness of Jatropha sap ointment 10% (Jatropha curcas Linn.) and gentamicin ointment 0.1% on combustion injury II healing on mice skin (Mus musculus). J. Med. Vet., 10(2): 120-122.

37. Salim, M.N., Darmawi , Balqis, U., Iskandar, C.D. and Masyitha, D. (2016) Wound healing effect of leaf extract of Jatropha curcas Linn in mice. Proc. Ann. Int. Con. (AIC) Syiah Kuala Univ., 6: 181-184.

38. Fauzi, F., Salim, M.N. and Nazaruddin, N. (2017) Effectivity of Jatropha Sap ointment (Jatropha curcas, Linn) on epithelialization phase of incision wound recovery on mice (Mus musculus). Jim. Vet., 1(3): 324-333.

39. Murti, D.A., Salim, M.N. and Sabri, M. (2017) The effectivity excretion of Jatropha salve (Jatropha curcas, L) to epithelization phase of mice (Mus musculus) cutaneous wound healing with masson trichrome stain. Jim. Vet., 1(3): 465-472.

40. Nanda, Y., Salim, M.N. and Iskandar, C.D. (2017) Histopathology of mice (Mus-musculus) skin on remodeling phase of wound healing incision using Jatropha curcas ointment sap. Jim. Vet., 1(4): 780-787.

41. Sabirin, I.P.R., Maskoen, A.M. and Hernowo, B.S. (2013) Role of noni (Morinda citrofolia L.) leaf ethanolic topical application on wound healing examined from CD34 immunoexpression and collagen on wistar rats. J. Ked. Bandung, 45(4): 226-233.

42. DiPietro, L.A. (2016) Angiogenesis and wound repair: When enough is enough. J. Leukoc. Biol., 100(5): 979-984. [Crossref] [PubMed]

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