Combined Treatment Effect of Topical CM-hWJMSCs and Oral Moringa oleifera extract on Wound Healing of Diabetic Rat

Dian Ratih Laksmitawati; Umi Marwati; Wahyu Widowati; Rachmawati Noverina; Tri Suciati; Ahmad Faried

doi:10.3889/oamjms.2023.7551

Authors

Dian Ratih Laksmitawati Department of Pharmacology and Biochemistry, Pharmacy Faculty, Pancasila University, Jakarta, Indonesia
Umi Marwati Department of Pharmacology and Biochemistry, Pharmacy Faculty, Pancasila University, Jakarta, Indonesia
Wahyu Widowati Medical Research Center, Faculty of Medicine, Maranatha Christian University, Bandung, West Java, Indonesia
Rachmawati Noverina Laboratory Animal and Stem Cells, PT Bio Farma (Persero) Hospital, Bandung, West Java, Indonesia
Tri Suciati School of Pharmacy, Institute Technology Bandung, Bandung, West Java, Indonesia
Ahmad Faried Department of Neurosurgery and Stem Cell Working Group, Faculty of Medicine, Universitas Padjadjaran, Dr. Hasan Sadikin, Bandung, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2023.7551

Keywords:

Conditioned Medium,, Mesenchymal Stemcell, Moringa oleifera, Wound Healing, Streptozotocin, Diabetic Rat

Abstract

AIMS: The aim of the study was to determine the activity of topical conditioned medium (CM) mesenchymal stem cells as single or combined with oral therapy of Moringa oleifera extract (ME) in lowering blood glucose levels and healing diabetic wounds.

MATERIALS AND METHODS: Male Sprague-Dawley rats were induced hyperglycemia with Streptozotocin and injured by a biopsy punch on the dorsal side. Then, the rats were divided into five groups, namely, the CM group, which was given topically; the CM–ME group, which was given CM gel topically and ME orally; the CM–Met group, which was given Metformin (Met) as the positive control; commercial gel containing neomycin and placenta extract (BP); and placebo as the negative control. The treatments were given once daily for 16 days. On the 3rd, 8th, and 16th days of treatment, blood glucose level was measured, and anatomical observations of wounds and histology were performed using hematoxylin-eosin and Masson’s Trichrome staining.

RESULTS: The wounds treated with CM–ME and CM–Met have a similar profile of lowering blood glucose levels; however, Met was faster to reach blood glucose levels below 250 mg/dL (day 8) compared with ME (day 16). As shown in data on anatomical and histological wound healing parameters, untreated mice exhibited moist wounds with poor healing. Meanwhile, the group that received CM gel alone or along with oral ME showed an improvement in wound parameters.

CONCLUSION: CM–ME has a similar profile to CM–Met in reducing blood glucose levels and healing diabetic wounds parameters in rats.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Yuan X, Li X, Hao H, Cui Y, Chen M, Liu L, et al. Secretome of mesenchymal stem cells. In: Essentials of Mesenchymal Stem Cell Biology and its Clinical Translation. Netherlands: Springer; 2013. p. 33-46.

Lopes L, Setia O, Aurshina A, Liu S, Hu H, Isaji T, et al. Stem cell therapy for diabetic foot ulcers: A review of preclinical and clinical research. Stem Cell Res Ther. 2018;9(1):188. https://doi.org/10.1186/s13287-018-0938-6 PMid:29996912

Navadiya SK, Vaghani YL, Patel MP. Study of topical placental extract versus povidone iodine and saline dressing in various diabetic wounds. Natl J Med Res. 2012;2(4):411-3.

Lambole V, Kumar U. Effect of Moringa oleifera Lam. on normal and dexamethasone suppressed wound healing. Asian Pac J Trop Biomed. 2012;2(1):S219-23. https://doi.org/10.1016/S2221-1691(12)60163-4

Panchal MA, Murti K, Lambole V, Gajera V. Pharmacological properties of Moringa oliefera lam.-a review. Pharmacologyonline. 2010;1(2):768-75.

Shrestha C, Zhao L, Chen K, He H, Mo Z. Enhanced healing of diabetic wounds by subcutaneous administration of human umbilical cord derived stem cells and their conditioned media. Int J Endocrinol. 2013;2013:592454. https://doi.org/10.1155/2013/592454 PMid:24089612

Villarruel-López A, la Mora DA, Vázquez-Paulino OD, Puebla-Mora AG, Torres-Vitela MR, Guerrero-Quiroz LA, et al. Effect of Moringa oleifera consumption on diabetic rats. BMC Complement Altern Med. 2018;18(1):127. https://doi.org/10.1186/s12906-018-2180-2 PMid:29636032

Furman BL. Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol. 2015;70(1):5.47.1-5.47.20. https://doi.org/10.1002/0471141755.ph0547s70 PMid:26331889

Laksmitawati DR, Prasanti AP, Larasinta N, Syauta GA, Hilda R, Ramadaniati HU, et al. Anti-inflammatory potential of gandarusa (Gendarussa vulgaris nees) and soursoup (Annona muricata L) extracts in LPS stimulated-macrophage cell (RAW264.7). J Nat Remedies. 2016;16(2):73-81. https://doi.org/10.18311/jnr/2016/5367

Azevedo IM, Araújo-Filho I, Teixeira MM, de Carvalho Moreira MD, Moreira AC. Wound healing of diabetic rats treated with Moringa oleifera extract. Acta Cir Bras. 2018;33(9):799-805. https://doi.org/10.1590/s0102-865020180090000008 PMid:30328912

Nagarchi K, Ahmed S, Sabus A, Saheb SH. Effect of streptozotocin on glucose levels in Albino Wister rats. J Pharm Sci Res. 2015;7(2):67-9.

Galehdari H, Negahdari S, Kesmati M, Rezaie A, Shariati G. Effect of the herbal mixture composed of aloe vera, henna, Adiantum capillus-veneris, and myrrha on wound healing in streptozotocin-induced diabetic rats. BMC Complement Altern Med. 2016;16(1):386. https://doi.org/10.1186/s12906-016-1359-7 PMid:27716154

Suvik A, Effendy AW. The use of modified Masson’s trichrome staining in collagen evaluation in wound healing study. Malays J Vet Res. 2012; 3(1):39-47.

Goud BJ, Dwarakanath V, Swamy BK Streptozotocin-a diabetogenic agent in animal Models. Int J Pharm Pharm Res. 2015;3(1):253-69.

Eleazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord. 2013;12(1):60. https://doi.org/10.1186/2251-6581-12-60 PMid:24364898

Chinedu AA, Alani SO, Olaide AO. Effect of the ethanolic leaf extract of Moringa oleifera on insulin resistance in streptozotocin induced diabetic rats. J Plant Sci. 2014;2(6-1):5-12. https://doi.org/10.11648/j.jps.s.2014020601.12

Salkovic-Petrisic M, Knezovic A, Hoyer S, Riederer P. What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research. J Neural Transm (Vienna). 2013;120(1):233-52. https://doi.org/10.1007/s00702-012-0877-9 PMid:22886150

Utary N, Murti K, Septadina IS. Effects of Moringa (Moringa oleifera) leaf extract on alveolar diameter of breastfeeding and weight of infant Wistar rats. J Phys Conf Ser. 2019;12067:012067. https://doi.org/10.1088/1742-6596/1246/1/012067

Reinke JM, Sorg H. Wound repair and regeneration. Eur Surg Res. 2012;49(1):35-43. https://doi.org/10.1159/000339613

PMid:22797712

Li M, Zhao Y, Hao H, Dai H, Han Q, Tong C, et al. Mesenchymal stem cell-conditioned medium improves the proliferation and migration of keratinocytes in a diabetes-like microenvironment. Int J Low Extrem Wounds. 2015;14(1):73-86. https://doi.org/10.1177/1534734615569053 PMid:25759411

Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219-29. https://doi.org/10.1177/0022034509359125 PMid:20139336

Dunnill C, Patton T, Brennan J, Barrett J, Dryden M, Cooke J, et al. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int Wound J. 2017;14(1):89-96. https://doi.org/10.1111/iwj.12557 PMid:26688157

Wu AS, Kalghatgi S, Dobrynin D, Sensenig R, Cerchar E, Podolsky E, et al. Porcine intact and wounded skin responses to atmospheric nonthermal plasma. J Surg Res. 2013;179(1):e1-12. https://doi.org/10.1016/j.jss.2012.02.039 PMid:22480830

Fukuoka H, Narita K, Suga H. Hair regeneration therapy: Application of adipose-derived stem cells. Curr Stem Cell Res Ther. 2017;12(7):531-4. https://doi.org/10.2174/15748 88X12666170522114307 PMid:28530535

Winarsih W, Wientarsih I, Sutardi LN The activity of turmeric extract ointment in the wound healing process of induced diabetic mice. J Vet. 2012;13(3):242-50.

Widowati W, Wijaya L, Murti H, Widyastuti H, Agustina D, Laksmitawati DR, et al. Conditioned medium from normoxia (WJMSCs-norCM) and hypoxia-treated WJMSCs (WJMSCs-hypoCM) in inhibiting cancer cell proliferation. Biomarkers Genomic Med. 2015;7(1):8-17. https://doi.org/10.1016/j.bgm.2014.08.008

Prasetyono TO. General concept of wound healing, revisited. Med J Indones. 2009;18:208-16.

Xue M, Jackson CJ. Extracellular matrix reorganization during wound healing and its impact on abnormal scarring. Adv Wound Care (New Rochelle). 2015;4(3):119-36. https://doi.org/10.1089/wound.2013.0485 PMid:25785236