Wound Healing Activity of Transdermal Patches of Carica Papaya, Chromolaena Odorata, and Averrhoa Bilimbi Leaves on Incision Wounds of Hyperglycemic Rat

Authors

  • Tahara Dilla Santi Graduate School of Mathematics and Applied Science, Universitas Syiah Kuala, Aceh 23111, Indonesia
  • Tongku Nizwan Siregar Laboratory of Reproduction, Faculty of Veterinary Medicine, Universitas Syiah Kuala, Aceh 23111, Indonesia
  • Amalia Sutriana Laboratory of Pharmacology, Faculty of Veterinary Medicine, Universitas Syiah Kuala, Aceh 23111, Indonesia
  • Rita Andini Department of Forestry, Faculty of Agriculture, Universitas Syiah Kuala, Aceh 23111, Indonesia
  • Aditya Candra Faculty of Medicine, University of Abulyatama, Aceh 24415, Indonesia

DOI:

https://doi.org/10.48048/tis.2023.6944

Keywords:

Leaves extract, Wistar rats, Transdermal patches, Wound healing

Abstract

Transdermal patches have been used for drug delivery to accelerate the wound healing process with minimum negative effect.  This study evaluated the wound healing potential of transdermal patches containing Carica papaya, Chromolaena odorata, and Averrhoa bilimbi leaves extract on hyperglycemic rat as a diabetic wound model. For this purpose, a total of 40 Wistar rats aged 2 - 3 months were randomly distributed into 10 groups.  The first 5 groups (P1, P2, P3, P4 and P5) consisted of normal rats which received normal dressing, TP Dermafix, TP of C. papaya, TP of C. odorata, and TP of A. bilimbi, respectively. The second 5 groups (P6, P7, P8, P9 and P10) were hyperglycemic rats that received normal dressing, TP Dermafix, TP of C. papaya, TP of C. odorata, and TP of A. bilimbi, respectively. Skin incisions were made perpendicular to the spine in the thickest part of the skin with an incision length of 2 cm and a depth of 0.5 cm. Patches were applied to the incisions according to the test group and replaced every 2 days for a period of 13 days. Wound healing activity was determined by evaluating the Clinical Sign of Inflammation (CSI) score, wound closure, TGF-β1 concentration, and histology of skin tissue. Data were analyzed using oneway analysis of variance (ANOVA). The results showed that for each parameter observed, the rats intervened with transdermal patches loaded with extract leaves had higher healing potential and different from the control group (normal dressing without intervene) both in normal and hyperglycemic rats. This made us concluded that the TP loaded with C. papaya, C. odorata, and A. bilimbi extract leaves have potential as wound healing agents and could be considered as alternate to the synthetic transdermal patches.

HIGHLIGHTS

  • The use of drugs-loaded transdermal patches has been widely studied for the treatment of diabetic wounds, however, the potency of one’s containing Carica papaya, Chromolaena odorata, and Averrhoa bilimbi leaf extracts have not been studied. The present study reports the effectiveness of Carica papaya, Chromolaena odorata, and Averrhoa bilimbi impregnated transdermal patches in treating diabetic rat wounds based on CSI score, histological feature of rat skin and TGF- β concentration.


GRAPHICAL ABSTRACT

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

EJ Mulholland, N Dunne and HO McCarthy. MicroRNA as therapeutic targets for chronic wound healing. Mol. Ther. Nucleic Acids 2017; 8, 46-55.

S Singh, A Young and CE McNaught. The physiology of wound healing. Surgery 2017; 35, 473-7.

C Qing. The molecular biology in wound healing & non-healing wound. Chin. J. Traumatol. 2017; 20, 189-93.

RG Frykberg and J Banks. Challenges in the treatment of chronic wounds. Adv. Wound Care 2015; 9, 560-82.

A Shrivastav, AK Mishra, SS Ali, A Ahmad, MF Abuzinadah and NA Khan. In vivo models for assesment of wound healing potential: A systematic review. Wound Med. 2018; 20, 43-53.

L Cañedo-Dorantes and M Cañedo-Ayala. Skin acute wound healing: A comprehensive review. Int. J. Inflamm. 2019; 2019, 3706315.

M Kucharzewski, E Rojczyk, K Wilemska-Kucharzewska, R Wilk, J Hudecki and MJ Los. Novel trends in application of stem cells in skin wound healing. Eur. J. Pharmacol. 2019; 843, 307-15.

Suryadi. 2004, Hubungan antara tingkat gangguan kognitif dengan stadium retinopati diabetika pada diabetes melitus tipe 2. Master Thesis. Diponegoro University, Jawa Tengah, Indonesia.

A Maryunani. Step by step luka diabetes dengan metode perawatan luka modern. In Media, Bogor, Indonesia, 2013.

S Saghazadeh, C Rinoldi, M Schot, SS Kashaf, F Sharifi, E Jalilian, K Nuutila, G Giatsidis, P Mostafalu, H Derakhshandeh, K Yue, W Swieszkowski, A Memic, A Tamayol and A Khademhosseini. Drug delivery systems and materials for wound healing applications. Adv. Drug Deliv. Rev. 2018; 127, 138-66.

TD Santi, TN Siregar, A Sutriana, R Andini and A Candra. Phytochemical test and optimization of transdermal patches of Carica papaya extract: Formulation design of candidate drug for wound healing. Biodiversitas 2022; 23, 2904-13.

M Khatoon, KU Shah, FU Din, SU Shah, AU Rehman, N Dilawar and AN Khan. Proniosomes derived niosomes: Recent advancements in drug delivery and targeting. Drug Deliv. 2017; 24, 56-69.

A Sharma, V Puri and P Kumar. Rifampicin-loaded alginate-gelatin fibers incorporated within transdermal films as a fiber-in-film system for wound healing applications. Membranes 2021; 11, 7.

S Gupta, N Raghuwanshi, R Varshney, IM Banat, AK Srivastava, PA Pruthi and V Pruthi. Accelerated in vivo wound healing evaluation of microbial glycolipid containing ointment as a transdermal substitute. Biomed. Pharmacother. 2017; 94, 1186-96.

A Kumar, M Rana, T Joshi, S Bhoj and AJ Rana. Potential of Cissus qudrangularis transdermal patch for fracture healing. Plant Arch. 2018; 18, 121-7.

Y Özay, S Güzel, Ö Yumrutaş, B Pehlivanoğlu, İH Erdoğdu, Z Yildirim, BA Türk and S Darcan. Wound healing effect of kaempferol in diabetic and nondiabetic rats. J. Surg. Res. 2019; 233, 284-96.

M Kumari, AM Vittalrao, Charitha, P Kumar and S Prabhath. Evaluation of wound healing activity of an ethanolic extract of Anacardiumoccidentale leaves in wistar rats. Biomed. Pharmacol. J. 2020; 13, 2061-8.

R Ummah, WS Monica, DK Sari, YM Adikurniawan and MN Amir. Effects of sugar and honey on the formation of collagen fibers in incision wounds af domestic cat (Felis domestica). IOP Conf. Ser. Earth Environ. Sci. 2020; 575, 012025.

NT Saputra, IN Suartha and AAGO Dharmayudha. Diabetagonik agent streptozocin to make white rats male diabetes mellitus. Buletin Veteriner Udayana 2018; 10, 116-21.

A Akbarzadeh, D Norouzian, MR Mehrabi, JS Jamshidi, A Farhangi and AA Verdi. Induction of diabetes by streptozotocin in rats. Indian J. Clin. Biochem. 2007; 22, 60-4.

I Rosyadi, E Romadhona, AT Utami, YN Hijrati and CM Santosa. Gambaran kadar gula darah tikus wistar diabetes hasil induksi streptozotocin dosis tunggal. ARSHI Vet. Lett. 2018; 2, 41-2.

S Lenzen. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia 2008; 51, 216-26.

V Waisundara. Scutellaria baicalensis enhances the antidiabetic activity of metformin in streptozotocin-induced diabetic wistar rats. Am. J. Chin. Med. 2008; 36, 517-40.

FS Greenspan, JD Baxter, C Wijaya, RF Maulany and S Samsudin. Endokrinologi dasar dan klinik. 4th ed. EGC, Jakarta, Indonesia, 1998.

D Adji. Hubungan konsentrasi mda, glukosa dan total kolesterol pada tikus putih yang diinjeksi dengan streptozotocin. J. Sain Vet. 2006; 26, 73-7.

Veranita, D Wahyuni and Hikayati. Hubungan antara kadar glukosa darah dengan derajat ulkus kaki diabetik. Jurnal Keperawatan Sriwijaya 2016; 3, 44-50.

MJ Lede, T Hariyanto and VM Ardiyani. Pengaruh kadar gula darah terhadap penyembuhan luka diabetes mellitus di Puskesmas Dinoyo Malang. Nurs. News 2018; 3, 539-49.

AHR Dewiyanti, H Ratnawati and S Puradisastra. Perbandingan pengaruh ozon getah jarakcina (Jatropha multifida, L.) dan povide iodine 10 % terhadap waktu penyembuhan luka pada mencit betina galur swiss webster. J. Med. Health 2009; 8, 132-7.

P Wulandari, MR Hutagalunga and DS Perdanakusuma. Deteksi kadar transforming growth factor (TGF-β) pada luka akut. Jurnal Rekonstruksi dan Estetik 2021; 6, 1-3.

CA Oskeritzian. Mast cells and wound healing. Adv. Wound Care 2012; 1, 23-8.

N Takzaree, G Hassanzadeh, MR Rouini, A Manayi, A Hadjiakhondi and MM Zolbin. Evaluation of the effects of local application of thyme honey in open cutaneous wound healing. Iranian J. Publ. Health 2017; 46, 545-51.

R Rubin, D Strayer and E Rubin. Rubin’s pathology clinicopathologic foundations of medicine. 6th ed. Lippincott Williams and Wilkins, Philadelphia, 2012.

PA Borges, I Waclawiak, JL Georgii, VDS Fraga-Junior, JF Barros, FS Lemos, T Russo-Abrahão, EM Saraiva, CM Takiya, R Coutinho-Silva, C Penido, C Mermelstein, JR Meyer-Fernandes, FB Canto, JS Neves, PA Melo, C Canetti and CF Benjamim. Adenosine diphosphate improves wound healing in diabetic mice through P2Y12 receptor activation. Front. Immunol. 2021; 12, 651740.

R Nijveldt, EV Nood, DEV Hoorn, PG Boelens, KV Norren and PAV Leeuwen. Flavonoids: A review of probable mechanisms of action and potential applications. Am. J. Clin. Nutr. 2001; 74, 418-25.

BS Nayak and LMP Pereira. Catharanthus roseus flower extract has wound-healing activity in sprague dawley rats. BMC Compl. Alternative Med. 2006; 21, 41.

A Mahmood, Ak Tiwari, K Sahin, Ö Küçük and S Ali. Triterpenoid saponin-rich fraction of Centella asiatica decreases IL-1β and NF-κB, and augments tissue regeneration and excision wound repair. Turk. J. Biol. 2016; 40, 399-409.

PP Kumar, S Kumaravel and C Lalitha. Screening of antioxidant activity, total phenolics and GC-MS study of Vitex negundo. Afr. J. Biochem. Res. 2010; 4, 191-5.

A Rochmat. Uji kemampuan tanin daun ketapang sebagai inhibisi korosi pada baja mild steel dalam pipeline. Jurnal Integrasi Proses 2019; 8, 45-50.

RP Rijayanti1, S Luliana and HF Trianto. Uji aktivitas antibakteri ekstrak etanol daun mangga bacang (Mangifera foetida L.) terhadap Staphylococcus aureus secara in vitro. Jurnal Mahasiswa PSPD FK Universitas Tanjungpura 2014; 1, 165-71.

B Pejin, A Savic, M Sokovic, J Glamoclija, A Ciric, M Nikolic, K Radotic and M Mojovic. Further in vitro evaluation of antiradical and antimicrobial activities of phytol. Nat. Prod. Res. 2014; 28, 372-6.

AR Jalalvand, M Zhaleh, S Goorani, MM Zangeneh, N Seydi, A Zangeneh and R Moradi. Chemical characterization and antioxidant, cytotoxic, antibacterial, and antifungal properties of ethanolic extract of Allium saralicum R.M. Fritsch leaves rich in linolenic acid, methyl ester. J. Photochem. Photobiol. B Biol. 2019; 192, 103-12.

M Sermakkani and V Thangapandian. GC-MS analysis of Cassia italica leaf methanol extract. Asian J. Pharmaceut. Clin. Res. 2012; 5, 90-4.

COD Souza, CA Valenzuela, EJ Baker, EA Miles, JCR Neto and PC Calder. Palmitoleic acid has stronger anti-inflammatory potential in human endothelial cells compared to oleic and palmitic acids. Mol. Nutr. Food Res. 2018; 62, e1800322.

R Kavitha, MAM Uduman. Identification of bioactive components and its biological activities of Abelmoschas moschatus flower extract. A GC-MS study. IOSR J. Appl. Chem. 2017; 101, 19-22.

RO Silva, F Sousa, SRB Damasceno, NS Carvalho, VG Silva, FRMA Oliveira, DP Sousa, KS Aragão, ALR Barbosa, RM Freitas and JVR Medeiros. Phytol, a diterpene alcohol, inhibits the inflammatory response by reducing cytokine production and oxidative stress. Fund. Clin. Pharmacol. 2014; 28, 455-64.

M Pal and M Ghosh. Prophylactic effect of α-linolenic acid and α-eleostearic acid against MeHg induced oxidative stress, DNA damage and structural changes in RBC membrane. Food Chem. Toxicol. 2012; 50, 2811-18.

C Carrillo, MDM Cavia and S Alonso-Torre. Role of oleic acid in immune system; mechanism of action; a review. Nutr. Hosp. 2012; 27, 978-90.

LA Zhuravleva, SS Zykova, VS Talismanov and ОG Karmanova. Antioxidant and anti-radical effects of quercetin and rutin: Methyl linoleate model. Int. J. Pharmaceut. Res. 2019; 11, 168-75.

SH Huh, YS Kim, E Jung, J Lim, KS Jung, MO Kim, J Lee and D Park. Melanogenesis inhibitory effect of fatty acid alkyl esters isolated from Oxalis triangularis. Biol. Pharmaceut. Bull. 2010; 33, 1242-5.

Downloads

Published

2023-09-25

How to Cite

Santi, T. D. ., Siregar, T. N. ., Sutriana, A. ., Andini, R. ., & Candra, A. . (2023). Wound Healing Activity of Transdermal Patches of Carica Papaya, Chromolaena Odorata, and Averrhoa Bilimbi Leaves on Incision Wounds of Hyperglycemic Rat . Trends in Sciences, 20(12), 6944. https://doi.org/10.48048/tis.2023.6944