Electronic Theses and Dissertation

ABSTRAK
Penyembuhan luka merupakan proses yang kompleks meliputi inflamasi, proliferasi sel, sintesis matriks ektraseluler, angiogenesis dan remodeling. Beberapa penelitian menunjukkan TGF-β berperan dalam penyembuhan luka dengan menginduksi α5β1 yang penting dalam migrasi sel endotel selama proses angiogenesis. Selain itu TGF-β memiliki aktivitas kemo-antraktan bagi fibroblas dan menstimulasi proliferasi untuk membentuk jaringan granulasi baru, peningkatan kontraksi luka dan migrasi sel keratinosit. Masyarakat Indonesia menggunakan tanaman herbal untuk penyembuh luka. Tumbuhan C. papaya, C. odorata dan A. bilimbi merupakan tanaman obat yang telah digunakan secara turun temurun oleh masyarakat Aceh untuk menyembuhkan luka. Penelitian ini bertujuan mengetahui efektivitas ekstrak daun C. papaya, C. odorata dan A. bilimbi dalam penyembuhan luka insisi pada tikus normal dan hiperglikemia.
Penelitian awal adalah skrining fitokimia ketiga ekstrak daun. Hasil yang diperoleh menunjukkan semua sampel mengandung flavonoid, alkaloid, saponin, fenolik, steroid dan terpenoid. Kandungan tanin hanya terdeteksi pada daun C. papaya dan C. odorata. Selanjutnya dilakukan identifikasi senyawa kimia aktif melalui Gas Chromatography-Mass Spectrometry (GC-MS) dan diperoleh 16 senyawa ekstrak daun C. papaya, 20 senyawa ekstrak daun C. odorata dan 17 senyawa ekstrak daun A. bilimbi. Hasil optimasi formulasi transdermal patch daun menunjukkan ketebalan patch antara 0.15-0.16 mm, bobot 80.17-80.43 mg, moisture content 1.41-1.62%, dan uji lipatan >300. Hasil ini menunjukkan patch sesuai dan dapat diaplikasikan pada kulit manusia.
Penelitian selanjutnya menguji transdermal patch pada tikus yang dibagi menjadi 10 kelompok yaitu kontrol negatif (P1), kontrol positif (P2), transdermal patch daun C. papaya (P3), transdermal patch daun C. odorata (P4), transdermal patch daun A. bilimbi (P5), kontrol negatif-hiperglikemia (P6), kontrol positif-hiperglikemia (P7), transdermal patch daun C. papaya-hiperglikemia (P8), transdermal patch daun C. odorata-hiperglikemia (P9), transdermal patch daun A. bilimbi-hiperglikemia (P10). Seluruh tikus dibuat luka insisi dan diberikan transdermal patch yang diganti setiap 2 hari selama 14 hari. Hasil analisis one-way ANOVA dengan program SPSS versi 26 diperoleh skor CSI tertinggi pada P1 dan P6 dibandingkan P7. Selanjutnya penutupan luka meningkat dari hari ke-3 sampai 13 pada semua kelompok dan penutupan luka terbesar pada kelompok P2 dan P4. Konsentrasi TGF-β mengalami penurunan dari hari ke 14 dibandingkan hari ke-7 dan penurunan paling signifikan pada kelompok P4. Hasil histologi pada hari ke-7 menunjukkan lapisan epidermis lebih tebal dan jaringan granular terisi penuh sel dan arteri mengisi luka secara penuh pada kelompok kontrol positif dan eksperimen dibandingkan dengan kontrol negatif. Pada hari ke-14 kolagen lebih banyak, keropeng sangat kecil dan epitelisasi meningkat.

Kata kunci: penyembuhan luka, C. papaya, C. odorata, A. bilimbi, transdermal patch

ABSTRACT Wound healing is a complex process involving inflammation, cell proliferation, extracellular matrix synthesis, angiogenesis and remodeling. This study compared growth factors and incision wound healing in normal and diabetic rats. Several studies have shown that TGF-β plays a role in wound healing by inducing α5β1 which is important in endothelial cell migration during the process of angiogenesis. In addition, TGF-β has chemoantractant activity for fibroblasts and stimulates proliferation to form new granulation tissue, increases wound contraction and migration of keratinocyte cells. Medicinal plants for wound healing have been used for generations by the people of Indonesia, especially Aceh, including C. papaya, C. odorata, A. bilimbi. This study aims to determine the effectiveness of C. papaya, C. odorata, A. bilimbi leaf extracts in wound healing in normal and hyperglycemic rat. Preliminary research is a phytochemical screening of the three leaf extracts. The results obtained showed that all samples contained flavonoids, alkaloids, saponins, phenolics, steroids and terpenoids. The tannin content was only detected in the leaves of C. papaya and C. odorata. Furthermore, identification of active chemical compounds was carried out through Gas Chromatography-Mass Spectrometry (GC-MS) and obtained 16 compounds of C. papaya leaf extract, 20 compounds of C. odorata extract and 17 compounds of A. bilimbi leaf extract. Optimization results of leaf patch transdermal formulation showed patch thickness between 0.15-0.16 mm, weight 80.17-80.43 mg, moisture content 1.41-1.62%, and fold test >300. These results show that the patch is suitable and can be applied to human skin. Subsequent studies tested transdermal patches on mice which were divided into 10 groups: negative control (P1), positive control (P2), transdermal patches of C. papaya leaves (P3), transdermal patches of C. odorata leaves (P4), transdermal patches of A. bilimbi (P5), negative control-hyperglycemia (P6), positive control-hyperglycemia (P7), transdermal patch of C. papaya-hyperglycemia leaf (P8), transdermal patch of leaf of C. odorata-hyperglycemia (P9), transdermal patch of leaf of A. bilimbi-hyperglycemia (P10). All mice were made incisions and given a transdermal patch which was replaced every 2 days for 14 days. The results of the one-way ANOVA analysis with the SPSS version 26 program obtained the highest CSI scores at P1 and P6 compared to P7. Furthermore, wound closure increased from day 3 to 13 in all groups and wound closure was greatest in groups P2 and P4. The TGF-β concentration decreased from day 14 compared to day 7 and the decrease was most significant in the P4 group. Histological results on the 7th day showed a thicker epidermal layer and granular tissue full of cells and arteries filling the wound completely in the positive control and experimental groups compared to the negative control. On the 14th day there is more collagen, very small scabs and increased epithelialization. Keywords: wound healing, C. papaya, C. odorata, A. bilimbi, transdermal patch