Revista Cienﬁca, FCV-LUZ / Vol. XXXV Recıbıdo: 28/07/2025 Aceptado:06/11/2025 Publicado: 06/12/2025 UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico 1 of 7 Revista Cienﬁca, FCV-LUZ / Vol. XXXVI https://doi.org/10.52973/rcfcv-e361759 UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico Rosa damascena extract is as eﬀecve as Centella asiaca in wound healing El extracto de Rosa damascena es tan eﬁcaz como la Centella asiaca en la cicatrización de heridas Mehmet Nuri Yildiz 1 , Abidin Tüzün 1 , Hüseyin Bilge 1 * , Eda Yildizhan 2 , Alpay Cetin 3 ¹ University of Health Sciences Gazi Yaşargil, Department of Surgical Medical Sciences,Training and Research Hospital, Diyarbakır, Turkey. ² Dicle University, Faculty of Medicine, Department of Histology and Embryology, Diyarbakır, Turkey. ³ University of Health Sciences, Department of Pathology,Gazi Yaşargil Training and Research Hospital, Diyarbakır, Turkey. *Correspondent Adress: dr.huseyinbilge@hotmail.com ABSTRACT Since prolonged wound healing processes not only compromise paent comfort but also increase paent care costs, extracts obtained from various plants are preferred in clinical and experimental studies to accelerate wound healing and contribute to curaon. The aim was to compare the eﬃcacy of Centella asiaca, whose eﬀecveness on wound healing has been proven in previous studies, with that of Rosa damascena, for which research is sll ongoing. Twenty-one Wistar albino rats aged 8-10 weeks were used in the study. The rats’ back region was shaved with a shaving machine, cleaned with physiological serum, and a 2x2 cm incision was made to create a full-thickness excisional wound in the interscapular area. Group I: Control group, Group II: Rosa damascena group, Rosa damascena extract was applied once a day and dressed with gauze. Group III: Centella asiaca group received a similar applicaon. The wound surface dimensions were measured on days 0, 7, 14, and 21 by drawing on acetate paper to calculate the surface area. On days 7, 14, and 21, punch biopsies were taken from diﬀerent areas for histopathological examinaon. On day 14, no signiﬁcant diﬀerence was observed between Rosa damascena and Centella asiaca in terms of wound surface area (P = 0.415). Again, no stascally signiﬁcant diﬀerence was observed between the groups in terms of ﬁbroblast acvity on days 7 and 21, and neovascularizaon was also found to be insigniﬁcant on days 14 and 21. Collagen regularity and density increased in both the Rosa damascena group and the Centella asiaca group. VEGF retenon did not show a signiﬁcant diﬀerence between the two groups on day 21 (P = 0.762). It was concluded that Rosa damascena extract may contribute to wound healing more eﬀecvely than Centella asiaca ointment. Keywords: Wound healing; Rosa damascena; Centella asiaca; VEGF. RESUMEN Dado que la cicatrización prolongada de heridas no solo compromete la comodidad del paciente, sino que también incrementa los costos de atención médica, los extractos obtenidos de diversas plantas son los preferidos en estudios clínicos y experimentales para acelerar la cicatrización de heridas y contribuir a su curación. El objevo fue comparar la eﬁcacia de Centella asiaca, cuya eﬁcacia en la cicatrización de heridas ha sido demostrada en estudios previos, con la de Rosa damascena, cuya invesgación aún está en curso. Se ulizaron veinún ratas albinas Wistar de 8 a 10 semanas de edad. Se afeitó la región dorsal de las ratas con una máquina de afeitar, se limpió con suero ﬁsiológico y se realizó una incisión de 2 x 2 cm para crear una herida escisional de espesor completo en la zona interescapular. Grupo I: Grupo control. Grupo II: Grupo Rosa damascena. El extracto de Rosa damascena se aplicó una vez al día y se cubrió con una gasa. Grupo III: Grupo Centella asiaca recibió una aplicación similar. Las dimensiones de la superﬁcie de la herida se midieron los días 0, 7, 14 y 21 dibujando en papel acetato para calcular el área superﬁcial. Los días 7, 14 y 21 se tomaron biopsias por punción de diferentes áreas para su examen histopatológico. El día 14, no se observó diferencia signiﬁcava entre Rosa damascena y Centella asiaca en cuanto al área superﬁcial de la herida (P = 0,415). De nuevo, no se observó diferencia estadíscamente signiﬁcava entre los grupos en cuanto a la acvidad de ﬁbroblastos los días 7 y 21, y la neovascularización también fue insigniﬁcante los días 14 y 21. La regularidad y la densidad del colágeno aumentaron tanto en el grupo de Rosa damascena como en el de Centella asiaca. La retención de VEGF no mostró una diferencia signiﬁcava entre los dos grupos el día 21 (P = 0,762). Se concluyó que el extracto de Rosa damascena puede contribuir a la cicatrización de heridas con mayor eﬁcacia que el ungüento de Centella asiaca. Palabras clave: Cicatrización de heridas; Rosa damascena; Centella asiáca; VEGF.

Rosa damascena extract in wound healing / Yildiz et al. UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico INTRODUCTION Wound healing is a process involving interacons between cellular and molecular events, consisng of the stages of hemostasis, inﬂammaon, proliferaon, and remodeling, which are necessary to maintain ssue funconality and connuity aﬅer ssue damage. This process begins with wound formaon and can take a long me depending on the eﬀects of local and systemic factors that inﬂuence healing and cause chronicity. A prolonged wound healing process not only compromises paent comfort but also increases paent care costs [1],2,3]. In recent years, increasing chronic diseases, poor nutrion, and a sedentary lifestyle have been among the factors that disrupt the wound healing process. For this reason, extracts obtained from various plants are preferred in clinical and experimental studies to accelerate wound healing and contribute to wound healing [4 , 5 , 6]. Centella asiaca is more commonly known as gotu kola, ger grass, or Asian pennywort. It is a ﬂowering plant belonging to the umbellifer family that grows in tropical countries and humid regions, primarily in Southeast Asia and Australia. It is used in both the food industry and tradional medicine [7 , 8 ,9]. Studies on Centella asiaca have shown that its hydrogel form enhances epithelializaon and possesses anxiolyc, an-inﬂammatory, anoxidant, an-ulcer, an-cancer, neuroprotecve, and wound-healing properes [10]. Rosa damascena, commonly known as Damask rose, is an ornamental plant belonging to the Rosaceae family, originang from the Middle East. It grows to an average height of 1 to 2 meters and has colorful ﬂowers. It is culvated all over the world, parcularly in Türkiye, Iran, and India. In tradional medicine, Rosa damascena is said to have an-inﬂammatory and wound- healing eﬀects, and it has been observed to be eﬀecve for coughs, abdominal pain, and dysmenorrhea. Rosa damascena is also known to be eﬀecve in vasorelaxaon, andepressant, analgesic, an-diabec, an-inﬂammatory, bronchodilator, anoxidant, anmicrobial, an-aging, skin repair, and aphthous stomas treatment [11 , 12 , 13 , 14]. As a result of the literature review, it was determined that there are limited studies based on concrete data from a methodological perspecve regarding the eﬀects of Rosa damascena on wound healing. Therefore, in this study, the potenal eﬀects of Centella asiaca and Rosa damascena, which have proven eﬃcacy on wound healing, on congeson, collagen density and irregularity, ﬁbroblast acvity, neovascularizaon, mononuclear cell inﬁltraon, immunohistochemical density, and changes in wound surface area. MATERIALS AND METHODS Ethics commiee approval Approval was obtained with the ethical commiee decision No. 2023/17, which was decided at the meeng of the Dicle University Animal Experiments Local Ethics Commiee on November 30, 2023. The experimental animals were obtained from the Sabahan Payzın Research Center (DUSAM) at Dicle University. The experimental procedures were conducted at the DUSAM animal care center, while ssue analyses were performed at the Pathology Laboratory of the Diyarbakır Gazi Yaşargil Health Applicaon and Research Center at the University of Health Sciences. Obtaining Rosa damascena extract Commercially available Rosa Damascena extract, boled as Rose Hydrosol, is obtained by dislling Rosa Damascena roses in chrome-made (inox) slls at the rose factory (Sincer rose oil factory, Isparta, Türkiye), without separang the rose oil, resulng in a 100 % pure and natural rose hydrolate. Aﬅer opening the boles, they are stored at a temperature of 4-6 °C, away from sunlight. Wound model and formaon of experimental groups The study used 21 Wistar albino rats (Raus norvegicus) weighing 200-300 grams (g) and aged 8-10 weeks.The rats were housed in stainless steel cages (temperature 22±2 °C, humidity 60 %) with a 12-hour (h) light/dark cycle and without food or water restricons. Aﬅer being randomly divided into 3 groups of 7 rats each, the rats were sedated on days (d) 0, 7, 14, and 21 with intramuscular (i.m.) injecons of 90 mg/kg Ketamine (Ketalar®, Pﬁzer Inc., USA) and 10 mg/kg Xylazine (Rompun®, Bayer HealthCare AG, Germany). The depth of sedaon and the need for addional doses were assessed by observing limb responses. The rats’ back region was shaved with a razor without irritang the skin, cleaned with physiological serum, and marked with a 2x2 cm ruler. The area to be operated on was cleaned with alcohol and a 2x2 cm full-thickness (epidermis, dermis) excisional wound was created in the interscapular area with a No. 15 scalpel. This wound model is simple and widely used. Thus, the rate of wound closure over me can be observed. Important stages such as granulaon ssue development, collagen accumulaon, re-epithelializaon process, and wound contracon can be examined in detail with this model [15 , 16]. Aﬅer the wounds were created, Paracetamol (Atabay Pharmaceucals, Istanbul, Türkiye) was added to the rats’ drinking water at a dose of 2 mg/ml/d to control pain. Group I (n=7): Control group, no other procedures were performed except for d dressing with gauze. Group II (n=7): Aﬅer creang a 2x2 cm excisional wound in the rats in the Rosa damascena group, Rosa damascena extract was applied once a d and dressed with gauze. Group III (n=7): This was the Centella asiaca group, where Centella asiaca ointment was applied once d, followed by dressing care. The wound surface areas of rats were measured on d 0, 7, 14, and 21 by drawing the wound surfaces on acetate paper. Punch biopsies were taken from diﬀerent areas of the wounds on d 7, 14, and 21 for histopathological examinaon. Histopathological examinaon Tissue samples were obtained by punch biopsy from the upper leﬅ corner on d 7, the upper right corner on d 14, and the lower right corner on d 21. The samples were ﬁxed in 10 2 of 7

Revista Cienﬁca, FCV-LUZ / Vol. XXXVI UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico % formalin for 24 h, then rinsed in running water, dehydrated, and embedded in paraﬃn blocks. Secons 4–5 microns (µ) thick were taken from the paraﬃn blocks and subjected to roune histological examinaon. The secons were stained with hematoxylin and eosin (H&E) and examined under a light microscope (Zeiss microscope, Germany) [16]. Immunohistochemical examinaon For immunohistochemical examinaons, secons 4-5 μm thick were prepared following roune histological ssue follow-up, and the prevalence of Vascular Endothelial Growth Factor (VEGF) (Santa Cruz, USA) expression (brown areas) was evaluated. Gill Hematoxylin was used in the counterstaining protocol. The secons were examined under a light microscope (Zeiss microscope, Germany), and the degree of damage was determined according to the method developed by Erdogan and Yalcin [17]. Stascal analysis Stascal Package for Social Sciences (SPSS, Inc., Chicago, IL, USA) for Windows 24.0 was used for stascal analysis of the obtained data. The Kolmogorov Simirnov test was used to check the distribuon of the data. ANOVA test was used for mulple group comparisons of normally distributed data, and the relaonship between groups was evaluated using the Posthoc Tukey test. For data that did not show a normal distribuon, the Kruskal-Wallis test was used for mulple group comparisons, and the Mann-Whitney U test was used to compare groups. Data were considered signiﬁcant when P < 0.05. RESULTS AND DISCUSSIONS Macroscopic evaluaon results When the wound surface areas were calculated on d 7, 14, and 21,it was found that the Centella asiaca group was lagging behind in wound healing on d 7 and had a larger wound area. No stascally signiﬁcant diﬀerence was observed between the control group and the Rosa damascena group (P = 0.08). A stascally signiﬁcant diﬀerence was calculated between the control group and the Centella asiaca group (P = 0.033). No signiﬁcant diﬀerence was observed between wound surface areas on d 14 (P = 0.415). On d 21, the Centella asiaca group had the largest wound surface area, and the diﬀerence between it and both the Rosa damascena and control groups was stascally signiﬁcant (P C-B = 0.017, P A-B = 0.009). The Centella asiaca group had a larger wound surface area and was morphologically behind in wound healing (TABLE I) (FIG. 1). Bardaa et al. [18] created an excisional wound model in diabec rats and compared the wound surface area of Ginkgo biloba and Centella asiaca, observing that Centella asiaca had a smaller wound surface area. According to Kim et al. [19] experimental study, the Rosa damascena group showed faster wound closure compared to the control group. Nie et al. [20] created skin ulcers in diabec rats and found that the Centella asiaca and nitric oxide mixture resulted in a signiﬁcantly smaller wound area on d 3 and 14 compared to the control group. TABLE I Comparison of wound surface areas on days 7, 14, and 21 Control Rosa damascena Centella asiaca p 7 th d 2.77±0.18 2.89±0.44 3.2±0.34 0.033 a Intragroup comparisons p-value X A-C 0.800 C-A 0.800 B-A 0.033 A-B 0.033 B-C 0.114 B-C 0.114 14 th d 0.8±0.6 0.9±0.27 0.91±0.12 0.415 a 21 th d median (IQR) 0.24(0.07) 0.25(0.09) 0.36(0.20) 0.014 b Intragroup comparisons P-value Y A-C 0.847 C-A 0.847 B-A 0.009 A-B 0.009 C-B 0.017 B-C 0.017 A-C : P-value in the comparison between the control group and the Rosa damascena group, A-B : P-value in the comparison between the control group and the Centella asiaca group, B-C : In the comparison between the Rosa damascena group and the Centella asiaca group, the p-value was, IQR: Inter Quanle Range, a: ANOVA test, x: Evaluaon according to the intra-group post hoc Tukey test on day 7, b: Kruskal Wallistest, y: Evaluaon according to the Mann Whitney-U test in the subgroup analysis on day 21. FIGURE 1. A; Rosa damascena, B; Centella asiaca, C; Wound images taken on the 7th day of the control groups. D; Rosa damascena, E; Centella asiaca, F; Wound images from control groups on day 14. G; Rosa damascena, H; Centella asiaca, I; Wound images from control groups on day 21. In the wound surface area comparison on d 7, we observed that the control group had the smallest wound area, while the Centella asiaca group had the largest wound area. No stascally signiﬁcant diﬀerence was observed between the control group and the Rosa damascena group. On d 14, Centella asiaca was calculated to be behind in wound healing according to wound surface area calculaons. On d 21, when evaluang wound surface areas, Centella asiaca was found to have a higher wound surface area than both the Rosa damascena group and the control group.The morphological ﬁndings were not consistent with the literature for Centella asiaca but showed more meaningful results for Rosa damascena. Histopathological examinaons Tissue samples taken on d 7, 14, and 21 were stained with H&E and examined under a light microscope to assess collagen 3 of 7

Rosa damascena extract in wound healing / Yildiz et al. UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico regularity, collagen density, ﬁbroblast acvity, myoﬁbroblast density, congeson, neovascularizaon, and mononuclear cell inﬁltraon were scored on a scale of 1 to 4 by a blinded pathologist (FIG. 2). FIGURE 2. A; Rosa damascena, B; Centella asiaca, C; Hematoxylin & Eosin staining images of control groups on day 7. D; Rosa damascena, E; Centella asiaca, F; Hematoxylin & Eosin staining images of control groups on day 14. G; Rosa damascena, H; Centella asiaca, I; Hematoxylin & Eosin staining images of control groups on day 21. No stascally signiﬁcant diﬀerence in collagen regularity was found between the groups on d 7 and 21. On d 14, collagen regularity was found to be higher in the Rosa damascena group than in both the control group and the Centella asiaca group (P C-B = 0.028, P C-A = 0.001). Similarly, collagen density was observed to be higher in both the Rosa damascena group and the Centella asiaca group compared to the control group on d 14 (P C-A = 0.049, P B-A = 0.003). In terms of ﬁbroblast acvity, no stascally signiﬁcant diﬀerence was observed between the groups on d 7 and 21, while on d 14, the control group was found to have higher ﬁbroblast acvity than both the Rosa damascena group and the Centella asiaca group, with the diﬀerence between them being stascally signiﬁcant (P A-C = 0.011, P A-B = 0.034). No signiﬁcant diﬀerence was observed between the Rosa damascena and Centella asiaca groups(P = 0.849) (TABLE II). TABLE II Comparison of collagen regularity, collagen density, and ﬁbroblast acvity on days 7, 14, and 21 Control Rosa damascena Centella asiaca P 7 th d 1.86±0.690 1.71±0.488 2.00±0.816 0.737 a 14 th d 1.14±0.378 2.29±0.488 1.57±0.535 0.001 a Intragroup comparisons p-value X A-C 0.001 C-A 0.001 B-A 0.232 A-B 0.232 C-B 0.028 B-C 0.028 21 th d 1.86±0.378 2.29±0.488 2.43±0.535 0.088 a Control Rosa damascena Centella asiaca p 7 th d 2.86±0.690 2.14±0.690 2.29±1.11 0.279 a 14 th d 2.29±0.488 2.86±0.378 3.14±0.378 0.004 a Intragroup comparisons p-value X A-C 0.049 C-A 0.049 B-A 0.003 A-C 0.003 C-B 0.424 B-C 0.424 21 th d 3.14±0.378 3 3 0.387 a Control Rosa damascena Centella asiaca p 7 th d 2.43±0.535 2.71±0.756 3±0.577 0.263 a 14 th d 3 2.14±0.378 2.29±0.756 0.009 a Intragroup comparisons p-value X A-C 0.011 C-A 0.011 B-A 0.034 A-B 0.034 C-B 0.849 B-C 0.849 21 th d 2.14±0.378 2 2.43±0.535 0.126 a A-C : P-value in the comparison between the control group and the Rosa damascena group, A-B : P-value in the comparison between the control group and the Centella asi- aca group, B-C : In the comparison between the Rosa damascena group and the Cen- tella asiaca group, the p-value was, a: ANOVA test, x: Evaluaon according to the intra-group post hoc Tukey test on day 14. Fibroblasts are known to be eﬀecve in contracon, cell migraon, and collagen producon, and to play a role in all stages of wound healing [21]. On the 14th d of the proliferaon phase, ﬁbroblasts transform into myoﬁbroblasts [22]. In a study comparing the eﬀect of Centella asiaca on the proliferaon of human dermal ﬁbroblasts with that of renoic acid, it was found to have a stronger eﬀect than renoic acid [23]. A systemac review of Centella asiaca indicates that it has an acvang eﬀect on ﬁbroblasts and contributes to granulaon ssue formaon by increasing angiogenesis [24]. Rosa damascena has been shown to increase the lifespan of human ﬁbroblast cells by inducing morphological changes [25]. It is known that saponins, ﬂavonoids, tannins, and terpenoids in plants support wound healing by acvang ﬁbroblasts and increasing their growth [26]. On the 14th d of this study, ﬁbroblast acvity was stascally higher in the control group, which is in favor of Rosa damascena and Centella asiaca and is consistent with the literature data. Collagen density and regularity are important indicators that determine granulaon ssue formaon and the wound healing process. During the remodeling phase of skin wounds, collagen accumulaon is a crical process and serves as a criterion for evaluang wound healing [27]. According to an in vitro study examining human collagen 1 and ﬁbroblast acvity, asiacoside in Centella asiaca has been shown to increase collagen 1 and ﬁbroblast synthesis separately 4 of 7

Revista Cienﬁca, FCV-LUZ / Vol. XXXVI UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico [28]. In an experimental study by Maquart et al.[29], triterpenes derived from Centella asiaca were found to increase collagen matrix and hydroxyproline in rat wound healing. In another study, it was shown that topical applicaon of Centella asiaca gel contributes to an increase in collagen content [30]. In their study on radiaon-induced skin aging, Park et al. [31] found that Rosa damascena improves collagen synthesis by reducing matrix metalloproteinases through TGF-β smulaon, thereby providing protecon against skin aging. According to our study, we observed that Rosa damascena is as eﬀecve as Centella asiaca in collagen synthesis. In the intergroup comparison of collagen regularity and density, we found that the Rosa damascena group was stascally signiﬁcantly superior to both the control group and the Centella asiaca group on d 14. The severity of congeson increased in the Centella asiaca group compared to the control group on d 7 (P = 0.018), while no stascally signiﬁcant diﬀerence was found with the Rosa damascena group (P = 0.233) (TABLE III). No stascally signiﬁcant diﬀerence was observed between the groups in the comparison of neovascularizaon on d 14 and 21 (TABLE III). TABLE III Comparison of congeson severity and neovascularizaon on days 7, 14, and 21 Control Rosa damascena Centella asiaca p 7 th d 1.71±0.488 2.43±0.976 3±0.816 0.023 a Intragroup comparisons p-value X A-C 0.233 C-A 0.233 B-A 0.018 A-B 0.018 C-B 0.383 B-C 0.383 14 th d 2.71±0.756 2.43±0.535 2.86±0.690 0.487 a 21 th d 2.43±0.535 2.14±0.378 2 0.126 a Control Rosa damascena Centella asiaca p 7.d 1.71±0.756 2.43±0.787 3±1 0.037 a Intragroup comparisons p-value X A-C 0.286 C-A 0.286 B-A 0.029 A-B 0.029 C-B 0.440 B-C 0.440 14 th d 3.29±0.756 2.43±0.787 3.43±0.976 0.83 a 21 th d 2.71±0.488 2.14±0.690 2.57±0.787 0.274 a A-C : P-value in the comparison between the control group and the Rosa damascena group, A-B : P-value in the comparison between the control group and the Centella asi- aca group, B-C : In the comparison between the Rosa damascena group and the Cen- tella asiaca group, the p-value was, a: ANOVA test x: Evaluaon according to the int- ra-group post hoc Türkiye test on day 7. Congeson limits damage to the wound during the inﬂammatory phase through hemostasis, chemotaxis, and increased vascular permeability. It aids cell migraon to clear cellular debris and bacteria, thereby playing an important role in wound healing [27]. Cesarone et al. [32] reported that Centella asiaca increases microcirculaon and improves venous hypertensive microangiopathic paents. The severity of congeson was beer in the Centella asiaca group on d 7, and there was no signiﬁcant diﬀerence between it and the Rosa damascena group. It has been shown that oral administraon of Centella asiaca in rats increases angiogenesis compared to the control group by acvang the kinase-independent pathway through collagen type 1, ﬁbroblast increase, and VEGF increase [33]. In their experimental studies comparing Polypodium vulgare and Centella asiaca in rats, Batur et al. [34], demonstrated that Centella asiaca contributed to greater new vessel formaon and granulaon ssue development compared to the control group. Immunohistochemical studies Tissue samples taken on d 7, 14, and 21 were subjected to VEGF anbody tesng. Following VEGF anbody tesng, VEGF binding intensity (graded from 1 to 3) and VEGF density (weak = 1, strong = 2) were calculated. Immunohistochemical staining images are shown in FIG. 3. FIGURE 3. A; Rosa damascena, B; Centella asiaca, C; VEGF staining images of control groups on day 7. D; Rosa damascena, E; Centella asiaca, F; VEGF staining images of control groups on day 14. G; Rosa damascena, H; Centella asiaca, I; VEGF staining images of control groups on day 21. VEGF: Vascular Endothelial Growth Factor. It was observed that VEGF retenon was best in the Rosa damascena group on d 7, and that the Rosa damascena group and Centella asiaca group were beer than the control group, with a stascally signiﬁcant diﬀerence between them (P C-A = 0.001, P B-A = 0.020). No stascally signiﬁcant diﬀerence was observed between groups on d 14 and 21 (P = 0.510, P = 0.093) (TABLE IV). It was determined that VEGF density showed a signiﬁcant increase in the Centella asiaca group compared to the control group only on d 14 (P = 0.029). On d 21, no signiﬁcant diﬀerence was observed between the Rosa damascena group and the Centella asiaca group (P = 0.762) (TABLE IV). 5 of 7

Rosa damascena extract in wound healing / Yildiz et al. UNIVERSIDAD DEL ZULIA Serbiluz Sistema de Servicios Bibliotecarios y de Información Biblioteca Digital Repositorio Académico TABLE IV Comparison of VEGF retenon and density on days 7, 14, and 21 Control Rosa damascena Centella asiaca p 7 th d 1.14±0.378 2 1.71±0.488 0.001 a Intragroup comparisons p-value X A-C 0.001 A-C 0.001 B-A 0.020 A-B 0.020 C-B 0.314 B-C 0.314 14 th d 2.14±0.9 2±0.577 2.43±0.535 0.510 a 21 th d 1.86±0.690 1.57±0.535 2.29±0.488 0.093 a Control Rosa damascena Centella asiaca p 7 th d 1.29±0.488 1.43±0.535 1.57±0.535 0.598 a 14 th d 1.43±0.535 1.86±0.378 2 0.029 a Intragroup comparisons p-value X A-C 0.114 C-A 0.114 B-A 0.029 A-B 0.029 C-B 0.762 B-C 0.762 21 th d 1.57±0.535 1.71±0.488 1.57±0.535 0.840 a A-C : P-value in the comparison between the control group and the Rosa damascena group, A-B : P-value in the comparison between the control group and the Centella asiaca group, B-C : In the comparison between the Rosa damascena group and the Centella asiaca group, the p-value was, a: ANOVA test, x: Evaluaon according to the intra-group post hoc Tukey test on day 14. VEGF: Vascular Endothelial Growth Factor. In Zang and Lineweaver [35] study on the eﬀect of VEGF on the survival of ﬂaps and skin graﬅs, they reported that VEGF levels increased and new blood vessel formaon occurred in the Centella asiaca group.Instead of Kim et al. [19] reported that Rosa damascena triggered more new blood vessel formaon than the control groups in an excisional wound model. In a study comparing the eﬀect of Centella asiaca on skin ﬂap survival in rats with a control group, it was demonstrated that Centella asiaca had improved microcirculaon and exhibited higher VEGF expression [36]. It was revealed that the ﬁndings of our study were consistent with the literature. In this study, VEGF uptake was found to be opmal in the Rosa damascena group on d 7, and the Rosa damascena group and Centella asiaca group were found to be stascally signiﬁcantly superior to the control group. VEGF density was found to be stascally signiﬁcantly higher in the Centella asiaca group compared to the control group on d 14. CONCLUSION Macroscopic examinaons revealed that Rosa damascena extract yielded beer results than Centella asiaca in wound healing. Microscopic evaluaon showed that the group treated with Rosa damascena extract yielded similar results to the Centella asiaca group. When evaluang our macroscopic and microscopic ﬁndings as a whole, we believe that Rosa damascena extract may contribute to wound healing more eﬀecvely than Centella asiaca ointment, and we recommend that studies in this ﬁeld be supported by more comprehensive studies. Conﬂict of interest The authors declare no conﬂicts of interest regarding this arcle’s research, authorship, and/or publicaon. BIBLIOGRAPHIC REFERENCES [1] Armstrong DG, Boulton AJM, Bus SA. Diabec foot ulcers and their recurrence. N. Engl. J. Med. 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Acute and sustained eﬀects of vascular endothelial growth factor on survival of ﬂaps and skin graﬅs. Ann. Plast. Surg. [Internet]. 2011; 66(5):581-582. doi: hps://doi.org/cbx3mf [36] Feng X, Huang D, Lin D, Zhu L, Zhang M, Chen Y, Wu F. Eﬀects of asiacoside treatment on the survival of random skin ﬂaps in rats. J. Invest. Surg. [Internet]. 2021; 34(1):107-117. doi: hps://doi.org/g62z5v 7 of 7