Polat İPEK1 ,
Ayşe BARAN 2 ,
Mehmet Fırat BARAN 3 ,
Mahmut YILDIZTEKİN 4 ,
Aziz EFTEKHARI5 ,
Musa KARADAĞ 6 ,
Behzat TEBRİZİ 7 ,
Mehmet Nuri ATALAR 8
1 Dicle University, Faculty of Veterinary Medicine, Department of Physiology, Diyarbakır, Türkiye
2 Mardin Artuklu University, Kiziltepe Faculty of Agricultural Sciences and Technologies, Field Crops Department, Field Crops Department, Mardin, Türkiye
3 Batman University, Vocational School of Technical Sciences, Department of Food Technology, Batman, Türkiye
4 Muğla Sıtkı Kocman University, Koycegiz Vocational School, Department of Herbal and Animal Production, Muğla, Türkiye
5 Ege University, Faculty of Science, Department of Biochemistry, İzmir, Türkiye
6 Iğdır University, Iğdır Technical Sciences Vocational School, Department of Chemistry and Chemical Processing Technologies, Cosmetics Technology Program, Iğdır, Türkiye
7 Dicle University, Faculty of Veterinary Medicine, Department of Pathology, Diyarbakır, Türkiye
8 Iğdır University, Faculty of Health Sciences, Department of Nutrition and Dietetic, Iğdır, Türkiye
Abstract
Several studies report that different parts of the Pistacia vera L. plant effectively heal wounds. However, there is no documented scientific report on Pistacia vera L. hull's in vivo wound healing activities so far. This study evaluates the wound healing efficacy of ointment prepared from the extract obtained from the peels of P. vera L. fruits collected from Turkey through an excision wound model. The ointment was prepared with 0.5% methanolic extract obtained from P. vera L. hull was applied topically on the wound excision created on the back of rats. Wound healing effects were evaluated by wound closure percentage. The samples taken after healing examined the effect of P. vera L. hull on the protein expression levels of TNF-α, an inflammation marker, and some growth factors involved in wound healing. Compared to the other groups, P. vera L. hull ointment showed significant wound healing on the 21st day. TNF-α showed lower protein expression levels than the untreated and vehicle control groups. Bek, VEGF, and FGFR protein expression levels were lower than all groups. These results confirmed the wound closure percentages of the relevant tissues. The study suggested that P.vera L. hull shortens the wound healing period and is a potential agent in wound treatment.
Keywords
Bek,EGFR,Pistacia vera L. hull,TNF-α,VEGF,Western blot,Wound healing
How to Cite
İPEK, P., BARAN , A., BARAN , M. F., YILDIZTEKİN , M., EFTEKHARI, A., KARADAĞ , M., TEBRİZİ , B., & ATALAR , M. N. (2026). Evaluation of in Vivo Wound Healing Activity of Pistacia vera L. Hull Extract on Excision Wound Model in Rats. MAS Journal of Applied Sciences, 11(2), 206–221. https://doi.org/10.5281/zenodo.20303049
📄Aburjai, T., Natsheh, F.M., 2003. Plants used in cosmetics. Phytotherapy Research, 17(9): 987–1000.
📄Arndt, S., Unger, P., Berneburg, M., Bosserhoff, A.K., Karrer, S., 2018. Cold atmospheric plasma (CAP) activates angiogenesis-related molecules in skin keratinocytes, fibroblasts and endothelial cells and improves wound angiogenesis in an autocrine and paracrine mode. Journal of Dermatological Science, 89(2): 181-190.
📄Beg, S., Swain, S., Hasan, H., Barkat, M.A., Hussain, M.S., 2011. Systematic review of herbals as potential anti-inflammatory agents: Recent advances, current clinical status and future perspectives. Pharmacognosy Reviews, 5(10): 120-137.
📄Ben Khedir, S., Mzid, M., Bardaa, S., Moalla, D., Sahnoun, Z., Rebai, T., 2016. In vivo evaluation of the anti‐inflammatory effect of pistacia lentiscus fruit oil and its effects on oxidative stress. Evidence‐Based Complementary and Alternative Medicine, 2016(1): 6108203.
📄Bosanquet, D.C., Harding, K.G., 2014. Wound duration and healing rates: Cause or effect? Wound Repair and Regeneration, 22(2): 143–150.
📄Bozorgi, M., Memariani, Z., Mobli, M., Salehi Surmaghi, M.H., Shams-Ardekani, M.R., Rahimi, R., 2013. Five Pistacia species (P. vera, P. atlantica, P. terebinthus, P. khinjuk, and P. lentiscus): a review of their traditional uses, phytochemistry, and pharmacology. The Scientific World Journal, 2013(1): 219815.
📄Cañedo-Dorantes, L., Cañedo-Ayala, M. 2019. Skin acute wound healing: A comprehensive review. International Journal of Inflammation, 2019: 3706315.
📄Catalani, S., Palma, F., Battistelli, S., Nuvoli, B., Galati, R., Benedetti, S., 2017. Reduced cell viability and apoptosis induction in human thyroid carcinoma and mesothelioma cells exposed to cidofovir. Toxicology in Vitro, 41: 49-55.
📄Chandra, P., Faizan, M., Porwal, M., Sharma, H., Sachan, N., 2026. An overview and review of growth factors in wound healing: emerging trends and innovations. Current Diabetes Reviews, 22(1): E15733998332692.
📄Childs, D.R., Murthy, A.S., 2017. Overview of wound healing and management. Surgical Clinics of North America, 97(1): 189–207.
📄Chuhuaicura, P., Rodríguez-Niklitschek, C., Oporto, G.H., Salazar, L.A., 2025. Distinct molecular mechanisms in oral mucosal wound healing: translational insights and future directions. International Journal of Molecular Sciences, 26(21): 10660.
📄Cui, J., Xu, F., Bai, W., Zhao, T., Hong, J., Zuo, W., 2023. HDAC inhibitor ITF2357 reduces resistance of mutant-KRAS non-small cell lung cancer to pemetrexed through a HDAC2/miR-130a-3p-dependent mechanism. Journal of Translational Medicine, 21(1): 125.
📄Dabiri, G., Damstetter, E., Phillips, T., 2016. Choosing a wound dressing based on common wound characteristics. Advances in Wound Care, 5(1): 32–41.
📄Datta, S., Bhattacharjee, S., Seal, T., 2022. Anti-diabetic, anti-inflammatory and anti-oxidant properties of four underutilized ethnomedicinal plants of West Bengal, India: An in vitro approach. South African Journal of Botany, 149: 768–780.
📄Masi, E.C.D.J.D., Campos, A.C.L., Masi, F.D. J.D., Ratti, M.A.S., Shin Ike, I., Masi, R.D. J.D., 2016. The influence of growth factors on skin wound healing in rats. Brazilian Journal of Otorhinolaryngology, 82(05): 512-521.
📄Djerrou, Z., Maameri, Z., Hamdi-Pacha, Y., Serakta, M., Riachi, F., Djaalab, H., Boukeloua, A., 2010. Effect of virgin fatty oil of Pistacia lentiscus on experimental burn wound's healing in rabbits. African Journal of Traditional, Complementary, and Alternative Medicines, 7(3): 258.
📄Eming, S.A., Wynn, T.A., Martin, P., 2021. Inflammation and metabolism in tissue repair and regeneration. Science, 356(6342): 1026–1030.
📄Farahpour, M.R., Mirzakhani, N., Doostmohammadi, J., Ebrahimzadeh, M., 2015. Hydroethanolic Pistacia atlantica hulls extract improved wound healing process; evidence for mast cells infiltration, angiogenesis and RNA stability. International Journal of Surgery, 17: 88-98.
📄Farooq, M., Hwang, M., Khan, A.W., Batool, M., Ahmad, B., Kim, W., Kim M.S. Choi, S., 2025. Identification of a novel fibroblast growth factor receptor-agonistic peptide and its effect on diabetic wound healing. Life Sciences, 364: 123432.
📄Gentile, C., Allegra, M., Angileri, F., Pintaudi, A.M., Livrea, M.A., Tesoriere, L., 2012. Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. European Journal of Nutrition, 51(3): 353-363.
📄Gökçimen, A., Özgüner, M., Bayram, D., Ural, M., Sulak, O., 2009. Effects of metamizol sodium on liver, kidney and lung tissues of the rat. Medical Journal of Süleyman Demirel University, 13(1): 27–31.
📄Grace, M.H., Esposito, D., Timmers, M.A., Xiong, J., Yousef, G., Komarnytsky, S., Lila, M.A., 2016. In vitro lipolytic, antioxidant and anti-inflammatory activities of roasted pistachio kernel and skin constituents. Food & Function, 7(10): 4285-4298.
📄Gupta, N., Jain, U., 2011. Investigation of wound healing activity of methanolic extract of stem bark of Mimusops elengi Linn. African Journal of Traditional, Complementary and Alternative Medicines, 8(2): 98–103.
📄Gupta, R., Gupta, J., 2019. Investigation of antimicrobial activity of Euphorbia hirta leaves. International Journal of Life Sciences Pharma Research, 9(1): 32–37.
📄Han, G., Ceilley, R., 2017. Chronic wound healing: A review of current management and treatments. Advances in Therapy, 34(3): 599–610.
📄Han, H.J., Hyun, C.G., 2023. Acenocoumarol exerts anti-inflammatory activity via the suppression of NF-κB and MAPK pathways in RAW 264.7 cells. Molecules, 28(5): 2075.
📄Hiller, J., Stratmann, B., Timm, J., Costea, T. C., Tschoepe, D. 2022. Enhanced growth factor expression in chronic diabetic wounds treated by cold atmospheric plasma. Diabetic Medicine, 39(6): e14787.
📄Ipek, P., Atalar, M.N., Baran, A., Baran, M.F., Ommati, M.M., Karadag, M., Zor, M., Eftekharii, A., Alma, M.H., Benis, K.Z., Nuriyeva, F., Fidan, Z., Khalilov, R., 2024. Determination of chemical components of the endemic species Allium turcicum L. plant extract by LC-MS/MS and evaluation of medicinal potentials. Heliyon, 10(6).
📄Kang, D., Wang, W., Li, Y., Ma, Y., Huang, Y., Wang, J., 2023. Biological macromolecule hydrogel based on recombinant type I collagen/chitosan scaffold to accelerate full-thickness healing of skin wounds. Polymers, 15(19): 3919.
📄Karadag, M., Doğan, S., 2024. Mask for moisturizing skin and body made from cold-pressed paste of peanuts (Arachis hypogaea L.). Advances in Biology & Earth Sciences, 9(1): 155-60.
📄Karakayalı, E.M., Önal, T., Öztatlıcı, M., Duruşma, R., Çavuşoğlu, T., Kocamaz, E., Tuğlu, M.İ., 2022. Effect of Probiotics on Diabetic Rat Skin Wound Healing. Journal of Celal Bayar University Institute of Health Sciences, 9(1): 151-158.
📄Kaya, Y., 2019. Türkiye’de yaygın olarak bilinen bazı bitki türlerinin özütlerinin elde edilmesi, kozmetik kremlerdeki antimikrobiyal etkisinin incelenmesi. Yüksek Lisans Tezi, Mersin Üniversitesi, Fen Bilimleri Enstitüsü, Mersin.
📄Kim, H.J., Neophytou, C., 2009. Natural anti-inflammatory compounds for the management and adjuvant therapy of inflammatory bowel disease and its drug delivery system. Archives of Pharmacal Research, 32(7): 997–1004.
📄Lambebo, M.K., Kifle, Z.D., Gurji, T.B., Yesuf, J.S., 2021. Evaluation of wound healing activity of methanolic crude extract and solvent fractions of the leaves of Vernonia auriculifera Hiern (Asteraceae) in mice. Journal of Experimental Pharmacology, 677-692.
📄Landén, N. X., Li, D., Ståhle, M., 2016. Transition from inflammation to proliferation: A critical step during wound healing. Cellular and Molecular Life Sciences, 73(20): 3861–3885.
📄Mandalari, G., Barreca, D., Gervasi, T., Roussell, M.A., Klein, B., Feeney, M.J., Carughi, A. 2021. Pistachio nuts (Pistacia vera L.): Production, nutrients, bioactives and novel health effects. Plants, 11(1): 18.
📄Minaiyan, M., Karimi, F., Ghannadi, A., 2015. Anti-inflammatory effect of Pistacia atlantica subsp. kurdica volatile oil and gum on acetic acid-induced acute colitis in rat. Research in Pharmaceutical Sciences, 10(1): 1–12.
📄Mokhtare, B., Saglam, Y.S., 2025. Investigation of zingerone’s effects on wound healing in induced diabetic rats model. Archives of Dermatological Research, 317: 484.
📄Naouar, M.S., Mekki, L.Z., Charfi, L., Boubaker, J., Filali, A., 2016. Preventive and curative effect of Pistacia lentiscus oil in experimental colitis. Biomedicine & Pharmacotherapy, 83: 577-583.
📄Napoli, E., Boudjelal, A., Benkhaled, A., Chabane, S., Gentile, D., Ruberto, G., 2021. Chemical composition, safety and efficacy of Pistacia vera L. oleoresin essential oils in experimental wounds. Journal of Essential Oil Research, 33(5): 464-470.
📄Papalois, A., Gioxari, A., Kaliora, A.C., Lymperopoulou, A., Agrogiannis, G., Papada, E., Andrikopoulos, N.K., 2012. Chios mastic fractions in experimental colitis: implication of the nuclear factor κB pathway in cultured HT29 cells. Journal of Medicinal Food, 15(11): 974-983.
📄Pastar, I., Stojadinovic, O., Yin, N.C., Ramirez, H., Nusbaum, A.G., Sawaya, A., Tomic-Canic, M., 2014. Epithelialization in wound healing: a comprehensive review. Advances in Wound Care, 3(7): 445-464.
📄Paterniti, I., Impellizzeri, D., Cordaro, M., Siracusa, R., Bisignano, C., Gugliandolo, E., Cuzzocrea, S., 2017. The anti-inflammatory and antioxidant potential of pistachios (Pistacia vera L.) in vitro and in vivo. Nutrients, 9(8): 915.
📄Sarkhail, P., Navidpour, L., Rahimifard, M., Hosseini, N.M., Souri, E., 2020. Bioassay-guided fractionation and identification of wound healing active compound from Pistacia vera L. hull extract. Journal of ethnopharmacology, 248: 112335.
📄Shahouzehi, B., Sepehri, G., Sadeghiyan, S., Masoomi Ardakani, Y., 2018. Effect of Pistacia atlantica resin oil on anti-oxidant, hydroxyprolin and VEGF changes in experimentally-induced skin burn in rat. World Journal of Plastic Surgery, 7(3): 357-365
📄Spyridopoulou, K., Tiptiri-Kourpeti, A., Lampri, E., Fitsiou, E., Vasileiadis, S., Vamvakias, M., Bardouki, H., Goussia, A., Malamou-Mitsi, V., Panayiotidis, M.I., Galanis, A., Pappa, A., Chlichlia, K., 2017. Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models. Scientific Reports, 7(1): 3782.
📄Taghipour, Z., Hassanipour, M., Mohammadian, B., Khanjari, A., Taghizadeh, R., Kaeidi, A., Shamsizadeh, A., Allahtavakoli, M., Fatemi, I., 2018. The effects of the topical administration of Pistacia vera oil on the second-degree burn model in rats. Pistachio and Health Journal, 1(2): 7-11.
📄Takaya, K., Aramaki-Hattori, N., Sakai, S., Okabe, K., Asou, T., Kishi, K., 2022. Fibroblast growth factor 7 suppresses fibrosis and promotes epithelialization during wound healing in mouse fetuses. International Journal of Molecular Sciences, 23(13): 7087.
📄Tottoli, E.M., Dorati, R., Genta, I., Chiesa, E., Pisani, S., Conti, B., 2020. Skin wound healing process and new emerging technologies for skin wound care and regeneration. Pharmaceutics, 12(8): 735.
📄Uchiyama, A., Nayak, S., Graf, R., Cross, M., Hasneen, K., Gutkind, J.S., Brooks, Sr., Morasso, M.I., 2019. SOX2 epidermal overexpression promotes cutaneous wound healing via activation of EGFR/MEK/ERK signaling mediated by EGFR ligands. Journal of Investigative Dermatology, 139(8): 1809-1820.
📄Uyar, A., Akyol, T., Yaman, T., Keleş, Ö.F. 2017. A histopathological and biochemical investigation of the wound healing and oxidative stress effect on the wound model of Achillea millefolium in rats. Van Veterinary Journal, 28(3): 157–163.
📄Werner, S., Grose, R., 2003. Regulation of wound healing by growth factors and cytokines. Physiological Reviews, 83(3): 835–870.
📄Wu, B., Tang, X., Zhou, Z., Ke, H., Tang, S., Ke, R., 2021. RNA sequencing analysis of FGF2-responsive transcriptome in skin fibroblasts. PeerJ, 9: e10671.
📄Yayeh, T., Hong, M., Jia, Q., Lee, Y.C., Kim, H.J., Hyun, E., Kim, T.W., Rhee, M.H., 2012. Pistacia chinensis inhibits NO production and upregulates HO-1 induction via PI-3K/Akt pathway in LPS stimulated macrophage cells. The American Journal of Chinese Medicine, 40(05): 1085-1097.
📄Zhou, S., Li, Z., Li, K., Ye, Y., Liang, H., Wang, N.O., Liu, W., Jiang, J., Chiang, M.Y.M., Chen, A., Xiang, X., Lei, M., 2025. Contact cooling-induced ELOVL4 enhances skin wound healing by promoting the ınflammation-to-proliferation phase transition. International Journal of Biological Sciences, 21(5): 2067.