Potential Effect of Red Algae Content on Fibroblasts and Collagen Type 3 in Oral Mucosa Wound Healing Diabetes-Induced <i>Rattus Norvegicus</i>



  • Rachmi F. Hakim Graduate School of Mathematics and Applied Sciences, Syiah Kuala University, Banda Aceh 23111, Indonesia.
  • Rinaldi Idroes Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Syiah, Kuala University, Banda Aceh 23111, Indonesia.
  • Olivia A. Hanafiah Faculty of Dentistry, University of North Sumatra, Medan, North Sumatera, Indonesia.
  • Binawati Ginting Department of Chemistry, Faculty of Mathematics and Natural Sciences, Syiah, Kuala University, Banda Aceh 23111, Indonesia.
  • Fakhrurrazi Fakhrurrazi Faculty of Dentistry, Syiah Kuala University, Banda Aceh 23111, Indonesia


Rattus Norvegicus, Diabetes, collagen type 3, Fibroblast, Red Algae


Diabetes can lead to abnormalities in the mouth. Diabetes-related oral mucosal disorders are abnormalities associated with impaired salivary gland function and immune system modifications.Red algae are currently of concern because of their potency levels that affect the wound healing process, such as polysaccharides, amino acids, fatty acids, saponins, terpenoids, steroids, flavonoids, tannins, phenols, alkaloids, quinones, terpenoids. This study evaluated the effect of Red algae compositions from Kajhu, Aceh Besar, Indonesia on the oral mucosa wound healing process in diabetes-induced Rattus norvegicus. Red algae extract was produced by the maceration
process with 70% ethanol 25L. Phytochemical and GCMS tests were carried out, to determine Red Algae content. Red algae gel was applied to the oral mucosa incision in diabetic Rattus norvegicus to investigate the wound healing process. The parameters studied included wound healing contraction, epithelialization, fibroblast counts, and collagen type 3. The composition of the red algae (Gracilaria sp.) from Kajhu was dominated (39.80%) Hexadecanoic acid. (9e)-9- octadecanoic acid, (11.34%). 1,2-Benzenedicarboxylic acid (6.7%), followed by Erythritol (6.49%), and Cholesterol (5,12%). The data was analyzed using the ANOVA test with significance
(p <0.05), post hoc test with Tukey HSD. The gel contains a 3% extract of Glacilaria sp. improves wound healing clinically and histologically. During the proliferative phase, the number of fibroblasts increased, the thickness of the epithelium increased, and it showed regular and crosslinked collagen. 

Author Biographies

Rachmi F. Hakim, Graduate School of Mathematics and Applied Sciences, Syiah Kuala University, Banda Aceh 23111, Indonesia.

Faculty of Dentistry, Syiah Kuala University, Banda Aceh 23111, Indonesia

Rinaldi Idroes, Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Syiah, Kuala University, Banda Aceh 23111, Indonesia.

Department of Chemistry, Faculty of Mathematics and Natural Sciences, Syiah, Kuala University, Banda Aceh 23111, Indonesia.


Punthakee Z, Goldenberg R, Katz P. Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome. Can J Diabetes. 2018;42:S10–5.

Spampinato SF, Caruso GI, Pasquale R De, Sortino MA, Merlo S. The Treatment of Impaired Wound Healing in Diabetes : Looking among Old Drugs. 2020;1–17.

Al-Maskari AY, Al-Maskari MY, Al-Sudairy S. Oral manifestations and complications of diabetes mellitus: A review. Sultan Qaboos Univ Med J. 2011;11(2):179–86.

Hu F, Manson J.E, Stampfer MJ, Colditz G, Liu S, Solomon, C G, Willett W C. Diet, Lifestyle, and the Risk of Type 2 Diabetes Mellitus in Women. The New England journal of medicine. 2001; 345 (11). 790-7.

Hakim RF, Fakhrurrazi, Dinni. Effect of Carica papaya Extract toward Incised Wound Healing Process in Mice (Mus musculus) Clinically and Histologically. Evidence-based Complement Altern Med. 2019;2019.

Indurkar MS, Maurya AS, Indurkar S. Oral manifestations of diabetes. Clin Diabetes. 2016;34(1):54–7.

Gandara BK, Morton TH. Non-periodontal oral manifestations of diabetes: A framework for medical care providers. Diabetes Spectr. 2011;24(4):199–205.

Rashmi B, Chinna SK, Rodrigues C, Anjaly D, Bankur PK. Oral Mucosal Changes in Type II Diabetes Mellitus Patients : Case – control Study. 2018;6(June):32–5.

Lim YY, Lee W kang, Genomics C, Namasivayam P, Abdullah JO, Yield A, et al. Sulfated galactans from red seaweeds and their potential applications Sulfated Galactans From Red Seaweeds and Their Potential Applications. Pertanika J Sch Res Rev. 2018;4(March):1–17.

Bleakley S and maria hayes. Algal Proteins: Extraction, Application, and Challenges Concerning Production. Foods. 2017;6(33):1–34.

Foseid L, Devle H, Stenstrøm Y, Naess-Andresen CF, Ekeberg D. Fatty Acid Profiles of Stipe and Blade from the Norwegian Brown Macroalgae Laminaria hyperborea with Special Reference to Acyl Glycerides, Polar Lipids, and Free Fatty Acids . J Lipids. 2017;2017:1–9.

Gamero-Vega G, Palacios-Palacios M, Quitral V. Nutritional Composition and Bioactive Compounds of Red Seaweed: A Mini-Review. J Food Nutr Res. 2020;8(8):431–40.

Kurniasari KDWI, Arsianti A, Nugrahayning Aziza YA, Dyahningrum Mandasari BK, Masita R, Ruhama Zulfa F, Kusumaning Dewi, M., Zahira Zagloel, C. R., Azizah, N. N. U. R., & Putrianingsih, R. Phytochemical analysis and anticancer activity of seaweed Gracilaria verrucosa against

colorectal HCT-116 cells. Orient J Chem. 2018;34(3):1257–62.

Hakim RF, Rezeki FS, Sari LM, Marfirah Z. Hemostatic and wound healing effects of Gracilaria verrucosa extract gel in albino rats. Trop J Nat Prod Res. 2020;4(11):912–7.

Aprinaldi B, Idacahyati K, Lestari T. Skrining Fitokimia Dan Uji Aktivitas Ekstrak Etanol Rumput Laut Merah ( Gracilaria Verrucosa ) Terhadap Penyembuhan Luka Sayat Pada Tikus Jantan galur Wistar. J Pharmacopolium. 2020;3(1):36–42.

Guimarães I, Baptista-Silva S, Pintado M, Oliveira AL. Polyphenols: A promising avenue in therapeutic solutions for wound care. Appl Sci. 2021;11(3):1–20.

Orlowski P, Zmigrodzka M, Tomaszewska E, RanoszekSoliwoda K, Czupryn M, Antos-Bielska M, et al. Tannic acid-modified silver nanoparticles for wound healing: The importance of size. Int J Nanomedicine. 2018;13:991–1007.

Chuah X, Okechukwu P, Amini F, Teo S. Eicosane, pentadecane and palmitic acid: The effects in in vitro wound healing studies. Asian Pac J Trop Biomed. 2018;8(10):490–9.

Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci. 2016 Oct;73(20):3861-85. doi: 10.1007/s00018-016-2268-0. Epub 2016 May 14. PMID: 27180275; PMCID: PMC5021733.

Salas-Arias K, Irías-Mata A, Sánchez-Kopper A, HernándezMoncada R, Salas-Morgan B, Villalta-Romero F, CalvoCastro LA. Strawberry Fragaria x ananassa cv. Festival: A Polyphenol-Based Phytochemical Characterization in Fruit and Leaf Extracts. Molecules. 2023 Feb 16;28(4):1865. doi:10.3390/molecules28041865. PMID: 36838852; PMCID: PMC9966301;

Iron PN zero V, Abdelfatah AM, Fawzy M, El-khouly ME. Efficient Adsorptive Removal of Tetracycline from Aqueous Solution using Efficient adsorptive removal of tetracycline from aqueous solution using phytosynthesized nano-zero valent iron. J Saudi Chem Soc [Internet].

;25(12):101365. Available from: https://doi.org/10.1016/j.jscs.2021.101365

Haida S, Bakkouche K, Kribii AR, Kribii A. Chemical Composition of Essential Oil , Phenolic Compounds Content , and Antioxidant Activity of Cistus monspeliensis from Northern Morocco. 2021;2021.

Yakubu OE, Otitoju O, Onwuka J. Gas ChromatographyMass Spectrometry (GC-MS) Analysis of Aqueous Extract of Daniellia oliveri Stem Bark. Pharm Anal Acta. 2017;8(11).

Hanafiah OA, Hanafiah DS, Dohude GA, Satria D, Livita L, Moudy NS, et al. Effects of 3% binahong (Anredera cordifolia) leaf extract gel on alveolar bone healing in postextraction tooth socket wound in Wistar rats (Rattus norvegicus). F1000Research. 2021;10:923.

Firdaus, Marliyati SA, Roosita K. Model Tikus Diabetes Yang Diinduksi Sterptozotocin- Sukrosa Untuk Pendekatan Penelitian Diabetes Melitus Gestasional. J MKMI. 2016;12(1):29–34.

Kim SW, Roh J, Park CS. Immunohistochemistry for pathologists: Protocols, pitfalls, and tips. J Pathol Transl Med. 2016;50(6):411–8.

Salazar JJ, Ennis WJ, Koh TJ. HHS Public Access. 2017;30(4):746–52.

Qing C. The molecular biology in wound healing & nonhealing wound. Chinese J Traumatol - English Ed [Internet]. 2017;20(4):189–93. Available from: http://dx.doi.org/10.1016/j.cjtee.2017.06.001

Mahibalan S, Stephen M, Nethran RT, Khan R, Begum S. Dermal wound healing potency of single alkaloid (betaine) versus standardized crude alkaloid enriched-ointment of Evolvulus alsinoides. Pharm Biol. 2016;54(12):2851–6.

Wicke C, Halliday B, Allen D, Roche NS, Scheuenestuhl H, Spencer MM, et al. Effects of steroids and retinoids on wound healing. Arch Surg. 2000;135(11):1265–70.

Lodhi S, Singhai AK. Wound healing effect of flavonoid rich fraction and luteolin isolated from Martynia annua Linn. on streptozotocin induced diabetic rats. Asian Pac J Trop Med. 2013;6(4):253–9.

Antonia de SL, Laynne H de CL, Davi da S, Livio CCN, Jose ADL. Incorporation of tannic acid in formulations for topical use in wound healing: A technological prospecting. African J Pharm Pharmacol. 2015;9(26):662–74.

Agar OT, Dikmen M, Ozturk N, Yilmaz MA, Temel H, Turkmenoglu FP. Comparative studies on phenolic composition, antioxidant, wound healing and cytotoxic activities of selected achillea L. species growing in Turkey. Molecules. 2015;20(10):17976–8000.

Działo M, Mierziak J, Korzun U, Preisner M, Szopa J, Kulma A. The potential of plant phenolics in prevention and therapy of skin disorders. Int J Mol Sci. 2016;17(2):1–41.

Agra LC, Ferro JNS, Barbosa FT, Barreto E. Triterpenes with healing activity: A systematic review. Journal of Dermatological Treatment. 2015; 26(5):465–470. https://doi.org/10.3109/09546634.2015.1021663

Carta G, Murru E, Banni S, Manca C. Palmitic acid: Physiological role, metabolism and nutritional implications.Front Physiol. 2017;8(NOV):1–14.

Thomas A, Kadam A, Jiwane R, Nanda R, Kothapalli L. Biodegradable macromolecule based topical gels containing natural oils in the management of burn wounds. Pharmacol Drug Dev Ther. 2018;2(1):1–11.

Boesten DMPHJ, den Hartog GJM, de Cock P, Bosscher D, Bonnema A, Bast A. Health effects of erythritol. Nutrafoods. 2015;14(1):3–9.

Edgar S, Hopley B, Genovese L, Sibilla S, Laight D, Shute J. Effects of collagen-derived bioactive peptides and natural antioxidant compounds on proliferation and matrix protein synthesis by cultured normal human dermal fibroblasts. Sci Rep [Internet]. 2018;8(1):1–6. Available from: http://dx.doi.org/10.1038/s41598-018-28492-w

Kopylov AT, Malsagova KA, Stepanov AA, Kaysheva AL. Diversity of plant sterols metabolism: The impact on human health, sport, and accumulation of contaminating sterols. Nutrients. 2021;13(5).

Volunteers H, Shady NH, Altemani AH, Altemani FH, Maher SA, Mohamed NM, et al. The Potential of Corchorus olitorius Seeds Buccal Films for Treatment of Recurrent Minor Aphthous Ulcerations in. 2022;1–27.

Hamidi SA, Tabatabaei Naeini A, Oryan A, Tabandeh MR, Tanideh N, Nazifi S. Pistacia atlantica Jel Formülasyonunun Haricen Uygulamasının Sıçanlarda Oluşturulan Deri Yaraları Üzerindeki İyileştirici Etkisi. Turkish J Pharm Sci. 2017;14(1):65–74.

Weimann E, Silva MBB, Murata GM, Bortolon JR, Dermargos A, Curi R, et al. Topical anti-inflammatory activity of palmitoleic acid improves wound healing. PLoS One. 2018;13(10):1–10.



How to Cite

Hakim, R. F., Idroes, R., Hanafiah, O. A., Ginting, B., & Fakhrurrazi, F. (2023). Potential Effect of Red Algae Content on Fibroblasts and Collagen Type 3 in Oral Mucosa Wound Healing Diabetes-Induced <i>Rattus Norvegicus</i>: http://www.doi.org/10.26538/tjnpr/v7i8.18. Tropical Journal of Natural Product Research (TJNPR), 7(8), 3683–3690. Retrieved from https://tjnpr.org/index.php/home/article/view/2407