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Biomaterials Developed with an Oxyresveratrol-Rich Artocarpus lakoocha Extract Exhibiting High Phenolic and Flavonoid Contents, Strong Antioxidant Activity, and In Vitro Fibroblast Compatibility

Yıl 2025, Cilt: 8 Sayı: 4, 486 - 493, 31.12.2025
https://doi.org/10.36516/jocass.1743614
https://izlik.org/JA96EH54DZ

Öz

Aim: Wounds pose significant clinical challenges due to delayed healing and a high risk of infection. Advanced biomaterials that provide structural support and are enriched with bioactive compounds offer promising solutions. The aim of this study was to determine the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activities (DPPH) of biomaterials enriched with extracts derived from Artocarpus lakoocha (A. lakoocha), which were identified as Oxyresveratrol-rich based on LC–MS Q-TOF phenolic profiling; and to evaluate the effects of these biomaterials on cytotoxicity, cell adhesion, and cytoskeletal organization using NIH-3T3 fibroblast cells in vitro.
Methods: Extracts of A. lakoocha were prepared and analyzed for TPC, TFC, antioxidant activity using the DPPH assay, and phenolic profiling by LC–MS Q-TOF. Biomaterials enriched with the extract were fabricated using an appropriate synthesis approach. Cytocompatibility was evaluated in NIH-3T3 cells by MTT assay at 24, 48, and 72 hours, and immunofluorescence imaging was performed to examine cell adhesion and cytoskeletal organization.
Results: The A. lakoocha extract exhibited high phenolic (541.3 ± 14.1 mg GAE/g) and flavonoid (96.3 ± 5.1 mg QE/g) contents, along with strong antioxidant activity (IC₅₀ = 98.03 ± 0.57 µg/mL). LC–MS Q-TOF analysis revealed Oxyresveratrol as the predominant phenolic compound in the extract. Extract-enriched biomaterials exhibited porous structures with high surface area and maintained excellent swelling capacity (>415%). The MTT assay demonstrated a significant increase in cell viability, particularly at 48 hours (approximately 12.9% increase). Immunofluorescence imaging revealed enhanced F-actin organization and improved intercellular interactions.
Conclusions: Biomaterials enriched with A. lakoocha extract and rich in Oxyresveratrol demonstrated favorable physicochemical properties, strong antioxidant activity, and superior cytocompatibility, indicating strong potential as advanced wound dressings. Further in vivo studies are recommended to confirm therapeutic efficacy.

Destekleyen Kurum

The work was supported by Adana Alparslan Türkeş Science and Technology University Scientıfic Research Projects Coordınation Unit (Grant Number: 24303002 | Recipient: Sibel ÖZDAŞ, PhD).

Proje Numarası

24303002

Kaynakça

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  • 3.Fluhr JW, Feingold KR, Elias PM. Transepidermal water loss reflects permeability barrier status: validation in human and rodent in vivo and ex vivo models. Exp Dermatol. 2006;15(7):483-92. [Crossref]
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  • 7.Wang D, Cui F, Xi L, Tan X, Li J, Li T. Preparation of a multifunctional non-stick tamarind polysaccharide-polyvinyl alcohol hydrogel immobilized with a quorum quenching enzyme for maintaining fish freshness. Carbohydr Polym. 2023;302:120382. [Crossref]
  • 8.Peppas NA, Hilt JZ, Khademhosseini A, Langer R. Hydrogels in biology and medicine: From molecular principles to bionanotechnology. Adv Mater. 2006;18(11):1345-1360. [Crossref]
  • 9.Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer. 2008;49(8):1993-2007. [Crossref]
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  • 11.Boateng J, Catanzano O. Advanced therapeutic dressings for effective wound healing—a review. J Pharm Sci. 2015;104(11):3653-3680. [Crossref]
  • 12.Okay O. Macroporous copolymer networks. Prog Polym Sci. 2010;35(7):777-819.
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  • 27.Teanpaisan R, Senapong S, Puripattanavong J. In vitro antimicrobial and antibiofilm activity of Artocarpus lakoocha (Moraceae) extract against some oral pathogens. Tropical Journal of Pharmaceutical Research. 2014;13(7):1149-1155. [Crossref]
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  • 31.Razavi M, Hu S, Thakor AS. A collagen based cryogel bioscaffold coated with nanostructured polydopamine as a platform for mesenchymal stem cell therapy. J Biomed Mater Res A. 2018;106(8):2213-2228. [Crossref]
  • 32.Canatar I, Özdaş S, Baydemir Peşint G. Phyllanthus emblica‐Loaded Cryogels for Improved Wound Care: Characterization and In Vitro Studies. Macromolecular Materials and Engineering. 2024;309(4):2300404. [Crossref]
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  • 35.Yılmaz Ü, Seyhan MF. Effect of Ellagic Acid and Cryptotanshinone on Cell Viability/Cytotoxicity, Metastasis, and Oxidative Stress in Triple-Negative Breast Cancer Cells. Experimed. 2024;14(1):46-53. [Crossref]
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Oksiresveratrol Açısından Zengin Artocarpus lakoocha Ekstraktı ile Geliştirilen, Yüksek Fenolik ve Flavonoid İçeriğe Sahip, Güçlü Antioksidan Aktivite Gösteren ve In Vitro Fibroblast Uyumluluğu Sergileyen Biyomalzemeler

Yıl 2025, Cilt: 8 Sayı: 4, 486 - 493, 31.12.2025
https://doi.org/10.36516/jocass.1743614
https://izlik.org/JA96EH54DZ

Öz

Giriş: Yaralar, gecikmiş iyileşme ve yüksek enfeksiyon riski nedeniyle önemli klinik zorluklar oluşturmaktadır. Yapısal destek sağlayan ve biyoaktif bileşikler ile zenginleştirilen ileri biyomalzemeler, umut verici çözümler sunmaktadır. A. lakoocha ekstraktı ile zenginleştirilmiş ve fenolik profili oksiresveratrolün baskın bileşen olduğunu gösteren biyomalzemeler; uygun fizikokimyasal özellikleri, güçlü antioksidan aktiviteleri ve yüksek sitouyumlulukları ile gelişmiş yara örtüleri için umut verici bir potansiyel sunmaktadır. Bununla birlikte, biyolojik etkinliğin ve klinik uygulanabilirliğin doğrulanabilmesi için ileri in vivo çalışmaların yapılması gerekmektedir.
Materyal ve Metot: A. lakoocha ekstresi hazırlanarak TPC, TFC, DPPH testi ve LC–MS Q-TOF analizleri gerçekleştirilmiştir. Ekstre ile zenginleştirilmiş biyomalzemeler uygun bir sentez yaklaşımı kullanılarak hazırlanmıştır. Sitouyumluluk, NIH-3T3 hücrelerinde 24, 48 ve 72. saatlerde MTT testi ile değerlendirilmiş; hücre adezyonu ve hücre iskelet organizasyonunu incelemek amacıyla immünofloresan görüntüleme yapılmıştır.
Bulgular: A. lakoocha ekstresi yüksek fenolik (541,3 ± 14,1 mg GAE/g) ve flavonoid (96,3 ± 5,1 mg QE/g) içeriğe ve güçlü antioksidan aktiviteye (IC₅₀ = 98,03 ± 0,57 µg/mL) sahip bulunmuştur. LC–MS Q-TOF analizi, Oksiresveratrolün ekstraktın baskın fenolik bileşeni olduğunu ortaya koymuştur. Ekstre ile zenginleştirilmiş biyomalzemeler yüksek yüzey alanına sahip gözenekli yapılar sergilemiş ve yüksek şişme kapasitesini (> %415) korumuştur. MTT testi, özellikle 48. saatte (yaklaşık %12,9 artış) hücre canlılığında anlamlı bir artış olduğunu göstermiştir. İmmünofloresan görüntüleme, F-aktin organizasyonunun ve hücreler arası etkileşimlerin belirgin şekilde geliştiğini ortaya koymuştur.
Sonuç: Artocarpus lakoocha ekstraktı ile zenginleştirilmiş, Oksiresveratrol açısından zengin biyomalzemeler; uygun fizikokimyasal özellikleri, güçlü antioksidan aktiviteleri ve üstün sitouyumlulukları ile gelişmiş yara örtüleri için güçlü bir potansiyel sunmaktadır. Terapötik etkinliğin doğrulanması için ileri in vivo çalışmalar önerilmektedir.

Proje Numarası

24303002

Kaynakça

  • 1.Proksch E, Brandner JM, Jensen JM. The skin: an indispensable barrier. Exp Dermatol. 2008;17(12):1063-72. [Crossref]
  • 2.Engebretsen KA, Johansen JD, Kezic S, Linneberg A, Thyssen JP. The effect of environmental humidity and temperature on skin barrier function and dermatitis. J Eur Acad Dermatol Venereol. 2016;30(2):223-49. [Crossref]
  • 3.Fluhr JW, Feingold KR, Elias PM. Transepidermal water loss reflects permeability barrier status: validation in human and rodent in vivo and ex vivo models. Exp Dermatol. 2006;15(7):483-92. [Crossref]
  • 4.Elias PM. Stratum cornum defensive functions: An integrated view. J Invest Dermatol. 2005;125(2):183-200. [Crossref]
  • 5.Yao Z, Niu J, Cheng B. Prevalence of chronic skin wounds and their risk factors in an inpatient hospital setting in northern China. Adv Skin Wound Care. 2020;33(9):1-10. [Crossref]
  • 6.Sawadkar P, Lali F, Garcia-Gareta E, Garrido BG, Chaudhry A, Matharu P, et al. Innovative hydrogels in cutaneous wound healing: current status and future perspectives. Front Bioeng Biotechnol. 2025;13:1454903. [Crossref]
  • 7.Wang D, Cui F, Xi L, Tan X, Li J, Li T. Preparation of a multifunctional non-stick tamarind polysaccharide-polyvinyl alcohol hydrogel immobilized with a quorum quenching enzyme for maintaining fish freshness. Carbohydr Polym. 2023;302:120382. [Crossref]
  • 8.Peppas NA, Hilt JZ, Khademhosseini A, Langer R. Hydrogels in biology and medicine: From molecular principles to bionanotechnology. Adv Mater. 2006;18(11):1345-1360. [Crossref]
  • 9.Hoare TR, Kohane DS. Hydrogels in drug delivery: Progress and challenges. Polymer. 2008;49(8):1993-2007. [Crossref]
  • 10.Ahmed EM. Hydrogel: Preparation, characterization, and applications: A review. J Adv Res. 2015;6(2):105-121. [Crossref]
  • 11.Boateng J, Catanzano O. Advanced therapeutic dressings for effective wound healing—a review. J Pharm Sci. 2015;104(11):3653-3680. [Crossref]
  • 12.Okay O. Macroporous copolymer networks. Prog Polym Sci. 2010;35(7):777-819.
  • 13.Lozinsky VI. Cryogels: Applications in biotechnology and medicine. Gels. 2022;8(1):1-41.
  • 14.Memic A, Abudula T, Mohammed HS, Joshi Navare K, Colombani T, Bencherif SA. Latest advances in cryogel technology for biomedical applications. Adv Ther. 2019;2(4):1800114. [Crossref]
  • 15.Gun'ko VM, Savina IN, Mikhalovsky SV. Cryogels: Morphological, structural and adsorption characterization. Adv Colloid Interface Sci. 2017;246:1-39.
  • 16.Verheij EWM, Coronel RE. Plant Resources of South-East Asia No. 2. Edible Fruits and Nut. Prosea, Bogor, Indonesia. 1992.
  • 17.Perry LM. Medicinal plants of East and Southeast Asia: Attributed properties and uses. MIT Press. 1980. 18.Jagtap UB, Bapat VA. Artocarpus: A review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol. 2010;129(2):142-166. [Crossref]
  • 19.Likhitwitayawuid K, Sritularak B, Benchanak K, Lipipun V, Mathew J, Schinazi RF. Phenolics with antiviral activity from Millettia erythrocalyx and Artocarpus lakoocha. Nat Prod Res. 2005;19(2):177-182. [Crossref]
  • 20.Tsai MH, Liu JF, Chiang YC, Hu SC, Hsu LF, Lin YC, et al. Artocarpin, an isoprenyl flavonoid, induces p53-dependent or independent apoptosis via ROS-mediated MAPKs and Akt activation in non-small cell lung cancer cells. Oncotarget. 2017;8(17):28342-28358. [Crossref]
  • 21.Palanuvej C, Ruangrungsi N, Vacharabhongsa P, Boonarkart C. Pharmacognostic study of Artocarpus lakoocha heartwood. Journal of Health Research. 2007;21(4):257-262.
  • 22.Nazliniwaty N, Hanafiah OA, Pertiwi D, Muhammad M, Satria D. The activity of combination of ethanol extract of Artocarpus lacucha Buch.-Ham and Anredera cordifolia Steenis leaves to increase wound healing process on NIH-3T3 cell line. Open Access Maced J Med Sci. 2022;10:807-811. [Crossref]
  • 23.Tanjung SA, Silalahi J, Reveny J. Wound Healing Activity of Nanoemulgel Containing Artocarpus lakoocha Roxb. Extract on Burns Model in Rat. Open Access Maced J Med Sci. 2022;10(A):725-733. [Crossref]
  • 24.Hanafiah OA, Hanafiah DS, Dohude GA, Satria D, Putri MS, Harahap NIJ. Effects of 3% Mobe (Artocarpus lakoocha) leaf extract gel on the post-extraction socket: In-vivo study. Dental Journal (Majalah Kedokteran Gigi). 2024;57(2):102-109. [Crossref]
  • 25.Senapong S, Puripattanavong J, Teanpaisan R. Anticandidal and antibiofilm activity of Artocarpus lakoocha extract. Songklanakarin Journal of Science & Technology. 2014;36(4).
  • 26.Kaewkod T, Tragoolpua K, Tragoolpua Y. Encapsulation of Artocarpus lacucha Roxb. extract in alginate chitosan nanoparticles for inhibition of methicillin-resistant Staphylococcus aureus and bacteria causing skin diseases. Chiang Mai Journal of Science. 2016;43:946-958.
  • 27.Teanpaisan R, Senapong S, Puripattanavong J. In vitro antimicrobial and antibiofilm activity of Artocarpus lakoocha (Moraceae) extract against some oral pathogens. Tropical Journal of Pharmaceutical Research. 2014;13(7):1149-1155. [Crossref]
  • 28.Singleton VL, Rossi JA. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. American journal of Enology and Viticulture. 1965;16(3):144-158. [Crossref]
  • 29.Zhishen J, Mengcheng T, Jianming W. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food chemistry. 1999;64(4):555-559. [Crossref]
  • 30.Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958;181(4617):1199-1200. [Crossref]
  • 31.Razavi M, Hu S, Thakor AS. A collagen based cryogel bioscaffold coated with nanostructured polydopamine as a platform for mesenchymal stem cell therapy. J Biomed Mater Res A. 2018;106(8):2213-2228. [Crossref]
  • 32.Canatar I, Özdaş S, Baydemir Peşint G. Phyllanthus emblica‐Loaded Cryogels for Improved Wound Care: Characterization and In Vitro Studies. Macromolecular Materials and Engineering. 2024;309(4):2300404. [Crossref]
  • 33.Van Tonder A, Joubert AM, Cromarty AD. Limitations of the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay when compared to three commonly used cell enumeration assays. BMC Res Notes. 2015;8(1):47. [Crossref]
  • 34.Foo JB, Ng LS, Lim JH, Tan PX, Lor YZ, Loo JSE, et al. Induction of cell cycle arrest and apoptosis by copper complex Cu (SBCM) 2 towards oestrogen-receptor positive MCF-7 breast cancer cells. RSC Advances. 2019;9(32):18359-18370. [Crossref]
  • 35.Yılmaz Ü, Seyhan MF. Effect of Ellagic Acid and Cryptotanshinone on Cell Viability/Cytotoxicity, Metastasis, and Oxidative Stress in Triple-Negative Breast Cancer Cells. Experimed. 2024;14(1):46-53. [Crossref]
  • 36.Panichakul T, et al. Phytochemical constituents and biological activities of Artocarpus lakoocha Roxb. Natural Product Research. 2020;34(7):961-964.
  • 37.Tarbiat B. Antioxidant activity of phenolic compounds from Artocarpus lakoocha and their potential health benefits. Journal of Food Science and Technology. 2018;55(7):2625-2633.
  • 38.Ahamad J, Amin S, Mir SR, Ahmad MA, Ahmad W, Anwar F. Antioxidant and antimicrobial activity of heartwood extracts of Artocarpus lakoocha Roxb. Journal of Herbal Medicine. 2020;21:100345.
  • 39.Nazliniwaty N, Dalimunthe A, Sitorus P, Ahamad J. Phytochemical screening and antioxidant activity of Artocarpus lakoocha Roxb. extract. Pharmacognosy Journal. 2021;13(3):664-670.
  • 40.Sitorus P, Dalimunthe A, Nazliniwaty N. Evaluation of antioxidant properties of Artocarpus lakoocha extracts using DPPH and ABTS assays. Journal of Applied Pharmaceutical Science. 2022;12(6):35-41.
  • 41.Chan EWC, Lim YY, Omar M. Antioxidant and antibacterial activity of leaves of Etlingera elatior. Journal of Food Composition and Analysis. 2009;22(5):388-393.
  • 42.Sasidharan S, Chen Y, Saravanan D, Sundram KM, Latha LY. Extraction, isolation and characterization of bioactive compounds from plants' extracts. African journal of traditional, complementary and alternative medicines. 2011;8(1). [Crossref]
  • 43.Dai J, Mumper RJ. Plant phenolics: Extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010;15(10):7313-7352. [Crossref]
  • 44.Rice-Evans CA, Miller NJ, Paganga G. Antioxidant properties of phenolic compounds. Trends in Plant Science. 1997;2(4):152-159. [Crossref]
  • 45.Shahidi F, Ambigaipalan P. Phenolics and polyphenolics in foods, beverages and spices: Antioxidant activity and health effects. Journal of Functional Foods. 2015;18:820-897. [Crossref]
  • 46.Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. European Journal of Medicinal Chemistry. 2015;97:55-74. [Crossref]
  • 47.Baur JA, Sinclair DA. Therapeutic potential of resveratrol: The in vivo evidence. Nature Reviews Drug Discovery. 2006;5(6):493-506. [Crossref]
  • 48.Khameneh B, Iranshahy M, Soheili V, Fazly Bazzaz BS. Review on plant antimicrobials: A mechanistic viewpoint. Antimicrobial Resistance & Infection Control. 2019;8(1):1-28. [Crossref]
  • 49.Hankittichai P, Buacheen P, Pitchakarn P, Na Takuathung M, Wikan N, Smith DR, et al. Artocarpus lakoocha extract inhibits LPS-induced inflammatory response in RAW 264.7 macrophage cells. International Journal of Molecular Sciences. 2020;21(4):1355. [Crossref]
  • 50.Choi EJ, et al. Oxyresveratrol promotes cutaneous wound healing in rats. Phytotherapy Research. 2014;28(3):441-447.
  • 51.Boateng JS, Matthews KH, Stevens HNE, Eccleston GM. Wound healing dressings and drug delivery systems: A review. Journal of Pharmaceutical Sciences. 2008;97(8):2892-2923. [Crossref]
  • 52.Kamoun EA, Kenawy E-RS, Chen X. A review on polymeric hydrogel membranes for wound dressing applications. Materials Science and Engineering: C. 2017;77:1301-1312.
  • 53.Gopi S, George R, Thomas S. Polymeric biomaterials in wound healing: An overview. Polymers for Advanced Technologies. 2016;27(6):844-854.
  • 54.Canatar İ, Zenger O, Özdaş S, Baydemir Peşint G. Pterostilbene loaded poly (vinyl alcohol)‐gelatin cryogels as potential bioactive wound dressing material. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2023;111(6):1259-1270. [Crossref]
  • 55.Górska A, Krupa A, Majda D, et al. Poly(vinyl alcohol) cryogel membranes loaded with resveratrol as potential active wound dressings. Materials & Applications in Medicine and Engineering. 2021. [Crossref]
  • 56.Kolósova OY, Vasil'ev VG, Novikov IA, Sorokina EV, Lozinsky VI. Cryostructuring of polymeric systems: Properties and microstructure of PVA cryogels formed in the presence of phenolic compounds. Polymers. 2024;16(5):675. [Crossref]
  • 57.He Q, Feng T, Xie Y, Swamiappan S, Zhou Y, Zhou Y, et al. Recent Advances in the Development and Application of Cell-Loaded Collagen Scaffolds. International Journal of Molecular Sciences. 2025;26(9):4009. [Crossref]
  • 58.Zheng Y, Liu H. Influence of phenolic compounds on cryogel pore morphology. Cryobiology Journal. 2022.
  • 59.Sezen S, et al. Macroporous cryogels in biomaterials: Structure-function relationships. Journal of Biomaterials Science. 2021.
  • 60.Medeiros SF, Silva FE. Hydrogel dressings: A review. Journal of Advanced Research. 2021;6(2):105-121.
  • 61.Cañedo-Dorantes L, Cañedo-Ayala M. Skin acute wound healing: A comprehensive review. International Journal of Inflammation. 2019;2019:3706315. [Crossref]
Toplam 60 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Genel Cerrahi, Harp Cerrahisi
Bölüm Araştırma Makalesi
Yazarlar

Ahmet Burak Altunsöz 0009-0009-9266-0981

İpek Canatar 0000-0001-9448-8112

Sibel Ozdas 0000-0003-4610-2785

Gözde Baydemir Peşint 0000-0001-8668-8296

Proje Numarası 24303002
Gönderilme Tarihi 4 Ağustos 2025
Kabul Tarihi 30 Aralık 2025
Yayımlanma Tarihi 31 Aralık 2025
DOI https://doi.org/10.36516/jocass.1743614
IZ https://izlik.org/JA96EH54DZ
Yayımlandığı Sayı Yıl 2025 Cilt: 8 Sayı: 4

Kaynak Göster

APA Altunsöz, A. B., Canatar, İ., Ozdas, S., & Baydemir Peşint, G. (2025). Biomaterials Developed with an Oxyresveratrol-Rich Artocarpus lakoocha Extract Exhibiting High Phenolic and Flavonoid Contents, Strong Antioxidant Activity, and In Vitro Fibroblast Compatibility. Journal of Cukurova Anesthesia and Surgical Sciences, 8(4), 486-493. https://doi.org/10.36516/jocass.1743614
https://dergipark.org.tr/tr/download/journal-file/11303