Bazı Salvia türlerinin Drosophila melanogaster üzerindeki in vivo gelişimsel ve antioksidan etkileri

Öz

Tıbbi bitkiler, özellikle antioksidan ve antigenotoksik özellikleri nedeniyle uzun zamandır değerli terapötik ajan kaynakları olarak hizmet vermiştir. Zengin biyoçeşitliliği ve farklı iklim koşullarıyla bilinen Türkiye, yaklaşık 400'ü tıbbi potansiyele sahip yaklaşık 10.000 bitki türüne ev sahipliği yapmaktadır. Bunlar arasında, geleneksel olarak gastrointestinal, solunum, kardiyovasküler, böbrek ve bilişsel bozukluklar dahil olmak üzere çok çeşitli rahatsızlıkları tedavi etmek için kullanılan Salvia cinsine ait türler özellikle öne çıkmaktadır. Bu çalışmada, ilk defa Salvia candidissima, S. multicaulis, S. suffruticosa ve S. syriaca'nın su, metanol, etanol ve etil asetat özütlerinin gelişimsel toksisitesi ve in vivo antioksidan aktiviteleri, model organizma olarak Drosophila melanogaster (larva, pupa ve ergin) kullanılarak değerlendirilmiştir. Gelişimsel toksisite, pupalaşma yüzdesi, eklozyon yüzdesi ve genel sağkalım yüzdesi ölçülerek değerlendirilmiştir. In vivo antioksidan aktivite, DPPH, ABTS ve FRAP analizleri kullanılarak belirlenmiştir. Sonuçlar, S. suffruticosa'nın metanolik özütü dışında hiçbir özütünün pupalaşma ve yaşama oranlarını etkilemediğini (p>0,05), diğer bitki özütlerinin ise normal gelişim süreçlerini olumsuz etkilediğini gösterdi. S. suffruticosa'nın tüm özütleri ABTS testine göre yüksek in vivo antioksidan kapasiteler ( %80 aktivite) gösterirken, S. candidissima subsp. candidissima, S. multicaulis ve S. syriaca'nın metanol ve etanol özütleri DPPH testine göre yüksek antioksidan aktiviteler (> %50-70 aktivite) gösterdi. FRAP testi ayrıca, burada S. multicaulis (0.0025-0.0060 g TE/g) ve S. suffruticosa (0.0049-0.0061 g TE/g) için bildirilen Trolox eşdeğer antioksidan kapasitelerinin güçlü antioksidan potansiyeli gösterdiğini gösterdi. İn vivo antioksidan aktivite sonuçlarını özetlemek gerekirse; bu çalışmada, incelenen bitki ekstraktlarının tüm organizmanın fizyolojik antioksidan sistemine (dengesine) zarar vermediği ve incelenen Salvia türlerinin etkili doğal antioksidan takviyelerinin geliştirilmesi için güçlü bir potansiyele sahip olduğu gösterilmiştir.

Anahtar Kelimeler

• Salvia
• gelişimsel toksisite
• in vivo antioksidan aktivite
• Drosophila melanogaster

In vivo developmental and antioxidant effects of some Salvia species on Drosophila melanogaster

Öz

Medicinal plants have long served as valuable sources of therapeutic agents, primarily due to their antioxidant and antigenotoxic properties. Turkey, known for its rich biodiversity and diverse climatic conditions, hosts approximately 10000 plant species with nearly 400 possessing medicinal potential. Among these, species of the genus Salvia are particularly prominent, traditionally used to treat a wide range of ailments including gastrointestinal, respiratory, cardiovascular, renal and cognitive disorders. In this study, it is the first time that the developmental toxicity and in vivo antioxidant activities of aqueous methanolic, ethanolic and ethyl acetate extracts of S. candidissima subsp. candidissima subsp. candidissima, S. multicaulis, S. suffruticosa and S. syriaca were evaluated using Drosophila melanogaster (larvae, pupae and adult). Developmental toxicity was assessed by measuring percentage of puparation, eclosion and overall survival. In vivo antioxidant activity was determined using DPPH, ABTS and FRAP assays. The results indicated that none of the extracts of S. suffruticosa except the methanolic extract affected the puparation and survival rates (p>0.05), while other plant extracts negatively influenced the normal developmental processes. All extracts of S. suffruticosa demonstrated high in vivo antioxidant capacities ( 80 % activity) according to the ABTS test, while methanolic and ethanolic extracts of S. candidissima subsp. candidissima, S. multicaulis and S. syriaca showed high antioxidant activities according to DPPH test (>50-70 % activity). FRAP test also showed that the Trolox equivalent antioxidant capacities reported here for S. multicaulis (0.0025–0.0060 g TE/g) and S. suffruticosa (0.0049–0.0061 g TE/g) indicate strong antioxidant potential. To conclude the results of the in vivo antioxidant activity, it is demonstrated in this study that the studied plant extracts didn’t harm the physiological antioxidant system (balance) of the whole organism and the studied Salvia species have strong potential for the development of effective natural antioxidant supplements.

Anahtar Kelimeler

• Salvia
• developmental toxicity
• in vivo antioxidant activity
• Drosophila melanogaster

Kaynakça

1. Celikler, S., Vatan, O., Yildiz, G. and Bilaloglu, R., Evaluation of anti-oxidative, genotoxic and antigenotoxic potency of Codium tomentosum Stackhouse ethanolic extract in human lymphocytes in vitro, Food and Chemical Toxicology, 47, 4, 796–801, (2009).
2. Amani, Z., Gandomi, H., Akhondzadeh Basti, A., Derakhshandeh, A. and Noori, N., Cytotoxicity, genotoxicity, and mutagenicity potential of ethanolic extract of Heracleum persicum Desf. ex Fischer, J Food Saf, 39, 3, (2019).
3. Ozer, H., Erzurum Çevresinde Doğal Yayılış Gösteren Salvia Türleri ve Tıbbi Özellikleri, Tarla Bitkileri Merkez Araştırma Enstitüsü Dergisi, 25, OZEL SAYI-2, 340–345, (2016).
4. Tavares, W. R., Seca, A. M. L. and Barreto, M. C., Exploring the Therapeutic Potential of Artemisia and Salvia Genera in Cancer, Diabetes, and Cardiovascular Diseases: A Short Review of Clinical Evidence, J Clin Med, 14, 3, 1028, (2025).
5. Bayar, Y. and Genc, N., Determination of the chemical components, antioxidant and antifungal activities of essential oil and plant extract of Salvia candidissima Vahl., Mediterr Agric Sci, 31, 2, 93–99, (2018).
6. Özler, M. A., Duru, M. E., Diri, H. A. and Harmandar, M., Antioxidant Activity And Chemical Composition Of The Essential Oil Of Salvia candidissima Vahl. Grownig Wild In Turkey, Acta Hortic, 826, 363–370, (2009).
7. Guzel, K., Oksuz, Z., Gungor, U., Belveren, S. and Kahraman, A., Phytochemical analysis and biological activities of Salvia candidissima subsp. candidissima mericarps, Bot Serb, 47, 1, 19–29, (2023).
8. Erturk, E., Onur, O. E., Aydin, I., Ozel, M. Z., Firat, M. and Ari, F., Cytotoxic Potential of Rare Plant Salvia candidissima subsp. candidissima on Breast Cancer Cells, Brazilian Archives of Biology and Technology, 66, (2023).

9. Pehlivan, M. and Sevindik, M., Antioxidant and Antimicrobial Activities of Salvia multicaulis, Turkish Journal of Agriculture - Food Science and Technology, 6, 5, 628–631, (2018).
10. Rustaie A. et al., Phytochemical Constituents and Biological Activities of Salvia suffruticosa, Research Journal of Pharmacognosy (RJP), 25, 32, (2018).
11. Norouzi-Arasi H. et al., Volatile constituents and antimicrobial activities of Salvia suffruticosa Montbr. & Auch. ex Benth. from Iran, Flavour Fragr J, 20, 6, 633–636, (2005).
12. Bahadori, M. B. et al., Functional components, antidiabetic, anti-Alzheimer’s disease, and antioxidant activities of Salvia syriaca L., Int J Food Prop, 20, 8, 1761–1772, (2017).
13. Makris, S. L. et al., Current and future needs for developmental toxicity testing, Birth Defects Res B Dev Reprod Toxicol, 92, 5, 384–394, (2011).
14. Tuz, K., Juárez, O. X. and Ceapă, C. D., Editorial: Exploring novel targets and therapies to combat antimicrobial resistance, Front Microbiol, (2025).
15. Fiala, A., Meltzer, H., Schleyer, M., Turrel, O. and Widmann, A., Invertebrate brains as model systems for learning, memory, and recall: development, anatomy and function of memory systems, Front Physiol, (2025).
16. Martins, N., Barros, L. and Ferreira, I. C. F. R., In vivo antioxidant activity of phenolic compounds: Facts and gaps, Trends Food Sci Technol, 48, 1–12, (2016).
17. Ayikobua, E. T. et al., Synergistic action of propolis with levodopa in the management of Parkinsonism in Drosophila melanogaster, J Complement Integr Med, 17, 3, (2020).
18. Johnmark, N. and Kinyi, H. W., Amaranth leaf extract protects against hydrogen peroxide induced oxidative stress in Drosophila melanogaster, BMC Res Notes, 14, 1, 188, (2021).
19. Dai, J. and Mumper, R. J., Plant Phenolics: Extraction, Analysis and Their Antioxidant and Anticancer Properties, Molecules, 15, 10, 7313–7352, (2010).
20. Alexander, E. M. et al., The In vivo Antioxidant Protective Activity of Mangifera indica Cold Aqueous Leaf Extract in Drosophila melanogaster, J Adv Biol Biotechnol, 1–7, (2019).
21. Omoboyowa, D. A. et al., Modulatory effects of selected compounds on oxidative stress in hydrogen peroxide-induced Drosophila melanogaster, Pharmacological Research - Modern Chinese Medicine, 5, 100169, (2022).
22. Holden, J. J. and Suzuki, D. T., Temperature-sensitive mutations in Drosophila melanogaster XII. The genetic and developmental effects of dominant lethals on chromosome 3, Genetics, 73, 3, 445–458, (1973).
23. Cohet, Y. and David, J., Control of the adult reproductive potential by preimaginal thermal conditions, Oecologia, 36, 3, 295–306, (1978).
24. Lakhotia, S. C. and Ranganath, H. A., Experiments with Drosophila for Biology Courses, Indian Academy of Sciences, Bengaluru India, (2021).
25. Yakovleva, E. U., Naimark, E. B. and Markov, A. V., Adaptation of Drosophila melanogaster to unfavorable growth medium affects lifespan and age-related fecundity, Biochemistry (Moscow), 81, 12, 1445–1460, (2016).
26. Chung, H., Sztal, T., Pasricha, S., Sridhar, M., Batterham, P. and Daborn, P. J., Characterization of Drosophila melanogaster cytochrome P450 genes, Proceedings of the National Academy of Sciences, 106, 14, 5731–5736, (2009).
27. Yilmaz Kardas, B., Diken, M. E., Bayhan, H., Acar, M. and Dogan, S., Cytoprotective, antimutagenic/antirecombinogenic and antibacterial properties of Lallemantia iberica extracts, J Sci Food Agric, 103, 4, 1901–1911, (2023).
28. Ari, F., Ulukaya, E., Oran, S., Celikler, S., Ozturk, S. and Ozel, M. Z., Promising anticancer activity of a lichen, Parmelia sulcata Taylor, against breast cancer cell lines and genotoxic effect on human lymphocytes, Cytotechnology, 67, 3, 531–543, (2015).
29. Wild Korkmaz, F. J., Dogan, S., Yilmaz Kardas, B., Diken, M.E., Karasakal, Ö. F. and Acar, M., In vitro and in silico analyses of cytoprotective, antigenotoxic and antimutagenic potential of Phlomis pungens var. hirta extracts against oxidative damage, Genet Resour Crop Evol, (2024).
30. Depetris-Chauvin, A., Galagovsky, D., Chevalier, C., Maniere, G. and Grosjean, Y., Olfactory detection of a bacterial short-chain fatty acid acts as an orexigenic signal in Drosophila melanogaster larvae, Sci Rep, 7, 1, 14230, (2017).
31. Liu, Q. F. et al., In Vivo Screening of Traditional Medicinal Plants for Neuroprotective Activity against Aβ42 Cytotoxicity by Using Drosophila Models of Alzheimer’s Disease, Biol Pharm Bull, 38, 12, 1891–1901, (2015).
32. Macedo, G. E. et al., Senecio brasiliensis impairs eclosion rate and induces apoptotic cell death in larvae of Drosophila melanogaster, Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology, 198, 45–57, (2017).
33. Rand, M. D., Montgomery, S. L., Prince, L. and Vorojeikina, D., Developmental Toxicity Assays Using the Drosophila Model, Curr Protoc Toxicol, 59, 1, (2014).
34. Riaz, B. et al., Toxicity, Phytochemical Composition, and Enzyme Inhibitory Activities of Some Indigenous Weed Plant Extracts in Fruit Fly, Drosophila melanogaster, Evidence-Based Complementary and Alternative Medicine, (2018).
35. Yen, G.-C. and Hsieh, C.-L., Inhibitory effect of Eucommia ulmoides Oliv. on oxidative DNA damage in lymphocytes induced by H2O2, Teratog Carcinog Mutagen, 23, S1, 23–34, (2003).
36. Bayhan, H., Dogan, S., Yilmaz Kardas, B., Diken, M.E., Dirmenci, T. and Celikler, S., Comprehensive antigenotoxic profile of endemic Cirsium steriolepis Petrak extracts against hydrogen peroxide induced toxicity, Food Sci Biotechnol, 33, 13, 3131–3152, (2024).
37. Shakya, B. and Siddique, Y. H., Exploring the neurotoxicity and changes in life cycle parameters of Drosophila melanogaster exposed to arecoline, The Journal of Basic and Applied Zoology, 79, 1, 47, (2018).
38. Zhang, X. et al., Toxicity Evaluation of Potassium Sorbate In Vivo with Drosophila melanogaster, Insects, 15, 9, 703, (2024).
39. Rehman, N. and Varghese, J., Larval nutrition influences adult fat stores and starvation resistance in Drosophila, PLoS One, 16, 2, e0247175, (2021).
40. Chatterjee, T., Ghosh, S. K., Paik, S., Chakravarty, A. and Basak, A. K., Benzoic acid treated Drosophila melanogaster: the genetic disruption of larval brain stem cells and non-neural cells during metamorphosis, Toxicol Environ Health Sci, 13, 3, 215–223, (2021).
41. Güneş, E. and Nizamlıoğlu, H. F., The antioxidant effect of chitosan on virgin and mated Drosophila females, Carbohydrate Polymer Technologies and Applications, 5, p. 100297, (2023).
42. Lüersen, K. et al., Soy Extract, Rich in Hydroxylated Isoflavones, Exhibits Antidiabetic Properties In Vitro and in Drosophila melanogaster In Vivo, Nutrients, 15, 6, 1392, (2023).
43. Orr, W. C. and Sohal, R. S., The effects of catalase gene overexpression on life span and resistance to oxidative stress in transgenic Drosophila melanogaster, Arch Biochem Biophys, 297, 1, 35–41, (1992).
44. Kannangara, J. R., Mirth, C. K. and Warr, C. G., Regulation of ecdysone production in Drosophila by neuropeptides and peptide hormones, Open Biol, 11, 2, (2021).
45. Radyuk, S. N., Klichko, V. I. and Orr, W. C., Catalase expression inDrosophila melanogaster is responsive to ecdysone and exhibits both transcriptional and post-transcriptional regulation, Arch Insect Biochem Physiol, 45, 2, 79–93, (2000).
46. Wang, S.-P. et al., The involvement of several enzymes in methanol detoxification in Drosophila melanogaster adults, Comp Biochem Physiol B Biochem Mol Biol, 166, 1, 7–14, Sep. 2013, doi: 10.1016/j.cbpb.2013.05.008.
47. S. Ranganathan, D. G. Davis, and R. D. Hood, “Developmental toxicity of ethanol in Drosophila melanogaster,” Teratology, 36, 1, 45–49, (1987).
48. Martel, M. L., Baumgardner, C. A., Dybas, L. K. and Geer, B. W., The toxicities of short-chain primary alcohols and the accumulation of storage bodies in the larval fat body of Drosophila melanogaster, Comp Biochem Physiol C Pharmacol Toxicol Endocrinol, 111, 1, 99–108, (1995).
49. Kushalan, S., D’Souza, L. C., Aloysius, K., Sharma, A. and Hegde, S., Toxicity Assessment of Curculigo orchioides Leaf Extract Using Drosophila melanogaster: A Preliminary Study, Int J Environ Res Public Health, 19, 22, 15218, (2022).
50. Jabeen, A., Zaitoon, A., Lim, L.-T. and Scott-Dupree, C., Toxicity of Five Plant Volatiles to Adult and Egg Stages of Drosophila suzukii Matsumura (Diptera: Drosophilidae), the Spotted-Wing Drosophila, J Agric Food Chem, 69, 33, 9511–9519, (2021).
51. Pam, D., Etuh, A. M., Oyeniran, O. I. and Mdekere, I. W., Toxicity of Mangifera indica aqueous stem bark extract evaluated in Drosophila melanogaster used as model organism, Ann Pharm Fr, 79, 5, 539–546, (2021).
52. Llauradó Maury, G. et al., Antioxidants in Plants: A Valorization Potential Emphasizing the Need for the Conservation of Plant Biodiversity in Cuba, Antioxidants, 9, 11, 1048, (2020).
53. Kotha, R. R., Tareq, F. S., Yildiz, E. and Luthria, D. L., Oxidative Stress and Antioxidants—A Critical Review on In Vitro Antioxidant Assays, Antioxidants, 11, 12, 2388, (2022).
54. Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M. and Rice-Evans, C., Antioxidant activity applying an improved ABTS radical cation decolorization assay, Free Radic Biol Med, 26, 9–10, 1231–1237, (1999).
55. Kähkönen, M. P. et al., Antioxidant Activity of Plant Extracts Containing Phenolic Compounds, J Agric Food Chem, 47, 10, 3954–3962, (1999).
56. Bagci, E., Akbaba, E., Maniu, C., Ungureanu, E. and Hritcu, L., Evaluation of antiamnesic activity of Salvia multicaulis essential oil on scopolamine-induced amnesia in rats: in vivo and in silico approaches, Heliyon, 5, 8, e02223, (2019).
57. Furdak, P., Kut, K., Bartosz, G. and Sadowska-Bartosz, I., Comparison of Various Assays of Antioxidant Activity/Capacity: Limited Significance of Redox Potentials of Oxidants/Indicators, Int J Mol Sci, 26, 15, 7069, (2025).
58. Chaves, N., Santiago, A. and Alías, J. C., Quantification of the Antioxidant Activity of Plant Extracts: Analysis of Sensitivity and Hierarchization Based on the Method Used, Antioxidants, 9, 1, 76, (2020).
59. Rumpf, J., Burger, R. and Schulze, M., Statistical evaluation of DPPH, ABTS, FRAP, and Folin-Ciocalteu assays to assess the antioxidant capacity of lignins, Int J Biol Macromol, 233, 123470, (2023).
60. Fehresti Sani, M., Montasser Kouhsari, S. and Moradabadi, L., Effects of Three Medicinal Plants Extracts in Experimental Diabetes: Antioxidant Enzymes Activities and Plasma Lipids Profiles inComparison with Metformin., Iran J Pharm Res, 11, 3, 897–903, (2012).
61. Wang, H., Gao, X. D., Zhou, G. C., Cai, L. and Yao, W. B., In vitro and in vivo antioxidant activity of aqueous extract from Choerospondias axillaris fruit, Food Chem, 106, 3, 888–895, (2008).
62. Chen, Y., Huang, B., He, J., Han, L., Zhan, Y. and Wang, Y., In vitro and in vivo antioxidant effects of the ethanolic extract of Swertia chirayita, J Ethnopharmacol, 136, 2, 309–315, (2011).
63. Etuh, M. A. et al., The In vivo Antioxidant Protective Activity of Mangifera indica Cold Aqueous Leaf Extract in Drosophila melanogaster, J Adv Biol Biotechnol, 1–7, (2019).
64. Xu J. et al., Ethnopharmacology, phytochemistry, and pharmacology of Chinese Salvia species: A review, J Ethnopharmacol, 225, 18–30, (2018).
65. Chen, J. et al., Variation in flavonoid and antioxidant activities of Pyrrosia petiolosa (Christ) Ching from different geographic origins, Front Plant Sci, 14, (2023).
66. Proestos, C., Lytoudi, K., Mavromelanidou, O., Zoumpoulakis, P. and Sinanoglou, V., Antioxidant Capacity of Selected Plant Extracts and Their Essential Oils, Antioxidants, 2, 1, 11–22, (2013).
67. Mehmood, A., Javid, S., Khan, M. F., Ahmad, K. S. and Mustafa, A., In vitro total phenolics, total flavonoids, antioxidant and antibacterial activities of selected medicinal plants using different solvent systems, BMC Chem, 16, 1, 64, (2022).
68. Mueed, A. et al., Extraction, characterization of polyphenols from certain medicinal plants and evaluation of their antioxidant, antitumor, antidiabetic, antimicrobial properties, and potential use in human nutrition, Front Nutr, 10, (2023).
69. Rusaczonek, A., Sankiewicz, P., Duszyn, M., Górecka, M., Chwedorzewska, K. and Muszyńska, E., Interspecific Variation in the Antioxidant Potential of Culinary and Medicinal Herbs, Agriculture, 15, 15, 1586, (2025).