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Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri ve Sinerjik Etkilerinin Araştırılması

Year 2022, Volume: 12 Issue: 3, 628 - 636, 30.09.2022
https://doi.org/10.31020/mutftd.1131757

Abstract

Amaç: Bu çalışmanın amacı bazı türleri geleneksel olarak nevroz, sıtma, skrofula, uyuz, ateş, eksternal kanserler, incinme ve yara tedavisinde kullanılan Vincetoxicum cinsine ait iki taksonun (Vincetoxicum canescens subsp. pedunculata (VC) ve Vincetoxicum fuscatum subsp. fuscatum (VF)) tohumlarının antimikrobiyal, antibiyofilm aktiviteleri ve sinerjik etkilerini incelemektir.
Yöntem: Öğütülmüş tohumlardan elde edilmiş etanollü ekstrelerin antimikrobiyal etkinlikleri mikrodilüsyon yöntemiyle 5 referans bakteri suşu (Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae) ve 2 referans maya suşuna (Candida albicans and Candida parapsilosis) karşı test edilmiştir. Ayrıca ekstrelerin P. aeruginosa’nın biyofilm oluşumunu inhibe etme ve oluşmuş biyofilm üzerine etkisi kristal viyole yöntemi ile değerlendirilmiştir. Biyofilm testleri ile minimum biyofilm inhibisyon konsantrasyonu (MBIC50) ve minimum biyofilm azaltma konsantrasyonu (MBRC50) belirlenmiştir. E.coli'ye karşı iki ekstre arasındaki sinerjik etkiyi değerlendirmek için ise mikrodilüsyon dama tahtası yöntemi kullanılmıştır.
Bulgu: Ekstreler, test edilen bakteri ve mayaları 62,5–250 µg/mL minimum inhibisyon konsantrasyonları (MİK) aralığında inhibe etmiştir. VF ve VC ekstrelerinin 0,5X ve 0,25X MİK'de biyofilm oluşumunu sırasıyla %47, %39 ve %50, %34 oranında inhibe ettiği ve iki ekstrenin MBIC50 değerinin 62,5 µg/mL olduğu belirlenmiştir. Ayrıca ekstrelerin önceden oluşmuş biyofilmi 1X ve 2X MİK'de sırasıyla %54, %62 ve %56, %61 oranında inhibe ettiği ve MBRC50 değerinin 125 µg/mL olduğu belirlenmiştir. Dahası ekstrelerin E.coli'ye karşı aditif etki (FİK=0,62) gösterdikleri de tespit edilmiştir.
Sonuç: Test edilen ekstreler orta ve düşük antimikrobiyal etki göstermekle birlikte hem biyofilm oluşumunu engelleme hem de oluşmuş biyofilmi ortadan kaldırmada iyi etkinliğe sahiptir.

Thanks

Bitki örneklerinin teşhisinde katkılarından dolayı Dr. Ahmet İlçim'e teşekkür ederiz.

References

  • 1. DiTommaso A, Lawlor FM, Darbyshire SJ. The biology of invasive alien plants in Canada 2. Cynanchum rossicum (Kleopow) Borhidi (=Vincetoxicum rossicum (Kleopow) Barbar.) and Cynanchum louseae (L.) Kartesz&Gandhi (= Vincetoxicum nigrum (L.) Moench). Can J Plant Sci 2004;85(1):243-263.
  • 2. Güven S, et al. Pollinarium morphology of Vincetoxicum (Apocynaceae: Asclepiadoideae) in Turkey. Phytotaxa 2015;230(1):22-38
  • 3. Sliumpaite I, et al.Antioxidant properties and phenolic composition of swallowwort (Vincetoxicum lutea L.) leaves. Ind Crops Prod 2013;45:74-82.
  • 4. Mansoor A, et al. Antiprotozoal activities of Vincetoxicum stocksii and Carum copticum. Bangladesh J Pharmacol 2011;6(1):51-54.
  • 5. Browicz K. Vincetoxicum N.M. Wolf. In: Davis PH, editor, Flora of Turkey and the East Aegean Islands. Edinburgh, Scotland. 1978. pp:163-173
  • 6. Pavela R. Antifeedant activity of plant extracts on Leptinotarsa decemlineata Say. and Spodoptera littoralis Bois. larvae. Ind Crops Prod 2010;32(3):213-219.
  • 7. Lavault M, Richomme P, Bruneton J. New phenanthroindolizidine N-oxides alkaloids isolated from Vincetoxicum hirundinaria Medic. Pharm Acta Helv 1994;68(4):225-227
  • 8. Lavault M, Richomme P, Bruneton J. Acetophenones and new pregnane glycosides from the roots of Vincetoxicum hirundinaria. Fitoterapia 1999;70(2):216-220.
  • 9. Coassini-Lokar L, Poldini L. Herbal remedies in the traditional medicine of the Venezia Giulia Region (North East Italy). J Ethnopharmacol. 1988;22(3)231-279.
  • 10. Baytop T. Türkiye'de Bitkiler ile Tedavi Geçmişte ve Bugün. İlaveli 2. Baskı; İstanbul Üniversitesi Eczacılık Fakültesi, Nobel Tıp Kitap Evleri, İstanbul, Türkiye 1984.
  • 11. Slapšytė G, et al. Genotoxic properties of Betonica officinalis, Gratiola officinalis, Vincetoxicum luteum and Vincetoxicum hirundinaria extracts. Food and Chemical Toxicology. 2019;134:110815
  • 12. Tuzlacı E, Dogan A. Turkish folk medicinal plants, IX: Ovacık (Tunceli). Marmara Pharm J 2010;14:136-143
  • 13. Altundag E, Ozturk M. Ethnomedicinal studies on the plant resources of East Anatolia, Turkey. Procedia Soc Behav Sci 2011;19:756-777.
  • 14. Eker İ, Vural M, Aslan S. Ankara İli’nin Damarlı bitki çeşitliliği ve korumada öncelikli Taksonları. Bağbahçe Bilim Dergisi 2015;2(3):57-114
  • 15. Koyuncu O, Sezer O. Altıntaş (Kütahya) Turba (Torf) Ocağı Ve Çevresinin Damarlı Bitkiler Florası. IJABES 2019;1(1): 6-21. -15
  • 16. Mogg C, et al. Test of the antibiotic properties of the invasive vine Vincetoxicum rossicum against bacteria, fungi and insects. Biochem Syst Ecol 2008;36:383-391.
  • 17. Guzel S, et al. Evaluation of antimicrobial activity of five Vincetoxicum taxa growing in Turkey. Mamar Pharm J 2018;22(3):365-373.
  • 18. S. Guzel. Fatty acid, sterol, and tocol compositions; amino acid, mineral, total phenolic, and flavonoid contents; and antioxidant activity of seeds of two Vincetoxicum taxa. Chemistry of Natural Compounds, 2020;56(2):202-206.
  • 19. Shah AJ, et al. Antidiarrheal and antispasmodic activities of Vincetoxicum stocksii are mediated through calcium channel blockade. Bangladesh J. Pharmacol 2011;6:46
  • 20. Staerk D, et al. In vitro cytotoxic activity of phenantroindolizidine alkaloids from Cynanchum vincetoxicum and Tylophora tanakae against drug-sensitive and multidrug-resistant cancer cells. J Nat Prod 2002;65:1299-1302
  • 21. Akalın H. Antimikrobiyal Direnç Ve Önleme Politikaları. Ankem Derg 2011;25(3):190-195,
  • 22. Antimicrobial resistance. No time to wait: securing the future from drug-resistant infections. No action today, no cure tomorrow. 2022. Available from: https://openwho.org/channels/amr Accessed June 10, 2022.
  • 23. Morrison L, Zembower TR. Antimicrobial Resistance. Gastrointest Endosc Clin N Am 2020;30(4):619-635.
  • 24. Fernández L, et al. Creeping baselines and adaptive resistance to antibiotics. Drug Resist Updat 2011;14:1–21.
  • 25. Del Pozo JL. Biofilm-related disease. Expert Rev Anti Infect Ther 2018;16(1):51-65.
  • 26. Alhede M, et al. Phenotypes of non-attached Pseudomonas aeruginosa aggregates resemble surface attached biofilm. PloS One 2011;6:27943
  • 27. Haaber J, et al. Planktonic aggregates of Staphylococcus aureus protect against common antibiotics. PloS One 2012;7:41075.
  • 28. Ibberson, CB, Whiteley, M. The social life of microbes in chronic infection. Curr. Opin. Microbiol 2020;53:44–50.
  • 29. Lindsay D, von Holy A. Bacterial biofilms within the clinical setting: what healthcare professionals should know. J Hosp Infect 2006;64(4):313-25.
  • 30. Güzel S, Ülger M, Kahraman A. Chemical composition and some biological activities of Salvia longipedicellata Hedge mericarps. Chemistry of Natural Compounds 2020;56(5):788-792
  • 31. Jorgensen JH, Ferraro MJ. Antimicrobial susceptibility testing: general principles and contemporary practice. Clin Infect Dis 1998;26:973–80.
  • 32. O’Toole GA. Microtiter dish biofilm formation assay. J Vis Exp 2011;47:2437
  • 33. Zhong H, et al. Antibacterial and Antibiofilm Activity of Temporin-GHc and Temporin-GHd Against Cariogenic Bacteria, Streptococcus mutans. Front Microbiol 2019;10:2854.
  • 34. Moody J. Synergism testing: broth microdilution checkerboard and broth microdilution methods. In: Garcia LS editor. Clinical Microbiology Procedures Handbook. Washington, DC: ASM Press; 2010. pp 5.12.11-5.12.23.
  • 35. Zaidi MA, Crow JSA. Biologically active traditional medicinal herbs from Balochistan, Pakistan J Ethnopharmacol 2005;96:331-334
  • 36. Guzel S, Ulger M, Kokdil G. Anti(myco)bacterial and antifungal activities of seed pods of four Vincetoxicum taxa growing in Turkey. International Journal of Scientific and Technological Research 2018;4(3):27-38.
  • 37. Bazzaz F, Haririzadeh G. Screening of Iranian plants for antimicrobial activity. Pharm Biol 2003;41(8):573-583
  • 38. Guzel S, Pavela R, Kokdil G. Evaluation of antifungal effect of different polarity extracts from five Vincetoxicum taxa against Aspergillus fumigatus. International Anatolian Academic Online Journal/Health Science 2015;3(2):1-9.
  • 39. Ülger M, et al. Vincetoxicum canescens subsp. canescens ve Vincetoxicum cancescens subsp. pedunculata Tohumlarının Antimikrobiyal ve Antiproliferatif Aktiviteleri. Lokman Hekim Dergisi, 2019;9:367-375.
  • 40. Ben Haj Khalifa A, et al. Virulence factors in Pseudomonas aeruginosa: mechanisms and modes of regulation. Annales de biologie clinique 2011;69(4):393–403.
  • 41. Hengzhuang W, et al. In vivo pharmacokinetics/pharmacodynamics of colistin and imipenem in Pseudomonas aeruginosa biofilm infection. Antimicrobial Agents Chemotherapy 2012;56:2683-90

Investigation on Antimicrobial, Antibiofilm Activities; and Synergistic Effects of Seeds of Two Vincetoxicum Taxa Growing in Turkey

Year 2022, Volume: 12 Issue: 3, 628 - 636, 30.09.2022
https://doi.org/10.31020/mutftd.1131757

Abstract

Aim: The aim of this study is to examine the antimicrobial, antibiofilm activities, and synergistic effects of the seeds of two Vincetoxicum taxa [Vincetoxicum canescens subsp. pedunculata (VC) and Vincetoxicum fuscatum subsp. fuscatum (VP)] of which some species have been traditionally used to treat neurosis, malaria, scrofula, scabies, internal fever, external cancers, injuries, and wounds.
Methods: Antimicrobial activities of ethanolic extracts obtained from seeds were determined by the microdilution method against 5 reference bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae) and 2 reference fungal strains (Candida albicans and Candida parapsilosis). Effect of the extracts on inhibiting biofilm formation and on formed biofilm was determined by the crystal violet method. Minimum biofilm inhibition concentration (MBIC50) and minimum biofilm reduction concentration (MBRC50) were determined by biofilm tests. The microdilution checkerboard method was used to evaluate the synergistic effect between the two extracts against E.coli.
Results: The extracts inhibited the tested bacteria and yeasts in the minimum inhibition concentrations (MIC) range of 62.5–250 µg/mL. It was determined that tested VF and VC extracts inhibited biofilm formation by 47%, 39%, 50%, and 34% at 0.5X and 0.25X MIC, respectively, and the MBIC50 value of both extracts was 62.5 µg/mL. In addition, it was determined that the extracts inhibited the preformed biofilm by 54%, 62%, and 56%, and 61% at 1X and 2X MIC, respectively, and the MBRC50 value was 125 µg/mL. It was determined that the extracts showed an additive effect (FIC=0.62) against E.coli.
Conclusions: Although the tested extracts have moderate and low antimicrobial effects, they have well effects both in preventing the formation of biofilm and in removing the formed biofilm

References

  • 1. DiTommaso A, Lawlor FM, Darbyshire SJ. The biology of invasive alien plants in Canada 2. Cynanchum rossicum (Kleopow) Borhidi (=Vincetoxicum rossicum (Kleopow) Barbar.) and Cynanchum louseae (L.) Kartesz&Gandhi (= Vincetoxicum nigrum (L.) Moench). Can J Plant Sci 2004;85(1):243-263.
  • 2. Güven S, et al. Pollinarium morphology of Vincetoxicum (Apocynaceae: Asclepiadoideae) in Turkey. Phytotaxa 2015;230(1):22-38
  • 3. Sliumpaite I, et al.Antioxidant properties and phenolic composition of swallowwort (Vincetoxicum lutea L.) leaves. Ind Crops Prod 2013;45:74-82.
  • 4. Mansoor A, et al. Antiprotozoal activities of Vincetoxicum stocksii and Carum copticum. Bangladesh J Pharmacol 2011;6(1):51-54.
  • 5. Browicz K. Vincetoxicum N.M. Wolf. In: Davis PH, editor, Flora of Turkey and the East Aegean Islands. Edinburgh, Scotland. 1978. pp:163-173
  • 6. Pavela R. Antifeedant activity of plant extracts on Leptinotarsa decemlineata Say. and Spodoptera littoralis Bois. larvae. Ind Crops Prod 2010;32(3):213-219.
  • 7. Lavault M, Richomme P, Bruneton J. New phenanthroindolizidine N-oxides alkaloids isolated from Vincetoxicum hirundinaria Medic. Pharm Acta Helv 1994;68(4):225-227
  • 8. Lavault M, Richomme P, Bruneton J. Acetophenones and new pregnane glycosides from the roots of Vincetoxicum hirundinaria. Fitoterapia 1999;70(2):216-220.
  • 9. Coassini-Lokar L, Poldini L. Herbal remedies in the traditional medicine of the Venezia Giulia Region (North East Italy). J Ethnopharmacol. 1988;22(3)231-279.
  • 10. Baytop T. Türkiye'de Bitkiler ile Tedavi Geçmişte ve Bugün. İlaveli 2. Baskı; İstanbul Üniversitesi Eczacılık Fakültesi, Nobel Tıp Kitap Evleri, İstanbul, Türkiye 1984.
  • 11. Slapšytė G, et al. Genotoxic properties of Betonica officinalis, Gratiola officinalis, Vincetoxicum luteum and Vincetoxicum hirundinaria extracts. Food and Chemical Toxicology. 2019;134:110815
  • 12. Tuzlacı E, Dogan A. Turkish folk medicinal plants, IX: Ovacık (Tunceli). Marmara Pharm J 2010;14:136-143
  • 13. Altundag E, Ozturk M. Ethnomedicinal studies on the plant resources of East Anatolia, Turkey. Procedia Soc Behav Sci 2011;19:756-777.
  • 14. Eker İ, Vural M, Aslan S. Ankara İli’nin Damarlı bitki çeşitliliği ve korumada öncelikli Taksonları. Bağbahçe Bilim Dergisi 2015;2(3):57-114
  • 15. Koyuncu O, Sezer O. Altıntaş (Kütahya) Turba (Torf) Ocağı Ve Çevresinin Damarlı Bitkiler Florası. IJABES 2019;1(1): 6-21. -15
  • 16. Mogg C, et al. Test of the antibiotic properties of the invasive vine Vincetoxicum rossicum against bacteria, fungi and insects. Biochem Syst Ecol 2008;36:383-391.
  • 17. Guzel S, et al. Evaluation of antimicrobial activity of five Vincetoxicum taxa growing in Turkey. Mamar Pharm J 2018;22(3):365-373.
  • 18. S. Guzel. Fatty acid, sterol, and tocol compositions; amino acid, mineral, total phenolic, and flavonoid contents; and antioxidant activity of seeds of two Vincetoxicum taxa. Chemistry of Natural Compounds, 2020;56(2):202-206.
  • 19. Shah AJ, et al. Antidiarrheal and antispasmodic activities of Vincetoxicum stocksii are mediated through calcium channel blockade. Bangladesh J. Pharmacol 2011;6:46
  • 20. Staerk D, et al. In vitro cytotoxic activity of phenantroindolizidine alkaloids from Cynanchum vincetoxicum and Tylophora tanakae against drug-sensitive and multidrug-resistant cancer cells. J Nat Prod 2002;65:1299-1302
  • 21. Akalın H. Antimikrobiyal Direnç Ve Önleme Politikaları. Ankem Derg 2011;25(3):190-195,
  • 22. Antimicrobial resistance. No time to wait: securing the future from drug-resistant infections. No action today, no cure tomorrow. 2022. Available from: https://openwho.org/channels/amr Accessed June 10, 2022.
  • 23. Morrison L, Zembower TR. Antimicrobial Resistance. Gastrointest Endosc Clin N Am 2020;30(4):619-635.
  • 24. Fernández L, et al. Creeping baselines and adaptive resistance to antibiotics. Drug Resist Updat 2011;14:1–21.
  • 25. Del Pozo JL. Biofilm-related disease. Expert Rev Anti Infect Ther 2018;16(1):51-65.
  • 26. Alhede M, et al. Phenotypes of non-attached Pseudomonas aeruginosa aggregates resemble surface attached biofilm. PloS One 2011;6:27943
  • 27. Haaber J, et al. Planktonic aggregates of Staphylococcus aureus protect against common antibiotics. PloS One 2012;7:41075.
  • 28. Ibberson, CB, Whiteley, M. The social life of microbes in chronic infection. Curr. Opin. Microbiol 2020;53:44–50.
  • 29. Lindsay D, von Holy A. Bacterial biofilms within the clinical setting: what healthcare professionals should know. J Hosp Infect 2006;64(4):313-25.
  • 30. Güzel S, Ülger M, Kahraman A. Chemical composition and some biological activities of Salvia longipedicellata Hedge mericarps. Chemistry of Natural Compounds 2020;56(5):788-792
  • 31. Jorgensen JH, Ferraro MJ. Antimicrobial susceptibility testing: general principles and contemporary practice. Clin Infect Dis 1998;26:973–80.
  • 32. O’Toole GA. Microtiter dish biofilm formation assay. J Vis Exp 2011;47:2437
  • 33. Zhong H, et al. Antibacterial and Antibiofilm Activity of Temporin-GHc and Temporin-GHd Against Cariogenic Bacteria, Streptococcus mutans. Front Microbiol 2019;10:2854.
  • 34. Moody J. Synergism testing: broth microdilution checkerboard and broth microdilution methods. In: Garcia LS editor. Clinical Microbiology Procedures Handbook. Washington, DC: ASM Press; 2010. pp 5.12.11-5.12.23.
  • 35. Zaidi MA, Crow JSA. Biologically active traditional medicinal herbs from Balochistan, Pakistan J Ethnopharmacol 2005;96:331-334
  • 36. Guzel S, Ulger M, Kokdil G. Anti(myco)bacterial and antifungal activities of seed pods of four Vincetoxicum taxa growing in Turkey. International Journal of Scientific and Technological Research 2018;4(3):27-38.
  • 37. Bazzaz F, Haririzadeh G. Screening of Iranian plants for antimicrobial activity. Pharm Biol 2003;41(8):573-583
  • 38. Guzel S, Pavela R, Kokdil G. Evaluation of antifungal effect of different polarity extracts from five Vincetoxicum taxa against Aspergillus fumigatus. International Anatolian Academic Online Journal/Health Science 2015;3(2):1-9.
  • 39. Ülger M, et al. Vincetoxicum canescens subsp. canescens ve Vincetoxicum cancescens subsp. pedunculata Tohumlarının Antimikrobiyal ve Antiproliferatif Aktiviteleri. Lokman Hekim Dergisi, 2019;9:367-375.
  • 40. Ben Haj Khalifa A, et al. Virulence factors in Pseudomonas aeruginosa: mechanisms and modes of regulation. Annales de biologie clinique 2011;69(4):393–403.
  • 41. Hengzhuang W, et al. In vivo pharmacokinetics/pharmacodynamics of colistin and imipenem in Pseudomonas aeruginosa biofilm infection. Antimicrobial Agents Chemotherapy 2012;56:2683-90
There are 41 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Zehra Öksüz 0000-0002-1542-0556

Sevda Güzel 0000-0002-6642-5824

Publication Date September 30, 2022
Submission Date June 24, 2022
Published in Issue Year 2022 Volume: 12 Issue: 3

Cite

APA Öksüz, Z., & Güzel, S. (2022). Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri ve Sinerjik Etkilerinin Araştırılması. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi Ve Folklorik Tıp Dergisi, 12(3), 628-636. https://doi.org/10.31020/mutftd.1131757
AMA Öksüz Z, Güzel S. Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri ve Sinerjik Etkilerinin Araştırılması. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi. September 2022;12(3):628-636. doi:10.31020/mutftd.1131757
Chicago Öksüz, Zehra, and Sevda Güzel. “Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri Ve Sinerjik Etkilerinin Araştırılması”. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi Ve Folklorik Tıp Dergisi 12, no. 3 (September 2022): 628-36. https://doi.org/10.31020/mutftd.1131757.
EndNote Öksüz Z, Güzel S (September 1, 2022) Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri ve Sinerjik Etkilerinin Araştırılması. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi 12 3 628–636.
IEEE Z. Öksüz and S. Güzel, “Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri ve Sinerjik Etkilerinin Araştırılması”, Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi, vol. 12, no. 3, pp. 628–636, 2022, doi: 10.31020/mutftd.1131757.
ISNAD Öksüz, Zehra - Güzel, Sevda. “Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri Ve Sinerjik Etkilerinin Araştırılması”. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi 12/3 (September 2022), 628-636. https://doi.org/10.31020/mutftd.1131757.
JAMA Öksüz Z, Güzel S. Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri ve Sinerjik Etkilerinin Araştırılması. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi. 2022;12:628–636.
MLA Öksüz, Zehra and Sevda Güzel. “Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri Ve Sinerjik Etkilerinin Araştırılması”. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi Ve Folklorik Tıp Dergisi, vol. 12, no. 3, 2022, pp. 628-36, doi:10.31020/mutftd.1131757.
Vancouver Öksüz Z, Güzel S. Türkiye’de Yetişen İki Vincetoxicum Taksonunun Tohumlarının Antimikrobiyal, Antibiyofilm Aktiviteleri ve Sinerjik Etkilerinin Araştırılması. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi ve Folklorik Tıp Dergisi. 2022;12(3):628-36.

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