Microbial transformations of matrine and oxymatrine and in vitro biological evaulation of metabolites

Year 2020, Volume: 13 Issue: 1, 24 - 34, 30.04.2020

Ayşe Esra Karadağ Fatih Demirci

https://doi.org/10.26559/mersinsbd.546896

Abstract

Aim: It is aimed to examine the comparative biological activities of metabolites of matrine and oxymatrine compounds which were obtained by microbial transformation. Methods: After the cultivation of 30 different microorganisms in liquid medium, the transformation of substrates to new media was observed by adding them separately. The metabolites were initially identified by thin layer chromatography. Antimicrobial activity was investigated by microdilution method against microorganisms of Pseudomonas aeruginosa ATCC 10145, Escherichia coli NRLL B-3008, Staphylococcus aureus ATCC 6538, Helicobacter pylori ATCC 43504, Streptococcus epidermidis ATCC 14990, andCandida albicans ATCC 90028. The acetylcholinesterase enzyme inhibition was investigated by Ellman's method. 5-lipoxygenase enzyme inhibition experiments were determined by Baylac’s colorimetric method. Results: The biotransformation of the matrine with Mucor ramannianus and Enterococcus faecalis resulted in two metabolites (M1 and M2). Matrine was obtained as a metabolite by the biotransformation of oxymatrine with 5 different microorganisms. Conclusion: Matrine, oxymatrine, M1 and M2 metabolites were not effective for antimicrobial activity. Matrine (10.47%), oxymatrine (21.11%), M1 (24.23%) and M2 (26.42%) metabolites showed moderate activity compared to standard NDGA (96.35%) for 5-lipoxygenase enzyme inhibition. When acetylcholinesterase/ butyrylcholinesterase enzyme inhibitions are evaluated in terms of matrine (34,16%/ 20,49%), oxymatrine (23.68%/ 22.76%), M1 (27.72%/ 22.05%) and M2 (30.63%/23.98%) however, a slight increase in activity was observed in metabolites.

Keywords

Biotransformation, cholinesterase, lipoxygenase, matrine, oxymatrine

Matrin ve oksimatrinin mikrobiyal transformasyonu ve metabolitlerinin in vitro biyolojik aktivitelerinin incelenmesi

Abstract

Amaç: Matrin ve oksimatrin bileşiklerinin mikrobiyal transformasyon yolu ile metabolitlerin karşılaştırmalı olarak biyolojik aktivitelerinin incelenmesi hedeflenmiştir. Yöntem:30 farklı mikroorganizmanın sıvı besiyerinde üretilmesinden sonra, substratların ayrı ayrı ortama eklenerek yeni maddelere dönüşümü gözlemlenmiştir. Üretilen yeni maddeler besiyerinden uygun koşullarda ekstre edilerek, İnce Tabaka Kromatografisi ile maddelerin varlığı tespit edilmiştir. Antimikrobiyal aktivitePseudomonas aeruginosa ATCC 10145, Escherichia coli NRLL B-3008,Streptococcus epidermidis ATCC 14990, Staphylococcus aureus ATCC 6538, Helicobacter pylori ATCC 43504 ve Candida albicans ATCC 90028mikroorganizmalarına karşı mikrodilüsyon yöntemi kullanılarak incelenmiştir. Asetilkolinesteraz enzim inhibisyonu Ellman metodu ile araştırılmıştır. 5-lipooksijenaz enzim inhibisyonu deneyleri ise kolorimetrik yöntemlebelirlenmiştir. Bulgular: Matrin substratından Mucor ramannianus ve Enterococcus faecalis ile mikrobiyal biyotransformasyon sonucu iki metabolit (M1 ve M2) oluşmuştur. Oksimatrin substratının beş farklı mikroorganizma ile biyotransformasyonu sonucu matrin metabolit olarak elde edilmiştir. Sonuç: Matrin, oksimatrin, M1 ve M2 metabolitlerinin antimikrobiyal açıdan etkili olmadığı tespit edilmiştir. Matrin (%10.47), oksimatrin (%21.11), M1 (%24.23) ve M2 (%26.42)’nin 5-LOX enzim inhibisyonu açısından standart NDGA (%96.35) ile kıyaslandığında orta düzeyde aktivite gösterdiği görülmüştür. Asetilkolinesteraz/ bütirilkolinesteraz enzim inhibisyonu matrin (%34.16/ %20.49), oksimatrin (%23.68/ %22.76), M1 (%27.72/ %22.05) ve M2 (%30.63/ %23.98) açısından değerlendirildiğinde ise metabolitlerde az da olsa aktivitede artış gözlemlenmiştir.

Keywords

Biyotransformasyon, kolinesteraz, lipooksijenaz, matrin, oksimatrin

References

• 1. Dutta NN, Hammar F, Haralampidis D, Karanth NG. History and Trends in Bioprocessing and Biotechnology, Springer, Berlin Heidelberg, 2001:5-25.
• 2. Zhou Y, Wu Y, Deng L, Chen L. The alkaloids matrine of the root of Sophora flavescens prevents arrhythmogenic effect of ouabain. Phytomedicine 2014;21(7):931-935.
• 3. Kinghorn AD, Balandrin MF, Pelletier SW. Alkaloids. Chemical and Biological Perspectives 1984; 2:105.
• 4. Ma LD, Wen SH, Zhan Y, He YJ, Liu XS, Jiang JK. Anticancer effects of the Chinese medicine matrin on murine hepatocellular carcinoma cells. Planta Medica 2008;74:245-251.
• 5. Zhang G, Jiang L, Zhang L. Anti-tumor effect of matrine combined with cisplatin on rat models of chervical cancer. Assian Pac J Trop Med 2015; 8:1055-1059.
• 6. Ding T. The preparing and clinical applications of complex matrin Liniment. ACTA Chinese Medicine and Pharmacology 2002;30(2):4748.
• 7. Chen JX, Shen HH, Niu M, Guo YM, Liu XQ, Han YZ, Zhang Y, Zhao Y,Bau B, Zhou W, Xiao XH. Anti-hepatitis B virus effect of matrine-type alkaloid and involvement of p38 mitogen-activated protein kinase and tumor necrosis factor receptor-associated factor 6. Virus Res 2016;215: 104-113.
• 8. Zhang YB, Luo D, Yang L, Cheng W, He LJ, Kuang GK, Wang GC. Matrine-Type Alkaloids from the Roots of Sophora flavescens and Their Antiviral Activities against the Hepatitis B Virus. J Nat Prod 2018;81(10):2259-2265.
• 9. Zhang YB, Zhang XL, Chen NH, Wu ZN, Ye WC, Li YL, Wang GC. Four matrine-based alkaloids with antiviral activities against HBV from the seeds of Sophora alopecuroides. Org Lett 2017;19(2):424-427.
• 10. Liang N, Nikolova D, Jakobsen JC, Gluud C, Liu JP. Radix Sophorae flavescentis versus antiviral drugs for chronic hepatitis B. Cochrane Database Syst Rev2018; (8).
• 11. Higashiyama K, Takeuchi Y, Yamauchi T, Imai S, Kamei J, Yajima Y, Narita M, Suzuki T. Implication of the descending dynorphinergic neuron projecting to the spinal cord in the (+)-matrin and (+)-allomatrin induced antinociceptive effects. Biol Pharm Bull 2005;28:845-848.
• 12. Zhou J, Mei Y, Yi L. Research progress on pharmacology of the alkaloids in Sophora flavescens Ait. J Pediatr Pharmacol 2008; 14:61-64.
• 13. Zhu NX, Luo WJ, Yu RX, Lv QH, Xu RZ, Zhen S. Study on inducing and differentiating function and mechanism of matrine on leukaemia cells. ACTA Traditional Chinese Medicine Pharmacology 2001;15:43-44.
• 14. Zhang G, Jiang L, Zhang L. Anti-tumor effect of matrine combined with cisplatin on rat models of chervical cancer. Asian Pac J Trop Med 2015;8:1055-1059.
• 15. Krishna PM, Knv R, Sandhya S, Banji D. A review on phytochemical, ethnomedical and pharmacological studies on genus Sophora, Fabaceae. Braz J Pharmacog 2012; 22(5):1145-1154.
• 16. Jiang Y, Zhu Y, Mu Q, Luo H, Zhi Y, Shen X. Oxymatrine provides protection against Coxsackievirus B3-induced myocarditis in BALB/c mice. Antiviral Res 2017;141:133-139.
• 17. Long Y, Lin X.T, Zeng KL, Zhang L. Efficacy of intramuscular matrine in the treatment of chronic Hepatitis B. Hepatob Pancreat Dis 2004;3: 69-72.
• 18. Zhou YJ, Guo YJ, Yang XL, Ou ZL. Anti-cervical cancer role of matrine, oxymatrine and Sophora flavescens alkaloid gels and its mechanism. J Cancer 2018;9(8): 1357.
• 19. Jung Y, Shanmugam M, Narula A, Kim C, Lee J, Namjoshi O, Ahn K. Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model. Cancers 2019; 11(1): 49.
• 20. Zhang G, Jiang L, Zhang L. Anti-tumor effect of matrine combined with cisplatin on rat models of chervical cancer. Assian Pacific J TropMed2015;8:1055-1059.
• 21. Shi Y, Shen G, Fang H, Xu C, Hu S. Method for quantitative determinantion of matrine in Sophora alopecuroides L. and its inhibitory effect on breast cancer MCF-7 cell proliferation. Biomed Res2015;26(3):461-466.
• 22. Li Z, Zheng L, Shi J, Zhang G. Toxic Markers of Matrine Determined Using 1H-NMR-Based Metabolomics in Cultured Cells in vitro and rats in vivo. Evid Based Complement Alternat Med 2015;11:97-99.
• 23. Iverson CD. Identification of Glutathione S-Transferase Inhibiting Natural Products From Matricaria chamomilla and Biotransformation Studies on Oxymatrine and Harmine. PhD Thesis, Faculty of Graduate Studies of The University of Manitoba, Canada, 2010.
• 24. Baylac S, & Racine P. Inhibition of 5-lipoxygenase by essential oils and other natural fragrant extracts. International Journal of Aromatherapy 2003; 13(2-3):138-142.
• 25. Ellman GL, Courtney KD, Andres Jr V, & Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical pharmacology 1961;7(2):88-95.
• 26. Amsterdam D. Susceptibility testing of antimicrobials in liquid media, In Antibiotics in Laboratory Medicine, Fourth Edition, V. Lorian (Ed.), Williams & Wilkins, Baltimore 1996: 52-111.
• 27. Clinical and Laboratuary Standarts Institute (CLSI) (Formerly, NCCLS) Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, CLSI M7-A7, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne, Pennsylvania, USA 2006.