Inhibition of monoamine oxidase A (Mao-A) enzyme by some medicinal herbs

Abstract

Monoamine oxidase (MAO) is a flavin-containing enzyme responsible for the metabolism and regulation of neurotransmitter amines and plays a role in neuropsychiatric disorders such as depression and mania. In this study, the inhibitory effects of different concentrations of solutions prepared using distilled water, ethanol, ethyl acetate, petroleum ether, and mixed extracts of Hypericum perforatum, Ginkgo biloba , Lavandula angustifolia, Zingiber officinale, Tilia tomentosa., Cinnamomum aromaticum, Menthae piperita, Thymus cherlerioides, Portulaca oleracea, Trachystemon orientalis, Allium sativum, Petroselinum crispum, and Spinacia oleracea were investigated on monoamine oxidase obtained from rat liver. It was determined that the best inhibitor plant extract for MAO, which has a value of IC₅₀, was 0.071 mg/mL and with a ratio of inhibition of 70.15% ethanol extract of Hypericum perforatum. Following H. perforatum, the best inhibition effects were observed with the ethanol extract of Spinacia oleracea (IC₅₀ = 0.074 mg/mL), Ginkgo biloba (IC₅₀ = 0.075 mg/mL), Allium sativum (IC₅₀ = 0.080 mg/mL), and the distilled water extract of H. perforatum (IC₅₀ value of 0.081 mg/mL), respectively. The findings demonstrate that these species can inhibit the enzyme, highlighting their potential as therapeutic agents for neurological disorders.

Keywords

• Inhibition
• Monoamine oxidase-A (MAO-A)
• Medicinal Herbs

References

1. Al-Nuaimi, S.K., MacKenzie, E.M., & Baker, G.B. (2012). Monoamine oxidase inhibitors and neuroprotection: A review. American Journal of Therapeutics, 19(6), 436 448. https://doi.org/10.1097/MJT.0b013e31825b9eb5
2. Altar, C.A. (1999). Neurotrophins and depression. Trends in Pharmacological Sciences, 20(2), 59–62. https://doi.org/10.1016/S0165-6147(99)01309-7
3. Baker, G.B., Matveychuk, D., MacKenzie, E.M., Dursun, S.M., & Mousseau, D.D. (2012). Monoamine oxidase inhibitors and neuroprotective mechanisms. Bulletin of Clinical Psychopharmacology, 22(4), 293–296. https://doi.org/10.5455/bcp.20121030014051
4. Baljak, J., Bogavac, M., Karaman, M., Srđenović Čonić, B., Vučković, B., Anačkov, G., & Kladar, N. (2024). Chemical composition and biological activity of Hypericum species— H. hirsutum, H. barbatum, H. rochelii. Plants, 13(20), 2905. https://doi.org/10.3390/plants13202905
5. Bayır, E., & Cebe, G.E. (2023). Anksiyete ve uyku bozukluklarında kullanılan tıbbi bitkiler [Medicinal herbs used in anxiety and sleep disorders]. Ankara University Journal of Faculty of Pharmacy, 47(3), 1084–1100. https://doi.org/10.33483/jfpau.1270660
6. Bhalchim, V., & Undale, V. (2021). Assessment of metabolites: A new era in neurology. Turkish Journal of Physiotherapy and Rehabilitation, 32(3), 19580-19590.
7. Bhawna, K.A., Bhatia, M., Kapoor, A., Kumar, P., & Kumar, S. (2022). Monoamine oxidase inhibitors: A concise review with special emphasis on structure activity relationship studies. European Journal of Medicinal Chemistry, 242, 114655. https://doi.org/10.1016/j.ejmech.2022.114655
8. Bladt, S., & Wagner, H. (1994). Inhibition of MAO by fractions and constituents of Hypericum extract. Journal of Geriatric Psychiatry and Neurology, 7(1), 57 59. https://doi.org/10.1177/089198879400700115

9. Boku, S., Nakagawa, S., Toda, H., & Hishimoto, A. (2018). Neural basis of major depressive disorder: Beyond monoamine hypothesis. Psychiatry and Clinical Neurosciences, 72(1), 3 12. https://doi.org/10.1111/pcn.12604
10. Chauhan, N.B., & Sandoval, J. (2007). Amelioration of early cognitive deficits by aged garlic extract in Alzheimer's transgenic mice. Phytotherapy Research: PTR, 21(7), 629 640. https://doi.org/10.1002/ptr.2122
11. Chen, K., & Shih, J.C. (1997). Monoamine oxidase A and B: Structure, function, and behavior. Advances in Pharmacology, 42, 292–296. https://doi.org/10.1016/S1054-3589(08)60747-4
12. Chukwuere, P.C. (2021). Bio-psychosocial impact on the development of depression in adolescents. International Journal of Criminology and Sociology, 10, 1455-1463. https://doi.org/10.6000/1929-4409.2021.10.166
13. Das, T., Saha, S.C., Sunita, K., Majumder, M., Ghorai, M., Mane, A.B., … Dey, A. (2022). Promising botanical-derived monoamine oxidase (MAO) inhibitors: Pharmacological aspects and structure–activity studies. South African Journal of Botany, 146, 127 145. https://doi.org/10.1016/j.sajb.2021.09.019
14. Dimitrov, M., Nikolova, I., Benbasat, N., Kitanov, G., & Danchev, N. (2011). Acute toxicity, antidepressive and MAO inhibitory activity of mangiferin isolated from Hypericum aucheri. Biotechnology & Biotechnological Equipment, 25(4), 2668 2671. https://doi.org/10.5504/BBEQ.2011.0099
15. Dixon Clarke, S.E., & Ramsay, R.R. (2011). Dietary inhibitors of monoamine oxidase A. Journal of Neural Transmission, 118(7), 1031–1041. https://doi.org/10.1007/s00702-010-0537-x
16. Dhingra, D., & Kumar, V. (2008). Evidences for the involvement of monoaminergic and GABAergic systems in antidepressant-like activity of garlic extract in mice. Indian Journal of Pharmacology, 40(4), 175–179. https://doi.org/10.4103/0253-7613.43165
17. El-Alfy, A.T., Abourashed, E.A., & Matsumoto, R.R. (2012). Nature against depression. Current Medicinal Chemistry, 19(14), 2229–2241. https://doi.org/10.2174/092986712800229096
18. Farahani, M.S., Bahramsoltani, R., Farzaei, M.H., Abdollahi, M., & Rahimi, R. (2015). Plant-derived natural medicines for the management of depression: An overview of mechanisms of action. Reviews in the Neurosciences, 26(3), (305-321) https://doi.org/10.1515/revneuro-2014-0058
19. Fathinezhad, Z., Sewell, R.D.E., Lorigooini, Z., & Rafieian-Kopaei, M. (2019). Depression and treatment with effective herbs. Current Pharmaceutical Design, 25(6), 738 745. https://doi.org/10.2174/1381612825666190402105803
20. Fehske, C.J., Leuner, K., & Müller, W.E. (2009). Ginkgo biloba extract (EGb 761) influences monoaminergic neurotransmission via inhibition of NE uptake, but not MAO activity after chronic treatment. Pharmacological Research, 60(1), 68–73. https://doi.org/10.1016/j.phrs.2009.02.012
21. Gebreyohannes, G., & Gebreyohannes, M. (2013). Medicinal values of garlic: A review. International Journal of Medicine and Medical Sciences., 5(9), 401 408. https://doi.org/10.5897/IJMMS2013.0960
22. Ghenabzia, I., Hemmami, H., Ben Amor, I., Zeghoud, S., Ben Seghir, B., & Hammoudi, R. (2023). Different methods of extraction of bioactive compounds and their effect on biological activity: A review. International Journal of Secondary Metabolites, 10(4), 469 494. https://doi.org/10.21448/ijsm.1225936
23. Gudepu, R.L., Rampalli, S.M., & Krishna, J.Y. (2013). Evaluation of antidepressant activity of Spinacia oleracea using albino rats. International Journal of Pharmaceutical Sciences and Research, 4(12), 4692–4696. https://doi.org/10.13040/IJPSR.0975-8232.4(12).4692-96
24. Gülter, C., Girgin, F., Alper, G., Özgönül, M., Mentes, G., & Ersöz, B. (1999). Fizyolojik yaşlanma sürecinde prefrontal korteks biyojen aminler ve mao inhibitörlerinin etkileşimi [Interaction of the prefrontal cortex biogenic amines and mao inhibitors during the physiological aging process]. Turkish Journal of Geriatrics, 2(4),149-155. Microsoft Word - Geriatri 1999-4_149-155_.doc
25. Herraiz, T., & Guillén, H. (2018). Monoamine oxidase-a ınhibition and associated antioxidant activity in plant extracts with potential antidepressant actions. Biomed Research International, 2018(1), 4810394. https://doi.org/10.1155/2018/4810394
26. Hindmarch, I. (2001). Expanding the horizons of depression: Beyond the monoamine hypothesis. Human Psychopharmacology: Clinical and Experimental, 16(3), 203 218. https://doi.org/10.1002/hup.288
27. Hindmarch, I. (2002). Beyond the monoamine hypothesis: Mechanisms, molecules and methods. European Psychiatry, 17(3), 294–299. https://doi.org/10.1016/S0924-9338(02)00653-3
28. Holt, A., Sharman, D.F., Baker, G.B., & Palcic, M.M. (1997). A continuous spectrophotometric assay for monoamine oxidase and related enzymes in tissue homogenates. Analytical Biochemistry, 244(2), 384–392. https://doi.org/10.1006/abio.1996.9911
29. Jones, D.N., & Raghanti, M.A. (2021). The role of monoamine oxidase enzymes in the pathophysiology of neurological disorders. Journal of Chemical Neuroanatomy, 114, 101957. https://doi.org/10.1016/j.jchemneu.2021.101957
30. Kanazawa, I. (1994). Short review on monoamine oxidase and its inhibitors. European Neurology, 34(3), 6–39. https://doi.org/10.1159/000119540
31. Linde, K., Ramirez, G., Mulrow, C.D., Pauls, A., Weidenhammer, W., & Melchart, D. (1996). St John's wort for depression—An overview and meta-analysis of randomised clinical trials. BMJ, 313(7052), 253-258. https://doi.org/10.1136/bmj.313.7052.253
32. Liu, Y., Xin, H., Zhang, Y., Che, F., Shen, N., & Cui, Y. (2022). Leaves, seeds and exocarp of Ginkgo biloba L. (Ginkgoaceae): A comprehensive review of traditional uses, phytochemistry, pharmacology, resource utilization and toxicity. Journal of Ethnopharmacology, 298, 115645. https://doi.org/10.1016/j.jep.2022.115645
33. Mannan, A., Singh, T.G., Singh, V., Garg, N., Kaur, A., & Singh, M. (2022). Insights into the mechanism of the therapeutic potential of herbal monoamine oxidase inhibitors in neurological diseases. Current Drug Targets, 23(3), 286 310. https://doi.org/10.2174/1389450122666210707120256
34. Markom, M., Hasan, M., Daud, W.R.W., Singh, H., & Jahim, J.M. (2007). Extraction of hydrolysable tannins from Phyllanthus niruri Linn.: Effects of solvents and extraction methods. Separation and Purification Technology, 52(3), 487–496. https://doi.org/10.1016/j.seppur.2006.06.003
35. Mirzaei, M., Yasini Ardekani, S.M., Mirzaei, M., & Dehghani, A. (2019). Prevalence of depression, anxiety and stress among adult population: Results of yazd health study. Iranian Journal of Psychiatry, 14(2), 137. https://doi.org/10.18502/ijps.v14i2.993
36. Monagas, M., Brendler, T., & Brinckmann, J. (2022). Understanding plant to extract ratios in botanical extracts. Frontiers in Pharmacology, 13, 981978. https://doi.org/10.3389/fphar.2022.981978
37. Moragrega, I., & Ríos, J.L. (2021). Medicinal plants in the treatment of depression: Evidence from preclinical studies. Planta Medica, 87(9), 656–685. https://doi.org/10.1055/a-1338-1011
38. Müller, W.E., Rolli, M., Schäfer, C., & Hafner, U. (1997). Effects of hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry, 30(2), 102 107. https://doi.org/10.1055/s-2007-979528
39. Omara, T., Kiprop, A.K., & Kosgei, V.J., (2021). Intraspecific variation of phytochemicals, antioxidant, and antibacterial activities of different solvent extracts of Albizia coriaria leaves from some agroecological zones of Uganda, Evidience-Based Complementary Alternative. Medicine, 2021(1), 2335454. https://doi.org/10.1155/2021/2335454
40. Ostadkarampour, M., & Putnins, E.E. (2021). Monoamine oxidase inhibitors: A review of their anti-inflammatory therapeutic potential and mechanisms of action. Frontiers in Pharmacology, 12, 676239. https://doi.org/10.3389/fphar.2021.676239
41. Payne, M.E., Steck, S.E., George, R.R., & Steffens, D.C. (2012). Fruit, vegetable, and antioxidant intakes are lower in older adults with depression. Journal of Academic Nutrition and Dietetic., 112(12), 2022–2027. https://doi.org/10.1016/j.jand.2012.08.026
42. Remick, R.A., & Froese, C. (1990). Monoamine oxidase inhibitors: Clinical review. Canadian Family Physician, 36, 1151–1155.
43. Shah, M.S., Madhuri, T., Monika, W., & Oswal, D.R.J. (2020). Herbal supplements used in schizophrenia: An overview. World Journal of Pharmaceutical Research, 9(8), 842-857.
44. Shulman, K.I., Herrmann, N., & Walker, S.E. (2013). Current place of monoamine oxidase inhibitors in the treatment of depression. CNS Drugs, 27(10), 789–797. https://doi.org/10.1007/s40263-013-0097-3
45. Sparenberg, B.L., Demisch, J., & Holzl, J. (1993). Untersuchungen uber die antidepressiven Wirkstoffe von Johanniskraut [Research on the antidepressant properties of St. John's Wort]. Pharm Ztg Wiss, 138, 239-254.
46. Stafford, G.I., Pedersen, P.D., Jäger, A.K., & Van Staden, J. (2007). Monoamine oxidase inhibition by southern African traditional medicinal plants. South African Journal of Botany, 73(3), 384–390. https://doi.org/10.1016/j.sajb.2007.03.001
47. Suzuki, O., Katsumata, Y., Oya, M., Bladt, S., & Wagner, H. (1984). Inhibition of monoamine oxidase by hypericin. Planta Medica, 50(3), 272–274. https://doi.org/10.1055/s-2007-969700
48. Sloley, B.D., Urichuk, L.J., Morley, P., Durkin, J., Shan, J.J., Pang, P.K., & Coutts, R.T. (2000). Identification of kaempferol as a monoamine oxidase inhibitor and potential Neuroprotectant in extracts of Ginkgo biloba leaves. Journal of Pharmacy and Pharmacology, 52(4), 451-459. https://doi.org/10.1211/0022357001774075
49. Son, H., Jung, S., Shin, J.H., Kang, M.J., & Kim, H.J. (2018). Anti-stress and anti-depressive effects of spinach extracts on a chronic stress-induced depression mouse model through lowering blood corticosterone and increasing brain glutamate and glutamine levels. Journal of Clinical Medicine, 7(11), 406. https://doi.org/10.3390/jcm7110406
50. Thiede, H.M., & Walper, A. (1994). Inhibition of MAO and COMT by hypericum extracts and hypericin. Journal of Geriatric Psychiatry and Neurology, 7(1), 54 56. https://doi.org/10.1177/089198879400700114
51. Ushijima, M., Sumioka, I., Kakimoto, M., Yokoyama, K., Uda, N., Matsuura, H., ... & Amagase, H. (1997). Effect of garlic and garlic preparations on physiological and psychological stress in mice. Phytotherapy Research: An International Journal Devoted to Medical and Scientific Research on Plants and Plant Products, 11(3), 226-230. https://doi.org/10.1002/(SICI)1099-1573(199705)11:3<226::AID-PTR85>3.0.CO;2-E
52. Volz, H.P., & Gleiter, C.H. (1998). Monoamine oxidase inhibitors. Drugs & Aging, 13(5), 341–355. https://doi.org/10.2165/00002512-199813050-00002
53. White, H.L., Scates, P.W., & Cooper, B.R. (1996). Extracts of Ginkgo biloba leaves inhibit monoamine oxidase. Life Sciences, 58(16), 1315–1321. https://doi.org/10.1016/0024-3205(96)00097-5
54. Wu, W.R., & Zhu, X.Z. (1999). Involvement of monoamine oxidase inhibition in neuroprotective and neurorestorative effects of Ginkgo biloba extract against MPTP-induced nigrostriatal dopaminergic toxicity in C57 mice. Life Sciences, 65(2), 157–164. https://doi.org/10.1016/S0024-3205(99)00232-5
55. Yadav, M., Parle, M., Sharma, N., Jindal, D.K., Bhidhasra, A., Dhingra, M.S., Kumar, A., & Dhingra, S. (2018). Protective effects of Spinacia oleracea seeds extract in an experimental model of schizophrenia: Possible behavior, biochemical, neurochemical and cellular alterations. Biomedicine & Pharmacotherapy, 105, 1015–1025. https://doi.org/10.1016/j.biopha.2018.06.043
56. Yildiz, O., Karahalil, F., Can, Z., Sahin, H., & Kolayli, S. (2013). Total monoamine oxidase (MAO) inhibition by chestnut honey, pollen and propolis. Journal of Enzyme Inhibition and Medicinal Chemistry, 29(5), 690–694. https://doi.org/10.3109/14756366.2013.843171
57. Zirak, N., Shafiee, M., Soltani, G., Mirzaei, M., & Sahebkar, A. (2019). Hypericum perforatum in the treatment of psychiatric and neurodegenerative disorders: Current evidence and potential mechanisms of action. Journal of Cellular Physiology, 234(6), 8496 8508. https://doi.org/10.1002/jcp.27781