Review
BibTex RIS Cite

A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine

Year 2024, , 1654 - 1672, 01.12.2024
https://doi.org/10.35378/gujs.1395354

Abstract

Mitragynine is a natural compound found in the leaves of the Mitragyna speciosa tree, commonly known as kratom, which is primarily sourced from Southeast Asia. This review article highlights the methodologies of extraction techniques for isolating mitragynine, purification, characterization, and biosynthesis, including the complete synthesis of mitragynine and its derivatives, and briefly summarizes their biological activities and toxicology of mitragynine. The study was conducted by searching several scientific databases. There were extraction methods for mitragynine, including organic solvent extraction (hexane, chloroform, and methanol), green solvent extraction (distilled water), ultrasound-assisted extraction, and accelerated solvent extraction. The purification process of mitragynine using column chromatography with various eluen, including n-hexane, ethyl acetate, and petroleum ether. The natural mitragynine is mainly generated from the shikimate pathway and monoterpenoid secoiridoid pathway. Furthermore, there were several methods for the complete synthesis of mitragynine and the alteration of its structure. Mitragynine and its derivatives possess various pharmacological properties, including anticancer, Analgesic effects, gastrointestinal effects, antidepressant effects, Impact on cognitive function, antioxidant, and antidiabetic. The higher doses of mitragynine (100 mg/kg) in rats led to changes in hematology and the histopathological examination of the liver and brain indicates signs of toxicity.

References

  • [1] Kruegel, A. C., Uprety, R., Grinnell, S. G., Langreck, C., Pekarskaya, E. A., Le Rouzic, V., Ansonoff, M., Gassaway, M. M., Pintar, J. E., Pasternak, G. W., Javitch, J. A., Majumdar, S., Sames, D., “7-Hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects”, ACS Central Science, 5(6): 992–1001, (2019).
  • [2] Amrianto, A., Ishak, S. S. O., Putra, N., Salsabila, S., Al Muqarrabun, L. M. R., “Mitragynine: a review of its extraction, identification, and purification methods”, Current Research on Biosciences and Biotechnology, 3(1): 165–171, (2021).
  • [3] Ramanathan, S., Parthasarathy, S., Murugaiyah, V., Magosso, E., Tan, S. C., Mansor, S. M., “Understanding the physicochemical properties of mitragynine, a principal alkaloid of Mitragyna speciosa, for preclinical evaluation”, Molecules, 20(3): 4915-4927, (2015).
  • [4] Hassan, Z., Muzaimi, M., Navaratnam, V., Yusoff, N. H., Suhaimi, F. W., Vadivelu, R., Vicknasingam, B. K., Amato, D., von Hörsten, S., Ismail, N. I., Jayabalan, N., Hazim, A. I., Mansor, S. M., Müller, C. P., “From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction”, Neuroscience and Biobehavioral Reviews, 37(2): 138–151, (2013).
  • [5] Matsumoto, K., Horie, S., Ishikawa, H., Takayama, H., Aimi, N., Ponglux, D., Watanabe, K., “Antinociceptive effect of 7-hydroxymitragynine in mice: discovery of an orally active opioid analgesic from the Thai medicinal herb mitragyna speciosa”, Life Sciences, 74(17): 2143–2155, (2004).
  • [6] Beng, G. T., Hamdan, M. R, Siddiqui, M. J, Mordi, M. N., Mansor, S. M., “A simple and cost effective isolation and purification protocol of mitragynine from mitragyna speciosa korth (ketum) leaves”, The Malaysian Journal of Analytical Sciences, 15(1): 54–60, (2011).
  • [7] Tanti, Lalangi, C. A., Arfiyani, E., Ningtias, W., Maulida, E.N., “Mitragynine percentages of various Kratom variants seized in Indonesia: A quantitative analysis using liquid chromatography-photo diode array detector”, International Journal of Applied Pharmaceutic, 13(5): 252–256, (2021).
  • [8] Leksungnoen, N., Andriyas, T., Ngernsaengsaruay, C., Uthairatsamee, S., Racharak, P., Sonjaroon, W., Kjelgren, R., Pearson, B. J., McCurdy, C. R., Sharma, A., “Variations in mitragynine content in the naturally growing Kratom (mitragyna speciosa) population of Thailand”, Frontiers in Plant Science, 13: 1028547, (2022).
  • [9] Prozialeck, W. C., Edwards, J. R., Lamar, P. C., Plotkin, B. J., Sigar, I. M., Grundmann, O., Veltri, C. A., “Evaluation of the mitragynine content, levels of toxic metals and the presence of microbes in kratom products purchased in the western suburbs of Chicago”, International Journal of Environmental Research And Public Health, 17(15): 5512, (2020).
  • [10] Cinosi, E., Martinotti, G., Simonato, P., Singh, D., Demetrovics, Z., Roman-Urrestarazu, A., Bersani, F. S., Vicknasingam, B., Piazzon, G., Li, J. H., Yu, W. J., Kapitány-Fövény, M., Farkas, J., Di Giannantonio, M., Corazza, O., “Following "the Roots" of Kratom (Mitragyna speciosa): The evolution of an enhancer from a traditional use to increase work and productivity in Southeast asia to a recreational psychoactive drug in western countries”, BioMed Research International, 2015: 968786, (2015).
  • [11] Corkery, J. M., Streete, P., Claridge, H., Goodair, C., Papanti, D., Orsolini, L., Schifano, F., Sikka, K., Körber, S., Hendricks, A., “Characteristics of deaths associated with kratom use”, Journal of Psychopharmacology, 33(9): 1102–1123, (2019).
  • [12] Orio, L., Alexandru, L., Cravotto, G., Mantegna, S., Barge, A., “UAE, MAE, SFE-CO2 and classical methods for the extraction of Mitragyna speciosa leaves”, Ultrasonics Sonochemistry, 19(3), 591–595, (2012).
  • [13] Field E., “XCVIIL-Mitragynine and mitraversine”, Journal of the Chemical Society, Transactions, 119: 887–891, (1921).
  • [14] Tuntiyasawasdikul, S., Junlatat, J.,Tabboon, P., Limpongsa, E., Jaipakdee, N., “Mitragyna speciosa ethanolic extract: Extraction, anti-inflammatory, cytotoxicity, and transdermal delivery assessments”, Industrial Crops and Products, 208: 117909, (2004).
  • [15] Houghton, J. P., Latiff, A., Said, M. I., “Alkaloids from Mitrgyna Speciosa”, Phytochemistry, 30: 347–350, (1991).
  • [16] Parthasarathy, S., Ramanathan, S., Murugaiyah, V., Hamdan, M. R., Said, M. I., Lai, C. S., Mansor, S. M., “A simple HPLC-DAD method for the detection and quantification of psychotropic mitragynine in Mitragyna speciosa (ketum) and its products for the application in forensic investigation”, Forensic Science International, 226(1-3): 183–187, (2013).
  • [17] Mustafa, R. R., Sukor, R., Mohd Nor, S. M., Saari, N., Azri, F. A., “Enhancing extraction yield and purity of mitragynine from mitragyna speciosa through sequential solvent extraction and characterisation using nmr technique”, International Journal of Scientific and Technology Research, 9(3): 3846–3854, (2020).
  • [18] Flores-Bocanegra, L., Raja, H. A., Graf, T. N., Augustinović, M., Wallace, E. D., Hematian, S., Kellogg, J. J., Todd, D. A., Cech, N. B., Oberlies, N. H., “The chemistry of Kratom [Mitragyna speciosa]: updated characterization data and methods to elucidate indole and oxindole alkaloids”, Journal of Natural Products, 83(7): 2165–2177, (2020).
  • [19] Sharma, A., Kamble, S. H., León, F., Chear, N. J., King, T. I., Berthold, E. C., Ramanathan, S., McCurdy, C. R., Avery, B. A., “Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra-performance liquid chromatography-tandem mass spectrometry”, Drug Testing and Analysis, 11(8): 1162–1171, (2019).
  • [20] Khunnawutmanotham, N., Chimnoi, N., Nangkoed, P., Hasakunpaisarn, A., Wiwattanapaisarn, W., Techasakul, S., “Facile extraction of three main indole alkaloids from mitragyna speciosa by using hot water”, ChemistrySelect, 6(38): 10221–10225, (2021).
  • [21] Kikura-Hanajiri, R., Kawamura, M., Maruyamam T., Kitajimam M., Takayama, H., Goda, Y., “Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant “kratom” (Mitragyna speciosa) by LC-ESI-MS”, Forensic Toxicology, 27: 67–74, (2009).
  • [22] Haris, H. M., “An optimised recovery of mitragynine from mitragyna speciosa using freeze drying and ultrasonic-assisted extraction method”, The Experiment, 15: 1077–1083, (2013).
  • [23] Karunakaran, T., Goh, Y.S., Santhanam, R., Murugaiyah, V., Abu Bakar, M.H., Ramanathan, S., “RP-HPLC-DAD analysis of mitragynine content in Mitragyna speciosa Korth. (Ketum) leaf extracts prepared using ultrasound assisted extraction technique and their cytotoxicity”, Separations, 9(11): 345, (2022).
  • [24] Isnaeni, N., Saefumillah, A., Cahyana, A. H., “Preliminary study of isolation and purification mitragynine from kratom leaves”. Materials Science Forum, 1061: 173–179, (2022).
  • [25] Goh, Y. S., Karunakaran, T., Murugaiyah, V., Santhanam, R., Abu Bakar, M. H., Ramanathan, S., “Accelerated Solvent Extractions (ASE) of Mitragyna speciosa Korth. (Kratom) Leaves: Evaluation of Its Cytotoxicity and Antinociceptive Activity”, Molecules, 26(12): 3704, (2021).
  • [26] Váradi, A., Marrone, G. F., Palmer, T. C., Narayan, A., Szabó, M. R., Le Rouzic, V., Grinnell, S. G., Subrath, J. J., Warner, E., Kalra, S., Hunkele, A., Pagirsky, J., Eans, S. O., Medina, J. M., Xu, J., Pan, Y. X., Borics, A., Pasternak, G. W., McLaughlin, J. P., Majumdar, S., “Mitragynine/corynantheidine pseudoindoxyls as opioid analgesics with mu agonism and delta antagonism, which do not recruit β-arrestin-2”, Journal of medicinal chemistry, 59(18): 8381–8397, (2016).
  • [27] Sakamoto, J., Kitajima, M., Ishikawa, H., “Asymmetric total syntheses of mitragynine, speciogynine, and 7-hydroxymitragynine”, Chemical and Pharmaceutical bulletin, 70(9): 662–668, (2022).
  • [28] Fu H., “A mass spectrometric study of kratom compounds by direct infusion electrospray ionization triple quadrupole mass spectrometry”, Detection, 4(3): 66–67, (2016).
  • [29] Lelono, A, A., Latifah, I. L., Herdiawan, H., Cahyani, R. W., “Extraction and identification of Mitragynine from the Kratom Leaf (Mitragyna speciosa) using HFC-134a subcritical system”, IOP Conference Series: Materials Science and Engineering, 1011: 012045, (2021).
  • [30] Shamima, A. R., Fakurazi, S., Hidayat, M. T., Hairuszah, I., Moklas, M. A. M., Arulselvan, P., “Antinociceptive action of isolated mitragynine from Mitragyna Speciosa through activation of opioid receptor system”, International Journal of Molecular Sciences, 13(9): 11427–11442, (2012).
  • [31] Carvalho, P., Furr Iii, E. B., McCurdy, C., “(E)-Methyl 2-[(2S,3S,12bR)-3-ethyl-8-meth-oxy-1,2,3,4,6,7,12,12b-octa-hydro-indolo[2,3-a]quinolizin-2-yl]-3-methoxy-acrylate ethanol solvate”, Acta crystallographica. Section E, Structure reports online, 65(6), o1441–o1442, (2009).
  • [32] Charoonratanaa, T., Wungsintaweekul, J., Pathompak, P., Georgiev, M. I., Choi, Y. H., Verpoorte, R., “Limitation of mitragynine biosynthesis in Mitragyna speciosa (Roxb.) Korth. through tryptamine availability”, Zeitschrift fur Naturforschung. C, Journal of Biosciences, 68(9-10): 394–405, (2013).
  • [33] O'Connor, S. E., Maresh, J. J., “Chemistry and biology of monoterpene indole alkaloid biosynthesis”, Natural Product Reports, 23(4), 532–547, (2006).
  • [34] Jumali, S. S., Said, I. M., Baharum, S. N., Ismail, I., Rahman, R. A., Zainal, Z., “Molecular cloning and characterization of strictosidine synthase, a key gene in biosynthesis of mitragynine from mitragyna speciosa”, African Journal of Biotechnology, 10: 15238–15244, (2011).
  • [35] Tatsis, E. C., Carqueijeiro, I., Dugé de Bernonville, T., Franke, J., Dang, T. T., Oudin, A., Lanoue, A., Lafontaine, F., Stavrinides, A. K., Clastre, M., Courdavault, V., O'Connor, S. E., “A three enzyme system to generate the Strychnos alkaloid scaffold from a central biosynthetic intermediate”, Nature Communications, 8(1): 316, (2017).
  • [36] Schotte, C., Jiang, Y., Grzech, D., Dang, T. T., Laforest, L. C., León, F., Mottinelli, M., Nadakuduti, S. S., McCurdy, C. R., O'Connor, S. E., “Directed biosynthesis of mitragynine stereoisomers” Journal of the American Chemical Society, 145(9): 4957–4963, (2023).
  • [37] Takayama, H., Maeda, M., Ohbayashi, S., Kitajima, M., Sakai, SI., Aimi, N., “The first total synthesis of (-)-mitragynine, an analgesic indole alkaloid in mitragyna speciosa”, Tetrahedron Letter, 36(51): 9337–9340, (1995).
  • [38] Ma, J., Yin, W., Zhou, H., Cook, J. M., “Total synthesis of the opioid agonistic indole alkaloid mitragynine and the first total syntheses of 9-methoxygeissoschizol and 9-methoxy-Nb-methylgeissoschizol”, Organic Letters, 9(18): 3491–3494, (2007).
  • [39] Sun, X., Ma, D., “Organocatalytic approach for the syntheses of corynantheidol, dihydrocorynantheol, protoemetinol, protoemetine, and mitragynine”, Chemistry an Asian Journal, 6(8): 2158–2165, (2011).
  • [40] Kerschgens, I. P., Claveau, E., Wanner, M. J., Ingemann, S., Maarseveen, J. H. V., Hiemstra, H., “Total syntheses of mitragynine, paynantheine and speciogynine via an enantioselective thiourea-catalysed Pictet-Spengler reaction”, Chemical Communication, 48: 12243–12245, (2012).
  • [41] Takayama, H., Ishikawa, H., Kurihara, M., Kitajima, M., Aimi, N., Ponglux, D., Koyama, F., Matsumoto, K., Moriyama, T., Yamamoto, L. T., Watanabe, K., Murayama, T., Horie, S., “Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands”, Journal of Medicinal Chemistry, 45(9): 1949–1956, (2002).
  • [42] Chakraborty, S., DiBerto, J. F., Faouzi, A., Bernhard, S. M., Gutridge, A. M., Ramsey, S., Zhou, Y., Provasi, D., Nuthikattu, N., Jilakara, R., Nelson, M. N. F., Asher, W. B., Eans, S. O., Wilson, L. L., Chintala, S. M., Filizola, M., van Rijn, R. M., Margolis, E. B., Roth, B. L., McLaughlin, J. P., Che, T., Sames, D., Javitchi, J. A., Majumdar, S., “A Novel mitragynine analog with low-efficacy mu opioid receptor agonism displays antinociception with attenuated adverse effects”, Journal of Medicinal Chemistry, 64(18): 13873–13892, (2021).
  • [43] Bhowmik, S., Galeta, J., Havel, V., Nelson, M., Faouzi, A., Bechand, B., Ansonoff, M., Fiala, T., Hunkele, A., Kruegel, A. C., Pintar, J. E., Majumdar, S., Javitch, J. A., Sames, D., “Site selective C-H functionalization of Mitragyna alkaloids reveals a molecular switch for tuning opioid receptor signaling efficacy”, Nature Communications, 12(1):3858, (2021).
  • [44] Takayama, H., “Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa”, Chemical and Pharmaceutical Bulletin, 52(8):916–928, (2004).
  • [45] Goh, T. B., Koh, R. Y., Mordi, M. N., Mansor, S. M., “Antioxidant value and antiproliferative efficacy of mitragynine and a silane reduced analogue”, Asian Pacific Journal of Cancer Prevention, 15(14): 5659–5665, (2014).
  • [46] Domnic, G., Jeng-Yeou Chear, N., Abdul Rahman, S. F., Ramanathan, S., Lo, K. W., Singh, D., Mohana-Kumaran, N., Combinations of indole based alkaloids from Mitragyna speciosa (Kratom) and cisplatin inhibit cell proliferation and migration of nasopharyngeal carcinoma cell lines”, Journal of Ethnopharmacology, 279:114391, (2021).
  • [47] Priatna, P. A., Pratama, R. R., Widyowati, R., Sukardiman, S., “Molecular docking estrogen receptor alpha antagonist and p53- mdm2 inhibitor, admet prediction of alkaloid compound from mitragyna speciosa for breast cancer therapy”, Pharmacognosy Journal, 14(6s):912–916, (2023).
  • [48] Matsumoto, K., Yamamoto, L. T., Watanabe, K., Yano, S., Shan, J., Pang, P. K., Ponglux, D., Takayama, H., Horie, S., “Inhibitory effect of mitragynine, an analgesic alkaloid from Thai herbal medicine, on neurogenic contraction of the vas deferens”, Life Sciences, 78(2):187–194, (2005).
  • [49] Obeng, S., Wilkerson, J. L., León, F., Reeves, M. E., Restrepo, L. F., Gamez-Jimenez, L. R., Patel, A., Pennington, A., Taylor, V. A., Ho, N. P., Braun, T., Fortner, J. D., Crowley, M. L., Williamson, M. R., Pallares, V. L. C., Mottinelli, M., Londoño, C. L., McCurdy, C. R., McMahon, L. R., Hiranita, T., “Pharmacological comparison of mitragynine and 7-Hydroxymitragynine: In-vitro affinity and efficacy for m-opioid receptor and opioid-like behavioral effects in rats”, The Journal of Pharmacology and Experimental Therapeutics, 376(3):410–427, (2021).
  • [50] Tsuchiya, S., Miyashita, S., Yamamoto, M., Horie, S., Sakai, S., Aimi, N., Takayama, H., Watanabe, K., “Effect of mitragynine, derived from Thai folk medicine, on gastric acid secretion through opioid receptor in anesthetized rats”, European Journal of Pharmacology, 443(1-3):185–188, (2002).
  • [51] Matsumoto, K., Hatori, Y., Murayama, T., Tashima, K., Wongseripipatana, S., Misawa, K., Kitajima, M., Takayama, H., Horie, S., “Involvement of mu-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragyna speciosa”, European Journal of Pharmacology, 549(1-3):63–70, (2006).
  • [52] Idayu, N. F., Hidayat, M. T., Moklas, M. A., Sharida, F., Raudzah, A. R., Shamima, A. R., Apryani, E., “Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression”, Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 18(5):402–407, (2011).
  • [53] Apryani, E., Hidayat, M. T., Moklas, M. A., Fakurazi, S., Idayu, N. F., “Effects of mitragynine from Mitragyna speciosa Korth leaves on working memory”, Journal of Ethnopharmacology, 129(3):357–360, (2010).
  • [54] Ammar, I. H., Mustapha, Sharif, M. M., “The effects on motor behaviour and short-term memory tasks in mice following an acute administration of Mitragyna speciosa alkaloid extract and mitragynine”, Journal of Medicinal Plants Research, 5(24): 5810–5817, (2011).
  • [55] Lee, S. Y., Mediani, A., Ashikin, A. H. N., Azliana, A. B. S., Abas, F.. “Antioxidant and [alpha]-glucosidase inhibitory activities of the leaf and stem of selected traditional medicinal plants”, International Food Research Journal, 21(1):379–386, (2014).
  • [56] Yuniarti, R., Nadia, S., Alamanda, A., Zubir, M., Syahputra, R. A., Nizam, M., “Characterization, phytochemical screenings and antioxidant activity test of kratom leaf ethanol extract (mitragyna speciosa Korth) using dpph method”, Journal Phyic Conference Series, 1462(1):012026, (2020).
  • [57] Limcharoen, T., Pouyfung, P., Ngamdokmai, N., Prasopthum, A., Ahmad, A. R., Wisdawati, W., Prugsakij, W., Warinhomhoun, S., “Inhibition of α-Glucosidase and Pancreatic Lipase Properties of Mitragyna speciosa (Korth.) Havil. (Kratom) Leaves”, Nutrients, 14(19):3909, (2022).
  • [58] Niyomdecha, M., Muandao, K., Kuttiyod, T., Sanongkiet, S., “α-glucosidase inhibition activities of crude extract and mitragynine from Mitragyna Speciosa Korth”, International Journal of Health Sciences, 6(S3):10254–10261, (2022).
  • [59] Annuar, N. A., K., Azlan, U. K., Mediani, A., Tong, X., Han, R., Al-Olayan, E., Baharum, S. N., Bunawan, H., Sarian, M. N., Hamezah, H. S., Jantan, I., “An insight review on the neuropharmacological effects, mechanisms of action, pharmacokinetics and toxicity of mitragynine”, Biomedicine and Pharmacotherapy, 171:116134, (2024).
  • [60] Meireles, V., Rosado, T., Barroso, M., Soares, S., Gonçalves, J., Luís, Â., Caramelo, D., Simão, A. Y., Fernández, N., Duarte, A. P., Gallardo, E., “Mitragyna speciosa: clinical, toxicological aspects and analysis in biological and non-biological samples”, Medicines, 6(1):35, (2019).
  • [61] Kerrigan, S., Basiliere, S., “Kratom: A systematic review of toxicological issues”, Wiley Interdisciplinary Reviews: Forensic Science, 4(1):e1420, (2022).
  • [62] Macko, E., Weisbach, J. A., Douglas, B., “Some observations on the pharmacology of mitragynine”, Archives internationales de pharmacodynamie et de therapie, 198(1):145–161, (1972).
  • [63] Janchawee, B., Keawpradub, N., Chittrakarn, S., Prasettho, S., Wararatananurak, P., Sawangjareon, K., “A high-performance liquid chromatographic method for determination of mitragynine in serum and its application to a pharmacokinetic study in rats”, Biomedical chromatography : BMC, 21(2), 176–183, (2007).
  • [64] Saidin, N. A., Thomas, R., Hiromitsu, T., Elaine, H., Nigel, G., “Malaysian Kratom, a phyto-pharmaceutical of abuse: Studies on the mechanism of its cytotoxicity”, Toxicology, 253:19-20, (2008).
  • [65] Sabetghadam, A., Ramanathan, S., Sasidharan, S., Mansor, S. M., “Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats”, Journal of Ethnopharmacology, 146(3):815–823, (2013).
  • [66] Sabetghadam, A., Navaratnam, V., Mansor, S. M., “Dose-response relationship, acute toxicity, and therapeutic index between the alkaloid extract of Mitragyna speciosa and its main active compound mitragynine in mice”, Drug Development Research, 74(1):23–30, (2013).
  • [67] Chakraborty, S., Uprety, R., Slocum, S. T., Irie, T., Le Rouzic, V., Li, X., Wilson, L. L., Scouller, B., Alder, A. F., Kruegel, A. C., Ansonoff, M., Varadi, A., Eans, S. O., Hunkele, A., Allaoa, A., Kalra, S., Xu, J., Pan, Y. X., Pintar, J., Kivell, B. M., Majumdar, S., “Oxidative metabolism as a modulator of kratom's biological actions”, Journal of Medicinal Chemistry, 64(22):16553–16572, (2021).
  • [68] Wang, S., Xu, D. J., Cai, J. B., Huang, Y. Z., Zou, J. G., Cao, K. J., “Rapid component I(Kr) of cardiac delayed rectifier potassium currents in guinea-pig is inhibited by alpha(1)-adrenoreceptor activation via protein kinase A and protein kinase C-dependent pathways”, European Journal of Pharmacology, 608(1-3):1–6, (2009).
  • [69] Tay, Y. L., Teah, Y. F., Chong, Y. M., Jamil, M. F. A., Kollert, S., Adenan, M. I., Wahab, H. A., Döring, F., Wischmeyer, E., Tan, M. L., “Mitragynine and its potential blocking effects on specific cardiac potassium channels”; Toxicology and Applied Pharmacology, 305:22–39, (2016).
  • [70] Papsun, D. M., Chan-Hosokawa, A., Friederich, L., Brower, J., Graf, K., Logan, B., “The trouble with kratom: analytical and interpretative issues involving mitragynine”, Journal of Analytical Toxicology, 43(8):615–629, (2019).
Year 2024, , 1654 - 1672, 01.12.2024
https://doi.org/10.35378/gujs.1395354

Abstract

References

  • [1] Kruegel, A. C., Uprety, R., Grinnell, S. G., Langreck, C., Pekarskaya, E. A., Le Rouzic, V., Ansonoff, M., Gassaway, M. M., Pintar, J. E., Pasternak, G. W., Javitch, J. A., Majumdar, S., Sames, D., “7-Hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects”, ACS Central Science, 5(6): 992–1001, (2019).
  • [2] Amrianto, A., Ishak, S. S. O., Putra, N., Salsabila, S., Al Muqarrabun, L. M. R., “Mitragynine: a review of its extraction, identification, and purification methods”, Current Research on Biosciences and Biotechnology, 3(1): 165–171, (2021).
  • [3] Ramanathan, S., Parthasarathy, S., Murugaiyah, V., Magosso, E., Tan, S. C., Mansor, S. M., “Understanding the physicochemical properties of mitragynine, a principal alkaloid of Mitragyna speciosa, for preclinical evaluation”, Molecules, 20(3): 4915-4927, (2015).
  • [4] Hassan, Z., Muzaimi, M., Navaratnam, V., Yusoff, N. H., Suhaimi, F. W., Vadivelu, R., Vicknasingam, B. K., Amato, D., von Hörsten, S., Ismail, N. I., Jayabalan, N., Hazim, A. I., Mansor, S. M., Müller, C. P., “From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction”, Neuroscience and Biobehavioral Reviews, 37(2): 138–151, (2013).
  • [5] Matsumoto, K., Horie, S., Ishikawa, H., Takayama, H., Aimi, N., Ponglux, D., Watanabe, K., “Antinociceptive effect of 7-hydroxymitragynine in mice: discovery of an orally active opioid analgesic from the Thai medicinal herb mitragyna speciosa”, Life Sciences, 74(17): 2143–2155, (2004).
  • [6] Beng, G. T., Hamdan, M. R, Siddiqui, M. J, Mordi, M. N., Mansor, S. M., “A simple and cost effective isolation and purification protocol of mitragynine from mitragyna speciosa korth (ketum) leaves”, The Malaysian Journal of Analytical Sciences, 15(1): 54–60, (2011).
  • [7] Tanti, Lalangi, C. A., Arfiyani, E., Ningtias, W., Maulida, E.N., “Mitragynine percentages of various Kratom variants seized in Indonesia: A quantitative analysis using liquid chromatography-photo diode array detector”, International Journal of Applied Pharmaceutic, 13(5): 252–256, (2021).
  • [8] Leksungnoen, N., Andriyas, T., Ngernsaengsaruay, C., Uthairatsamee, S., Racharak, P., Sonjaroon, W., Kjelgren, R., Pearson, B. J., McCurdy, C. R., Sharma, A., “Variations in mitragynine content in the naturally growing Kratom (mitragyna speciosa) population of Thailand”, Frontiers in Plant Science, 13: 1028547, (2022).
  • [9] Prozialeck, W. C., Edwards, J. R., Lamar, P. C., Plotkin, B. J., Sigar, I. M., Grundmann, O., Veltri, C. A., “Evaluation of the mitragynine content, levels of toxic metals and the presence of microbes in kratom products purchased in the western suburbs of Chicago”, International Journal of Environmental Research And Public Health, 17(15): 5512, (2020).
  • [10] Cinosi, E., Martinotti, G., Simonato, P., Singh, D., Demetrovics, Z., Roman-Urrestarazu, A., Bersani, F. S., Vicknasingam, B., Piazzon, G., Li, J. H., Yu, W. J., Kapitány-Fövény, M., Farkas, J., Di Giannantonio, M., Corazza, O., “Following "the Roots" of Kratom (Mitragyna speciosa): The evolution of an enhancer from a traditional use to increase work and productivity in Southeast asia to a recreational psychoactive drug in western countries”, BioMed Research International, 2015: 968786, (2015).
  • [11] Corkery, J. M., Streete, P., Claridge, H., Goodair, C., Papanti, D., Orsolini, L., Schifano, F., Sikka, K., Körber, S., Hendricks, A., “Characteristics of deaths associated with kratom use”, Journal of Psychopharmacology, 33(9): 1102–1123, (2019).
  • [12] Orio, L., Alexandru, L., Cravotto, G., Mantegna, S., Barge, A., “UAE, MAE, SFE-CO2 and classical methods for the extraction of Mitragyna speciosa leaves”, Ultrasonics Sonochemistry, 19(3), 591–595, (2012).
  • [13] Field E., “XCVIIL-Mitragynine and mitraversine”, Journal of the Chemical Society, Transactions, 119: 887–891, (1921).
  • [14] Tuntiyasawasdikul, S., Junlatat, J.,Tabboon, P., Limpongsa, E., Jaipakdee, N., “Mitragyna speciosa ethanolic extract: Extraction, anti-inflammatory, cytotoxicity, and transdermal delivery assessments”, Industrial Crops and Products, 208: 117909, (2004).
  • [15] Houghton, J. P., Latiff, A., Said, M. I., “Alkaloids from Mitrgyna Speciosa”, Phytochemistry, 30: 347–350, (1991).
  • [16] Parthasarathy, S., Ramanathan, S., Murugaiyah, V., Hamdan, M. R., Said, M. I., Lai, C. S., Mansor, S. M., “A simple HPLC-DAD method for the detection and quantification of psychotropic mitragynine in Mitragyna speciosa (ketum) and its products for the application in forensic investigation”, Forensic Science International, 226(1-3): 183–187, (2013).
  • [17] Mustafa, R. R., Sukor, R., Mohd Nor, S. M., Saari, N., Azri, F. A., “Enhancing extraction yield and purity of mitragynine from mitragyna speciosa through sequential solvent extraction and characterisation using nmr technique”, International Journal of Scientific and Technology Research, 9(3): 3846–3854, (2020).
  • [18] Flores-Bocanegra, L., Raja, H. A., Graf, T. N., Augustinović, M., Wallace, E. D., Hematian, S., Kellogg, J. J., Todd, D. A., Cech, N. B., Oberlies, N. H., “The chemistry of Kratom [Mitragyna speciosa]: updated characterization data and methods to elucidate indole and oxindole alkaloids”, Journal of Natural Products, 83(7): 2165–2177, (2020).
  • [19] Sharma, A., Kamble, S. H., León, F., Chear, N. J., King, T. I., Berthold, E. C., Ramanathan, S., McCurdy, C. R., Avery, B. A., “Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra-performance liquid chromatography-tandem mass spectrometry”, Drug Testing and Analysis, 11(8): 1162–1171, (2019).
  • [20] Khunnawutmanotham, N., Chimnoi, N., Nangkoed, P., Hasakunpaisarn, A., Wiwattanapaisarn, W., Techasakul, S., “Facile extraction of three main indole alkaloids from mitragyna speciosa by using hot water”, ChemistrySelect, 6(38): 10221–10225, (2021).
  • [21] Kikura-Hanajiri, R., Kawamura, M., Maruyamam T., Kitajimam M., Takayama, H., Goda, Y., “Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant “kratom” (Mitragyna speciosa) by LC-ESI-MS”, Forensic Toxicology, 27: 67–74, (2009).
  • [22] Haris, H. M., “An optimised recovery of mitragynine from mitragyna speciosa using freeze drying and ultrasonic-assisted extraction method”, The Experiment, 15: 1077–1083, (2013).
  • [23] Karunakaran, T., Goh, Y.S., Santhanam, R., Murugaiyah, V., Abu Bakar, M.H., Ramanathan, S., “RP-HPLC-DAD analysis of mitragynine content in Mitragyna speciosa Korth. (Ketum) leaf extracts prepared using ultrasound assisted extraction technique and their cytotoxicity”, Separations, 9(11): 345, (2022).
  • [24] Isnaeni, N., Saefumillah, A., Cahyana, A. H., “Preliminary study of isolation and purification mitragynine from kratom leaves”. Materials Science Forum, 1061: 173–179, (2022).
  • [25] Goh, Y. S., Karunakaran, T., Murugaiyah, V., Santhanam, R., Abu Bakar, M. H., Ramanathan, S., “Accelerated Solvent Extractions (ASE) of Mitragyna speciosa Korth. (Kratom) Leaves: Evaluation of Its Cytotoxicity and Antinociceptive Activity”, Molecules, 26(12): 3704, (2021).
  • [26] Váradi, A., Marrone, G. F., Palmer, T. C., Narayan, A., Szabó, M. R., Le Rouzic, V., Grinnell, S. G., Subrath, J. J., Warner, E., Kalra, S., Hunkele, A., Pagirsky, J., Eans, S. O., Medina, J. M., Xu, J., Pan, Y. X., Borics, A., Pasternak, G. W., McLaughlin, J. P., Majumdar, S., “Mitragynine/corynantheidine pseudoindoxyls as opioid analgesics with mu agonism and delta antagonism, which do not recruit β-arrestin-2”, Journal of medicinal chemistry, 59(18): 8381–8397, (2016).
  • [27] Sakamoto, J., Kitajima, M., Ishikawa, H., “Asymmetric total syntheses of mitragynine, speciogynine, and 7-hydroxymitragynine”, Chemical and Pharmaceutical bulletin, 70(9): 662–668, (2022).
  • [28] Fu H., “A mass spectrometric study of kratom compounds by direct infusion electrospray ionization triple quadrupole mass spectrometry”, Detection, 4(3): 66–67, (2016).
  • [29] Lelono, A, A., Latifah, I. L., Herdiawan, H., Cahyani, R. W., “Extraction and identification of Mitragynine from the Kratom Leaf (Mitragyna speciosa) using HFC-134a subcritical system”, IOP Conference Series: Materials Science and Engineering, 1011: 012045, (2021).
  • [30] Shamima, A. R., Fakurazi, S., Hidayat, M. T., Hairuszah, I., Moklas, M. A. M., Arulselvan, P., “Antinociceptive action of isolated mitragynine from Mitragyna Speciosa through activation of opioid receptor system”, International Journal of Molecular Sciences, 13(9): 11427–11442, (2012).
  • [31] Carvalho, P., Furr Iii, E. B., McCurdy, C., “(E)-Methyl 2-[(2S,3S,12bR)-3-ethyl-8-meth-oxy-1,2,3,4,6,7,12,12b-octa-hydro-indolo[2,3-a]quinolizin-2-yl]-3-methoxy-acrylate ethanol solvate”, Acta crystallographica. Section E, Structure reports online, 65(6), o1441–o1442, (2009).
  • [32] Charoonratanaa, T., Wungsintaweekul, J., Pathompak, P., Georgiev, M. I., Choi, Y. H., Verpoorte, R., “Limitation of mitragynine biosynthesis in Mitragyna speciosa (Roxb.) Korth. through tryptamine availability”, Zeitschrift fur Naturforschung. C, Journal of Biosciences, 68(9-10): 394–405, (2013).
  • [33] O'Connor, S. E., Maresh, J. J., “Chemistry and biology of monoterpene indole alkaloid biosynthesis”, Natural Product Reports, 23(4), 532–547, (2006).
  • [34] Jumali, S. S., Said, I. M., Baharum, S. N., Ismail, I., Rahman, R. A., Zainal, Z., “Molecular cloning and characterization of strictosidine synthase, a key gene in biosynthesis of mitragynine from mitragyna speciosa”, African Journal of Biotechnology, 10: 15238–15244, (2011).
  • [35] Tatsis, E. C., Carqueijeiro, I., Dugé de Bernonville, T., Franke, J., Dang, T. T., Oudin, A., Lanoue, A., Lafontaine, F., Stavrinides, A. K., Clastre, M., Courdavault, V., O'Connor, S. E., “A three enzyme system to generate the Strychnos alkaloid scaffold from a central biosynthetic intermediate”, Nature Communications, 8(1): 316, (2017).
  • [36] Schotte, C., Jiang, Y., Grzech, D., Dang, T. T., Laforest, L. C., León, F., Mottinelli, M., Nadakuduti, S. S., McCurdy, C. R., O'Connor, S. E., “Directed biosynthesis of mitragynine stereoisomers” Journal of the American Chemical Society, 145(9): 4957–4963, (2023).
  • [37] Takayama, H., Maeda, M., Ohbayashi, S., Kitajima, M., Sakai, SI., Aimi, N., “The first total synthesis of (-)-mitragynine, an analgesic indole alkaloid in mitragyna speciosa”, Tetrahedron Letter, 36(51): 9337–9340, (1995).
  • [38] Ma, J., Yin, W., Zhou, H., Cook, J. M., “Total synthesis of the opioid agonistic indole alkaloid mitragynine and the first total syntheses of 9-methoxygeissoschizol and 9-methoxy-Nb-methylgeissoschizol”, Organic Letters, 9(18): 3491–3494, (2007).
  • [39] Sun, X., Ma, D., “Organocatalytic approach for the syntheses of corynantheidol, dihydrocorynantheol, protoemetinol, protoemetine, and mitragynine”, Chemistry an Asian Journal, 6(8): 2158–2165, (2011).
  • [40] Kerschgens, I. P., Claveau, E., Wanner, M. J., Ingemann, S., Maarseveen, J. H. V., Hiemstra, H., “Total syntheses of mitragynine, paynantheine and speciogynine via an enantioselective thiourea-catalysed Pictet-Spengler reaction”, Chemical Communication, 48: 12243–12245, (2012).
  • [41] Takayama, H., Ishikawa, H., Kurihara, M., Kitajima, M., Aimi, N., Ponglux, D., Koyama, F., Matsumoto, K., Moriyama, T., Yamamoto, L. T., Watanabe, K., Murayama, T., Horie, S., “Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands”, Journal of Medicinal Chemistry, 45(9): 1949–1956, (2002).
  • [42] Chakraborty, S., DiBerto, J. F., Faouzi, A., Bernhard, S. M., Gutridge, A. M., Ramsey, S., Zhou, Y., Provasi, D., Nuthikattu, N., Jilakara, R., Nelson, M. N. F., Asher, W. B., Eans, S. O., Wilson, L. L., Chintala, S. M., Filizola, M., van Rijn, R. M., Margolis, E. B., Roth, B. L., McLaughlin, J. P., Che, T., Sames, D., Javitchi, J. A., Majumdar, S., “A Novel mitragynine analog with low-efficacy mu opioid receptor agonism displays antinociception with attenuated adverse effects”, Journal of Medicinal Chemistry, 64(18): 13873–13892, (2021).
  • [43] Bhowmik, S., Galeta, J., Havel, V., Nelson, M., Faouzi, A., Bechand, B., Ansonoff, M., Fiala, T., Hunkele, A., Kruegel, A. C., Pintar, J. E., Majumdar, S., Javitch, J. A., Sames, D., “Site selective C-H functionalization of Mitragyna alkaloids reveals a molecular switch for tuning opioid receptor signaling efficacy”, Nature Communications, 12(1):3858, (2021).
  • [44] Takayama, H., “Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa”, Chemical and Pharmaceutical Bulletin, 52(8):916–928, (2004).
  • [45] Goh, T. B., Koh, R. Y., Mordi, M. N., Mansor, S. M., “Antioxidant value and antiproliferative efficacy of mitragynine and a silane reduced analogue”, Asian Pacific Journal of Cancer Prevention, 15(14): 5659–5665, (2014).
  • [46] Domnic, G., Jeng-Yeou Chear, N., Abdul Rahman, S. F., Ramanathan, S., Lo, K. W., Singh, D., Mohana-Kumaran, N., Combinations of indole based alkaloids from Mitragyna speciosa (Kratom) and cisplatin inhibit cell proliferation and migration of nasopharyngeal carcinoma cell lines”, Journal of Ethnopharmacology, 279:114391, (2021).
  • [47] Priatna, P. A., Pratama, R. R., Widyowati, R., Sukardiman, S., “Molecular docking estrogen receptor alpha antagonist and p53- mdm2 inhibitor, admet prediction of alkaloid compound from mitragyna speciosa for breast cancer therapy”, Pharmacognosy Journal, 14(6s):912–916, (2023).
  • [48] Matsumoto, K., Yamamoto, L. T., Watanabe, K., Yano, S., Shan, J., Pang, P. K., Ponglux, D., Takayama, H., Horie, S., “Inhibitory effect of mitragynine, an analgesic alkaloid from Thai herbal medicine, on neurogenic contraction of the vas deferens”, Life Sciences, 78(2):187–194, (2005).
  • [49] Obeng, S., Wilkerson, J. L., León, F., Reeves, M. E., Restrepo, L. F., Gamez-Jimenez, L. R., Patel, A., Pennington, A., Taylor, V. A., Ho, N. P., Braun, T., Fortner, J. D., Crowley, M. L., Williamson, M. R., Pallares, V. L. C., Mottinelli, M., Londoño, C. L., McCurdy, C. R., McMahon, L. R., Hiranita, T., “Pharmacological comparison of mitragynine and 7-Hydroxymitragynine: In-vitro affinity and efficacy for m-opioid receptor and opioid-like behavioral effects in rats”, The Journal of Pharmacology and Experimental Therapeutics, 376(3):410–427, (2021).
  • [50] Tsuchiya, S., Miyashita, S., Yamamoto, M., Horie, S., Sakai, S., Aimi, N., Takayama, H., Watanabe, K., “Effect of mitragynine, derived from Thai folk medicine, on gastric acid secretion through opioid receptor in anesthetized rats”, European Journal of Pharmacology, 443(1-3):185–188, (2002).
  • [51] Matsumoto, K., Hatori, Y., Murayama, T., Tashima, K., Wongseripipatana, S., Misawa, K., Kitajima, M., Takayama, H., Horie, S., “Involvement of mu-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragyna speciosa”, European Journal of Pharmacology, 549(1-3):63–70, (2006).
  • [52] Idayu, N. F., Hidayat, M. T., Moklas, M. A., Sharida, F., Raudzah, A. R., Shamima, A. R., Apryani, E., “Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression”, Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 18(5):402–407, (2011).
  • [53] Apryani, E., Hidayat, M. T., Moklas, M. A., Fakurazi, S., Idayu, N. F., “Effects of mitragynine from Mitragyna speciosa Korth leaves on working memory”, Journal of Ethnopharmacology, 129(3):357–360, (2010).
  • [54] Ammar, I. H., Mustapha, Sharif, M. M., “The effects on motor behaviour and short-term memory tasks in mice following an acute administration of Mitragyna speciosa alkaloid extract and mitragynine”, Journal of Medicinal Plants Research, 5(24): 5810–5817, (2011).
  • [55] Lee, S. Y., Mediani, A., Ashikin, A. H. N., Azliana, A. B. S., Abas, F.. “Antioxidant and [alpha]-glucosidase inhibitory activities of the leaf and stem of selected traditional medicinal plants”, International Food Research Journal, 21(1):379–386, (2014).
  • [56] Yuniarti, R., Nadia, S., Alamanda, A., Zubir, M., Syahputra, R. A., Nizam, M., “Characterization, phytochemical screenings and antioxidant activity test of kratom leaf ethanol extract (mitragyna speciosa Korth) using dpph method”, Journal Phyic Conference Series, 1462(1):012026, (2020).
  • [57] Limcharoen, T., Pouyfung, P., Ngamdokmai, N., Prasopthum, A., Ahmad, A. R., Wisdawati, W., Prugsakij, W., Warinhomhoun, S., “Inhibition of α-Glucosidase and Pancreatic Lipase Properties of Mitragyna speciosa (Korth.) Havil. (Kratom) Leaves”, Nutrients, 14(19):3909, (2022).
  • [58] Niyomdecha, M., Muandao, K., Kuttiyod, T., Sanongkiet, S., “α-glucosidase inhibition activities of crude extract and mitragynine from Mitragyna Speciosa Korth”, International Journal of Health Sciences, 6(S3):10254–10261, (2022).
  • [59] Annuar, N. A., K., Azlan, U. K., Mediani, A., Tong, X., Han, R., Al-Olayan, E., Baharum, S. N., Bunawan, H., Sarian, M. N., Hamezah, H. S., Jantan, I., “An insight review on the neuropharmacological effects, mechanisms of action, pharmacokinetics and toxicity of mitragynine”, Biomedicine and Pharmacotherapy, 171:116134, (2024).
  • [60] Meireles, V., Rosado, T., Barroso, M., Soares, S., Gonçalves, J., Luís, Â., Caramelo, D., Simão, A. Y., Fernández, N., Duarte, A. P., Gallardo, E., “Mitragyna speciosa: clinical, toxicological aspects and analysis in biological and non-biological samples”, Medicines, 6(1):35, (2019).
  • [61] Kerrigan, S., Basiliere, S., “Kratom: A systematic review of toxicological issues”, Wiley Interdisciplinary Reviews: Forensic Science, 4(1):e1420, (2022).
  • [62] Macko, E., Weisbach, J. A., Douglas, B., “Some observations on the pharmacology of mitragynine”, Archives internationales de pharmacodynamie et de therapie, 198(1):145–161, (1972).
  • [63] Janchawee, B., Keawpradub, N., Chittrakarn, S., Prasettho, S., Wararatananurak, P., Sawangjareon, K., “A high-performance liquid chromatographic method for determination of mitragynine in serum and its application to a pharmacokinetic study in rats”, Biomedical chromatography : BMC, 21(2), 176–183, (2007).
  • [64] Saidin, N. A., Thomas, R., Hiromitsu, T., Elaine, H., Nigel, G., “Malaysian Kratom, a phyto-pharmaceutical of abuse: Studies on the mechanism of its cytotoxicity”, Toxicology, 253:19-20, (2008).
  • [65] Sabetghadam, A., Ramanathan, S., Sasidharan, S., Mansor, S. M., “Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats”, Journal of Ethnopharmacology, 146(3):815–823, (2013).
  • [66] Sabetghadam, A., Navaratnam, V., Mansor, S. M., “Dose-response relationship, acute toxicity, and therapeutic index between the alkaloid extract of Mitragyna speciosa and its main active compound mitragynine in mice”, Drug Development Research, 74(1):23–30, (2013).
  • [67] Chakraborty, S., Uprety, R., Slocum, S. T., Irie, T., Le Rouzic, V., Li, X., Wilson, L. L., Scouller, B., Alder, A. F., Kruegel, A. C., Ansonoff, M., Varadi, A., Eans, S. O., Hunkele, A., Allaoa, A., Kalra, S., Xu, J., Pan, Y. X., Pintar, J., Kivell, B. M., Majumdar, S., “Oxidative metabolism as a modulator of kratom's biological actions”, Journal of Medicinal Chemistry, 64(22):16553–16572, (2021).
  • [68] Wang, S., Xu, D. J., Cai, J. B., Huang, Y. Z., Zou, J. G., Cao, K. J., “Rapid component I(Kr) of cardiac delayed rectifier potassium currents in guinea-pig is inhibited by alpha(1)-adrenoreceptor activation via protein kinase A and protein kinase C-dependent pathways”, European Journal of Pharmacology, 608(1-3):1–6, (2009).
  • [69] Tay, Y. L., Teah, Y. F., Chong, Y. M., Jamil, M. F. A., Kollert, S., Adenan, M. I., Wahab, H. A., Döring, F., Wischmeyer, E., Tan, M. L., “Mitragynine and its potential blocking effects on specific cardiac potassium channels”; Toxicology and Applied Pharmacology, 305:22–39, (2016).
  • [70] Papsun, D. M., Chan-Hosokawa, A., Friederich, L., Brower, J., Graf, K., Logan, B., “The trouble with kratom: analytical and interpretative issues involving mitragynine”, Journal of Analytical Toxicology, 43(8):615–629, (2019).
There are 70 citations in total.

Details

Primary Language English
Subjects Natural Products and Bioactive Compounds, Organic Chemical Synthesis
Journal Section Chemistry
Authors

Teni Ernawati 0000-0003-2235-8591

Faris Hermawan 0009-0006-6923-4050

Susi Kusumaningrum 0000-0002-5388-6285

Early Pub Date September 23, 2024
Publication Date December 1, 2024
Submission Date November 24, 2023
Acceptance Date May 16, 2024
Published in Issue Year 2024

Cite

APA Ernawati, T., Hermawan, F., & Kusumaningrum, S. (2024). A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine. Gazi University Journal of Science, 37(4), 1654-1672. https://doi.org/10.35378/gujs.1395354
AMA Ernawati T, Hermawan F, Kusumaningrum S. A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine. Gazi University Journal of Science. December 2024;37(4):1654-1672. doi:10.35378/gujs.1395354
Chicago Ernawati, Teni, Faris Hermawan, and Susi Kusumaningrum. “A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine”. Gazi University Journal of Science 37, no. 4 (December 2024): 1654-72. https://doi.org/10.35378/gujs.1395354.
EndNote Ernawati T, Hermawan F, Kusumaningrum S (December 1, 2024) A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine. Gazi University Journal of Science 37 4 1654–1672.
IEEE T. Ernawati, F. Hermawan, and S. Kusumaningrum, “A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine”, Gazi University Journal of Science, vol. 37, no. 4, pp. 1654–1672, 2024, doi: 10.35378/gujs.1395354.
ISNAD Ernawati, Teni et al. “A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine”. Gazi University Journal of Science 37/4 (December 2024), 1654-1672. https://doi.org/10.35378/gujs.1395354.
JAMA Ernawati T, Hermawan F, Kusumaningrum S. A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine. Gazi University Journal of Science. 2024;37:1654–1672.
MLA Ernawati, Teni et al. “A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine”. Gazi University Journal of Science, vol. 37, no. 4, 2024, pp. 1654-72, doi:10.35378/gujs.1395354.
Vancouver Ernawati T, Hermawan F, Kusumaningrum S. A Review on Isolation, Characterization, Biosynthesis, Synthesis, Modification, Pharmacological Activities and Toxicology of Mitragynine. Gazi University Journal of Science. 2024;37(4):1654-72.