Alkaloid Profiles and Activity in Different Mitragyna speciosa Strains
Abstract
Mitragyna speciosa (K.) H. (Kratom) is a tree that possesses stimulant and opioid-like analgesic effects, and is indigenous to Southeast Asia and Indochina, where it has seen widespread use for hundreds of years. The principal pharmacologically active alkaloids in kratom leaves include mitragynine (MG), 7-hydroxymitragynine (HMG), speciociliatine (SC), speciogynine (SG) and paynantheine (P). The pharmacological effects induced and their potency can vary dramatically according to variations in the proportions of alkaloid compounds present, which are related to geographic origin, stage of maturity and ecotype. Much of the analgesic and opiate-like psychoactive effect of kratom has been associated with the MG and HMG detected in M. speciosa (K.). H. Five different strains of M. speciosa (K.) H., which present differing vein colours and geographic origin, have been studied herein; red vein strains from Thailand, Malaysia and Bali, named Red Thai, Red Malay and Red Bali, a white vein strain from Borneo (White Borneo) and a green vein strain from Malaysia (Green Malay) were included in the study. Plant leaves were extracted under magnetic stirring at room temperature in a MeOH/H2O 1:1 mixture. Purified alkaloids were isolated in a number of organic extraction steps, from either aqueous basic or acidic phases, that culminated in precipitation (yields between 0.94 and 1.43%). These samples have been analysed using HPLC-DAD, HPLC-MS, HPLC-MS/MS and GC-MS to optimize the identification and quantification of the principal alkaloids present in the different strains. 24 alkaloids were detected in Red Bali whereas 11 compounds were found in the other varieties. Red Thai, Red Bali, Green Malay and White Borneo strains had a higher w/w percentage for MG than for P, while P was more abundant in Red Malay. The Green Malay variety (GMK) showed the highest w/w percentages for MG and total alkaloids in its extracts (59.7 and 94.9% respectively). The Green Malay variety was therefore chosen for in vivo pharmacological studies. The Green Malay extract has shown remarkable and significant antinociceptive and anti-inflammatory activity in mouse hot plate and carrageenan-induced paw edema tests.
References
1. Singh D., Narayanan S., Vicknasingam B. (2016) Traditional and non-traditional uses of Mitragynine (Kratom): A survey of the literature. Brain Research Bulletin, 126, 41–46.
2. Haviland G.D. (1897) A Revision of the Tribe Naucleeæ (Nat. Ord. Rubiaceæ). Botanical Journal of Linnean Society, 33, 69.
3. Field E. (1921) Mitragynine and mitraversine, two new alkaloids from species of Mitragyne. Journal of Chemical Society, 119, 887–891.
4. Hooper D. (1907) The anti-opium leaf. The Pharmaceutical Journal, 78, 453.
5. Beckett A.H., Shellard E.J., Phillipson J.D., Lee C.M. (1966) The Mitragyna species of Asia – Part. VI. Oxindole alkaloids from the leaves of Mitragyna speciosa Korth. Planta Medica, 14, 266–276.
6. Beckett A.H., Shellard E.J., Phillipson J.D., Lee C.M. (1966) The Mitragyna species of Asia – Part. VII. Indole Alkaloids from the leaves of Mitragyna speciosa Korth. Planta Medica, 14, 277–288.1
7. Shellard E.J. (1974) The alkaloids of Mitragyna with special reference to those of Mitragyna speciosa, Korth. Bulletin on Narcotics, 26, 41–55.
8. Brown P.N., Lund J.A., Murch S.J. (2017) A botanical, phytochemical and ethnomedicinal review of the genus Mitragyna Korth: Implications for products sold as kratom. Journal of Ethnopharmacology, 202, 302–325.
9. Barceloux D.G. (2012) Kratom [Mitragyna speciosa (Korth.) Havil.]. In Medical Toxicology of Drug Abuse: Synthesized Chemicals and Psychoactive Plants. John Wiley & Sons Inc. (Ed.). Hoboken, NJ, 880–885.
10. Houghton P.J., Latiff A., Said I.M. (1991) Alkaloids from Mitragyna speciosa. Phytochemistry, 30, 347–350.
11. Shellard E.J., Houghton P.J., Resha M. (1978) The Mitragyna species of Asia. Part XXXII. The alkaloids of Mitragyna speciosa Korth from Thailand. Planta Medica, 34, 253–263.
12. Leon F., Habib E., Adkins J.E., Furr E.B., McCurdy C.R., Cutler S.J. (2009) Phytochemical characterization of the leaves of Mitragyna speciosa grown in USA. Natural Product Communications, 4, 907–910.
13. Ponglux D., Wongseripipatana S., Takayama H., Kikuchi M., Kurihara M., Kitajima M., Aimi N., Sakai S. (1994) A new indole alkaloid, 7-alphahydroxy-7H-mitragynine, from Mitragyna speciosa in Thailand. Planta Medica, 60, 580–581.
14. Takayama H., Kurihara M., Kitajima M., Said I.M., Aimi N. (1998) New indole alkaloids from the leaves of Malaysian Mitragyna speciosa. Tetrahedron, 54, 8433–8440.
15. Babu K.M., McCurdy C.R., Boyer E.W. (2008) Opioid receptors and legal highs: Salvia divinorum and Kratom. Clinical Toxicology, 46, 146–152.
16. Prozialeck W.C., Jivan J.K., Andurkar S.V. (2012) Pharmacology of Kratom: An emerging botanical agent with stimulant, analgesic and opioid-like effects. The Journal of American Osteopathic Association, 112, 792–799.
17. 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. (2002) 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, 1949–1956.
18. Matsumoto K., Horie S., Ishikawa H., Takayama H., Aimi N., Ponglux D., Watanabe K. (2004) Antinociceptive effect of 7-hydroxymitragynine in mice: discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Science, 74, 2143–2155.
19. Matsumoto K., Mizowaki M., Suchitra T., Murakami Y., Takayama H., Sakai S., Aimi N., Watanabe H. (1996) Central antinociceptive effects of mitragynine in mice: contribution of descending noradrenergic and serotonergic systems. European Journal of Pharmacology, 317, 75–81.
20. Wantana R., Niwat K., Sawangjaroen K. (2007) Effects of the extracts from Mitragyna speciosa Korth. leaves on analgesic and behavioral activities in experimental animals. Songklanakarin Journal of Science and Technology, 29, Suppl. 1, 39–48.
21. Utar Z., Majid M.I.A., Adenan M.I., Jamil M.F.A., Lan T.M. (2011) Mitragynine inhibits the COX-2 mRNA expression and prostaglandin E-2 production induced by lipopolysaccharide in RAW264.7 macrophage cells. Journal of Ethnopharmacology, 136, 75–82.
22. Orio L., Alexandru L., Cravotto G., Mantegna S., Barge A. (2012) UAE, MAE, SFE-CO2 and classical methods for the extraction of Mitragyna speciosa leaves. Ultrasonics Sonochemistry, 19, 591–595.
23. Parthasarathy S., Ramanathan S., Murugaiyah V., Hamdan M.R., Said M.I., Lai C.S., Mansor S.M. (2013) 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, 183–187.
24. Mudge E.M., Brown P.N. (2017) Determination of Mitragynine in Mitragyna speciosa Raw Materials and Finished Products by Liquid Chromatography with UV Detection: Single-Laboratory Validation. Journal of AOAC International, 100, 18–24.
25. Kikura-Hanajiri R., Maruyama T., Kitajima M., Kawamura M., Takayama H., Goda Y. (2009) Simultaneous analysis of mitragynine, 7-hydroxy-mitragynine, and other alkaloids in the psychotropic plant “kratom” (Mitragyna speciosa) by LC-ESI-MS. Forensic Toxicology, 27, 67–74.
26. Avula B., Sagi S., Wang Y.H., Wang M., Ali Z., Smillie T.J., Zweigenbaum J., Khan I.A. (2015) Identification and characterization of indole and oxindole alkaloids from leaves of Mitragyna speciosa Korth using liquid chromatography-accurate QToF mass spectrometry. Journal of AOAC International, 98, 13–21.
27. Wang M., Carrell E.J., Ali Z., Avula B., Avonto C., Parcher J.F., Khan I.A. (2014) Comparison of three chromatographic techniques for the detection of mitragynine and other indole and oxindole alkaloids in Mitragyna speciosa (kratom) plants. Journal of Separation Science, 37, 1411–1418.
28. Kitajima M., Misawa K., Kogure N., Said I.M., Horie S., Hatori Y., Murayama T., Takayama H. (2006) A new indole alkaloid, 7-hydroxyspeciociliatine, from the fruits of Malaysian Mitragyna speciosa and its opioid agonistic activity. Journal of Natural Medicine, 60, 28–35.
29. Cao X.F., Wang J.S., Wang X.B., Luo J., Wang H.Y., Kong L.Y. (2013) Monoterpene indole alkaloids from the stem bark of Mitragyna diversifolia and their acetylcholine esterase inhibitory effects. Phytochemistry, 96, 389–396.
30. Chan K., Pakiam C., Rahim R.A. (2005) Psychoactive plant abuse: the identification of mitragynine in ketum and in ketum preparations. Bulletin of Narcotics, 57, 249–256.
31. Philipp A.A., Meyer M.R., Wissenbach D.K., Weber A.A., Zoerntlein S.W., Zweipfenning P.G., Maurer H.H. (2011) Monitoring of kratom or Krypton intake in urine using GC-MS in clinical and forensic toxicology. Analytical and Bioanalytical Chemistry, 400, 127–135.
32. Cornara L., Borghesi B., Canali C., Andrenacci M., Basso M., Federici S., Labra M. (2013) Smart drugs: green shuttle or real drug? International Journal of Legal Medicine, 127, 1109–1123.
33. Wang M., Carrell E.J., Ali Z., Avula B., Avonto C., Parcher J.F., Khan I.A. (2014) Comparison of three chromatographic techniques for the detection of mitragynine and other indole and oxindole alkaloids in Mitragyna speciosa (kratom) plants. Journal of Separation Science, 37, 1411–1418.
34. Shamina A.R., Fakurazi S., Hidayat M.T., Hairuszah I., Moklas M.A.M., Arulsevelan P. (2012) Antinociceptive action of isolated Mitragynine from Mitragyna speciosa through activation of opioide receptor system. International Journal of Molecular Sciences, 13, 11427–11442.
35. Di Rosa M., Capasso F., and Mascolo N. (1980) Endogenous inhibitor of prostaglandin biosynthesis in inflammation. Agents and Actions, 10, 358–360.
36. Higgs G.A., Flower R.J., and Vane J. (1979) A new approach to anti-infammatory drugs. Biochemical Pharmacology, 28, 1959–1961.
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Article first published online: September 1, 2018
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Crossref: 9
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