Citizen Plant Science - Exploring the Magnoliaceae Several alkaloids have been isolated from Magnoliaceae and Annonaceae with potentially intriguing psychopharmacological activity but extremely limited research and utilisation in the West. Of particular interest in this paper are the alkaloids of the Magnoliaceae Magnolia grandiflora , which include remerine, liriodenine and of particular note in this paper, anonaine. Common alkaloids in the Magnoliaceae The aporphine-type benzylisoquinolines including (-)-anonaine are found to often possess CNS activity, others including pukateine are currently being explored in disorders such as Parkinson's, where they are being explored as lead compounds for the design of therapeutics for increasing dopaminergic neurotransmission [1]. Others include nuciferine which seems to have an atypical antipsychotic-like receptor binding profile with unique mixed dopamine-stimulatory and dopamine-blockade effects [2]. 1 (-)-anonaine Several plants have been found to contain (-)-anonaine, including Annona spp., Magnolia grandiflora and other Magnolia spp. Goniothalamus australis and others. (-)-Anonaine is pharmacologically active and displays antitumour, vasorelaxation, antioxidative, antiparasitic and antimicrobial effects, as well as having an effect on the central nervous system (inhibiting dopamine reuptake and acting as an agonist at 5-HT1ARs, along with α1-adrenoceptor antagonism) [3]. The dopamine transporter inhibition is quite selective with limited affinity to D1 and D2 dopamine receptors. At low doses, it has displays antidepressant activity in animal models. The dopamine transporter inhibition by (-)- anonaine is relatively potent (0.8 μM), moreso than dexamphetamine and amineptine and of the same order of magnitude as nomifensine. Interestingly, despite relatively potent DAT inhibition, the longer-term net effect of (-)- anonaine on dopamine seems to be decreased dopamine content, potentially via interfering with dopamine biosynthesis via tyrosine hydroxylase [4]. This may be why, contrary to psychostimulant effects, the more traditional use of plants containing (-)-anonaine does not seem to reflect those expected in the case of more typical dopamine transporter inhibition. Also, caution is required as some studies have noted potential neurotoxicity from Annonaceae extracts [5] with some reports of atypical parkinsonism being noted. That said, while methanol extracts have displayed toxicity, hexane extracts were devoid of such, so it may not be the anonaine and related alkaloids responsible for neurotoxicity, instead it is possible Annonaceous acetogenins may be responsible. Nonetheless, psychostimulant activity seems to be lacking in anonaine containing plants: Several species of Annona (Annonaceae) are used in traditional Mexican medicine due to their anti-anxiety, anticonvulsant, and tranquilizing properties A study noted an increase in the 5-HT and DA turnover in the whole brain of mice, through both an increase in the concentration of the neurotransmitters and their metabolism from a non-polar extract of Annona cherimolia containing 1,2-dimethoxy-5,6,6a,7-tetrahydro-4H- dibenzoquinoline-3,8,9,10-tetraol, anonaine, liriodenine, and nornuciferine [6] Magnolia grandiflora leaf has been found to contain anonaine, remerine, liriodenine (0.54 % total alkaloids in the flowering leaf material) while the flowers contain liriodenine, anonaine, dehydroremerine (0.52% total alkaloids). The latter is culturally and pharmacologically interesting as the flowers are sometimes consumed, seemingly quite safely, for culinary purposes or as tea with little mention of any potential 2 psychopharmacological activity. Other Magnolia spp. are well known for their use medicinally as the bark or extracts of such, primarily due to the presence of neolignans such as magnolol and honokiol often used for their anxiolytic properties but there is no reports of any medicinal use of Magnolia in line with potentially a more psychostimulant activity that I've seen in my research. Another alkaloidal constituent is remerine. This alkaloid was found to be quite a potent antagonist at 5-HT2A and 5-HT2C receptors and α1 receptors. The 5-HT2A/C antagonism occurs with good selectivity. Liriodenine, practically devoid of DAT inhibition, retained some 5-HT1A and α1 affinity. It stimulates respiration in animals and has a short lasting hypotensive effect. It was shown to have antimicrobial activity with relatively low acute toxicity and relatively potent anti- cancer effects. It was found to be a muscarinic receptor antagonist. In combination with anonaine etc, it displayed anti-depressant effects. The purpose of this paper was to explore thin-layer chromatography of a variety of Magnolia grandiflora , a dwarf variety 'Little Gem'. Experimental : Plant material, mature leaf, was collected during Autumn flowering and dehydrated at 70 deg. C. The powdered dry leaf material was basified with aqueous ammonia solution and macerated with warm isopropanol. The isopropanol solution was concentrated to a small sample. TLC (silica, 0.2mm, glass backed, acetone:white spirits:1:1) gave separation of two visibly pigmented low and high Rf regions, Rf = 0.18 and 0.89. I 2 visualisation showed invisible broad regions at Rf =0.35 and 0.63. Other analyses have documented the presence of sesquiterpene lactones as major leaf constituents so these should be considered. TLC on plain leaf a) no visualisation b) I 2 visualisation References: [1] Federico Dajas-Bailador, Marcelo Asencio et al. Dopaminergic pharmacology and 3 antioxidant properties of pukateine, a natural product lead for the design of agents increasing dopamine neurotransmission, General Pharmacology: The Vascular System Volume 32, Issue 3, March 1999, Pages 373-379 https://doi.org/10.1016/s0306-3623(98)00210-9 [2] Farrell MS, McCorvy JD, Huang XP, Urban DJ, White KL, et al. (2016) In Vitro and In Vivo Characterization of the Alkaloid Nuciferine. PLOS ONE 11(3): e0150602. https://doi.org/10.1371/journal.pone.0150602 [3] Hsing-Tan Li,Hui-Ming Wu et al. The Pharmacological Activities of ( − )-Anonaine Molecules 2013, 18, 8257-8263. https://doi.org/10.3390/molecules18078257 [4] Lee JJ, Jin CM, Kim YK, Ryu SY, Lim SC, Lee MK. Effects of anonaine on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells. Molecules. 2008 Feb 27;13(2):475-87 https://doi.org/10.3390%2Fmolecules13020475 [5] Höllerhage, M., Rösler, T. W., Berjas, M., Luo, R., Tran, K., Richards, K. M., Smith, R. E. (2015). Neurotoxicity of Dietary Supplements from Annonaceae Species. International Journal of Toxicology, 34(6), 543–550. https://doi.org/10.1177/1091581815602252 [6] Martínez-Vázquez, M., Estrada-Reyes, R., Araujo Escalona, A. G., Ledesma Velázquez, I., Martínez-Mota, L., Moreno, J., & Heinze, G. (2012). Antidepressant-like effects of an alkaloid extract of the aerial parts of Annona cherimolia in mice. Journal of Ethnopharmacology, 139(1), 164–170. https://doi.org/10.1016/j.jep.2011.10.033 4