The effects of Sceletium tortuosum on cognitive impairment and it's possible activity in neurodegenerative disorders - a literature review While Sceletium spp are well known for their effects on mood and anxiety with growing evidence of clinical efficacy, there is growing research on the plants potential therapeutic effects in cognitive disorders. Clinically, there are preliminary indications of "promising cognitive enhancing effects" in humans [1] where it is assumed, alongside the monoaminergic effects, the PDE4 inhibition by mesembrine-type alkaloids plays a role in the cognitive benefits. In healthy controls, it improved executive function and cognitive flexibility. It may possibly have benefits in cognitive decline including Alzheimer's disease and in vitro pharmacological studies have indicated through induction of BDNF and elevation of cAMP [2] along with effects on AChE, MAO, NMDA [3] and other neuroprotective targets, it be of benefit in neuropsychiatric disorders "...in vitro experiments indicated that there are neuroprotective constituents in Sceletium tortuosum [that] could protect neurons to treat neurodegenerative disorders by scavenging radicals, inhibiting AChE, MAOs and NMDAR". The PDE4 inhibition has been suggested to be a potential novel therapeutic option for a broad range of neuropsychiatric conditions with cognitive impairment (improving cognitive flexibility, executive function, processing speed etc), including memory impairments and acquired brain injuries [4]. The use of herbal medicine for depression, anxiety and cognitive decline poses significant regulatory challenges [5]. References [1] Chiu S, Gericke N, Farina-Woodbury M, Badmaev V, Raheb H, Terpstra K, Antongiorgi J, Bureau Y, Cernovsky Z, Hou J, Sanchez V, Williams M, Copen J, Husni M, Goble L. Proof-of- Concept Randomized Controlled Study of Cognition Effects of the Proprietary Extract Sceletium tortuosum (Zembrin) Targeting Phosphodiesterase-4 in Cognitively Healthy Subjects: Implications for Alzheimer's Dementia. Evid Based Complement Alternat Med. https://doi.org/10.1155/2014/682014 [2] Asgharian Parina, Quispe Cristina, Herrera-Bravo Jesús, Sabernavaei Mahsa, Hosseini Kamran, Forouhandeh Haleh, Ebrahimi Tahereh, Sharafi-Badr Paria, Tarhriz Vahideh, Soofiyani Saiedeh Razi, Helon Paweł, Rajkovic Jovana, Durna Daştan Sevgi, Docea Anca Oana, Sharifi-Rad Javad, Calina Daniela, Koch Wojciech, Cho William C. Pharmacological effects and therapeutic potential of natural compounds in neuropsychiatric disorders: An update Frontiers in Pharmacology, 13, 2022 https://doi.org/10.3389/fphar.2022.926607 [3] Luo Y, Shan L, Xu L, Patnala S, Kanfer I, et al. (2022) A network pharmacology-based 1 approach to explore the therapeutic potential of Sceletium tortuosum in the treatment of neurodegenerative disorders. PLOS ONE 17(8): e0273583. https://doi.org/10.1371/journal.pone.0273583 [4] Arjan Blokland, Pim Heckman et al. Phosphodiesterase Type 4 Inhibition in CNS Diseases. Trends in Pharmacological Sciences Vol. 4 Is. 12 2019 https://doi.org/10.1016/j.tips.2019.10.006 [5] Brendler T, Brinckmann JA, Feiter U, Gericke N, Lang L, Pozharitskaya ON, Shikov AN, Smith M, Wyk BV. Sceletium for Managing Anxiety, Depression and Cognitive Impairment: A Traditional Herbal Medicine in Modern-Day Regulatory Systems. Curr Neuropharmacol. 2021;19(9):1384-1400. https://doi.org/10.2174/1570159X19666210215124737 2