Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Front Plant Sci. 2024 Mar 21;15:1268101. doi: 10.3389/fpls.2024.1268101. 
eCollection 2024.

Skeletons in the closet? Using a bibliometric lens to visualise phytochemical 
and pharmacological activities linked to Sceletium, a mood enhancer.

Reddy K(1), Stafford GI(2), Makunga NP(1).

Author information:
(1)Department of Botany and Zoology, Natural Sciences Faculty, Stellenbosch 
University, Stellenbosch, South Africa.
(2)Department of Plant and Soil Sciences, University of Pretoria, Pretoria, 
South Africa.

Plants from the Sceletium genus (Aizoaceae) have been traditionally used for 
millennia by the Khoe and Khoen people in southern Africa, as an appetite 
suppressant as well as a mood elevator. In more recent times, this 
mood-elevating activity has been commercialised in the South African natural 
products industry for the treatment of anxiety and depression, with several 
products available both locally and abroad. Research on this species has seen 
rapid growth with advancements in analytical and pharmacological tools, in an 
effort to understand the composition and biological activity. The Web of Science 
(WoS) database was searched for articles related to 'Sceletium' and 
'Mesembrine'. These data were additionally analysed by bibliometric software 
(VOSviewer) to generate term maps and author associations. The thematic areas 
with the most citations were South African Traditional Medicine for mental 
health (110) and anxiolytic agents (75). Pioneer studies in the genus focused on 
chemical structural isolation, purification, and characterisation and techniques 
such as thin layer chromatography, liquid chromatography (HPLC, UPLC, and more 
recently, LC-MS), gas chromatography mass spectrometry (GC-MS), and nuclear 
magnetic resonance (NMR) to study mesembrine alkaloids. Different laboratories 
have used a diverse range of extraction and preanalytical methods that became 
routinely favoured in the analysis of the main metabolites (mesembrine, 
mesembranol, mesembranone, and Sceletium A4) in their respective experimental 
settings. In contrast with previous reviews, this paper identified gaps in the 
research field, being a lack of toxicology assays, a deficit of clinical 
assessments, too few bioavailability studies, and little to no investigation 
into the minor alkaloid groups found in Sceletium. Future studies are likely to 
see innovations in analytical techniques like leaf spray mass spectrometry and 
direct analysis in real-time ionisation coupled with high-resolution 
time-of-flight mass spectrometry (DART-HR-TOF-MS) for rapid alkaloid 
identification and quality control purposes. While S. tortuosum has been the 
primary focus, studying other Sceletium species may aid in establishing 
chemotaxonomic relationships and addressing challenges with species 
misidentification. This research can benefit the nutraceutical industry and 
conservation efforts for the entire genus. At present, little to no 
pharmacological information is available in terms of the molecular physiological 
effects of mesembrine alkaloids in medical clinical settings. Research in these 
fields is expected to increase due to the growing interest in S. tortuosum as a 
herbal supplement and the potential development of mesembrine alkaloids into 
pharmaceutical drugs.

Copyright © 2024 Reddy, Stafford and Makunga.

DOI: 10.3389/fpls.2024.1268101
PMCID: PMC10991851
PMID: 38576783

Conflict of interest statement: The authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as a potential conflict of interest. The author(s) declared that 
they were an editorial board member of Frontiers, at the time of submission. 
This had no impact on the peer review process and the final decision.


2. J Ethnopharmacol. 2022 Apr 6;287:114711. doi: 10.1016/j.jep.2021.114711. Epub 
2021 Nov 8.

Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, 
biological, pre-clinical and clinical activities.

Olatunji TL(1), Siebert F(1), Adetunji AE(2), Harvey BH(3), Gericke J(4), Hamman 
JH(4), Van der Kooy F(5).

Author information:
(1)Unit for Environmental Sciences and Management, North-West University, 
Potchefstroom, South Africa.
(2)School of Life Sciences, University of KwaZulu-Natal, Durban, 4001, South 
Africa.
(3)Centre of Excellence for Pharmaceutical Sciences, North-West University, 
Private Bag X6001, Potchefstroom, 2520, South Africa; SAMRC Unit on Risk and 
Resilience in Mental Disorders, Department of Psychiatry and Neuroscience 
Institute, University of Cape Town, South Africa.
(4)Centre of Excellence for Pharmaceutical Sciences, North-West University, 
Private Bag X6001, Potchefstroom, 2520, South Africa.
(5)Centre of Excellence for Pharmaceutical Sciences, North-West University, 
Private Bag X6001, Potchefstroom, 2520, South Africa. Electronic address: 
frank.vanderkooy@nwu.ac.za.

Erratum for
    J Ethnopharmacol. 2021 Nov 15;280:114476. doi: 10.1016/j.jep.2021.114476.

ETHNOPHARMACOLOGICAL RELEVANCE: Sceletium tortuosum (L.) N.E.Br., the most 
sought after and widely researched species in the genus Sceletium is a succulent 
forb endemic to South Africa. Traditionally, this medicinal plant is mainly 
masticated or smoked and used for the relief of toothache, abdominal pain, as a 
mood-elevator, analgesic, hypnotic, anxiolytic, thirst and hunger suppressant, 
and for its intoxicating/euphoric effects. Sceletium tortuosum is currently of 
widespread scientific interest due to its clinical potential in treating anxiety 
and depression, relieving stress in healthy individuals, and enhancing cognitive 
functions. These pharmacological actions are attributed to its phytochemical 
constituents referred to as mesembrine-type alkaloids.
AIM OF THE REVIEW: The aim of this review was to comprehensively summarize and 
critically evaluate recent research advances on the phytochemistry, 
pharmacokinetics, biological, pre-clinical and clinical activities of the 
medicinal plant S. tortuosum. Additionally, current ongoing research and future 
perspectives are also discussed.
METHODS: All relevant scientific articles, books, MSc and Ph.D. dissertations on 
botany, behavioral pharmacology, traditional uses, and phytochemistry of S. 
tortuosum were retrieved from different databases (including Science Direct, 
PubMed, Google Scholar, Scopus and Web of Science). For pharmacokinetics and 
pharmacological effects of S. tortuosum, the focus fell on relevant publications 
published between 2009 and 2021.
RESULTS: Twenty-five alkaloids belonging to four structural classes viz: 
mesembrine, Sceletium A4, joubertiamine, and tortuosamine, have been identified 
from S. tortuosum, of which the mesembrine class is predominant. The crude 
extracts and commercially available standardized extracts of S. tortuosum have 
displayed a wide spectrum of biological activities (e.g. antimalarial, 
anti-oxidant, neuromodulatory, immunomodulatory, anti-HIV, neuroprotection) in 
in vitro or in vivo studies. While the plant has been studied in clinical 
populations, this has only been in healthy subjects, so that further study in 
pathological states remains to be done. Nevertheless, the aforementioned studies 
have demonstrated that S. tortuosum has potential for enhancing cognitive 
function and managing anxiety and depression.
CONCLUSION: As an important South African medicinal plant, S. tortuosum has 
garnered many research advances on its phytochemistry and biological activities 
over the last decade. These scientific studies have shown that S. tortuosum has 
various bioactivities. The findings have further established the link between 
the phytochemistry and pharmacological application, and support the traditional 
use of S. tortuosum in the indigenous medicine of South Africa.

Copyright © 2021. Published by Elsevier B.V.

DOI: 10.1016/j.jep.2021.114711
PMID: 34758918


3. J Ethnopharmacol. 2021 Nov 15;280:114476. doi: 10.1016/j.jep.2021.114476. Epub
 2021 Jul 30.

Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, 
biological and clinical activities.

Olatunji TL(1), Siebert F(2), Adetunji AE(3), Harvey BH(4), Gericke J(5), Hamman 
JH(6), Van der Kooy F(7).

Author information:
(1)Unit for Environmental Sciences and Management, North-West University, 
Potchefstroom, South Africa. Electronic address: lois.olatunji@gmail.com.
(2)Unit for Environmental Sciences and Management, North-West University, 
Potchefstroom, South Africa. Electronic address: Frances.Siebert@nwu.ac.za.
(3)School of Life Sciences, University of KwaZulu-Natal, Durban 4001, South 
Africa. Electronic address: adetunjiademola@hotmail.com.
(4)Centre of Excellence for Pharmaceutical Sciences, North-West University, 
Private Bag X6001, Potchefstroom, 2520, South Africa; SAMRC Unit on Risk and 
Resilience in Mental Disorders, Department of Psychiatry and Mental Health, 
University of Cape Town, South Africa; Department of Pharmacology, School of 
Pharmacy, North-West University, Potchefstroom Campus, 2520, South Africa. 
Electronic address: Brian.Harvey@nwu.ac.za.
(5)Centre of Excellence for Pharmaceutical Sciences, North-West University, 
Private Bag X6001, Potchefstroom, 2520, South Africa; Department of 
Pharmacology, School of Pharmacy, North-West University, Potchefstroom Campus, 
2520, South Africa. Electronic address: johane.gericke@gmail.com.
(6)Centre of Excellence for Pharmaceutical Sciences, North-West University, 
Private Bag X6001, Potchefstroom, 2520, South Africa. Electronic address: 
Sias.Hamman@nwu.ac.za.
(7)Centre of Excellence for Pharmaceutical Sciences, North-West University, 
Private Bag X6001, Potchefstroom, 2520, South Africa. Electronic address: 
frank.vanderkooy@nwu.ac.za.

Erratum in
    J Ethnopharmacol. 2022 Apr 6;287:114711. doi: 10.1016/j.jep.2021.114711.

ETHNOPHARMACOLOGICAL RELEVANCE: Sceletium tortuosum (L.) N.E.Br, the most sought 
after and widely researched species in the genus Sceletium is a succulent forb 
endemic to South Africa. Traditionally, this medicinal plant is mainly 
masticated or smoked and used for the relief of toothache, abdominal pain, and 
as a mood-elevator, analgesic, hypnotic, anxiolytic, thirst and hunger 
suppressant, and for its intoxicating/euphoric effects. Sceletium tortuosum is 
currently of widespread scientific interest due to its clinical potential in 
treating anxiety and depression, relieving stress in healthy individuals, and 
enhancing cognitive functions. These pharmacological actions are attributed to 
its phytochemical constituents referred to as mesembrine-type alkaloids.
AIM OF THE REVIEW: The aim of this review was to comprehensively summarize and 
critically evaluate recent research advances on the phytochemistry, 
pharmacokinetics, biological and clinical activities of the medicinal plant S. 
tortuosum. Additionally, current ongoing research and future perspectives are 
also discussed.
METHODS: All relevant scientific articles, books, MSc and Ph.D. dissertations on 
botany, behavioral pharmacology, traditional uses, and phytochemistry of S. 
tortuosum were retrieved from different databases (including Science Direct, 
PubMed, Google Scholar, Scopus and Web of Science). For pharmacokinetics and 
pharmacological effects of S. tortuosum, the focus fell on relevant publications 
published between 2009 and 2021.
RESULTS: Twenty-five alkaloids belonging to four structural classes viz: 
mesembrine, Sceletium A4, joubertiamine, and tortuosamine, have been identified 
from S. tortuosum, of which the mesembrine class is predominant. The crude 
extracts and commercially available standardized extracts of S. tortuosum have 
displayed a wide spectrum of biological activities (e.g. antimalarial, 
anti-oxidant, immunomodulatory, anti-HIV, neuroprotection, enhancement of 
cognitive function) in in vitro or in vivo studies. This plant has not yet been 
studied in a clinical population, but has potential for enhancing cognitive 
function, and managing anxiety and depression.
CONCLUSION: As an important South African medicinal plant, S. tortuosum has 
garnered many research advances on its phytochemistry and biological activities 
over the last decade. These scientific studies have shown that S. tortuosum has 
various bioactivities. The findings have further established the link between 
the phytochemistry and pharmacological application, and support the traditional 
use of S. tortuosum in the indigenous medicine of South Africa.

Copyright © 2021. Published by Elsevier B.V.

DOI: 10.1016/j.jep.2021.114476
PMID: 34333104 [Indexed for MEDLINE]


4. Angew Chem Int Ed Engl. 2018 Sep 17;57(38):12328-12332. doi: 
10.1002/anie.201807302. Epub 2018 Aug 28.

Efficient Synthesis of (-)-Corynoline by Enantioselective Palladium-Catalyzed 
α-Arylation with Sterically Hindered Substrates.

Rao X(1), Li N(1), Bai H(1), Dai C(1), Wang Z(2), Tang W(1).

Author information:
(1)State Key Laboratory of Bio-Organic and Natural Products Chemistry, Center 
for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, 
University of Chinese Academy of Sciences, 345 Ling Ling Rd, Shanghai, 200032, 
China.
(2)Informatics and Technology, Astra Zeneca China, Shanghai, China.

Sterically hindered substrates can be employed in an enantioselective 
palladium-catalyzed α-arylation with the chiral monophosphorus ligand BI-DIME. 
This process enabled an efficient synthesis of the antidepressant 
(S)-nafenodone, a four-step enantioselective synthesis of the Sceletium alkaloid 
(+)-sceletium A-4, a concise five-step enantioselective synthesis of 
(-)-corynoline, as well as a three-step preparation of (-)-DeN-corynoline.

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOI: 10.1002/anie.201807302
PMID: 30074668


5. J Pharm Pharm Sci. 2015;18(4):414-23. doi: 10.18433/j3330x.

Medicinal use of Sceletium: Characterization of Phytochemical Components of 
Sceletium Plant Species using HPLC with UV and Electrospray Ionization--Tandem 
Mass Spectroscopy.

Patnala S(1), Kanfer I.

Author information:
(1)Department of Chemistry, Rhodes University, Grahamstown, South Africa.

PURPOSE: Sceletium plants have been used for its medicinal properties for 
centuries. However, there is a wide range of Sceletium plant species in which 
various alkaloidal components such as ∆7mesembrenone, mesembrenol, mesembranol, 
mesembrenone, mesembrine hydrochloride, epimesembranol and, sceletium A4 differ 
between species. Hence, to ensure the quality of Sceletium products used as a 
medicine, it is imperative to identify the appropriate species using both 
botanical and chemical methods. The chemical approach to identify and 
characterize the phytochemical composition of a particular species facilitates 
the choice of species that will provide the purported therapeutic outcome. 
Hence, specific analytical methods to identify relevant constituents from 
complex matrices are necessary. Although HPLC-UV detection is commonly used to 
identify and estimate phytochemical content of medicinal plants, use of mass 
spectroscopy (MS) and tandem mass spectroscopy (MS/MS) can unequivocally confirm 
their presence/absence based on characteristic ions and fragmentation patterns.
METHODS: The various alkaloidal components were characterized by electrospray 
ionization (ESI) MS and MS/MS using an ionizing medium of 0.1% ammonium 
hydroxide in water mixed with acetonitrile. Compounds were purified and 
characterized for use as reference standards to identify the relevant alkaloidal 
constituents of several Sceletium plant species using HPLC with on-line UV-MS 
detection.
RESULTS: ESI-MS provided the [M+H](+) ions with respective m/z values that 
related to the respective molecular weights 287, 289, 291, 287, 289, 324 and 291 
for the above mentioned alkaloids, whereas, ESI MS/MS provided the 
characteristic fragment ions to confirm the structural identity of the 
individual alkaloids and subsequently used to confirm the presence and/or 
absence of specific alkaloids in various Sceletium plant samples.
CONCLUSIONS: Whilst HPLC-UV detection has been a widely-used conventional 
analytical technique for both qualitative and quantitative analyses, the results 
highlight the necessity of ESI-MS detection to avoid erroneous identification of 
phytochemical components, particularly with mesembrine-type compounds which have 
closely related chemical structures. This article is open to POST-PUBLICATION 
REVIEW. Registered readers (see "For Readers") may comment by clicking on 
ABSTRACT on the issue's contents page.

DOI: 10.18433/j3330x
PMID: 26626243 [Indexed for MEDLINE]