Research Insights: The Chemistry Of Kanna

Research Insights: Sceletium tortuosum: A Review on Its Phytochemistry, Pharmacokinetics, Biological, Pre-Clinical and Clinical Activities

This blog post is based on the article "Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, biological, pre-clinical and clinical activities" by T.L. Olatunji, F. Siebert, A.E. Adetunji, B.H. Harvey, J. Gericke, J.H. Hamman, and F. Van der Kooy, published in the Journal of Ethnopharmacology (2022, Volume 287, Article 114711). Read the full article here: Sceletium tortuosum: A review on its phytochemistry, pharmacokinetics, biological, pre-clinical and clinical activities.

Kanna, scientifically known as Sceletium tortuosum, is a succulent forb endemic to South Africa with a history of traditional use. This review summarizes research on its ethnomedicinal applications, phytochemistry, pharmacokinetics, and biological, pre-clinical, and clinical activities, focusing on publications from 2009 to 2021, with some historical context.

Background on Kanna from the Research

Sceletium tortuosum, commonly called "kanna" or "kougoed," belongs to the Aizoaceae family. Traditionally, its aerial parts are masticated, smoked, taken as tea or tincture. Ethnopharmacological relevance includes its use for relieving toothache, abdominal pain, as a mood-elevator, analgesic, hypnotic, thirst and hunger suppressant, and for intoxicating/euphoric effects. Modern interest stems from its potential in enhancing cognitive functions and supporting mood in healthy individuals, attributed to mesembrine-type alkaloids.

The review aims to comprehensively evaluate advances in ethnomedicinal use, phytochemistry, pharmacokinetics, biological and clinical activities. It retrieves data from databases like ScienceDirect, PubMed, Google Scholar, Scopus, and Web of Science, including theses and dissertations.

Ethnomedicinal Use

Historical records date back centuries, with traditional preparations involving fermentation. Indigenous groups like the Khoikhoi and San used it for endurance during hunts, social rituals, and as a trade item. Modern commercial cultivation began in 1996, expanding in South Africa and Namibia, with global export of raw materials and standardized extracts.

Phytochemistry

Twenty-five alkaloids in four classes—mesembrine, Sceletium A4, joubertiamine, and tortuosamine—have been identified, with mesembrine predominant. Key compounds include mesembrenone, mesembrine, mesembranol, and mesembrenol. Analytical methods like HPTLC, GC-MS, UHPLC-MS, and NMR have quantified these, showing variability based on cultivation, processing, and extraction. Standardized extracts aim for specific alkaloid ratios, e.g., mesembrenone plus mesembrenol ≥60% and mesembrine ≤20%.

Pharmacokinetics

Studies on absorption, distribution, metabolism, and excretion are limited. In vitro and in vivo data indicate rapid absorption, with mesembrine showing high permeability and quick metabolism. Human trials with standardized extracts report peak plasma concentrations within hours, with no accumulation over repeated doses. Alkaloids cross the blood-brain barrier, supporting central effects.

Biological and Pre-Clinical Activities

In vitro and in vivo studies demonstrate a spectrum of activities:

Antioxidant: Extracts scavenge DPPH radicals and protect against oxidative stress in cellular models.
Antimalarial: Moderate activity against Plasmodium falciparum strains.
Antimicrobial: Inhibitory effects on bacteria and fungi.
Anti-HIV: Potential against HIV enzymes like reverse transcriptase and protease.
Neuromodulatory: Influences serotonin uptake, PDE4 inhibition, and GABA binding; supports cognitive enhancement in animal models.
Immunomodulatory: Modulates cytokine release in monocytes and astrocytes.
Neuroprotection: Protects against neurotoxins in cell lines and animal models.

Animal studies show effects on brain electrical activity, with EEG profiles similar to other botanicals.

Clinical Activities

Clinical studies, primarily on standardized extracts in healthy subjects, include:

Safety and tolerability: Well-tolerated at doses up to 25 mg, with mild side effects.
Cognitive function: Enhancements in domains like executive function and processing speed via computerized tests.
Brain activity: Changes in EEG and fMRI responses to cognitive/emotional tasks.
Mood support: Reductions in anxiety scale scores in some trials.

No studies in pathological states are reported; focus is on healthy populations.

Potential Mechanisms and Implications

Activities link to mesembrine-type alkaloids' dual SRI and PDE4 inhibition, regulating serotonin and intracellular messengers. Findings support traditional uses and suggest potential for cognitive and mood support in healthy individuals.

Limitations and Future Research

Limitations include variability in alkaloid content, limited pharmacokinetic data, and focus on healthy subjects. Future perspectives involve expanded clinical trials, sustainable cultivation, and further mechanistic studies.