Sceletium tortuosum may delay chronic disease progression via alkaloid-dependent antioxidant or anti-inflammatory action

• Published in: Journal of physiology and biochemistry 2018-11, Vol.74 (4), p.539-547
• Main Authors: Bennett, A.C., Van Camp, A., López, V., Smith, C.
• Format: Article
• Language: English
• Subjects: Acetylcholinesterase - metabolism; Animal Physiology; Anti-inflammatory agents; Anti-Inflammatory Agents, Non-Steroidal - analysis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - isolation & purification; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antioxidants; Antioxidants - analysis; Antioxidants - chemistry; Antioxidants - isolation & purification; Antioxidants - pharmacology; Astrocytes; Astrocytes - drug effects; Astrocytes - immunology; Astrocytes - metabolism; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Cell Line; Cell Survival - drug effects; Central nervous system; Cholinesterase Inhibitors - analysis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - isolation & purification; Cholinesterase Inhibitors - pharmacology; Chronic illnesses; Cytokines; Cytokines - antagonists & inhibitors; Cytokines - metabolism; Cytotoxicity; Diabetes; Diabetes mellitus; Drug Discovery; E coli; Enzyme Inhibitors - analysis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - isolation & purification; Enzyme Inhibitors - pharmacology; Ethnopharmacology; Glucocorticoids; GPI-Linked Proteins - antagonists & inhibitors; GPI-Linked Proteins - metabolism; Human Physiology; Humans; Immunomodulation; Indole Alkaloids - analysis; Indole Alkaloids - chemistry; Indole Alkaloids - pharmacology; Inflammation; Insulin; Lipopolysaccharides; Lipopolysaccharides - toxicity; Medicine, African Traditional; Mesembryanthemum - chemistry; Monocytes; Monophenol Monooxygenase - antagonists & inhibitors; Monophenol Monooxygenase - metabolism; Nerve Tissue Proteins - analysis; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - isolation & purification; Nerve Tissue Proteins - pharmacology; Neuroprotective Agents - analysis; Neuroprotective Agents - chemistry; Neuroprotective Agents - isolation & purification; Neuroprotective Agents - pharmacology; Neurotoxins; Obesity; Original Article; Overdose; Oxidative Stress - drug effects; Plant Extracts - chemistry; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Polyphenols; Toxicity; Toxins
• ISSN: 1138-7548; 1877-8755
• DOI: 10.1007/s13105-018-0620-6

The link between obesity-induced systemic inflammation and decreased insulin signalling is well-known. It is also known that peripherally produced inflammatory cytokines can cross the blood-brain barrier, resulting in the release of neurotoxins that can ultimately lead to the demise of central nervous system integrity. A high-mesembrine Sceletium tortuosum extract was recently shown to possess cytoprotective and mild anti-inflammatory properties in monocytes and to target specific p450 enzymes to reduce adrenal glucocorticoid synthesis. This is significant since the aetiology of both obesity and diabetes is linked to inflammation and excess glucocorticoid production. Given the interlinked nature of glucocorticoid action and inflammation, central immunomodulatory effects of two Sceletium tortuosum extracts prepared by different extraction methods were investigated. Human astrocytes were pre-treated for 30 min, before exposure to Escherichia coli lipopolysaccharide for 23.5 h (in the presence of treatment). Cytotoxicity, mitotoxicity and cytokine responses (basally and in response to inflammatory stimulus) were assessed. In addition, total polyphenol content, antioxidant capacity and selected neural enzyme inhibition capacity were assessed for both extracts. The high-mesembrine Sceletium extract exerted cytoprotective and anti-inflammatory effects. In contrast, the high delta7-mesembrenone extract, rich in polyphenols, exhibited potent antioxidant effect, although with relatively higher risk of adverse effects with overdose. We conclude that both Sceletium tortuosum extracts may be employed as either a preventative supplement or complimentary treatment in the context of obesity and diabetes; however, current data also highlights the impact that extraction methods can have on plant product mechanism of action.