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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.

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 - Evid Based Complement Alternat Med (2014)

Bottom Line: Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P < 0.032) and executive function (P < 0.022), compared with the placebo group.Zembrin was well tolerated.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Lawson Health Research Institute, Lab FB125, 268 Grosvenor Street, London, ON, Canada N6A 4V2 ; Department of Psychiatry, University of Western Ontario, London, ON, Canada N6A 3K7.

ABSTRACT
Introduction. Converging evidence suggests that PDE-4 (phosphodiesterase subtype 4) plays a crucial role in regulating cognition via the PDE-4-cAMP cascade signaling involving phosphorylated cAMP response element binding protein (CREB). Objective. The primary endpoint was to examine the neurocognitive effects of extract Sceletium tortuosum (Zembrin) and to assess the safety and tolerability of Zembrin in cognitively healthy control subjects. Method. We chose the randomized double-blind placebo-controlled cross-over design in our study. We randomized normal healthy subjects (total n = 21) to receive either 25 mg capsule Zembrin or placebo capsule once daily for 3 weeks, in a randomized placebo-controlled 3-week cross-over design. We administered battery of neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale (HAM-D) at baseline and regular intervals and monitored side effects with treatment emergent adverse events scale. Results. 21 subjects (mean age: 54.6 years ± 6.0 yrs; male/female ratio: 9/12) entered the study. Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P < 0.032) and executive function (P < 0.022), compared with the placebo group. Positive changes in mood and sleep were found. Zembrin was well tolerated. Conclusion. The promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP-CREB cascade, a novel drug target in the potential treatment of early Alzheimer's dementia. This trial is registered with ClinicalTrials.gov NCT01805518.

No MeSH data available.


Related in: MedlinePlus

Chemical structures of alkaloids isolated from Sceletium tortuosum: mesembrine, mesembrenol, mesembrenone, and mesembranol.
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Related In: Results  -  Collection


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fig1: Chemical structures of alkaloids isolated from Sceletium tortuosum: mesembrine, mesembrenol, mesembrenone, and mesembranol.

Mentions: In the recombinant PDE4 in vitro assay, Sceletium tortuosum (Zembrin) selectively inhibited PDE-4 with IC50 (inhibitory constant) value of 8.5 μg/mL. Mesembrenone, a major alkaloid isolated from the extract (Figure 1), was active in inhibiting PDE4 with an IC50 value of <1 μM [19]. The in vitro findings are consistent with Zembrin in MWM test [20].


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.

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 - Evid Based Complement Alternat Med (2014)

Chemical structures of alkaloids isolated from Sceletium tortuosum: mesembrine, mesembrenol, mesembrenone, and mesembranol.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4217361&req=5

fig1: Chemical structures of alkaloids isolated from Sceletium tortuosum: mesembrine, mesembrenol, mesembrenone, and mesembranol.
Mentions: In the recombinant PDE4 in vitro assay, Sceletium tortuosum (Zembrin) selectively inhibited PDE-4 with IC50 (inhibitory constant) value of 8.5 μg/mL. Mesembrenone, a major alkaloid isolated from the extract (Figure 1), was active in inhibiting PDE4 with an IC50 value of <1 μM [19]. The in vitro findings are consistent with Zembrin in MWM test [20].

Bottom Line: Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P < 0.032) and executive function (P < 0.022), compared with the placebo group.Zembrin was well tolerated.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Lawson Health Research Institute, Lab FB125, 268 Grosvenor Street, London, ON, Canada N6A 4V2 ; Department of Psychiatry, University of Western Ontario, London, ON, Canada N6A 3K7.

ABSTRACT
Introduction. Converging evidence suggests that PDE-4 (phosphodiesterase subtype 4) plays a crucial role in regulating cognition via the PDE-4-cAMP cascade signaling involving phosphorylated cAMP response element binding protein (CREB). Objective. The primary endpoint was to examine the neurocognitive effects of extract Sceletium tortuosum (Zembrin) and to assess the safety and tolerability of Zembrin in cognitively healthy control subjects. Method. We chose the randomized double-blind placebo-controlled cross-over design in our study. We randomized normal healthy subjects (total n = 21) to receive either 25 mg capsule Zembrin or placebo capsule once daily for 3 weeks, in a randomized placebo-controlled 3-week cross-over design. We administered battery of neuropsychological tests: CNS Vital Signs and Hamilton depression rating scale (HAM-D) at baseline and regular intervals and monitored side effects with treatment emergent adverse events scale. Results. 21 subjects (mean age: 54.6 years ± 6.0 yrs; male/female ratio: 9/12) entered the study. Zembrin at 25 mg daily dosage significantly improved cognitive set flexibility (P < 0.032) and executive function (P < 0.022), compared with the placebo group. Positive changes in mood and sleep were found. Zembrin was well tolerated. Conclusion. The promising cognitive enhancing effects of Zembrin likely implicate the PDE-4-cAMP-CREB cascade, a novel drug target in the potential treatment of early Alzheimer's dementia. This trial is registered with ClinicalTrials.gov NCT01805518.

No MeSH data available.


Related in: MedlinePlus