A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordOBJECTIVE: To evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function. METHODS: Forty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6). RESULTS: Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p < 0.0123) with Cohen's effect size d = 0.92. No adverse effects were observed. CONCLUSION: This pilot study indicates that an oral preparation of SRM at the selected dose and for the period of administration is more effective than a placebo in supported verbal episodic memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment.Support by the following organisations is gratefully acknowledged, Ross Menzies Herbal Clinic, Bodyworks Therapy Centre; Wesnes Cognition Ltd, the Royal Botanic Gardens (RBG), Kew and Dilston Physic Garden. The phytochemical analysis was gratefully funded by the Sir Jeremiah Colman Gift Trust

A Soluble Acetylcholinesterase Provides Chemical Defense against Xenobiotics in the Pinewood Nematode

The pinewood nematode genome encodes at least three distinct acetylcholinesterases (AChEs). To understand physiological roles of the three pinewood nematode AChEs (BxACE-1, BxACE-2, and BxACE-3), BxACE-3 in particular, their tissue distribution and inhibition profiles were investigated. Immunohistochemistry revealed that BxACE-1 and BxACE-2 were distributed in neuronal tissues. In contrast, BxACE-3 was detected from some specific tissues and extracted without the aid of detergent, suggesting its soluble nature unlike BxACE-1 and BxACE-2. When present together, BxAChE3 significantly reduced the inhibition of BxACE-1 and BxACE-2 by cholinesterase inhibitors. Knockdown of BxACE-3 by RNA interference significantly increased the toxicity of three nematicidal compounds, supporting the protective role of BxACE-3 against chemicals. In summary, BxACE-3 appears to have a non-neuronal function of chemical defense whereas both BxACE-1 and BxACE-2 have classical neuronal function of synaptic transmission

Effects of cholinesterase inhibiting sage (salvia officinalis) on mood, anxiety and performance on a psychological stressor battery

Salvia officinalis (sage) has previously been shown both to possess in vitro cholinesterase inhibiting properties, and to enhance mnemonic performance and improve mood in healthy young participants. In this double-blind, placebo-controlled, crossover study, 30 healthy participants attended the laboratory on three separate days, 7 days apart, receiving a different treatment in counterbalanced order on each occasion (placebo, 300, 600 mg dried sage leaf). On each day mood was assessed predose and at 1 and 4 h postdose. Each mood assessment comprised completion of Bond–Lader mood scales and the State Trait Anxiety Inventory (STAI) before and after 20 min performance of the Defined Intensity Stress Simulator (DISS) computerized multitasking battery. In a concomitant investigation, an extract of the sage leaf exhibited dose-dependent, in vitro inhibition of acetylcholinesterase and, to a greater extent, butyrylcholinesterase. Both doses of sage led to improved ratings of mood in the absence of the stressor (that is, in pre-DISS mood scores) postdose, with the lower dose reducing anxiety and the higher dose increasing 'alertness', 'calmness' and 'contentedness' on the Bond–Lader mood scales. The reduced anxiety effect following the lower dose was, however, abolished by performing the DISS, with the same dose also being associated with a reduction of alertness during performance. Task performance on the DISS battery was improved for the higher dose at both postdose sessions, but reduced for the lower dose at the later testing session. The results confirm previous observations of the cholinesterase inhibiting properties of S. officinalis, and improved mood and cognitive performance following the administration of single doses to healthy young participants