2.16 Skullcap (Scutellaria lateriflora)
The aerial parts of skullcap have been used in European and North American traditional medicine [130, 131] for anticonvulsant, relaxant and nervous system tonic effects [132]. Research has identified diterpenoids, amino acids (GABA and glutamine), essential oil and phenolic compounds in skullcap [132, 133]. A total of 73 bioactive constituents have been identified in the volatile oil, which include mainly sesquiterpenes [134]. Flavones appear to be the main constituents with anxiolytic actions, which include baicalein, baicalin, chrysin and wogonin [131,133]. In vitro research has identified baicalein as a weak benzodiazepine receptor ligand, that has demonstrated anxiolytic and sedative effects that appear to be mediated by interaction at GABAA non-benzodiazepine sites [135]. In addition, baicalin has demonstrated selective partial GABAA receptor antagonism [135], and wogonin has shown anxiolytic effects via interaction with benzodiazapine receptors in the GABA system [136]. Other flavone glycosides have exhibited binding to a 5-HT7 receptor [132]. One in vitro study used a whole plant ethanol extract of skullcap, and found the extract inhibited both glutamic acid decarboxylase and GABA-transaminase, with preferential inhibition of GABA-transaminase that appears to contribute to the anxiolytic activity [36]. Awad et al. [99] studied an acute oral dose of 100 mg of skullcap aqueous extract to rats in the EPM. Results revealed that treated rats spent significantly more time in the open arms compared with placebo, and displayed significantly less risk assessment behaviour in the open field test. One double-bind crossover RCT that investigated the acute anxiolytic effects of skullcap in 19 healthy adults was found [137]. Three different extracts of skullcap (100, 200 and 350 mg) were compared with placebo with a minimum of 2 days separating treatments. Self-assessments of anxiety levels were provided at baseline, 30-, 60-, 90- and 120-min post-dose using an 11-point Likert scale. All three skullcap preparations demonstrated anxiolytic effects on the Acute Psycho-Activity Self-Rating Scale. Although a clinical effect was seen, no statistical data were reported and there were numerous methodological flaws making it impossible to draw conclusions on the anxiolytic effects of skullcap based on this study.