New Botanical Anxiolytics for Use in Companion Animals and Humans

Abstract

As part of our ongoing research into botanical therapies for anxiety disorders, the neotropical vine Souroubea sympetala was chosen for study as a phytochemical discovery strategy focusing on rare Central American plant families. When orally administered to male Sprague-Dawley rats, the crude plant extract, its ethyl acetate fraction, supercritical carbon dioxide fraction, or its isolated triterpenes reduced anxiety and/or fear-related behavior in standardized behavioral models. Pharmacological studies showed that the extracts acted at the benzodiazepine GABA receptor and reduced corticosterone levels. A preparation containing Souroubea fortified with a second triterpene containing plant, Platanus occidentalis, was shown to be safe in a 28-day feeding trial with beagles at 5 times the intended dose. Subsequent trials with beagles in a thunderstorm model of noise aversion showed that the material reduced anxiety behaviors and cortisol levels in dogs. The formulation has been released for the companion animal market in Canada and the USA under the Trademark "Zentrol." Ongoing research is exploring the use of the material in treatment of anxiety and post-traumatic stress in humans.

Neuropharmacology of Secondary Metabolites from Plants with Anxiolytic and Antidepressant Properties

“…These findings indicate that in some cases it may be necessary to keep the metabolites together at the concentrations present in the original infusion or extract that has a proven therapeutic effect. As explained herein, some metabolites share pharmacological targets, which explains why they lose their effect when separated and emphasizes the importance of using standardized extracts with demonstrated therapeutic effects in animal and human studies [97,98]. Unfortunately, very few clinical studies have evaluated the potential antidepressant or anxiolytic effects of isolated metabolites, so a great deal of work remains to be done.…”

Effect of an anxiolytic botanical containingSouroubea sympetalaandPlatanus occidentalisonin-vitrodiazepam human cytochrome P450-mediated metabolism

“…P. occidentalis showed threefold to fourfold stronger CYP450 inhibition relative to the traditionally used S. sympetala . The potency of the mixed extract was similar to that of P. occidentalis , suggesting that its addition to S. sympetala not only boosts the anxiolytic effect but also increases the potential risk of herb–drug interaction when co‐administrated with other therapeutic products.…”

“…[18,27] CYP450 inhibition may reduce the metabolic elimination of these components, resulting in earlier onset of activity and longer half-life that possibly contribute to the synergetic effect of the 1 : 1 v/v mixed plant extract observed in vivo. [4] Compared to the plant extracts, IC 50 values for individual triterpenes were at least twofold higher (except for UA towards CYP3A4). Other minor secondary metabolites reported in S. sympetala include: 2-hydroxyursolic acid, taraxenyl trans-4-hydroxy-cinnamate, naringenin, methyl ursolate, eriodytiol, methyl 2-a-hydroxyursolate, methyl 2a-hydroxymaslinate, methyl betulinate and condrilla sterol.…”

“…Several studies indicate that CYP450 isoforms are involved in the metabolism of the pharmacologically active pentacyclic triterpene . CYP450 inhibition may reduce the metabolic elimination of these components, resulting in earlier onset of activity and longer half‐life that possibly contribute to the synergetic effect of the 1 : 1 v/v mixed plant extract observed in vivo …”

“…A novel anxiolytic herbal medicine containing the dried extracts of Souroubea sympetala and Platanus occidentalis has been developed for the companion animal market and is currently being developed for clinical evaluation as a treatment for GAD for human. [2][3][4] Souroubea sympetala is a vine from the Marcgraviaceae family found in Central and South America that was selected for investigation by Costa Rican botanists based on dereplication strategy for poorly studied botanicals. [5] Souroubea sympetala extract was found to have significant dose-dependent anxiolytic effects in animal models including the elevated plus maze and fear-potentiated startle.…”