Efficacy of Souroubea-Platanus Dietary Supplement Containing Triterpenes in Beagle Dogs Using a Thunderstorm Noise-Induced Model of Fear and Anxiety.

Aleksandar Masic,Zul Merali,Pablo Sanchez Vindas,John Arnason,Mario Garcia,Gary Landsberg,Rui Liu,Bill Milgram,Tony Durst,John Baker

doi:10.3390/molecules26072049

Aleksandar Masic, Zul Merali + Show 8 more

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https://doi.org/10.3390/molecules26072049

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Abstract

A novel botanical dietary supplement, formulated as a chewable tablet containing a defined mixture of Souroubea spp. vine and Platanus spp. Bark, was tested as a canine anxiolytic for thunderstorm noise-induced stress (noise aversion). The tablet contained five highly stable triterpenes and delivered 10 mg of the active ingredient betulinic acid (BA) for an intended 1 mg/kg dose in a 10 kg dog. BA in tablets was stable for 30 months in storage at 23 °C. Efficacy of the tablets in reducing anxiety in dogs was assessed in a blinded, placebo-controlled study by recording changes in blood cortisol levels and measures of behavioral activity in response to recorded intermittent thunder. Sixty beagles were assigned into groups receiving: placebo, 0.5×, 1×, 2×, and 4× dose, or the positive control (diazepam), for five days. Reduction in anxiety measures was partially dose-dependent and the 1× dose was effective in reducing inactivity time (p = 0.0111) or increased activity time (p = 0.0299) compared with placebo, indicating a decrease in anxiety response. Cortisol measures also showed a dose-dependent reduction in cortisol in dogs treated with the test tablet.

Highlights

In our research program on botanicals with anxiety-reducing properties, we discovered that extracts of neotropical vines, Souroubea sympetala V.A
After the drug was administered in these dogs, the mean prethunder cortisol levels were not different Molecules 2021, 26, x FOR PEER RbEVetIEwWeen the control group, diazepam-treated dogs, or those treated with differ5eonft9 doses of Souroubea-Platanus tablets
The results showed that the main anxiolytic triterpenoid compounds, betulinic acid and α-amyrin, were stable in the tablet for 30 months—an important consideration in an efficacy trial and for future practical applications

Summary

Introduction

In our research program on botanicals with anxiety-reducing properties, we discovered that extracts of neotropical vines, Souroubea sympetala V.A. Richt and Souroubea gilgii Gilg. (Marcgraviaceae), had potent anxiety-reducing properties in several rat models of anxiety, including elevated plus-maze, fear-potentiated startle and social interaction [1]. Betulinic acid was found to be the most active component, but a combination of betulinic acid and amyrins was significantly more effective in reducing behaviors associated with anxiety than betulinic acid alone. Other phytochemicals found in whole extracts included hydroxyursolic acid, taraxenyl trans-4-hydroxy-cinnamate, and 2-α-hydroxyursolic acid, isolated as its methyl ester, 2-α-hydroxymaslinic acid [2]. The plant extracts and active principles were shown to act, at least in part, at the GABAA-benzodiazepine receptor.

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