AUTHOR=de Munter Johannes , Pavlov Dmitrii , Gorlova Anna , Sicker Michael , Proshin Andrey , Kalueff Allan V. , Svistunov Andrey , Kiselev Daniel , Nedorubov Andrey , Morozov Sergey , Umriukhin Aleksei , Lesch Klaus-Peter , Strekalova Tatyana , Schroeter Careen A. 

TITLE=Increased Oxidative Stress in the Prefrontal Cortex as a Shared Feature of Depressive- and PTSD-Like Syndromes: Effects of a Standardized Herbal Antioxidant

JOURNAL=Frontiers in Nutrition

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.661455

DOI=10.3389/fnut.2021.661455

ISSN=2296-861X

ABSTRACT=Major depression (MD) and post-traumatic stress disorder (PTSD) share common brain mechanisms and treatment strategies. Nowadays, dramatically developing COVID-19 situation unavoidably results in stress, psychological trauma and high incidence of MD and PTSD. Hence, the importance of the development of new treatments of these disorders cannot be overstated. Herbal medicine appears as an effective and safe treatment with fewer side-effects than classic pharmaca, affordable in low-income countries. Currently, oxidative stress and neuroinflammation attract an increasing attention as important mechanisms of MD and PTSD. We investigated the effects of standardized herbal cocktail (SHC), an extract of clove, bell pepper, basil, pomegranate, nettle and other plants that was designed as an antioxidant treatment, in mouse models of MD and PTSD. In the MD model of ultrasound ‘emotional’ stress (US), mice were subjected to ultrasound frequencies of 16-20kHz, mimicking rodent sounds of anxiety/ despair and ‘neutral’ frequencies of 25-45kHz, for 3 weeks, and concomitantly treated with SHC. US-exposed mice showed elevated concentrations of oxidative stress markers malondialdehyde and protein carbonyl, increased gene and protein expression of pro-inflammatory cytokines interleukin (IL)-1β and IL-6and other molecular changes in the prefrontal cortex, as well as weight loss, helplessness, anxiety-like behaviour and neophobia that were ameliorated by the SHC treatment. In the PTSD model of the modified forced swim test (modFST), in which a two-day swimming is followed by an additional swimming on day 5, mice were pre-treated with SHC for sixteen days. Increases in the floating behaviour and in oxidative stress markers malondialdehyde and protein carbonyl in the prefrontal cortex of modFST-mice were rescued by the administration of SHC.Chromatography–mass-spectrometry revealed bioactive constituents of SHC, including D-ribofuranose, beta-D-lactose, malic, glyceric, and citric acids that can modulate oxidative stress, immunity, gut and microbiome functions, and, thus, are likely to be active anti-stress elements underlying beneficial effects of SHC.Significant correlations of malondialdehyde concentration in the prefrontal cortex with altered measures of behavioural despair and anxiety-like behaviour suggest the accumulation of oxidative stress markers to be a common biological feature of MD and PTSDthat can be equally effectively targeted therapeutically with anti-oxidant therapy such as investigated here standardized herbal cocktail.