Dose-response assessment of neuroactive botanical extracts and their bioactive constituents using microelectrode array (MEA) recordings in rat primary cortical cultures

Our work in collaboration with the HESI Botanical Safety Consortium was recently published in Pharmaceutical Biology!

The HESI Botanical Safety Consortium collaborates to develop screening strategies to efficiently identify botanical-induced toxicity. Our study aimed at establishing the neuroactive potential of 13 botanical extracts using microelectrode array (MEA) recordings in rat primary cortical cultures.
Our results show that most extracts inhibited neuronal activity, albeit with distinct neuronal activity phenotypes. Despite differences in the degree of inhibition, all inhibitory extracts (milk thistle, usnea, green tea, aristolochia, ephedra, tripterygium, yohimbe, kratom, and kava) show No Observed Effect Levels (NOELs) of 1-5 µg/mL. Extracts of aconite, blue cohosh, goldenseal and oleander induced specific activity phenotypes characterized by hyperexcitation and/or intensification of (network) burst activity. While the extracts exhibit a narrow effective dose range, the extracts from aconite, goldenseal and oleander are most potent with NOELs of 0.25-0.5 µg/mL.
Next, 8 major constituents (Silybin B, epigallocatechin gallate, yohimbine, dihydrokavain, mitragynine, aconitine, berberine and oleandrin) were tested for their neuroactive potential. For most constituents the activity phenotype is comparable to the extract, although the extract generally has a higher potency. These botanical extracts and constituents evoke diverse activity phenotypes, highlighting the complexity of hazard characterization of botanicals.

For more details see the full article (open access) here: https://pubmed.ncbi.nlm.nih.gov/41204423/

For more insight into the achievements and progress of the Botanical Safety Consortium, see “From Vision to Reality: Five Years of the Botanical Safety Consortium”, which is (open access) here: https://pubmed.ncbi.nlm.nih.gov/41208233/