The formulation’s ingredients include Vitex agnus-castus, Crocus sativus, Melissa officinalis, Betula pendula Roth. and Betula pubescens, vitamin B6 and magnesium citrate.
Writing in Nutraceuticals, the university researchers from Italy and Turkey highlighted the beneficial effects on the serotoninergic and brain-derived neurotrophic factor (BDNF) pathways, which they partly attributed to the formulation’s “richness in specialized metabolites.”
Italian supplement company Cristalfarma, which funded the research, supplied the formulation ingredients, marketed as supplement for menstrual cycle support under the Elsa brand.
How plant metabolites may help symptoms
Previous evidence suggests that medicinal plants historically used as drugs and health foods may support PMS symptoms.
For example, Vitex agnus-castus may decrease prolactin and increase progesterone levels, reducing PMS symptoms. Its specialized metabolites, including flavonoids, terpenes and glycosides, may modulate neurotransmitter, pain, opioid and inflammatory signals.
Crocins in Crocus sativus may affect the serotonin system and reduce the neuroinflammation associated with depression, and the metabolites in Melissa officinalis, such as rosmarinic acid, may improve cognitive functions and reduce PMS symptoms such as sleep disorders and anxiety.
In addition to plant metabolites, the researchers on the study noted the neuroprotective properties of magnesium and vitamin B6 in the formula.
Study details
The researchers analyzed the phenol and flavonoid content and scavenging/reducing properties and found the formulation rich in benzoic acids and other compounds with antioxidant effects.
In mouse brain specimens, they used K+ 60 mM Krebs–Ringer buffer to induce the inflammation and oxidative stress seen in depressive conditions. Gene expression of biomarkers associated with neuroinflammation, depression and anxiety were then analyzed.
The results showed that the formula effectively prevented the expression of IL-6 and COX-2, established markers of neuroinflammation, and increased anti-inflammatory IL-10.
In addition, it “blunted” estrogen receptor-1 (ESR1) and prolactin receptor (PRLR), which are linked to anxiety and depression.
The membrane transport protein SERT is involved in 5-HT reuptake from neurons, and some antidepressants work by blocking it and making more serotonin available. The study showed the formula reduced the expression of SERT and BDNF, suggesting neuroprotective and anti-depressant effects.
“The abovementioned effects could be related to the content in crocins and safranal, agnuside, but also phenols and flavonoids, especially the hydroxycinnamic acids (gentisic acid, caftaric acid, rosmarinic acid),” the researchers wrote.
“These phytochemicals are known not only to exert anti-neuroinflammatory effects but also to improve neurotransmission, with particular regard to BDNF and serotoninergic targets, including SERT and monoamine oxidases (MAOs) inhibition,” they added.
While optimistic about Elsa’s potential neuroprotective and antidepressant effects, the researchers noted the study’s limitations and highlighted the need for future clinical studies to evaluate the formula’s efficacy.
Source: Nutraceuticals 2025, 5(1), 5. doi: 10.3390/nutraceuticals5010005. “Unravelling the Neuroprotective Effects of a Novel Formulation Based on Plant Extracts, Mg, and Vitamin B6”. Authors: S.C. Di Simone et al.