Herbal extracts for mental health: Are they safe for pregnant women?

By Neha MathurReviewed by Benedette Cuffari, M.Sc.Jun 18 2023

In a recent article published in Nature, researchers evaluate the T-cell modulating effects of St. John’s wort, valerian, hops, lavender, and California poppy.

Study: Immunological evaluation of herbal extracts commonly used for treatment of mental diseases during pregnancy. Image Credit: PattPaulStudio / Shutterstock.com

Background

Nonpsychotic mental diseases (NMDs), including depression, anxiety, dissociative and adjustment disorders, somatoform, and reactions to traumatic stresses, affect about 15% of pregnant women in the United States. 

Conventional therapy, antidepressants, selective serotonin reuptake inhibitors (SSRIs) like paroxetine, and benzodiazepines for NMDs could disturb the delicate immunological balance of fetal tolerance and protection of mother and child. Thus, changes in T-cell activity are needed for a successful pregnancy.

Fear of potential teratogenic effects causes nearly 86% of pregnant women not to seek treatment for NMDs, which can have fatal consequences for both the mother and unborn child. Untreated NMDs increase the risk for spontaneous preterm delivery, miscarriages, preeclampsia, low birth weight of neonates, as well as an increased risk of postpartum depression.

Herbal medicines are a safe alternative to conventional drugs with multiple side effects. One study involving around 10,000 women from 23 nations showed that 28% of pregnant women (used herbal medicines for NMDs. Likewise, according to a Swiss survey, about 90% of pregnant females used herbal preparations, 53.6% of whom used these agents to treat mild NMDs.

Regulatory T-cells (Tregs) in the blood increase during pregnancy, with estrogen increasing transcription factor forkhead box P3 (FoxP) levels. Other immune system functions are also altered during pregnancy to ensure a high baseline level of innate immune cells to promote inflammatory responses and downregulate adaptive immune responses.

About the study

In the present study, researchers obtained peripheral blood mononuclear cells (PBMCs) from healthy donors. PBMCs were then treated with extracts and pure compounds in a culture medium at concentrations of 0.03–100 µg/mL and 0.01-30 µM, respectively.

After 72 hours of incubation, the fraction of apoptotic cells was calculated through a flow cytometric readout. Likewise, a spectrometric assay was used to assess the viability of cells.

The genotoxic potential of the extracts was determined using a single-cell deoxyribonucleic acid (DNA) gel electrophoresis, for which surface and intracellular biomolecules were measured in a multifluorescence panel.

Results

The current study evaluated the safety of St. John’s wort, hops, valerian, lavender, and California poppy and their compounds protopine, hyperforin and hypericin, valerenic acid, valtrate, and linalool. The impact of these agents on the viability and function of primary human lymphocytes was also determined.

None of the evaluated herbal extracts demonstrated a marked effect on the viability or function of T-cells in vitro at their physiological concentration, nor did they induce apoptosis or genotoxicity. 

Previous studies have described the anti-inflammatory effects of St. John’s wort. In this study, 30 µg/mL of St. John’s wort and valerian exerted a marked inhibitory effect on the proliferation of T-cells. Preliminary evidence of valerian’s potential for immunomodulation, especially of the adaptive immune system, was also observed. Importantly, the current study did not identify any immunological effects of lavender.

Valerenic acid, protopine, and linalool showed no marked effects on the function of T-cells, including their viability, proliferation, induced apoptosis, or genotoxicity. Comparatively, hyperforin, hypericin, and valtrate induced apoptosis, as well as inhibited viability and cell division at 3.0 µM. 

At the functional level, all herbal compounds exhibited differential effects. For example, hyperforin and hypericin stimulated interferon-gamma (IFN-γ) production but inhibited cytokine production by T-helper and cytotoxic T-cells.

Conversely, valtrate decreased the expression of T-helper cell activation markers but not the cytotoxic T-cell activation markers. Stimulatory effects were observed for all other evaluated markers.

Conclusions

The use of herbal preparations for NMD treatment on defined subsets of human immune cells in vitro did not present any potential threat to the fragile immunological balance during pregnancy. Despite its use, pregnant females could likely tolerate an allogenic fetus and mounted an adequate defense against NMDs. 

There remains an urgent need for further investigations to confirm the effects of herbal substances and their metabolites on the adaptive immune system, especially T-cells, for a final safety assessment, as stronger effects have been reported.