# System-Level, Molecular and Cellular Mechanisms of Selected Plant Adaptogens—A Review

## TL;DR

This review explores how seven plant adaptogens work at the molecular level to help the body resist stress and treat stress-related disorders.

## Contribution

The paper systematically reviews molecular mechanisms of seven key adaptogens, linking their bioactive compounds to specific signaling pathways and physiological effects.

## Key findings

- Adaptogens regulate the HPA axis and modulate stress-related signaling pathways like SAPK/JNK and NF-κB.
- Bioactive compounds from adaptogens show antioxidant, mitoprotective, and neuroprotective effects in preclinical and clinical studies.
- Clinical trials show adaptogens reduce cortisol levels by 14–30%, decrease fatigue, and improve cognitive function.

## Abstract

Background/Objectives: Adaptogens are plant-derived substances that enhance the body’s nonspecific resistance to physical, chemical, biological, and psychological stressors by normalizing physiological functions. This article discusses the molecular mechanisms of action of seven key plant adaptogens—Rhodiola rosea, Schisandra chinensis, Withania somnifera, Eleutherococcus senticosus, Panax ginseng, Ocimum tenuiflorum, and Bacopa monnieri—in the context of chronic stress and lifestyle-related diseases. Methods: A review of the scientific literature is performed, including preclinical in vitro and in vivo studies, randomized placebo-controlled clinical trials, and studies employing network pharmacology analyses, molecular docking, and genomic techniques such as gene expression profiling. The interactions of active constituents with signaling pathways, molecular targets, and synergistic mechanisms were analyzed based on publications from the years 2010–2025. Results: Adaptogens exhibit pleiotropic activity: they regulate the HPA axis (Hypothalamic–Pituitary–Adrenal axis); induce Hsp70/Hsp16 expression; modulate SAPK/JNK, FOXO, and NF-κB pathways; and demonstrate antioxidant and mitoprotective effects. Specific mechanisms include: salidroside from R. rosea activating PI3K/Akt; schizandrin B from S. chinensis stimulating Hsp70; withanolides from W. somnifera inhibiting PDE4D; ginsenosides from P. ginseng suppressing FKBP51; and bacosides from B. monnieri enhancing acetylcholine synthesis. Clinical studies confirm reductions in cortisol levels (14–30%), decreased fatigue, and improved cognitive function without adverse effects. Conclusions: Understanding the molecular mechanisms of adaptogens supports their application in integrative medicine for the treatment of stress-related disorders, depression, anxiety, and neurodegenerative diseases. Further clinical studies are needed to optimize dosages and standardize extracts.