Effect of Adaptogens on the Central Nervous System and The Molecular Mechanism Associated with Their Stress (Protective Activity)

Pooja Rasal, Saurabh Tribhuvan, Suraj Pathak, Prashant Pawar, Nikhil Sandhan, Om Pawar,

doi:10.5281/zenodo.17560236

Review Paper | Open Access
Volume 02 | Issue 11 | Article Id IJSRT/250311038

Effect of Adaptogens on the Central Nervous System and The Molecular Mechanism Associated with Their Stress (Protective Activity)
Pooja Rasal* Saurabh Tribhuvan Suraj Pathak Prashant Pawar Nikhil Sandhan Om Pawar
Department of Pharmacology, JES’s SND College of Pharmacy, Babhulgaon (Yeola), India

Abstract

Adaptogens are natural compounds derived mainly from plants and fungi that enhance resilience against stress, fatigue, and anxiety by modulating the hypothalamic?pituitary?adrenal (HPA) axis and related neuroendocrine pathways. They protect the central nervous system (CNS) from the adverse effects of chronic stress through mechanisms involving regulation of cortisol, heat shock proteins, neurotransmitters, and intracellular signaling pathways such as PI3K/Akt and ERK1/2. Adaptogens like Rhodiola rosea, Withania somnifera, and Eleutherococcus senticosus demonstrate neuroprotective, anti-fatigue, antidepressant, and anxiolytic properties by balancing stress hormones, enhancing mitochondrial energy metabolism, and reducing neuroinflammation and oxidative stress. Growing evidence also highlights their role in cognitive enhancement and neuroplasticity, while market expansion and AI-driven research are driving innovation in adaptogen discovery, formulation, and quality control. However, challenges remain due to limited large-scale clinical evidence, safety concerns, regulatory inconsistencies and potential herb?drug interactions. Overall, adaptogens represent a promising but evolving domain bridging traditional medicine and modern pharmacological science.

Keywords

Adaptogens; Stress; Metabolic Syndrome; Biomarkers; HPA Axis; Insulin Resistance; Oxidative Stress

Introduction

Adaptogens are a class of natural compounds derived primarily from plants and fungi that enhance the body’s resilience to stress, fatigue, and anxiety, primarily by modulating the hypothalamic–pituitary–adrenal (HPA) axis and other neuroendocrine pathways. First conceptualized in the mid-20th century, adaptogens have since gained significant attention due to their potential neuroprotective, anti-fatigue, antidepressant, and anxiolytic effects, particularly under conditions of chronic stress and central nervous system (CNS) dysfunction. [1] The central nervous system is particularly susceptible to the detrimental effects of chronic stress, which can lead to neuroinflammation, oxidative stress, and neurotransmitter imbalances. Adaptogens such as Rhodiola rosea, Withania somnifera (Ashwagandha), and Eleuthero coccus senticosus exert stress-protective effects by influencing molecular targets involved in stress response, including heat shock proteins (Hsp70), cAMP-response element-binding protein (CREB), and key mediators of the HPA axis such as corticotropin-releasing hormone (CRH) and cortisol. [2] On a molecular level, adaptogens have been shown to regulate intracellular signaling pathways such as PI3K/Akt, JNK, and ERK1/2, which are involved in cellular adaptation, survival, and neuroplasticity. They also modulate the expression of neuropeptides, reduce cortisol release, and enhance mitochondrial function and ATP production, which are critical for maintaining CNS homeostasis during stress. [3]

Table 1: Difference between CNS Stimulants and Adaptogens

	Stimulants	Adaptogens
Recovery process after exhaustive physical load	Low	High
2. Energy depletion	Yes	No
3. Performance in stress	Decreased	Increased
4. Survival in stress	Decreased	Increased
5. Quality of arousal	Bad	Good
6. Insomnia	Yes	No
7. Side effects	Yes	No
8. DNA/RNA and protein synthesis	Decreased	Increased

Mechanism of action of Adaptogens:

Adaptogens exert their stress-protective effects through a variety of interconnected molecular, cellular, and systemic mechanisms. Their primary action is to modulate the stress response system, particularly the hypothalamic–pituitary–adrenal (HPA) axis, the sympathoadrenal system, and key intracellular signaling pathways. Below is an outline of their key mechanisms