For many patients, chronic stress is a familiar and ubiquitous aspect of life. 

Yet, while most practitioners are keenly aware that stress can play a major role in the development of disease, it’s also important to recognise how adrenal function and immunity are intricately linked.  

There is a bidirectional crosstalk between the hypothalamus-adrenal-pituitary (HPA) axis and the immune system.^1,2 The HPA axis contributes to modulating inflammation in the body.^1,3 In addition, the immune system can contribute to the function of the HPA axis, as pro inflammatory cytokines, such as interleukin (IL)-6, can activate the HPA axis⁴ and alter neurotransmitters resulting in mood changes.³ It is also thought that inappropriate function of the HPA axis can lead to inflammatory conditions such as allergies and auto-immune reactions.^3,4

Stressors, including emotional stressors are processed in the brain through the amygdala, hippocampus, prefrontal cortex, and hypothalamus to affect the HPA axis.⁴ As stress increases cortisol levels, multiple body processes are affected. Available energy from glucose, amino acids and fatty acids is increased for a body in stress, while other processes begin to exhibit reduced function in order to redirect energy. The chronic over production of cortisol can lead to aberrant function of multiple organ systems. For example, the immune system may inappropriately become over active.^1,4,5,6

Immune health is not typically targeted with adrenal herbs. However, in light of the physiological links; the regulatory aspects connecting the stress response and the immune system, it is worthwhile to provide treatment that strengthens the body’s resistance to illness through effects on immune and adrenal system components. Below we discuss four key herbs that are utilised to address stress-induced immune dysregulation.

Withania

Withania somnifera (withania or ashwagandha) root, also called Indian ginseng, is considered to be the preeminent adaptogen from the Ayurvedic medical system.  As an Ayurvedic Rasayana (restorative tonic) herb it nourishes the body tissues, enhances vitality and longevity, builds strength, promotes physical and mental health and supports immune function.^7,9 The major biochemical constituents in withania are steroidal alkaloids and lactones, a class of constituents together known as withanolides.^9,10 

Withania has been clinically demonstrated to:

• Possess adaptogenic effects through its anti-stress and cognition-enhancing activity.^13,14
• Decrease cortisol levels in persons under chronic stress, restore healthy adrenal function, and normalise the sympathetic nervous system.^13,15
• Negate the effects of chronic stress by suppressing stress-induced increases in dopamine receptors, reducing serum cortisol levels and act as a GABA-mimetic agent by binding to GABA receptors.^13,16,17

Liquorice

Liquorice, the dry root of Glycyrrhiza glabra, is one of the main adrenal restorative herbs. It has been used therapeutically in both Western and Eastern systems of traditional medicine for millennia.^18,20 The adrenal cortex participates in the stress response via its generation of glucocorticoids. Therefore, liquorice may support the adrenal cortex during periods of prolonged stress, as well as being a valuable component of treatment for recuperation after disease or an especially exhausting phase.^21,22 

Constituents of liquorice (primarily glycyrrhizin – a triterpenoid saponin) are structurally similar to corticoids which can bind to glucocorticoid and mineralocorticoid receptors, mimicking the role of endogenous steroid hormones. There is also some evidence that liquorice fortifies cortisone levels - arguably the most important hormone in stress and adrenal fatigue – as it reduces the breakdown of hydrocortisone into inactive cortisol metabolites.²³ By enhancing cortisol activity, liquorice helps to increase energy, ease stress and reduce the symptoms of conditions sensitive to cortisol levels such as chronic fatigue syndrome, Addison’s disease and fibromyalgia.^17,21,24

Liquorice root is used in traditional medicine for immune health and respiratory illnesses. It is employed extensively in the treatment of cough as it is an effective expectorant. In addition, its anti-tussive effects help to relax bronchial spasms. Its soothing demulcent, antiinflammatory properties can bring relief to a sore throat, asthma and bronchial infections.^21,22,24

Echinacea

Echinacea is well known and widely used for its ability to fortify the body’s resistance to illness by enhancing general defensive responses and host resistance.^17,21,25 Echinacea’s unique and characteristic phytochemicals are found mostly in the roots. The constituents with the most pronounced pharmacological activity are the alkylamides.²⁸

Alkylamides of echinacea have been reported to have cannabinomimetic properties on both endocannabinoid receptor 1 (CB1) and endocannabinoid receptor 2 (CB2), which may be attributed to their structural similarity to the endogenous cannabinoid receptor ligand anandamide.²⁷ Anandamide's effects can occur in either the central and peripheral nervous system by CB1 and CB2 receptors. The activation of the former with endogenous ligands plays a considerable role in controlling anxiety and the latter is mainly involved in immune system activities.²⁸

The immunomodulatory component of echinacea is in part due to the interaction of alkylamides with CB2 receptors.^29,30,31 CB2 receptors predominate in immune cells and the spleen, while the endocannabinoid system is an important modulator of the immune system and appears to be mediated by the cytokine network.^32,33 One study revealed that Nalkylamides from echinacea induced synergistic activity on CB2 receptors, which resulted in immunomodulatory effects. There was super stimulation of interleukin-10 (IL-10), along with the inhibition of tumour necrosis factor (TNF-α) in vitro.³¹

Observations in experimental models have led researchers to suggest that echinacea may play a role in stress-related disorders such as depression and anxiety.^27,34 Chronic stress dysregulates the HPA axis and the sympathetic nervous system. It is theorised that echinacea may regulate the HPA axis stress response by the interaction of alkylamides with CB1 receptors.^21,25  Endocannabinoids not only influence the immune system but also HPA axis regulation and mood, as they are involved in HPA axis cortisol regulation via a fast feedback loop.³⁶ 

Rehmannia

Rehmannia, the root of Rehmannia glutinosa, is considered a prime adrenal tonic and adrenal restorative in Western herbal medicine. It has been used extensively in traditional Chinese medicine (TCM) for “hot” conditions, as it is thought to possess heat-dispersing and bloodcooling properties. It is used for conditions including fevers, rashes, inflammation, infections and rheumatoid arthritis. It is also indicated for kidney yin deficiency or to invigorate the kidneys, a concept akin to that of adrenal exhaustion.^37-39 

Research indicates that rehmannia supports the adrenal cortex and pituitary gland during times of stress. For example, rehmannia treatment has been shown to delay the breakdown of cortisol and resultantly, lowers the levels expressed, thereby helping to attenuate adrenal depletion.⁴⁰ Moreover, it is thought that rehmannia may work by inhibiting the negative feedback to the pituitary gland.⁴¹

Conditions that relate to improper immune function such as autoimmune disorders and allergies may benefit from rehmannia via its immunomodulatory effects. In an experimental model, immune modulating effects were observed with rehmannia administration.⁴² Rehmannia has also produced therapeutic effects in trials involving patients with rheumatoid arthritis, asthma and urticaria.^21,43,44

Conclusion

Many people in modern society do not have the luxury of a recovery period for their overworked adrenal glands. The changes caused by the overproduction of adrenal hormones stays with them. The stimulation of the adrenal glands causes a decrease in immune system function, so an individual under constant stress may have a tendency to catch colds or suffer from ailments related to suppressed immunity. Along with appropriate diet and lifestyle modifications, the above herbal combination simultaneously supports adrenal and immune health, through its tonifying effects and ability to reduce stress. 

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