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Stress, Anxiety & Inflammation

Stress & Anxiety
 

Posted: March 2023
Author: Katie Donnelly, Adv Dip HSc Naturopathy
 

The role of chronic stress and anxiety on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, and subsequently inflammatory markers, has been extensively researched in recent years.1 Resulting oxidative stress (OS) and suboptimal antioxidant availability then contribute to a perpetuation of symptoms, linking psychological stress to chronic inflammation, and increasing the prevalence of cases in clinic.

Some of the most well-utilised medicinal herbs have been extensively studied to highlight suitability for use in stress and anxiety. This helps identify the role of specific constituents and interactions with the central nervous system and improve client outcomes.


Stress and Anxiety

There is a growing prevalence of stress-related illness and anxiety among New Zealanders, particularly in younger populations.  Recent studies show one in four people are experiencing anxiety at some point in their life, with mental distress noted in one in three people. Contributing factors include increased alcohol intake, loneliness, work stress and poor exercise routines, as established in comparative studies.2 Current pharmaceutical options to treat anxiety include selective serotonin reuptake inhibitors (SSRI’s), benzodiazepines, and tricyclic antidepressants. However, the argument exists that much of their action may be attributed to the placebo effect and they come with a vast array of side effects.

Increasing research on these conditions has identified the role that phytotherapy can play in managing stress and anxiety.3,4 Supplementation of Hericium erinaceus (lion’s mane) showed reduced anxiety in participants over a four-week period, with much of the benefit recognised in the ability of constituents hericenones and erinacines, to cross the blood-brain barrier (BBB).5 Actions on monoamine neurotransmitter regulation were identified, with reduced prevalence of interleukin-6, tumour-necrosis factor alpha (TNF-a) and Nuclear factor-kappa B (NF-κB), noted as influencing anxiety levels.6 Similarly, stress-induced changes to the HPA axis, noted in cases of depression relative to consistent cortisol release, were reduced in separate in vivo animal model studies.7 Neurogenesis from lion’s mane was also a contributing factor in reduced anxiety and depression.8  

The role of Magnolia officinalis (magnolia) on anxiety has been recently studied identifying neolignans, primarily magnolol and honokiol, in supporting regulated neuron function. These constituents regulate the HPA axis and gamma-aminobutyric acid (GABA) neurotransmissions, decreasing the likelihood of depression and anxiety development. Specific interactions with the benzodiazepine GABA sites and increased 5-hydroxytryptophan (5-HT) and receptor sites are noted actions of neolignans. This also presents significant potential for use in preventing the development of neurodegenerative conditions with reductions in OS, amyloid-beta accumulation, and inflammation. The protection of brain microvascular endothelial cells, part of the BBB composition, has been identified as a key factor in preventing disease and treating post-traumatic brain injury.9 

In cases where medications are successfully being utilised, plants can be used in conjunction to reduce undesired effects.  Well known as a nervous system support and aphrodisiac, Turnera diffusa (damiana) has been identified in reducing the side effects of anti-depressant and anxiety medication in vivo. Studies on amitriptyline, also utilised for nerve pain conditions, associate the medication with impotence, endocrine dysfunction, and testicular swelling. Constituents including alpha and beta-pinene, tannins, thymol, and glycosides present in T.diffusa, have shown reduced deoxyribonucleic acid (DNA) damage, cellular death, and OS in animal model studies through potent antioxidant and anti-inflammatory actions. This suggests that damania supplementation may be beneficial alongside amitriptyline, where appropriate.10

 

The Role of the Gut

Gastrointestinal (GI) health directly impacts anxiety and stress management, with the microbiome playing a role in neurotransmitter signalling.  Another of the mushroom favourites, Ganoderma lucidum (reishi), has been identified as a regulator of the central nervous system through interactions with the GI system. Recent animal model studies identified reduced anxiety and depressive tendencies through lowered inflammation levels, attributed to the high polysaccharide content of this herb and the influence of the gut microbiome.11,12 The prebiotics, phenols, and saccharides in this herb regulate microbial variation, preventing the proliferation of harmful microbes and reducing the likelihood of dysbiosis and associated inflammation. This contributes to antimicrobial and antioxidant actions. Triterpenes also contribute, acting to downgrade the release of TNF-a, interleukin-2 (Il-2), and prostaglandin E2 in vivo, and inhibiting mitogen-activated protein kinase (MAPK) activation, associated with stress. As an antioxidant and free radical scavenger, reishi increases superoxide dismutase activity thereby reducing the presence of reactive oxygen species.13

 

Classics for a Reason 

Some of the most well-utilised herbs throughout history are still some of the most effective in cases of stress and anxiety management. The polysaccharides of Rehmannia glutinosa (rehmania), an established adaptogen, have gained recent interest in clinical studies, exhibiting significant anti-inflammatory actions.14 Separate studies on stress-induced behaviour changes, noted antidepressant-like results in animals treated with rehmania hydroethanolic.15 The phytochemical catalpol has also been explored in relation to stress of the endoplasmic reticulum and neuron health, as measured in animal model studies. This is important in managing inflammation, alongside antioxidant effects reducing stress-related oxidation.16

A classic for a reason, Humulus lupulus (hops), is regularly used as a sedative to counteract stress and aid in sleep. In vitro studies have expanded on this knowledge, highlighting the role of humulones and lupulones in antidepressant actions through interactions with GABA neurotransmissions. Further to this, combinations of hops with Valeriana officinalis (valerian) has shown 5-HT and melatonin receptor interaction.17

The use of Matricaria recutita (chamomile) as an anxiolytic and anti-inflammatory has also been reiterated by recent in vivo studies. Mild sedative effects are attributed to apigenin binding to benzodiazepine receptors, aiding in reducing the stress response, while also exhibiting anxiolytic actions by acting as a neurokinin-1 receptor antagonist. In vivo animal model studies support the actions of chamomile on the HPA axis by reducing adrenocorticotropic hormone, associated with stress.18

 

Herbs Featured

Hericium erinaceus (lion’s mane)

Magnolia officinalis (magnolia)

Turnera diffusa (damiana)

Ganoderma lucidum (reishi)

Rehmannia glutinosa (rehmania)

Humulus lupulus (hops)

Valeriana officinalis (valerian)

Matricaria recutita (chamomile)

 

References

  1. Jelinek M, Jurajda M, Duris K. Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke. Antioxidants (Basel) [Internet]. Nov 25 2021;10(12):1886. Available from: https://doi.org/10.3390/antiox10121886.
  2. Te hiringa hauora. Mental Health in Aotearoa. 1 Oct 2020. Available from: https://www.hpa.org.nz/sites/default/files/Mental_Health_Aotearoa_Insight_2020.pdf
  3. Kirsch I. Placebo Effect in the Treatment of Depression and Anxiety. Front Psychiatry [Internet]. 2019; 10: 407. Available from: https://doi.org/10.3389/fpsyt.2019.00407
  4. Powers SW, Coffey CS, Chamberlin LA, Ecklund DJ, Klingner EA, Yankey JW, Korbee LL, Porter LL, Hershey AD. Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine. The New England Journal of Medicine [Internet]. January 12, 2017; 376:115-124. Available from: https://doi.org/10.1056/NEJMoa1610384 
  5. Rodriguez MN, Lippi SLP. Lion's Mane (Hericium erinaceus) Exerts Anxiolytic Effects in the rTg4510 Tau Mouse Model. Behav Sci (Basel) [Internet]. 2022 Jul 15;12(7):235. Available from: https://doi.org/10.3390/bs12070235.
  6. Chong PS, Fung ML, Wong KH, Lim LW. Therapeutic Potential of Hericium erinaceus for Depressive Disorder. Int J Mol Sci [Internet]. 2019 Dec 25;21(1):163. Available from: https://doi.oeg/10.3390/ijms21010163
  7. Chou M-Y, Ho J-H, Huang M-J, Chen Y-J, Yang M-D, Lin L-H, Chi C-H, Yeh C-H, Tsao T-Y, Tzeng J-K, Hsu RJ-c, Huang P-H, Lu W-C, Li P-H and Wang M-F (2022) Potential antidepressant effects of a dietary supplement from the chlorella and lion's mane mushroom complex in aged SAMP8 mice. Front. Nutr [Internet]. 24 June 2022; 9:977287. Available from: https://doi.org/10.3389/fnut.2022.977287
  8. Li I-C, Chang H-H, Lin C-H, Chen W-P, Lu T-H, Lee L-Y, Chen Y-W, Chen Y-P, Chen C-C and Lin DP-C (2020) Prevention of Early Alzheimer’s Disease by Erinacine A-Enriched Hericium erinaceus Mycelia Pilot Double-Blind Placebo-Controlled Study. Front. Aging Neurosci [Internet]. 03 June 2020; 12:155. Available from: https://doi.org/10.3389/fnagi.2020.00155
  9. Zhu S, Liu F, Zhang R, Xiong Z, Zhang Q, Hao L, Chen S. Neuroprotective Potency of Neolignans in Magnolia officinalis Cortex Against Brain Disorders. Front Pharmacol [Internet]. 2022 Jun 16;13:857449. Available from: https://di.org/10.3389/fphar.2022.857449.
  10. Tousson E, Hafez E, Zaki S, Gad A, Elgharabawy RM. Evaluation of the testicular protection conferred by damiana (Turnera diffusa Willd.) against amitriptyline-induced testicular toxicity, DNA damage and apoptosis in rats. Biomedicine an Pharmacotherapy [Internet].Dec 2020;132:110819. Available from: https://doi.org/10.1016/j.biopha.2020.110819
  11. Kim JH, Kim DH, Jo S. Immunomodulatory functional foods and their molecular mechanisms. Exp Mol Med [Internet]. 2022;54: 1–11. Available from: https://doi.org/10.1038/s12276-022-00724-0
  12. El Sheikha AF. Nutritional Profile and Health Benefits of Ganoderma lucidum "Lingzhi, Reishi, or Mannentake" as Functional Foods: Current Scenario and Future Perspectives. Foods [Internet]. 2022;11(7):1030. Available from: https://doi.org/10.3390/foods11071030.
  13. Zhang RR, Zhang J, Guo X, Chen YY, Sun JY, Miao JL, Carpena M, Prieto MA, Li NY, Zhou QX, Liu C. Molecular mechanisms of the chemical constituents from anti-inflammatory and antioxidant active fractions of Ganoderma neo-japonicum Imazeki. Curr Res Food Sci [Internet]. 2023;6:100441. Available from: https://doi.org/10.1016/j.crfs.2023.100441.
  14. Lu MK, Chang CC, Chao CH, Hsu YC. Structural changes, and anti-inflammatory, anti-cancer potential of polysaccharides from multiple processing of Rehmannia glutinosa. Int J Biol Macromol[Internet]. 2022 May 1;206:621-632.Available from: https://doi.org/10.1016/j.ijbiomac.2022.02.112 .
  15. Wang JM, Pei LX, Zhang YY, Cheng YX, Niu CL, Cui Y, Feng WS, Wang GF. Ethanol extract of Rehmannia glutinosa exerts antidepressant-like effects on a rat chronic unpredictable mild stress model by involving monoamines and BDNF. Metab Brain Dis [Internet]. 2018 Jun;33(3):885-892. Available from: https://doi.org/10.1007/s11011-018-0202-x.
  16. Huang Z, Gong J, Lin W, Feng Z, Ma Y, Tu Y, Cai X, Liu J, Lv C, Lv X, Wu Q, Lu W, Zhao J, Ying Y, Li S, Ni W, Chen H. Catalpol as a Component of Rehmannia glutinosa Protects Spinal Cord Injury by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis. Front Pharmacol [Inernet]. 2022 Jul 8;13:860757. Available from: https://doi.org/10.3389/fphar.2022.860757
  17. Kyrou I, Christou A, Panagiotakos D, Stefanaki C, Skenderi K, Katsana K, Tsigos C. Effects of a hops (Humulus lupulus L.) dry extract supplement on self-reported depression, anxiety and stress levels in apparently healthy young adults: a randomized, placebo-controlled, double-blind, crossover pilot study. HORMONES [Internet]. 2017; 16(2):171-180. Available from: https://doi.org/10.14310/horm.2002.1738
  18. Sah A, Naseef PP, Kuruniyan MS, Jain GK, Zakir F, Aggarwal G. A Comprehensive Study of Therapeutic Applications of Chamomile. Pharmaceuticals (Basel)[Internet]. 2022 Oct 19;15(10):1284. Available from: https://doi.org/10.3390/ph15101284  
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