Lion's Mane (Hericium erinaceus)

What is Lion's Mane?

Lion's mane is a medicinal wood-rotting fungus with a characteristic growth pattern that resembles the shaggy mane of a lion.

The fungus prefers temperate forests in North America, Europe, and Asia where it thrives on living oak, beech, or conifer trees.

The medicinal benefit of lions mane primarily involve the nervous system. Modern applications use the mushroom for general cognitive health and as a natural nootropic substance.

This mushroom is also eaten as a delicacy — with a flavor similar to lobster when cooked with butter.

In recent years lion's mane has caught the eye of the nootropic community for its ability to up-regulate nerve growth factor.

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How Is Lion's Mane Used?

Lion's mane is mainly used for neurodegenerative disorders like dementia and multiple sclerosis. It's also popular as a nootropic agent for supporting optimal cognitive function long term.

Most of the people using this fungus take it in the form of a powdered capsule or tincture on a daily basis. Like most medicinal mushrooms, the biggest benefit comes from using the herb on a regular basis over long periods of time — rather than short bursts for quick impact of effects.

Traditional Use of Lion’s Mane

Lion’s mane mushrooms have a long history of use in Eastern Asia — including China, Korea, and Japan. Each of these regions used the mushroom for treating neurological disorders, including neurasthenia, and age-related cognitive decline, as well as for general health.

Herb Details: Lion's Mane

Herbal Actions:

• Antibacterial
• Anticancer
• Antidiabetic
• Antioxidant
• Cardioprotective
• Hepatoprotective
• Nervine
• Immunomodulator

Weekly Dose

• (1:2 Liquid Extract)
  20-60 mL
• View Dosage Chart

Part Used

• Fruiting Body

Family Name

• Hericiaceae

Distribution

• North America, Europe, Russia, Mountainous regions of Asia

Constituents of Interest

• Hericnones
• Erinacines
• Lactones
• Polysaccharides

Common Names

• Lion's Mane
• Monkey's Head
• Hedgehog Fungus
• Pom Pom
• Houtou (China)
• Shishigashira (China)
• Yamabushitake (Japan)

Pregnancy

• Safe during pregnancy.

Duration of Use

• Long term use acceptable and recommended.

Mycological Information

The Hericiaceae family of fungi are saprophytic (consumes dead wood), yet can be found growing on living trees as well. Many experts believe the mushroom has a mutualistic relationship with the tree for some time — helping it resist disease and infection, but will eventually consume the tree after it dies.

Hericium mushrooms normally grow in cooler, mountainous regions across the globe. It contains a number of species used medicinally and nutritionally.

Hericium spp. has characteristic "tooth" structures on its fruiting body, giving it a hair-like appearance.

Pharmacology & Medical Research

+ Neuroprotective

Lion’s mane offers several different mechanisms to produce its overall neuroprotective benefits:

1. Antioxidant and free-radical scavenging activity [6]
2. Anti-inflammatory activity
3. Nerve-growth factor stimulation (hericium and erinacenes)
4. Reduction of endoplasmic reticulum stress-dependant cell death (dilinoleolyl-phosphatidylethanolamine (DLPE) [7]
5. Attenuation of beta-amyloid-related cognitive decline in animals (dementia model) [8]
6. Enhance mylenation of neurons [9, 10, 11]

In animal studies, lion’s mane has been shown to reduce the severity of damage after a stroke — effectively protecting the sensitive neurons from ischemic damage [6].

Clinical Trials:

Study: Mori et al., 2009 — Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double‐blind placebo‐controlled clinical trial. [5]

This randomized, double-blind, placebo-controlled clinical trial involving 30 Japanese men and women with mil cognitive impairment found that after 16 weeks, the lion’s mane group had significantly increased cognitive scores. These improvements were noted as early as the 8 week checkup, and continued to improve compared to placebo over the rest of the 16-week trial.

The dose of lion’s mane used in this study was 1 gram of dried lion’s mane taken three times per day.

Unfortunately, 4 weeks after the trial concluded, the scores had significantly decreased — indicating that these effects are not permanent and the mushroom needs to be continued to remain effective.

+ Nootropic

A nootropic is a substance that improves cognition without causing harm. There are a lot of nootropic substances that range from herbs like lion’s mane or rhodiola, to synthetic or prescription drugs like Modafinil or Noopept.

Lion’s mane is thought to be a nootropic through its ability to promote nerve-growth factor (NGF) in the brain. NGF is the most potent growth factor for the cholinergic neurons. it influences everything from the proliferation, differentiation, and survival of neuronal cells in the brain [8, 12].

Reductions in NGF has been considered a major implication in conditions such as depression, substance abuse, Alzheimer’s disease, and Huntington’s disease [12].

There have been a lot of studies looking at the role of lion’s mane and nerve growth factor — most of which have concluded that lion’s mane applications directly lead to an increase in NGF. This research has been done both in vivo and in vitro [13, 14, 15, 16].

This effect is very important. We can give peptides like NGF to people to treat these neurodegeneration, but these peptides rarely cross the blood brain barrier [9]. Therefore, finding alternative ways to boost NGF or other peptides in the brain are of the utmost importance in the treatment, prevention, and management of neurodegenerative disorders.

+ Immunomodulation

Like many other medicinal mushrooms, lion’s mane contains a high concentration of polysaccharides with immunomodulatory effects.

A lot of this study has been done in vitro with dendritic immune cells. These cells serve as the antigen-presenting cells that act as central mediators for the immune response as a whole. They’re responsible for a lot of the tolerance formed by the immune system to help maintain homeostasis.

Studies involving lions mane extracts have shown the fungus can stimulate the maturation of dendritic cells, induce dendritic cell activation, and modulate key T-helper (Th1) immune responses [17].

+ Anti-Inflammatory

Lion’s mane has been shown to influence a variety of inflammatory mediators, including:

Induces IL-1β expression through Nf-kB, NF-IL6, and activator protein 1 (AP-1) [18]

Induces iNOS gene expression to increase nitric oxide (NO) production in macrophages

Inhibits toll-like receptor 4 (TLR4)-JNK signalling on macrophages [19]

Phytochemistry of Lion’s Mane Mushrooms

Lion’s mane fruiting body and myclelia contain an exceptionally diverse range of unique bioactive substances — including polysaccharides, meroterpenoids (hericinones), cyathane diterpenoids (erinacines), steroids, alkaloids, and lactones.

The most significant constituents in terms of the mushrooms medicinal action are the hericenones and erinacines. Both of these substances have been shown to stimulate nerve growth factor in the central nervous system. This is thought to be the primary mechanism for which the fungus an improve the health and function of the nervous system.

Clinical Applications Of Lion's Mane:

Lion's mane has many uses, but the most well-known is as a neuroprotective, and nootropic benefits. It's useful for neurodegenerative disorders including multipple sclerosis, Alzheimer's disease, and Parkinson's disease.

Other uses include depression and anxiety, cancer, diabetes, gastrointestinal infection, and fatigue.

Cautions & Safety

Lion’s mane is a culinary mushroom that’s been used for both food and medicine by countless individuals over several hundreds of years. There are no expected short-term or long-term side effects from using the fungus.

Throughout the clinical research there have been no reports of serious side effects from using the fungus — including very high-potency extracts and long-term durations of use.

Caution advised with any blood clotting conditions or medications due to possible agonistic interactions — including haemophilia or other bleeding disorder, thrombocytopenia, or post-surgery. Lion’s mane may interact with blood thinners or anti-platelet medications.

Author:

Justin Cooke, BHSc

The Sunlight Experiment

(Updated April 2020)

Recent Blog Posts:

References

[1] — Friedman, M. (2015). Chemistry, nutrition, and health-promoting properties of Hericium erinaceus (lion’s mane) mushroom fruiting bodies and mycelia and their bioactive compounds. Journal of agricultural and food chemistry, 63(32), 7108-7123.

[2] — Liu, J., Du, C., Wang, Y., & Yu, Z. (2015). Anti-fatigue activities of polysaccharides extracted from Hericium erinaceus. Experimental and therapeutic medicine, 9(2), 483-487.

[3] — Thongbai, B., Rapior, S., Hyde, K. D., Wittstein, K., & Stadler, M. (2015). Hericium erinaceus, an amazing medicinal mushroom. Mycological progress, 14(10), 91.

[4] — Wong, K. H., Naidu, M., David, R. P., Bakar, R., & Sabaratnam, V. (2012). Neuroregenerative potential of lion's mane mushroom, Hericium erinaceus (Bull.: Fr.) Pers.(higher Basidiomycetes), in the treatment of peripheral nerve injury. International journal of medicinal mushrooms, 14(5).

[5] — Mori, K., Inatomi, S., Ouchi, K., Azumi, Y., & Tuchida, T. (2009). Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double‐blind placebo‐controlled clinical trial. Phytotherapy Research, 23(3), 367-372.

[6] — Lee, K. F., Chen, J. H., Teng, C. C., Shen, C. H., Hsieh, M. C., Lu, C. C., ... & Huang, W. S. (2014). Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine. International journal of molecular sciences, 15(9), 15073-15089.

[7] — Nagai, K., Chiba, A., Nishino, T., Kubota, T., & Kawagishi, H. (2006). Dilinoleoyl-phosphatidylethanolamine from Hericium erinaceum protects against ER stress-dependent Neuro2a cell death via protein kinase C pathway. The Journal of nutritional biochemistry, 17(8), 525-530.

[8] — Mori, K., Obara, Y., Moriya, T., Inatomi, S., & Nakahata, N. (2011). Effects of Hericium erinaceus on amyloid β (25-35) peptide-induced learning and memory deficits in mice. Biomedical Research, 32(1), 67-72.

[9] — Phan, C. W., David, P., Naidu, M., Wong, K. H., & Sabaratnam, V. (2015). Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism. Critical Reviews in Biotechnology, 35(3), 355-368.

[10] — Kolotushkina, E. V., Moldavan, M. G., Voronin, K. Y., & Skibo, G. G. (2003). The influence of Hericium erinaceus extract on myelination process in vitro. Fiziol Zh, 49(1), 38-45.

[11] — Moldavan, M., Grygansky, A. P., Kolotushkina, O. V., Kirchhoff, B., Skibo, G. G., & Pedarzani, P. (2007). Neurotropic and trophic action of lion's mane mushroom Hericium erinaceus (Bull.: Fr.) Pers.(Aphyllophoromycetideae) extracts on nerve cells in vitro. International Journal of Medicinal Mushrooms, 9(1).

[12] — Chao, M. V., Rajagopal, R., & Lee, F. S. (2006). Neurotrophin signalling in health and disease. Clinical science, 110(2), 167-173.

[13] — Zhang, C. C., Yin, X., Cao, C. Y., Wei, J., Zhang, Q., & Gao, J. M. (2015). Chemical constituents from Hericium erinaceus and their ability to stimulate NGF-mediated neurite outgrowth on PC12 cells. Bioorganic & medicinal chemistry letters, 25(22), 5078-5082.

[14] — Samberkar, S., Gandhi, S., Naidu, M., Wong, K. H., Raman, J., & Sabaratnam, V. (2015). Lion's Mane, Hericium erinaceus and Tiger Milk, Lignosus rhinocerotis (Higher Basidiomycetes) medicinal mushrooms stimulate neurite outgrowth in dissociated cells of brain, spinal cord, and retina: an in vitro study. International journal of medicinal mushrooms, 17(11).

[15] — Lai, P. L., Naidu, M., Sabaratnam, V., Wong, K. H., David, R. P., Kuppusamy, U. R., ... & Malek, S. N. A. (2013). Neurotrophic properties of the Lion's mane medicinal mushroom, Hericium erinaceus (Higher Basidiomycetes) from Malaysia. International Journal of Medicinal Mushrooms, 15(6).

[16] — Mori, K., Obara, Y., Hirota, M., Azumi, Y., Kinugasa, S., Inatomi, S., & Nakahata, N. (2008). Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biological and Pharmaceutical Bulletin, 31(9), 1727-1732.

[17] — Sheu, S. C., Lyu, Y., Lee, M. S., & Cheng, J. H. (2013). Immunomodulatory effects of polysaccharides isolated from Hericium erinaceus on dendritic cells. Process biochemistry, 48(9), 1402-1408.

[18] — Son, C. G., Shin, J. W., Cho, J. H., Cho, C. K., Yun, C. H., & Han, S. (2006). Induction of murine interleukin‐1 beta expression by water‐soluble components from Hericium erinaceum 1. Acta Pharmacologica Sinica, 27(8), 1058-1064.

[19] — Mori, K., Ouchi, K., & Hirasawa, N. (2015). The anti-inflammatory effects of lion's mane culinary-medicinal mushroom, hericium erinaceus (higher basidiomycetes) in a coculture system of 3t3-L1 adipocytes and raw264 macrophages. International journal of medicinal mushrooms, 17(7).

Rhodiola (Rhodiola rosea)

Rhodiola Summary

Rhodiola was made famous by some earlier research done by Russian scientists in the 1960's. Although a lot of this research still hasn't been released to the public, there has been a lot of new studies put forward to make up for this loss.

Rhodiola is well revered as an adaptogen for treating fatigue, cognitive decline, depression, and for athletic enhancement. It's considered to be a mild stimulant, though it doesn't produce the "wired" feeling many other stimulants produce. It increases energy levels and makes us more tolerant of stressful situations.

Although there is still a lot of research lacking, we know that Rhodiola can reduce cortisol levels in the body after exposure to stress, however, the details on how this interaction exists is still not well understood. There is also a great deal of confusion around which chemicals are active in the herb, some studies showing the rosavins, others tyrosol and the rhodiolasides.

As a result, each manufacturer tends to have a preference for one chemical group over the other in their products.

What is Rhodiola Used For?

*Rhodiola rosea* is mainly used for its adaptogenic qualities, especially those specific to lowering cortisol levels. It's reliable for improving fatigue in debilitated or chronically fatigued people, as well as those experiencing generalized adaptive disorder, depression, or acute periods of extreme stress.

Rhodiola is a popular nootropic additive for increasing focus and mental endurance and is popular among athletes for increasing physical endurance as well.

Herb Details: Rhodiola

Weekly Dose

• (1:2 Liquid Extract)
  20–40 mL
• View Dosage Chart

Part Used

• Root/Rhizome

Family Name

• Crassulaceae

Distribution

• Northern climates of North America, Asia, and Europe

Herbal Actions:

• Adaptogen
• CNS Stimulant (mild)
• Antidepressant
• Cardioprotective
• Nootropic

Constituents of Interest

• Rosavin
• Tyrosol
• Salidroside
• Rhodiolaside

Common Names

• Rhodiola
• Rose Root
• Arctic Root
• Golden Root
• King's Crown

CYP450

Unknown

Duration of Use

• Long-term use of rhodiola is acceptable.

Botanical Information

Although Rhodiola rosea is the preferred species used, there are many species used in various indigenous medical systems such as Rhodiola alterna, Rhodiola brevipetiolata, Rhodiola crenulata, Rhodiola kirilowii, Rhodiola quadrifida, Rhodiola sachalinensis, and Rhodiola sacra.

The Crassulaceae family contains 34 genera and 1400 species. Most of the plants in this family can be found in colder climates.

Another medicinal species in this family is Kalanchoe.

Habitat Ecology, & Distribution:

Rhodiola grows at high altitude, mountainous regions of Europe, Asia, the Arctic, and North America.

Pharmacology & Medical Research

+ Altitude Sickness

Salidroside and Tyrosol from Rhodiola cerrulea extracts have been shown to regulate AMPK [11], which plays a major role in energy homeostasis [10]. It was also shown to maintain sodium channel transport by preserving NA+, K+, ATPase activity. The authors concluded that this mechanism may be responsible for Rhodiolas ability to reduce the symptoms of altitude sickness, particularly HAPE [11].

+ CNS Stimulant

Numerous clinical trials have demonstrated the CNS stimulating activity of Rhodiola rosea [8] based on various cognitive and fatigue scores.

Other studies have found the use of rhodiola at varying doses inconclusive as a stimulant [7].

+ Memory & Cognitive Performance

Rhodiola extracts have been shown in animal models to improve learning capacity and short/long-term memory in animals trained to perform certain tasks [2].

Rhodiola has been shown to inhibit monoamine oxidase (both MAO-A and MAO-B) in animal studies [4].

+ Depression

MAO-A inhibitors are effective in the treatment of depression [20]. Rhodiola has been shown to inhibit MAO-A & B in animal studies [4]. Other animal studies investigating the use of rhodiola on depression has shown a non-dose dependent improvement on depression scores in mice, which is due to the tyrosin and rhodiolaside content specifically [16, 18, 19].

A randomized double-blind clinical trial using a standardized Rhodiola rosea extract showed a significant antidepressant activity in the treatment group compared to placebo. This was based on various depressive symptoms including insomnia, emotional instability, and somatization. [17].

+ Stress And Fatigue (Adaptogenic)

A group of 56 healthy physicians in a double-blind randomized clinical trial were either given Rhodiola rosea extracts or placebo control for 2 weeks. Physicians were chosen based on criteria that investigated the likelihood that these physicians would experience mental exhaustion during a normal shift. A series of tasks were then given after each night shift to investigate any changes on mental fatigue as measured by a set of complex tasks. All of the physicians treated with Rhodiola rosea were noted to show improved test scores compared to those not treated with the herb. These effects were observed to be most active after two weeks of use, and not a single adverse reaction was reported during the study. [3].

Another study investigating the mental and physical effects of a long term, low dose (SHR-5 50 mg) on students during examination periods found significant improvements on test scores among the treatment group [9]. They were looking for the presence of mental and physical fatigue indications. The only test that showed no improvement in this study was the tapping test (muscular activation).

A study investigating the effects of Rhodiola rosea on free cortisol levels in chronically fatigues patients noted a reduction in cortisol levels after just a single treatment, and significantly after a 28-day course of treatment [21]. Rhodiola was also shown to reduce serum blood levels of cortisol after a stressful event in rabbits [22].

Animal research has shown that Rhodiola rosea extracts can reduce the expression of c-Fos in the hypothalamus of rats [23]. The expression of this gene is considered to be a valuable marker for identifying the activation of cells in the central nervous system associated with the stress response [24]. This suggests the mechanism of action for Rhodiola rosea on reducing cortisol levels is the result of HPA modulation in the hypothalamus, such as increasing feedback sensitivity and therefore reducing overall CRH release rather than acting directly on the adrenal glands.

+ Withdrawal

A Rhodiola rosea extract was shown to improve withdrawal symptoms in mice, with a noted increase in 5HT activity in treated animals. [1].

Clinical Applications Of Rhodiola:

Rhodiola serves as a reliable adaptogen with little to no side effects noted in any of the studies listed. It's useful for those suffering from high-stress conditions, chronically fatigued, or depressed.

This herb is also useful for increasing athletic performance in athletes and reducing the chances of being affected by altitude sickness when traveling above 2500 meters.

Cautions:

Caution when using Rhodiola with mania as the mental stimulation may produce negative side effects.

Author:

Justin Cooke, BHSc

The Sunlight Experiment

(Updated May 2019)

Recent Blog Posts:

References

1. Mannucci, C., Navarra, M., Calzavara, E., Caputi, A. P., & Calapai, G. (2012). Serotonin involvement in Rhodiola rosea attenuation of nicotine withdrawal signs in rats. Phytomedicine, 19(12), 1117-1124. [animal studies]

2. Petkov, V. D., Yonkov, D., Mosharoff, A., Kambourova, T., Alova, L., Petkov, V. V., & Todorov, I. (1986). Effects of alcohol aqueous extract from Rhodiola rosea L. roots on learning and memory. Acta physiologica et pharmacologica Bulgarica, 12(1), 3-16. [animal studies]

3. Darbinyan, V., Kteyan, A., Panossian, A., Gabrielian, E., Wikman, G., & Wagner, H. (2000). Rhodiola rosea in stress induced fatigue—a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine, 7(5), 365-371. [RCT]

4. Van Diermen, D., Marston, A., Bravo, J., Reist, M., Carrupt, P. A., & Hostettmann, K. (2009). Monoamine oxidase inhibition by Rhodiola rosea L. roots. Journal of ethnopharmacology, 122(2), 397-401. [animal studies]

5. Ganzera, M., Yayla, Y., & Khan, I. A. (2001). Analysis of the marker compounds of Rhodiola rosea L.(golden root) by reversed phase high performance liquid chromatography. Chemical and pharmaceutical bulletin, 49(4), 465-467. [chemical analysis]

6. Panossian, A., Wikman, G., & Sarris, J. (2010). Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine, 17(7), 481-493. [review article]

7. Shevtsov, V. A., Zholus, B. I., Shervarly, V. I., Vol'skij, V. B., Korovin, Y. P., Khristich, M. P., ... & Wikman, G. (2003). A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work. Phytomedicine, 10(2), 95-105. [RCT]

8. Panossian, A., & Wagner, H. (2005). Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration. Phytotherapy Research, 19(10), 819-838. [Review]

9. Spasov, A. A., Wikman, G. K., Mandrikov, V. B., Mironova, I. A., & Neumoin, V. V. (2000). A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen. Phytomedicine, 7(2), 85-89. [RCT].

10. Lee, S. Y., Shi, L. S., Chu, H., Li, M. H., Ho, C. W., Lai, F. Y., ... & Chang, T. C. (2013). Rhodiola crenulata and its bioactive components, salidroside and tyrosol, reverse the hypoxia-induced reduction of plasma-membrane-associated Na, K-ATPase expression via inhibition of ROS-AMPK-PKCξ pathway. Evidence-Based Complementary and Alternative Medicine, 2013. [in vitro].

11. Reznick, R. M., & Shulman, G. I. (2006). The role of AMP‐activated protein kinase in mitochondrial biogenesis. The Journal of physiology, 574(1), 33-39.

12. Kerharo, J., & Adam, J. G. (1974). La pharmacopée sénégalaise traditionnelle: plantes médicinales et toxiques. (Pharmacopoeia).

13. Steinegger, E., & Hansel, R. (1992). Pharmakognosie 5 Aufl. Kap 6.2. 1. Freie Phenolcarbonsauren Springer Verlag Berlin. (Pharmacopoeia).

14. Hjaltalin, O. J. (1830). Islenzk grasafrædi. Koben havn.

15. insert

16. Kurkin, V. A., Dubishchev, A. V., Ezhkov, V. N., Titova, I. N., & Avdeeva, E. V. (2006). Antidepressant activity of some phytopharmaceuticals and phenylpropanoids. Pharmaceutical Chemistry Journal, 40(11), 614-619.

17. Darbinyan, V., Aslanyan, G., Amroyan, E., Gabrielyan, E., Malmström, C., & Panossian, A. (2007). Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nordic journal of psychiatry, 61(5), 343-348.

18. Perfumi, M., & Mattioli, L. (2007). Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1% salidroside Rhodiola rosea L. extract in mice. Phytotherapy Research, 21(1), 37-43.

19. Panossian, A., Nikoyan, N., Ohanyan, N., Hovhannisyan, A., Abrahamyan, H., Gabrielyan, E., & Wikman, G. (2008). Comparative study of Rhodiola preparations on behavioral despair of rats. Phytomedicine, 15(1-2), 84-91.

20. Priest, R. G., Gimbrett, R., Roberts, M., & Steinert, J. (1995). Reversible and selective inhibitors of monoamine oxidase A in mental and other disorders. Acta Psychiatrica Scandinavica, 91(s386), 40-43.

21. Olsson, E. M., von Schéele, B., & Panossian, A. G. (2009). A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta medica, 75(02), 105-112.

22. Panossian, A., Hambardzumyan, M., Hovhanissyan, A., & Wikman, G. (2007). The adaptogens Rhodiola and Schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol. Drug target insights, 2, 117739280700200011.

23. Xia, N., Li, J., Wang, H., Wang, J., & Wang, Y. (2016). Schisandra chinensis and Rhodiola rosea exert an anti-stress effect on the HPA axis and reduce hypothalamic c-Fos expression in rats subjected to repeated stress. Experimental and therapeutic medicine, 11(1), 353-359.

24. Luckman, S. M., Dyball, R. E., & Leng, G. (1994). Induction of c-fos expression in hypothalamic magnocellular neurons requires synaptic activation and not simply increased spike activity. Journal of Neuroscience, 14(8), 4825-4830.