Medicinal & Aromatic Plants

Medicinal & Aromatic Plants
Open Access

ISSN: 2167-0412

+44 1300 500008

Research Article - (2017) Volume 6, Issue 6

View PDF Download PDF

Biomolecules from Plants as an Adaptogen

Mandeep Kumar Singh1*, Garima Jain1, Bhrigu Kumar Das2 and Umesh K Patil1
1Department of Pharmaceutical Sciences, Dr. HS. Gour University, Madhya Pradesh, India
2Department of Pharmacology, KLEU's College of Pharmacy, Hubballi, Karnataka, India
*Corresponding Author: Mandeep Kumar Singh, Department of Pharmaceutical Sciences, Dr. HS. Gour University, Sagar, Madhya Pradesh, India, Tel: 09826910278 Email:

Abstract

In present scenario, stress is a common problem which affects not only elders, but also to older and youngster. Long term stress can be detrimental and causes various diseases related to CNS, immune system, neuro-endocrine system, liver, blood, learning, memory defeat and irregular sleeping pattern. A combined approach of traditional and modern system i.e., adaptogens help to overcome the stress and stress related problems. Adaptogens are generally the plant-derived biologically active substances that help to increase the body resistance against physical, biological, emotional and environmental stressors in nonspecific manner through maintenance of internal homeostasis. Adaptogenic herbs exhibit neuro-protective, anxiolytic, anti-fatigue, nootropic, anti-depressive, and CNS stimulating activity. Non-specific action of the adaptogenic herbs decreases the targeted phenomenon and efficiency so that more study, research and clinical trials are required to find the targeted action of adaptogens. In recent years, focus has been shifted towards the adaptogens due to its safety, cost effectiveness and efficacy for maintaining and improving the quality of life. The present review focuses on the mechanism of stress induction, its relation with anxiety, depression and immune system. It also highlights the different herbal biomolecules as an adaptogens that are used in either Ayurveda or Traditional Chinese Medicine [TCM].

Keywords: Adaptogenic herbs; Adaptogens; Stress; Homeostasis; Biomolecule

Introduction

In the modern era, most of illnesses are caused by stress and stressrelated disorders. Generally, stress increases the level of stress hormone known as cortisol. Cortisol is responsible for the alert and arouses response, thereby affecting sympathetic nervous system, thyroid and adrenal glands [1]. High level of cortisol affects the physiological system resulting in anxious and irritability, weight gain, bone loss and may also contribute to risk of diabetes and heart disease [2].

To overcome these problems, multiple approaches like drugs, exercise and relaxation techniques have been employed, but these methods provide mixed results and sometime often unsatisfactory results also. Further, scientist followed Ayurveda concept, an adaptogens as a novel approach to reduce stress and prevent stressrelated problems [3].

Various plants have been used for hundreds of years in the Indian system of Ayurvedic medicine as an adaptogens for its medicinal properties. They are available as adaptogenic drugs which increase the body’s resistance to physical, biological, emotional and environmental stressors in nonspecific manner [4]. Also, increase of attention, endurance in fatigue, reduction of stress-induced impairments and disorders related to the neuro-endocrine and immune systems to balance and maintenance of homeostasis in the body are reported [5]. Previous studies and reports revealed that adaptogens exhibit neuroprotective, anti-fatigue, anti-depressive [6], anxiolytic [7], nootropic [8] and CNS stimulating activity [9].

In this review, the plant biomolecule with their mechanism are discussed thoroughly because these molecules are available as principle constituents which possess adaptogenic property in plants. The main focus of discussion is those biomolecules which strengthen the HPA axis and having anti-stress, antianxiety, antidepressant and immunomodulatory like activity. The mechanism by which stress is related to anxiety, depression and immune system dysfunction are also discussed briefly.

The relationship between stress and anxiety

Stress represents an interface between a certain type of stressors and specific stress response systems, such as hypothalamic-pituitaryadrenal (HPA) axis and/or catecholamines. Anxiety and fear associate a set of behavioral, cognitive, and physiological responses to nasty situations or insecurity [10]. Thus, anxiety and fear can be a part of the stress response, and a component of a potential stressor [11].

The main stress hormone system is the hypothalamic-pituitaryadrenal (HPA) axis, which activates secretion of different hormones such as cortisol [12]. In response to a stressor (such as exercise, hypoglycemia, and infection), hypothalamus synthesize corticotropinreleasing hormone (CRH), acts as secretagogue to release adrenocorticotropic hormone (ACTH) from pituitary corticotrophs into the circulatory system, which targets the adrenal cortex and stimulates glucocorticoids synthesis and secretion. It further act to suppress immune activity and maintain and/or increase glucose in the blood, thereby prevents glucose-dependent tissue from starvation and, thus provides enough energy to maintain its alert state in stress [13].

Glucocorticoids have an ability to inhibit their own release and secretion by the negative feedback effects on CRH and ACTH secretion, and provide immediate inhibition to limit the stress response and prevent excess production of glucocorticoids [14]. The downregulation of the HPA axis is mediated mainly by three brain regions. Firstly, stressors activate neurons containing gammaaminobutyric acid (GABA) and inhibiting further secretion of glucocorticoids. Secondly, excessive glucocorticoid receptor (GR) in the hippocampus increase glucocorticoid level by activating GABA mediated neurons, thus diminishing HPA activity. And finally, the medial prefrontal cortex reduces HPA activation [15].

Furthermore, stress as an activator of CRH/ACTH/glucocorticoid secretion initiate secretion from the HPA axis in a circadian pattern. Thus, increased HPA axis activity is assumed to organize an organism for the upcoming increase in activity.

The relationship between stress and depression

The adaptive response to stress is characterized by activation of neural and neuroendocrine cascades mediated mainly by the sympathetic and limbic-hypothalamic-pituitary-adrenal (HPA) systems respectively. Chronic psychosocial stress has been associated with depression where increased levels of cortisol could be directly involved in the mood fluctuations, and also alter the serotonergic neurotransmission [16].

Cortisol is a vital catabolic hormone produced by the adrenal cortex and elevated plasma level is seen in psychosocial depression and an altered circadian pattern of cortisol secretion is due to the HPA axis dysfunction, which is substantiation that treatment with antidepressants leads to normalization of HPA axis activity [17].

The 5-HT system interacts with the various stress hormones on several levels, i.e., increase CRH release, decrease 5-HT turnover and increase cortisol level, may cause decrease serotenergic activity of neurons, decrease 5-HT1A and 5-HT2 receptor expression and binding. Sustained stress or sustained increase of plasma cortisol is accompanied by diminution of 5-HT turnover and reduced 5-HT release in all areas.

In depression, the 5-HT level may decrease due to altered 5-HT metabolism and downregulation of the 5-HT1A receptor and, possibly, upregulation of the 5-HT2C receptor. Moreover, the CRH/cortisol is hyperactive, causing or aggravating the disturbances in the 5-HT system [18].

The relationship between stress and immune system

Chronic stress is known to have numerous adverse effects on health, which are mediated through stress actions on the immune system. During short-term stress, multiple physiological systems are activated to frame the cardiovascular, musculoskeletal, and neuroendocrine systems for fight-or-flight, thus enable survival. A stressor may shape up the immune system for challenges in certain condition such as wounding or infection. Short-term stress, at the time of immune activation, augments significant subsequent immune response, thus can enhance innate and adaptive, primary and secondary immune responses [19].

Stress-induced immunosuppression may be adaptive, because this may preserve energy to deal with the abrupt demands enforced by the stressor [20]. Acute stress induced immunosuppression, such as inhibition of prostaglandin synthesis, cytokine production, or leukocyte proliferation is significantly longer. Acute stress may suppress adaptive immunity and enhance only innate immunity during energy-conservation.

Short-term stress induces an initial increase followed by a decrease in lymphocyte and monocyte numbers and an increase in neutrophils numbers, with glucocorticoids and catecholamines, major mediators of stress. Short-term stress results in a significant increase in immune response, mediated by memory and effector helper T cells at the time of primary immunization [21].

Chronic stress, suppress or deregulates immune function and decrease leukocyte mobilization from the blood to other body compartments is thought to be a suppressor of cell mediated immunity (CMI) [22]. Chronic stress has been revealed to suppress different type of immune cell such as CMI, antibody production, NK activity, leukocyte proliferation, virus-specific T cell and NK cell activity, and anti-mycobacterial activity of macrophages [23].

Basic mechanism of stress induction

The general mechanism of stress induction due to predisposing factors correlating with the stress hormone system and sympathetic nervous system has been illustrated in Figure 1.

medicinal-aromatic-plants-mechanism

Figure 1: General mechanism of stress induction.

General mechanism of action of adaptogenic drugs

Adaptogens help to establish homeostasis especially against stress and the relief from stress is favored by various types of mechanisms directly or indirectly by maintaining the level of hormones i.e., cortisol, adrenaline, ACTH and CRH.

Adaptogen generally act on the amygdale, hypothalamus, pituitary, thyroid, adrenal. During the state of fatigue and stress, nor-adrenaline becomes imbalanced. The adaptogens activates the hormonal response to produce and release more adrenaline and nor adrenaline hormones, and help to respond more effectively and efficiently to the excess in hormones and shut down more quickly [24]. During stressful situations, the energy consumption is increased and body unable to fulfill the requirement result in enhanced generation of free radicals and the body’s defense system combat against the oxidative stress [25,26]. Adaptogens support adrenal functions by allowing cells to access more energy and preventing oxidative damage [27].

Functions of adaptogen

The various function reported for adaptogens in literature are explained in Figure-2. Adaptogens boost the immune system, protect the liver by detoxification and speed up its regeneration process [28]., increase the number and activity of T-cells and natural killer cells [29]., lower the risk of cancer, improve memory, learning ability [30]., resistance to stress, reduce high cholesterol, improve blood circulation, purify the blood, strengthen the heart, inhibit platelet aggregation and control blood clotting mechanisms. It also helps in prevention of breast and prostate cancer, relieve menopause symptoms and erectile dysfunctions [31]. Further, herbs also increase natural production of growth hormone and an increase in testosterone, stabilize the blood sugar levels [32]., improve general well-being and slowing down the aging process [33]., revitalize entire body by stimulating the production of stem cells in the bone marrow [34].

medicinal-aromatic-plants-adaptogen

Figure 2: Functions of adaptogen.

Biomolecules from plants as an adaptogen

Most of the herbal adaptogens that are used in either Ayurveda or Traditional Chinese Medicine [TCM]. are discussed in Table 1.

Sl No Phytoconstituent Biological effect Tests/Models Mechanism of action Ref
1. Curcumin Adaptogenic activity Antidepressant-like effects Chronic stress,
Chronic unpredictable stress Forced swimming		 Alter functional homeostasis and memory deficit and cause normalization of the hyper-activated HPA axis with subsequent decrease in corticosterone secretion.
Acts on serotonergic system, which may be mediated by an interaction with 5-HT1A/1B and 5-HT2C receptors responsible for depression.		 [35,36].
2. Rutin Anti-stress activity Anxiolytic-like activity Forced swimming,
Tail Suspension,
Elevated plus-maze Elevated plus-maze,
Ambulatory activity		 Modulates GABA receptors and also acts as NMDA receptor antagonist.
Cause inhibition of prostaglandin synthesis thereby, regulation of HPA axis activity under basal and stress conditions.
Modulates GABAergic neurotransmission in the basolateral amygdala.		 [37,38]
3. Ginsenosides Rb1 and Rg1 Adaptogenic activity Radical scavenging,
Nrf2 activation,
Mitochondrial dysfunction,
BBB permeability		 Attenuates oxidative stress and mitochondrial dysfunction, thus resulting in a reduced apoptotic cell death. The promising effects is due to activation of cytoprotective Nrf2 signaling and a mitochondrial-targeted protective action. [39].
4. Glycyrrhizin Antidepressant-like activity Anti-stress activity Forced swimming,
Tail suspension,
Immobilization stress Locomotor activity,
Muscle co-ordination		 Acts by interaction with α1-adrenergic and D2-receptors, thereby increasing the levels of norepinephrine and dopamine in brains, and also have MAO inhibiting activity.
Attenuates the HPA axis activation and free radical scavenging activity.		 [40,41]
5. Piperine Antidepressant-like activity Antianxiety-like activity Elevated plus-maze,
Light and dark box,
Social interaction,
Tail suspension,
Forced swimming,
Open field test.		 Possibly mediated through benzodiazepine-GABA receptor and increase in GABA levels and inhibition of neuronal nitric oxide synthase.
Cause augmentation of the neurotransmitter synthesis or the reduction of the neurotransmitter reuptake and also mediated via the regulation of serotonergic system.		 [42,43]
6. Eugenol Anti-stress activity Restraint stress model Activity is mediated through the HPA axis and BMS pathways and also changes in brain noradrenergic, serotonergic, and dopaminergic system in hippocampus, hypothalamus, prefrontal cortex, and amygdala. [44]
7. Andrographolide Adaptogenic activity Stress-induced hyperthermia,
Pentobarbital-induced hypnosis		 Cause upregulation of benzodiazepine site of GABA-A receptors, which involved in stress-triggered physiological responses. [45]
8. Ocimumosides Anti-stress activity Restraint stress model Anti-stress activity by normalizing acute stress-induced hyperglycemia, corticosterone levels, creatine kinase, and adrenal hypertrophy. [46]
9. Astragaloside IV Anti-stress activity Immobilized stressors,
Elevated Plus-maze		 Astragaloside IV may ameliorate anxiety via serotonergic receptors and inflammation by decreasing serum levels of corticosterone, IL-6 and TNF-α. [47]
  Astragaloside II Immunomodulatory activity Splenic-T-lymphocyte activation,
Cyclophosphamide induced immunosuppression		 Astragaloside II enhances T cell activation by regulating the activity of CD45 PTPase in primary T cells.
Astragaloside II also increased IL-2 and IFN-γ secretion, upregulated of IFN-γ and T-bet in primary splenocytes, and promoted of primary CD4 + T cells.		 [48]
10. Bergenin Immunomodulatory activity Adjuvant-induced arthritis Inhibits IL-2 production by CD4 + T-cells, which is regulator of immune response, stimulates the synthesis of IFN-ϒ in T-cells and also induces the secretion of pro-inflammatory cytokines such as TNF-α by activated macrophages. The inhibition of IL-2 is possibly responsible for reduced IFN-ϒ secretion by CD8 + T cells and TNF-α by macrophages and also promote IL-4 and IL-5 production. [49]
11. Syringin Immunomodulatory activity Croton oil and arachidonic acid-induced mouse ear oedema Inhibits TNF-α production and CTLL-2 cell proliferation thus, may possess anti-allergic activity. [50]
12. Berberine Antidepression and anti-anxiety-like activity Forced swimming,
Elevated plus-maze,
Locomotor activity		 Acts by modulating hypothalamic Corticotrophin releasing factor and the noradrenergic system in the CNS and decrease serotonergic system activity by activating somatodendritic 5-HT1A and inhibiting postsynaptic 5-HT1A and 5-HT2 receptors. [51,52]
13. β-pinene Antidepressant-like activity Forced swimming Acts through interaction with the serotonergic pathway through postsynaptic 5-HT1A receptors and also interact with the adrenergic system through β-receptors and the dopaminergic systems through D1 receptors. [53]
14. Zeatin Immunomodulatory activity Thioglycollate-induced peritonitis Modulates T lymphocyte activity via adenosine A2A receptor, which induces the production of cAMP, potently inhibits the production of both TH1 and TH2 cytokines and also modulate either directly or indirectly, both humoral and cell-mediated responses. [54]
15. Scopoletin Antidepressant-like activity Forced swimming,
Tail suspension,
Open-field test		 Interact with the 5-HT2A/2C, α1 and α­­2, D1 and D2 receptors systems thereby antidepressant-like effect. [55]
16. Ginkgolide B Adaptogenic and anti-stress activity in-situ hybridization of CRH and AVP mRNA Acts at the hypothalamic level, modulate the monoaminergic inputs to the CRH synthesizing cell bodies depending upon both the nature of stress and substance. [56]
17. Quercetin Anti-fatigue activity Forced swimming Improves endurance capability to fatigue during exhaustion and also prevent endothelial dysfunction via enhancing the activities of antioxidant enzymes and attenuating the levels of inflammatory cytokines. [57]
18. Gallic acid Antidepressant-like activity Sucrose preference test, Forced swimming Inhibits MAO-A activity and increase levels of monoamine in brain and reduces plasma nitrite levels and reduced nitrosative stress, thus plays key role in chronic stress-induced depression. [58]
19. Valerenic Acid Anti-stress activity Anxiolytic activity Forced swimming Elevated plus-maze Mitigate stress e by decreasing the turnover of 5-HT to 5-hydroxyindoleacetic acid and NE to 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in the hippocampus and amygdala. Modulates GABA-A channel and possess anxiolytic activity. [59,60]
20. Picracin Immunomodulatory activity Pro-inflammatory cytokine release,
DTH response		 Inhibits mitogen induced proliferation of T cells, are potent inhibitors of IL-2 release through induction of apoptosis. [61]
21. Esculetin Anti-inflammatory and depressive-like activity Tail suspension,
Forced swimming,
Open field test		 Inhibits pro-inflammatory cytokines including interleukin-6, interleukin-1β and tumor necrosis factor-α and also attenuated inducible nitric oxide synthase and cyclooxygenase-2 protein expression by inhibiting nuclear factor-κB pathway in hippocampus, cause upregulations of brain derived neurotrophic factor and phosphorylated tyrosine kinase B protein expression in hippocampus which provides neuroprotection. [62]
22. Catechin Anxiolytic activity Forced swimming,
Elevated plus-maze		 Inhibits the HPA axis-associated psychological dysfunction induced by corticosterone, and modulates hypothalamic CRF activity and the noradrenergic system within the CNS. [63]
23. Asiaticoside Antidepressant-like activity Tail suspension,
Forced swimming		 Regulates α2-adrenergic receptor and increase the level of adrenalin in brain. [64]
24. Tumerone Antidepressant-like activity Forced swimming,
Tail suspension,
Open-field test		 Increase the level of 5-HT in cortex, striatum, hippocampus, and hypothalamus, the level of NE in striatum and hippocampus, the level of 3-Methoxy-4-hydroxyphenylglycol and 3,4-dihydroxyphenylacetic acid in hypothalamus, the level of 5-Hydroxyindoleacetic acid in striatum, and the level of DA in striatum, hippocampus, and hypothalamus. [65]
25. Rosavin Adaptogenic activity Forced swimming light/dark test,
Tail-flick latencies		 Modulates biogenic monoamines in cerebral cortex, brain stem and hypothalamus. In cerebral cortex and brain stem, level of nor-epinephrine and dopamine decreased, while serotonin increase, due to change in monoamine level, i.e. inhibition of monoamine oxidase and catechol-o-methyltransferase. [66]
26. Shatavarin Immunomodulatory Activity Human peripheral blood lymphocytes stimulation assay Stimulates immune cell proliferation, induce IgG, interleukin-12 and inhibit IL-6 production. It also had strong modulatory effects on Th1/Th2 cytokine profile. [67]
27. Salidroside Antifatigue activity Forced swimming Decrease the activities of CK and CK-MB and increase the GSH-Px and SOD activities and also decrease the MDA content in liver tissue. [68]
28. β-sitosterol Anxiolytic-sedative activity Pentobarbital-induced sleeping time Modulates GABAA receptor and producing anxiolytic effect similar to that of benzodiazepines. [69]
29. Ellagic Acid Antidepressant and anti-anxiety activity Novelty-suppressed feeding,
Forced swimming,
Sucrose intake test		 Acts probably by interaction through adrenergic and serotonergic systems. On the other hand, cause inhibition of inducible NOS thereby acts as antidepressant. [70]
30. Puerarin Antidepressant and anti-stress activity Tail Suspension,
Forced swimming		 Ameliorates depression and pain via, activating ERK, CREB, and BDNF pathways, and inhibits corticotropin releasing hormone, corticosterone, adrenocorticotropic hormone, and normalization the activity of serotonergic system thereby preventing HPA axis dysfunction. [71,72]
31. Chlorogenic acid Antidepressant activity Tail Suspension,
Elevated plus-maze.		 Cross blood-cerebrospinal barrier and exhibit neuroprotection and promote serotonin release through enhancing synapsin I expression. [73]
32 Ursolic acid Antidepressant and Anxiolytic-like activity Tail suspension,
Forced swimming,
Open field test		 Action is mediated by an interaction with the dopaminergic system, through the activation of dopamine D1 and D2 receptors. [74]
33. Caffiec acid Anti-depressive and anxiolytic-like activity Elevated plus-maze,
Open field test		 Indirectly modulates α1-adrenoceptor i.e. α1A-adrenoceptor in cortical membranes and directly modulates second messenger acting through glutamate or GABAergic receptors thereby involved in the expression of its anti-depressive and/or anxiolytic-like effects. [75,76]
34. Sulforaphane Antidepressant and anxiolytic-like activity Forced swimming,
Tail suspension,
Chronic stress,
Open field test		 Normalize the stress-induced HPA axis dysfunction and have inhibitory effects on the inflammatory response to stress. [77]
35. Chicoric acid Antidepressant activity Immunomodulatory activity Forced swimming,
Learned helplessness Chronic restraint stress induced altered T lymphocyte distribution		 Modulates nor-adrenaline, dopamine and 5- hydroxy tryptamine in chronically stressed condition.
Imparted immune-stimulation by upregulating the expression of CD28 and CD80 and downregulating CTLA-4, stimulatory effect on IL-12, IFN-gamma and IL-2 and suppress the increased IL-10 and also lower corticosterone levels, thereby showing its normalizing effect on HPA axis.		 [78,79]
36. 3,4,5-trimethoxycinnamic acid Anti-stress, anxiety and depression-like activity Repeated cold exposure test Augment norepinephrine in brain and also ameliorated chronic stress and induced ΔFosB protein and SC1 mRNA expression in a nucleus accumbens shell sub region. [80,81]
37. Rosmarinic acid Anxiolytic-like activity Elevated plus-maze,
Step-down avoidance,
Open field test		 Involved in direct modulation of a second messenger through glutamate receptors, since these are directly involved in several CNS disorders, and the anxiolytic effect is seen at lower doses, without affecting the short & long-term memory retention or locomotion, exploration and motivation. [82]
38. Ferulic Acid Immunomodulatory activity Carbon clearance,
Neutrophil adhesion,
Serum immunoglobulins,
DTH response		 Acts by stimulating cell mediated immunity as well as humoral immunity by acting on B-cell and T-cell. [83]

Table 1: Reported plant biomolecules as adaptogen.

Conclusion

Adaptogens may be considered as a novel pharmacological group of herbal preparations not only for stress-induced and stress-related problems, but also for enhancing and maintaining the quality of life when co-administered along with the standard therapy for many diseased related pathological conditions. The concept of adaptogens is sufficient to be considered in the assessment of traditional herbal medicinal products. The use of adaptogens eliminates or significantly decreases the classical signs of the prolonged stress reactions due to minimal side effects, cost-effectiveness and efficacy. The principle of an adaptogenic action needs further research and studies in the preclinical and clinical area to evaluate the specific molecular mechanism of action.

Conflict of Interest

The authors declare that they have no conflicts of interest to disclose.

References

  1. Panossian AG (2003) Adaptogens: Tonic Herbs for Fatigue and Stress. Altern Complement Ther 9: 327-331.
  2. Sumanth M, Mustafa SS (2009) Antistress, Adoptogenic Activity of Sida cordifolia Roots in Mice. Indian J Pharm Sci 71: 323-324.
  3. Wagner H, Nörr H, Winterhoff H (1994) Plant adaptogens. Phytomedicine 1: 63-76.
  4. Panossian A, Wikman G (2010) Effects of adaptogens on the central nervous system and the molecular mechanisms associated with their stress-Protective activity. Pharmaceuticals 3: 188-224.
  5. Puri S, Kumar B, Debnath J, Tiwari P, Salhan M, et al. (2011) Comparative pharmacological evaluation of adaptogenic activity of Holoptelea integrifolia and Withania somnifera. Int J Drug Dev Res 3: 84-98
  6. Azmathulla S, Hule A, Naik SR (2006) Evaluation of adaptogenic activity profile of herbal preparation. Indian J Exp Biol 44: 574-579.
  7. Provino R (2010) The role of adaptogens in stress management. Aust J Med Herbal 22: 41-50.
  8. Sreemantula S, Nammi S, Kolanukonda R, Koppula S, Boini KM (2005) Adaptogenic and nootropic activities of aqueous extract of Vitis vinifera (grape seed): an experimental study in rat model. BMC Complement Altern Med 5: 1.
  9. Veena SD, Mishra RN (2011) Adaptogenic actvity of megaext of triamrit. Int J Res Pharm Chem 1: 12-16.
  10. Brook CA, Schmidt LA (2008) Social anxiety disorder: A review of environmental risk factors. Neuropsychiatric Disease and Treatment 4: 123-143.
  11. Steimer T (2002) The biology of fear- and anxiety-related behaviors. Dialogues in Clinical Neuroscience 4: 231-249.
  12. Stephens MAC, Wand G (2012) Stress and the HPA axis: role of glucocorticoids in alcohol dependence. Alcohol Res 34: 468-483.
  13. Majzoub JA (2006) Corticotropin-releasing hormone physiology. Eur J Endocrinol 155: S71-S76.
  14. Groeneweg FL, Karst H, de Kloet ER, Joëls M (2011) Rapid non-genomic effects of corticosteroids and their role in the central stress response. J Endocrinol 209: 153-167.
  15. Shi Di JGT, Marc Maxson M, Franco A (2013) Glucocorticoids Regulate Glutamate and GABA Synapse-Specific Retrograde Transmission via Divergent Non-Genomic Signaling Pathways. J Neurosci 80: 631-637.
  16. Tafet GE, Smolovich J (2004) Psychoneuroendocrinological studies on chronic stress and depression. Ann NY Acad Sci 1032: 276-278.
  17. McKay MS, Zakzanis KK (2010) The impact of treatment on HPA axis activity in unipolar major depression. J Psychiatr Res 44: 183-192.
  18. De Mello ADAF, De Mello MF, Carpenter LL, Price LH (2003) Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA) axis Uma atualização sobre estresse e depressão : o papel do eixo. Rev Bras Psiquiatr 25: 231-238.
  19. Dhabhar FS (2008) Enhancing versus Suppressive Effects of Stress on Immune Function : Implications for Immunoprotection versus. Clin Immunol 4: 2-11.
  20. Miyazaki H, Kinoshita M (2015) Stress-induced immunosuppression and physical performance. J Phys Fit Sport Med 4: 295-298.
  21. Dhabhar FS, Mcewen BS (1997) Acute Stress Enhances while Chronic Stress Suppresses Cell-Mediated Immunityin Vivo: A Potential Role for Leukocyte Trafficking. Brain Behav Immun 11: 286-306.
  22. Firdaus BSM, Dhabhar S, Malarkey WB (2012) Stress-Induced Redistribution of Immune Cells-From Barracks to Boulevards to Battlefields: A Tale of Three Hormones-Curt Richter Award Winner. Psychoneuroendocrinology 37: 1345-1368.
  23. Dhabhar FS (2009) A hassle a day may keep the pathogens away: The fight-or-flight stress response and the augmentation of immune function. Integr Comp Biol 49: 215-236.
  24. Gupta V, Gupta A, Saggu S, Divekar HM, Grover SK et al. (2005) Anti-stress and adaptogenic activity of L-arginine supplementation, Evidence-based Complement. Altern Med 2: 93-97.
  25. Shivaprasad HN, Kharya MD, Rana AC (2008) Antioxidant and adaptogenic effect of an herbal preparation, Triphala. J Nat Remedies 8: 82-88.
  26. Kumar MR, Reddy AG, Anjaneyulu Y, Reddy GD (2010) Oxidative stress induced by lead and antioxidant potential of certain adaptogens in poultry. Toxicol Int, 17: 45-48.
  27. Jain G, Rangari VD (2015) Effect of piperine in combination with 4-hydroxyisoleucine enriched Trigonella Foenum-Graecum extract and silymarin on paracetamol induced liver damage in rats. Int J Pharm Sci 7: 73-75.
  28. Kormosh N, Laktionov K, Antoshechkina M (2006) Effect of a combination of extract from several plants on cell-mediated and humoral immunity of patients with advanced ovarian cancer. Phytother Res 20: 424-425.
  29. Siripurapu KB, Gupta P, Bhatia G, Maurya R, Nath C, et al. (2005) Adaptogenic and anti-amnesic properties of Evolvulus alsinoides in rodents. Pharmacol Biochem Behav 81: 424-432.
  30. Nocerino E, Amato M, Izzo AA (2000) The aphrodisiac and adaptogenic properties of ginseng. Fitoterapia 71: 1-5.
  31. Lakshmi BVS, Sudhakar M (2009) Adaptogenic activity of Lagenaria siceraria: An experimental Study using acute stress models on rats. Journal of Pharmacology and Toxicology 4: 300-306.
  32. Cheng Y, Shen LH, Zhang JT (2005) Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action. Acta Pharmacol Sin 26: 143-149.
  33. Provalova NV (2002) Mechanisms underlying the effects of adaptogens on erythropoiesis during paradoxical sleep deprivation. Bull Exp Biol Med 133: 428-432.
  34. Bhatia N, Jaggi AS, Singh N, Anand P, Dhawan R (2011) Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis. J Nat Med 65: 532-543.
  35. Wang R (2008) The antidepressant effects of curcumin in the forced swimming test involve 5-HT1 and 5-HT2 receptors. Eur J Pharmacol 578: 43-50.
  36. Amogh AJM, Lotankar R, Wankhede S, Sharma JB (2016) Anti-Stress Activity of Flavonoids Rutin and Quercetin Isolated from the Leaves of Ficus benghalensis. Int J Pharm Pharm Res 5: 5-19.
  37. Hernandez-Leon A, González-Trujano ME, Fernández-Guasti A (2017) The anxiolytic-like effect of rutin in rats involves GABA A receptors in the basolateral amygdala. Behav Pharmacol 28: 303-312.
  38. Fernández-Moriano C, González-Burgos E, Iglesias I, Lozano R, Gómez-Serranillos MP (2017) Evaluation of the adaptogenic potential exerted by ginsenosides Rb1 and Rg1 against oxidative stress-mediated neurotoxicity in an in vitro neuronal model. PLOSONE pp: 1-22.
  39. Dhingra D, Sharma A (2005) Evaluation of antidepressant-like activity of glycyrrhizin in mice. Indian J Pharmacol 37: 390-394.
  40. Patidar G, Shaikh A (2012) Antistress potential of glycyrrhizin in chronic immobilization stress. Biomed Pharmacol J 5: 273-283.
  41. Neeraj Q (2014) Pharmacological Reports Possible involvement of GABAergic and nitriergic systems for antianxiety-like activity of piperine in unstressed and stressed mice. Pharmacol Reports.
  42. Li S, Wang C, Li W, Koike K, Nikaido T, et al. (2007) Antidepressant-like effects of piperine and its derivative, antiepilepsirine. J Asian Nat Prod Res 9: 421-430.
  43. Garabadu D (2011) Eugenol as an anti-stress agent: modulation of hypothalamic-pituitary-adrenal axis and brain monoaminergic systems in a rat model of stress. Stress 14: 145-155.
  44. Kumar A, Sunder S, Kumar V (2015) Adaptogenic potential of andrographolide: An active principle of the king of bitters (Andrographis paniculata). J Tradit Chinese Med Sci pp: 1-9.
  45. Gupta P, Yadav DK, Siripurapu KB, Palit G, Maurya R (2007) Constituents of Ocimum sanctum with antistress activity. J Nat Prod 70: 1410-1416.
  46. Oh H, Jai H, Jae N, Kim D (2014) Anti-stress effect of astragaloside IV in immobilized mice. J Ethnopharmacol 153: 928-932.
  47. Wan C (2013) Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity. Acta Pharmacol Sin 34: 522-530.
  48. Nazir N (2007) Immunomodulatory effect of bergenin and norbergenin against adjuvant-induced arthritis-A flow cytometric study. J Ethnopharmacol 112: 401-405.
  49. Cho JY (2001) In-vitro and in-vivo immunomodulatory effects of syringing. J Pharm Pharmacol 53: 1287-1294.
  50. Lee B, Sur B, Yeom M, Shim I, Lee H, et al. (2012) Effect of berberine on depression- and anxiety-like behaviors and activation of the noradrenergic system induced by development of morphine dependence in rats. Korean J Physiol Pharmacol 16: 379-386.
  51. Peng WH, Wu CR, Chen CS, Chen CF, Leu ZC, et al. (2004) Anxiolytic effect of berberine on exploratory activity of the mouse in two experimental anxiety models: Interaction with drugs acting at 5-HT receptors. Life Sci 75: 2451-2462.
  52. Guzmán-Gutiérrez SL, Bonilla-Jaime H, Gómez-Cansino R, Reyes-Chilpa R (2015) Linalool and β-pinene exert their antidepressant-like activity through the monoaminergic pathway. Life Sci 128: 24-29.
  53. Lappas CM (2015) The plant hormone zeatin riboside inhibits T lymphocyte activity via adenosine A 2A receptor activation. Cell Mol Immunol 1233: 107-112.
  54. Capra JC (2010) Antidepressant-like effect of scopoletin, a coumarin isolated from Polygala sabulosa (Polygalaceae) in mice: Evidence for the involvement of monoaminergic systems. Eur J Pharmacol 643: 232-238.
  55. Marcilhacl CO, Dakinel N , Bourhiml N, Guillaumel V, Grinol M, et al. (1999) Effect of chronic administration of ginkgo biloba extract or ginkgolide on the hypothalamic-pituitary-adrenal axis in tha rat. Life Sci 62: 2329-2340.
  56. Lin Y, Liu HL, Fang J, Yu CH, Xiong YK, et al. (2014) Anti-fatigue and vasoprotective effects of quercetin-3-O-gentiobiose on oxidative stress and vascular endothelial dysfunction induced by endurance swimming in rats. Food Chem Toxicol 68: 290-296.
  57. Chhillar R, Dhingra D (2013) Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress. Fundam Clin Pharmacol 27: 409-418.
  58. Jung HY (2015) Valerenic Acid Protects Against Physical and Psychological Stress by Reducing the Turnover of Serotonin and Norepinephrine in Mouse Hippocampus-Amygdala Region. J Med Food 18: 1333-1339.
  59. Becker A, Felgentreff F, Schröder H, Meier B, Brattström A (2014) The anxiolytic effects of a Valerian extract is based on Valerenic acid. BMC Complement Altern Med 14: 267.
  60. Smit H (2001) Immunomodulatory activity of cucurbitacins from Picrorhiza scrophulariiflora Chapter 8 in Picrorhiza scrophulariiflora, from traditional use to immunomodulatory activity. pp: 112-124.
  61. Zhu L (2016) Esculetin attenuates lipopolysaccharide (LPS)-induced neuroinflammatory processes and depressive-like behavior in mice. Physiol Behav 163: 184-192.
  62. Lee B (2013) Chronic administration of catechin decreases depression and anxiety-like behaviors in a rat model using chronic corticosterone injections. Biomol Ther 21: 313-322.
  63. Liang X (2008) Antidepressant-like effect of asiaticoside in mice. Pharmacol Biochem Behav 89: 444-449.
  64. Liao JC, Tsai JC, Liu CY, Huang HC, Wu LY, et al. (2013) Antidepressant-like activity of turmerone in behavioral despair tests in mice. BMC Complement Altern Med 13: 299.
  65. 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. Phytother Res 21: 37-43.
  66. Pise MV, Rudra JA, Upadhyay A (2015) Immunomodulatory potential of shatavarins produced from Asparagus racemosus tissue cultures. J Nat Sci Biol Med 6: 415-420.
  67. Ma S, Li L, Cai C, Dong-lian D, Li L, et al. (2009) Protective effects of salidroside on oxidative damage in fatigue mice. Zhong Xi Yi Jie He Xue Bao, vol. 4, no. 7, pp. 237-41, 2009.
  68. Aguirre-Hernández E, Rosas-Acevedo H, Soto-Hernéndez M, Martínez AL, Moreno J, et al. (2007) Bioactivity-guided isolation of β-sitosterol and some fatty acids as active compounds in the anxiolytic and sedative effects of Tilia americana var. Mexicana. Planta Med 73: 1148-1155.
  69. Dhingra D, Bansal S (2015) Antidepressant-like activity of ellagic acid in unstressed an acute immobilization-induced stressed mice. Pharmacol Reports 67: 1024-1032.
  70. Zhao J, Luo D, Liang Z, Lao L, Rong J (2017) Plant Natural Product Puerarin Ameliorates Depressive Behaviors and Chronic Pain in Mice with Spared Nerve Injury (SNI). Mol Neurobiol 54: 2801-2812.
  71. Qiu ZK (2017) Puerarin ameliorated the behavioral deficits induced by chronic stress in rats. Sci Rep 7: 6266.
  72. Wu J, Chen H, Li H, Tang Y, Yang L, et al. (2016) Antidepressant potential of chlorogenic acid-enriched extract from Eucommia ulmoides Oliver bark with neuron protection and promotion of serotonin release through enhancing synapsin I expression. Molecules 21: 1-17.
  73. MacHado DG (2012) Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: Evidence for the involvement of the dopaminergic system. Pharmacol Biochem Behav 103: 204-211.
  74. Pereira P, De Oliveira PA, Ardenghi P, Rotta L, Henriques JAP, et al. (2006) Neuropharmacological analysis of caffeic acid in rats. Basic Clin Pharmacol Toxicol 99: 374-378.
  75. Takeda H, Tsuji M, Miyamoto J, Masuya J, Iimori M, et al. (2003) Caffeic acid produces antidepressive- and/or anxiolytic-like effects through indirect modulation of the α1A-adrenoceptor system in mice. Neuroreport 14: 1067-1070.
  76. Wu S (2016) Sulforaphane produces antidepressant-and anxiolytic-like effects in adult mice. Behav Brain Res 301: 55-62.
  77. Kour K, Bani S (2011) Augmentation of immune response by chicoric acid through the modulation of CD28/CTLA-4 and Th1 pathway in chronically stressed mice. Neuropharmacology 60: 852-860.
  78. Kour K, Bani S (2011) Chicoric acid regulates behavioral and biochemical alterations induced by chronic stress in experimental Swiss albino mice. Pharmacol Biochem Behav 99: 342-348.
  79. Kawashima K, Miyako D, Ishino Y, Makino T, Saito KI, et al. (2004) Anti-stress effects of 3,4,5-trimethoxycinnamic acid, an active constituent of roots of Polygala tenuifolia (Onji). Biol Pharm Bull 27: 1317-1319.
  80. Leem YH, Oh S (2015) 3,4,5-Trimethoxycinnamin acid ameliorates restraint stress-induced anxiety and depression. Neurosci Lett 585: 54-59.
  81. Pereira P, Tysca D, Oliveira P, Brum LFDS, Picada JN, et al. (2005) Neurobehavioral and genotoxic aspects of rosmarinic acid. Pharmacol Res 52: 199-203.
  82. Singh MK, Das BK, Trivedi R (2016) In Vivo Evaluation of Immunomodulatory Potential of Ferulic Acid. Int Res J Pharm 7: 12-17.
Citation: Singh MK, Jain G, Das BK, Patil UK (2017) Biomolecules from Plants as an Adaptogen. Med Aromat Plants (Los Angeles) 6: 307.

Copyright: © 2017 Sing MK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Top