Adaptogens Stimulate Neuropeptide Y and Hsp72 Expression and Release in Neuroglia Cells

The beneficial stress–protective effect of adaptogens is related to the regulation of homeostasis via mechanisms of action associated with the hypothalamic–pituitary–adrenal axis and the regulation of key mediators of the stress response, such as molecular chaperones, stress-activated c-Jun N-terminal protein kinase, forkhead box O transcription factor, cortisol, and nitric oxide (NO). However, it still remains unclear what the primary upstream targets are in response to stimulation by adaptogens. The present study addresses this gap in our knowledge and suggests that an important target for adaptogen mediated stress–protective effector functions is the stress hormone neuropeptide Y (NPY). We demonstrated that ADAPT-232, a fixed combination of adaptogens Eleutherococcus senticosus root extract, Schisandra chinensis berry extract, Rhodiola rosea root extract SHR-5, and its active constituent salidroside, stimulated the expression of NPY and 72 kDa heat shock protein (Hsp72) in isolated human neuroglia cells. The central role of NPY was validated in experiments in which pre-treatment of human neuroglia cells with NPY-siRNA and HSF1-siRNA resulted in the significant suppression of ADAPT-232-induced NPY and Hsp72 release. Taken together our studies suggest that the stimulation and release of the stress hormones, NPY and Hsp72, into systemic circulation is an innate defense response against mild stressors (ADAPT-232), which increase tolerance and adaptation to stress

Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms Associated with Their Stress—Protective Activity

Adaptogens were initially defined as substances that enhance the “state of nonspecific resistance” in stress, a physiological condition that is linked with various disorders of the neuroendocrine-immune system. Studies on animals and isolated neuronal cells have revealed that adaptogens exhibit neuroprotective, anti-fatigue, antidepressive, anxiolytic, nootropic and CNS stimulating activity. In addition, a number of clinical trials demonstrate that adaptogens exert an anti-fatigue effect that increases mental work capacity against a background of stress and fatigue, particularly in tolerance to mental exhaustion and enhanced attention. Indeed, recent pharmacological studies of a number of adaptogens have provided a rationale for these effects also at the molecular level. It was discovered that the stress—protective activity of adaptogens was associated with regulation of homeostasis via several mechanisms of action, which was linked with the hypothalamic-pituitary-adrenal axis and the regulation of key mediators of stress response, such as molecular chaperons (e.g., HSP70), stress-activated c-Jun N-terminal protein kinase 1 (JNK1), Forkhead box O (FOXO) transcription factor DAF-16, cortisol and nitric oxide

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

Adaptogens possess anti-fatigue and anti-stress activities that can increase mental and physical working performance against a background of fatigue or stress. The aim of the present study was to ascertain which mediators of stress response are significantly involved in the mechanisms of action of adaptogens, and to determine their relevance as biochemical markers for evaluating anti-stress effects in rabbits subjected to restraint stress. Blood levels of stress-activated protein kinase (SAPK/JNK), the phosphorylated kinase p-SAPK/p-JNK, nitric oxide (NO), cortisol, testosterone, prostaglandin E2, leukotriene B4 and thromboxane B2 were determined in groups of animals prior to daily oral administration of placebo, rhodioloside or extracts of Eleutherococcus senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng over a 7 day period. Ten minutes after the fi nal treatment, animals were immobilized for 2 hours and blood levels of the markers re-determined. In the placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly (by 200–300% cf basal levels) following restraint stress, whilst in animals that had received multiple doses of adaptogens/stress-protectors, the levels of NO and cortisol remained practically unchanged after acute stress. Rhodioloside and extracts of S. chinensis and R. rosea were the most active inhibitors of stress-induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea and S. chinensis on p-SAPK/p-JNK activation may be associated with their anti-depressant activity as well as their positive effects on mental performance under stress

Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of Metabolic Regulation of Isolated Neuroglial Cells

Gene expression profiling was performed on the human neuroglial cell line T98G after treatment with adaptogen ADAPT-232 and its constituents – extracts of Eleutherococcus senticosus root, Schisandra chinensis berry, and Rhodiola rosea root as well as several constituents individually, namely, eleutheroside E, schizandrin B, salidroside, triandrin, and tyrosol. A common feature for all tested adaptogens was their effect on G-protein-coupled receptor (GPCR) signaling pathways, i.e. cAMP, phospholipase C and phosphatidylinositol signal transduction pathways. Adaptogens may reduce the cAMP level in brain cells by downregulation of adenylate cyclase gene ADC2Y and upregulation of phosphodiestherase gene PDE4D that is essential for energy homeostasis as well as for switching from catabolic to anabolic states and vice versa. All tested adaptogens up-regulated the PLCB1 gene, which encodes phosphoinositide-specific phospholipase C (PLC) and phosphatidylinositol 3-kinases (PI3Ks), key players for the regulation of NF-B-mediated defense responses. Other common targets of adaptogens included genes encoding ERα estrogen receptor(2.9-22.6 fold down-regulation), cholesterol ester transfer protein (5.1-10.6 fold down-regulation), heat shock protein Hsp70 (3.0-45.0 fold up-regulation), serpin peptidase inhibitor (neuroserpin), and 5-HT3 receptor of serotonin (2.2-6.6 fold down-regulation). These findings can be reconciled with the observed beneficial effects of adaptogens in behavioral, mental and aging-associated disorders. Combining two or more active substances in one mixture significantly changes deregulated genes profiles: synergetic interactions result in activation of genes that none of the individual substances affected, while antagonistic interactions result in suppression some genes activated by individual substances. Merging of deregulated genes array profiles and intracellular networks is specific to the new substance with unique pharmacological characteristics

A double‐blind study with a new monodrug Kan Jang: Decrease of symptoms and improvement in the recovery from common colds

In a placebo‐controlled double‐blind study, the therapeutic effect of Kan Jang tablets made from Andrographis paniculata (Barm. F.) (Ness) dried extract was tested in patients with common colds. The patients were divided in two groups, in which group 1 (n = 33) received 1200 mg of Andrographis paniculata and group 2 (n = 28) a placebo (P). On day 3–4 after treatment the possible effect of Kan Jang tablets on selected symptoms and clinical signs of common cold was evaluated. A significant reduction in clinical symptoms at day 4 of administration of the Kan Jang tablets was observed. A better efficacy against the placebo is discussed. The differences in the total ‘sumscores’ of clinical and symptomatic findings indicate that the Kan Jang treated group did far better than the placebo group. We conclude that Kan Jang in a dose of 1200 mg daily has the capacity to significantly shorten the course/duration of the disease and therefore is indicated for an enhanced resistance to common colds

Comparative Study of Femineral® and Floradix® in Women of Child-Bearing Age and Adolescent Girls with Iron Deficiency Anaemia

This double blind randomised trial compared the clinical efficacy of Femineral®, a proprietary herbal preparation containing highly soluble iron compounds, minerals, and vitamins, with Floradix®, the most popular iron supplement in Scandinavia for patients with iron deficiency anaemia (IDA). Fifty women of childbearing age and adolescent girls, all diagnosed with IDA, were randomised into two groups. One group (n = 26) was treated with Femineral (10 ml twice a day; 15 mg of iron supplement/day), while the second (n = 24) received Floradix® (10 ml twice a day; 20 mg of iron supplement/day). The efficacy of 28 days of treatment in each group was evaluated by analysis of serum iron levels, blood haemoglobin and erythrocyte counts; by the mental performance of the patients on days one and 28; and by assessment of IDA symptoms, such as pale skin colour, fatigue, irritability, weakness, constipation, brittle nails, cold hands and feet, headache, blue tinge to sclera, and feeling of well being on days one, seven, 14 and 28. The Femineral group showed significant improvements in blood haemoglobin levels and red cell counts after 28 days, while the Floradix group did not. The Femineral group showed better improvements in other IDA symptoms, such as impaired mental performance, pale skin colour, fatigue, irritability, weakness, constipation, brittle nails, cold hands and feet. Both groups showed significant improvements in serum iron levels at the end of the study. Such improvements correlate with the results of memory tests: the number of errors by both groups was significantly lower at the end of the study. There were no significant differences in memory tests between the two groups. Eight patients in the Floradix group and one in the Femineral group reported drowsiness. The Femineral group reported two other adverse events (nausea and vomiting). Femineral can be used safely in the treatment of iron deficiency anaemia. It is more efficient and safe than Floradix