Stress-protective Activity Research Articles

Comparative Analysis of Stress-Protective Activity and Prevention of Fatigue during Physical Load of Standardized Humic Acids from Peat and Officinal Preparations of Succinic Acid in Experiment.

The effect of humic acids and substances with similar action - derivatives of succinic acid (ethylmethylhydroxypyridine succinate) and combined agent consisting of succinic acid, nicotinamide, riboflavin, and riboxin on the performance and stress resistance of experimental rats was studied. Performance was assessed in the test of exhaustive forced swimming with a load, stress resistance was evaluated by the serum level of corticosterone and open field behavior, and the state of anaerobic metabolism was estimated by the serum level of lactate after swimming test. Humic acids from peat showed anti-stress activity comparable to that of the officinal preparation and preventive effect on fatigue during physical exercise. They can be recommended as a component for the development of drugs that increase human performance and stress resistance.

STRESS-PROTECTIVE ACTIVITY OF THE COMPLEX REMEDY IN ACUTE IMMOBILIZATION STRESS

Relevance. The range of medicinal remedies in the traditional Tibetan medicine contains several tens of formulae named bchud len. They are multicomponent remedies of natural origin having a stimulating non-specific effect on the human body. The analysis of such formula under the name ‘Rejuvenating-35’ has been presented in the paper. The complex remedy on the base of this formula was developed. Its composition includes 14 species of the plants and chitosan as a source of mineral substances. Previous phytochemical studies have revealed that the given remedy contains a wide spectrum of biologically active substances, namely triterpene saponins, flavonoids, ether oils, tannins, polysaccharides, etc. The aim of the present work was to evaluate stress-protective activity of the complex remedy in acute restraint stress. Material and methods. Experiments were carried out on white Wistar rats. The acute stress was simulated by immobilization of animals in supine position for 18 hours. The tested remedy was introduced in the form of decoction for 7 days before exposure to stress. Results. It has been established that the course administration of the complex remedy decreases the manifestation of the Selye’s triad signs: 26% decrease of adrenal glands hypertrophy, 45% and 60% decrease in involution of thymus and spleen respectively as compared to the data in the control group of animals. Besides, its administration prevents the development of rough destructions in the stomach mucosa in the form of erosions and linear ulcers. Against the background of the complex remedy administration there was noted twofold decrease of TBA-active products concentra-tion, fourfold increase of superoxide dismutase activity, 30% increase of catalase activity and the content of the reduced glutathione was 30% in-creased as compared to the data in the control. Conclusions. The preventive administration of the complex remedy has stress-protective effect against the background of acute restraint stress. Molecular-cell mechanisms of its anti-stress effect are connected with the inhibition of free-radical oxidation processes and the increased activity of the endogenic antioxidant system.

Study of the Magnesium Comenate Structure, Its Neuroprotective and Stress-Protective Activity.

The crystal structure and the biological activity of a new coordination compound of magnesium ions with comenic acid, magnesium comenate, was characterized and studied. Quantitative and qualitative analysis of the compound was investigated in detail using elemental X-ray fluorescent analysis, thermal analysis, IR-Fourier spectrometry, UV spectroscopy, NMR spectroscopy, and X-ray diffraction analysis. Based on experimental analytical data, the empirical formula of magnesium comenate [Mg(HCom)2(H2O)6]·2H2O was established. This complex compound crystallizes with eight water molecules, six of which are the hydration shell of the Mg2+ cation, and two more molecules bind the [Mg(H2O)6]2+ aquacation with ionized ligand molecules by intermolecular hydrogen bonds. The packing of molecules in the crystal lattice is stabilized by a branched system of hydrogen bonds with the participation of solvate water molecules and oxygen atoms of various functional groups of ionized ligand molecules. With regard to the biological activity of magnesium comenate, a neuroprotective, stress-protective, and antioxidant effect was established in in vitro and in vivo models. In in vitro experiments, magnesium comenate protected cerebellar neurons from the toxic effects of glutamate and contributed to the preservation of neurite growth parameters under oxidative stress caused by hydrogen peroxide. In animal studies, magnesium comenate had a stress-protective and antioxidant effect in models of immobilization-cold stress. Oral administration of magnesium comenate at a dose of 2 mg/kg of animal body weight for 3 days before stress exposure and for 3 days during the stress period led to a decrease in oxidative damage and normalization of the antioxidant system of brain tissues against the background of induced stress. The obtained results indicate the advisability of further studies of magnesium comenate as a compound potentially applicable in medicine for the pharmacological correction of conditions associated with oxidative and excitotoxic damage to nerve cells.

The influence of non-steroidal anti-inflammatory drugs with different mechanisms of action on the course of stress reaction, the functional state of kidneys, liver, and heart on the model of acute general cooling

Inhibitors of the arachidonic acid cascade have significant potential as the agents for the prevention of severe cold injuries. The results of the previous studies have demonstrated the pronounced frigoprotective properties of certain non-steroidal anti-inflammatory drugs, primarily diclofenac sodium, etoricoxib, darbufelone mesylate, under the conditions of acute general cooling.
 The aim of the study: to investigate the effect of non-steroidal anti-inflammatory drugs with various mechanisms of action on the course of the stress reaction, the functional state of the kidneys, liver, and heart using the model of acute general cooling.
 Materials and Methods: The experiment was carried out using 35 outbreed male rats weighing 256±5 g. The studied drugs were administered intragastrically 30 minutes before cold injury modelling: diclofenac sodium at a dose of 7 mg/kg, etoricoxib at a dose of 5 mg/kg, darbufelone mesylate at a dose of 20 mg/kg. Acute general cooling was induced by exposure at –18 °C for 2 hours. The efficacy of the studied drugs was evaluated by the values as follows: the body temperature (measured rectally), the course of a stress reaction according to the criteria of “the stress triad”, the functional state of the kidney and liver according to the changes in the blood serum biochemical parameters, the functional state of the heart according to the electrocardiogram.
 Results: It was found that etoricoxib and darbufelone mesylate, and especially diclofenac sodium, demonstrate frigoprotective properties, reducing the severity of hypothermia, have stress-protective activity and a beneficial effect on the functional state of the kidneys. All investigated non-steroidal anti-inflammatory drugs prevent a decrease in myocardial contractility (by the effect on the systolic index) and lengthening of the QT interval caused by acute cold injury. Diclofenac sodium, unlike etoricoxib and darbufelone mesylate, does not enhance the effect of acute general cooling on intraventricular conduction. Under acute exposure to cold, no significant changes in the functional state of the liver were observed, including the groups receiving the nonsteroidal anti-inflammatory medicines.
 Conclusions: The prophylactic administration of the arachidonic acid cascade inhibitors, especially the non-selective COX-2 inhibitor diclofenac sodium, reduces the severity of the stress response, contributes to the maintenance of the renal and cardiac function. There are no significant changes in the functional state of the liver under conditions of the experiment

Rhaponticum uniflorum and Serratula centauroides Extracts Attenuate Emotional Injury in Acute and Chronic Emotional Stress.

In modern life, the use of plant stress-protectors has taken on particular significance due to the wide distribution of neurosis-like and neurotic diseases caused by neuroendocrine-immune system imbalance. Special attention has been paid to the plants containing ecdysteroids, i.e., hormone-like bioactive substances with high adaptogenic activity. The article deals with the study of bioactivity of two plant extracts as Rhaponticum uniflorum (L.) DC. and Serratula centauroides L. with a high content of ecdysteroids and phenolic compounds. The models of acute and chronic emotional stress in white rats were used to estimate the stress-protective activity of R. uniflorum and S. centauroides extracts. Both extracts showed the stress-protective effect via inhibiting the development of signs induced by single and long-term effects of stress factors. In acute stress, the development of Selye's triad signs was less pronounced against the background of the plant remedies introduction. In chronic stress, the extracts prevented the development of anxiety-depressive syndrome. Besides, R. uniflorum and S. centauroides extracts banned the development of stress-induced injuries in the brain cortex and had a neuroprotective effect on ischemia against chronic stress. The stress-protective effects of both plant extracts were based on a decrease of hyperactivation of the central stress-promoting systems (sympathoadrenal, hypothalamic-pituitary-adrenal) due to their GABA-mimetic effects. Peripheral mechanisms were connected with the inhibition of free radical oxidation processes and with an increase in the endogenous antioxidant system activity. Thus, R. uniflorum and S. centauroides extracts have a high potential to increase non-specific body resistance against acute and chronic emotional stress effects.

Ashwagandha for reduced stress and anxiety

Ashwagandha for reduced stress and anxiety

POSSIBILITIES OF REGULATING STRESS-PROTECTIVE ACTIVITY OF FOOD PRODUCTS TO IMPROVE IMMUNITY UNDER THE CONDITIONS OF THE COVID-19 PANDEMIC

Aim. The paper aims to develop food products that contribute to the resistance of active people to stress factors, especially during the COVID-19 pandemic. Materials and methods. The cohort study was conducted in three parallel groups of volunteers aged from 20 to 40 years (n = 45) who were consistently involved in sports (low-intensity training at least 3 times a week). As food products with stress-protective activity, freeze-dried taxifolin nanoemulsion and whole-wheat flour from wheatgrass were used. As mental and informational stress, media coverage of global and Russian COVID-2019 dynamics was used. To assess the impact of the developed products on stress resistance, a study of health and psychoemotional status (the SF-36 questionnaire) and biochemical blood analysis (leukocyte formula and cortisol) were carried out. Results. The results demonstrated the possibility of using stress-protective food products such as freeze-dried taxifolin nanoemulsion and whole-wheat flour from wheatgrass for improving immunity. The assessment of the psychoemotional status revealed an equally positive effect from the inclusion of taxifolin nanoemulsion and whole-wheat flour from wheatgrass in the composition of food products. Biochemical blood analysis and leukocyte indices revealed a greater positive effect of taxifolin nanoemulsion on the human body, while regular consumption of whole-wheat flour-based products from wheatgrass reduces blood cortisol and increases the body's resistance to stress factors. Conclusion. People involved in low-intensity sports are recommended to consume foods enriched with taxifolin nanoemulsion and whole-wheat flour from wheatgrass to improve their psychoemotional status and resistance to stress factors such as the COVID-19 pandemic.

The preclinical studies of the stress-protective activity of “Tonus-aktiv” homeopathic granules

Aim. To perform the preclinical studies of the stress-protective activity of a new “Tonus-Aktiv” homeopathic medicinal product.Materials and methods. The stress-protective effect of the “Tonus-Aktiv” homeopathic medicinal product (MP) and the reference drug – “Stress-gran” homeopathic granules were studied on the model of neuromuscular tension by Selye. The stress-protective effect of the drugs was assessed by the conventional methods described in the scientific literature and the corresponding current instructional guidelines. All factual material was processed by variational statistics methods using parametric (Newman-Keuls test) and non-parametric methods of analysis (Kruskal-Wallis, Mann-Whitney).Results and discussion. It was found that “Tonus-Aktiv” had a pronounced gastro-protective effect, reducing the area of ulcers by almost 3 times, having a statistically significant antioxidant effect, reducing the level of TBA (thiobarbituric acid) active products in the liver homogenate. It did not have a normalizing effect on the protein metabolism, but it did contribute to enhancing energy-supplying metabolic processes: aerobic glycolysis indicated by a reliable increase of the pyruvic acid level in the blood serum, and lipolysis, as evidenced by a significantly higher level of the total blood lipids. “Tonus-Aktiv” showed a pronounced antioxidant activity: it reduced the TBA level of active products in the liver homogenate. At the same time, the level of endogenous antioxidant of reduced glutathione was observed to be lower than in the stressed animals against the background of the “Tonus-Aktiv” application. It indicates the physiological nature of the stress protective activity of the drug.Conclusions. A moderate stress-protective activity of “Tonus-Aktiv” homeopathic granules can be observed; it is caused by antioxidant properties, as well as a probable activating effect on the hypothalamic-pituitary-adrenal system, which may be manifested by the protective action.

Anti Stress Activity of Phytoecdysteroids Isolated from Aerial Part of Silene claviformis

Aims: The aim of present study was to isolate the phytoedysteroids from aerial part of Silene claviformis (Caryophyllaceae) and investigate their biological activity.
 Place and Duration of Study: The investigation were carried out during 2019 and 2020 at laboratory of the chemistry of glycosides and department of the pharmacological and toxicology of Institute of the Chemistry of Plant Substances AS RUz, Tashkent, Uzbekistan.
 Methodology: The phytoecdysteroids were isolated from aerial part of Silene claviformis using chromatographic methods. Thin-layer chromatography made on Silufol UV-254 and Merck plates, Fluka Analytical Germany, by spraying with alcohol solution of vanillin and heating for 1-2 minutes for 90-1000, UV lamp light at 254 nm and 365 nm. Their structures were confirmed by NMR and IR spectroscopy. Sum of phytoecdysteroids was administered at a dose of 10 mg/kg orally. The data obtained during the experiments were processed and analyzed by the method of variation statistics using the Student t-criterion.
 Results: Silene claviformis contains 2-deoxyecdysterone (1), polypodine B (2), 20-hydroxyecdysone (3), ecdysterone-20,22-acetalisovaleric aldehyde (4),integristeron A (5),cyasterone (6), ecdysterone-20,22-acetalisovalerian (7), 2-deoxy-α-ecdysone (8). The compounds 2 and 6 are reported for the first time from this genus. The biological activity (stress-protective effect) of the mentioned phytoecdysteroids studied for the first time. These compounds were tested on male mice for their biological activities and results showed that, the adrenal gland mass increased in relation to the adrenal gland mass of intact animals by 42.6%, they showed a significant decrease in the content of ascorbic acid and cholesterol by 56.5 and 49.1%, respectively. A significant decrease in glycogen content (by 30.1%) and a noticeable activation of lipid peroxidation processes were noted in the liver, as indicated by an increase of 69.2% in the content of malondialdehyde in the organ.
 Conclusion: This is the first study reporting an orally biological investigation for Silene claviformis. The sum of phytoecdysteroids showed potent stress-protective activity. The stress-protective effect of phytoecdysteroids was more pronounced in compared the eleutherococcus extract.

USE OF NEW COMPOUNDS OF THE QUINOLINE SERIES AS EFFECTIVE STIMULANTS OF GROWTH PROCESSES

The results of a study of the action of compounds of the general formula: 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2-dihydroquinoline and 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2,3,4-tetrahydroquinoline are presented. The most effective growth stimulants from compounds of the series 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2-dihydroquinoline and 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2,3,4-tetrahydroquinoline for yellow rhododendron (Rhododendron luteum) and Ledebur rhododendron (Rhododendron ledebourii) were revealed. Rhododendron seedlings were counted to study laboratory germination and planted in crates in closed ground on 21 days after the start of the experiment. It was established that the synthesized chemicals cause stimulation of the growth of species of the genus Rhododendron in comparison with existing commercial preparations. The efficiency of using solutions of compounds of the series 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2-dihydroquinoline and 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2,3,4-tetrahydroquinoline and their concentrations. A method of using compounds of this series as growth stimulants is disclosed, which allows increasing seed germination of species of the genus Rhododendron from 20 to 50%, increasing the height of Rhododendron luteum seedlings from 18 to 63%, and Rhododendron ledebourii from 33 to 183 %. Dihydroquinolines are most effective for species of the genus Rhododendron. Compounds containing a dihydro-6-quinolinyl substituent stimulate the growth of these plants. The specificity of the action of growth stimulants is noted. The expediency of using quinoline series compounds for the production of planting material of ornamental plants for landscaping is shown. It is suggested the auxin activity of compounds of the general formula: 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2-dihydroquinoline and 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2,3,4-tetrahydroquinoline. It is assumed that compounds of the series 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2-dihydroquinoline and 1-alkyl-2,2,4-trimethyl-6-aminocarbothioyl-1,2,3,4-tetrahydroquinoline may have the stressprotective activity for species of the genus Rhododendron. The materials of the article are of practical value forbiologists, ecologists, plant growers.

The Influence of Selank on the Level of Cytokines Under the Conditions of "Social" Stress.

It was previously thought that inflammation and an immune response were the only factors capable of causing IL-1β, IL-6 and other cytokine`s production. In recent years data have appeared that stressful effects can also occupy an important place, enhancing production of IL- 1β, IL-6 and other cytokines; the result will be a change in the functional activity of a particular cell element, for example immunocompetent cells with subsequent development of inflammation, or a change in the functional activity of neurons. This experiment is aimed at studying the effect of the Selank glyprolin neuropeptide drug on the level of cytokines in animals under conditions of "social" stress, the results of which indicate the presence of stress-protective activity. White nonlinear rats were used as experimental animals. A model of confrontations between males was chosen to create a "social" stress. The animals were in pairs in a cage which were separated by a septum preventing physical contact but having openings that provide sensory contact. Each day, the septum was removed for 10 minutes leading in an overwhelming majority to agonistic collisions (confrontations). Laboratory animals were divided into 3 groups: a group of intact males, a group of animals that were subjected to stress (sensory contact) for 20 days and a group that received intraperitoneally Selank at a dose of 100 mcg/kg/day under conditions of 20-day stress. The level of cytokines under study was determined by enzyme-linked immunosorbent assay. As a result of the work performed to determine the concentration of pro-inflammatory and anti- inflammatory cytokines, it was found that in the serum of animals exposed to stress, there was a statistically significant increase in the level of IL-1β, IL-6 and TGF-β1 in individuals with both types of behavior. It should be noted that, under the conditions of this stressful impact, there was a tendency to decrease the concentration of IL-4 and increase the level of TNF-α but these indicators were not statistically significant. Evaluation of the effect of Semax on the level of the cytokines in a stress-induced state showed that this neuropeptide causes a decrease in the concentration of IL-1β and IL-6, restoration of the level of IL-4, as well as suppression of the production of TGF-β1 and TNF-α in these conditions. This peptide is able to reduce the concentration of IL-1β, IL-6 and TNF-α, as well as TGF-β1, practically reaching control values, when studying the effect of Selank on the level of cytokines under conditions of " social" stress. There is the need for a detailed study of the role of cytokines in the development of stress-induced changes in order to find optimal correction tools.

Effects of an Adaptogenic Extract on Electrical Activity of the Brain in Elderly Subjects with Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled, Two-Armed Cross-Over Study.

Background: The current and potential uses of adaptogens are mainly related to treatment of stress-induced fatigue, impaired cognitive function, mental illness, and behavioral- and age-related disorders. However, clinical evidence regarding the efficacy of adaptogens is limited. The primary aim of this study is to determine whether a combination of adaptogenic plant extracts from Andrographis paniculata and Withania somnifera (Adaptra® Forte) could be used as effective and safe treatment for impaired cognitive, memory, or learning ability functions and sleep disorders. Methods: The changes in electroencephalogram (EEG) frequency ranges in 17 different brain regions, psychometric tests of cognitive performance, as well as standard questionnaires of assessment of mood and sleep were measured after single and repeated administration of Adaptra® or placebo for four weeks and after a two-week treatment-free follow-up period within a randomized, double-blind, placebo-controlled two-armed cross-over study. Results: Adaptra® Forte significantly improved cognitive performance in the d2-Test for attention and the concentration performance test after four weeks’ treatment, and was positively correlated with increases in δ and θ power in the quantitative EEG compared with placebo during cognitive challenges. Conclusion: The results of this study suggest that Adaptra® Forte exhibits a calming and anxiolytic effect without sedation, and is associated with overall stress-protective activity.

Function of Prion Protein and the Family Member, Shadoo.

Lowering cellular prion protein (PrPC) levels in the brain is predicted to be a powerful therapeutic strategy for the prion disease. PrPC may act as an antiapoptotic agent by blocking some of the internal environmental factors that initiate apoptosis. Prion protein (PrP)-knockout methods provide powerful indications on the neuroprotective function of PrPC. Using PrPC-knockout cell lines, the inhibition of apoptosis through stress inducible protein1 (STI1) is mediated by PrPC-dependent superoxide dismutase (SOD) activation. Besides, PrP-knockout exhibited wide spread alterations of oscillatory activity in the olfactory bulb as well as altered paired-pulse plasticity at the dendrodendric synapse. Both the behavioural and electro-physiological phenotypes could be rescued by neuronal PrPC expression. Neuprotein Shadoo (Sho), similarly to PrPC, can prevent neuronal cell death induced by the expression of PrP△HD mutants, an artificial PrP mutant devoid of internal hydrophobic domain. Sho can efficiently protect cells against exito-toxin-induced cell death by glutamates. Sho and PrP seem to be dependent on similar domains, in particular N-terminal (N), and their internal hydrophobic domain. Sho△N and Sho△HD displayed a reduced stress-protective activity but are complex glycosylated and attached to the outer leaflet of the plasma membrane via glycosylphosphatidylinositol (GPI) anchor indicating that impaired activity is not due to incorrect cellular trafficking. In Sho, over-expressed mice showed large amyloid plaques not seen in wild-type mice. However, Shadoo is not a major modulator of abnormal prion protein (PrPSc) accumulation. Sho and PrP share a stress-protective activity. The ability to adopt a toxic conformation of PrPSc seems to be specific for PrP.

Biosynthesis of isocitric acid in repeated-batch culture and testing of its stress-protective activity.

Biosynthesis of Ds(+)-threo-isocitric acid from ethanol in the Yarrowia lipolytica batch and repeated-batch cultures was studied. Repeated-batch cultivation was found to provide for a good biosynthetic efficiency of the producer for as long as 748h, probably due to maintenance of high activities of enzymes involved in the biosynthesis of isocitric acid. Under optimal repeated-batch cultivation conditions, the producer accumulated 109.6g/L Ds(+)-threo-isocitric acid with a production rate of 1.346g/Lh. The monopotassium salt of isocitric acid isolated from the culture liquid and purified to 99.9% was found to remove neurointoxication, to restore memory, and to improve the learning of laboratory rats intoxicated with lead and molybdenum salts. Taking into account the fact that the neurotoxic effect of heavy metals is mainly determined by oxidative stress, the aforementioned favorable action of isocitric acid on the intoxicated rats can be explained by its antioxidant activity among other pharmacological effects.

СТРЕСС-ИНДУЦИРОВАННЫЕ ГОРМОНАЛЬНЫЕ ПОКАЗАТЕЛИ РЕПРОДУКТИВНОЙ ФУНКЦИИ У ЗДОРОВЫХ ДЕВУШЕК С РАЗЛИЧНЫМ ИНДЕКСОМ МАССЫ ТЕЛА

Aim. The article deals with the study of the dynamics of gonadotropins, sex steroids, leptin and ghrelin in healthy girls with a different body mass index for the assessment of reproductive function under stress conditions. Materials and methods. Based on anthropometric data, we formed three groups of girls with a different body mass index (BMI): the first group consists of girls with BMI less than 18.5 kg/m2 which corresponds with body mass deficiency (BMD); the second group – with BMI from 18.5 to 24.9 kg/m2 which corresponds with standard body mass (SBM); the third group – with BMI more than 30 kg/m2 which corresponds with Class I obesity (OCI). We determined hormone concentration in blood sample using the enzyme-linked immunosorbent assay in the conditions of daily study routine (background) and exams (emotional stress model). Results. We assessed stress-induced shifts in the cyclic activity of the hypothalamicpituitary-ovarian link of the endocrine system, as well as the contribution of energy homeostasis to adaptation of the reproductive system. Stress-induced reactions in the dynamics of hypothalamic response are especially significant for girls with body mass deficiency and Class I obesity. In girls with body mass deficiency, this level of emotional stress stimulates the reproductive system, in particular, by the positive dynamics of luteinizing hormone release. In girls with standard body mass, such responses are less pronounced. Class I obesity decreases the stress-protective activity of prolactin as its content changes significantly under these conditions. Conclusion. The stress-induced dynamics of leptin depends on the body mass index: in girls with body mass deficiency, the dynamics was positive (p < 0.05); in girls with standard body mass, such dynamics decreased; in girls with Class I obesity, the response was minimal because of the development of leptin resistance. In all the groups examined, we registered the positive dynamics of ghrelin determined by its participation in the storage of plastic and energy resources during energy homeostasis under stress conditions.

Rhodiola rosea L.: an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention.

Rhodiola rosea extracts have been used as a dietary supplement in healthy populations, including athletes, to non-specifically enhance the natural resistance of the body to both physical and behavior stresses for fighting fatigue and depression. We summarize the information with respect to the new pharmacological activities of Rhodiola rosea extracts and its underlying molecular mechanisms in this review article. In addition to its multiplex stress-protective activity, Rhodiola rosea extracts have recently demonstrated its anti-aging, anti-inflammation, immunostimulating, DNA repair and anti-cancer effects in different model systems. Molecular mechanisms of Rhodiola rosea extracts's action have been studied mainly along with one of its bioactive compounds, salidroside. Both Rhodiola rosea extracts and salidroside have contrast molecular mechanisms on cancer and normal physiological functions. For cancer, Rhodiola rosea extracts and salidroside inhibit the mTOR pathway and reduce angiogenesis through down-regulation of the expression of HIF-1α/HIF-2α. For normal physiological functions, Rhodiola rosea extracts and salidroside activate the mTOR pathway, stimulate paracrine function and promote neovascularization by inhibiting PHD3 and stabilizing HIF-1α proteins in skeletal muscles. In contrast to many natural compounds, salidroside is water-soluble and highly bioavailable via oral administration and concentrated in urine by kidney excretion. Rhodiola rosea extracts and salidroside can impose cellular and systemic benefits similar to the effect of positive lifestyle interventions to normal physiological functions and for anti-cancer. The unique pharmacological properties of Rhodiola rosea extracts or salidroside deserve further investigation for cancer chemoprevention, in particular for human urinary bladder cancer.

Understanding adaptogenic activity: specificity of the pharmacological action of adaptogens and other phytochemicals.

Adaptogens are stress-response modifiers that increase an organism's nonspecific resistance to stress by increasing its ability to adapt and survive. The classical reductionist model is insufficiently complex to explain the mechanistic aspects of the physiological notion of "adaptability" and the adaptogenic activity of adaptogens. Here, I demonstrate that (1) the mechanisms of action of adaptogens are impossible to rationally describe using the reductionist concept of pharmacology, whereas the network pharmacology approach is the most suitable method; and (2) the principles of systems biology and pharmacological networks appear to be more suitable for conceptualizing adaptogen function and are applicable to any phytochemical. Molecular targets, signaling pathways, and networks common to adaptogens have been identified. They are associated with stress hormones and key mediators of the regulation of homeostasis. In this context, the mechanisms of action of adaptogens are specifically related to stress-protective activity and increased adaptability of the organism. Consequently, adaptogens exhibit polyvalent beneficial effects against chronic inflammation, atherosclerosis, neurodegenerative cognitive impairment, metabolic disorders, cancer, and other aging-related diseases. Current and potential uses of adaptogens are mainly related to stress-induced fatigue and cognitive function, mental illness, and behavioral disorders. Their prophylactic use by healthy subjects to ameliorate stress and prevent age-related diseases appears to be justified. It is very unlikely that the pharmacological activity of any phytochemical is specific and associated only with one type of receptor, particularly adaptogenic compounds, which affect key mediators of the adaptive stress response at intracellular and extracellular levels of communication.

국내산 법제 하수오의 라디칼 소거능 및 산화적 스트레스 개선 효과

In this study, we confirmed biological compounds from methanol (MeOH) extract of processed Polygoni Multiflori Radix (PPMR), and the radical scavenging effect and oxidative stress protective activity of MeOH extract of PPMR were investigated under in vitro conditions using LLC-PK1 renal epithelial cells. In HPLC analysis, MeOH extract of PPMR contained four species of biological compounds named 2,3,5,4-tetrahydroxystilbene 2-O-β-D-glucoside, emodin, chrysophanol, and rhein. 2,3,5,4-Tetrahydroxystilbene 2-O-β-D-glucoside was detected as the main compound in PPMR as 115.02 mg/kg. MeOH extract of PPMR showed 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS), and hydroxyl radical scavenging activities in a concentration-dependent manner. In particular, upon 50 μg/mL of PPMR extract treatment, DPPH, ABTS, and hydroxyl radical scavenging activities were approximately 48.4%, 57.9%, and 81.2%, respectively. LLC-PK1 cell viability declined in response to oxidative stress induced by pyrogallol, sodium nitroprusside (SNP), and morpholinosydnonimine (SIN-1) generators of NO, O₂-, and ONOO-, respectively. However, MeOH extract of PPMR significantly and dose-dependently inhibited oxidative-stressed LLC-PK1 cell cytotoxicity. In fact, upon 50 μg/mL of PPMR extract treatment, LLC-PK1 cell viabilities were approximately 82.1%, 89.1%, and 77.6% compared to stress levels induced by pyrogallol, SNP, and SIN-1, respectively.

Antioxidant, antimicrobial, toxicity and analgesic properties of ethanol extract of Solena amplexicaulis root.

BackgroundThis study was subjected to investigate different pharmacological properties of ethanol extract of Solena amplexicaulis root.ResultsThe extract contains flavonoid, alkaloid, saponin and steroid compounds. The extract exhibited excellent antioxidant activity in DPPH radical scavenging activity. The extract also showed potent activity in brine shrimp lethality bioassay. The LC50 value was found to 44.677 μg/ml. The extract showed better anti-bacterial activity against gram-negative bacteria. In antifungal assay, the maximum 79.31% of anti-mycotic activity was observed against Aspergillus ochraceus while minimum 44.2% against Rhizopus oryzae. MIC value ranged between 1500–3000 μg/ml. The extract was found moderately toxic with a 24-hr LD50 value of 81.47 mg/kg in Swiss albino mice. The degree of inhibition by the ethanolic extract of the root was found less than that of standard analgesic drug diclofenac sodium. The extract also showed moderate anti-inflammatory and antinociceptive activity and anti-diabetic property. Reducing power of the extract was comparable with standard ascorbic acid. Moderate in vitro thrombolytic activity, lipid peroxidation inhibition property, metal chelating ability and stress-protective activity was also observed.ConclusionEthanol extract of Solena amplexicaulis root can be valuable for treatment of different diseases.

A current status of adaptogens: natural remedy to stress

Stress is a normal part of everyday life but it is important to be able to use tools for its management otherwise chronic stress, if left untreated, can lead to a variety of stress related illnesses including hypertension, heart disease, anxiety, depression, memory impairment and chronic fatigue syndrome. The aim of this literature review is to summarize and critically analyze research conducted on the adaptogenic herbs. The aim of this review article is to assess the level of scientific evidence presented by the adaptogens from natural origin by different screening methods and to provide a rationale at the molecular level. Strong scientific evidence is available in relation with the molecular mechanisms associated with their stress-protective activity against acute and chronic paradigms. The beneficial stress-protective effect of adaptogens is in relation with regulation of homeostasis via several mechanisms of action associated with the hypothalamic-pituitary-adrenal axis and the control of key stress mediators and biochemical markers such as nitric oxide (NO), cortisol, cholesterol, triglycerides, glucose etc. Good scientific evidence has been documented with active secondary metabolites present in adaptogens.