Immunomodulating and antistress activity of ecdysterone and turkesterone under immobilization-induced stress conditions in mice

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The phytoecdysteroids ecdysterone and turkesterone isolated from Rhaponticum integrifolium and Ajuga turkestanica herbs, respectively, increase the adaptation capacity of mice under immobilization-induced stress conditions. These compounds prevent involution of the thymicolymphatic system, decrease trophic disorders in gastric mucosa, prevent an increase in the weight of adrenal glands and a decrease in them of the content of ascorbic acid and cholesterol (to a much greater degree than does T-activin), and stimulate immunogenesis in animals with experimental immune deficiency developed on the background of immobilization-induced stress. Key wordsecdysterone-turkesterone-T-activin-immobilization-induced stress-immobilization.

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... (Lamiaceae) is rich in biologically active substances the leaves and stems contain up to 3.76% flavonoids, iridoids, phytoectisteroids and up to 0.1% of the plant leaves contain a compound called turkesterone (Baltaev 2000;Ramazanov 2005). The medicinal plant A. turkestanica contains biologically active substances with high pharmacological effects, such as ecdysterone, turkesterone, cyasterone, ajugasterone, ajugalactone, cyasterone-22 acetate and phytoecdysteroid used in the treatment of cancer, malaria, gastrointestinal, in cardiovascular problems (Mamatkhanov et al., 1998;Syrov, 2001;Abdukadirov et al., 2005;Shakhmurova et al., 2010). ...
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This research work aims to isolate endophytic bacteria from the Ajuga turkestanica plant that have plant growth promoting properties. The microscopic, enzymatic and biochemical properties of the isolated endophytic bacteria are described. Twelve isolates of endophytic bacteria were isolated by standard microbiological methods. Isolated endophytic bacteria were identified by (MALDI-TOF MS). Endophytic bacteria isolated from the plant were detected in MALDI-TOF MS. Bacterial isolates were dominated by endophytic bacteria belonging to the genus Bacillus, Pseudomonas, Siccibacter. When the growth-enhancing properties of cultivated plants used in sustainable agriculture were studied, the isolated bacterial strains showed positive results in siderophor, ammonia, indole acetic acid production, and nitrogen fixation properties. Numerous endophytic bacteria have been found to have the enzymatic activity of oxidase, catalase, amylase, lecithinase and lipase. The results showed that endophytic bacteria isolated from the plant A. turkestanica are have plant stimulating properties which can be shown as a candidate for the production of bioinoculants individually or as part of a consortium.
... Apart from protein synthesis (227), ecdysteroids reportedly affect lipid (218,(228)(229)(230) and carbohydrate metabolisms (231,232) in mammals. They may also have hepatoprotective (233), nephroprotective (234), immune-protective (235,236), antioxidant (237), anti-obesity and anti-diabetic (215,230) properties. Ecdysteroid showed favorable effect on the subcutaneous thickness of the fat layer (238) as well as reducing abdominal fat depots of ovariectomized rats (239). ...
Conference Paper
Cyclooxygenase (COX), which can be expressed as COX-1 or COX-2 in endothelial cells has the unique ability to regulate microvascular tone through balanced production of dilator/constrictor prostanoids. This study investigated the roles of these isoforms in microvascular endothelial dilator function and how these are affected by supplement-derived ecdysteroids. Acetylcholine or 20-hydroxyecdysone relaxation were recorded in Skeletal muscle (SKM) and mesenteric (ME) arteries from healthy sheep and omental (OM) and subcutaneous (SC) fat arteries from obese humans by wire myography in the absence and presence of inhibitors of nitric oxide synthase, cyclooxygenase (COX) isoforms 1 and 2 and endothelium-derived hyperpolarizing factors. Gene and protein expression analysis were also carried out to fully characterize the roles of COX in these arteries. Non-selective COX inhibition attenuated acetylcholine relaxation in SKM arteries but enhanced it in ME arteries. Selective inhibition of COX-1 in both SKM and ME arteries also attenuated acetylcholine relaxation. In contrast, selective inhibition of COX-2 enhanced acetylcholine relaxation in ME arteries and had no effect in SKM arteries. In OM arteries from obese patients, selective inhibition of COX-1 but not COX-2 significantly improved acetylcholine relaxation. The OM arteries also displayed enhanced responsiveness to thromboxane A2 mimetic (U46619) compared with SC arteries. 20-hydroxyecdysone caused relaxation which was attenuated by NOS inhibition compared with COX inhibition in SKM and ME arteries. COX roles in microvascular endothelial dilator function are isoform-specific and dependent on type and health of the vasculature. In healthy arteries, COX-1 promotes but COX-2 opposes vasodilation. In human obesity, COX-1 opposes while COX plays no part in OM endothelial dilator function. Although 20-hydroxyecdysone alters COX expression, its vasodilatory effect is more eNOS-dependent than COX-dependent.
... Rodgers & di Zerega, 2013;Rodgers et al., 2013Syrov et al., 1997Nakada et al., 2014 Liver protective Lubel et al., 2009 ;Pereira et al., 2007;Li, 2013Suski et al., 2012Shakhmurova et al., 2010aXia et al., 2013bTian et al., 2012 Lung protective Imai et al., 2008;Klein et al., 2013;Uhal et al., 2013;Shenoy et al., 2015 ;Cao et al., 2019Klein et al., 2013Rodrigues-Machado et al., 2013;Cao et al., 2019Wu et al., 1998Li et al., 2013;Xia et al., 2016;Song et al., 2019Hamidi et al., 2011Breithaupt-Faloppa et al., 2013 Kidney protective Zhou et al., 2012;Xu et al., 2013;Barroso et al., 2012;Suski et al., 2013 ;Silveira et al., 2010Silveira et al., , 2013Pinheiro et al., 2004. Syrov et al., 1992Zou et al., 2010;Hung et al., 2012Iran-Nejad et al., 2015Wu et al., 2016 Gastric protective Zhu et al., 2014;Pawlik et al., 2016Pawlik et al., 2016Shakhmurova et al., 2010bDu et al., 2010Liu et al., 2010 Bone protective Krishnan et al., 2013 ...
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20-Hydroxyecdysone (20E) is a steroid hormone that plays a key role in insect development through nuclear ecdysone receptors (EcRs) and at least one membrane GPCR receptor (DopEcR) and displays numerous pharmacological effects in mammals. However, its mechanism of action is still debated, involving either an unidentified GPCR or the estrogen ERβ receptor. The goal of our study was to better understand 20E mechanism of action. A mouse myoblast cell line (C2C12) and the gene expression of myostatin (a negative regulator of muscle growth) was used as a reporter system of anabolic activity. Experiments using protein-bound 20E established the involvement of a membrane receptor. 20E-like effects were also observed with Angiotensin-(1-7), the endogenous ligand of Mas. Additionally, the effect on myostatin gene expression was abolished by Mas receptor knock-down using small interfering RNA (siRNA) or pharmacological inhibitors. 17β-Estradiol (E2) also inhibited myostatin gene expression, but protein-bound E2 was inactive, and E2 activity was not abolished by angiotensin-(1-7) antagonists. A mechanism involving cooperation between Mas receptor and a membrane-bound palmitoylated estrogen receptor is proposed. The possibility to activate the Mas receptor with a safe steroid molecule is consistent with the pleiotropic pharmacological effects of ecdysteroids in mammals and indeed this mechanism may explain the close similarity between angiotensin-(1-7) and 20E effects. Our findings open a lot of possible therapeutic developments by stimulating the protective arm of the renin-angiotensin-aldosterone system (RAAS) with 20E.
... Ecdysteroid-enriched extracts of A. turkestanica (or pure turkesterone) display anabolic effects on muscles Syrov et al., 2001;Zubeldia et al., 2012), even in a sarcopenia context (Lawrence, 2012). In addition, turkesterone and 20-hydroxyecdysone have antistress and immunostimulating effects (Shakhmurova et al., 2010). Extracts of A. turkestanica are already marketed for all these symptoms (e.g. ...
Ajuga turkestanica is a plant used in traditional medicine for its high ecdysteroid content, including the presence of the particularly active turkesterone, which possess efficient anabolic activity. To isolate and identify minor ecdysteroids present in a semi-purified plant fraction containing ca. 70% turkesterone. Multi-step preparative HPLC (combining RP- and NP-HPLC systems) was used to purify the different components present in the turkesterone fraction. Isolated compounds were identified by high-resolution mass spectrometry and 2D-NMR. Fourteen ecdysteroids (including turkesterone and 20-hydroxyecdysone) were isolated. Seven of these, all bearing an 11α-hydroxy group, were previously unreported. Ajuga turkestanica ecdysteroids are characterised by the abundance of 11α-hydroxylated compounds and by the simultaneous presence of 24C, 27C, 28C and 29C ecdysteroids. It is expected that even more ecdysteroids are to be found in this plant since the starting material for this study lacked the less polar ecdysteroids. The simultaneous presence of 20-hydroxyecdysone and turkesterone (its 11α-hydroxy analogue) as the two major ecdysteroids suggests that every ecdysteroid is probably present in both 11α-hydroxy and 11-deoxy forms. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
... The adaptogenic activity of ecdysterone was proven by tests on rats either after immobilization or swimming; a decrease in the involution of the thymicrolymphatic apparatus was observed, but hypertrophy of adrenal glands, decrease of ascorbic acid content, and stomach ulceration did not occur [49,50]. By comparison of the ecdysterone effect on thymocyte energy metabolism with that of nerobol, more distinctive positive energy changes were observed in mitochondria of cells in suspension culture [51]. ...
Beside ecdysone (1), ecdysterone (2) is one of the most common 5beta-cholest-7-en-6-one (ecdysteroid) derivatives, which, besides having a hormonal effect on invertebrates, possesses a number of favorable non-hormonal biological effects on mammals. The most interesting of these is that on degenerative diseases, one of which, up to now not clarified in detail, is the so-called adaptogenic effect (protection of the organism against adverse stress factors) associated with anabolic, gastroprotective, and antioxidant effects. A second group of favorable effects is the possibility of suppression of neurodegenerative processes and protection of the cardiovascular system (metabolic syndrome symptom suppression, antidiabetic activity, and protection of heart and blood vessels). Because of these properties, ecdysterone has the potential to be developed as a medicinal agent.
Natural-derived steroids and their analogues are present in various plants and insects. To minimize the chance of missing a positive doping test and avoiding potentially serious health problems, adequate screening methods are necessary for the detection of a wide range of natural-derived steroids and their analogues in dietary supplements. In this study, an accurate and simple liquid-chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine and quantify the natural-derived steroids and their analogues according to the International Conference on Harmonization of technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The validation results indicating excellent extraction efficiency and low matrix effects show that the LC-MS/MS method is reliable for the detection of natural-derived steroids and their analogues. In addition, we established the ion fragmentation of turkesterone and ion fragmentation of four natural-derived steroids and their analogues. The validated method was applied to 60 dietary supplements purchased online and in person from international vendors in 2020. Ecdysterone and 5α-hydroxylaxogenin were detected respectively in 3 and 14 of 60 dietary supplements. Especially, a high amount of 5α-hydroxylaxogenin, an FDA-unapproved ingredient, was detected in two of dietary supplements (44.4 and 32.3 mg/g). This component should be controlled since it may cause unexpected side effects if administered excessively. Thus, this method will be helpful for the continuous control and supervision of unlicensed dietary supplements containing natural-derived steroids and their analogues.
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There is growing interest in the pharmaceutical and medical applications of 20-hydroxyecdysone (20E), a polyhydroxylated steroid which naturally occurs in low but very significant amounts in invertebrates, where it has hormonal roles, and in certain plant species, where it is believed to contribute to the deterrence of invertebrate predators. Studies in vivo and in vitro have revealed beneficial effects in mammals: anabolic, hypolipidemic, anti-diabetic, anti-inflammatory, hepatoprotective, etc. The possible mode of action in mammals has been determined recently, with the main mechanism involving the activation of the Mas1 receptor, a key component of the renin–angiotensin system, which would explain many of the pleiotropic effects observed in the different animal models. Processes have been developed to produce large amounts of pharmaceutical grade 20E, and regulatory preclinical studies have assessed its lack of toxicity. The effects of 20E have been evaluated in early stage clinical trials in healthy volunteers and in patients for the treatment of neuromuscular, cardio-metabolic or respiratory diseases. The prospects and limitations of developing 20E as a drug are discussed, including the requirement for a better evaluation of its safety and pharmacological profile and for developing a production process compliant with pharmaceutical standards.
The tincture from biomass of ginseng tissue culture was shown to exert the immunomodulatory effect on humoral immunity and to increase the thymus and spleen weight. It is of interest to note that the biomass preparation did not change the immunity of intact animals but exerted a strong immunomodulatory action on mice previously treated with cyclophosphane. Similar results have been obtained also for another adaptogen--Eleutherococcus.
Joint injection of the activators of carbohydrate (thiamine, riboxin) and lipid (carnitin, biotin) metabolism in pairs reduces the expression of the decrease of the functional-metabolic activity of blood leukocytes and the inhibition of the immunological reactivity of organism, caused by air and immersion cooling. The most expressed immunomodulative effect is caused by the joint injection of thiamine and biotin.
The response to the second antigen of a sequence of two related antigens appears to consist of two qualitatively different antibody populations. Antibodies specific for the second antigen are of primary-response quality while the antibodies which cross-react with the first antigen are of secondary-response quality.
Khavinson, Resistance, Stress, Regulation
  • G M Yakovlev
  • V S Novikov
  • V Kh
Erythrocytes and Metabolic Immunomodulation
  • L G Prokopenko
  • A I Konoplya
  • I L Laskova