Ecdysterone (other names: Maral root extract, Rhaponticum carthamoides) [333 mg maral root extract of which 300 mg is ecdysterone per capsule]: It works like a charm. Its effect is comparable to MACA when I first began to use it, so it is definitely better than Tribulus or Berberine. It has a potent antidepressive effect that appears around 4 hours after consumption. In general it has a good effect on symptom reduction, however it can't completely overcome POIS at least in the used dosage. It reduces bloodshot eyes, but it is not the best in this regard.
The first time I used it I took one Ecdy capsule 3 hours before an O and POIS onset was rather usual (e.g. bloodshot eyes). However unexpectedly one hour later when I would have expected my POIS symptoms only to become worse, suddenly my vision cleared and I could think more clearly. The bloodshot eyes symptom also reduced, however 2 hours later the depression and eye problems appeared again. Before going to sleep I took another Ecdy and in the morning POIS was relatively weak. I also took one in the morning and felt relatively well during work. I could also perceive the anti-depressive effect at 4 hours. So although Ecdy couldn't completely stop POIS on its own, still it has a considerably beneficial effect.
The most relevant facts seem to be:
The one I bought is also marketed as a testosterone booster, however recent studies claim that in reality its anabolic effect is exerted through the estrogen receptor beta. Ecdy proved to increase protein synthesis in skeletal muscle. Ecdy can behave both as an agonist or an antagonist depending on concentration and/or the presence of E2. Ecdy can ameliorate respiratory burst in relation with neutrophil activity.
Further information on Ecdysterone:
Recent studies suggest that the anabolic effect of ecdysterone is mediated by estrogen receptor (ER) binding. The ecdysterone administration led to increased serum IGF1 concentrations in comparison to the control group while thyroxin (T4) concentrations decreased. Significantly higher increases in muscle mass were observed in those volunteers that were dosed with the ecdysterone supplements.https://www.wada-ama.org/sites/default/files/resources/files/15c18mp_dr._parr_final_report.pdfIn the 1980s the most active phytoecdysteroid, ecdysterone (beta-ecdysone, a "Russian secret"), was suspected to be used by Russian Olympic athletes. The levels of ecdysteroids in western diet are generally low (usually in the range of less than 1 mg x day-1), while the doses used by bodybuilders are stated in a range of up to 1000 mg x day-1.
Ecdysterone has been demonstrated to increase protein synthesis in skeletal muscle. Gorelick et al. proposed direct or indirect stimulation of the PI3K/Akt signaling pathway as mechanism for this increased protein synthesis.
Conversely to anabolic-androgenic steroids (AAS) that increase muscle mass mainly through their binding to the androgen receptor (AR), no nuclear receptor that is homologous to the ecdysone nuclear receptor found in insects has yet been described in mammals so far. Only recently, binding of ecdysterone to the human ERB (ED50 = 13 nM) could be shown in cell culture experiments and induction of hypertrophy in C2C12 cells was shown to be mediated by the ERB activation.
The generated docking poses support the hypothesis that ecdysterone shows no significant binding at the AR, but to ER with preference to the ERB subtype.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447764/In male rats, Ecdy treatment increased muscle fiber size, serum IGF-1 increased, and corticosteron and 17B-estradiol (E2) decreased. In differentiated C2C12 myoblastoma cells, treatment with Ecdy, dihydrotestosterone, IGF-1 but also E2 results in hypertrophy. Hypertrophy induced by E2 and Ecdy could be antagonized with an antiestrogen but not by an antiandrogen. In HEK293 cells transfected with ER alpha (ERA) or ERB, Ecdy treatment transactivated a reporter gene. To elucidate the role of ERB in Ecdy-mediated muscle hypertrophy, C2C12 myotubes were treated with ERA (ALPHA) and ERB (BETA) selective ligands. Ecdy and BETA treatment but not ALPHA induced hypertrophy. The effect of Ecdy, E2, and BETA could be antagonized by an ERB-selective antagonist (ANTIBETA). In summary, our results indicate that ERB is involved in the mediation of the anabolic activity of the Ecdy.https://onlinelibrary.wiley.com/doi/abs/10.1002/mnfr.201300806For uses in gene therapy, it may be necessary to investigate more thoroughly the natural sources of ecdysteroids in humans (which appear to include dietary phytoecdysteroids, gut flora, helminth infections, and other diseases).
There is some in vitro evidence to show that 20-hydroxyecdysone has effects on some kinds of blood cells such as lymphocytes and neutrophils, and may act as an immunomodulator.https://en.wikipedia.org/wiki/20-HydroxyecdysoneThe principal moulting and metamorphosis hormone in insects, 20-hydroxyecdysone, is known to have tonic, stressprotective, anabolic, cardiotropic, membrane stabilizing, ATP-ase activating, immunomodulating, and red blood regenerating activities in vertebrates as well as antiradical and antioxidant properties. It has also been shown that 20-hydroxyecdysone-containing phytoextracts are effective against burns and chemical injuries of the skin, streptodermia, and itching dermatoses both experimentally and clinically.
We studied 20-hydroxyecdysone’s immunomodulating activity, which depends at least in part on its ability to change, or enhance, some functions of lymphocytes and neutrophils. Such "critical" functions are receptor expression/presentation by lymphocytes and the respiratory burst of neutrophils. For example, the alternative pathway of T-cell activation is closely connected with CD2, the sheep erythrocytes binding receptor. The CD2 molecule is known to be suppressed in secondary immunodeficient persons or by pharmacologically increased intracellular cAMP level, for example, via theophylline-induced phosphodiesterase blockade. Some immuno-active compounds are known to restore this suppression. Furthermore, human neutrophils exposed to soluble or particulate stimuli undergo a large increase in cyanide insensitive oxygen consumption together with reactive oxygen metabolite production termed the respiratory burst, which is responsible for microbicidal activity.
Several compounds, calmodulino- and beta-adrenoblockers, antioxidants, and anti-inflammatory agents, are known to suppress or enhance the respiratory burst of neutrophils.https://sci-hub.se/https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1520-6327(1999)41:3%3C156::AID-ARCH7%3E3.0.CO;2-QEcdysterone (Ecdy) is the principal constituent of several plants used in the Chinese, Ayurvedic, and Russian traditional medicines to treat various ailments. Ecdy has been shown to exert anabolic properties in vitro and in vivo. Although the mechanisms underlying these effects are not yet elucidated, it is advertised as a food supplement to increase muscle mass and physical performance and is used by bodybuilders. We showed that an ethanol extract of E. excelsa exhibits estrogenic/anti-estrogenic and cytotoxic effects.
We confirmed the skeletal muscle growth-promoting effects of IGF1, DHT, E2, Ecdy, and the phytoestrogen genistein. Co-treatment of myotubes with ZK and Ecdy led to an inhibition of Ecdy-induced hypertrophy. In addition, a co-treatment of myotubes with E2 or Ecdy and the selective ERB antagonist prevented both substances to induce myotube hypertrophy, what unequivocally shows an ERB-mediated effect.
In general, the results of this work show that the extract of Erythrina excelsa has biological activities that are in close agreement with its reported traditional use to manage menopausal complaints and to treat female gynecological tumors.
Ecdysteroids are steroids mainly found in Arthropods but that are also present in large amounts in certain plants including spinach.
ERA is predominantly expressed in the uterus, prostate (stroma), ovary (theca cells), testes (Leydig cells), epididymis, bone, breast, liver, kidney, white adipose tissue, and various regions of the brain. ERB is predominantly expressed in the intestine, prostate (epithelium), testis, ovary (granulosa cells), bone marrow, salivary gland, vascular endothelium, lung, bladder and certain regions of the brain.
Recent studies from our lab show that ERB is the major ER isoform mediating estrogens effects on skeletal muscle growth and repair.
Phytoestrogens (PEs) are naturally-occurring plant compounds that are structurally and/or functionally similar to mammalian estrogens and their active metabolites. They are commonly divided into 4 groups: isoflavones (e.g. genistein, daidzein, glycitein, and formonetin), lignans (e.g. secoisolariciresinol, matairesinol, pinoresinol, and lariciresinol), coumestans (e.g. coumestrol), and stilbens (e.g. resveratrol). Lignans are found in many fiber-rich foods such as berries, seeds (particularly flaxseeds), grains, nuts and fruits. Isoflavones are components of berries, wine, grains and nuts but are most abundant in soybeans and other legumes. Coumestans are found in many plants but especially in clover and alfalfa sprouts, and stilbens in grape-containing products, particularly red wine.
Genistein and daidzein, the predominant isoflavones, occur in soy mainly as biologically inactive glycoside conjugates (genistin and daidzin). After oral ingestion, the glycoside conjugates are either hydrolyzed into their corresponding aglycones bioactive form (genistein and daidzein) by intestinal glucosidases or absorbed as conjugates. Genistein and daidzein can also be obtained from the intestinal hydrolysis of their respective precursor biochanin A and formonetin that are found in high amounts in red clover.
Most PEs bind to ERA and ERB and activate ER-dependent gene transcription through both ERs. However, unlike E2 that binds with equal affinity to both ERs, they bind predominantly to ERB and may exert both agonistic and antagonistic effects depending on the cellular context. Therefore, most PEs are termed as selective estrogen receptor modulators (SERMs). They have been reported to produce their effects either via direct binding to ER or by acting indirectly to modulate the concentration of endogenous estrogens. PEs modulate the brainpituitary-gonad axis which is the principal endocrine system to regulate mammalian reproduction. They induce changes in the concentration of circulating steroid hormones by inhibiting the secretion and activity of gonadotropin releasing hormone (GnRH), by increasing sex hormone binding globulin (SHBG) synthesis, and through direct inhibition of some steroidogenic enzymes.
Additionally, PEs exert non-genomic rapid effects for example through the binding of early intermediate genes such as jun and fos.
The effects of PEs on female reproductive health depend on applied dose, route of exposure, and hormonal or developmental status of the exposed individual: different tissues have species-specific windows of sensitivity to morphological and functional disruption. Since Bennetts et al reported that sheep that grazed on red clover were infertile due to the estrogenic content in clover.
Although weaker than natural estrogens, PEs mimic estrogenic effects on the reproductive organs. This raises some concerns because estrogens are implicated in the pathology of hormone-dependent cancers. However, epidemiologic studies show that Asiatic women have a significant lower incidence of hormone-dependent cancers compared to their age-matched Caucasian women and that this lower risk is positively correlated to PE consumption. Nevertheless, recent studies report beneficial effects of PE consumption on gynecological cancer risk.
Bone cell culture and the rat model of postmenopausal osteoporosis have been extensively used to show that PE can prevent postmenopausal bone loss.
Rhaponticum carthamoides is used in the Siberian traditional medicine in cases of overstrain and common weakness after illness.
Estrogens have been shown to prevent apoptosis of normal and breast tumor cells through the activation of Bcl-2 gene expression.
E2, genistein, and Ecdysone induce hypertrophy of C2C12 murine skeletal muscle cells.
This selectivity of action may be explained by different ratio of coactivators to corepressors proteins or by the fact that the extract may induce a different conformation of the ER in both organs.
Bcl-2 family members play an important role in the mediation and regulation of apoptotic signaling pathways acting to either inhibit (e.g. Bcl-2) or promote cell death (e.g. Bax). The Bax/Bcl-2 ratio has been recognized as a key factor and determines whether a cell will undergo apoptosis. Cancer cells are resistant to apoptosis and it is proposed that drugs or treatment strategies that can restore the apoptotic signaling pathways towards normality have the potential to eliminate cancer cells.
Conversely to Ecdy that increase the protein synthesis in the muscle, E2 and genistein have been shown to rather decrease protein breakdown in porcine skeletal muscle cells.https://fis.dshs-koeln.de/portal/files/3477509/Dissertation_Sadrine_Tchoukouegno_Ngueu.pdf
