DHEA lowers inflammatory cytokine IL6 late-onset B cell neoplasia, RA, etc

[rydra_wong]

Look what I found of interest! I know next to nothing baout this supplement (I take it on a testimonail of how it worked on a cat - I know, I know, usually I research things first, but this seemed innocuous and I did not). I take this only when sick, but looks like I could make more use of it. One reference (by the manufacturer so suspect) claims it helps chronic fatigue. I have to track that down, may not be true but worth a look. Anyway, this is what I found so far w/o really looking (just trying to find out what component is the active component):

http://www.ncbi.nlm.nih.gov/pubmed/17408058
J Int Med Res. 2007 Jan-Feb;35(1):84-90.
Effects of Astragalus polysaccharides and astragalosides on the phagocytosis of Mycobacterium tuberculosis by macrophages.Xu HD, You CG, Zhang RL, Gao P, Wang ZR.

The herb Astragalus membranaceus is used in traditional Chinese medicine to boost immunity. This study investigated the effects of Astragalus polysaccharides (APS) and astragalosides (AS) on the phagocytosis of Mycobacterium tuberculosis by macrophages. Peritoneal macrophages were obtained by peritoneal lavage from mice stimulated by starch gravy culture medium and cultured with M. tuberculosis and varying concentrations of APS and AS. Phagocytotic activity was measured using a real-time polymerase chain reaction assay to detect M. tuberculosis DNA. Levels of interleukin-1beta, interleukin-6 and tumour necrosis factor-a secreted by activated macrophages in the culture supernatant were determined using an enzyme-linked immunosorbent assay. Macrophage phagocytotic activity and secreted cytokine levels were significantly increased after treatment with APS and AS. This study provides evidence that APS and AS have strong promoting effects on the phagocytosis of M. tuberculosis by macrophages and the secretion of interleukin-lbeta, interleukin-6 and tumour necrosis factor-alpha by activated macrophages.

http://www.ncbi.nlm.nih.gov/pubmed/18067226
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2007 Nov;36(6):543-8.
[Astragalus polysaccharides and astragalosides regulate cytokine secretion in LX-2 cell line].[Article in Chinese]
Li SP, Xu XY, Sun Z, Chen Z.

OBJECTIVE:
To investigate the anti-fibrosis mechanism of radix astragali through the observation on regulating cytokine secretion by astragalosides and astragalus polysaccharides in hepatic stellate cell line LX-2.
METHODS:
Astragalus polysaccharides and astragalosides at concentration of 25 microg/ml and 300 microg/ml were added to LX-2 cell culture.After 24 h culture total RNA contents were extracted and TGF-beta1, HGF, MP2 and MMP9 mRNA were measured by real time fluorescence quantification PCR technique. The cell growth curves were detected by Real Time Cell Electronics Sensing.
RESULTS:
300 microg/ml of astragalus polysaccharides suppressed LX-2 cell proliferation (P<0.05, in 94.7 h), while astragalosides induced an significant cell proliferation (P<0.05) both at lower and higher concentration. 25 microg/ml astragalus polysaccharides and astragalosides induced TGF-beta1 expression. For other cytokines, astragalus polysaccharides induced a 104.9 fold higher expression of MMP2, while astragalosides induced a 550.65 fold higher expression of IL-10. Astragalus polysaccharides at 300 microg/ml concentration exhibited an inhibition effect on TGF-beta1, HGF, MMP9 and IL-10 mRNA expression, while up-regulated MMP2 mRNA expression. Astragalosides at 300 mug/ml concentration inhibited TGF-beta1 mRNA expression, while up-regulated MMP2, MMP9 and IL-10 mRNA expression.
CONCLUSION:
The anti-fibrosis function of astragalus polysaccharides might be associated with up-regulation of MMP2 expression, while that of astragalosides with up-regulation of MMP2, MMP9 and IL-10 expression.

 

[rydra_wong]

(Also note it has hormonal action - I will have to look at studies on that)

AstragalusMechanism of Action
Pharmacology:

Constituents: Active constituents of astragalus root have been identified and characterized. These components include: polysaccharide cycloartane glycoside fractions (astragalosides I-IV and trigonosides I-III), four major isoflavonoids (formononetin, ononin, calycosin, and its glycoside), saponins, several minor isoflavonoids, and other biogenic amines.25,26,27,28,29,8,30,31 Astragalus also contains triterpenoids. Triterpenoids and saponins have a structural similarity to steroid hormone precursors.
Antidiabetic effects: According to animal and human study, saponins, isoflavones and polysaccharides in astragalus can lower blood glucose.24,5,17,32,33,6,7 Based on experimental study, astragaloside IV, a saponin isolated from Astragalus membranaceus, inhibited protein tyrosine phosphorylase and protein kinase C activation, as well as improving F-actin rearrangements, thereby altering insulin sensitivity.30,34 Several investigators have observed increased in vitro cellular uptake of glucose and increased protein synthesis in adipocytes.35,4 Isoflavones in Astragalus membranaceus, including formononectin and biochanin A, were potent activators of both peroxisome proliferator-activated receptors (PPAR) and receptors that are used to restore glycemic balance.33
Anti inflammatory effects: The anti-inflammatory activity in vivo may be mediated by inhibition of NF-kappaB activation and mRNA expression.36,37
Antimicrobial activity: Astragalus polysaccharides have been shown to induce endogenous interferon production in animals and humans and to potentiate the actions of interferon in viral infections.38,9,22,2 Mice pretreated with astragalus and exposed to Coxsachie B3, Japanese encephalitis virus, NDV, and Sendai viruses have significantly higher interferon levels and macrophage production compared to animals that are not pretreated with astragalus.39,21 Several investigators have reported that mice with viral myocarditis exhibited improvement in overall outcomes and cardiac function, as well as reduced myocardial lesions, viral load, and viral replication in response to astragalus.40,41,20,10,42 Astragalus polysaccharide fractions have also been reported to stimulate the production of IgA, IgM, IgG, and antigen-specific splenocytes in response to bacterial infections in poultry.14,15,16 In contrast, astragalus exhibited no in vitro cytotoxic or antiviral activity against HIV infection.43,39
Antineoplastic properties/amelioration of chemotherapy side effects: There is in vitro evidence that astragalus can potentiate the efficacy and reduce the adverse effects of chemotherapy via stimulation of the immune system.18,19,2 Wei et al. reported that astragalus extract significantly increased in vitro cytokine secretion and gene expression in blood mononuclear cells of lung cancer patients.44 Astragalus extracts have been shown to induce LAK cell activity in the lymphocytes of cancer and HIV patients and stimulate the blastogenic response of lymphocytes to mutagens in patients with various cancers.45,46,47,48,49,50 Lau et al. reported that an astragalus-containing herbal combination inhibited tumor growth in vivo while augmenting macrophage and lymphokine-activated killer cell activities.51 Treatment with astragalus-containing herbal remedies also inhibited tumor growth and prolonged survival in rats compared to rats treated with conventional chemotherapy. Other authors have reported the potentiation of interleukin-2 (IL-2)-generated cytotoxicity in animal models45,52 and reduction of mutagenesis53.
Antioxidant and cellular protective properties: Astragalus constituents, particularly the flavonoids, exert significant cellular antioxidant effects that appear to be protective against cardiovascular, hepatic, pulmonary, and renal pathological changes.54,55 In vitro, astragalus has been reported to protect against free radical-mediated renal tubular damage induced by high-energy shock waves56 and against radiation injury23. In the hearts of healthy animals and animal models of cardiovascular disease, astragalus polysaccharide and flavonoid fractions have been reported to scavenge mitochondrial free radicals, protect against lipid peroxidation, protect mitochondria from isoproterenol-induced injury, prevent diabetes-induced myocardial hypertrophy, and attenuate pathophysiological decrements in cardiac structure and function in congestive heart failure, diabetes, and experimental hypertension.57,58,59,11,60,61 Astragalus polysaccharide and flavonoid extracts have been shown to preserve kidney function in animal models of renal failure and liver functions in response to hepatotoxins.56,62,63,4,64,65,66 Similarly, astragalus appears to protect cells against hypoxic challenges. Astragaloside IV has been reported to protect human endothelial cells and intestinal epithelial cells against reperfusion injury in vitro following hemorrhagic shock.67 Cellular protection from anoxia has also been observed in cultured neurons68 and in mouse brains after transient focal ischemia69. Astragaloside IV has also inhibited platelet aggregation, decreased plasminogen activation, and facilitated intravascular lysis of fibrin clots in humans and in animal disease models.18,70 In a model of ototoxicity, Xuan et al. reported that astragalus protected cells from pathologic injury via enhanced DNA and RNA synthesis.65 In an animal study, Astragalus membranaceus had preventive and therapeutic potential in experimental colitis.1 The anti-inflammatory actions involved antioxidation along with the inhibition of adhesion molecule synthesis in the colonic tissues. In an in vitro study, astragalus and astragalus saponins potently protected endothelium-dependent relaxation against the acute injury from homocysteine through nitric oxide regulatory pathways, in which antioxidation played a key role.31
Cardiovascular effects: Experimental studies indicate that astragalosides affect cardiovascular function at the cellular, isolated tissue, and whole-body levels in both animals and humans. In isolated working rat hearts, Wang et al. reported that astragalus extract produced positive inotropic actions at higher doses and negative inotropic effects at lower doses.52 Astragalus also produces hypotensive actions via peripheral vasodilation in healthy and hypertensive animals.71,72 Chen et al. reported that astragalus significantly reduced arterial pressure in the rat model of renal hypertension and improved cardiac function in experimental congestive heart failure.73 This effect was confirmed by Ma et al. who reported that astragalus improved left ventricular systolic function and potentiated the cardiotonic, diuretic, and natriuretic renal responses to atrial natriuretic peptide in rats with experimentally induced chronic heart failure.13 There is in vitro evidence that astragalus may also stimulate angiogenesis and revascularization in ischemic myocardium66 and amnion74 and promote vascular endothelial cell proliferation and DNA synthesis74. Astragalus has been suggested to increase sodium pump activity in erythrocytes.75
Hormonal/reproductive effects: Astragalus has significant effects on various hormonal systems. Astragalosides are reported to significantly increase growth hormone release in rat pituitary cell culture compared to controls.12 Astragalus polysaccharide fractions have also been shown to prevent bone loss in ovariectomized rats.76 In vitro sperm motility and viability have been shown to be significantly increased in healthy rats and men.77 Astragalus has also been reported to inhibit in rats decrements in sperm production and motility caused by cadmium exposure.25 Liu et al. recently reported that astragalus extract significantly increased in vitro sperm motility and viability in 30 infertile men.78
Immune system effects: Astragalus flavonoids are reported to increase in vivo cell-mediated immunity in guinea pigs79 and mice42. Astragalus appears to enhance cell-mediated immunity by increasing the number of T-helper cell type 2 cytokines, increasing levels of tumor necrosis factor and interleukin-6.80,81,48,82,83,84 It has been shown to stimulate macrophage and natural killer cell activity.45,85,3 According to animal study, astragalus enhanced both cellular and humoral immune responses to bacterial infections when compared to controls.15 Marrow blood collected from patients with ischemia of the lower limbs and exposed to astragalus had a significantly increased ratio of CD34+ cells (p<0.05).86


Pharmacodynamics/Kinetics:

Astragalosides appear to exert their immunomodulatory actions via direct interaction with cellular membrane receptors. Shao et al. reported that astragalus root polysaccharide fractions activated mouse B cells and stimulated macrophage production via direct interaction between the polysaccharide fractions and TLR4 on cell surfaces.35 Hao et al. demonstrated in rat endothelial cells that astragalus root polysaccharide fractions stimulated the adhesion between neutrophils and endothelial cells by promoting the expression of superficial I-1 on the cell surface.87 This action would hypothetically facilitate the inflammatory response in wound healing and possibly underlie the detoxification and cellular protective actions of astragalus polysaccharides observed in several tissues. Astragalus polysaccharides also are known to increase RNA activity and protein synthesis in various tissues and increase the activity of enzymes that regulate specific cellular metabolic functions.2 Astragalus has been shown to modulate ornithine decarboxylase activity and increase insulin-induced protein tyrosine phosphorylase activity in the livers and skeletal muscles of animal models of type 2 diabetes.34
There is insufficient available data on the pharmacokinetic parameters for individual chemical constituents of astragalus.


References (see http://www.sigmaaldrich.com/life-sc...earning-center/plant-profiler/astragalus.html)

 

[heapsreal]

I am not saying that anyone else should raise their DHEA above normal range, I am just letting you know that you might not want to be boud by normal ranges. For instance, I had high estrogen when I was young and that is how *I* function best. I also want to mention that if it helps you know immediately - like withoin a half hour for me. So you need not try for days to be sure it works. (All bets are off if you're taking tiny doses though). When I tried it, I started with 50mg DHEA at one time and 30mg pregnenolone (because I wasn't sure how much pregnenolone since I was already taking the full tested dose of DHEA and pregnenolone itself will make DHEA). The 50mg at one time DHEA immediately cured panic and stabilized my blood pressure. But I noticed I would become ineffective - wasting time stupidly etc. in the mornings so I tried 25mg morning and 25mg at dinner. I was no longer effective at all (well maybe for a very short time right after each 25mg. I knew taking more had been tested in depressives, I knew that had not been tested adequately, but that it had bene tested, so I decided to try it. The 75 mg DHEA works very well for me. I then tried to raise the pregnenolone because I thought I should have more of a balance. I tried 50mg and it caused water retention. So I dropped back to 30. I talked to Fredd and found out he takes 100mg pregnenolone and 25mg DHEA so I decided that maybe if I drop my DHEA I can take more pregnenolone. I tried his regime...it did not work for me and it caused water retention (which I believe raised my blood pressure but I didn't really test that). I also tried DHEA 50 and oregnenolone 50. Again it did not work.

Since I had a reaction to flea control products sometimes when I take DHEA it feels like going into a fun house with the mirrors that shrink you and make you bigger for a few minutes and then settles down to not working. I believe that is because it works for a second and then gets blocked and breaks through for a second and then gets blocked...end result is it can't get through. That's what it feels like anyway. So...if you feel like that for a few minutes after you take it, then I would think DHEA is what you need but something else is blocking it.

I don't know what X**** is so I know nothing about any interactions between that and something else. I believe that when there is a disease for which there is no known cure that listening too closely to what the medical community says about that disease may not be beneficial (because they have not found the way), although of course all things must be considered.

I do think fixing the top hormones first is the best way to get sorted out. This is not my idea but I can't remember what doctor I read it from. I can only point to ther things, like the fact that DHEA kills things (cann be used to treat flu for instance) and so will help with the inflammation cascade. (For instance as you said inhibiting IL-6).

Gotta go
Rydra

I think alot of the info on dosing of these hormones on antiaging and hormone replacement therapy are way to high for us, especially to start with. A few articles have said that pregnenolone has no side effects even at large doses of 500mg, now that sort of dose would blow my mind. I went into a rage within a week on 50mg, one forum i was on said to keep increasing the dose until you felt sleepy, WT? i was having the opposite of what they were having effects wise. 5-10mg of pregnenolone is plenty for me any more and it would greatly interfer with sleep, but i do think its a good hormone and at the top of the cascade.

I agree start at the top of the cascade with pregnenolone and then dhea and or progesterone. If no luck with this then need to look into hydrocortisone, testosterone and estrogen which are at the bottom of the cascade. The hormones at the top have a flow down effect. For me pregnenolone has a flow down to cortisol and testosterone with minimal effect on other hormones so need to top up progesterone and dhea, which is my work in progress at the moment. I think by still having low dhea after supplementing with pregnenolone is showing that pregnenolone steal is going on and my body needs more cortisol.

cheers!!!

 

[wastwater]

What is B cell neoplasia