Turns out Icariin may be pro-chondrogenic after all:
Icariin: a potential promoting compound for cartilage tissue engineering.
"Icariin was added into cell-hydrogel constructs derived from neonatal rabbit chondrocytes and collagen type I. The effects of icariin-added cell-hydrogel constructs on the restoration of supercritical-sized osteochondral defects of adult rabbit were investigated by histological observation. The cell-hydrogel constructs without Icariin were set for controls.
Icariin obviously up-regulate the expressions included aggrecan, sox9, and collagen type II of seeded chondrocytes form 99.7% to 248%[That's huge]. It increases the synthesis of glycosaminoglycan and collagen type II about fourfolds to fivefolds from week 1 to week 4, and accelerates the formation of chondroid tissue in the cell-hydrogel constructs. [Icariin] improves the restoration efficiency of super critical-sized osteochondral defects in adult rabbit model, and enhances the integration of new-formed cartilage with subchondral bone.
Icariin can be a substitute for the use of some growth factors."
"Herb Epimedium (HEP) [contains Icariin]"
"Icariin could regulate the anabolism of osteoblasts through the up-regulation of BMP-4, BMP-2 and SMAD4 expression"
"the osteoinductive effect of icariin in vivo might be expressed through the process of endochondral ossification"
"icariin [may] be a promoter of cartilage tissue engineering"
"the addition of icariin could help to increase the synthesis of cartilage-specific matrixes of the seeded chondrocytes, promote the formation of chondroid tissue"
It's possible that Icariin promotes the induction of Sox9 itself which would make it a very promising chondroinductive supplement but even if Icariin only enhances Sox9, COL2A1, and Aggrecan it may still help increase height in existing growth plates or help induce new growth plates with LSJL.
[Effect of icariin on the mRNA expressions of Cbfalpha1, BMP2, BMP4 in rat osteoblasts].
"Primary rat osteoblastic cells were obtained. The passage 3-5 cells were treated with icariin at the concentration of 0 mol/L, 10(-8) mol/L, 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L, 10(-4) mol/L for 24 h, 48 h, 72 h, and the proliferation of the cells was measured.
Icariin showed no effect on the proliferation of osteoblasts, but improved ALP activity. The Cbfalpha1, BMP2, BMP4 mRNA were significantly upregulated after icariin treatment."
Icariin can increase BMP-2 expression in osteoblasts that BMP-2 expression may help induce chondrogenic differentiation in mesenchymal stem cells.
Analysis of the effects of androgens and training on myostatin propeptide and follistatin concentrations in blood and skeletal muscle using highly sensitive Immuno PCR.
"Myostatin propeptide (MYOPRO) and follistatin (FOLLI) are potent myostatin inhibitors. we analysed effects of training and androgens on MYOPRO and FOLLI concentrations in blood and skeletal muscle using Immuno PCR. Young healthy males performed either a 3-month endurance training or a strength training. Training did not significantly affect MYOPRO and FOLLI concentrations in serum and muscle. Blood samples of tetraplegic patients, untrained volunteers and bodybuilders were analysed. MYOPRO was significantly increased exclusively in the bodybuilder group[but it could be that the high levels of MYOPRO are causing the increased muscle mass rather than the other way around, longitudinal studies would have to performed]. In orchiectomised rats MYOPRO increased in blood and muscle after treatment with testosterone. Moderate training does not affect the concentrations of MYOPRO to FOLLI. In contrast androgen treatment results in a significant increase of MYOPRO in skeletal muscle and serum."
Testosterone inhibits myostatin through MYOPRO and horny goat weed(icariin) mimcs the effects of testosterone.
"there is only a moderate inter-individual variability with respect to the measured MYOPRO and FOLLI serum levels. In our study the serum concentrations varied between 6 and 10 ng/ml for FOLLI and between 35 and 50 pg/ml for MYOPRO."<-providing evidence that it's muscle mass that reduces concetration of myostatin inhibitors.
"no major effects of long term training on myostatin or its propeptide could be detected."<-so it's the muscle itself that inhibits myostatin and not the training.
Also note that there was no difference between the extremely low muscle mass group and the control group so there could be other factors. The scientists mention steroids.
The testosterone mimetic properties of icariin
"Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each: the control group (C), the model group (M), the icariin group (ICA) and the testosterone group (T). The reproductive system was damaged by cyclophosphamide (intraperitoneal injection, 20 mg/kgday) for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA (gastric gavage, 200 mg/kgday) for the ICA group and sterandryl (subcutaneous injection, 5 mg/ratday) for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), serum bone Gla-protein (BGP) and tartrate-resistant acid phosphatase activity in serum (StrACP) were determined.
(1) Icariin improved increased the circulating levels of testosterone.
(2) Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption.
Icariin has testosterone mimetic properties."
Icariin "stimulates the differentiation of osteoblasts and increases the activity of alkaline phosphatase (ALP) and the expression of I-collagen protein in rats and promotes bone formation"<-this does not mean that Icariin is anti-chondrogenic.
The increase in Testosterone by Icariin was insane, 3 fold versus the control group and only 1/3rd of the direct testosterone group.
Icariin promotes bone formation. BGP is also known as osteocalcin which is secreted by osteoblasts so it's used as a measure of bone formation. Therefore, Icariin increase bone formation. It's Icariin's usage as a testosterone mimetic that is intriguing however as myostatin inhibition has the most potential usage during endochondral ossification.
[Experimental study of icariin in inducing bone marrow mesenchymal stem cell differentiation]
"To research the effect of icariin (ICA) on the proliferation and differentiation of bone mesenchymal stem cells (BMSCs) and to study its influence on the expressions of transforming growth factor-beta1 (TGF-beta1) and bone morphogenetic protein-2 (BMP-2) in the progress of BMSCs differentiating into osteoblast, for providing an experimental evidence to explain the mechanism of ICA.
After the most effective concentration of ICA for promoting the differentiation of BMSCs into osteoblast was judged with the indices like alkaline phosphatase (ALP), etc., a grouped experiment was conducted for the sake of studying the effect and mechanism of ICA in its process of inducing BMSCs differentiation into osteoblast through detecting expression of ALP and calcium nodes, as well as the expressions of TGF-beta1, and BMP-2 with ELISA.
The most effective concentration of the ICA on the BMSCs differentiation was judged as 1 x 10(-9) mol/L, ICA of that concentration showed effects in enhancing the expressions of osteoblast-indices and increasing the secretion of TGF-beta1, and BMP-2. the increase of TGF-beta1, and BMP-2 was revealed in all the groups, in which ICA showed its influence visibly.
ICA could promote the differentiation of BMSCs into osteoblast; the up-regulation of TGF-beta1, and BMP-2 expressions is possibly one of the action mechanisms of various interventional drugs in their differentiation promoting progress."<-Note this shows that it increased BMP-2 secretion so definitely potential to induce chondrogenic differentiation. The study mentions encouraging the differentiation of MSCs into osteoblasts but both TGF-Beta1 and BMP-2 are pro-chondrogenic.
On the bone resorption inhibition(and remember bone resorption may be an important part of endochondral ossification):
Icariin inhibits osteoclast differentiation and bone resorption by suppression of MAPKs/NF-kappaB regulated HIF-1alpha and PGE(2) synthesis.
"We examined the detail molecular mechanisms of icariin on lipopolysaccharide (LPS)-induced osteolysis. Icariin [inhibits] osteoclast differentiation and bone resorption by suppressing MAPKs/NF-kappaB regulated HIF-1alpha and PGE(2) synthesis[HIF-1alpha and the NF-kappaB pathway are both good for chondrogenesis/height growth]. After treatment with icariin, the activity of osteoclasts differentiation maker, tatrate resistances acid phosphatease (TRAP), significantly decreased at the concentration of 10(-8)M. Icariin (10(-8)M) reduced the size of LPS-induced osteoclasts formation, and diminished their TRAP and acid phosphatease (ACP) activity without inhibition of cell viability. Icariin also inhibited LPS-induced bone resorption and interleukin-6 (IL-6)[at 10(-8)M], and tumor necrosis factor-alpha (TNF-alpha) expression. The gene expression of osteoprotegerin (OPG) was up-regulated, while receptor activator of NF-kappaB ligand (RANKL) was down-regulated. Icariin also inhibited the synthesis of cyclo-oxygenase type-2 (COX-2) and prostaglandin E(2) (PGE(2)). In addition, icariin had a dominant repression effect on LPS-induced hypoxia inducible factor-1alpha (HIF-1alpha) expression of osteoclasts. On osteoclasts, icariin suppresses LPS-mediated activation of the p38 and JNK; while on the osteoblasts, icariin reduced the LPS-induced activation of ERK1/2 and I-kappa-B-alpha (IkappaBalpha), but increased the activation of p38. Icariin has an in vitro inhibitory effects on osteoclasts differentiation that can prevent inflammatory bone loss. Icariin inhibited LPS-induced osteoclastogenesis program by suppressing activation of the p38 and JNK pathway."
"In macrophages, LPS induces hypoxia-inducible factor-1α (HIF-1α) protein accumulation under normoxic condition"<-this could be important for us as hypoxia is pro-chondrogenic.
Icariin has inhibitory effects on hypoxia in this study and chondrocytes like to grow in low oxygen environments but the inhibitory effects may be specific to LPS.
According to [Comparative study on effect of icariin and genistein on proliferation and mineralization of osteoblasts in vitro]., Icariin may also increase bFGF and IGF-1.
Icariin Promotes Extracellular Matrix Synthesis and Gene Expression of Chondrocytes In Vitro.
"Rabbit chondrocytes were isolated from articular cartilage and cultured in vitro with different concentrations of icariin. Icariin at concentrations under 1 × 10(-5) m showed low cytotoxicity toward chondrocytes, but icariin at 5 × 10(-5) m inhibited the proliferation of chondrocytes. Icariin hardly affected the cell morphology with concentrations ranging from 1 × 10(-7) m to 5 × 10(-5) m. the higher concentration of icariin produced more extracellular matrix (ECM) synthesis and expression of chondrogenesis genes of chondrocytes. Indeed, the promotion of icariin on the synthesis of glycosaminoglycans (GAGs) and collagen of chondrocytes, and finally exerting a potent chondrogenic effect, might be due to its ability to up-regulate the expression of aggrecan, collagen II and Sox9 genes and to down-regulate the expression of the collagen I gene of chondrocytes. Icariin [is] an effective accelerant for chondrogenesis. 1 × 10(-5) m may be a suitable concentration of icariin with chondrogenic effect for tissue engineering"
"icariin media at a concentration of 5 × 10−5 m inhibited the proliferation of chondrocytes, it violently promoted GAG synthesis of cells."<-Whether this is beneficial to height growth is the question. If chondrocytes are not proliferating they are not approaching senescence.
Icariin: Does It Have An Osteoinductive Potential for Bone Tissue Engineering?
"Icariin, a typical flavonol glycoside, is considered to be the main active ingredient of the Herba Epimedii from which icariin has been successfully extracted. Icariin can be delivered locally by biomaterials and that it has an osteoinductive potential for bone tissue engineering. The osteoinductive potential of icariin could be attributed to its multiple functions in the musculoskeletal system which is involved in the regulation of multiple signaling pathways in anti-osteoporosis, osteogenesis, anti-osteoclastogenesis, chondrogenesis, angiogenesis, and anti-inflammation."
This paper mentions a study where cell-hydrogel construct delivery of icariin in rabbits increased cartilage formation.
"Icariin inhibited LPS-induced osteoclastogenesis by suppressing the activation of the p38 and JNK pathway"
"The effect of icariin on the synthesis of glycosaminoglycans (GAGs) and collagen of chondrocytes, and its potent chondrogenic effect, might be due to its ability to up-regulate the expression of aggrecan, collagen II, and Sox9 genes and to down-regulate the expression of the collagen I gene of chondrocytes"
" Icariin can up-regulate the expression of Sox9 and Cbfa1 in controlling osteogenesis and chondrogenesis."
homeopathy train?
ReplyDeleteIn order to increase height above genetic potential,there is more than "increased" growth hormone and igf-1 production needed.Unless one manages to obtain the required hormonal and signaling-molecules profile; a profile literally impossible to sustain for the body without supportive means provided,it is impossible to prevent the impeding of growth even in teenagers. In order to fully increase height and bodily potentials, human body should be enabled to preserve this very neuro-endocrinal and paracrine profile for sufficient time.
ReplyDeleteI have successfully managed to increase the heights of 129 individuals by varying degrees from 1.75 to 4 inches,they all being between the ages 19-29 by using hybrid formulations that combines amino acids,highly standardised herbal extracts(99% at least) and quaternary ammonium compounds to activate several growth factors, signaling molecules and C-reactive natruetic peptide expression,to inhibit the Core 2 GlcNAc-T enzyme and so on...
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Deletehi i recently came across this blog. i think it's awesome. i was just wondering if there's a limit to how much height you can attain through lsjl and also how long does it take until you see actual results?
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ReplyDelete------------>>>>>I have successfully managed to increase the heights of 129 individuals by varying degrees from 1.75 to 4 inches,they all being between the ages 19-29 by using hybrid formulations that combines amino acids,highly standardised herbal extracts(99% at least) and quaternary ammonium compounds to activate several growth factors, signaling molecules and C-reactive natruetic peptide expression,to inhibit the Core 2 GlcNAc-T enzyme and so on..
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Alkoclar said that it works by enhancing FGF2 receptor sensitivity and local expression modulation of CNP. He said it costs $2000 for a 3 month supply, and he issues refunds.
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