Tuesday, July 5, 2011

Can height increase due to diosgenin?

11-Keto-Diosgenin is a part of Alkoclar's new CNP inducing formula.  CNP does have height increasing potential as it inhibits FGFR3(which can cause dwarfism) and stimulates ECM extracellular matrix synthesis which helps you grow taller[stem cells have the ability to respond to the extracellular matrix environment].  Forms of Diosgenin are available for sale like Dioscorea Villosa (Dioscorea Villosa (Potency: 15C)).  The effectiveness of such compounds can not be verified.

Does Diosgenin increase CNP expression?  Does Diosgenin have other height augmenting effects other than increasing CNP expression?  It seems that the growth plate beneficial effects are mostly from reducing things like inflammation.  I don't know if it would have any impact on adults.

Diosgenin stimulates osteogenic activity by increasing bone matrix protein synthesis and bone-specific transcription factor Runx2 in osteoblastic MC3T3-E1 cells.

"Diosgenin, a steroid saponin extracted from the root of wild yam (Dioscorea villossa).  murine MC3T3-E1 osteoblastic cells were cultured with varying levels of diosgenin (0-10 μM) within 25 days of bone formation period. Diosgenin was found to stimulate proliferation within the range of 0.01-5 μM using MTT assay[Diosgenin stimulates osteoblast proliferation]. The medium and cellular levels of Type 1 collagen and alkaline phosphatase (ALP), both of which are major bone matrix proteins, increased within the low range of diosgenin concentration (>0-3 μM), and this pattern was further confirmed by collagen and ALP staining of the extracellular matrix (ECM). The cellular protein expression of ALP and collagen Type 1 was also increased at 0.1-1 μM diosgenin treatment. Calcium deposition within the ECM also showed the same pattern. Bone-specific transcription factor runt-related transcription factor 2 (Runx2) and Runx2-regulated osteopontin protein expressions were induced at low concentration (0.1-1 μM) and again decreased with high diosgenin concentrations. diosgenin can enhance bone formation by stimulating the synthesis and secretion of Type 1 collagen and ALP and bone marker proteins Runx2 and osteopontin expression. The increased levels of these marker proteins, in turn, can increase the formation of calcium deposits within the ECM thereby increasing bone formation."

The fact that Diosgenin inhibits Runx2 at higher concentrations could be a good thing for height growth as Zfp521 which inhibits Runx2 and augments height growth.  Diosgenin does not inhibit Beta-Catenin and to grow taller you always want Beta-Catenin levels to be higher than your Sox 9 levels.

Diosgenin may inhibit parts of the Nitric Oxide pathway.  There are good and bad parts of the NO pathway(bad being inflammatory cytokines).  The Nitric Oxide pathway includes cGMP which is needed for CNP to function properly.

Nitric oxide inhibitory substances from the rhizomes of Dioscorea membranacea.

"Thai medicinal plants locally known as Hua-Khao-Yen were examined for their inhibitory activities against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cell lines. Among the plant species studied, an ethanolic extract of Dioscorea membranacea exhibited the most potent inhibitory activity, with an IC(50) value of 23.6 microg/ml. From this extract, eight compounds [two naphthofuranoxepins (1, 2), one phenanthraquinone (3), three steroids (4-6) and two steroidal saponins (7, 8)] were isolated and further investigated for their inhibitory properties of NO production. It was found that diosgenin-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-glucopyranoside (7) possessed the highest activity (IC(50)=3.5 microM), followed by dioscoreanone (3, IC(50)=9.8 microM) and dioscorealide B (2, IC(50)=24.9 microM). Regarding structural requirements of diosgenin derivatives for NO production inhibitory activity, compound 7 which has a rhamnoglucosyl moiety at C-3 exhibited much higher activity than compounds that have either a diglucosyl substitution (8) or its aglycone (9); whereas, hydroxyl substitution at position 8 of naphthofuranoxepin derivatives conferred higher activity than the methoxyl group. I diosgenin-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-glucopyranoside (7), dioscoreanone (3) and dioscorealide B (2) are active principles for NO inhibitory activity of Dioscorea membranacea. Compounds 1-3 were also tested for the inhibitory effect on LPS-induced TNF-alpha release in RAW 264.7 cells. The result revealed that 3 possessed potent activity against TNF-alpha release with an IC(50) value of 17.6 microM, whereas, 1 and 2 exhibited mild activity."

"Nitric oxide (NO) is one of the inflammatory mediators causing inflammation in many organs. This inorganic free radical has been implicated in physiologic and pathologic processes, such as vasodilation, non-specific host defense and acute or chronic inflammation. NO is produced by the oxidation of l-arginine by NO synthase (NOS). In the family of NOS, inducible NOS (iNOS) is involved in pathological aspects, and can be expressed in response to pro-inflammatory agents such as tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β) and lipopolysaccahride (LPS) in various cell types including macrophages. NO acts as a host defense by damaging pathogenic DNA and as a regulatory molecule with homeostatic activities[one of the good attributes of NO]. However, excessive production of this free radical is pathogenic to the host tissue itself, since NO can bind with other superoxide radicals and acts as a reactive radical which directly damages the function of normal cells"<-So you want an equilibrium amount of NO or you want to augment the good features of NO while inhibiting the bad.

Diosgenin seems to uniformly inhibit all parts of the Nitric Oxide Pathway.  However, it is unclear whether it lowers the NO pathway below equilibrium(meaning it decreases levels too much so the positive benefits of NO start to be reduced).  If Diosgenin has another benefit on CNP expression outside of the NO pathway then it would be very good as Diosgenin would boost CNP(the good part of NO) while avoiding inflammatory cytokines(bad part of NO except for IL-6).

According to Effects of diosgenin on cell proliferation induced by IGF-1 in primary human thyrocytes., diosgenin decreases cyclin D1 and causes cell cycle arrest.

Diosgenin may also inhibit Stat3, which is a good thing for height growth, according to Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells.

Methyl Protodioscin is a part of Dioscorea.  Protodioscin does stimulate the NO pathway and increases testosterone levels.  Dioscin's direct effect on CNP has not been studied.  Diosgenin may help keep the inflammatory inducing parts of Protodioscin in check  The effect of diosgenin has not been studied at all on chondrocytes so there may again be stuff there.

Advances in the pharmacological activities and mechanisms of diosgenin

"Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPARγ. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases."<-decreasing oxidative stress and preventing inflammatory events may help with height growth too.

Couldn't get this full study.

Diosgenin prevents bone loss on retinoic acid-induced osteoporosis in rats<-I need this full study because it measures diosgenin effects on femur length.  But in the study it said that diosgenin partially reversed some of the retinoic acid reductions in femur length.

According to Effects of diosgenin on the skeletal system in rats with experimental type 1 diabetes, diosgenin reduced some of the negative effects on the growth plate from diabetes.

1 comment:

  1. hmm diosgenin may not will be too good, beacuse '' In addition, diosgenin significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that diosgenin inhibited NF-κB activity.The results suggested that diosgenin inhibited migration and invasion of PC-3 cells by reducing MMPs expression. It also inhibited ERK, JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for diosgenin in anti-metastatic therapy.''