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From: waseda
Date: 03 May 2001
Time: 16:20:29
Remote Name: 211.13.143.10
And a kind of Heparin derivative is now under study for hair growth product here. For Heparan Sulfate and Heparin have FGF1, 2 binding domain and HGF binding domain. (1), (2).
F-fucoidan, which is Fucose sulfate, a kind of mucopolyasccharide and the kindred of Heparin, Heparan Sulfate, was found to be an 'inducer' of HGF(3). There is already a hair growth product using fucoidan as HGF inducer here( Octave Scalp Narurient), though it is for female.(http://www.milbon.co.jp/homecare/agn/octave/oct4.html).
Perhaps, this may be a weak inducer because fucoidan has big molecule and very hard to penetrate through skin barrier. But, Takara contrived to reduce the big molecule to smaller parts with enzime last year and the parts seem to induce HGF more strongly. We are looking forward to coming out of hair product which includes smaller molecular fucoidan or Herarin derivative.
Anyway, as you correctly suggest, Heparin, Heparan, Heparan Sulfate, etc. are without doubt the main constituents of next generation hair grower.
(1) Biochem Biophys Res Commun 1999 Feb 5;255(1):80-7
Hepatocyte growth factor is a major mediator in heparin-induced angiogenesis.
Okada M, Matsumori A, Ono K, Miyamoto T, Takahashi M, Sasayama S
Department of Cardiovascular Medicine, Kyoto University, 54 Kawaracho Shogoin, Sakyo-ku, Kyoto, 606-8397, Japan.
Heparin has a potent angiogenic effect in experimental animals and patients with ischemic diseases; however, the precise mechanism behind this angiogenesis remains to be clarified. The aim of this study was to determine whether the administration of heparin affects the levels of heparin-binding angiogenic factors in human plasma, and to identify the molecule responsible for heparin-induced angiogenesis. Plasma levels of hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were measured before and after administration of 100 U, 3,000 U or 10,000 U of heparin in patients with coronary artery disease. Administration of 3,000 U or 10,000 U of heparin caused significant increases in plasma HGF (40- and 54-fold, respectively), in absence of obvious increases in bFGF and VEGF levels. Furthermore, compared with the serum collected before heparin administration, the serum collected after heparin administration had more prominent growth-promoting and vascular tube-inducing properties on endothelial cells, and these increased activities were completely inhibited by neutralization of HGF, whereas neutralization of bFGF and VEGF had no effect. These findings suggest that HGF plays a significant role in heparin-induced angiogenesis.
PMID: 10082659
(2) Br J Clin Pharmacol 2000 Sep;50(3):221-6
Heparin-mediated selective release of hepatocyte growth factor in humans.
Salbach PB, Bruckmann M, Turovets O, Kreuzer J, Kubler W, Walter-Sack I
University of Heidelberg, Medical School Departments of Internal Medicine III, Bergheimerstrasse 58, D-69115 Heidelberg, Germany. peter_salbach@med.uni-heidelberg
AIMS: The aim of this investigation was to compare the effects of standard (S) with low molecular weight (LMW) heparin on circulating levels of heparin-binding growth factors (HBGF), known to have angiogenic properties in humans. METHODS: In two consecutive trials 18 healthy male volunteers were studied on three separate occasions, following a placebo-controlled crossover design. Subjects were randomised to receive either S-heparin or LMW heparin or placebo. Heparins were administered either by intravenous (i.v.) or subcutaneous (s.c.) injection and saline placebo by i.v. injection. Serum concentrations of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured before and up to 24 h after injection. RESULTS: Administration of i.v. S-or LMW-heparin (50 IU kg(-1) resulted in rapid, highly significant (47 fold for S, 30.9 fold for LMW) increases in HGF serum values, reaching maxima of 10.51+/-1.65 ng ml(-1) (S) and 8.28+/-1.04 ng ml(-1) (LMW), respectively, 10 min after drug application. S.c. injection of S-heparin or LMW heparin resulted in 4.1 and 5.4 fold increases in HGF serum values, respectively. Both agents showed no effects on circulating VEGF or bFGF levels, independent of the route of administration. CONCLUSIONS: Circulating HGF levels were selectively increased in response to pharmacological doses of two, widely used heparin preparations. This may, in part, explain some of the biological effects of heparin separate from its anticoagulant properties. By this mechanism, the systemic administration of heparin may facilitate collateral vessel formation in various clinical settings of tissue ischaemia.
Publication Types: Clinical trial Randomized controlled trial
PMID: 10971306
(3)
http://www.takara.co.jp/english/index.htm
15 July 1999
Discovered that the polysaccharide F-fucoidan contained in the seaweed kombu can induce the production of HGF (Hepatocyte Growth Factor) in vivo experiment
Over the past decade, Biotechnology Research Laboratories of Takara has been conducting research into the functional dietary fiber contained in various types of seaweed. On this occasion, Takara has discovered that the polysaccharide known as F-fucoidan, which is contained in kombu and other types of brown seaweed, can significantly enhance the production of Hepatocyte Growth Factor (HGF) in vivo experiment. HGF is a cytokine that has been reported to be effective in slowing down the aging process, as well having other types of benefits. Details of Takara's discovery will be presented at the Annual Meeting of the Japanese Biochemical Society that will be held in Yokohama from October 6 to 9. (snip)
4. F-fucoidan enhance the production of HGF
In the course of their research, scientists at Takara utilized human lung fibroblast MRC-5 cell line, which is universally used in experiments related to HGF. Having F-fucoidan react with MRC-5 cells caused HGF to be produced in significant quantities. However, when a similar experiment was carried with U-fucoidan, only minor levels of induction of HGF production were detected.
Experiments conducted with fucoidan derived from other types of seaweed such as wakame-mekabu and mozuku (harvested at Ishikawa prefecture) also demonstrated significant induction of HGF production. However, a parallel test conducted on fucoidan derived from Okinawa-mozuku demonstrated only minor levels of induction of HGF production. It is thought that these results were caused by the differences in the chemical structure of the various types of fucoidan that were used in the experiments. In another experiment, fucoidan derived from a sea cucumber, which is an echinoderm and not a seaweed, has a strong induction activity of the production of HGF.
Injecting F-fucoidan derived from Gagome kombu into the peritoneal cavity of rats that had been partially hepatectomized led, as expected, to increase in HGF concentration in the rats' blood. This confirmed that F-fucoidan can enhance the production of HGF even in vivo experiment.
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