33 replies to this topic

[Lufega]

I'm trying to boost my body's production of Hyaluronic acid. There's tons of research on this stuff but I can't seem to find any of it. So far, it seems that magnesium and manganese are both needed as cofactors. What else can stimulate some, far from taking it as a supp???

Brain extracellular matrix

Hyaluronic acid and hyaluronic acid-binding proteins in brain extracellular matrix.

Bignami A, Hosley M, Dahl D.
Research and Development Service, Department of Veterans Affairs Medical Center, West Roxbury, MA 02132.
Hyaluronic acid (HA) plays the main structural role in the formation of brain extracellular matrix (ECM). The extracellular space appears empty by electron microscopy because HA is readily dissolved during the preparation of tissues for ultrastructural studies. The HA-binding proteins so far identified in brain ECM are versican, aggrecan and the glial HA-binding protein. Versican is a large fibroblast proteoglycan preferentially expressed in embryonic cartilage at the time of mesenchymal condensation. Glial HA-binding protein (GHAP) is probably a proteolytic product of versican corresponding to its HA-binding amino-terminal domain. It is mainly a white-matter protein, suggesting that the proteinase responsible for its cleavage from versican is normally activated in this location. Versican is found in both white matter and gray matter, where it forms pericellular coats around large neurons. Aggrecan, the aggregating proteoglycan of mature cartilage, co-localizes with versican in this location. In white matter, the localization of GHAP and versican is identical to that of the glial fibrillary acid protein, suggesting that both proteins are produced by astrocytes. An important difference between GHAP and versican is that GHAP but not versican is released from the tissues by hyaluronidase digestion, which suggests that versican is anchored to the cell membranes lining the extracellular space. GHAP was localized at the ultrastructural level in the granule cell layer of rat cerebellum, the only region of gray matter that is positive for GHAP in this species. Rats were perfused with aqueous fixatives containing cetylpyridinium chloride or tannic acid to prevent the solubilization of HA. GHAP is found throughout the extracellular space, the synaptic clefts being a notable exception. GHAP appears late in development, and the same is true for versican, the characteristic perineuronal coats first becoming apparent in the third postnatal week. It is suggested that a marked change occurs in the structure of brain ECM when HA-binding proteins first appear, and that the change is similar to that observed in prechondrogenic mesenchyme, i.e., reduction of the extracellular space and cell aggregation.

[Lufega]

The repair of brain lesion by implantation of hyaluronic acid hydrogels modified with laminin

Résumé / Abstract
The hyaluronic acid (HA) hydrogels modified with laminin were used lor implantation in rat brain in present study, in order to investigate its effects in reparation of injury in the CNS. Cross-linked HA hydrogels were synthesized and their characteristics were analyzed. Laminin, an extracellular matrix protein, which participates in neuronal development and survival, was immobilized on the backbone of the hydrogels. Hydrogels unmodified and modified with laminin were implanted into cortical defects mechanically created in rats and their ability to improve tissue reconstruction was then evaluated. After 6 and 12 weeks of implantation, sections of brains were processed with NissI and Glees staining for revealing neural cell bodies and fibers, with DAB histochemistry for detecting the blood vessels, as well as with immunocytochemistry for recognizing GFAP. The sections were also taken to SEM and TEM for ultrastructral examination. The results showed that the HA hydrogels synthesized had mechanical properties and rheological behavior similar to the brain tissue. After being implanted into the lesion of the cortex, the porous hydrogels created a scaffold, which could support cell infiltration and angiogenesis, and simultaneously inhibit the formation of glial scar. In addition, HA hydrogels modified with laminin could promote neurile extension. It seems possible that the tissue engineering technique may pave the way to repair injury in the CNS as suggested by the results in present study.
Revue / Journal Title
Journal of neuroscience methods ISSN 0165-0270 CODEN JNMEDT [/quote]

HA..repair CNS injury? That's pretty neat. I wonder if it can do anything for the ANS?

[Ben K]

A few years ago, one of the TV newsmagazine shows ran a story claiming that you could raise your HA levels by eating certain Asian root vegetables. But as far as I know, there was never a lick of proof.

[Lufega]

A few years ago, one of the TV newsmagazine shows ran a story claiming that you could raise your HA levels by eating certain Asian root vegetables. But as far as I know, there was never a lick of proof.

I think the pictures speak for themselves. That was a segment on Primetime (?) on "the village of long life" in Japan. Bill Sardi traveled there and he came up with a few conclusions. The foods themselves are not high in HA, rather, they encourage the innate production of it. That, in combination with other health promoting methods, like exercise, low iron diet, etc.

http://www.mimsgloba.../yuzurihara.pdf

[Lufega]

I searched pubmed for the terms ¨hyaluronic acid¨and ¨lyme¨. Came up with three studies:

Borrelia burgdorferi decreases hyaluronan synthesis but increases IL-6 production by fibroblasts.
Jones NC, Germain A, Riley KE, Bautista C, Taylor W, Wells AF.

University of South Florida, College of Medicine, Division of Rheumatology, Tampa 33620.

Despite the prevalence of clinical data on human Lyme disease, little is known about the immunopathologic effects of the causative organism on the host. We studied the effect of Borrelia burgdorferi on hyaluronan (hyaluronic acid, HYA) production and the effect on interleukin-6 (IL-6) synthesis by cultured fibroblasts. The cell line employed in this study produced an average of 1406 ng of hyaluronan/ml within 48 h. Using both a morphological staining protocol and a quantitative radiometric assay, we noted that in the presence of a low dose of Borrelia (9.4 x 10(5) cells/ml) the hyaluronan production decreased to an average of 1008 ng/ml, a significant difference (p < 0.05) from the amount of hyaluronan produced by the cells alone. The reduction was even more significant (p < 0.01) when a higher dose of Borrelia (9.4 x 10(6) cells/ml) was used giving an average hyaluronan concentration of 682 ng/ml. In contrast, we found that Borrelia stimulated the cells to produce IL-6 from a baseline of 293 pg/ml to a maximal value of 842 pg/ml (p < 0.01). The spirochetes had no significant effect on cell viability, nor were we able to demonstrate invasion of the cells by the bacteria. Both a decrease in hyaluronan and an increase in IL-6 may correlate with the pathogenicity of Lyme disease in man.

PMID: 7968455 [PubMed - indexed for MEDLINE]

[Indicators of articular cartilage degeneration in synovial fluid]
[Article in Czech]

Krsová D, Krajícková J, Trnavský K.

Výzkumný ústav chorob revmatických, Praha.

Detection of proteoglycans in biological fluids is a perspective method for the evaluation of the degree of catabolic processes in articular cartilage. The demand of accuracy and specificity of detection of substructures of the degradation products of the cartilaginous matrix, with the perspective of routine large scale examinations, restricts available possible methods practically only to the use of immunochemical methods. In the present investigation in the inhibitory ELISA test polyclonal antibodies with a double specificity in relation to basic structures of the cartilage--proteoglycans--were used. The highest concentrations of degradation products of proteoglycans in punctates of synovial fluid were found in diseases where the clinical picture is dominated by repeated attacks of the joints with longer remission periods, and where the attack is stimulated, usually by stimuli of an intermittent systemic or exogenous character (gout, reactive arthritis incl. Reiter's syndrome, Lyme disease).

PMID: 2031318 [PubMed - indexed for MEDLINE

Motility of Lyme disease spirochetes in fluids as viscous as the extracellular matrix.
Kimsey RB, Spielman A.

Department of Tropical Public Health, Harvard School of Public Health, Boston, Massachusetts.

When properties of extracellular fluids that might regulate the ability of the Lyme disease spirochete to locomote were investigated, the rate of progression correlated with viscoelasticity. Such spirochetes flexed and rotated but did not progress in relatively nonviscous fluids and migrated increasingly rapidly as the viscous characteristics of the medium increased. The viscoelastic properties of various kinds of hyaluronic acid resembled those of a methylcellulose standard. The maximum velocity that spirochetes achieved in such solutions related directly to viscoelasticity rather than to chemical composition. Spirochetes remained motile during 3 h of observation despite 100-fold dilution of the standard nutrient medium. The immobility of Lyme disease spirochetes in media less viscous in character than fixed tissue suggests dissemination via the intercellular ground substance of skin.

PMID: 2230247 [PubMed - indexed for MEDLINE]

Can anyone interpret the 3rd study? Could higher concentration of hyaluronic acid in the body, slow down the spirochetes??

Manganese is needed to make Hyaluronic Acid. BB needs manganese. BB also lowers HA. Could this be the mechanism??

I know I´m on to something with this manganese/Hyaluronic acid business but I could use help.

Edited by Lufega, 17 September 2009 - 02:16 PM.

[Lufega]

http://www.ra-infect...ticles/Lyme.htm

Chondroitin is quite similar in structure to hyaluronate (hyaluronic acid) and spoofs the spreading-factor enzymes produced by the bacteria.`

------------------------------

Binding of human plasminogen and urokinase-type plasminogen activator to the Lyme disease spirochete, Borrelia burgdorferi.

Klempner MS, Noring R, Epstein MP, McCloud B, Hu R, Limentani SA, Rogers RA

Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.

Many bacteria that spread in the skin produce enzymes that digest extracellular matrix components. Borrelia burgdorferi spreads from a skin inoculation site to form the characteristic erythema migrans skin lesion. It was determined that B. burgdorferi does not produce collagenase, elastase, hyaluronidase, or other enzymes that digest extracellular matrix components. However, B. burgdorferi bound human plasmin, plasminogen (Pgn), and urokinase-type plasminogen activator (uPA). When spirochetes were sequentially incubated with Pgn and uPA, bioactive plasmin was generated on the surface of B. burgdorferi. B. burgdorferi did not produce an endogenous Pgn activator. Fluorochrome-conjugated uPA and Pgn colocalized to the terminus of the spirochete. In a mouse model, uPA-treated B. burgdorferi were more infectious than control spirochetes. Binding of host uPA and Pgn to form a bioactive extracellular matrix protease on B. burgdorferi represents a mechanism that could facilitate dissemination and localization of spirochetes to sites of vascular injury.

UI: 95271064

So, Borrelia burg breaks down the extracellular matrix, mostly composed of HA, and this facilitates its dissemination throughout the body.

-----------------------

In this article, there is one mention of Hyaluronic acid as having an inhibitory effect. On what? BB?

http://www.paru.cas....f.php?pdf=20769

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TREATMENT OF LYME DISEASE WITH POLYSULFATED GLYCOSAMINOGLYCAN FORMULATIONS

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[Lufega]

</h2>

<h2>Enhancement of fibroblast proliferation, collagen biosynthesis and production of growth factors as a result of combining sodium hyaluronate and aminoacids.
Mariggiò MA, Cassano A, Vinella A, Vincenti A, Fumarulo R, Lo Muzio L, Maiorano E, Ribatti D, Favia G. Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy. mariada@dimo.uniba.it

Fibroblasts play a key role in tissue healing by producing the majority of extracellular matrix components, favouring granulation tissue formation, and stimulating re-epithelialization. Hyaluronan is a component of ECM and its anti-inflammatory effects and properties in enhancing wound closure are well known. In this study, we examined the effects of Aminogam gel, a new pharmacological preparation suggested to improve wound healing, composed of hyaluronic acid, proline, lysine, glycine and leucine, on human fibroblasts. Results show that fibroblasts treated with hyaluronic acid plus aminoacid solution increased their proliferative activity, collagen I and III, and fibronectin synthesis. Moreover, HA plus aminoacid solution increased the expression of transforming growth factor beta, connective tissue growth factor, interleukin-6 and -8, assayed by RT-PCR. These results suggested that Aminogam gel, involved in several stages of wound healing, as fibroblast proliferation, granulation tissue formation, ECM component deposition, and production of cytokines, may be a useful device to favour and accelerate wound closure.

PMID: 19505400 [PubMed - indexed for MEDLINE]

[Lufega]

Hyaluronan inhibits cytokine production by lipopolysaccharide-stimulated U937 macrophages through down-regulation of NF-kappaB via ICAM-1.
Yasuda T.

Department of Sports Medicine, Faculty of Health, Budo, and Sports Studies, Tenri University, Tenri 632-0071, Japan. tadyasu@sta.tenri-u.ac.jp

OBJECTIVE: This study investigated the inhibitory mechanism of hyaluronan (HA) on lipopolysaccharide (LPS)-stimulated production of proinflammatory cytokines in U937 macrophages. METHODS: HA was added to U937 macrophage cultures in the presence of LPS, with or without pretreatment with anti-intercellular adhesion molecule-1 (ICAM-1) antibody. Secreted levels of tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6 were determined by enzyme-linked immunosorbent assay. The phosphorylation of nuclear factor (NF)-kappaB, IkappaBalpha, and mitogen-activated protein kinases (MAPKs) was analyzed by immunoblotting. RESULTS: LPS stimulated production of TNFalpha, IL-1beta, and IL-6. In contrast to 800 kDa HA, 2700 kDa HA at 1 mg/ml inhibited LPS-induced cytokine production. Anti-ICAM-1 antibody blocked the effects of HA on the LPS actions on U937 cells. LPS activated NF-kappaB and MAPK pathways, whereas HA down-regulated p65 NF-kappaB and IkappaBalpha phosphorylation by LPS without affecting MAPKs. Inhibition studies revealed the requirement of NF-kappaB for LPS-stimulated cytokine production. Anti-ICAM-1 antibody reversed the inhibitory effects of HA on phosphorylation of p65 NF-kappaB and IkappaBalpha. CONCLUSION: HA of intrinsic molecular weight suppresses LPS-stimulated production of proinflammatory cytokines via ICAM-1 through down-regulation of NF-kappaB and IkappaB. Exogenous HA injected into arthritic joints could act as an anti-NF-kappaB agent by the mechanism demonstrated in the present study.

Looks like HA itself can inhibit IL-6??

[Lufega]

Interest article about HA and diabetes.

[Hyaluronic acid, receptor CD44, and their role in diabetic complications]

[Article in Ukrainian]

Ievdokimova NIu.
Hyaluronic acid (HA) is a straight chain glycosaminoglycan polymer composed of repeating units of the disaccharide [-D-glucuronic acid-beta1,3-N-acetyl-D-glucosamine-beta1,4-]n, and is found in vertebrates and certain microorganisms. The molecular weight of HA chains is usually equal to approximately 1-10 and MDa, n > 10(3-4), although it can exists as oligosaccharides under some physiological and pathological conditions. HA resides on the cell surface or in the extracellular space, but it also occurred inside the mammalian cells. HA is synthesized in mammals by three enzymes with polymers of varying chain length. The biological functions of HA include the maintenance of elastoviscosity of liquid connective tissues, control of tissue hydration, supramolecular assembly of proteoglycans in the extracellular matrix and besides numerous receptor-mediated functions in cell attachment, mitosis, migration, tumor development, wound healing and inflammation. The extensive repertoire of biological functions of HA corresponds to the existence of a large repertoire of HA-binding proteins (hyaladherins). Many hyaladherins contain a common structural domain, termed a Link module, which is involved in ligand binding. The most important member of the Link module superfamily is the main HA receptor, CD44. CD44 has diverse functions including not only the organization and metabolism of extracellular matrix, but also engage the cytoskeleton and co-ordinate signaling events to enable the cell responce to changes in the environment. HA has an extraordinary high rate of turnover, and at the cellular level it is considered to be degraded progressively by a series of enzymatic reactions that generate polymers of decreasing sizes. HA biological effects are known to be determined by the polymer size and depend on the cell type. For example, the native high molecular weight HA is anti-angiogenic, while its degradation products (6-20 saccharides) stimulate endothelial cell proliferation, migration and differentiation. In contrast, these fragments inhibit the proliferation of vascular smooth muscle cells, whereas high molecular weight HA promotes cell growth and migration. The dysregulation of HA metabolism is a typical feature of diabetes complications, and increased glucose level is considered to be the main cause of this phenomenon. The HA depolymerization due to the effect of free radicals and advanced glycation end products leads to the vitreous body liquefaction, and may be the reason of the proliferative retinopathy in diabetes. The enrichment of extracellular matrix with high molecular weight HA under the action of high glucose level was demonstrated for vascular smooth muscle cells, skin fibroblasts, endothelial and mesangial cells. This effect is considered to accelerate the development of atherosclerosis stimulating the proliferation of vascular smooth muscle cells, and to promote the transformation of acute wounds into chronic ulcers deepening the pathological state of dermal fibroblasts in diabetes. And, on the contrary, the accumulation of high molecular weight HA on the surface of endothelial cells may have positive value for the glycocalyx integrity. Since high molecular weight HA is known to possess the anti-inflammatory and anti-fibrotic effect, the enrichment of mesangial matrix with it may represent an endogenous mechanism to limit renal injury in diabetes. Thus, the investigation of HA metabolism in diabetes mellitus emphasizes the dependence of HA biological effects on cell type and demonstrates the importance of this molecule for tissue homeostasis.

[Lufega]

<h2>Enhancement of fibroblast proliferation, collagen biosynthesis and production of growth factors as a result of combining sodium hyaluronate and aminoacids.
Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy. mariada@dimo.uniba.it

Fibroblasts play a key role in tissue healing by producing the majority of extracellular matrix components, favouring granulation tissue formation, and stimulating re-epithelialization. Hyaluronan is a component of ECM and its anti-inflammatory effects and properties in enhancing wound closure are well known. In this study, we examined the effects of Aminogam gel, a new pharmacological preparation suggested to improve wound healing, composed of hyaluronic acid, proline, lysine, glycine and leucine, on human fibroblasts. Results show that fibroblasts treated with hyaluronic acid plus aminoacid solution increased their proliferative activity, collagen I and III, and fibronectin synthesis. Moreover, HA plus aminoacid solution increased the expression of transforming growth factor beta, connective tissue growth factor, interleukin-6 and -8, assayed by RT-PCR. These results suggested that Aminogam gel, involved in several stages of wound healing, as fibroblast proliferation, granulation tissue formation, ECM component deposition, and production of cytokines, may be a useful device to favour and accelerate wound closure.

PMID: 19505400 [PubMed - indexed for MEDLINE]

I wonder if this combination would be effective orally?

http://www.professio.....icle June.pdf

An amino acid-based gel
has recently been introduced to the market: L-Proline , L-Leucine, L-Lysine, Glycine
and Sodium Ialuronate (AMINOGAM® GEL). Such ingredients are supposed to
form the basis for the fibroblasts’ activity stimulating the production of extra-cell
matrix and collagen. As a consequence the product is expected to influence the tissue
repairing process after surgical incision leading to faster re-epithelize the wounded
area together with better functional recovery and less post-operative pain.

[Lufega]

Hyaluronic acid in degraded by the enzyme Hyaluronidase. These are some hyaluronidase inhibitors:

Guggul


Ascorbyl palmitate derivative

Aescins (Horse chestnut)

Butcher's broom inhibits Elastase very well. This is going to help me a lot with my alpha-1-antitrypsin problem and hopefully, halt the destruction of lung tissue. I was using BB to increase my BP but stopped because I wasn't convinced. I think this coincided with the modest increases I saw in A1AT. I guess it wasn't the SOD working here.

A1AT - wiki
Elastase is inhibited by the acute phase protein α1-antitrypsin (A1AT), which binds almost irreversibly to the active site of elastase and trypsin. A1AT is normally secreted by the liver cells into the serum. α1-antitryspin deficiency (A1AD) leads to uninhibited destruction of elastic fiber by elastase; the main result is pulmonary emphysema.

[apache]

You mention that reason you don't take hyaloronic acid is that you can't find it. Dude, it's everywhere - the Vitamin Shoppe, etc. Use Google "Shopping" search - it's a goldmine. Apart from that, it's a common ingredient in horse health supplements, so alternatively, you could just purchase a horse supplement.

[Lufega]

You mention that reason you don't take hyaloronic acid is that you can't find it. Dude, it's everywhere - the Vitamin Shoppe, etc. Use Google "Shopping" search - it's a goldmine. Apart from that, it's a common ingredient in horse health supplements, so alternatively, you could just purchase a horse supplement.

w00t? I think you misread. Can you point to where I said that?? It WOULD be funny if I did ALL this research on HA and didn't know that CVS was selling it, wouldn't it?. I'm going to add HA to my stack once again. Seems like small molecular HA stimulates fibroblasts to produce more. Here's the apparent logic behind that:


http://www.smartskin...ronic-acid.html

It is important to note that physiological effects of hyaluronic acid depend to a large degree on the size (molecular weight) of its chains. In particular, relatively small HA molecules (weighing less than about 20,000 Da) appear to trigger the early phases of wound healing, including activation of various types of immune cells and inflammatory responses. This is understandable. Considering that tissue injury would typically result in increased degradation of extracellular matrix (and HA in particular), it makes sense that the degradation fragments (i.e. small size HA fragments) would act as indicators of injury and trigger wound healing. On the other hand, large HA molecules appear to suppress local immune response and inflammation. By the similar logic, the predominance of large HA molecules sends a signal that the skin is intact and defense and/or repair are not required.

Edited by Lufega, 23 September 2009 - 03:54 AM.

[Lufega]

Hyaluronic acid protects against lipofuscin induced oxidative stress.

Perineuronal nets potentially protect against oxidative stress.

Morawski M, Brückner MK, Riederer P, Brückner G, Arendt T.
Department of Neuroanatomy, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, D-04109, Germany.

A specialized form of extracellular matrix (ECM) termed perineuronal nets (PNs) consisting of large aggregating chondroitin sulfate proteoglycans (CSPGs), with hyaluronan and tenascin as main components, surrounds subpopulations of neurons. The glycosaminoglycan components of perineuronal nets form highly charged structures in the direct microenvironment of neurons and thus might be involved in local ion homeostasis. The polyanionic character suggests that perineuronal nets also potentially contribute to reduce the local oxidative potential in the neuronal microenvironment by scavenging and binding redox-active iron, thus providing some neuroprotection to net-associated neurons. Here, we show that neurons ensheathed by a perineuronal net in the human cerebral cortex are less frequently affected by lipofuscin accumulation than neurons without a net both in normal-aged brain and Alzheimer's disease (AD). As lipofuscin is an intralysosomal pigment composed of cross-linked proteins and lipids generated by iron-catalyzed oxidative processes, the present results suggest a neuroprotective function of perineuronal nets against oxidative stress, potentially involved in neurodegeneration.

[Lufega]

Aloe Vera stimulated HA production

[Influence of Aloe polysaccharide on proliferation and hyaluronic acid and hydroxyproline secretion of human fibroblasts in vitro.]

Provincial Burns Institute, Union Hospital, Fujian Medical University, Fuzhou 350001, Fujian Province, China;E-mail: fzxdchen@sina.com.
Abstract

Objective: To investigate the effect of Aloe polysaccharide on proliferation and hyaluronic acid and hydroxyproline secretion of human fibroblasts in vitro. Methods: The fibroblasts were treated with different doses of polysaccharide (0, 25, 50, 100, 200, 400 mg/L). Subsequently, cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, cell cycle by flow cytometry, evaluation of the Aloe polysaccharide toxic effect by acridine orange-ethidium bromide staining, evaluation of the cell injury by lactate dehydrogenase (LDH) assay, and the collagen synthesis by (3)H-proline incorporation. In addition, hyaluronic acid and hydroxyproline levels in the supernatants of cultured fibroblasts were measured by enzyme-linked immunosorbent assay. Results: The proliferation of fibroblasts was induced with polysaccharide in a dose-dependent manner, reaching its highest level on 5th day. Meanwhile, the percentage of cells at phase G0/G1 was decreased, while that at phases G(2)/M and S was increased significantly in Aloe polysaccharide-treated groups as compared with those in the control group (P<0.05). Additionally, the apoptosis of the fibroblasts showed no differences among all groups. The collagen synthesis was increased and cell injury decreased in polysaccharide-treated groups as compared with those in control group (P<0.05), while the levels of hyaluronic acid and hydroxyproline in the supernatants of fibroblasts treated with polysaccharide were significantly higher than those in the control group (P<0.05). Conclusion: The Aloe polysaccharide promotes both the proliferation of fibroblasts and the production of hyaluronic acid and hydroxyproline in fibroblasts. This indicates that the Aloe polysaccharide may play an important role in the extracellular matrix remodeling during wound healing.

Influence of Aloe vera on the glycosaminoglycans in the matrix of healing dermal wounds in rats.


Department of Biochemistry, Central Leather Research Institute, Madras, India.
Abstract

The influence of Aloe vera (L.) Burman f. on the glycosaminoglycan (GAG) components of the matrix in a healing wound was studied. Wound healing is a dynamic and complex sequence of events of which the major one is the synthesis of extracellular matrix components. The early stage of wound healing is characterized by the laying down of a provisional matrix, which is then followed by the formation of granulation tissue and synthesis of collagen and elastin. The provisional matrix or the ground substance consists of GAGs and proteoglycans (PGs), which are protein GAG conjugates. In the present work, we have studied the influence of Aloe vera on the content of GAG and its types in the granulation tissue of healing wounds. We have also reported the levels of a few enzymes involved in matrix metabolism. The amount of ground substance synthesized was found to be higher in the treated wounds, and in particular, hyaluronic acid and dermatan sulphate levels were increased. The levels of the reported glycohydrolases were elevated on treatment with Aloe vera, indicating increased turnover of the matrix. Both topical and oral treatments with Aloe vera were found to have a positive influence on the synthesis of GAGs and thereby beneficially modulate wound healing.

PMID: 9507902 [PubMed - indexed for MEDLINE]

[KimberCT]

Good for heart valves as well.

[NeuroGuy]

So have you decided to take a certain regime for this?

[Lufega]

I take HA itself plus NAG and I mix aloe in a smoothie I drink daily.

[NeuroGuy]

I'm trying to raise production of HA too...my only concern is the mixed feelings of Glycosamine on the brain.


http://cancerres.aac..._Part_1/912.pdf - Bottom right hand side of first page,

observed that glucosamine is phosphorylated by ATP in the presense of hexokindase from brain tissue and that the rate of acetylcholine synthesis in brain extracts is inhibited by the presence of D-glucosamine

Dont have the link for this second abstract, I found it on a futurepundit.com comment on an alzheimers article,

Abstract:

The role of polysaccharides in the pathogenesis of Alzheimer disease (AD) is unclear. However, in light of studies indicating impaired glucose utilization in AD and increased activation of the hexosamine pathway that is seen with hyperglycemia, in the brains of patients with AD, aberrantly high levels of glucosamine may result in synthesis of glucosamine polymers such as chitin, a highly insoluble polymer of N-acetyl glucosamine, linearized by b1-4 linkages. To examine this further, we studied brain tissue at autopsy from subjects with sporadic and familial AD using calcofluor histochemistry. Calcofluor excites on exposure to ultraviolet light and exhibits a high affinity for chitin in vivo by interacting with b1-4 linkages. Amyloid plaques and blood vessels affected by amyloid angiopathy showed bright fluorescence. Moreover, treatment with chitinase, followed by b-N-acetyl glucosaminidase showed a decrease in calcofluor fluorescence. Since chitin is a highly insoluble molecule and a substrate for glycan-protein interactions, chitin-like polysaccharides within the brain could facilitate nucleation of amyloid proteins in various amyloidoses including AD.
Keywords: alzheimer disease; amyloid; chitin; n-acetyl glucosamine

Document Type: Review article

DOI: 10.2174/156720505774330555

Affiliations: 1: Department of Pathology, Robert C. Byrd Health Sciences, Center of West Virginia University, P.O. Box 9203, Morgantown, WV 26506-9203, USA.

Edited by NeuroGuy, 26 April 2010 - 07:04 PM.

[Lufega]

Neuroguy,

It's difficult to interpret that. For example, when cirrhosis occurs in the liver, there are deposits of collagen, GAG's and hyaluronic acid combined in such a way to replace normal tissues and cells. But this process is pathological and not seen under normal circumstances. So we must not think that collagen, GAG and HA, even that administered exogenously, will lead to cirrhosis.

What we need to investigate from those two links you posted is under WHAT conditions are these changes seen? Other than, I don't see a reason to worry.

Edited by Lufega, 27 April 2010 - 05:38 AM.

[niner]

I'm trying to raise production of HA too...my only concern is the mixed feelings of Glycosamine on the brain.

http://cancerres.aac..._Part_1/912.pdf - Bottom right hand side of first page,

observed that glucosamine is phosphorylated by ATP in the presense of hexokindase from brain tissue and that the rate of acetylcholine synthesis in brain extracts is inhibited by the presence of D-glucosamine

Yeah, but it's in vitro. Does glucosamine cross the BBB? Glucose certainly gets in. Even if it gets in, are the conditions even close to those in the in vitro work?

[NeuroGuy]

Neuroguy,

It's difficult to interpret that. For example, when cirrhosis occurs in the liver, there are deposits of collagen, GAG's and hyaluronic acid combined in such a way to replace normal tissues and cells. But this process is pathological and not seen under normal circumstances. So we must not think that collagen, GAG and HA, even that administered exogenously, will lead to cirrhosis.

What we need to investigate from those two links you posted is under WHAT conditions are these changes seen? Other than, I don't see a reason to worry.

You have a really good point...I should've considered that first bit, and like you said, under what conditions chitin and other glucosamine polymers are increased might be recommended to know if your going to supplement glucosamine.


Still it should be noted, if that first study I posted has any truth to it, that if your mood improves on glucosamine a slight anti-cholinergic effect could atleast partly be responsible.


Edit: Niner, from what I remember it does a small amount, but part of the reason for supplementing N-acetylglucosamine is it crosses the BBB more readily. I'l try to find links.

Edited by NeuroGuy, 27 April 2010 - 11:28 AM.

[Lufega]

Neuroguy,

If NAG can have a noticeable anti-cholinergic effect, this worries me. I need to be on a pro-cholinergic status at all times!

Found this:

Action of glucosamine on acetylcholine-sensitive channels.
Marchais D, Marty A.

Abstract
The action of glucosamine was studied on voltage clamped neurones of Aplysia, presenting an excitatory response to acetylcholine. Noise and relaxation experiments show that glucosamine increases the mean channel open time and reduces the amplitude of the elementary current associated with the acetylcholine response. Both effects are enhanced by hyperpolarization of the cell membrane. The results are interpreted by a model assuming glucosamine binding to open channels. This binding impedes the flow of permeant ions and decreases the closing rate of the channels.

[NeuroGuy]

Neuroguy,

If NAG can have a noticeable anti-cholinergic effect, this worries me. I need to be on a pro-cholinergic status at all times!

Found this:

Action of glucosamine on acetylcholine-sensitive channels.
Marchais D, Marty A.

Abstract
The action of glucosamine was studied on voltage clamped neurones of Aplysia, presenting an excitatory response to acetylcholine. Noise and relaxation experiments show that glucosamine increases the mean channel open time and reduces the amplitude of the elementary current associated with the acetylcholine response. Both effects are enhanced by hyperpolarization of the cell membrane. The results are interpreted by a model assuming glucosamine binding to open channels. This binding impedes the flow of permeant ions and decreases the closing rate of the channels.

I hear ya there...unfortunately my anecdotal report agrees with this anti-cholinergic effect. I've been taking 1000mg Glucosamine sulfate for about 6 days, and each day about 1-2 hours after I get a noticeable moodlift. I'd pass it off as placebo, but my girlfriend also noted it, she follows through with everything I take as well and guessed it was the glucosamine without knowing about this effect.

Until I get my methylb12 shots, I've actually started using it for social events

[Alec]

Vitamin A can stimulate HA synthesis in keratinocytes. This is good, you can get good amounts of it in many multivitamins.

J Invest Dermatol. 1989 Mar;92(3):326-32.

Hyaluronate accumulation in human epidermis treated with retinoic acid in skin organ culture.
Tammi R, Ripellino JA, Margolis RU, Maibach HI, Tammi M.

Department of Anatomy, University of Kuopio, Finland.

Abstract
Retinoic acid (RA) has been shown to retard the differentiation of epidermal keratinocytes by several morphologic and biochemical criteria. In this study, the epidermal content and localization of hyaluronate (HA), as well as its synthesis and disappearance in human skin organ culture, were characterized to test the idea that some of the RA influences on epidermal differentiation are associated with keratinocyte HA metabolism. RA stimulated the incorporation of 3H-glucosamine into HA by up to 60% at concentrations between 50 nM and 5 microM, while pulse-chase experiments revealed little change in its disappearance rate from epidermis. After 5 d in culture, the chemically quantified HA was more than doubled in the treated epidermis. The accumulation of HA was substantiated by light and electron microscopy with a specific probe prepared from the HA binding region of cartilage proteoglycan. The staining was particularly enhanced between the upper spinous cell layers, where the terminal differentiation into corneocytes normally takes place. A patchy, discontinuous staining was also seen in stratum granulosum and corneum layers, which are not stained at all in control cultures. The present study demonstrates that RA leads to an accumulation of HA in the superficial layers of epidermis by stimulating its synthesis in keratinocytes. This may account for the delay in terminal differentiation, and the weakened cohesion of the keratinocytes previously observed both in vivo and vitro.

[JLL]

Vitamin A can stimulate HA synthesis in keratinocytes. This is good, you can get good amounts of it in many multivitamins.

J Invest Dermatol. 1989 Mar;92(3):326-32.

Hyaluronate accumulation in human epidermis treated with retinoic acid in skin organ culture.
Tammi R, Ripellino JA, Margolis RU, Maibach HI, Tammi M.

Department of Anatomy, University of Kuopio, Finland.

Abstract
Retinoic acid (RA) has been shown to retard the differentiation of epidermal keratinocytes by several morphologic and biochemical criteria. In this study, the epidermal content and localization of hyaluronate (HA), as well as its synthesis and disappearance in human skin organ culture, were characterized to test the idea that some of the RA influences on epidermal differentiation are associated with keratinocyte HA metabolism. RA stimulated the incorporation of 3H-glucosamine into HA by up to 60% at concentrations between 50 nM and 5 microM, while pulse-chase experiments revealed little change in its disappearance rate from epidermis. After 5 d in culture, the chemically quantified HA was more than doubled in the treated epidermis. The accumulation of HA was substantiated by light and electron microscopy with a specific probe prepared from the HA binding region of cartilage proteoglycan. The staining was particularly enhanced between the upper spinous cell layers, where the terminal differentiation into corneocytes normally takes place. A patchy, discontinuous staining was also seen in stratum granulosum and corneum layers, which are not stained at all in control cultures. The present study demonstrates that RA leads to an accumulation of HA in the superficial layers of epidermis by stimulating its synthesis in keratinocytes. This may account for the delay in terminal differentiation, and the weakened cohesion of the keratinocytes previously observed both in vivo and vitro.

Wouldn't this apply to topical application of retinoids rather than consuming vitamin A?

[Alec]

Vitamin A can stimulate HA synthesis in keratinocytes. This is good, you can get good amounts of it in many multivitamins.

J Invest Dermatol. 1989 Mar;92(3):326-32.

Hyaluronate accumulation in human epidermis treated with retinoic acid in skin organ culture.
Tammi R, Ripellino JA, Margolis RU, Maibach HI, Tammi M.

Department of Anatomy, University of Kuopio, Finland.

Abstract
Retinoic acid (RA) has been shown to retard the differentiation of epidermal keratinocytes by several morphologic and biochemical criteria. In this study, the epidermal content and localization of hyaluronate (HA), as well as its synthesis and disappearance in human skin organ culture, were characterized to test the idea that some of the RA influences on epidermal differentiation are associated with keratinocyte HA metabolism. RA stimulated the incorporation of 3H-glucosamine into HA by up to 60% at concentrations between 50 nM and 5 microM, while pulse-chase experiments revealed little change in its disappearance rate from epidermis. After 5 d in culture, the chemically quantified HA was more than doubled in the treated epidermis. The accumulation of HA was substantiated by light and electron microscopy with a specific probe prepared from the HA binding region of cartilage proteoglycan. The staining was particularly enhanced between the upper spinous cell layers, where the terminal differentiation into corneocytes normally takes place. A patchy, discontinuous staining was also seen in stratum granulosum and corneum layers, which are not stained at all in control cultures. The present study demonstrates that RA leads to an accumulation of HA in the superficial layers of epidermis by stimulating its synthesis in keratinocytes. This may account for the delay in terminal differentiation, and the weakened cohesion of the keratinocytes previously observed both in vivo and vitro.

Wouldn't this apply to topical application of retinoids rather than consuming vitamin A?

No. Most of these creams are most likely useless.

See these:

The human hyaluronan synthase 2 gene is a primary retinoic acid and epidermal growth factor responding gene

All-trans retinoic acid-induced hyaluronan production and hyperplasia are partly mediated by EGFR signaling in epidermal keratinocytes

[JLL]

Retinoid creams are useless? Me and a zillion others would disagree. Or do you mean just useless regarding hyaluronic acid?

Not sure how the studies you posted prove/disprove your point.

[Alec]

Retinoid creams are useless? Me and a zillion others would disagree. Or do you mean just useless regarding hyaluronic acid?

Not sure how the studies you posted prove/disprove your point.

What I said was, "most" of these creams are most likely useless. A lot of them also have other ingredients that are probably bad for your skin. I'm sure there are some good creams out there. But still, I'd rather not use them. The studies just have more info on a RA/HA connection.

[paymanz]

taurine is also very important for connective tissue health.