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Joined: Jun 20, 2004 Posts: 1040 Location: Tennessee
Posted: Sat Nov 06, 2004 9:04 am Post subject: Allicin (garlic) & ALA as VLA-4 antagonists
Hey....here's something VERY interesting!
Looks like there are some additional "dietary" methods to possibly use, also, if an MSer is undergoing inflammation (remember, not all MSers experience inflammation - i.e. progressive MS), but this might be interesting to RRMSers particularly!
Deb
Immunology. 2004 Apr;111(4):391-9. Related Articles, Links
Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression.
Sela U, Ganor S, Hecht I, Brill A, Miron T, Rabinkov A, Wilchek M, Mirelman D, Lider O, Hershkoviz R.
Department of Immunology, The Weizmann Institute of Science, Rehovot 76 100, Israel. uri.sela@weizmann.ac.il
Allicin, a major ingredient of fresh garlic extract that is produced during the crushing of garlic cloves, exerts various beneficial biological effects, including a broad spectrum of antimicrobial activity, antihyperlipidaemic and antihypertensive effects. However, how allicin affects the immune system is less well known, and its effect on human T cells has never been studied. Here, we examined the in-vitro effects of allicin on the functioning of T cells related to their entry to inflamed extravascular sites. We found that allicin (20-100 microm) inhibits the SDF-1alpha (CXCL12)-induced T cell migration through fibronectin (FN), and that this inhibition is mediated by the down-regulation of (i) the reorganization of cortical actin and the subsequent T cell polarization, and (ii) T cell adhesion to FN. Moreover, allicin also inhibited T cell adhesion to endothelial cells and transendothelial migration. The mechanisms underlying these inhibitory effects of allicin are associated with its ability to down-regulate the phosphorylation of Pyk2, an intracellular member of the focal adhesion kinases, and to reduce the expression of the VCAM-1- and FN-specific alpha4beta1-integrin (VLA-4). The ability of allicin to down-regulate these chemokine-induced and VLA-4-mediated T cell functions explains its beneficial biological effects in processes where T cells play an important role and suggests that allicin may be used therapeutically with chronic inflammatory diseases.
PMID: 15056375 [PubMed - indexed for MEDLINE]
Last edited by OddDuck on Sat Nov 06, 2004 9:25 am; edited 1 time in total
Portland Veterans Affairs Medical Center, Portland, Oregon.
We have demonstrated previously the ability of the antioxidant alpha lipoic acid (ALA) to suppress and treat a model of multiple sclerosis (MS), relapsing experimental autoimmune encephalomyelitis (EAE). We describe the effects of ALA and its reduced form, dihydrolipoic acid (DHLA), on the transmigration of human Jurkat T cells across a fibronectin barrier in a transwell system. ALA and DHLA inhibited migration of Jurkat cells in a dose-dependent fashion by 16-75%. ALA and DHLA reduced matrix metalloproteinase-9 (MMP-9) activity by 18-90% in Jurkat cell supernatants. GM6001, a synthetic inhibitor of MMP, reduced Jurkat cell migration, but not as effectively as ALA and DHLA did. Both ALA and DHLA downmodulated the surface expression of the alpha4beta1 integrin (very late activation-4 antigen; VLA-4), which binds fibronectin and its endothelial cell ligand vascular cell adhesion molecule-1 (VCAM-1). Moreover, ALA, but not DHLA, reduced MMP-9-specific mRNA and extracellular MMP-9 from Jurkat cells and their culture supernatants as detected by relative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. ALA and DHLA inhibited Jurkat cell migration and have different mechanisms for inhibiting MMP-9 activity. These data, coupled with its ability to treat relapsing EAE, suggest that ALA warrants investigation as a therapy for MS. (c) 2004 Wiley-Liss, Inc.
Joined: Feb 02, 2004 Posts: 864 Location: California, USA
Posted: Sat Nov 06, 2004 5:27 pm Post subject:
So Deb, given what you've posted in the VLA-4 Antagonist thread, would you also feel that ALA also pose a pregnancy risk for women of child-bearing age? If not, what do you feel is the difference?
Joined: Jun 20, 2004 Posts: 1040 Location: Tennessee
Posted: Sat Nov 06, 2004 10:42 pm Post subject:
It's the potency, Arron. An actual drug VLA-4 antagonist, such as Antegren, is FAR more potent. There's really no comparison in the strength between dietary aids and a drug such as Antegren. To slightly inhibit VLA-4 and to BLOCK VLA-4 are totally separate things.
Stengthening the BBB via VLA-4 antagonism isn't necessarily a bad thing. It's the "chronic" use, the dose, method of delivery, and how far you go with it that's the probable problem (that even Biogen itself found). You couldn't eat enough garlic to pose the level of VLA-4 antagonism that you will get with chronic infusion of a drug as potent as Antegren.
Plus, as you will notice, those same substances (ALA and allicin) also do other things in addition to inhibiting VLA-4 (which makes a big difference), and work via different pathways, too. ALA and allicin reach the bloodstream after digestion, also.
It's just like with anything. This sounds sort of blatant, but think of the difference between drinking a drink of alcohol, for instance, as opposed to shooting it straight into your bloodstream.
Plus, as I mentioned before, a VLA-4 antagonist DRUG is specific for acting ONLY via that one mechanism of action - to block VLA-4. There is no broad spectrum of action. For another example, maybe, think of the difference between rubbing cortisone cream on your skin, as opposed to getting a shot right into your joint. There is a difference....a big one.
The method of delivery, and the additional mechanisms of action that any substance produces physiologically make big differences.
That's what concerns me. A substance such as Antegren only acts on ONE thing and that's it. Where's the "balance"?
Plus, remember...........this isn't something I put together. I simply found what laboratory tests and other clinical researchers found, and I just told you about it. That's it. It's not a "theory" of mine. I just related facts as I located them. I tried like hell (excuse my language) to find ANYTHING that contradicted those clinical researchers' findings.
The real question is, what are they going to do with the information that they know about? Bottom line is, if I know about the risk, you can bet they do, too.
Remember, Vioxx itself is only an NSAID (just like ibuprofen). The problem with Vioxx was its strength. An NSAID is still a useful drug, just not at the strength and for the chronic ongoing use like Vioxx was prescribed for.
I still say that something like Antegren might prove to be more helpful utilized similarly to a steroid on an acute basis, but not a chronic one (and this one IS my supposition only).
You can't take a steroid for long periods of time, either. But are there dietary substances that work similary to a steroid? Sure! But you can't eat enough of them to work like a steroid drug can do. But those same dietary substances can help keep your body in balance. Same principal.
I hope this helps explain? I know it all seems to be the same thing, but truly.........it's not.
Deb
EDIT: Plus, remember.........a weak BBB isn't the only physiological process that is going on in MS. If that's all that was needed, then Antegren would be a "cure", wouldn't it?
SECOND EDIT: Ok...think of it this way. Since we know that some of the CRABS also inhibit VLA-4 AND have other mechanisms of action which may help produce more balance, then why risk taking Antegren at all? Stick with a CRAB that helps do the same thing. Like I said, there are just too many questions, and this simply gives me an uncomfortable feeling. Over the years, I've just learned to not ignore my gut feelings. But it is yet to be determined.
THIRD EDIT: LOL Well, I thought of another example. Green tea, for example. They find it is a good supplement for inhibiting tumor growth and warding off cancer (laboratory proven). But........is it the same as chemotherapy? No.
Joined: Jun 18, 2004 Posts: 1472 Location: Bedfordshire UK
Posted: Tue Nov 09, 2004 5:03 am Post subject:
Quote:
You couldn't eat enough garlic to pose the level of VLA-4 antagonism that you will get with chronic infusion of a drug as potent as Antegren.
.........and if you could you wouldn't be very popular! Garlic does seem to be enormously good for many things quite apart from MS, though. We grow it by the ton and eat it at slightly lower amounts.
Joined: Jun 20, 2004 Posts: 1040 Location: Tennessee
Posted: Tue Nov 09, 2004 7:08 am Post subject:
Sarah,
You know.........I'm asked that a lot! I think I should ask for a raise at work then, huh? The only thing I can think of is that I MUST speed-read (without realizing it), and I have been told I multi-task and handle large volumes of material and workload in a way that's amazing or something. Doesn't seem like much to me!
Shoot.......I do lots of stuff! Work, sleep, eat, go places with my son, watch tv (a lot.... ) Lay around when I should be mowing the lawn. You know.....all the regular stuff.
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