Garlic anti-arthritis

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Hi All,

See the below introduction and pdf-available not in Medline yet paper suggesting

that garlic benefits lessens arthritis.

Tuesday, August 16, 2005 Posted: 1420 GMT (2220 HKT)

RELATED • Proceedings of the National Academy of Sciences

Garlic: It hurts so go0d

WASHINGTON (AP)

-- People tend to love garlic or hate it, but few probably associate it with

pain.

Nonetheless, it turns out that pain-sensing nerves respond to the sulfur-based

chemicals in garlic.

Indeed, the same mechanism the body uses to react to the sharpness of chili

peppers

and spicy condiments like mustard and wasabi is the one that detects garlic,

according to a study in Tuesday's Proceedings of the National Academy of

Sciences.

Julius of the department of cellular and molecular pharmacology at the

University of California, San Francisco, said the finding was made during

research

on the mechanisms of pain sensation.

Julius discovered that when a subset of pain neurons in rats activates a cell

membrane channel called TRPA1 the result is a release of brain chemicals that

stimulate blood vessel dilation and inflammation.

Understanding how such nerves work, he said, can help researchers learn more

about

how arthritis and some muscular problems develop.

" You can use these natural products as very interesting pharmacological probes

of

the pain pathways, " Julius explained.

Travers of Ohio State University said the most interesting finding of the

paper is that the neurons that respond to garlic compounds are only a subset of

those that respond to the capsaicin in hot peppers.

This type of specificity would give some basis for why people can tell the

compounds

apart, said Travers, who was not part of Julius' research team.

Garlic, sometimes called the stinking rose, belongs to the group of plants

called

allium, which also includes onions, leeks, chives and shallots. All of them

produce

sulfur-based compounds that make them pungent. One, called allicin, actives the

set

of pain sensors and is especially prominent in garlic.

In addition to its culinary properties, garlic has a long history of use in folk

medicine, having been used to treat such ailments as high blood pressure, high

cholesterol and even blood clots.

Capsaicin, the chemical that gives hot peppers their heat, is currently a major

ingredient in a cream used by arthritis sufferers.

This and similar studies " clearly do not explain the complex sensory experience

that

this ingredient lends to food. It seems likely that garlic also stimulates

olfactory

receptors, and the olfactory system is probably largely responsible for garlic's

distinctive aroma, and yet other compounds stimulate specific receptors in taste

buds, " Travers said.

Many cooks know that roasted garlic produces a much milder taste than the raw

bulbs

and Travers noted that a separate study had found that baking garlic eliminated

its

ability to stimulate the TRPA1 channels.

The pdf-available paper is:

M. Bautista, Pouya Movahed, Hinman, Helena E. Axelsson, Olov

Sterner,

D. Högestätt, Julius, Sven- Jordt, and M. Zygmunt

Pungent products from garlic activate the sensory ion channel TRPA1

PNAS published August 15, 2005, 10.1073/pnas.0505356102

Garlic belongs to the Allium family of plants that produce organosulfur

compounds,

such as allicin and diallyl disulfide (DADS), which account for their pungency

and

spicy aroma. Many health benefits have been ascribed to Allium extracts,

including

hypotensive and vasorelaxant activities. However, the molecular mechanisms

underlying these effects remain unknown. Intriguingly, allicin and DADS share

structural similarities with allyl isothiocyanate, the pungent ingredient in

wasabi

and other mustard plants that induces pain and inflammation by activating TRPA1,

an

excitatory ion channel on primary sensory neurons of the pain pathway. Here we

show

that allicin and DADS excite an allyl isothiocyanate-sensitive subpopulation of

sensory neurons and induce vasodilation by activating capsaicin-sensitive

perivascular sensory nerve endings. Moreover, allicin and DADS activate the

cloned

TRPA1 channel when expressed in heterologous systems. These and other results

suggest that garlic excites sensory neurons primarily through activation of

TRPA1.

Thus different plant genera, including Allium and Brassica, have developed

evolutionary convergent strategies that target TRPA1 channels on sensory nerve

endings to achieve chemical deterrence.

.... Discussion

Plants have evolved ingenious defensive strategies to ward off

herbivorous predators. In many cases this is achieved through the

production of chemical agents that produce irritation and in-f

lammation (26, 27). Our findings support an emerging theme

whereby irritants such as capsaicin, isothiocyanates, and thio-sulfinates

produce their psychophysical effects by targeting

excitatory TRP channels on primary afferent nerve fibers of the

pain pathway. Moreover, the ability of these agents to produce

neurogenic inflammation and vasodilation can be attributed to

the fact that their molecular sites of action (TRPV1 and TRPA1)

are expressed on neurons whose activation leads to the periph-eral

release of CGRP, substance P, and other inflammatory

neurotransmitters.

Garlic has for centuries been appreciated for its culinary and

medicinal properties, which likely reflect its effects on olfactory,

gustatory, and somatosensory systems. Here we have focused on

understanding the molecular basis of garlic’s somatosensory

actions, which contribute to its pungent and vasodilatory actions.

Namely, we have shown that allicin and DADS, two of the main

pungent ingredients of garlic, directly activate TRPA1 on sen-sory

neurons of the trigeminal ganglia and DRG.

Several lines of evidence suggest that TRPA1 is the major,

if not sole site of isothiocyanate and garlic derivative action on

nociceptive sensory neurons. First, our functional studies show

complete overlap between AITC and allicinDADS sensitive

neurons; that is, no cells were found to respond to one agonist

but not the other. Second, the cellular pattern of TRPA1

expression based on histochemical analyses is consistent with

functional imaging studies. Third, calcium responses, mem-brane

currents, and vasodilatory actions are inhibited by

ruthenium red, a blocker of TRPA1 (and TRPV1) channels on

sensory neurons. In contrast, capsazepine, a TRPV1-specific

blocker had no effect on responses to AITC, allicin, or DADS.

At the same time, no differences were observed in either the

magnitude or prevalence of allicinDADS-evoked responses in

sensory neurons from WT or TRPV1-deficient mice. This

result suggests that TRPV1 does not contribute significantly to

the pungent effects of these compounds in vivo.

Animal studies indicate that garlic extracts and garlic deriv-atives

may have beneficial cardiovascular effects. For example,

garlic has been found to reduce hypertension and to lower serum

cholesterol levels (29, 30). Our data indicate that garlic extracts

and garlic derivatives can, indeed, mediate vasodilation through

activation of TRPA1 channels on sensory neurons in vitro.It

remains to be established whether this mechanism contributes to

the systemic hypotensive activity of garlic in vivo. Moreover,

whether garlic has beneficial effects on human cardiovascular

health remains controversial (6). Future genetic and pharma-cological

studies will help to resolve these issues.

However, as discussed above, we found no significant effect of garlic

extract and derivatives on native TRPV1.

Al Pater, PhD; email: old542000@...

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