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Update 26.07.2023 ACHTUNG mein Hoster hat vor kurzem ein merkwürdiges Problem "aus dem Nichts" erzeugt...Links enthalten beim ersten Laden einer Forums-Seite offenbar manchmal eine "PHP Session ID" mitten im Link (also im "Inline Link", also "von außen nicht sichtbar", außer, wenn man über den Link mit der Maus fährt), was dazu führt, dass man, wenn man auf einen solchen Link klickt, auf der Hauptseite des Forums oder wieder auf genau der Seite, von der man ausgegangen ist, landet, d.h. man wird im Kreis geschickt bzw. zur Hauptseite zurückgeführt und kommt nie zum Ziel-Link. Wenn das passiert, bitte die ganze Seite mit den defekten Links im Browser NEU LADEN, d.h. STRG + F5 drücken, bzw. STRG + R drücken, damit der Browser gezwungen wird, die Seite neu zu laden, dann verschwinden alle "PHP Session IDs" aus den Links und die Links auf der Seite funktionieren wieder ganz normal.

Update 26th of July 2023: A strange problem emerged out of the blue, probably caused by my current hoster...if links do not properly work, the reason probably is that a "PHP Session ID" is added to the link (for whatever reason), in this case, reload the page (CTRL + F5 or CTRL + R in most browsers) and the link will work properly again!! This only applies to links which lead to this forum here, all other links works, except .de.vu links, as the old forwarding service does not exist anymore. You can learn how to easily repair .de.vu links in the following link (see below).

Die im Forum an verschiedenen Stellen enthaltenen, nicht mehr funktionierenden .de.vu Links - das war ein Weiterleitungsdienst, der leider seinen Betrieb komplett eingestellt hat - können folgendermaßen "repariert" werden: http://meulengrachtforum.altervista.org/forum/index.php/topic,1161.msg4069.html#msg4069

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811
User introduction / Please introduce yourself here in this thread
« am: 02. September 2006, 21:02:48 »
Hello,

this thread is for introducing yourself.

As I did not introduce myself too I will do it now...

I am Medizinmann99 (well, thats not my real name indeed) from Austria (thats in Central Europe  ;D ) , I am 28 years old and have been diagnosed with GS some years ago. My mother tongue is german but I can speak english as well (at least to a certain extent).

Still I considered GS to be an illness without any consequences as probably many of you also thought in the first place.

Recently, I realized by doing some research on the topic that GS is NOT a symptome free illness but that it has a lot of consequences...and that is is individually different, some people hardly notice it, some people have it quite severe and others have it so severe that they are basically not able to do a full time job anymore.

And as I saw that the english EZ Board is partially falling apart ("missing post that cannot be restored" messages...lol) and that another german board obviously did not have an admin (so no backups there) I decided to found another board.  I know the internet quite well in the meantime and I know that every board or internet presence that is not maintained has a habit of disappearing in the electronic nirvana - somewhen, usually it does not take very long according to the internets "flux speed". My idea is that this should not happen here therefore I make regular forum backups and with them I can transfer the forum anywhere, the address always stays
www.meulengracht.de.vu
(forwarding service that always "points" to the real forum location).

I do not have GS very severely personally, but I think "it is sufficient" lol and therefore I also have a significant interest to get completely symptome free...

:-)

So much,

Medizinmann99

812
Hello and welcome to Gilberts Syndrome forum :)

This forum here gets backed up regularly, it is always at the location
http://www.meulengracht.de.vu

(= a forwarder that forwards to the actual forum location).

We currently have 2 admins Bigmam and me (Medizinmann99).

Altough I fear bigmam is not so familiar with the english language, she will still be able to run the forum if for example an asteroid from outer space falls on my head (or something). So the forum should be "future proof", at least to a certain extent :-)

Please act accordingly to what you agreed to do or not to do in the registration agreement - plus the below mentioned things :) :

Please participate in the forum, especially when you can provide information that others might not yet have.

So please if you have a valuable information that others probably dont, make a posting (preferrably in the appropriate subboard if it already exists, if not just make it one board above) so that others can benefit from your information.


You can do so for example when you do a blood test (report your bilirubine levels) and then take some substances that are supposed to help with GS you can report back and also report the results of a 2nd blood test if the substances helped you. Or you can post personal experience reports with medicines and stuff that you think helped you. Etc. etc. etc. I think you get the idea. 

Also, as in my personal opinion having Gilberts Syndrome is already enough a pain in the ass I also ask you to also share good and cheap suppliers for drugs and medicines that might help with gilberts syndrome so that people here can save money too because every medicine costs money and money is "rare" (currently we have the 2nd big world depression thanks to our greatest and best system, capitalism).

But remember that money is not everything when it comes to medicines, also the quality needs to be right, it does not serve anyone to get "double poisoned" by the reduced detoxification ability that comes with GS and by a substandard or worthless medicine bought at some fraudulent backstreet vendor.

Still, the price differences regarding medicines are often ridiculous and you can very often get 1:1 the same medicine from some other vendor for a much, much lower price (I have some ridiculous examples about all this what shows how big the profit span is in many cases...).
This is what I am talking about, please share such information if you found such a good source or if you can see on this forum that all known other sources are more expensive. I think you get the idea  :)

If you see some information on any other board that you consider to be important please make a thread and copy it here into my board or notify me of it. Forums come and go because hosters pop up and die all the time and most forum hosters are too silly to make regular forum backups (also, many forum hosters dont even offer the possibility to backup the forum, because this costs A LOT of bandwith and bandwith costs money). It is always advisable to have important information stored in as many places as possible. It does not harm anyone to have the same information double and triple, but it does harm one if the information does not exist at all because then someone might be missing out an important information that might have helped him or her. Just watch the english EZ Board which has a habit of continually falling apart and loosing postings ("posting missing and cannot be restored"). In some threads, I would really be interested "what was there" but it is impossible to find that out now, as it disappeared in the electronic nirvana.

So much for the moment,

Medizinmann99
Forum Administrator

813
How to register / How to register
« am: 02. September 2006, 13:51:05 »
If you have any problems with the below mentioned registering process please write an email to
medicineman9
AT
protonmail
DOT
ch

How to register:

Open a 2nd window with this page so that you can jump between the 2 pages to read these instructions while doing the registering process :-)

Click on
http://meulengrachtforum.altervista.org/forum/index.php?topic=109.msg506#msg506
and say "open in new window" to do so.

1.) Click on "Registrieren" (almost on top of screen, in the middle somewhere) which means register
2.) Fill out the form
Benutzernamen = username

Enter your email address in the "Emailadresse" field. Check the box next to the email address "Emailadresse nicht anzeigen (empfohlen) which means "do not show email address (recommended)"

The password line below must have a certain minimum length and must not resemble parts of the username. Furthermore it must be alphanumeric (contain numbers).
The next line is for the purpose that you retype the same password for verification that you wrote it right.

Regarding the verification letters picture firefox seems to have some problems with the function of getting a new picture (at least at my place, LOL!!!), try another browser then if this function does not work. Also the "listen to letters" function does not seem 100% operational with all browers yet.

3.) Read the english agreement statement

4.) Scroll down to "Ich bin einverstanden" (I agree), check the box and click on "Ich bin einverstanden". Ehm, only if you agree, of course  ;D ;D ;D

5.) The next message (hopefully!) means that a verification email was sent to your email address.

Go to the inbox of your email account and click on the appropriate email, then click on the verification link inside.

Then go to this forum again and click on "login" above, then enter your username and password and then click on login.

The first thing you should do now if the login process worked is that you click on "profil" above, then "benutzerkonto" on the left side, then change "verwendete sprachdatei" (= forum language) to english. From now on, every menu button etc. should be english :-) Of course, this only affects buttons and forum menus etc. and not the german section (hehe :) ).

814
Hello,

also check out
www.gilbertssyndrome.com

I think the highest probability of success can be achieved if you try the "anti gilberts syndrome" measures and medicines in the following order:

------------
It is advisable that you try to find a COMPETENT health practitioner and get a COMPLETE screening of your health status because the GS symptoms tend to mix up with other health issues and it is important to know what is caused by GS and what is caused by other health problems. However, finding a good health practitioner can be - hm - lets say "difficult".

You should do the first two points BEFORE you try anything else:
1.) liver cleanse according to Dr. Hulda Regehr Clark (until you expelled 2000 stones). The slightly modified version with superphos 30 is said to be much less exhausting and more convenient while maintaining the same efficiency. I have not yet tried the method with superphos 30 but will try it soon.
Links to "standard liver cleanse":
http://www.curezone.com/cleanse/liver/huldas_recipe.asp
Link to liver cleanse with superphos 30:
http://www.shanti.com.au/body/liver.htm#Hulda

2.) heavy metal test + thyroid test

Make a heavy metal test, for example with DMSA (I do not have english information about this at the moment, only in german). Asking your doctor will probably be not very helpful as doctors are absolutely incompetent regarding this. Inform yourself about the CONTRAINDICATIONS OF DMSA before doing the test, you will also need a doctors prescription for this substance. It must be injected, then you gather an urine sample and send it to a lab to do a multielement analysis. I do not have detailed information about the procedure at the moment.

Get information about this from the web or read specialized books about the dangers of amalgame and how to resolve this. Check out the "mercury toxicity" section on www.gilbertssyndrome.com, read the internet site
http://www.noamalgam.com/

If you are heavy metal intoxicated (which is very likely for GS sufferers as GS sufferers tend to pick up heavy metals due to their low detoxification ability!) make an appropriate detoxification (amalgame fillings need to be removed BEFORE doing detoxification of course! )

Please note that removal of amalgame fillings requires several protective measures.

99,99% of all dentists have absolutely no idea about the correct protective measures...search for a dentist who is able to remove your amalgame fillings with the appropriate security measures so that you do not get even more intoxicated with heavy metals!!!

The correct removal protocal includes several protective measures, for example
-->artificial respiration with oxygene
-->slowly rotating, water cooled dental drillers (so that the damn stuff does not get evaporated)
-->special security measures to suck off the extremely toxic vapors and fragments
-->coffer dam to prevent fragments from being swallowed
-->prophylactical administration of chlorella algae or other substances that can bind heavy metals , rinsing of mouth with special chemicals afterwards

DO NOT LEAVE AWAY THESE MEASURES AND DONT GET FOOLED BY INCOMPETENT DENTISTS OR FACE THE CONSEQUENCES OF HEAVY METAL INTOXICATION.
It is EXTREMELY important that you find a dentist who can do amalgame filling removal CORRECTLY.
Dont believe any dentist who freewheelingly says that he uses protective measures without informing yourself what this person means with "protection".

There are a lot of indications that GS is linked to heavy metals and GS sufferers tend to pick up heavy metals much easier due to their reduced detoxification ability...the heavy metals then makes Gilberts syndrome worse what further reduces detoxification ability what makes it more likely that you pick up heavy metals and so on and so on (vicious circle).


AFTER THIS, DO AN APPROPRIATE HEAVY METAL DETOXIFICATION IF NEEDED (ACCORDING TO HEAVY METAL TEST).


You can do this in several ways, for example with algae and bear´s garlic or with DMSA (or other substances like this). There are several other methods available. Check out the internet about the topic or read books regarding amalgame filling removel and heavy metal intoxication etc.. for example see
http://www.noamalgam.com/

Regarding the thyroid, see here:
http://www.gilbertssyndrome.com/hypothyroidism.php

Stuff that enhances the UDP encyme system (which so to say acts on the "origin" of Gilberts Syndrome):
3.) Sulforaphane (for example in the form of Brocco Max, please wait some more time until we have collected some experience with it and made blood tests to see if it helps in any way!)

UPDATE:
It looks like as if you cannot get sufficient dosages with Brocco Max (furthermore its expensive).

According to my actual information, it is much better to eat
-->FRESH BROCCO SPROUTS (30 Grams per day)<-- to activate the encyme system that is not fully functional in Gilbert Syndrome sufferers. Sulforaphane is 20 - 50 times more concentrated in SPROUTS than in the adult form of broccoli. You can probably buy brocco sprouts on local markets (quite cheap usually) or grow them yourself.
Regarding the seeds, of course it would be better if you use broccoli sprouts of "broccoli races" (sorry for my english) which have even higher sulforaphane concentrations but sprouts from "normal broccoli race seeds" should be sufficient.
At least two users of the german board are currently trying this and will have blood tests after some months.

There exist some scientific papers that show a good effect on HUMANS (so not only animal studies :) ), you can look this up here:
http://meulengrachtforum.altervista.org/forum/index.php?topic=187.0

4.) Yin Zhi Huang tea
http://meulengrachtforum.altervista.org/forum/index.php?topic=104.0
The same stuff also comes in capsule form (and is therefore much easier to take as the tea is quite a "pain in the ass" regarding the taste  ;D ), see
http://meulengrachtforum.altervista.org/forum/index.php?topic=161.0

5.) "Sub-Stuffs" of sulforaphane like DIM, I3C etc. - we did not yet try this, I do not yet have a lot of information about this and am still waiting for information from a french board regarding a scientific paper that is said to contain information that some of these medicines might help with GS

Stuff that enhances the system that comes after the UDP System:
6.) MSM (very cheap if you know where to get it from, see www.makana.de, the exact link is
http://81.169.162.205/juergen993-s68h67-MSM_Beutel.html
2 kilograms for 30 EUR or so)

7.) The 3 "forerunner substances" of Glutathione
-->N-Acetyl-L-Cystein (NAC) or L-Cystein (better form is said to be L-Cystein, you can get it cheap at www.drclark.com))
-->Glutamine
-->Glycine
There exists at least one success report with high dosages of these substances (4 x 1.000 mg Glycine, 4 x 1.000 mg Glutamine and 3 x 500 mg L-Cystein (do not take more than that of L-Cystein)), see here (taken from the english EZ Board):
--------
Hi all,
I've had GS since 1984 and haven't found anything that would clear up my eyes.......until now.
I am taking:
NAC (N-Acetyl-L-Cysteine) 600 mg twice a day
Glutamine 1000 mg four times a day
Glycine 1000 mg four times a day
always on an empty stomach.
My eyes are white each morning but tend to color just a bit as the day goes on.
Works for me, hope it'll help some of you.
arotai
-------------

8.) flower pollen
see the actual report about it in the english EZ board:
-----------------------------------------
Hi all!!
I was diagnosed with GS over 6 years ago. Since then i had two severe liver/bilirrubin crises. In both of them ended up in a light/medium depression.
After seeing this post i tried to get the product but with no results... So i tried some of the "local Pollen" ;) , it's from "Serra D'Arrábida" , a local mountain system.
IT WORKS LIKE A CHARM!!!! Been taking it since yesterday, and my eyes are already as white as i didn't saw them in years(didn't even remember seeing them so white). I had some joint and back pain, don't see much diference yet, but i feel some relief. The fatigue is almost gone!!!!!!
Can't say it helped with my depression since i'm taking drugs for that... but i'm feeling much hapier today! :D
It's sold in grain, and you should mix it with tea or milk.
Of course the doctor's here(Portugal) don't know nothing about this syndrome.

Will try to find it on sale on the net.

So i think this is really working even with only two takes, yesterday in the afternoon and today at breakfast!!! I'll keep you posted!!!
THX Man!!! :rollin
---------------------------------------------


9.) Glutathione itself (in the form of stomach acid resistant capsules), VERY EXPENSIVE tough
and then all the rest (for a probably complete listing of all available or known stuff see www.gilbertssyndrome.com )

-->IF YOU DO NOT HAVE HEAVY METALS<-- (heavy metals can come from MANY sources, NOT only "silver" fillings) - make a DMSA heavy metal test to be SURE - it is generally advisable to take high dosages of Vitamin C and antioxidants because this detoxifies the body and supports liver function etc.. It is important not to take Vitamin C, Glutathione, folic acid, selenium or B12 when you are heavy metal intoxication because of a phenomenon called METHYLATION which can transfer the heavy metals into the brain when you take high dosages of the above mentioned substances!



There exists one more treatment that you in the english board have probably never heard about...its the horvi encymes treatment. You can read a "general description" about it here:
http://meulengrachtforum.altervista.org/forum/index.php?board=37.0

The prerequisite before using horvi encymes is that you got rid of amalgame fillings (also gold fillings if they contain palladium and stuff, generally metal is not good anywhere in your body) and of heavy metals in your body because heavy metals are a "treatment barrier". Furthermore gold teeth have a habit to "hold" heavy metals like mercury within your body.

According to the manufacturer it can cure "acquired gilberts syndrome" in almost 100% of all cases. Acquired means gilberts syndrome which you did not yet have from your birth, but which occurred due to a genetic mutation caused by heavy metal poising somewhen in your life.
Regarding original gilberts syndrome it has helped some users of the german board and at least eased their symptomes and lowered their bilirubine levels.

An individual therapy plan can be made for you by the supplier of the horvi medicines, but you have to include your complete medical history and what medicines you currently take, because some substances (even if they are natural) can conflict with the horvi encyme therapy.

Here is the manufacturers data:
Horvi-EnzyMed Holland B.V.
- Peter den Boer Netherland -
Leeuwerik 2
NL - 3191 DL Hoogvliet
Telefon: +49 (0) 6835-5004-0
Telefax: +49 (0) 6835-500444
E-Mail : [email protected]
internet address: http://www.horvi-enzymed.nl/

The horvi medicines that are usually used to treat Gilberts syndrome can be looked up here:
http://meulengrachtforum.altervista.org/forum/index.php?topic=39.msg127#msg127

The problem is this is still in german. I will have to make a translation (eeeeeeeeeek! WORK!!!  :P ) ... you can look up single words you dont understand here in the meantime: http://dict.leo.org



It is important that you share your experiences and blood tests (before and after you tried something) with us. You can do this for example here in this forum (the english section still has almost no entries but I am working on it). You can attach scanned in pictures here.

This above mentioned list here is very basic without detailed information or links, is is basically just a draft so that I can later on start building sub boards and stuff with detailed information around it so to say. This is already almost finished in the german board...but I still have to do this here. The most complete site about Gilberts Syndrome I have found so far is www.gilbertssyndrome.com btw.

I make regular forum backups so this forum should stay stable and not fall apart like the english ezboard ("post missing and cannot be restored" <--  :o )...  :)

The forum location is always www.meulengracht.de.vu (a forwarding service where I can always enter the "real link" to the forum no matter where it is really hosted)
"Morbus Meulengracht" btw is the german term for gilberts syndrome. The simplemachines forum software is known to be 99,999% (...) resistant to hacking attempts (unlike the phpbb forums who have a habit of getting hacked due to security flaws etc.).

Medizinmann99
Forum administrator

815
Horvi Encymes / English information brochure about horvi enzyme therapy
« am: 02. September 2006, 00:50:57 »
Hello,

this is a general information brochure about horvi encyme therapy (in PDF format) and therefore not focused on gilberts syndrome.

You need Acrobat Reader (better alternative is Foxit Reader!) installed on your system to view it. You can get Foxit Reader from here:
http://www.foxitsoftware.com/foxitreader/foxitreader.zip

It explains what the therapy is about in general and how it is supposed to work. PLEASE NOTE THAT YOU SHOULD DO A HEAVY METAL TEST BEFORE YOU TRY HORVI ENCYME THERAPY because there is a strong link between heavy metals and gilberts syndrome and heavy metals are a "treatment barrier" that can hinder the success of horvi encyme therapy (and any other therapy against gilberts syndrome!).

It is the only ENGLISH material I have about it so far, except some experience reports that the german users of my board had made with the therapy. I will put more information about the supplier and which horvi encyme medicines (there exist many for all sorts of conditions) are good for gilberts syndrome in this board soon :-)

There exist positive experiences in the treatment of gilbert syndrome, especially "acquired gilbert syndrome" (if you acquired gilberts syndrome through heavy metals and did not originally have it from birth!), which is said can be cured in almost all cases (while "original" gilbert syndrome can at least be eased with horvi encyme therapy).

Click on the link below to download the file.

Best regards,

Medizinmann99
Forum Administrator

816
"Yin Zhi Huang" tea / Yin Zhi Huang tea recipe :-)
« am: 30. August 2006, 22:03:12 »
Hello,

I have spent a complete day searching for the Yin Zhi Huang tea recipe and was finally able to find it in the internet.

:)

Here is the recipe:

Tea recipe for
Yin Zhi Huang

Name of Herb - Quantity
Artemisia capillaris - 40 gram (54%)
Gardenia jasminoides Ellis - 14.6 gram (20%)
Rheum officinale Baill - 7.2 gram (10%)
Scutellaria baicalensis Georgi - 12 gram (16%)


TOTAL 73,8 gram
(100%)
(If you want to buy more tea at once just double or triple or quadruple etc. each value)

As you can see the tea is made up of 4 different herbs in different quantities.

Your local drugstore or any (chinese) herb stores vendors in your area should be able to sell these herbs to you, so you probably dont have to import them from god-knows-where.

You just have to transmit the above mentioned recipe to them so that they can mix it for you.
((The only problem that could theoretically arise is that they want the CHINESE names of the herbs, ROFL...but this is highly unlikely (altough Murphys Law says something different  :P ).))

Please note that some vendors or drugstores may not sell the herbs without a doctors prescriptio n. If you encounter this problem, it would be wise to search for doctors in your area who practise TCM (Traditional chinese medicine) and ask them for such a prescriptio n. It should be no problem to persuade them that the tea can be helpful against gilberts syndrome if you print out information about the tea like mentioned in these links (for example, you can print out your own info from the internet of course):
http://www.medscape.com/medline/abstract/1914791
http://www.bcm.edu/fromthelab/vol03/is1/04feb_n1.htm
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=300773
http://www.med.upenn.edu/lazarlab/Pubs_pdf/Lazar_JCI_04.pdf

It is possibly also possible to get this tea in the form of granulate (a powder that you mix into the water instead of brewing tea with leaves)...I am not sure tough if this is possible to get via your LOCAL drugstores / herb shops here in europe etc..
IF YOU FIND AN EUROPEAN SOURCE FOR THIS TEA IN THE FORM OF GRANULATE PLEASE TELL ME (preferrably in this thread here).

So far, I only know that you can get this granulate stuff for example from here (USA):
http://www.kalyx.com/store/proddetail.cfm/ItemID/286348.0/CategoryID/1000.0/SubCatID/10.0/file.htm

But if you order it from there you would have to make an import of course and it is not 100% sure that this stuff will get through your local customs (regulations differ in every country what you can import or what you cannot import). You may be asked to provide some sort of certification from certain health authorities that this stuff is harmless. Altough I think this is unlikely. The worst thing that can happen is that they confiscate your package, or that they send it back because customs rejected it (you will of course get a refund in the last case then).

There exists also another product called JAUNDICLEAR which is made up of the above mentioned herbs and some more herbs which probably also works well against jaundice, the only source for this stuff I know so far is again in the USA:
http://www.activeherb.com/jaundiclear/

So much for the moment, best regards,

Medizinmann99
Forum Administrator


Origin of information:
----------------

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=300765

----------------
J Clin Invest. 2004 January 1; 113(1): 137–143.
doi: 10.1172/JCI200418385.
Copyright © 2004, American Society for Clinical Investigation

A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR

Wendong Huang, Jun Zhang, and David D. Moore
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

Address correspondence to: David D. Moore, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. Phone (713) 798-3313; Fax (713) 798-3017; E-mail: [email protected].

Received March 19, 2003; Accepted October 21, 2003.
Small right arrow pointing to: See commentary "East meets West: an herbal tea finds a receptor" on page 23.
Small right arrow pointing to: This article has been cited by other articles in PMC.
Top
>Abstract
Introduction
Methods
Results
Discussion
References
   
Abstract

Yin Zhi Huang, a decoction of Yin Chin (Artemisia capillaris) and three other herbs, is widely used in Asia to prevent and treat neonatal jaundice. We recently identified the constitutive androstane receptor (CAR, NR1I3) as a key regulator of bilirubin clearance in the liver. Here we show that treatment of WT and humanized CAR transgenic mice with Yin Zhi Huang for 3 days accelerates the clearance of intravenously infused bilirubin. This effect is absent in CAR knockout animals. Expression of bilirubin glucuronyl transferase and other components of the bilirubin metabolism pathway is induced by Yin Zhi Huang treatment of WT mice or mice expressing only human CAR, but not CAR knockout animals. 6,7-Dimethylesculetin, a compound present in Yin Chin, activates CAR in primary hepatocytes from both WT and humanized CAR mice and accelerates bilirubin clearance in vivo. We conclude that CAR mediates the effects of Yin Zhi Huang on bilirubin clearance and that 6,7-dimethylesculetin is an active component of this herbal medicine. CAR is a potential target for the development of new drugs to treat neonatal, genetic, or acquired forms of jaundice.

Top
Abstract
>Introduction
Methods
Results
Discussion
References
   
Introduction

Jaundice, the accumulation of high levels of bilirubin in the circulation, is particularly common in human neonates (1). Bilirubin is cleared by the liver, and both certain genetic defects and liver diseases can cause hyperbilirubinemia in adults (2, 3). Bilirubin is highly hydrophobic, and chronic hyperbilirubinemia results in its deposition in the central nervous system, causing neurotoxicity and encephalopathy. Some evidence suggests that chronic jaundice may also suppress the immune system as well as other normal physiological functions (4, 5). Four distinct steps of bilirubin metabolism have been proposed (3, 6). Bilirubin is first imported via the sinusoidal surface of the hepatocyte by solute carrier family 21, member 6 (SLC21A6; also known as organic anion transporter 2, OATP2) (7). Ligandin, a homodimer or heterodimer of glutathione-S-transferase (GST) A1 and A2, binds bilirubin with high affinity and thus increases uptake. Bilirubin is then glucuronidated by a specific microsomal bilirubin uridine diphosphate-5′-glucuronosyltransferase (UDP-glucuronosyltransferase 1A1, UGT1A1). The resulting hydrophilic bilirubin diglucuronide is then secreted across the bile-canalicular membrane of the hepatocytes by an active transporter, multidrug resistance–related protein 2 (MRP2) (cMOAT, ABC-C2).

For the last several decades, phototherapy has been used to treat neonatal jaundice. Recently, however, both older and more recent pharmacological approaches to jaundice have been considered (8). Phenobarbital, which induces UGT1A1 activity (9, 10) and decreases bilirubin levels in patients (11–13), is the best studied of the older treatments, but there are also numerous remedies for jaundice in various traditional medicines. Yin Zhi Huang and a number of other herbal decoctions containing Yin Chin have been used for centuries in Asia to prevent and treat neonatal jaundice (14). Yin Zhi Huang contains extracts from four different plants: Artemisia capillaris, Gardenia jasminoides Ellis, Rheum officinale Baill, and Scutellaria baicalensis Georgi. Several clinical reports in the Chinese medical literature indicate that Yin Zhi Huang treatment can enhance bilirubin clearance in newborns (15–17). In studies in rats, both Yin Zhi Huang and phenobarbital induced bilirubin glucuronyl transferase and GST activity, and Yin Zhi Huang had a somewhat more potent stimulatory effect on bilirubin clearance than phenobarbital (18, 19).

Constitutive androstane receptor (CAR) NR1I3 has been shown to mediate the response of liver to phenobarbital and other “phenobarbital-like” compounds (20–23). Recently, we demonstrated that CAR is a key regulator of the bilirubin clearance pathway and that CAR activation increases the rate of bilirubin clearance (24). Here we test the prediction that CAR mediates the effect of Yin Zhi Huang on bilirubin clearance. By screening for CAR activators, we also identify an active compound in Yin Zhi Huang that accelerates this clearance.

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Methods

Yin Zhi Huang and Yin Chin decoction preparations. A Yin Zhi Huang decoction containing four different herbs for gavage was prepared by boiling 40 g Artemisiae, 14.6 g Gardenniae, 7.2 g Rheum, and 12 g Scutellariae in water for 30 minutes and adjusting the final volume to 40 ml.

For Yin Chin decoction, only Artemisiae 40 g was added. Yin Zhi Huang and Yin Chin were obtained from Chinese Herb Inc. (Houston, Texas, USA).

Animal treatment. Mice were hosted in a pathogen-free animal facility under a standard 12-hour light/12-hour dark cycle. Mice were fed standard rodent chow and water ad libitum. A humanized CAR transgenic mouse line was generated by crossing an albumin promoter/human CAR transgene into the CAR null background, as described previously (25). Different groups of mice appropriately matched in genetic background (n = 3–4) were injected i.p. with a solvent (corn oil) or 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) (3 mg/kg), 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN) (40 mg/kg), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (100 μg/kg) for 3 days. [4-Chloro-6-(2,3-xylidino)-pyrimidynylthio]acetic acid (WY-14,643) (0.1%) was added to the food, and the mice were fed for 1 week. For Yin Zhi Huang or Yin Chin treatments, appropriately matched groups of mice were gavaged once daily for 3 days with a Yin Zhi Huang or Yin Chin decoction (10 ml/kg/day). For 6,7-dimethylesculetin (Indofine Chemical Company, Hillsborough, New Jersey, USA) treatment, the compound was first dissolved in a small volume of DMSO and then mixed well with corn oil. Groups of WT and CAR null mice were injected i.p. twice daily for 3 days with vehicle control or 6,7-dimethylesculetin (100 mg/kg). On the fourth day, the animals were intravenously infused with bilirubin solution (10 mg/kg) via the tail vein. After 1 hour, blood was collected and total serum bilirubin was determined as described (24). Livers were removed and total bilirubin from liver was measured by diazotization with p-iodoaniline as described (26). Bilirubin (Sigma-Aldrich, St. Louis, Missouri, USA) was first dissolved in 0.1 N NaOH, then adjusted to pH 8.5–9.5 with 1 N HCl, and finally diluted with isotonic saline to a concentration of 3 mg/ml. The solution was always freshly prepared under low-light conditions.

Northern hybridization. Total liver RNA was prepared using Trizol reagent (Invitrogen, Rockville, Maryland, USA) according to the manufacturer’s instructions. Equivalent amounts of RNA from three to four mice were pooled, and 15 μg of each sample were used for Northern blot analysis. A cytochrome P450 1A1 (CYP1A1) cDNA probe was generated by RT-PCR from mouse liver RNA. The primers used were 5′-AGATACCTGGGCCTCAGAGAACT-3′ and 5′-CAGTCCATAATACAAAGCTC-3′. All the other murine cDNA probes were generated as previously described (23, 24). In all cases, a single blot was serially hybridized with the various probes, with β-actin serving as a control for equivalent loading.

Primary hepatocyte culture. Mouse primary hepatocytes were prepared and maintained in William’s E medium (Invitrogen), supplemented with 10 μg/ml insulin (Sigma-Aldrich) and 10–7 M triamcinolone acetonide as described (27). Cells were treated with different concentrations of 4′-hydroxyacetophenone (Sigma-Aldrich) and 6,7-dimethylesculetin (ICC) dissolved in DMSO for 24 hours. Total RNA was isolated using the Qiagen RNeasy minikit (Qiagen, Valencia, California, USA) according to the manufacturer’s instructions, and 15 μg RNA were used for Northern blot analysis. For protein analysis, cells were incubated with either solvent or 50 μM 6,7-dimethylesculetin for 3 hours. Fifty micrograms of nuclear extract or 50 μg of cell total protein were fractionated by PAGE and immunoblotted; hCAR was then detected with a monoclonal antibody to the c-Myc epitope tag (Roche Molecular Biochemicals, Indianapolis, Indiana, USA).

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Results

CAR coordinately regulates the bilirubin clearance pathway. In addition to its function as a xenobiotic receptor, CAR responds to elevated levels of bilirubin by increasing the hepatic clearance of this toxic endobiotic (24). Several other ligand-dependent transcriptional regulators have also been shown to regulate liver responses to both xenobiotics and endobiotics, including the pregnane X receptor (PXR), PPARα, and the aryl hydrocarbon receptor (AhR). Several lines of evidence suggest potential roles for these proteins in bilirubin clearance. Thus, the PPARα ligand clofibrate has been reported to induce UGT1A1 expression (28) and to decrease circulating bilirubin levels in humans (29, 30). PXR has been reported to activate expression of components of the bilirubin clearance pathway, including UGT1A1 (31) and MRP2 (32). AhR, which can be activated by bilirubin (33, 34), has also recently been reported to activate the expression of UGT1A1 (35). Hydroxylation of bilirubin by CYP1A1, another well-known AhR target, may also contribute to bilirubin detoxification (36).

To compare the roles of these four receptors in bilirubin metabolism, groups of mice were pretreated with specific activators of each protein for 3 days, and their ability to remove bilirubin from the circulation was examined using an acute clearance assay (24). In this assay, a bolus dose of bilirubin is administered i.v., and measuring residual circulating levels after 1 hour assesses the rate of clearance. TCPOBOP significantly increased clearance as expected (24), but little or no effect was observed with the PXR activator PCN, the PPARα activator WY-14,643, or the AhR activator TCDD (Figure 1a). Total hepatic bilirubin was also measured to determine whether the decrease in serum bilirubin is due to increased hepatic accumulation or actual clearance from the liver. As expected from the activation of multiple components of the clearance pathway by CAR (24), hepatic bilirubin was much lower in TCPOBOP-treated mice (Figure 1b). In contrast, PXR, PPARα or AhR activation did not significantly affect hepatic bilirubin levels.

To investigate the basis for the differential responses, the expression of five genes encoding components of the bilirubin clearance pathway plus CYP1A1 was examined. TCPOBOP induced expression of all five clearance genes as expected, but PCN, WY-14,643, and TCDD had more restricted and moderate effects (Figure 1c). TCPOBOP increased UGT1A1 mRNA levels fourfold, for example, whereas the response to PCN and TCDD was less than twofold, and WY-14,643 had no apparent effect. The limited responses are not due to lack of effects of the activators, since appropriate target genes were induced in each case. Thus, PXR activation by PCN strongly induced glutathione transferase GSTA1 expression, and TCDD-activated AhR strongly induced CYP1A1 expression. Similarly, PPARα activation by WY-16,643 increased liver cell proliferation in these mice as expected (data not shown). Although it remains possible that other receptors contribute to bilirubin metabolism in at least some circumstances, these results identify CAR as a particularly important regulator of this process.

Yin Zhi Huang stimulation of bilirubin clearance is dependent on CAR. The primary role of CAR in bilirubin metabolism is consistent with earlier studies showing positive effects of phenobarbital on jaundice (37, 38). To test the possibility that CAR also mediates the effect of Yin Zhi Huang on bilirubin clearance, both WT and CAR knockout mice were pretreated with Yin Zhi Huang or saline control by oral gavage for 3 days. On the fourth day, mice were subjected to an acute bilirubin clearance assay. In agreement with previous results (19), Yin Zhi Huang treatment of WT mice increased the clearance rate. However, this effect was completely absent in CAR knockout animals, demonstrating that CAR is required to mediate the effect of this herbal decoction on bilirubin clearance (Figure 2a).

To examine the mechanism of enhanced bilirubin clearance by Yin Zhi Huang, hepatic expression of the primary CAR target gene CYP2B10 and the five components of the clearance pathway were examined. In the WT mice, all the genes showed at least some response, with particularly strong induction of CYP2B10 and UGT1A1 (Figure 2b). Except for UGT1A1, which showed a modest residual response, these inductions were absent in the CAR null animals. The weak induction of UGT1A1 in CAR knockout animals may indicate some effect of Yin Zhi Huang on PXR or other receptors.

The effect of Yin Zhi Huang on bilirubin clearance decreases with decreasing doses (Figure 2c). Additional support for the role of CAR in this response is provided by the observation that a similar dose dependence is observed for the increased rate of bilirubin clearance and the induction of CYP2B10 mRNA. Yin Zhi Huang treatment did not affect CAR expression.

Because murine and human CAR can show quite different responses to different activators, it was important to test whether human CAR can also mediate effects of Yin Zhi Huang on bilirubin clearance. These studies used previously described humanized mice expressing human instead of murine CAR in the liver (24, 25). These humanized mice do not respond to TCPOBOP, which is specific for the murine CAR, but they do respond to the general CAR activator phenobarbital and the specific human CAR agonist 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (39). Three groups of humanized mice received either saline control, Yin Zhi Huang, or Yin Chin alone, which is considered to be the major active herb in the Yin Zhi Huang mixture. Although the response was somewhat less than that of the WT mice, as previously observed with phenobarbital activation of human CAR (24), both Yin Zhi Huang and Yin Chin significantly enhanced the clearance of the exogenously infused bilirubin (Figure 3a). As expected from the results with the WT mice, expression of a number of CAR target genes was also increased by Yin Zhi Huang and Yin Chin in the humanized mice (Figure 3b).

6,7-Dimethylesculetin activates both mouse and human CAR. These results indicate that Yin Chin contains an agent or agents that can activate both mouse and human CAR. Among a number of compounds present in Yin Chin are the coumarin 6,7-dimethylesculetin (scoparone) and 4′-hydroxyacetophenone (Figure 4a). 6,7-Dimethylesculetin is a major constituent, comprising up to 2% of Yin Chin by dry weight and has been associated with a number of potential biologic actions (40).

In tests of the effects of the compounds in primary hepatocytes from WT mice, 6,7-dimethylesculetin treatment significantly induced CYP2B10 expression, but CAR knockout hepatocytes showed no response (Figure 4b). 4′-Hydroxyacetophenone had no effect in either case. In primary hepatocytes from humanized CAR mice, 6,7-dimethylesculetin also induced expression of CAR target genes, especially CYP2B10, UGT1A1, and MRP2; lesser responses of SLC21A6 and GSTA1 and GSTA2 were confirmed by densitometry (Figure 4c).

A variety of transient transfections with full-length receptors or mammalian two-hybrid assays for coactivator recruitment failed to provide evidence that either these compounds or several other candidates tested function as direct CAR agonist ligands (data not shown). In hepatocytes, however, CAR can also be activated by an indirect mechanism based on a specifically induced translocation from the cytoplasm to the nucleus (41). The effect of 6,7-dimethylesculetin on the levels of CAR present in the nuclei of primary hepatocytes from humanized CAR mice was examined by Western blotting. A low basal level of nuclear CAR was detected in the untreated hepatocytes, which may account for the increased basal expression of CYP2B10 in the cultured cells relative to the liver. As expected, however, 6,7-dimethylesculetin treatment significantly increased the levels of CAR in the nucleus but did not affect the total amount of human CAR (Figure 4d).

To investigate the effect of 6,7-dimethylesculetin on bilirubin clearance in vivo, we treated the WT and CAR null mice twice daily with 6,7-dimethylesculetin or a vehicle control for 3 days. The effects of the pure compound were quite similar to those of the Yin Chin extract, with an increase in both bilirubin clearance and expression of CAR target genes (Figure 5). Overall, we concluded that 6,7-dimethylesculetin is a specific CAR activator that is likely to contribute to the ability of Yin Zhi Huang to increase bilirubin clearance.

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Discussion

Both previous results (24) and those described here demonstrate that CAR is a key regulator of bilirubin clearance. Under ordinary circumstances, CAR is sequestered in the hepatocyte cytoplasm and thus does not affect bilirubin levels. In response to elevated bilirubin levels, however, CAR activates expression of multiple components of the bilirubin clearance pathway, resulting in an increased rate of clearance.

Several other receptors have been reported to induce expression of the primary bilirubin-conjugating enzyme UGT1A1, including the nuclear receptors PXR (31) and PPARα (28) and the per-arnt-sim domain protein AhR (35). The potential response of this important detoxifying enzyme to diverse signals is a reflection of the complexity of the functional interrelationships of these regulators. For example, numerous studies indicate that both CAR and PXR can induce expression of a number of genes encoding various components of drug metabolism pathways (42–44). Although this can result in common regulatory effects, the regulation of common target genes does not mean that the distinct receptors have the same physiologic effects. Thus, the results described here indicate that acute activation of CAR has a particularly significant impact on the overall bilirubin clearance rate, although it remains possible that important functions for the other receptors would be observed under other circumstances.

The results described here also demonstrate that CAR mediates the effects of the Chinese traditional medicine Yin Zhi Huang on bilirubin clearance. In Chinese and other traditional medicines, disease is thought to be a consequence of imbalances in the body, and it is often considered necessary to incorporate multiple components into a therapeutic approach to restore balance to different processes. Yin Zhi Huang is a typical example of such a combination. Because other combinations of Yin Chin with quite different components are also used in Chinese and other Asian traditional medicines with apparently similar effects, Yin Chin is thought to be the primary active agent in this mixture. Consistent with this, both Yin Chin and 6,7-dimethylesculetin are sufficient to induce both bilirubin clearance and CAR target gene expression, and we conclude that 6,7-dimethylesculetin is an active component of Yin Zhi Huang and other Yin Chin–containing herbal medicines that contributes to their biological effects. Particularly because previous studies indicate that extracts of the other plants in Yin Zhi Huang can increase GST or UGT1A1 activity (45), it is possible that other components also contribute.

It is intriguing that Artemisia species related to Yin Chin (e.g., wormwood, absinthe, mugwort, and tarragon) have been used in traditional medicines from many cultures for a variety of indications, including liver ailments, and a number of studies in animal models indicate hepatoprotective effects for various Artemisia extracts (46, 47). These effects have been attributed to antioxidant or other properties of the components of these extracts, but it is an interesting possibility that CAR activation is a contributing factor.

In summary, we have demonstrated the particular importance of CAR in regulating bilirubin clearance, demonstrated that this nuclear receptor mediates the effect of the natural herbal medicine Yin Zhi Huang on this process, and identified a specific active compound present in this mixture. CAR thus joins farnesoid X receptor (FXR) (48) and PXR (49, 50) as recently identified targets of significant biological effects of herbal medicines. We believe that these and other nuclear receptors with important metabolic regulatory functions will be found to mediate activities of other natural products. Based on the recent identification of a specific human CAR agonist (39), we also anticipate that more modern approaches to drug design based on CAR may yield new treatments for neonatal and other forms of jaundice.

    
Acknowledgments

We thank Steve S. Chua for generating the humanized CAR mice and Amethyst C. Kurbegov for preliminary results. This work was supported by NIH grant DK46546.

    
Footnotes

See the related Commentary beginning on page 23.

Conflict of interest: The authors have declared that no conflict of interest exists.

Nonstandard abbreviations used: solute carrier family 21, member 6 (SLC21A6); glutathione-S-transferase (GST); uridine diphosphate-5′-glucuronosyltransferase (UGT); multidrug resistance–related protein 2 (MRP2); constitutive androstane receptor (CAR); 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP); 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN); 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); cytochrome P450 1A1 (CYP1A1); pregnane X receptor (PXR); aryl hydrocarbon receptor (AhR).

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References
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817
Hallo,

nach ewigem Herumsuchen habe ich jetzt endlich  ::) das tatsächliche REZEPT für diesen Yin Zhi Huang Tee gefunden.

Tea recipe for
Yin Zhi Huang

Name of Herb - Quantity
Artemisia capillaris - 40 gram (54%)
Gardenia jasminoides Ellis - 14.6 gram (20%)
Rheum officinale Baill - 7.2 gram (10%)
Scutellaria baicalensis Georgi - 12 gram (16%)


TOTAL 73,8 gram
(100%)
(If you want to buy more tea at once just double or triple or quadruple etc. each value)

Damit sollte es jetzt endlich möglich sein den Tee über ganz normale Tee- und Kräutergeschäfte bzw. Apotheken zu beziehen (manche Apotheken wollen aber ein Rezept!), d.h. also man muß überhaupt nichts mehr importieren  :)

Liebe Grüße

Medizinmann99

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Quelle / origin of information:
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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=300765

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J Clin Invest. 2004 January 1; 113(1): 137–143.
doi: 10.1172/JCI200418385.
Copyright © 2004, American Society for Clinical Investigation

A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR

Wendong Huang, Jun Zhang, and David D. Moore
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

Address correspondence to: David D. Moore, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. Phone (713) 798-3313; Fax (713) 798-3017; E-mail: [email protected].

Received March 19, 2003; Accepted October 21, 2003.
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Abstract

Yin Zhi Huang, a decoction of Yin Chin (Artemisia capillaris) and three other herbs, is widely used in Asia to prevent and treat neonatal jaundice. We recently identified the constitutive androstane receptor (CAR, NR1I3) as a key regulator of bilirubin clearance in the liver. Here we show that treatment of WT and humanized CAR transgenic mice with Yin Zhi Huang for 3 days accelerates the clearance of intravenously infused bilirubin. This effect is absent in CAR knockout animals. Expression of bilirubin glucuronyl transferase and other components of the bilirubin metabolism pathway is induced by Yin Zhi Huang treatment of WT mice or mice expressing only human CAR, but not CAR knockout animals. 6,7-Dimethylesculetin, a compound present in Yin Chin, activates CAR in primary hepatocytes from both WT and humanized CAR mice and accelerates bilirubin clearance in vivo. We conclude that CAR mediates the effects of Yin Zhi Huang on bilirubin clearance and that 6,7-dimethylesculetin is an active component of this herbal medicine. CAR is a potential target for the development of new drugs to treat neonatal, genetic, or acquired forms of jaundice.

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Introduction

Jaundice, the accumulation of high levels of bilirubin in the circulation, is particularly common in human neonates (1). Bilirubin is cleared by the liver, and both certain genetic defects and liver diseases can cause hyperbilirubinemia in adults (2, 3). Bilirubin is highly hydrophobic, and chronic hyperbilirubinemia results in its deposition in the central nervous system, causing neurotoxicity and encephalopathy. Some evidence suggests that chronic jaundice may also suppress the immune system as well as other normal physiological functions (4, 5). Four distinct steps of bilirubin metabolism have been proposed (3, 6). Bilirubin is first imported via the sinusoidal surface of the hepatocyte by solute carrier family 21, member 6 (SLC21A6; also known as organic anion transporter 2, OATP2) (7). Ligandin, a homodimer or heterodimer of glutathione-S-transferase (GST) A1 and A2, binds bilirubin with high affinity and thus increases uptake. Bilirubin is then glucuronidated by a specific microsomal bilirubin uridine diphosphate-5′-glucuronosyltransferase (UDP-glucuronosyltransferase 1A1, UGT1A1). The resulting hydrophilic bilirubin diglucuronide is then secreted across the bile-canalicular membrane of the hepatocytes by an active transporter, multidrug resistance–related protein 2 (MRP2) (cMOAT, ABC-C2).

For the last several decades, phototherapy has been used to treat neonatal jaundice. Recently, however, both older and more recent pharmacological approaches to jaundice have been considered (8). Phenobarbital, which induces UGT1A1 activity (9, 10) and decreases bilirubin levels in patients (11–13), is the best studied of the older treatments, but there are also numerous remedies for jaundice in various traditional medicines. Yin Zhi Huang and a number of other herbal decoctions containing Yin Chin have been used for centuries in Asia to prevent and treat neonatal jaundice (14). Yin Zhi Huang contains extracts from four different plants: Artemisia capillaris, Gardenia jasminoides Ellis, Rheum officinale Baill, and Scutellaria baicalensis Georgi. Several clinical reports in the Chinese medical literature indicate that Yin Zhi Huang treatment can enhance bilirubin clearance in newborns (15–17). In studies in rats, both Yin Zhi Huang and phenobarbital induced bilirubin glucuronyl transferase and GST activity, and Yin Zhi Huang had a somewhat more potent stimulatory effect on bilirubin clearance than phenobarbital (18, 19).

Constitutive androstane receptor (CAR) NR1I3 has been shown to mediate the response of liver to phenobarbital and other “phenobarbital-like” compounds (20–23). Recently, we demonstrated that CAR is a key regulator of the bilirubin clearance pathway and that CAR activation increases the rate of bilirubin clearance (24). Here we test the prediction that CAR mediates the effect of Yin Zhi Huang on bilirubin clearance. By screening for CAR activators, we also identify an active compound in Yin Zhi Huang that accelerates this clearance.

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Methods

Yin Zhi Huang and Yin Chin decoction preparations. A Yin Zhi Huang decoction containing four different herbs for gavage was prepared by boiling 40 g Artemisiae, 14.6 g Gardenniae, 7.2 g Rheum, and 12 g Scutellariae in water for 30 minutes and adjusting the final volume to 40 ml.

For Yin Chin decoction, only Artemisiae 40 g was added. Yin Zhi Huang and Yin Chin were obtained from Chinese Herb Inc. (Houston, Texas, USA).

Animal treatment. Mice were hosted in a pathogen-free animal facility under a standard 12-hour light/12-hour dark cycle. Mice were fed standard rodent chow and water ad libitum. A humanized CAR transgenic mouse line was generated by crossing an albumin promoter/human CAR transgene into the CAR null background, as described previously (25). Different groups of mice appropriately matched in genetic background (n = 3–4) were injected i.p. with a solvent (corn oil) or 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) (3 mg/kg), 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN) (40 mg/kg), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (100 μg/kg) for 3 days. [4-Chloro-6-(2,3-xylidino)-pyrimidynylthio]acetic acid (WY-14,643) (0.1%) was added to the food, and the mice were fed for 1 week. For Yin Zhi Huang or Yin Chin treatments, appropriately matched groups of mice were gavaged once daily for 3 days with a Yin Zhi Huang or Yin Chin decoction (10 ml/kg/day). For 6,7-dimethylesculetin (Indofine Chemical Company, Hillsborough, New Jersey, USA) treatment, the compound was first dissolved in a small volume of DMSO and then mixed well with corn oil. Groups of WT and CAR null mice were injected i.p. twice daily for 3 days with vehicle control or 6,7-dimethylesculetin (100 mg/kg). On the fourth day, the animals were intravenously infused with bilirubin solution (10 mg/kg) via the tail vein. After 1 hour, blood was collected and total serum bilirubin was determined as described (24). Livers were removed and total bilirubin from liver was measured by diazotization with p-iodoaniline as described (26). Bilirubin (Sigma-Aldrich, St. Louis, Missouri, USA) was first dissolved in 0.1 N NaOH, then adjusted to pH 8.5–9.5 with 1 N HCl, and finally diluted with isotonic saline to a concentration of 3 mg/ml. The solution was always freshly prepared under low-light conditions.

Northern hybridization. Total liver RNA was prepared using Trizol reagent (Invitrogen, Rockville, Maryland, USA) according to the manufacturer’s instructions. Equivalent amounts of RNA from three to four mice were pooled, and 15 μg of each sample were used for Northern blot analysis. A cytochrome P450 1A1 (CYP1A1) cDNA probe was generated by RT-PCR from mouse liver RNA. The primers used were 5′-AGATACCTGGGCCTCAGAGAACT-3′ and 5′-CAGTCCATAATACAAAGCTC-3′. All the other murine cDNA probes were generated as previously described (23, 24). In all cases, a single blot was serially hybridized with the various probes, with β-actin serving as a control for equivalent loading.

Primary hepatocyte culture. Mouse primary hepatocytes were prepared and maintained in William’s E medium (Invitrogen), supplemented with 10 μg/ml insulin (Sigma-Aldrich) and 10–7 M triamcinolone acetonide as described (27). Cells were treated with different concentrations of 4′-hydroxyacetophenone (Sigma-Aldrich) and 6,7-dimethylesculetin (ICC) dissolved in DMSO for 24 hours. Total RNA was isolated using the Qiagen RNeasy minikit (Qiagen, Valencia, California, USA) according to the manufacturer’s instructions, and 15 μg RNA were used for Northern blot analysis. For protein analysis, cells were incubated with either solvent or 50 μM 6,7-dimethylesculetin for 3 hours. Fifty micrograms of nuclear extract or 50 μg of cell total protein were fractionated by PAGE and immunoblotted; hCAR was then detected with a monoclonal antibody to the c-Myc epitope tag (Roche Molecular Biochemicals, Indianapolis, Indiana, USA).

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Results

CAR coordinately regulates the bilirubin clearance pathway. In addition to its function as a xenobiotic receptor, CAR responds to elevated levels of bilirubin by increasing the hepatic clearance of this toxic endobiotic (24). Several other ligand-dependent transcriptional regulators have also been shown to regulate liver responses to both xenobiotics and endobiotics, including the pregnane X receptor (PXR), PPARα, and the aryl hydrocarbon receptor (AhR). Several lines of evidence suggest potential roles for these proteins in bilirubin clearance. Thus, the PPARα ligand clofibrate has been reported to induce UGT1A1 expression (28) and to decrease circulating bilirubin levels in humans (29, 30). PXR has been reported to activate expression of components of the bilirubin clearance pathway, including UGT1A1 (31) and MRP2 (32). AhR, which can be activated by bilirubin (33, 34), has also recently been reported to activate the expression of UGT1A1 (35). Hydroxylation of bilirubin by CYP1A1, another well-known AhR target, may also contribute to bilirubin detoxification (36).

To compare the roles of these four receptors in bilirubin metabolism, groups of mice were pretreated with specific activators of each protein for 3 days, and their ability to remove bilirubin from the circulation was examined using an acute clearance assay (24). In this assay, a bolus dose of bilirubin is administered i.v., and measuring residual circulating levels after 1 hour assesses the rate of clearance. TCPOBOP significantly increased clearance as expected (24), but little or no effect was observed with the PXR activator PCN, the PPARα activator WY-14,643, or the AhR activator TCDD (Figure 1a). Total hepatic bilirubin was also measured to determine whether the decrease in serum bilirubin is due to increased hepatic accumulation or actual clearance from the liver. As expected from the activation of multiple components of the clearance pathway by CAR (24), hepatic bilirubin was much lower in TCPOBOP-treated mice (Figure 1b). In contrast, PXR, PPARα or AhR activation did not significantly affect hepatic bilirubin levels.

To investigate the basis for the differential responses, the expression of five genes encoding components of the bilirubin clearance pathway plus CYP1A1 was examined. TCPOBOP induced expression of all five clearance genes as expected, but PCN, WY-14,643, and TCDD had more restricted and moderate effects (Figure 1c). TCPOBOP increased UGT1A1 mRNA levels fourfold, for example, whereas the response to PCN and TCDD was less than twofold, and WY-14,643 had no apparent effect. The limited responses are not due to lack of effects of the activators, since appropriate target genes were induced in each case. Thus, PXR activation by PCN strongly induced glutathione transferase GSTA1 expression, and TCDD-activated AhR strongly induced CYP1A1 expression. Similarly, PPARα activation by WY-16,643 increased liver cell proliferation in these mice as expected (data not shown). Although it remains possible that other receptors contribute to bilirubin metabolism in at least some circumstances, these results identify CAR as a particularly important regulator of this process.

Yin Zhi Huang stimulation of bilirubin clearance is dependent on CAR. The primary role of CAR in bilirubin metabolism is consistent with earlier studies showing positive effects of phenobarbital on jaundice (37, 38). To test the possibility that CAR also mediates the effect of Yin Zhi Huang on bilirubin clearance, both WT and CAR knockout mice were pretreated with Yin Zhi Huang or saline control by oral gavage for 3 days. On the fourth day, mice were subjected to an acute bilirubin clearance assay. In agreement with previous results (19), Yin Zhi Huang treatment of WT mice increased the clearance rate. However, this effect was completely absent in CAR knockout animals, demonstrating that CAR is required to mediate the effect of this herbal decoction on bilirubin clearance (Figure 2a).

To examine the mechanism of enhanced bilirubin clearance by Yin Zhi Huang, hepatic expression of the primary CAR target gene CYP2B10 and the five components of the clearance pathway were examined. In the WT mice, all the genes showed at least some response, with particularly strong induction of CYP2B10 and UGT1A1 (Figure 2b). Except for UGT1A1, which showed a modest residual response, these inductions were absent in the CAR null animals. The weak induction of UGT1A1 in CAR knockout animals may indicate some effect of Yin Zhi Huang on PXR or other receptors.

The effect of Yin Zhi Huang on bilirubin clearance decreases with decreasing doses (Figure 2c). Additional support for the role of CAR in this response is provided by the observation that a similar dose dependence is observed for the increased rate of bilirubin clearance and the induction of CYP2B10 mRNA. Yin Zhi Huang treatment did not affect CAR expression.

Because murine and human CAR can show quite different responses to different activators, it was important to test whether human CAR can also mediate effects of Yin Zhi Huang on bilirubin clearance. These studies used previously described humanized mice expressing human instead of murine CAR in the liver (24, 25). These humanized mice do not respond to TCPOBOP, which is specific for the murine CAR, but they do respond to the general CAR activator phenobarbital and the specific human CAR agonist 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (39). Three groups of humanized mice received either saline control, Yin Zhi Huang, or Yin Chin alone, which is considered to be the major active herb in the Yin Zhi Huang mixture. Although the response was somewhat less than that of the WT mice, as previously observed with phenobarbital activation of human CAR (24), both Yin Zhi Huang and Yin Chin significantly enhanced the clearance of the exogenously infused bilirubin (Figure 3a). As expected from the results with the WT mice, expression of a number of CAR target genes was also increased by Yin Zhi Huang and Yin Chin in the humanized mice (Figure 3b).

6,7-Dimethylesculetin activates both mouse and human CAR. These results indicate that Yin Chin contains an agent or agents that can activate both mouse and human CAR. Among a number of compounds present in Yin Chin are the coumarin 6,7-dimethylesculetin (scoparone) and 4′-hydroxyacetophenone (Figure 4a). 6,7-Dimethylesculetin is a major constituent, comprising up to 2% of Yin Chin by dry weight and has been associated with a number of potential biologic actions (40).

In tests of the effects of the compounds in primary hepatocytes from WT mice, 6,7-dimethylesculetin treatment significantly induced CYP2B10 expression, but CAR knockout hepatocytes showed no response (Figure 4b). 4′-Hydroxyacetophenone had no effect in either case. In primary hepatocytes from humanized CAR mice, 6,7-dimethylesculetin also induced expression of CAR target genes, especially CYP2B10, UGT1A1, and MRP2; lesser responses of SLC21A6 and GSTA1 and GSTA2 were confirmed by densitometry (Figure 4c).

A variety of transient transfections with full-length receptors or mammalian two-hybrid assays for coactivator recruitment failed to provide evidence that either these compounds or several other candidates tested function as direct CAR agonist ligands (data not shown). In hepatocytes, however, CAR can also be activated by an indirect mechanism based on a specifically induced translocation from the cytoplasm to the nucleus (41). The effect of 6,7-dimethylesculetin on the levels of CAR present in the nuclei of primary hepatocytes from humanized CAR mice was examined by Western blotting. A low basal level of nuclear CAR was detected in the untreated hepatocytes, which may account for the increased basal expression of CYP2B10 in the cultured cells relative to the liver. As expected, however, 6,7-dimethylesculetin treatment significantly increased the levels of CAR in the nucleus but did not affect the total amount of human CAR (Figure 4d).

To investigate the effect of 6,7-dimethylesculetin on bilirubin clearance in vivo, we treated the WT and CAR null mice twice daily with 6,7-dimethylesculetin or a vehicle control for 3 days. The effects of the pure compound were quite similar to those of the Yin Chin extract, with an increase in both bilirubin clearance and expression of CAR target genes (Figure 5). Overall, we concluded that 6,7-dimethylesculetin is a specific CAR activator that is likely to contribute to the ability of Yin Zhi Huang to increase bilirubin clearance.

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Discussion

Both previous results (24) and those described here demonstrate that CAR is a key regulator of bilirubin clearance. Under ordinary circumstances, CAR is sequestered in the hepatocyte cytoplasm and thus does not affect bilirubin levels. In response to elevated bilirubin levels, however, CAR activates expression of multiple components of the bilirubin clearance pathway, resulting in an increased rate of clearance.

Several other receptors have been reported to induce expression of the primary bilirubin-conjugating enzyme UGT1A1, including the nuclear receptors PXR (31) and PPARα (28) and the per-arnt-sim domain protein AhR (35). The potential response of this important detoxifying enzyme to diverse signals is a reflection of the complexity of the functional interrelationships of these regulators. For example, numerous studies indicate that both CAR and PXR can induce expression of a number of genes encoding various components of drug metabolism pathways (42–44). Although this can result in common regulatory effects, the regulation of common target genes does not mean that the distinct receptors have the same physiologic effects. Thus, the results described here indicate that acute activation of CAR has a particularly significant impact on the overall bilirubin clearance rate, although it remains possible that important functions for the other receptors would be observed under other circumstances.

The results described here also demonstrate that CAR mediates the effects of the Chinese traditional medicine Yin Zhi Huang on bilirubin clearance. In Chinese and other traditional medicines, disease is thought to be a consequence of imbalances in the body, and it is often considered necessary to incorporate multiple components into a therapeutic approach to restore balance to different processes. Yin Zhi Huang is a typical example of such a combination. Because other combinations of Yin Chin with quite different components are also used in Chinese and other Asian traditional medicines with apparently similar effects, Yin Chin is thought to be the primary active agent in this mixture. Consistent with this, both Yin Chin and 6,7-dimethylesculetin are sufficient to induce both bilirubin clearance and CAR target gene expression, and we conclude that 6,7-dimethylesculetin is an active component of Yin Zhi Huang and other Yin Chin–containing herbal medicines that contributes to their biological effects. Particularly because previous studies indicate that extracts of the other plants in Yin Zhi Huang can increase GST or UGT1A1 activity (45), it is possible that other components also contribute.

It is intriguing that Artemisia species related to Yin Chin (e.g., wormwood, absinthe, mugwort, and tarragon) have been used in traditional medicines from many cultures for a variety of indications, including liver ailments, and a number of studies in animal models indicate hepatoprotective effects for various Artemisia extracts (46, 47). These effects have been attributed to antioxidant or other properties of the components of these extracts, but it is an interesting possibility that CAR activation is a contributing factor.

In summary, we have demonstrated the particular importance of CAR in regulating bilirubin clearance, demonstrated that this nuclear receptor mediates the effect of the natural herbal medicine Yin Zhi Huang on this process, and identified a specific active compound present in this mixture. CAR thus joins farnesoid X receptor (FXR) (48) and PXR (49, 50) as recently identified targets of significant biological effects of herbal medicines. We believe that these and other nuclear receptors with important metabolic regulatory functions will be found to mediate activities of other natural products. Based on the recent identification of a specific human CAR agonist (39), we also anticipate that more modern approaches to drug design based on CAR may yield new treatments for neonatal and other forms of jaundice.

    
Acknowledgments

We thank Steve S. Chua for generating the humanized CAR mice and Amethyst C. Kurbegov for preliminary results. This work was supported by NIH grant DK46546.

    
Footnotes

See the related Commentary beginning on page 23.

Conflict of interest: The authors have declared that no conflict of interest exists.

Nonstandard abbreviations used: solute carrier family 21, member 6 (SLC21A6); glutathione-S-transferase (GST); uridine diphosphate-5′-glucuronosyltransferase (UGT); multidrug resistance–related protein 2 (MRP2); constitutive androstane receptor (CAR); 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP); 5-pregnen-3β-ol-20-one-16α-carbonitrile (PCN); 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); cytochrome P450 1A1 (CYP1A1); pregnane X receptor (PXR); aryl hydrocarbon receptor (AhR).

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50.
Wentworth JM, Agostini M, Love J, Schwabe JW, Chatterjee VK. St. John’s wort, a herbal antidepressant, activates the steroid X receptor. J. Endocrinol. 2000;166:R11–R16. [PubMed]
---------------

818
WEB: http://members.aol.com/amalgami/klinghardtvortrag.html
PDF-Format: http://www.hpz.com/insider/VortragKlinghardt.pdf

Hier steht im Grunde alles, was wissenswert in dem Zusammenhang Schwermetallausleitung nach Dr. Klinghardt ist.

Sicherheitshalber habe ich die PDF Version hier auch noch als Attachment angehängt :-)

819
Hallo,

hier:
-----------------------
http://www.activeherb.com/jaundiclear/
-----------------------
JaundiclearTM
Concentrated Herbal Formula

JaundiclearTM (Yin Chen Hao Wan, Yin Chen Hao Tang, Yin Zhi Huang, Yin Zhi Huang Pian, 茵陈蒿汤, 茵栀黄汤) is a regarded Chinese herbal medicine commonly used by Chinese doctors for jaundice in newborn babies and hepatitis. Recently, a USA research in Baylor College of Medicine confirmed that the herbal remedy can accelerate the clearance of bilirubin (jaundice) and revealed the molecular pathway that links the formula to jaundice clearance.1

What does it do?
Jaundiclear was originally invented about 2000 years ago under the name of Yin Chen Hao Tang with a composition of 3 herbs: Artemisia capillaris (Yin Chen, Yin Chin), Gardenia jasminoides Ellis (Zhi Zi), Rheum officinale Baill (Da Huang). Artemisiae is the major herb in the formula that helps clear the jaundice. It also clears heat and dampness. Gardeniae and Rheum act to enhance the function of Artemisiae.

In the past 40 years, There have been some modifications of the original Jaundiclear recipe. Often times more herbs are added to the formula to reflect our current understanding on herbology and supposedly to enhance the action. The recipe we have here (see below) contains 10 herbs and carries the original name of Yin Chen Hao. The recipe used in the breakthrough study contains one extra herb, Scutellaria baicalensis Georgi (Huang Qin), and is named as Yin Zhi Huang.1

What does the study find?
Jaundice is the yellowing of the skin and whites of the eyes resulted from the accumulation of bile pigment bilirubin. In the new study published in the Journal of Clinical Investigation in 20041, the scientists led by Dr. David Moore were first able to confirm what scientists in China have long reported, that is, Yin Zhi Huang can significantly enhance the clearance of bilirubin from the serum and the liver in the animal model. Then, they were able to track down the protein in the body that mediates this effect of Yin Zhi Huang. The protein is a liver receptor called CAR (Constitutive androstane receptor), which is a key regulator of the bilirubin clearance pathway. When CAR is missing in the body, then Yin Zhi Huang can no longer clear bilirubin. Interestingly, Artemisiae by itself can increase the bilirubin clearance albeit at lower efficacy.

Surprisingly, the scientists were able to further narrow down a single molecule in Artemisiae that activates CAR which causes subsequent activation of proteins in the the bilirubin clearance pathway.

The study on Yin Zhi Huang is wonderful and nicely illustrated both the wisdom a Traditional Chinse medicine could be and how powerful the modern biomedical research can be in uncovering the mystery surrounding traditional Chinese medicines.
What is the formula composition?
A proprietary blend* of

Artemisia capillaris
Gardenia jasminoides Ellis
Rheum officinale Baill
Caulis Bambusae In Taeniam
Radix Isatidis
Cortex Phellodendri
Radix Bupleuri
Adix Curcumae
Poria
Pericarpium Citri Reticulatae
   
(Yin Chen, Yin Chin)
(Zhi Zi)
(Da Huang)
(Zhu Ru)
(Ban Lan Gen)
(Huang Bo)
(Chai Hu)
(Yu Jin)
(Fu Ling)
(Chen Pi)

*JaundiclearTM is made of 100% pure authentic Chinese herbs of highest qualities. Traditional preparation procedures are combined with modern pharmaceutical processes to extract the active ingredients from the herbs and to further concentrate them into pills or tablets. It is produced in the certified GMP facility of the famous Shanghai No. 1 Traditional Chinese Medicine Factory (Guang Ci Tang) and is imported to USA in accordance with the FDA guidelines.

It contains no pharmaceuticals, no artificial colors, and no sugar. Heavy metals are within or well beyond the standards set by US Pharmacopeia. Additionally, Plum Flower only uses its own brand unsulfured herbs for production.

What is Available?
Guang Ci Tang (40 grams in 200 pills per bottle).

How do I use it?
Take 6-8 pills 2-3 times daily for adults.
For children, dose should be reduced accordingly to the weight.

Use Discrimination

Side Effects
JaundiclearTM has been safely used with few adverse effects when used as directed.

Cautious Notes
1. Not suitable for jaundice with cold feeling of the body.
2. Keep out of reach of children.

References
1. Huang W, Zhang J, Moore DD. A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR. J Clin Invest. 2004 Jan;113(1):137-43.
----------------------------

821
Hallo,

im Moment kann ich noch nichts darüber sagen, angeblich existiert ein englisches Wissenschaftspapier aus dem man das herauslesen könne, nur haben es die Franzmänner in ihrem französischen Forum noch nicht geschafft, es mir zukommen zu lassen.

Sobald das passiert kann ich mir das ansehen und dann kann man mehr sagen...

Liebe Grüße

Medizinmann99

822
Blütenpollen / Blütenpollen
« am: 11. August 2006, 14:12:54 »
Hallo,

im englischen EZ Board gibt es dazu einen Erfolgsbericht, hier:

----------
http://p075.ezboard.com/fgilbertswebfrm3.showMessage?topicID=52.topic
----------

Hi
I must share a good news with you peers.
I’m from Poland and I have GS and hemolysis (intrinsic membrane defect of red cells) so I have higher bilirubin count then you - 6.4mg (120mmol).
I’ve tried everything possible to low down my bilirubin and be less yellow – at last a little bit.
My eyes were really yellow without a bit of white. It was very nasty when people suspect me to have hepatitis didn’t want give me a hand and look at me strangly. As a result I stoped to socialize and closed myself in my house. I hated mirrors.
It was pretty hard to find some medication that you talked about here (problem to translate into polish adequate names).I’ve never managed to translate and get the SAM - “S-adenosyl-methionine” (combine of amino acid methionine with adenosyl-triphosphate (ATP)).
Lets go to the point:
I tried milk thistle and dandelion root – helps only for my abdominal pain
natural amino acids eg. “Amino 2000”-Ultimate Nutrition Corporation ( you can buy it in stores with body building supplements). It gets what we need: glutamine, glycine, taurine,cysteine, methionine etc. It is wanderful to give you a lot of energy and a little lower bilirubin.
I’ve never wanted to try phenobarbital and glutethimide – it lower bilirubin but side effects are more harmful then yellow eyes. Tin-protoporphyrin is probably really good without side effects but I have problem to find sth adequate or medication with it in Poland.
What we (with GS) need to get rid of bilirubin is more glucuronic acid produced by liver or medication with it – I ‘ve got problem to find sth that consist it – if you find please let me know. I tried lots more staff but wrote only about that with good effects.
The only thin that really works is “Pollen”- I’m sorry it’s a polish name. It droped my bilirubin from 6.4 to 2.8 !!!
I tried to find translation for it but I failed. I try to explain to you what it is:
It is not medication but dietetic article of consumption, it is consist of flower pollen. The product is close related to Royal Jelly –(it didn’t work noticebly for me).
Let me know if it works for you.
Please visit www.emedicine.com/MED/topic870.htm - about GS

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

What I've taken is Pollen - the name is the same what it means in English.
To make it clear:

"Pollen - male generative element of seed plant. The shape of seed depends
on plant species, what can tell us about pollen derivation.
Pollen chemical composition depends not only on plant, but also on soil
fertility which is basic soil for a plant, on humidity and atmospheric
conditions during formulation and maturing of anthers. Pollen is obtain in a
pollen load form using special pollen traps, which are installed in hive
entrance.
Pollen content:
Chemical compound in % of different plant species.
Carbohydrates of pollen in 97% contain glucose, fructose, 3% residual are
vitamins, organic acids and amino acids. From 24 known amino acids in pollen
detected 20 of them. Floral pollen contains 36 bio-elements, which are
important ingredients of organism and which takes active role in it's
processes, for example Ca, Fe, Mg, Si, S, Cu, Br, Sr, Zn, Cr and others.
Average content of vitamins in floral pollen mixture.
Studies on pollen properties showed that it can be used in diabetics very
rich in vitamins, microelements and easy digestible protein resource. It
contain also some biological active agents. Consuming pollen in not large
amount is a good foodstuff, which improves good frame of mind and increases
body weight. Besides regulates intestines function in inflammation, helpful
during diarrhoea and obstruction. Pollen proofs clearly intellectually, what
is concerning with better blood supply. Pollen treatment gives positive
results in prostate gland inflammation. Antibiotics contain in pollen brakes
bacteria develop, particularly from Salmonella group, which are very
difficult to feight with another pharmaceutical preparations. "


Please visit the site of producer: www.apipol.com.pl/ang
-this is in English.
You can also order it (business info)-the price is aprox. 3 $ per packet (60
tablets).
Please let me know if you find any good article on internet on the pollen.

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


Bis jetzt habe ich nur herausgefunden (habe noch nicht wirklich recherchiert :-)) daß man die auch bei uns kaufen kann:

----------------------------
Blütenpollen werden in den Neuform Reformhäusern verkauft.
In dem indianischen Buch steht da unheimlich viel, da muß ich mal am Wochenende wieder alles lesen.
Sie werden auch in Rußland gegessen und wie gesagt, es ist ziemlich umfangreich.
Das Buch heißt Die Apotheke Manitus und ist von Stammel, einem sehr guten und seriösen Autor, also kein "verquaster Esofritze".
----------------------------

823
----------------------------------

A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR

Yin Zhi Huang, a decoction of Yin Chin (Artemisia capillaris) and three other herbs, is widely used in Asia to prevent and treat neonatal jaundice. We recently identified the constitutive androstane receptor (CAR, NR1I3) as a key regulator of bilirubin clearance in the liver. Here we show that treatment of WT and humanized CAR transgenic mice with Yin Zhi Huang for 3 days accelerates the clearance of intravenously infused bilirubin. This effect is absent in CAR knockout animals. Expression of bilirubin glucuronyl transferase and other components of the bilirubin metabolism pathway is induced by Yin Zhi Huang

Yin Zhi Huang contains extracts from four different plants:
Artemisia capillaris,
Gardenia jasminoides Ellis,
Rheum officinale Baill,
Scutellaria baicalensis Georgi.


Bilirubin is highly hydrophobic, and chronic hyperbilirubinemia results in its deposition in the central nervous system, causing neurotoxicity and encephalopathy. Some evidence suggests that chronic jaundice may also suppress the immune system as well as other normal physiological functions (4, 5).

CAR coordinately regulates the bilirubin clearance pathway. In addition to its function as a xenobiotic receptor, CAR responds to elevated levels of bilirubin by increasing the hepatic clearance of this toxic endobiotic (24)… Yin Zhi Huang stimulation of bilirubin clearance is dependent on CAR. The primary role of CAR in bilirubin metabolism is consistent with earlier studies showing positive effects of phenobarbital on jaundice (37, 38) .

Yin Chin (Artemisia capillaris) alone is considered to be the major active herb in the Yin Zhi Huang mixture.

6,7-Dimethylesculetin activates both mouse and human CAR. These results indicate that Yin Chin contains an agent or agents that can activate both mouse and human CAR. Among a number of compounds present in Yin Chin are the coumarin 6,7-dimethylesculetin (scoparone) and 4′-hydroxyacetophenone (Figure 4a). 6,7-Dimethylesculetin is a major constituent, comprising up to 2% of Yin Chin by dry weight and has been associated with a number of potential biologic actions (40).

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

Ich bin derzeit auf der Suche nach europäischen Bezugsquellen.

824
Hallo,

günstige Bezugsquellen für viele der hier genannten Dinge siehe
http://www.symptome.ch/vbboard/showthread.php?t=1701

sowie:
http://www.symptome.ch/vbboard/candida/6366-candida-medikamenten-preise-guenstige-medikamente-bezugsquellen.html
für Anti-Candida und Darmaufbaumittel

Ich bestelle auch regelmäßig Nahrungsergänzungsmittel aus den Vereinigten Staaten (USA). Siehe Sammelbestellungsboard, wer mitbestellen will!

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