encyclopedia

Bitters

Natural Sources:    

Artichoke leaves, flowers and seeds, Belgian endive, blessed thistle leaves and flowers, burdock root, chicory leaf and root, wild lettuce, milk thistle seeds and leaves, dandelion greens and flowers, other bitter Asteraceae plants, gentian root, Turkish rhubarb root, and many other bitter herbs traditionally used in bitter tonics.    
     

Forms:    

Standardized extracts in capsules and tablets, liquid tonics, dry herb blends, and tinctures.    

     
Therapeutic Uses:    

– Addiction
– Alcoholism
– Anorexia
– Anti-inflammatory
– Antioxidant
– Appetite Loss
– Bile Deficiency
– Cellular Regeneration
– Cholesterol Reduction
– Cirrhosis
– Cleansing
– Colds and Flu
– Detoxifying
– Digestive Disorders
– Dyspepsia
– Eyesight Disorders
– Fatty Liver Deposits
– Fever
– Gallstones
– Gastrointestinal Disorders
– Headaches
– Hepatitis
– High Cholesterol
– Hormone Imbalances
– Immune System
– Infections
– Jaundice
– Liver Health Maintenance
– Poisoning
– Scars (externally)
– Skin Disorders (Externally and Internally)
– Spasms
– Tonic
– Toxin Exposure     
     
    
Overview:

Herbs traditionally used as 'bitters' act to cleanse and rejuvenate the liver and stimulate bile flow for flushing the gallbladder and liver. All long-standing traditional schools of medicine, such as those from Europe, China and India, recognize the importance of regularly using a bitter tonic. When 'bitters' are tasted in the mouth, they stimulate the body to secrete saliva and convert cholesterol into bile. Studies confirm that bitters increase gastric juice and bile acid secretions by increasing the flow of saliva through stimulation of specific receptors on the mucous membrane lining of the mouth. Bitters also increase bile solubility and this aids digestion tremendously and reduces the likelihood of gallstone formation. Because bile breaks down fats, the more bitters in the diet, the more cholesterol is converted into bile and the faster fat digestion works, cutting cholesterol naturally. Bitters also stimulate appetite while at the same time cleansing the body of poisons and toxins and relieving a condition known as fatty liver congestion, associated with poor eyesight, hormone imbalances, skin problems and many other diseases. Clinical trials done on artichoke leaf juice and extract for lowering cholesterol have shown dramatic results within only 6-12 weeks. Several conventional cholesterol-lowering drugs are based on bile acid metabolism. Supporting the liver with bitter herbs is also considered essential in Traditional Chinese Medicine for normalizing hormone levels; the liver filters excess estrogen from the blood so it is very important that the liver is not clogged with fatty deposits and impaired in this vital function. The most highly researched 'bitter herb' for treating severe liver conditions is milk thistle, Silybum marianum. Many Europeans still use bitters before or after eating. Our ancestors well knew the importance of regularly using 'bitters' to strengthen and tone the body, but most North Americans no longer do this.
    
   
Chemistry:    

Bitter compounds from the plant family, Asteraceae, are often sesquiterpene lactones. The primary active ingredient of blessed thistle is a bitter tasting sesquiterpene lactone called cnicin. The bitter principles in artichoke, burdock and milk thistle are flavonolignans. Other bitter compounds include bitter-tasting flavonoid glycosides such as those from bitter orange peels including neohesperidin and naringin.    
     
    
Suggested Amount:    

Bitter tonics such as Swedish Bitters are recommended with the daily dosage of one to two teaspoons daily when using alcoholic extracts or four to five teaspoons daily for water extracts. Even just a teaspoon of 'bitters' daily can immediately improve the health of many individuals whose diet, high in animal products and sugar, is far too acidified and whose systems are clogged with bad fats. It is recommended not to use alcoholic bitters daily as this has been known to lead to alcoholism – aqueous extracts are much safer for this purpose. Alcoholic extracts are, however, useful for short-term use and for disinfecting skin sores and wounds externally. Swedish Bitters is reputedly effective for preventing scars and even reversing scars, however, there is no clinical evidence to substantiate this. Standardized milk thistle seed extract products are recommended with a dosage of 400-500mg daily for 6 to 8 weeks followed by a reduction to 200-300mg daily. Long-term therapy with the higher dosages may be required in serious or chronic cases. Crushed milk thistle seed, rarely used today, is generally taken as an herbal tea three to four times per day. As an aromatic bitter, a cup of the unsweetened tea is drunk half-an-hour before meals. German authorities recommend using 3-5g of the crushed seed per cup of tea (1 teaspoon of milk thistle seed weighs approximately 3.5 grams). It is recommended that boiling water be poured over the powdered seeds, or alternatively that cold water is added to the seed material and brought to the boil and after 20-30 minutes strained. See other individual herbs for specific dosages.    
     
    
Drug Interactions:    

Bitters may lower blood glucose levels in diabetics and interfere with existing hypo- or hyperglycemia therapy, therefore careful monitoring of blood glucose levels is required in these cases. Hypoglycemic drugs include: insulin, Glucophage(R) metformin, DiaBeta(R) Glynase(R) glyburide, Glucotrol(R) glipizide).    
     
    
Contraindications:    

Bitters may lower blood glucose levels in diabetics and interfere with existing hypo- or hyperglycemia therapy, therefore careful monitoring of blood glucose levels is required in these cases. Milk thistle as a source of bitters is considered safe for use during pregnancy and has a long history of use by nursing mothers.    
   
     
Side Effects:    

Many bitter tonics contain herbs with laxative action and may produce a mild laxative action when taken in recommended dosages. Depending upon the herb being used and the dosage being taken, bitters can also produce a strong laxative action when taken excessively. No side effects have been reported during clinical trials with standardized milk thistle extracts. Milk thistle products may produce a mild laxative effect in some people due to stimulating effects on bile secretion. Use of milk thistle extract may also lower blood glucose levels.    
     
    
References:     
     
Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, Meryn S, Base W, Schneider B. 1989. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul; 9(1): 105-13.
 
Gebhardt R. 2001. Anticholestatic activity of flavonoids from artichoke (Cynara scolymus L.) and of their metabolites. Med Sci Monit 2001 May; 7 Suppl 1: 316-20.
 
Kondo Y, Takano F, Hojo H. 1994. Suppression of chemically and immunologically induced hepatic injuries by gentiopicroside in mice. Planta Med 1994 Oct; 60(5): 414-6.
 
Pittler MH, Thompson CO, Ernst E. 2002. Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database Syst Rev 2002; (3): CD003335.
 
Zhou L, Hao R, Jiang L. 1999. [Clinical study on retarding aging effect of tongbu recipe to traditional Chinese medicine]. [Article in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi 1999 Apr; 19(4): 218-20.

References:
1. Stitch etal. Occurrence of lignans, enterolactone and enterodiol in man and animal species. Nature. 1980; 287: 238.

2. Duke J; Handbook of Biologically Active Phytochemicals and their Activities. Boca Raton, FL: CRC Press; 1991: 32.

3. Rodriguez etal. Biological activities of sesquiterpene lactones. Phytochemistry. 1976; 15: 1573-1580.

4. Bradley PRe; British Herbal Compendium. Volume 1, A handbook of scientific information on widely used plant drugs. Holy Thistle. Bournemouth, Dorset: British Herbal Medicine Association; 1992.

5. Hardman eae; Goodman and Gilmans “The Pharmacological Basis of Therapeutics. 9th ed. McGraw-Hill Health Professions Division; 1996.

6. Weiss RF; Herbal Medicine. Translated from the 6th German edition of Lehrbuch der Phytotherapie by A.R. Meuss, FIL, MITI. Beaconsfield, Bucks, England: Beaconsfield Publishers, Ltd.; 1988.

7. Schneider G, Lachner I. A contribution to analytics and pharmacology of cnicin. Planta Medica. 1987; 53: 247.

8. European Scientific Cooperative on Phytotherapy; Wormwood, Dandelion, Gentian. Execter, U.K.: ESCOP Secretariat Argyle House; 1997.

9. Facino ea. Free radical scavenging action and anti-enzyme activities of procyanidines from Vitis vinifera. Arzneim-Foprusch. Drug Res. 1994; 44: 592-601.

10. Vanhaelen-Fastre R, Vanhaelen M. Antibiotic and cytotoxic activity of cnicin and of its hydrolysis products. Chemical structure – biological activity relationship. Planta Medica. 1976; 29: 179-189.
    

Additional Information:     
     
Bitter Herbs Once Popular:
Cultivated lettuce has been bred to remove the bitterness so unless individuals eat bitter greens or use bitter herbs, most do not receive the benefits of 'bitters'. Many modern drugs today are based on traditional herbs that had strong bitter properties to complement the active ingredients. For example, the first person to organize a clinical trial of willow bark (containing salicylate or 'natural aspirin'), Reverend Edward Stone of Oxfordshire, was surprised by the bitter taste, which reminded him of cinchona bark (containing quinine), then being used to treat malaria.
 
The Master Bitter Herb – Milk Thistle:
Genetic research has shown that there is a significant percentage of the human population that has a gene that predisposes them to like the bitter taste. However, bitter herbs are generally perceived as quite unpleasant to taste for many people. For those wanting to avoid the bitter taste while still benefiting from bitter herbs, it is possible to use milk thistle seed extract in capsule form, which has proven efficacy for treating liver disease. Milk Thistle, Silybum marianum (L.) GAERTN. [Fam. Asteraceae], is most well known for its ability to prevent death from death cap mushroom poisoning. Many Poison Control Centers across Europe are said to carry the extract. In Amanita poisoning, silibinin dramatically reduces death rates from 30 to 50% down to less than 10%. In the 1890s and early 1900s, pharmacies across the U.S. also carried the extract for treating liver, spleen and kidney congestion. Milk thistle has been used as a medicine since early Greco-Roman times, particularly for supporting the liver in detoxifying the blood. Through its bitter properties, milk thistle increases the flow of gastric juices relieving dyspepsia, indigestion and headaches associated with liver congestion. The liver is considered by many to be the master organ of the body (together with the kidneys in Traditional Chinese Medicine). Milk thistle cleanses the liver and once the liver is free of excessive fatty deposits and toxins, it is better able to properly filter the blood. Detoxification also helps prevent abnormal growths within the body. The German Pharmacopoeia recognizes milk thistle extracts for preventing and treating damage to the body from poisons and toxins, and as supportive treatment in chronic inflammation and cirrhosis of the liver. Based on double-blind placebo controlled trials, milk thistle seed extract improves symptoms of viral hepatitis including jaundice, nausea, weakness, appetite loss, fatigue, and pain and also prevents damage from pharmaceutical drugs. A double-blind placebo-controlled trial following 146 people with cirrhosis for 3 to 6 years found that for the treated group, the 4-year survival rate was 58% as compared to only 38% in the placebo group. Another controlled study following 106 people with alcoholic cirrhosis over a period of 4 weeks showed a significant decrease in elevated liver enzymes and improvements in cell health as evaluated by biopsy, benefits also documented with hepatitis. Another controlled trial with 172 people with cirrhosis found a significant reduction in mortality over 4 years. A 2-year study showed no lifespan benefits, suggesting long-term use is required.

Blessed Thistle as a Bitter Herb (Cnicus benedictus L.)
 
Composition
The primary active ingredient of blessed thistle is a bitter tasting compound called cnicin, a sesquiterpene lactone.  The seed contains several lignans that are phytoestrogen precursors for the key mammalian lignans: enterolactone and enterodiol, which are present in humans and animals1. Cnicin aids digestion and has considerable antitumor, cytotoxic, antimicrobial and phytotoxic activity2,3.
 
Mechanism of action
1) Choleretic and hypolipidemic action: Through its bitter properties, blessed thistle increases the flow of gastric juices relieving dyspepsia, indigestion and headaches associated with liver congestion4.  British and German Pharmacopoeias recognize that 'bitters', including blessed thistle, stimulate bile flow and cleanse the liver.  Bitter compounds and commercial anti-cholesterolemic drugs such as cholestyramine and colestipol promote bile acid excretion and conversion of cholesterol to bile acids5.  In Europe “bitter vegetable drugs” are considered medicinal agents and used to stimulate appetite, aid digestion, and promote health6.  Studies confirm that bitters increase gastric juice and bile acid secretions by increasing the flow of saliva through stimulation of specific receptors on the mucous membrane lining of the mouth7.
2) Tonifying:  Traditionally in most countries, including England, Germany, Russia, China, India and Africa, bitters are used to strengthen and tonify the body8.  Certain bitter compounds found in the leaves, stems and barks of many plants such as the oligomeric proanthocyanidins concentrated in pine bark and grape seed, have been shown to improve blood circulation by binding to the membranes of blood vessels and capillaries, repairing collagen and elastin and preventing their degradation by enzymes and free radicals, thereby strengthening the vascular system9.
3) Antibiotic activity:  Blessed thistle extracts have anti-bacterial activity.  Research on blessed thistle herb has demonstrated antibiotic properties for: 1) cnicin10, 2) the essential oil which includes n-paraffin (C-9 – C-13), aromatic aldehydes (cinnamaldehyde, benzaldehyde, cuminaldehyde) and monoterpenes (citronellol, fenchone, p-cymene and others), and 3) the polyacetylenes contained in the herb.  The essential oil has bacteriostatic action against Staphylococcus aureus, S. faecalis, but not E. coli.

Traditional Use of Bitters:
Supporting the liver with bitter herbs is considered essential in Traditional Chinese Medicine for normalizing hormone levels; the liver filters excess estrogen from the blood so it is very important that the liver is not clogged with fatty deposits and impaired in this vital function. The most highly researched 'bitter herb' for treating severe liver conditions is milk thistle, Silybum marianum. The young leaves of this plant, with the spines removed, are edible and can be eaten as a vegetable. Like all of the other plants mentioned above, milk thistle is closely related to lettuce and is part of the plant family Compositae which contains many safe food-type herbs for stimulating bile flow and cleansing the liver. Traditionally, a tea made from the whole plant was used to improve appetite, allay indigestion and restore liver function. Milk thistle seed extract is widely recognized throughout Europe by medical doctors for it's ability to save a person's life from death cap mushroom poisoning. Medical researchers explain it this way: milk thistle seed extract stimulates the liver to produce the proteins and enzymes it is supposed to produce in order to detoxify the blood (of alcohol or any other poison). The active ingredients, called silymarin flavonoids, are concentrated in the seeds and include silybin and silychristin – which are also found in minor amounts in the leaves and stems. In fact, standardized milk thistle seed extract products, like Flora's Sil-Mar, are available at every poison control center of Europe. Milk thistle seed extract products used to be available at pharmacies across North America, that is, until the advent of modern medicine and it's accompanying irrational bias against herbal medicines prevented them from helping many people. Milk thistle seed extract is listed in the German Pharmacopeia and is used for treating: fatty liver, enlarged liver, to help reverse the symptoms of liver cirrhosis, including alcohol induced, to speed the recovery from hepatitis B and C and reverse the nausea and other symptoms of liver congestion and jaundice, often within only 5 to 8 days with 430 mg/day of standardized extracts containing 70-80% silymarin.
 
If liver function is impaired and estrogen levels rise abnormally high, this can pose a real health risk. In fact, it is not uncommon for alcoholic men to begin developing breasts and losing body hair because alcohol is “estrogenic” and damages the liver so that it no longer is able to filter excess estradiol from the blood. Synthetic estrogens from plastics and pesticides in our environment can also tax the liver and skew hormone levels, as can many animal products with residual growth hormones. Many cancers are estrogen-related or fed by estrogen, so it is a good idea to support proper liver health. The condition commonly referred to as Estrogen Dominance is marked by high blood levels of estradiol which skew the body's normal estrogen to progesterone ratio. Estrogen Dominance is associated with many hormone-related diseases of both men and women including breast, ovarian, uterine, prostate, and testicular cancers, menopausal problems, osteoporosis, mastalgia, PMS and eczema, to name only a few (Lee 1993; Lee 1991; Lee 1990; Lee 1990b). The current diet, high in 'bad fats' (Erasmus 1993) and sources of 'xenoestrogens' (synthetic estrogen mimickers from plastics, pesticides and certain pharmaceutical drugs) (Raloff 1993) tend to elevate estrogen levels, causing havoc within the body. So regular use of safe food-type bitter herbs in the diet can help to prevent this process.

One example of a traditional bitter tonic that has been used successfully to treat many conditions comes from the famous Austria herbalist, Maria Treben. The original formula was found among the writings of the well-known Swedish physician, rector of medicine, Dr. Samst. He died in his 104th year in a riding accident. His parents and grandparents all reached a patriachal age, attributed in no small part to their regular use of recognized and healing bitter herbs. Maria Treben herself was cured of a very serious complaint by using Swedish Bitters. In her best selling book, Health Through God's Pharmacy, Maria recounts the story of her own near-death encounter with typhoid fever. She was a refugee from the German speaking area of Czechoslovakia and contracted typhoid fever in a camp in Bavaria caused by contaminated meat and through it, came jaundice and an obstruction in the intestines. She spent more than 6 months in hospital and when her husband got her child and herself to Austria, she was a young but sick woman. She described herself as a helpless bundle of misery with the afterpains of the typhoid fever leaving her listless. She then describes how an old woman brought her a small bottle containing a dark brown, strong smelling liquid along with an “old manuscript” containing information on the 'Swedish Bitters' contained in the bottle. The old manuscript explained, in 46 pionts, how these drops can help to heal every illness. She was skeptical but decided to try it anyway. She first used the Swedish Bitters externally as a compress to her abdomen. She writes that with this one compress, which she left on all day, all complaints of the preceding months disappeared, never to return. Maria remarks on several other applications of Swedish Bitters, not least of which includes scar healing.
 
Upon reading the old manuscript, she discovered that point 33 stated that this tincture can help significantly with the healing and removal of scars, wounds and cuts, even if very old, if moistened up to 40 times. She treated the scars of a relative of her's in this way and soon they disappeared, even the very deep ones. For many decades she helped other people with this formula and found it effective for treating: headaches; pneumonia; frontal sinusitis; loss of appetite; melancholy and depression; stiffness and crippling of the hands; deformation of the legs; deformation of the joints; skin discoloration; swelling; poisonous insect bites; black eye; gall bladder attacks; localized pain and itching; hearing problems (in combination with oil – as directed by Maria in her book); Meningitis; head injuries; stuttering and speech disorders; bursitis; detached and/or porous retina; eye strain; fatigue; colds; bronchitis; renal colic; knee and ankle sprains; spasms; epilepsy; acute gastritis and disorders of the pancreas; swollen liver; anaemia; diabetes; toothache and festering jaw fistulas; worms; constipation; warts; liver spots; corns; moles; haemorrhoides; thrombosis and cancers of many different kinds.
 
Many people, at this point, may be asking how it is that one tonic can be helpful for so many different and seemingly unrelated conditions. But the fact is that the state of the liver is fundamentally related to health in so many different ways that it is actually understandable. Renowned Ayervedic doctor and researcher from India, Dr. S. Farooq M.Sc., Ph.D. (Gold Medalist), Av.R., P.G.D.B.M, F.R.S.II. (London), expresses the importance of bitters in this way, “In the text of Indian Traditional Medicine books of Ayurveda it is time and again mentioned that when your body gets disease – take bitters or if there are ailments of unknown etiology then also bitters should be given” (Farooq 1998, pers. comm.).

Clinical Research on Bitter Herbs:

Gebhardt R. 2001. Anticholestatic activity of flavonoids from artichoke (Cynara scolymus L.) and of their metabolites. Med Sci Monit 2001 May; 7 Suppl 1: 316-20.
 
It is well known that water-soluble extracts of artichoke (Cynara scolymus L.) leaves exert choleresis. When studying this effect in vitro using primary cultured rat hepatocytes and cholephilic fluorescent compounds, it was noticed that the artichoke leaf extracts not only stimulated biliary secretion, but that they also reestablished it when secretion was inhibited by addition of taurolithocholate to the culture medium. Furthermore, taurolithocholate-induced bizarre bile canalicular membrane distortions detectable by electron microscopy could be prevented by artichoke leaf extracts in a dose-dependent manner when added simultaneously with the bile acid. These effects were exerted by the flavonol luteolin and, to a lesser extent, by luteolin-7-O-glucoside, while chlorogenic acid and 1.5-dicaffeoyl quinic acid were almost ineffective. Surprisingly, metabolites produced by the cultured hepatocytes were able to stimulate biliary secretion substantially as well as prevent canalicular membrane deformation. These results demonstrate that artichoke leaf extracts exert a potent anticholestatic action at least in the case of taurolithocholate-induced cholestasis. Flavonoids and their metabolites may contribute significantly to this effect.
 
Pittler MH, Thompson CO, Ernst E. 2002. Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database Syst Rev 2002; (3): CD003335.
 
BACKGROUND: Hypercholesterolaemia is directly associated with an increased risk for coronary heart disease and other sequelae of atherosclerosis. Artichoke leaf extract (ALE), which is available as an over-the-counter remedy, has been implicated in lowering cholesterol levels. Whether ALE is truly efficacious for this indication, however, is still a matter of debate.
OBJECTIVES: To assess the evidence of ALE versus placebo or reference medication for treating hypercholesterolaemia defined as mean total cholesterol levels of at least 5.17 mmol/L (200 mg /dL).
SEARCH STRATEGY: We searched MEDLINE, Embase, Amed, Cinahl, CISCOM and the Cochrane Controlled Trial Register. All databases were searched from their respective inception until June 2001. Reference lists of articles were also searched for relevant material. Manufacturers of preparations containing artichoke extract and experts on the subject were contacted and asked to contribute published and unpublished material.
SELECTION CRITERIA: Randomized controlled trials of ALE mono-preparations compared with placebo or reference medication for patients with hypercholesterolaemia were included. Trials assessing ALE as one of several active components in a combination preparation or as a part of a combination treatment were excluded.
DATA COLLECTION AND ANALYSIS: Data were extracted systematically and methodological quality was evaluated using a standard scoring system. The screening of studies, selection, data extraction and the assessment of methodological quality were performed independently by two reviewers. Disagreements in the evaluation of individual trials were resolved through discussion.
MAIN RESULTS: Two randomised trials including 167 participants met all inclusion criteria. In one trial ALE reduced total cholesterol levels from 7.74 mmol/l to 6.31 mmol/l after 42 +/- 3 days of treatment whereas the placebo reduced cholesterol from 7.69 mmol/l to 7.03 mmol/l (p=0.00001). Another trial did state that ALE significantly (p<0.05) reduced blood cholesterol compared with placebo in a sub-group of patients with baseline total cholesterol levels of more than 230 mg/dl. Trial reports and post-marketing surveillance studies indicate mild, transient and infrequent adverse events.
REVIEWER'S CONCLUSIONS: Few data from rigorous clinical trials assessing ALE for treating hypercholesterolaemia exist. Beneficial effects are reported, the evidence however is not compelling. The limited data on safety suggest only mild, transient and infrequent adverse events with the short term use of ALE. More rigorous clinical trials assessing larger patient samples over longer intervention periods are needed to establish whether ALE is an effective and safe treatment option for patients with hypercholesterolaemia.
 
Zhou L, Hao R, Jiang L. 1999. [Clinical study on retarding aging effect of tongbu recipe to traditional Chinese medicine]. [Article in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi 1999 Apr; 19(4): 218-20.
 
OBJECTIVE: To study the mechanism of Tongbu No. 1 (TB1, a prescription for reinforcing Kidney and Spleen, clearing up the bowel viscera to send Turbid downward and regulating Qi and blood) in retarding aging.
METHODS: A controlled, multiple indexes study was conducted in 56 old subjects randomized into 3 groups.
RESULTS: TB1 (containing ginseng leaf, cistanche, fleeceflower root, immature bitter orange, rhubarb, etc) could improve various symptoms of aging, and had the effect in regulating immune and endocrinal function, scavenging free radicals and adjusting coli flora. The effects of TB1 and TB2 (containing ginseng leaf, cistanche and fleeceflower root) were different significantly (P < 0.05, P < 0.01).
CONCLUSION: TB1 has a good comprehensive effect in retarding aging.
 
Kondo Y, Takano F, Hojo H. 1994. Suppression of chemically and immunologically induced hepatic injuries by gentiopicroside in mice. Planta Med 1994 Oct; 60(5): 414-6.
 
Gentiopicroside (GPS), a main bitter secoiridoid constituent of roots of Gentiana macrophylla Pall., was tested for therapeutic effects on the two hepatic injury models, the CCl4-induced and lipopolysaccharide (LPS)/bacillus Calmette-Guerin (BCG)-induced hepatitides. An increase in serum level of hepatic aminotransferases (GOT: EC 2.6.1.1. and GPT: EC 2.6.1.2.) induced by a p.o. treatment of CCl4 was suppressed by pretreatment with GPS at 30-60 mg/kg/day for 5 consecutive days. An increase of these enzymes triggered by an i.v. treatment with LPS in mice primed with bacillus Calmette-Guerin (BCG) was also inhibited by GPS pretreatment at the same dose of GPS. In the BCG/LPS model, tumor necrosis factor (TNF), a major inflammatory mediator, was increased in serum with a peak at 90-120 min, followed by an increase of serum transaminase activities. GPS treatment significantly suppressed the increase of TNF in serum at the therapeutic doses, suggesting that GPS protected against hepatitis by inhibiting the production of TNF.
 
Vane JR. 2000. The fight against rheumatism: from willow bark to COX-1 sparing drugs. J Physiol Pharmacol 2000 Dec; 51(4 Pt 1): 573-86.
 
The William Harvey Research Foundation, London, UK.
 
Man has been fighting rheumatism for thousands of years. Early therapy began with the use around the world of decoctions or extracts of herbs or plants such as willow bark or leaves. Most or all of these turned out to contain salicylates. The first record was about 3,500 years ago in the Ebers papyrus. Hippocrates, Celsus, Pliny the Elder, Dioscorides and Galen all recommended decoctions containing salicylate for rheumatic pain. A country parson, the Reverend Edward Stone of Chipping Norton in Oxfordshire, made the first “clinical trial” of willow bark (1). He was surprised by its bitter taste, which reminded him of cinchona bark (containing quinine), then being used to treat malaria. He harvested a pound of willow bark, dried it, pulverized it and dispersed it in tea, small beer or water. He found in 50 patients that doses of 1 dram (1.8g) cured their fever. He concluded “I have no other motives for publishing this valuable specific, than that it may have a fair and full trial in all its variety of circumstances and situations, and that the world may reap the benefits accruing from it”. Salicylic acid was chemically synthesised in 1860 by Kolbe in Germany and its ready supply led to even more extended usage as an external antiseptic, as an antipyretic and in the treatment of rheumatism.
 
Gebhardt R. 2001. Anticholestatic activity of flavonoids from artichoke (Cynara scolymus L.) and of their metabolites. Med Sci Monit 2001 May; 7 Suppl 1: 316-20.
 
High-dose aqueous extracts from artichoke leaves were found to inhibit cholesterol biosynthesis from (14)C-acetate rather moderately in HepG2 cells in contrast to primary cultured rat hepatocytes in which the inhibition was stronger. Preincubation of the extracts with several glycohydrolases revealed that pretreatment with beta-glucosidase considerably reinforced the inhibition. A significant reduction of acetate incorporation was found above extract concentrations of 0.01 mg/mL and at 0.2 mg/mL almost 60% inhibition was observed. Cytotoxic effects detected by the MTT-assay were restricted to higher concentrations of the extracts with and without beta-glucosidase pretreatment. Since cynaroside represents a major glucoside in artichoke extracts, both cynaroside and its aglycone luteolin were tested. It could be demonstrated that cynaroside is indeed one of the targets of beta-glucosidase and that the liberated luteolin is responsible for the inhibitory effect. Direct measurements of beta-glucosidase activity in rat hepatocytes and HepG2 cells revealed that endogenous enzyme activity in hepatocytes may be sufficient to convert cynaroside to its aglycone, while in HepG2 cells this may not be the case. These findings emphasize the importance of beta-glucosidase-dependent liberation of luteolin for the ability of artichoke extracts to inhibit hepatic cholesterol biosynthesis. Copyright 2002 John Wiley & Sons, Ltd.
 
Englisch W, Beckers C, Unkauf M, Ruepp M, Zinserling V. 2000. Efficacy of Artichoke dry extract in patients with hyperlipoproteinemia. Arzneimittelforschung 2000 Mar; 50(3): 260-5.
 
Efficacy and tolerability of artichoke dry extract (drug/extract ratio 25-35:1, aquous extract, CY450) as coated tablets containing 450 mg extract (tradename: Valverde Artischocke bei Verdauungsbeschwerden) was investigated in the treatment of hyperlipoproteinemia and compared with placebo. 143 adult patients with initial total cholesterol of > 7.3 mmol/l (> 280 mg/dl) were included in a double blind, randomized, placebo controlled, multi-center clinical trial. Patients received 1,800 mg artichoke dry extract per day or placebo over 6 weeks. Changes of total cholesterol and LDL-cholesterol from baseline to the end of treatment showed a statistically significant superiority (p = 0.0001) of artichoke dry extract over placebo. The decrease of total cholesterol in the CY450 group was 18.5% compared to 8.6% in the placebo group. LDL-cholesterol decrease in the CY450 group was 22.9% and 6.3% for placebo. LDL/HDL ratio showed a decrease of 20.2% in the CY450 group and 7.2% in the placebo group. There were no drug related adverse events during this study indicating an excellent tolerability of artichoke dry extract. This prospective study could contribute clear evidence to recommend artichoke dry extract CY450 for treating hyperlipoproteinemia and, thus, prevention of atherosclerosis and coronary heart disease.