By Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon

BACKGROUND

One of the functions an herb may have is designated cholagogue, meaning, to promote the flow of bile (Latin: chole). Herbs reputed to be cholagogues have several indications for use, but have been primarily given for alleviating diseases of the liver and gallbladder. Today, we have some additional information about how the flow of bile affects health, so that we can better appreciate the action of cholagogues.

The gallbladder and the fluid it stores, bile, are considered part of the digestive system, though there are also other important functions of bile production and secretion not directly related to digestion of foods. Bile is produced by liver cells (hepatocytes) which secrete it into microscopic canals (canaliculi) that empty into larger bile ducts (also called hepatic ducts), of which there are two branches (labeled left and right). The bile secreted by liver cells has large amounts of bile acids (cholic acids), which are metabolites of cholesterol, as well as cholesterol itself, and some other fatty molecules. In addition, bilirubin, a breakdown product of hemoglobin from red blood cell recycling, is also excreted by the hepatocytes. The bile flows via the left and right bile ducts that join together to form the common bile duct, which then joins into a branch duct, the cystic duct, that empties into the gallbladder; the common duct continues on to an exit duct (distil common bile duct) that opens into the small intestine. As the bile flows through these ducts, it is modified by secretions from the cells lining the ducts (ductal epithelial cells), which provide watery bicarbonate (calcium and sodium carbonates). The bile acids thus become bile salts. The gallbladder is located just a few inches below the stomach and the common bile duct enters the upper part of the small intestine, adjacent to the pancreatic duct where digestive enzymes are released.

The bile entering the common duct flows either into the gallbladder for temporary storage, or is emptied directly into the small intestine via the distal common bile duct; it is about equally divided between these two destinations. While residing in the gallbladder, much of the water is transported out (going into the blood stream), and the remaining material becomes highly concentrated. Consuming foods triggers certain hormones (e.g. cholecystokinin and secretin) and nerve signals that cause the gallbladder to contract while a sphincter at the end of the bile duct (sphincter of Oddi) relaxes, so that a large portion of the concentrated bile in the gallbladder is quickly dumped into the small intestine.

The bile mixes with food and solubilizes the fats. Bile salts essentially function like soap to dissolve the fats (so that they are not in clumps), leaving them to be readily absorbed and exposing them to enzymes (e.g., lipases discharged by the pancreas) that break down any of the fats that are in complex form. Aside from caloric fats, the bile also solubilizes other fatty nutrients, such as vitamins A, D, and E. Most of the bile salts in the intestines are recycled: they are absorbed through the intestine wall and eventually make it back to the liver and then into to the biliary ducts. It is estimated that bile salts are recycled 10-12 times per day. Some of the bile salts are excreted or broken down by intestinal bacteria.

Impairments to the flow of bile can arise from damage to the hepatocytes (e.g., with liver diseases); obstructions in the ducts or gallbladder; and dietary habits that might adversely affect emptying of the gallbladder. Among the adverse consequences from any such disruption of bile flow are digestive disorders due to fats being inadequately solubilized and absorbed (symptoms can include nausea, gas, and loose stool), formation and growth of gallstones (with abdominal pain and possible need for surgery), and liver damage (due to stasis of flow in the ducts).

CHOLORGENIC ACIDS

Chlorogenic acids are cholegogues; their regular ingestion helps the flow of bile and thus reduces the adverse effects of bile stagnation. Chlorogenic acids (see basic structure, below) are found in all higher plants and are understood to have a role in the plants response to stress, particularly to damage such as breaking of leaves and flowers or nicking the skin of fruits (1). The quantities present in most plants are miniscule, and thus they do not play an important part in human diet or herbal medicines. However, a few plants accumulate chlorogenic acids in quantities sufficient to have a physiological effect. The primary dietary source of chlorogenic acid is coffee; the green coffee beans typically contain 6-7% of this component (range: 4-10%); roasted coffee beans contain somewhat less, as the roasting transforms chlorogenic acids into other molecules, which may still retain the same functions.

It has been estimated that coffee drinkers may consume about a gram of chlorogenic acid each day. This amount of chlorogenic acid, when consumed regularly, appears to be sufficient to yield obvious therapeutic effects. Women are at greatest risk of forming gallstones, about twice that for men. In a large study conducted by Harvard University tracking of over 80,000 women, it was found that regular coffee intake reduced gallstone formation (2). The researchers correlated daily coffee consumption with incidence of gallbladder surgery due to stones: with increasing coffee consumption, gallstone surgery went down compared to those who did not drink coffee: 1 cup per day had no evident effect, but 2 cups per day reduced the incidence of the surgery by 9%, 3 cups reduced the incidence by 22%, and 4 or more cups reduced the incidence by 28%. Clearly, 3 cups per day, which is a typical amount for people who drink coffee routinely, had a dramatic effect.

Further, coffee consumption was associated with a lower risk of a variety of liver diseases, including liver cirrhosis and liver cancer (3, 4). This effect may come from a combination of cholagogue action (keeping toxins and fats flowing with the bile) and antioxidant effects (chlorogenic acid is a potent antioxidant and coffee drinking is one of the main sources of antioxidant activity in the American diet).

In response to the growing evidence of the value of chlorogenic acid, green coffee bean extracts, standardized to 50% chlorogenic acid, have been produced and sold has health products. Chlorogenic acid is also found as a significant component in certain commonly used medicinal herbs. In Chinese medicine, the primary source is lonicera flowers (jinyinhua); extracts are standardized according to chlorogenic acid content, often at 25% of the extract. Eucommia bark and gardenia fruit are also major sources, with extracts standardized to 20% chlorogenic acid. These extracts would yield a dose of about 1 gram of chlorogenic acids in 4-5 grams of extract, a rather large amount. Other Chinese herbs known for their chlorogenic acid content include chrysanthemum flower, crataegus fruit, artemisia leaves, and epimedium leaves.

In Western herbal medicine, an herb especially known for its chlorogenic acid content is artichoke leaves; the extracts are usually standardized to 15% of this compound. Other medicinal herbs known for content of chlorogenic acid include burdock root, dandelion root, and echinacea root. When using any of these herbs (Western or Chinese) and the concentrated herb extracts, other compounds that may contribute to a therapeutic benefit are also present. For example, artichoke leaves contain caffeol quinic acids (as found in roasted coffee) and cynarin, which is reputed to relieve abdominal gas and bloating, symptoms that occur with gallstones and poor bile flow.

While chlorogenic acids are not the only compounds that serve well as cholagogues, the evidence for their effectiveness is by far the strongest. This is primarily because of the coffee research which has allowed for tracking of large numbers of people over a long period of time. For other herbs, their effects on bile flow are usually observed in laboratory animal experiments, though the action might also be inferred from routine use of herbs in clinical applications of treating gallstones, abdominal bloating, upper abdominal pain, and constipation. In a data base for herbs, 140 species (representing 90 genera) were listed as cholagogues (5).

OTHER FACTORS INFLUENCING LIVER/GALLBLADDER HEALTH

High fat diet and high levels of blood cholesterol can lead to accumulations of fats in the liver, a syndrome which can eventually impair liver function. The fatty liver disorder is often diagnosed after a finding of elevated liver enzymes, especially in persons who are obese and/or have diabetes; other prominent causes are excessive alcohol consumption and effects of hepatic viruses. Viral hepatitis and chronic excess alcohol consumption can also lead to liver fibrosis, a scarring of liver tissue, which is (for the most part) irreversible.

Rapid weight loss is a significant factor in gallstone formation; this may come from shedding large amounts of fats via the bile while having too little bile flow stimulus from eating fats. Therefore, gradual weight loss is recommended instead. Also, some people mistakenly believe that a healthy diet is one which is free from coffee, and if this bile-flow promoter is discontinued at the same time a weight loss regimen is pursued, gallstones may form rapidly. Low to moderate alcohol use appears to help prevent gallstone formation, and excessive coffee consumption (e.g., more than six cups per day) may promote rather than inhibit gallstone formation.

A TRADITIONAL CHINESE HERB FORMULA FOR PURGING THE GALLBLADDER

The formula known as Capillaris Combination (Yin Chen Hao Tang) is well known for its ability to purge bile (6). Two of its herb ingredients, capillaris (Artemisia capillaris) and gardenia, have chlorogenic acid as an active component; rhubarb acts as a bile stimulant and laxative based on its content of anthraquinones, such as emodin. This formula was traditionally used for jaundice, hepatitis, and discomfort and fullness in the upper abdomen. Recently, there was much publicity about the use of a related formula called Yin Zhi Huang. This formula also contains capillaris, rhubarb, and gardenia, but adds a fourth ingredient: scute (huangqin). Among its traditional uses is treatment of jaundice, and contributing to relief of neonatal jaundice is one of the possible applications. It was shown that bilirubin clearance was promoted, at least in part, by activation of a nuclear receptor in hepatocytes (7).

REFERENCES

Dixon RA and Palva NL, Stress-induced phenylpropanoid metabolism, Plant Cell 1995; 7:1085-1097.
Leitzmann MF, et al., Coffee intake is associated with lower risk of symptomatic gallstone disease in women, Gastroenterology 2002; 123(6): 1823-1830.

Tverdal A and Skurtveit S, Coffee intake and mortality from liver cirrhosis, Annals of Epidemiology 2003; 13(6): 419-423.

Gelatti U, et al., Coffee consumption reduces the risk of hepatocellular carcinoma independently of its aetiology: a case-control study, Journal of Hepatology, 2005; 42(4): 528-534.
Plants for a Future Database: http://www.pfaf.org/database/search_use.php?K%5B%5D=Cholagogue

Shiguru A, et. al., A study of the effect of Capillaris Combination on the gallbladder, Bulletin of the Oriental Healing Arts Institute 1982; 7(3): 1-5.

Elferink RO, Yin Zhi Huang and other plant-derived preparations: where herbal and molecular medicine meet, Journal of Hepatology 2004; 41(4): 691-693.