Liver Health and Botanicals

By Yousry Naguib, Ph.D.

Vitamin Retailer magazine, June 2005

The liver is the largest single organ (1.5 kg in the adult) in the human body that contains more than 10 percent of the total volume of blood at any moment, and is well known for its role in metabolism and detoxification. It weighs about three pounds, is roughly the size of a football, and is located in the upper right-hand part of the abdomen, behind the lower ribs. It filters over a liter of blood each minute and plays a central role in nearly all body functions, including:

• Converting food into chemicals the body needs to remain healthy;

• Detoxifying the blood by filtering out toxins from blood into digestive system for excretion;

• Producing bile, a liquid that is essential for digestion;

• Controlling the production and excretion of cholesterol;

• Maintaining the proper levels of chemicals and drugs in the blood; and

• Regulating hormone levels.

Many of the body’s metabolic functions occur primarily in the liver, including the metabolism of cholesterol and the conversion of proteins and fats into glucose. The liver is also where most drugs and toxins, including alcohol, are metabolized.

The bile secreted by the liver is a complex aqueous liquid composed of electrolytes, proteins, lipids, bilirubin, amino acids, and vitamins. The components of bile are synthesized in hepatocytes (the predominant cell type in the liver) and secreted into small ducts within the liver itself. These small ducts form a branching network of progressively larger ducts that ultimately become the common bile duct that takes bile to the small intestine.

The main functions of bile are to eliminate toxic lipophilic compounds, excrete cholesterol, and participate in the digestion and absorption of lipids and lipid-soluble vitamins.

There are many types of liver diseases, and some can be life-threatening unless treated, such as chronic hepatitis (inflammation of the liver), cirrhosis, and fatty liver (steatosis). Symptoms of liver disease include: jaundice (yellowing of the skin or eyes), dark urine, nausea, vomiting of blood, bloody or black stools, fatigue, and abdominal swelling or pain.

Chronic hepatitis can lead to cirrhosis of the liver. Cirrhosis occurs when the liver cells die and are replaced by fibrous tissue which leads to fibrosis (scarring). Cirrhosis interferes with blood flow through the liver leading to an inability of the liver to perform its biochemical functions. Symptoms of cirrhosis include weight loss, fatigue, nausea, vomiting, and loss of appetite.

Complementary and alternative medicine is becoming popular among patients with liver disease.

Milk Thistle

Milk thistle (Silybum marianum) has been used medicinally for over 2,000 years, most commonly for the treatment of liver and gallbladder disorders. The biologically active component extracted from the seeds of milk thistle is believed to be a group of flavone lignans including silybin, silidianin, silychristin, isosilybin, collectively called silymarin.

Silymarin and other flavone lignans seem to protect liver cells by acting as antioxidants. Milk thistle also stimulates protein synthesis, which accelerates cell regeneration within the liver.

Clinical studies suggest benefits of milk thistle for liver cirrhosis. In an Austrian study involving 170 alcoholic and non-alcoholic patients with cirrhosis, those received 140 mg silymarin three times daily for an average of 41 months had a 58 percent four-year survival rate; while those receive a placebo had a 39 percent four-year survival rate. The study also found that silymarin treatment was more effective in patients with alcoholic cirrhosis.¹

However, another double-blind, randomized and multi-center found that silymarin had no effect on survival and the clinical course in alcoholics with liver cirrhosis.²

In a 2004 study, 177 residents of an Egyptian village with chronic hepatitis C were randomly assigned to receive either silymarin or multivitamin supplements for one year. At the end of treatment period, both the silymarin and vitamins groups reported feeling better, although symptoms and quality-of-life scores, serum alanine aminotransferase (ALT) levels, and serum hepatic fibrosis markers did not differ between the two groups.

ALT is an enzyme that is found primarily in the liver. It is released into the bloodstream as a result of liver damage. The study suggested that more prolonged treatment and a higher dose may be required to ascertain whether milk thistle supplements prevent complications of chronic hepatitis C virus.³

In a trial assessing the effect of a silybin-phosphatidylcholine complex in chronic hepatitis, eight patients with chronic hepatitis B or C were given a silybin-phosphatidylcholine complex equivalent to 120 mg silybin twice daily for 60 days. At the end of the 60-day period, levels of the liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), total bilirubin, and serum malondialdehyde (a marker of lipid peroxidation) were significantly reduced.⁴

AST is an enzyme present in liver cells; its level in blood is raised in conditions that affect the liver such as viral hepatitis. GGT is an enzyme that is often elevated above normal levels in hepatitis and conditions that cause chemical liver damage.

Schisandra

Schisandra (Schisandra chinensis) is used in traditional Chinese medicine for cough, diarrhea, and sweating. It is also used as an adaptogen. In animal models, schisandra was demonstrated to protect the liver against various toxins. In one study, rats administered 1ml/kg carbon-tetrachloride (CCl4) 24 hours after receiving schisandra extract showed protection from hepato-toxicity.^{5, 6} CCl4-induced hepato-toxicity is a commonly used model for investigating tissue injury.

Various lignans, including schisandrin, schisandrol, and deoxy-schisandrin are believed responsible for the activity of schisandra, but limited research evaluates its mechanism of action. A synthetic analogue of schisandrin called DDB (Dimethyl-4,4’-dimethoxy-5,6,5’, 6-dimethylenedioxybiphenyl-2,2’-dicarboxylate) is now used widely in China as a hepato-protective drug.

DDB has the ability to lower the elevated liver enzymes levels of patients suffering from chronic viral hepatitis. DDB treatment of patients (10 with chronic hepatitis C, 1 with chronic hepatitis B, 2 with non-alcoholic hepatitis) with persistently elevated ALT levels rapidly normalized their ALT levels and remained normal during treatment. The levels of AST, and GGT were not affected.⁷ A typical dosage of DDB is 7.5 mg three times per day.

Glycyrrhizin

In Europe, a daily injection of glycyrrhizin has been shown to normalize ALT levels in patients with chronic viral hepatitis. Patients with chronic hepatitis C were administered intravenous glycyrrhizin three or six times per week for four weeks. At the end of treatment, ALT levels were significantly decreased by 26 percent and 47 percent for three times per week and six times per week, respectively.⁸

Shosaiko-to

Shosaiko-to (Xiao Chai Hu Tang) is widely used for the treatment of chronic hepatitis. Shosaiko-to (SST) is made from the hot water extraction of seven herbal components: Bupleurum root, Pinellia tuber, Scutellaria root, Jujube fruit, Ginseng root, Glycyrrhiza root and ginger rhizome. SST contains several active compounds, including baicalin, wogonin-7-O-glucuronide, liquiritin and their three a glycons, liquiritin apioside, baicalein, glycyrrhizin, glycyrrhetic acid, saikosaponin b1, saikosaponin b2, ginsenoside Rg1, ginsenoside Rb1, gingerol, shogoal, and arginine.

In a multi-center, double-blind placebo clinical trial on 122 patients with chronic active hepatitis, treatment with SST at a daily dose of 5.4 g for 24 weeks significantly reduced serum AST and ALT levels.⁹

Sho-saiko-to contains bupleurum (Bupleurum chinense, Bupleurum scorzoneraefolium) as the major ingredient. Bupleurum is a common herb used in traditional Chinese medicine. Its actives saiko saponins are believed to contribute to bupleurum’s medicinal properties. Saiko saponin-d has immuno-regulatory activity by promoting interleukin-2 production.¹⁰ Interleukin-2 is a hormone like substance released by T-lymphocytes (subpopulation of white blood cells that fight infection and disease) that can improve the body’s response to disease.

Picrorhiza kurroa

The root and rhizomes of Picrorhiza kurroa have traditionally been used in the Ayurvedic medicine to treat disorders of the liver and upper respiratory tract. The hepato-protective action of Picrorhiza kurroa has been attributed to Picrorhiza’s ability to inhibit the generation of oxygen anions and to scavenge free radicals.¹¹ Picrorhiza extract, when given at a dose of 3-12 mg per kg orally for 45 days, was also shown to be effective in reversing ethanol-induced liver damage in rats.¹²

In a clinical trial, 33 patients diagnosed with acute viral hepatitis were given either 375 mg Picrorhiza root powder three times daily or placebo for two weeks. The levels of the liver function markers-bilirubin, AST, and ALT-were significantly lower in the treatment group as compared to placebo. The typical dosage of Picrorhiza powder extract, standardized to 4 percent kutkin, is 400 to 1500 mg per day.¹³

S-Adenosylmethionine (SAMe)

SAMe is a key precursor of cysteine—the rate-limiting amino acid of the tri-peptide glutathione, an antioxidant that plays a key role in the defense mechanism. It has been suspected that a deficiency in hepatic SAMe may contribute to the pathogenesis of liver cirrhosis. Depletion of SAMe can be corrected by the administration of SAMe. And the efficacy of SAMe in liver cirrhosis was demonstrated in a clinical trial on 123 patients with alcoholic cirrhosis. Patients received either 1,200 mg SAMe or placebo daily for two years. The overall mortality and liver transplantation at the end of the trial decreased from 30 percent in the placebo group to 16 percent in the SAMe group, although the difference was not statistically significant.¹⁴

Burdock

Historically, burdock (Arctium lappa L.) has been used as a diuretic and to lower blood sugar. In an animal study, oral administration of Burdock at a dosage of 300 mg/kg body weight three times per day was shown to alleviate hepato-toxicity induced by ethanol and potentiated by carbon tetrachloride. The hepato-protective mechanism of Burdock was attributed, at least in part, to its antioxidant property, which decreases the oxidative stress of hepatocytes (liver cells).¹⁵

Ligustrum

The fruit of Ligustrum (Ligustrum lucidum) is commonly used as a tonic and in liver formulae in Chinese medicine. In an animal study, pretreatment of mice with an oleanolic acid-enriched extract of Ligustrum was shown to protect against CCl4-induced hepato-toxicity. This hepato-protection was attributed to the antioxidant property of oleanoilc acid which enhances hepatic-glutathione regeneration capacity. Reduced glutathione is a crucial determinant of tissue susceptibility to oxidative damage, and the depletion of glutathione content has been shown to be associated with an enhanced toxicity to chemicals including CCl4.¹⁶

Wasabi

Wasabi (Wasabia japonica), commonly known as Japanese horseradish, contains compounds called glucosinolates, which can be enzymatically converted into the bioactive form isothiocyanates. Wasabi is considered the richest source of 6-methylsulfinylhexyl isothiocyanate (6-HITC), a potent inducer of phase II detoxification enzymes, such as glutathione S transferase (GST). GST is abundant in the liver and kidney, and is required to prevent toxic compounds from accumulating in the cells.¹⁷

Although studies suggest that certain herbs can decrease liver enzyme levels, the effects on hepatic histopathology and long-term survival rates need further investigation.

References

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[2] Pares A et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998; 28: 615

[3] Tanamly MD et al. Randomized double-blinded trial evaluating silymarin for chronic hepatitis C in an Egyptian village: study description and 12-month results. Dig Liver Dis 2004; 36:752

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[5] (Zhu M et al. Evaluation of the protective effects of schisandra chinensis on phase I drug metabolism using a CCl4 intoxication model. J Ethnopharmcol 1999; 67:61

[6] Zhu M et al. Improvement of phase I drug metabolism with schisandra chinensis against CCl4 hepatotoxicity in a rat model. Planta Med 2000; 66:521

[7] Huber R et al. DDB treatment of patients with chronic hepatitis. Hepatology 2004; 39:1732

[8] Van Rossum TG et al. Glycyrrhizin-induced reduction of ALT in European patients with chronic hepatitis C. Am J Gastroenterol 2001; 96:2291

[9] Hirayama C et al. A multicenter randomized controlled clinical trial of Shosaiko-to in chronic active hepatitis. Gastroenterol Jpn 1989; 24:715

[10] Bensky D, Gamble A. Chinese Herbal Medicine: Materia Medica. Revised Ed. Seatle: Eastland Press; 1993

[11] Visen PK et al. Curative effect of picroliv on primary cultured rat hepatocytes against different hepatotoxins: an in vitro study. J Pharmacol Toxicol Methods 1998; 40:173

[12] Saraswat B et al. Ex vivo and in vivoinvestigations of picroliv from Picrorhiza kurroa in an alcohol intoxication model in rats. J Ethnopharmacol 1999; 66:263

[13] Vaidya AB et al. Picrorhiza kurroa (Kutaki) Royle ex Benth as a hepatoprotective agent – experimental and clinical studies. J Postgrad Med 1996; 42:105

[14] Mato JM et al. S-adenosylmethionine in alcoholic liver cirrhosis: a randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999; 30:1081

[15] Lin SC, et al. Hepatoprotective effects of Arctium lappa linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride. J Biomed Sci 2002; 9:401

[16] Yim TK et al. Hepatoprotective action of an oleanolic acid-enriched extract of Ligustrum lucidum fruits is mediated through an enhancement on hepatic glutathione regeneration capacity in mice. Phytother Res 2001; 15:589

[17] Morimitsu Y et al. A sulforaphane analogue that potently activates the Nrf2-dependent detoxification pathway. J Biol Chem 2002; 277:3456