A Pharmacological Study Of Licorice Biology Essay

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Scientifically this plant is known by its Greek name Glycyrrhiza Glabra or the Latin name Liquiritra Officinalis. More commonly is it known as Licorice, while sweet wood, sweet root and liquirizia to name but a few are other names associated with this plant. Categorically, this plant belongs to the Fabaceae family, also known as the bean family. However the plant is unlike its family members, its seed pods are hairless, hence the plants Greek name Glycyrrhiza Glabra, meaning sweet root with hairless seed pods. From the meaning of its Greek name and all of the names associated with this plant, it is easy to see what part of the plant is medically used, the root.

The earliest record of this plant was in China in 206 BC during the Han dynasty, but remained undocumented until it surfaced again around 2000 BC on Assyrian clay tablets and Egyptian papyri. The origins of the plant lie to the east in China and Russia but other varieties were later found to exist in the Mediterranean. However the plant did not get its botanical name until around 50 AD when the Greek physician Dioscorides named the plant in Greek, glukos meaning sweet and riza meaning root. In the 16th century, the plant was brought to Europe where it was cultivated in Spain and Italy, which now harvests the sweetest Licorice plants.

Traditionally, the plant was used for many different things depending on the individual culture. In China, traditional medicines were split into 3 classes according to their properties and cautions. In the first class, also known as the "superior class", have properties capable of expelling illness and nourishing life. The strength and function of these herbs is gentle and are given over a long period of months and years. The nature of the herbs in the second class also known as the "middle" class are more associated with curing the illness and so they are given in quick, short bursts. Those herbs in the third class or "inferior class" are more aggressive and potent, they are used more to attack an illness and so must only be taken until the disease is gone and then ceased. Licorice was listed with the herbs of the first class as it was attributed for the preservation of life. Licorice was also considered as non toxic, like the rest of the first class herbs, it was safe to take as much and as often as necessary without harm. As licorice was considered non toxic, it was also considered to have harmonizing qualities. In addition to its medicinal uses, licorice was also added as a flavouring agent to sweets and other foods as it was also considered a spice. Traditional Chinese indications for Licorice include infections, skin disorders, inflammatory diseases and respiratory problems, while its actions were listed as being a carminative and expectorant. In Japan, licorice was listed for the treatment of chronic hepatitis and viruses such as HIV and CMV among others and topically for skin disorders.

Once discovered by the Romans, the Roman legion used the herb to stem hunger and sate thirst for long periods. Theophrastus of Lesbos, writing in the fourth century BC wrote that "it has the property of quenching thirst if one holds it in the mouth". They also believed the herb to have stamina building properties. The herb was again praised in later years when a 9th century herbalist called Macer Floridus listed it for its actions on the respiratory system saying "For the brest, for the lunges. Liquorice sodden in watir til it be nesshe and than pressed well and oft dryed is clethid chylum whan it is dried pus. This wole helpe pe lunges and abates the stiffness's and diseases of it. No medecyne helpith swether the instrumentis of the lunges, of the brest, than doth liquorice. These instrumentis helpith liquorice wonderly nat in turmentyng, as doth cost, neither in fretyng, as doth aloe, but in softe likynnge." What Macer was saying, was that no drug was as effective as licorice in healing the lungs.

Today, it is still used for a variety of conditions, though not all its traditional uses are supported by scientific evidence. However it is still used for respiratory problems and as a hydrocortisone cream for skin problems. Officially it is recognised by the German Commission E for treating respiratory catarrh and gastric ulcers and by ESCOP for gastritis and duodenal ulcers. WHO support the use of licorice for gastric and duodenal ulcers after a study showed improvement when used as a treatment. The BHC supports the use of the herb for bronchitis, peptic ulcers and chronic gastritis. Research of Licorice and its active ingredients, in recent years has also shown certain support for hormones in both men and women.

There are many ingredients in Licorice and many of those contribute to its various medicinal effects. The largest component is a water soluble active complex, which makes up to 50% of the herb. This active complex is made of triterpene saponins, Flavonoids, polysaccharides, pectin's, amino acids, mineral salts and simple sugars among other substances. Licorice's characteristic yellow colour is due to the Flavonoids of the herb, these include liquiritin and isoliquiritin. More than 30 different Flavonoids have been identified from licorice, these included phytoestrogens, formononetin and genistein. The sweet taste of the herb comes from the component glycyrrhizin which is a triterpenoid. The natural saponins, such as glycyrrhizic acid, are another constituent of the herb and are comprised of potassium-calcium and magnesium salts making between 2-25% of the total herb. Studies have also revealed up to 25 different antifungal and 20 antibacterial compounds found in the roots. Other ingredients such as asparagines, sterols, glycosides and vitamin E and B1 to B9 have also been found in Licorice. The anti inflammatory components of the herb act as natural steroid hormones in the body.

Glycyrrhetic acid

There are two methods for administration of licorice; these are oral and topical application. There are 2 types of oral administration, these are; tea made from the dried herb and an extract of the herb. For topical application, the herb is made in the form of a cream.

When it comes to dosage, no more than 15g or 600mg of glycyrrhizin a day should be exceeded with duration of no more than 6 weeks without medical advice. For tea, a standard of one teaspoon per cup of boiling water with a maximum of 3 cups per day and for extract, a standard of 15-40mls per week. The dosage set out above is a standard, with medical advice the dosage can be higher or lower depending on certain factors and the condition being treated. For example; for an adult suffering with bronchial catarrh, a dose of 1.5-5mls of extract is the recommended treatment. WHO suggest a daily dose of 200mg-800mg for no more than 6 weeks without professional direction. Traditionally the Chinese recommend 1 tsp. rootstock with 1 cup water and taken once a day while they also recommend licorice, mixed with wild cherry, and flaxseed makes a wonderful cough syrup. For sore throat, phlegm, hoarseness, coughs, and bronchial irritations, the following Chinese formula was used: 1/2 oz of Kan-ts'ao (licorice root) and 1 oz of Chih-ma (flaxseed).

Like generations before us, licorice is at present still indicated for respiratory problems, as an antiviral and many other indications. Today licorice is indicated for; skin problems like acne and eczema, Addison's disease, androgen excess, ovarian cyst, polycystic ovarian syndrome and gastrointestinal problems like gastrointestinal ulcers and gastritis.

Like its list of many indications, licorice has many actions a well. These actions include; adrenal restorative, adaptogen, antispasmodic for the muscles, respiratory tract and uterus, oestrogenic and an antiulcerogenic to name but a few. However, like most herbs and drugs, licorice is contraindicated for use in pregnancy and breastfeeding. The herb is also contraindicated for those suffering from liver disease, hypokalaemia, cardiovascular disorders, and impaired renal function. Licorice has also been known to interact with certain drugs, such as diuretics, cardiac, corticosteroid, spironolactone, amiloride or digitalis drugs. It has also been discouraged for use by those receiving hypoglycaemia and hormonal therapy or those taking. Most of the adverse effects reported have been due to licorice's primary component Glycyrrhiza and disappear once discontinued.

Licorice has many pharmacodynamics properties and has been shown to have many activities such as expectorant, anti inflammatory, antiviral and antiulcerogenic activity. Its expectorant activity is due to the saponin content which in vitro decreased surface tension by reducing the viscosity of mucus, thus increasing secretolytic and expectorant activity in the body. In another in vitro experiment antiviral activity was demonstrated when licorice was added to infected cultures of human aneuploid Hep2 cells. The 8mM glycyrrhizic acid inhibited the growth of herpes simplex, vesicular stomachitis viruses and vaccinia, while at 0.003M a complete disappearance of hemagglutinating activity of influenza A and B in infected hen eggs. In a HIV in vitro study, complete inhibition of the cytopathic effect of HIV and HIV specific antigen expression in MT4 cells at a concentration of 0.3 and 0.6mM respectively, but it had no direct effect on the reverse transcriptase of HIV. In an anti inflammatory in vitro experiment, an aqueous extract of Chinese licorice at 1mg/ml, the component isoliquiritin had a major role in the inhibition of tube formation in angiogenesis.

In an experiment into licorice's antiulcerogenic activity, licorice extract or deglycyrrhized licorice significantly reduced the size and number of mucosal legions and ulcers in the rat gastric mucosa. This is due to the fact that licorice stimulates the body's defence mechanism to prevent the occurrence of ulcers by increasing mucus secreting cells in the digestive tract. Licorice also stimulates the production of 2 steroids, cortisone and aldosterone in the body.

Studies into the anti tumour activity of licorice have also been carried out, though not enough have been conducted to officially back this claim up yet. Studies into the herb's triterpenoid content for the capability to inhibit the growth of cancer cells are currently being accessed. One study conducted on the skin of rats where tumours were present, showed significant inhibition of 50% by topical pre-treatment with 18 b glycyrrhetic acid over a 16 week period.

In a pharmacokinetic study, carried out in vitro under anaerobic conditions, glycyrrhizic acid was hydrolysed to aglycone by human intestinal bacteria and was then isomerised through 3-hydro-glycyrrhertic cid to 3 epi-lycyrrhetic acid and vice versa. In general, in a human study into glabridin, the component was absorbed and reached a maximum concentration after 4 hours. Following the peak concentration, it was eliminated from the body slowly in a single phase with a T12 of 10 hours. Plasma glabridin levels steadied within 2 weeks with a single daily dose of 300mg. In relation to absorption, when delivered intravenously, glycyrrhizin resulted in 54-67ml/kg volume of distribution and when reviewed it was considered to have a half life of 5 hours. Metabolically, glycyrrhizin is broken down by intestinal flora which hydrolyses the compound to aglycone and is then isomerised to 3 epi-18 b-glycyrrhetic acid. Once broken down, it is theorized that it is excreted hepatically into the bile. Studies in relation to elimination of glycyrrhizin have shown that the compound is fully eliminated at 3.5 hours in humans.

Many clinical studies have been conducted in relation to licorice. One open study of 15 patients with peptic ulcers, were treated with 3 g of powdered root three times a day for three months showed the beneficial effects in relieving epigastric burning and pain in the epigastrium. In another clinical study, licorice extract combined with antacids demonstrated an effectiveness equivalent to carbenoxolone, cimetidine and ranitidine with improvement in mouth ulcers after one day of treatment. An effect on PCOS was also demonstrated when licorice combined with white peony, lowered the LH/FSH ratio and reduced ovarian testosterone production, thus inducing regular ovulation.

In a study reported in 2002, Supplementation of licorice root extract to patients for 1 month was followed by an additional 1 month of placebo consumption. Licorice consumption reduced patients' plasma susceptibility to oxidation, reduced plasma cholesterol levels, which was due to a 9% reduction in plasma LDL cholesterol levels; and reduced plasma triacylglycerol levels. The study concluded that dietary consumption of licorice-root extract by patients with high cholesterol acted as a moderate cholesterol-lowering agent, and as a potent antioxidant agent.

In a review of licorice and its effects reported in 2001, it was suggested that licorice may possess anti-cancer properties by a few different means. An in vitro study reported in 2002, certain compounds in licorice root inhibited some enzymes responsible for the formation of certain cancers in humans. This suggested that licorice root may possess cancer-inhibiting properties.

Many reports of toxicity from licorice have been reported and thankfully all symptoms have disappeared after the consumption of the herb stopped. Therefore administration of the herb is generally given under professional supervision. There are 3 types of toxicity in relation to licorice, these are acute toxicity, sub acute toxicity and sub chronic toxicity.

Acute toxicity was observed in rats when a dry root extract was administered containing 58% glycyrrhizic acid. The oral LD50 of glycyrrhizic acid was determined as 560mg/kg in mice.

Sub acute toxicity with symptoms of decreased weight gain, blood cell count and atrophic cortex formation of the thymus gland were observed when 2.5g/kg/day of the dry root extract for a period of 90 days was administered to rats. However when 0.63g/kg/day of the extract was administered for the same period of time, no toxicity symptoms was observed.

Finally, when a daily diet of 2.6g/kg of glycyrrhizic acid was given to rats for a period of 6 months, sub chronic toxicity was observed with symptoms of increased blood pressure, weight of the kidneys and heart.

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