Anthraquinone glycosides

Characteristics
Often orange-red compounds Usually soluble in hot water or dil. Alcohol Identification: Borntragers test The powdered drug is macerated with an immiscible organic solvent (ether), after filtration aqueous ammonia or caustic soda is added, when a pink, red or violet color in the aqueous layer after shaking ----- indicates the presence of free anthraquinone They are present as free (called anthranoids) or as glycosides

O O

8 7 6 5
O

1 9 10 4 2 3

8 7 6 5
H

1 9 10 4
H

2 3

Anthraquinone

anthrone

8 7 6 5 8 7 6 5
O

1 9 10 4 1 9 10 4 2 3 2 3

dianthrone

Pharmacological activity
Anthranoids bound to sugars are pharmacologically inert and enter the colon unchanged. There they are metabolically altered by intestinal bacteria to products considered the true active principles (free anthrones). They act as stimulant laxatives that induce bowel movement with loose stools and frequent griping. The effect is shown after 6-12 hours after ingestion, thus it should be taken at night

Mechanism of action
Stimulates the receptors in the mucosa, leading to increased propulsive colonic motility, a shortened transit time, and a net decrease in the absorption of water and electrolytes. Blocks the sodium pump on the bowel epithelium which inhibits the absorption of sodium and water in the colon. The subsequent increase in water and electrolytes in the colonic lumen results in a greater pressure in the intestine that leads to a laxative action.

Indications:
In constipation in patients who do not respond to milder drugs or have disorders such as anal fissures, hemorrhoids, and after anal-rectal surgery in which an easy evacuation of the bowel with a soft stool is desired.

Adverse effects
Most of the metabolites are excreted in stool but some are excreted in urine as conjugates turning the urine to dark yellow or even red. In nursing mothers, anthranoid metabolites can enter the milk and give it a brownish tinge The principal side effect is abdominal pain and griping and losses of fluid and electrolytes Anthranoids cause engorgement of abdominal blood vessels throughout the pelvis, with a substantial increase of blood flow to the uterus which can increase the risk of fetal loss in case of pregnancy and increase the intensity of menstrual bleeding.

Precautions :
Anthranoids should not be taken for long-term. They should be used intermittently and at low doses (not beyond one week).
Chronic abuse, with diarrhea and consequent fluid electrolyte losses, may cause dependence and need for increased dosages, disturbance of the water and electrolyte balance. The chronic hypokalemia may cause damage to the renal tubules and may result in cardiac and neuromuscular dysfunction, especially if cardiac glycosides, diuretics are taken. They can also promote reduction of spontaneous bowel function leading to the development of the laxative habit.

Contraindications
Partial or complete bowel obstruction Pregnancy Lactation Cardiac glycosides (indirect potentiation due to the electrolyte imbalance) Thiazide diuretics, adrenocorticosteroids, liquorice root Severe dehydration Should not be used in children under the age of 10 years

Senna
Origin: is the dried leaflets of Cassia senna known as Alexandrian senna growing along the Nile in Egypt and Sudan, and of Cassia angustifolia known as Tinnevelly senna native to the region about the Red Sea: Leguminoseae

Constituents
Anthraquinone glycosides (dianthrones): Sennosides A -D based on the aglycones sennidin A and sennidin B Yellow flavonol kaempferol Mucilage, calcium oxalate
OGlu O OH

10 10'

R1 R2

OGlu

OH

R1 Sennoside A Sennoside B COOH COOH

R2 COOH COOH

10-10' trans meso

Uses
Useful purgative for either habitual constipation or occasional use It lacks the astringent after-effect of rhubarb

Dose
A bitter tasting tea can be prepared from 0.5-2 g of the herb. The tea is prepared by soaking the leaflets in cold water for 10-12 hours then straining.

Senna fruit (pods)

Origin: are the dried ripe fruits of Cassia senna and C. angustifolia: Leguminoseae Active constituents:
located in the pericarp Same as in the leaves with the major anthraquinone glycoside sennoside A

Rhubarb
Origin: is the dried underground parts (root and rhizome) of Rheum palmatum: Polygonaceae or R. officinalis or mixture of the two (Chinese rhubarb) The high grade (Shensi rhubarb) is bitter and slightly astringent in taste with aromatic odor and breaks with a marbled fracture. The freshly broken surface shows a bright pink color The lower grade (Canton rhubarb): the freshly broken surface is of pale pink color. The fracture is granular When chewed, it colors the saliva yellow and produces a gritty sensation between the teeth caused by large calcium oxalate crystals.

Active constituents
Anthraquinones: chrysophanol, aloeemodin, emodin, rhein and their glycosides: chrysophanein and glucoaloe-emodin and glucorhein
OH O OH

OH

Chrysophanol

Aloe-emodin

Rhein

Active constituents
Anthraquinone of the type dianthrone: dianthrone glucoside of rhein (sennosides A-B) and of chrysophanol or aloe-emodin Astringent compounds (tannins): glucogallin, epicatechin and catechin Starch and calcium oxalate

glucogallin

Uses
Rhubarb contains anthranoids which have a purgative action but it also contains tannins which produce antidiarrheal effect. The overall effect is dose-dependant. Rhubarb in small doses (0.1-0.3 g) exhibits astringent, bitter stomachic and tonic properties, and is employed in dyspepsia, gastritis and diarrhea assisting digestion and creating a healthy action of the digestive organs. It is especially useful in cases of diarrhea, caused by an irritating body in the intestines: the cause of irritation is removed and the after-astringent action checks the diarrhea. In large doses, Rhubarb powder acts as a simple and safe purgative, being regarded as one of the most valuable remedies we possess, effecting a brisk, healthy purge, without clogging the bowels

Antioxidant due to the stilbenes glycosides In clinical trials on patients with chronic renal failure, it showed slower progression of renal failure

Toxicity
The plant itself is considered poisonous due to the high concentration of oxalic acid in the leaf (though not in the stem which is edible). Toxic effects result from hypocalcaemia caused by removal of calcium from the blood stream by forming the insoluble calcium oxalate People with a tendency to rheumatism, arthritis, gout, kidney stones or hyperacidity should take especial caution if including this plant in their diet since it can aggravate their condition

ALOES
Aloe latex, commonly referred to as "aloe juice," is a bitter yellow exudate from the pericyclic tubules just beneath the outer skin of the leaves . Prepared by evaporating the liquid which solidifies by cooling. Powdered aloe latex is greenish-brown having a pungent odor and bitter unpleasant taste.

Active constituents
C-glycosides and resins
Barbaloin: C-glycoside Small quantities of aloe-emodin

barbaloin

Uses
Purgative (not widely used as senna) Research on the long-term toxicity and pharmacokinetics is still incomplete.

Contraindications
Hemorrhoids and kidney diseases In addition to all the contraindications mentioned in the anthraquinones

Buckthorn bark
Origin: is the dried bark from the trunk and branches of Rhamnus frangula: Rhamnaceae. Widely distributed in Europe and Western Asia. buckthorn means rotten tree referring to the offensive odor of the friable wood.

Contents
6-9 % anthraquinone glycosides: glucofrangulin A, B.
RO O OGlu O OH

R = Rhamnose, Glucofrangulin A R = Apiose, glucofrangulin B

Uses
The bark should be aged one year before use in order to allow the reduced glycosides (anthrones) present in the freshly dried herb with their harsh laxative action to be converted to milder oxidized forms. Aging can be artificially by heating. It is a mild laxative (anthraquinone derivatives in the oxidized form)

Dosage
0.5-2.5 g /day crude drug taken directly or as a decoction at bedtime

Hypericum (St Johns wort)

Origin: is the dried aerial parts of Hypericum perforatum: Hypericaceae gathered usually at the time of flowering or shortly before The name is derived from hyper-above and icon-picture, referring to the ancient practice of hanging the plant above religious pictures to ward off evil spirits. The name st. Johns wart comes from that it flowers around st. Johns day (june 24th). The name perforatum comes from the oil glands which are visible in the leaves as transparent areas and as black dots on the lower surface It was known in ancient Greece as anti-inflammatory and healing properties as well as the treatment of mental illnesses.

 The harvested material should be dried rapidly but carefully to preserve the contents of secretory glands. The drying temperature should not exceed 30- 40. The key constituents are most concentrated in the buds, flowers and leaves. Rubbing a bud or flower between the fingers immediately creates a red- to purple stain caused by certain constituents of the plant (naphthodianthrones)

Active constituents
OH O OH

2-3 % Anthraquinone (naphthodianthrone): hypericin and pseudohypericin Commercial extracts are standardized as their hypericin content

HO HO

CH2R CH3

OH

OH

Hypericin Pseudohypericin

R=H R=OH

 Prenylated phloroglucinol derivatives: hyperforin Flavonoids: kaempferol, quercetin Volatile oil Caffeic acid, amino acids, vitamin C, tannins, carotenoids

HO

Hyperforin

Uses
Antidepressant in mild to moderate depression in USA, in 1999, it was ranked 2nd to ginkgo as the best selling product of the herbal mainstream market it was called Natures prozac without the disadvantages of the latter
Until recently, the hypericins were regarded as the sole antidepressant principle but a number of papers demonstrated that the hyperforins have the same effect In some countries, such as Germany, Hypericum is prescribed for mild depression far more commonly than synthetic antidepressant medication. In most countries, standardized extracts are available over the counter usually in tablet or capsule form, and also in teabags and tinctures. Preparations of SJW do not produce acute effects, so they are not suitable for use as daily sedatives or sleeping aids

 Hypericum oil: made by macerating the ground fresh flowers in olive oil (25:100 ratio). After several weeks standing in the sun, it acquires a reddish color and called red oil which is used as a traditional topical remedy for use on wounds and burns to relieve inflammation and promote healing. Internally, the oil may be taken for peptic ulcers and gastric inflammation.

Antiviral activity against herpes simplex virus I and II, HIV in vitro and vivo, influenza A and B, hepatitis C Eases menopausal anxiety, nervousness, and sleep disorders

Mechanism of antidepressant action:

St Johns wort alcoholic extracts have been tested in almost all biochemical models. All the studies showed an inhibitory effect on the uptake of serotonin, dopamine, and norepinephrine.

Dosage:
Normal dose range of 500-900 mg daily of the extract. If we use the fresh herb, 2 teaspoonfuls (2-4 g) of finely chopped herb in 150 ml of boiling water, steep 10 minutes then drain. As for all antidepressant drugs, there is a lag phase of up to 8 weeks before the full therapeutic effect becomes manifest.

Side effects
Photosensitization or phototoxic reactions (hypericism):
It is known to occur in grazing animals, especially sheep and cattle that have consumed large amounts of St Johns wort then exposed to sunlight. Animals manifests rhythma, restlessness and diarrhea. In humans, studies have proved that the phototoxic reaction will occur after the consumption of about 0.3-0.6 g/kg which is about 30 times the therapeutic daily dose. If there is an event of overdose of several times the recommended therapeutic dose, the patient should avoid exposure to UV light for one week due to the relatively long elimination half-life of hypericin and pseudohypericin.

Contraindications
Pregnancy (it might have teratogenic effects) Lactation (it might cause colic, drowsiness in nursing infants) Drugs that are metabolized by cytochrome p450 enzymes as it increases their activities Drugs that affect serotonin such as selective serotonin reuptake inhibitors

Clinical trials
Over 25 controlled trials have demonstrated the effectiveness of st johns wort in treating mild to moderate depression. They showed that st johns wort is significantly superior to placebo and may be as effective as traditional agents

 Several observational studies have shown that the incidence of adverse effects with SJW extracts is only about 1-3 % (sedation, GIT symptoms, fatigue, allergic reactions, headache, weight gain and dry mouth), which is at least 10 times lower than with synthetic antidepressants (cardiac side effects).

Naphthoquinones and glycosides

In plants, they commonly occur in the reduced and glycosidic forms (glucoside of hydrojuglone. On extraction, the compounds are oxidatively converted to the colored naphthoquinone
OH

OH

O Glucosyl

OH

-hydrojuglone

Juglone

Henna
Origin: is the dried leaves of Lawsonia inermis: Lythraceae Cultivated in North Africa including Egypt, India, Ceylon The leaves are greenish brown to brown

Active constituents
O

Hydroxynaphthoquinone Lawson, a coloring matter Coumarins, xanthones, -sitosterol glucoside, flavonoids, , fats, resin, henna-tannin Used as a dye for hair and wool (titan red) The stem-bark is used in India for the treatment of jaundice, enlargement of liver and spleen and for various skin diseases due to its astringent properties Isoplumbagin was isolated from the stem bark and was proved to have antiinflammatory

OH

OH

Lawson
OH O CH3

Isoplumbagin