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Phytochemistry 1
Lecture 10
Anthraquinones + hypericum
Date : 10/3/2015
Done By : Sanaa Otoom
Today we will continue with the plants that contains Anthraquinones :
1- Rhubarb )‫ (الروند‬:
We talk here about the Rhizome of the plant , Rhubarb has different species which is
known as rheum either Rheum rhaponticum or other species , whatever when we talk
about the rhubarb we talk about the rheum species from family ploygonaceae . It
consists of glycoside rhein ,rhein anthrone, chrysophanol and aloe emodin.
The presence of tannins in rhubarb makes the drug constipating. So in small doses,
rhubarb exerts no purgative action but acts only as intestinal astringent, but large doses
cause purgation.
 Tannins are polyphenolic compounds responsible for astringent effect, rhubarb
consists of about 30% of tannins beside anthraquinones .
 in the upper part of the plant we have the leaves ,the upper part of it DO NOT
contain any anthraquinones it contains they contain other substances like oxalic
acids  it can be eaten either raw or cooked or salad and it’s safe if we boil it
and remove oxalic acids.
 The Rhizome of Rhubarb is similar to ginger and it has yellow color due to the
presence of yellow pigments due to anthraquinone glycosides.
 For conclusion : what we use from rhubarb are the rhizomes , it has cathartic
effect but it’s not common like other drugs like cascara or senna leaf.
 In Pharmacy we have drug known Pyralvex℗  this drug consisting of
anthraquinone glycosides of Rhubarb and it’s available in solution form and it’s
used for mouth ulcers and as antimicrobial for herpes simplex or others in the
mouth or oral cavity.
2- Aloes )‫ (الصبار‬:
When we talk about Aloes most commonly we mean Aloe-vera and Aloe barbadensis ,
they are the most important species .
The part used is the leaf of the plant thick leaves contains juice (Latex)  we get
glycosides by pressing the leaves either by using glass material or stainless-steal , we
should avoid using any metal like iron cupper or zinc because they interact with the
chemical components in the plant. Also we have to know the latex is not rich only in
anthraquinones , we have other compounds presented such as mucilage
compounds and polysaccharides .
 Uses :
- In therapy : The 1ry glycosides are more active than the aloins while the free
anthraquinon have little purgative activity.
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It’s one of the most valuable plants among other plants containing anthraquinone
glycosides , widely used in cosmetic industry in skin preparations in case of
sunburns , chemical burns .
- Food industry  as soft aloe drinks.
The anthraquinones presented in aloe : aloe-emodin , barbaloin (barbaloin is the major
C-glycoside).
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Now let’s talk about General Uses of ALL anthraquinone glycosides :
The laxative action of the crude drugs is always higher than from their content of
anthracene derivatives The different anthracene der. contained by the crude drug are
said to exert a synergistic action: when we talk about the plants we talk about the major
glycosides presented but actually the plants contains other glycosides presented and all
of them exert synergistic activity. Also the anthraquinone glycosides are more potent
than free anthraquinones.
Thus, the naturally occurring anthracene glycosides were found superior to the synthesis
of numerous hydroxyl anthracene der.
Some of these synthetic compounds act too drastically and also caused kidney
damage.(natural are much better than synthetic)
The only compound which is used to some extent in current medicine is danthrone
(synthetic one). It is also used as a standared in colorimetric assays of anthraquinone
glycosides.
Danthrone :
It’s not natural compound , it’s synthetic , it’s anthraquinone derivatives that is the least
active .
- Effect of storage on the active of anthracene glycosides:
Prolonged storage of anthracene bearing drugs may bring oxidation of anthranols and
anthrones (contains keto group) to give the less active anthraquinones. Thus, the activity
of drugs decreases by time. However, anthraquinone glycosides do not cause any
griping action (like anthranol and anthone), thus no antispasmodic such as belladonna is
prescribed with them.
- Drugs as senna, Aloe and cascara preparations retain their activity for a long time 
due to synergistic effect.
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Cascara and frangula must be aged for one year before it is used for medicinal
preparation (they need one year for the biosynthetic process).
Official anthraquinone drugs in B.P and U.S.P. :
- Senna leaf & senna fruit (pod).
- Aloes.
- Cascara tablets, elixir, dry exract, liquid extract.
- Rhubarb powdered, tincture.
- Danthrone (synthetic one)
- Frangula bark
3- Asphodelus spp. :
Asphodelus aestivus Brot. (Syn. Asphodelus microcarpus Salzm), Family
Liliaceae, is a perennial herb with short vertical rhizome (the rhizome is used) is widely
distributed throughout Jordan. Flowering period is January-April.
Asphodelus contains anthraquinone glycoside Ramosein , Ramosein is Dimer :
First portion
Third portion
second portion
If we see the first and second portions are oxanthrone , and the third portion is glucose sugar
(C-Sugar).
We standardize the product according to the % of ramosein , it’s exactly like pyralvex but from
different source .
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Expected uses :
Due to the presence of anthraquinone glycosides.
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To treat sore gums and mouth ulcers.
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To treat oral infectious diseases like dental caries and periodontitis.
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To treat oral aphthous.
St. John’s Wort
‫عشبة القديس جون‬
‫عشبة القديس يوحنا‬
This plant is pereannial mostly present in summer , it has very bright yellow color , the name of
it Hypericum perforatum , in Jordan we have other species which is Hypericum virginicum .
History of Plant :
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St. John’s Wort was first documented in the first century A.D. by Gaius Plinius
Secundus, a Roman philosopher, who discussed the herbs ability to treat diarrhea and
bladder problems.
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Following this, the ancient Greek physician Dioscorides recommended it to expel
“choleric excrements” and to treat burns.
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Theophrastus wrote about the use of St. John’s wort to treat wounds and psychotic
symptoms (phatasmata)
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In 1630AD announced that St. John’s Wort had the ability to treat illnesses of the
“imagination, melancholia, anxiety and disturbances of understanding”
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It was brought to the Northeastern United States by European colonists and was used to
treat breathing problems (tuberculosis), fever, nosebleeds, bladder and bowel problems,
and for venereal diseases.
Now the plant is classified as Anti-Depressant .
Naming St. John’s Wort :
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St. John’s Wort is harvested and flowers by June 24th, which is St. John’s (feast) day
(John the Baptist) . When the petals are squeezed or rubbed, they leak red sap which is
believed to be representative of the blood of the martyred saint (John the Baptist).
Chemistry :
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The plant contains compounds called Hypericin is a fluorescent red pigment , classified
as a dianthrone, it’s not glycoside . ( we mention that all anthraquinones are highly
colored materials because they are highly aromatic conjugated compounds)
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OH
O
OH
Anthrone
HO
CH3
HO
CH3
Anthrone
OH
O
OH
hypericin
In the past , they believed the activity of the plant is due to hypericin and standardization of any
synthetic drug based on hypericin , but later they found we have another compound which is
responsible for the activity ( NOT hypericin the active constituent) and this compound is called
hyperforin :
If we look at the structure , hyperforin is not anthraquinone it’s derivative of phloroglucinol
, if you see we have three hydroxyl groups (ketone is hydroxyl in origin) “blue arrows” are meta
to each other , and also we have four isoprene units “red arrows”  acetate malonate
derivative.
Hyperforin vs. Hypericin :
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Scientists used to think the active constituent in St. John’s Wort (SJW) was only due to
Hypericin and its inhibitory effects on the monoamine oxidase enzymes. However,
recent studies have shown that SJW may owe its main effects on depression through
Hyperforin.
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It is able to pass through the blood-brain barrier and may inhibit the action of the
enzyme dopamine ß-hydroxylase, which is required in converting dopamine to
norepinephrine. As a result of this enzyme inhibition, this may lead to increased
dopamine levels - thus possibly decreasing norepinephrine and epinephrine. (Dopamine
is the major player in depression)
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Hypericin does not cross the blood-brain barrier.
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Although many St. John’s Wort extracts are still standardized for hypericin, increasing
research shows that hypericin may play little or no role in the mood-related effects of St.
John’s Wort. Rather, it seems likely that hyperforin is the primary (but probably not the
only) active constituent.
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Hyperforin is now thought to be the main active factor in St. John’s Wort that has
beneficial effects on anxiety and depression. Hyperforin has strong reuptake inhibitor
effects on all four of the mood neurochemicals (serotonin, norepinephrine, dopamine
and GABA). It is also believed that Hyperforin may be actually responsible for inducing
the P450 liver enzymes, which may increase the metabolism of other drugs in the body.
As a result of the P450 liver enzymes activation, St. John’s Wort does have some
herbal-drug interactions.
 So this plant present in the pharmacy and is classified as a drug (NOT OTC drug) ,
other countries may classify it as food supplement .
o Commission E “approved” for this use:
 Commission E- psychological disturbances, depression,
anxiety,nervous unrest; topically the oil for bruises,myalgi, burns.
 So the plant can be used internally in case of depression or externally in bruises or
some burns.
Other Uses: (less well documented )
– Hypericin antiviral studies
– Hypericin activity against glioma cells
– SJW long used to heal wounds
– Plant oil has antimicrobial activity
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 Pharmacokinetics:
Metabolized by cytochrome P450 in the liver (like many drugs)
Hypericin may not cross the blood-brain barrier, hyperforin more likely an active
ingredient
Most of the purported active ingredients are heterocyclic and are metabolized quickly
(half-life < 6 hrs).
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 Dosage :
- The drug is considered one of the most herpal drug which has extremely drug-drug
interaction and side effects , Many people who take the drug feel inconvenient.
• Standardized extract containing about 0.3% hypericin or 2-3% hyperforin; 300mg
TID for treatment.
• Takes about 6 weeks to notice a difference , the patient will not immediately feel the
difference.
• Generally takes longer to reach full effectiveness than prescription antidepressants like
Prozac or any other drugs.
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Forms of Hypericum :
Capsules
Teas
Tablets in Jordan
Tinctures
Oil-based skin lotions (not to be ingested)
Chopped/powered
 Cautions:
• Should not be used during pregnancy or while breast feeding as there is no information
on its safety under these conditions
• Should not be used for severe depression (melancholia) or bipolar disorder as not
enough research is yet available to show effectiveness in these circumstances , it’s used
mainly for mild depression or nervousness .
• Do not take St. John’s Wort in combination with MAOI’s (Monoamine oxidase inhibitors)
– Can produce a dangerous rise in blood pressure
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Should not be taken in combination with prescription SSRI’s (selective serotonin
reuptake inhibitors) as this can lead to serotonin syndrome – too much serotonin.
 Adverse effects :
– Photosensitivity-animals
– Photosensitivity- humans- in high doses is a risk
Sensitivity due to hypericin , hypericin for somehow located in the epidermis, so upon
exposure to sunlight , the sunlight will act as photosensitizer and will energize hypericin
(it’s fully aromatic highly conjugated compound)  conjugation and resonance of the
electrons will cause the photosensitivity. we have to advise patient taking this plant not
to expose to the sun.
Good Luck 
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