2. Anthraquinone Glycosides

3. Introduction to Anthraquinones
Historically: Rhubarb, Senna, Aloes and Cascara were all used as purgative drugs.
Monocotyledons: Only Liliaceae.
Most commonly C-glycoside: barbaloin.
Dicotyledons: Rubiaceae, Leguminosae, Polygonaceae, Rhamnaceae, Ericaceae, Euphorbiaceae, Lythraceae, Saxifragaceae, Scrophulariaceae and Verbenacacea. Also in certain fungi and lichen.

4. Reduced derivatives of anthraquinones
Oxanthrones, anthranols and anthrones
Compounds formed by the union of 2 anthrone molecules
Dianthrones
Aglycones:
Chrysophanol/Chrysophanic acid  Rhubarb and Senna.
Rhein  Rhubarb and Senna
Aloe-emodin  Rhubarb and Senna
Emodin  Rhubarb and Cascara

5. Anthraquinones – Chemical Properties
Anthraquinone derivatives: orange-red compounds
Soluble in hot water/dilute alcohol.
Identified via Borntrager’s test
Powdered drug – macerated with ether
Filter
Add ammonia/caustic
Shake  pink, red or violet colour – positive for anthraquinone derivatives
If the Anthraquinones are reduced (within the herb) or stable (glycosides) test will be negative

6. Anthraquinone Structure

7. Anthranonls and Anthrones
Reduced anthraquinone derivatives
Occur either freely (aglycones) or as glycosides.
Isomers
Anthrone: Parent structure (pale yellow, non-soluble in alkali, non-fluorescent)
Anthronol: brown-yellow, soluble in alkali, strongly fluorescent
Anthronol derivatives (e.g. in Aloe – have similar properties – fluorescence used for identification)

8. Oxanthrones Found in Cascara bark
Intermediate products (between anthraquinones and anthranols)
When oxidised  form anthraquinones
Accomplished via Modified Borntrager’s Test
(oxanthrones oxidised using hydrogen peroxide)

9. Dianthrones Derived from 2 anthrone molecules
2 molecules may/not be identical
Form easily due to mild oxidation of anthrones
Form important aglycones
Cassia
Rheum
Rhamnus

11. Senna - Leguminosae
Definition: Consists of the dried leaflets of Cassia senna (Alexandrian senna), or Cassia angustifolia (Tinnevelly senna).

12. Cassia spp - Senna Indigenous to Africa (tropical regions)
Used since 9th – 10th century
Introduced into medicine by Arab physicians (used both the leaves and pods)
Exported by Alexandria – name of the Sudanese drug.

13. Senna - Collection Collected in September
Whole branches bearing leaves are dried in the sun.
Pods and large stalks are separated with sieves.
Leaves are graded (whole leaves, whole leaves and half-leave mix, siftings).
Whole leaves – sold to public
Rest – used for galenicals.

14. Senna - Constituents 2 active glycosides: Sennoside A Sennoside B
Both hydrolyse: 2 molecules glucose + aglycones: Sennidin A and Sennidin B.
Sennoside C & Sennoside D
Rhein
Aloe-emodin
Palmidin A (Rhubarb)

16. Senna - Constituents Kaempferol (yellow flavanol)
+ glucoside (kaempferin)
Mucilage
Calcium oxalates
Resin

17. Comparison of Alexandrian and Tinnevelly Senna
Macroscopical
Seldom larger than 4 cm in length
Grey-green
Asymmetric at base
Broken and curled at edges
Few press markings
Macroscopical
Seldom exceeds 5cm in length
Yellow-green
Less asymmetric at base
Seldom broken and normally flat
Often shows impressions (mid vein)

18. Comparison between Alexandrian and Tinnevelly Senna
Microscopical
Hairs – numerous (approximately 3 epidermal cells apart)
Most stomata have 2 subsidiary cells
Microscopical
Hairs less numerous (approximately 6 epidermal cells apart)
Stomata have 2-3 subsidiary cells with the respective ratio 7:3

19. Comparison between Alexandrian and Tinnevelly Senna
Chemical Tests
Ether extract of hydrolysed acid solution of herb with methanolic magnesioum acetate solution gives
Pink colour in daylight
Pale green-orange colour in filtered UV light
Chemical Tests
Same Test
Orange colour in daylight
Yellow-green colour in filtered UV light

20. Comparison between Alexandrian and Tinnevelly Senna
TLC
Hydroxymusizin glycoside present
TLC
Tinnevellin glycoside present

21. Senna – Allied Drugs & Substitutes
Bombay, Mecca and Arabian Sennas (found in Cassia angustifolia from Arabia).
Dog senna – Cassia obovata
Cassia auriculata – Indian Senna
Cassia podocarpa
Substitutes or Adulterants
Argel leaves – Solenostemma argel
Coriario myrtifolia

22. Senna Fruit
Definition: Senna pods are the dried, ripe fruits of Cassia senna and Cassia angustifolia, which are commercially known as Alexandrian and Tinnevelly senna pods respectively. Both have separate monographs

23. Senna Fruit - Collection
Pods are collected with the leaves and dried in a similar fashion. After separation of the leaves, the pods are hand-picked into various qualities, the finer being sold (commercially), while the finer pieces are used to make galenicals.

24. Senna Fruit - Constituents
Active constituents – found in the pericarp
Similar to those actives of the leaves
Sennoside A
Sennidin

25. Senna - Uses Laxatives (habitual constipation or occasional use).
Lacks astringent after-effect (Rhubarb)

26. Senna - Additional Contra-indications Medicinal Actions
Gout, colitis, GI inflammation.
Should not be used with cardiac glycosides.
Seeds/pods give gentler action than leaves: more appropriate for the young, elderly and those prone to stomach cramps.
NB: Over-use causes dependency.
Overdose: nausea, bloody diarrhoea, vomiting and nephritis.
Long-term use: dehydration & electrolyte depletion, worsening constipation and weakening intestinal muscles.
Medicinal Actions
Vermifuge, diuretic, febrifuge
Other uses: laxative candy (bitter taste).
Also used to treat flatulence, gout, fever.
Topically: poultice prepared with vinegar to treat pimples.
NOTE: Senna may cause urine to become reddish – no clinical significance.

27. Cascara Bark- Rhamnaceae
Definition: Official cascara sagrada is the dried bark of Rhamnus purshianus. Bark is collected from wild trees
(depletion is leading to the increase of cultivation)

28. Rhamnus purhsianus - Cascara
Etymology
Rhamnos – Greek, branch, shiny shrub. Purshiana after Pursh, botanist 1st described herb in 1814.
Other Common Names
Bearwood, bitterbark, buckthorn, coffeeberry, mountain cranberry, persiana, sacred bark.

29. Cascara Bark - History Recently introduced to Modern Medicine.
Known to early Mexican and Spanish priests.
Not introduced to medicine until 1877.

30. Cascara – Collection & Preparation
Collected form mid-April to end of August, when it separates readily from the rest of the trunk.
Longitudinal incisions are made 10cm apart and the bark removed.
Tree is then usually felled and the branch bark separated.
Bark is then dried in the shade with the cork facing upwards. This is referred to as ‘natural’ cascara. Commercial supplies are comminuted to give small, even fragments called ‘evenized’, ‘processed’, or ‘compact’ cascara.

31. Cascara Bark - Storage
During preparation and storage the bark should be protected from rain and damp (partial extraction of constituents may occur or bark may become mouldy).
Should be stored for at least 1 year before use (although no longer a BP requirement).
Bark appears to increase in medicinal value up unto its 4 years old (stored bark)

32. Cascara Bark – Why Stored for a Year?
When stored for at least a year – better tolerated by patient (less griping pains due to increased peristalsis)
Yet as effective as fresh bark.
Reason?
Due to Hydrolysis and other changes that occur during storage.
Bitter taste of Cascara can also be reduced by treating the bark with alkali (alkali earths or MgO).

33. Cascara Bark – Constituents 1
4 main glycosides – Called Cascarosides
Cascaroside A
Cascaroside B
Cascaroside C
Cascaroside D

34. Cascara Bark – Constituents 2
2 aloins:
C – Glycosides
Breakdown products of Cascarosides A-D
Barbaloin (derived from aloe-emodin)
Chrysaloin (derived from chrysopanol anthrone)

35. Cascara Bark – Constituents 3
O-glycosides
Derived from
Emodin
Emodin oxanthrone
Aloe emodin
chrysophanol

36. Cascara Bark – Constituents 4
Dianthrones
Those from
Emodin
Aloe-emodin
Chrysophanol
Hetrodianthrones
Palmidin A, B and C (Rhubarb)

37. Cascara Bark – Constituents 5
Emodin
Aloe-emodin
Chrysophanol
(in the free state)

38. Cascara Bark - Substitutes
Rhamnus alnifolia (too rare)
Rhamnus crocea (bark is very different from official drug)
Rhamnus californica (so closely related to Rhamnus purshianus some botanists do not consider them to be separate species).
Rhamnus fallax

39. Cascara Bark - Uses Purgative Similar to Senna Normally as a tablet
Also used on animals

40. Cascara Bark – Additional
Physiological Action
Astringent (bark – tannins), bitter tonic, chologogue, emetic, hepatic, stomachic.
Medicinal Uses
Move stagnation, clear heat.
The most widely used laxative world-wide.
Topically: Used as a wash for herpes lesions
Excessive use: nausea, vomiting, heamatorrhoea. Long term use: Weakens intestinal muscles.
Contra-indications: children younger than 14, during pregnancy, lactation, IBS, Crohn’s, intestinal obstruction, and idiopathic abdominal pain.

41. Rhubarb - Polygonaceae
Definition: Rhubarb/Chinese Rhubarb is the rhizome of Rheum palmatum. Other species and hybrids of Rheum, except R. rhaponticum, may also be included.

42. Chinese Rhubarb - History
Chinese Rhubarb has a long history.
Mentioned in a herbal of 2700BC.
Formed an important article of commerce on the Chinese trade routes to Europe.
Still used medicinally today.

43. Chinese Rhubarb – Collection & Preparation
Rhizomes are grown at high altitudes (+3000m).
Collected in Autumn or spring (6-10yrs old)
Cork is removed, cut.
Artificially dried.
Packed in tin-lined wooden cases.
Inferior quality herbs are packed in hessian bags

44. Chinese Rhubarb - Constituents
Anthraquinones without a carboxyl group – chrysophanol, emodin, aloe-emodin & physcion.
Also the glycosides of these substances.
2. Anthraquinones with a carboxyl group (rhein and its glycoside: glucorhein).

45. Chinese Rhubarb - Constituents
Anthrones and dianthrones of chrysophanol, emodin, aloe-emodin or physcoin.
4. Dianthrone glucosides of rhein (Sennosides A and B).
5. Hetrodianthrones derived from 2 different anthrone molecules: Palmidin A and Palmidin B.

46. Chinese Rhubarb - Constituents
Free anthraquinones: chrysophanol, emodin, aloe-emodin and rhein.
Some of the above constituents may also occur as glycosides.

47. Chinese Rhubarb - Uses Bitter stomachic
Diarrhoea (low doses) – contains tannins
Purgative (high doses) – followed by an astringent effect.
Suitable only for occasional for occasional use, not for chronic constipation.

48. Rhubarb - Additional Etymology Medicinal Actions Topical Uses:
Rheo – Greek, ‘to flow’, in reference to the purgative properties.
Medicinal Actions
Anti-helminthic, anti-bacterial, anti-inflammatory, antiseptic, astringent (low doses), sialagoge, vulnerary
Topical Uses:
Poultice to treat boils, burns, wounds. Used to stop bleeding (tannins – stypic and astringent). Used as a mouthwash for oral ulcers.
Other uses: Acid content: fresh root can be used to polish brass.
Caution
Leaves should be avoided – high calcium oxalate - toxic

49. Aloe - Liliaceae
Definition: Aloes are the solid residue obtained by evaporating the liquid which drains from the transversely cut leaves of various Aloe species.
The juice is usually concentrated by boiling and solidifies on cooling.
Official varieties are the Cape Aloes from SA and Kenya (Aloe ferox), and the Curacao Aloes from West Indies (Aloe barbadensis).

50. Preparation of Cape Aloes
Cape Aloes are prepared from the wild plants of Aloe ferox.
Leaves are cut transversely near the base.
200 leaves arranged around a shallow hole in the ground (lined with canvas or goatskin).
Cut ends overlap & drain into the canvas.
After 6hrs all the juice is collected.
Transferred to a drum.
Boiled for 4hrs on an open fire.
Poured into tins while hot  solidifies.

51. Preparation of Cape Aloes

52. Cape Aloes - Characteristics
Dark brown or Green-brown
Glassy masses
Thin fragments have a deep olive colour
Semi-transparent.

53. Cape Aloes - Characteristics
Powder: green-yellow
Rub 2 pieces of drug together – powder is found on the surfaces.
Characteristic sour odour (rhubarb/apple-tart odour).
Taste: nauseous and bitter.
Microscopy: powder in lactophenol – amorphous.

54. Characteristics of Curacao Aloes
Colour: yellow-brown – chocolate brown.
Poor qualities (overheated) black colour.
Opaque
Breaks with a waxy facture
Semi-transparent
More opaque on keeping.
Nauseous and bitter taste.
Characteristic iodoform odour.
Microscopy: lactophenol – acicular crystals

55. Aloes - Constituents C-glycosides Resins Glycosides Aloe-emodin
Aloin
Barbaloin
Isobarbaloin
Aloe-emodin
Cape Aloes: Also Contain
Aloinoside A & Aloinoside B (O-glycosides of barbaloin)

56. Aloe - Constituents

57. Aloe Constituents & Chemical Tests:
Unlike C-glycosides, O-glycosides of Aloe are not hydrolysed by heating with dilute acids or alkali.
Can be decomposed with ferric chloride & dilute HLC - NB: Modified Borntrager’s Test – oxidative hydrolysis. Anthraquinones give a red colour when shaken with dilute ammonia.
NB: All Aloes give a strong green fluorescence with borax (characteristic of anthranols) - General test for aloes.

58. Aloe - Uses
Purgative
Seldom prescribed alone – activity is increased when administered with small quantities of soap or alkaline salts; Carminatives moderate griping tendency.
Ingredient in Friar’s Balsam.

59. Aloe – Additional Notes
Medicinal Uses:
Anti-bacterial, anti-fungal, chologoge, emmenogogue, anti-inflammatory (juice), anti-inflammatory , demulcent, vulnerary, immune-stimulating (gel).
Radiation burns (internal and external use)
Contra-indications
Pregnancy & lactation (internal uses)
Etymology
Name derives from Arabic alu, meaning shiny or bitter in reference to the gel.
Other uses
Khoi-San hunters rub gel on their bodies to reduce sweating and mask their scent.
Used to break nail-biting habit.

60. Aloe vera Products
These are derived from the mucilage gel – parenchyma cells
Should not be confused with aloes (juice of pericycle – juice used for laxative effect).
Cosmetic industry (usefulness often exaggerated) - Used as suntan lotions, tonics and food additives.
Mucilage = polysaccharide of glucomannans and pectin

61. Cochineal
Definition: Cochineal is the dried female insect, Dactylopius coccus, containing eggs and larvae.
Insects are indigenous to Central America, commercial supplies are derived from Peru.

62. Eggs are protected during the rainy season are ‘sown’ on cacti – on which it is intended to breed.
Both male and females arise. After a time, fecundation occurs. Females attach themselves to the cacti and the males die out.
Females swell to x2 their original size due to developing larvae & develop red colouring matter.
Cochineal

63. Cochineal
Larvae mature after 14days and escape from the now dead body of the parent.
Only a small portion develop into males.
For next 2 weeks, males fly and young females crawl on the plant.
Life cycle = 6 weeks.
3-5 generations may be produced in 1 season.

64. Cochineal - Collection
Insects are brushed from plants with small brooms and killed (some left to provide for subsequent crops).
First crop killed contains the most colouring matter.
Insects are killed by plunging them in boiling water, stove heat or exposure to fumes by burning sulphur or charcoal.
If heat is used – insects change to purple – black – called ‘black grain’.
Fume killed – turn purple-grey called ‘silver grain’.
Small immature insects and larvae which can be separated by sieves are sold as ‘granilla’ or siftings.

65. Cochineal Collection

66. Cochineal - Characteristics
Oval in shape
Half cm in length
Examined microscopically after removing the colouring matter (ammonia solution).
Each insect contains 60 – 450 eggs and larvae.

67. Cochineal - Constituents
C-glycoside – anthraquinone derivative  bright purple, water-soluble colouring matter
Carminic acid
Fat
Wax
Adulteration: occurs by increasing the weight of the insects by ‘dressing’ it with inorganic matter in a colour which blends in with that of the insect.
Detected when insects are placed in water

68. Last Word on Anthraquinones
Anthraquinones take about 10hours to produce an effect (take overnight)
Should not be used for more than 10 days.
Should not be used by children, pregnant and lactating women.
Cause griping pain.
Are habit-forming.
Anthraquinones = phenolic glycosides, used as an irritating laxative