Review of categories of medicinally active phytochemicals with special emphasis on the complexity of Echinacea spp.

1. Phytochemistry
Dr. Michael Tims

2. How do we Come with a
Classification Scheme?
 Chemical structure
 Biosynthetic pathway

3. Classification scheme
 Carbohydrates
 Lipids
 Alkaloids
 Terpenoids
 Steroids
 Phenols

6. Glycosides (sugar ethers)
 Break down to yield sugar(s) (glycone), plus a non-
sugar component (aglycone).
 Can be difficult to isolate together

7. Carbohydrates
 Mucilage – demulcent activity
 Gums
 Polysaccharides

8. Mucilage
• Althea officinalis or
marshmallow
Demulcent - reduce
irritation of
bowels/urinary passage.

9. Gums
 Wound or injury products of woody plants
 Their acidic groups interact with small amounts of
calcium, magnesium and potassium to create
viscous solutions or gels in water

10. Industrial Uses
 Alter texture of food products
 Stabilize emulsions, retain moisture, thicken liquids
and suspend particles - toothpaste
 In frozen products prevent ice crystals
 Coat "instant mixes" so won’t react water in air
 Hold some tablets together or create time release
 Make the paper more water resistant

11. Gums
• Diabetes
• Cholesterol
Cyamopsis tetragonolobus
Guar gum

12. Polysaccharides
 -glucan - high molecular weight polymers consisting of
chains of sugars (mono- or oligo-saccharides)
 The simplest polysaccharides are cellulose and starch which
are polymers of glucose only
 Immune function - structurally dependent activity
 Gandelan active as anti-cancer agent
Ganoderma lucidum
reishi mushroom
O
O
O
O
O
CH2
CH2OH
OH
OH
OH
OH
O
CH2
OH
OH
O
CH2
OH
OH
Section of
Beta-1,6'D-Glucan

13. -glucans
 Amount of -glucan
chains greater in fruiting
body vs mycelium
 Structure also different

14.  Wild vs. Grain culture
 -glucan vs. α-glucan

15. Lipids
 Plant oils
 Flax seed oil
• Source omega-3 fatty acid - alpha-linolenic acid
• Alkylamides

16. Alkylamides (aka alkamides)
 Essential fatty acids linked to an amine
group
 Structurally related to animal
endocannabinoids

17. Distribution of Amides
 Echinacea angustifolia
 E. purpurea
 Prickly ash bark
 Spilanthes
 Black peppers
 Red peppers (chilis)
commons.wikimedia.org/wiki/
We will return to Echinacea

18. Alkaloids
Group Structure Examples
Pyrrolidine Nicotine, tetrapyrroles
Tropane Cocaine, atropine
Piperidine Coniine
Pyrrolizidine Retrosine
Quinolizidine Lupinine
Isoquinoline Berberine, morphine
Indole
Strychnine, vinblastine,
psilocybin

19. Purine Alkaloids (methylxanthines)

20. CNS Activity
 Why?

22. Terpenoids

23. Essential oils
 Aromatic herbs and spices
 Distillation, occasionally solvent extraction
 May contain hundreds of components
 Largely monoterpenes
http://commons.wikimedia.org/wiki/Category:Distillation

24. Monoterpene Synthesis
in Thymus vulgaris
Chemotypes
Thymus vulgaris ct. linalool
Thymus vulgaris ct. thymol
Thymus vulgaris ct. carvacrol
Thymus vulgaris ct. gerinol
Thyme vulgaris ct. thuyanol

25. Sesquiterpenes (C15)
 Absinthin, a dimeric
sesquiterpene lactone
 Considered a volatile oil
 Anti-malarial drug
Artemisia annua, Sweet Annie

26. Diterpenes (C20)
 Gingkolides from
Gingko biloba
 Cannibinoids (C21)

27. Diterpene Volatiles Oils
 Podophyllum peltatum
Mayapple
 Genital warts caused by
human papillomavirus
 Antimitotic
Podophyllotoxin

28. Triterpenes (C30)
Actaea racemosa (Cimicifuga racemosa)
Black cohosh
25-acetylcimigenol xylopyranoside (ACCX)
triterpene glycoside

29. Tetraterpenes (carotenoids)
Phytoene
Lycopene
-carotene

30. Steroid Glycoside
 Source of prednenolone and progesterone
 Co-occurs with isomer yamogenin
 Hard to cultivate wild yams
Diosgenin
www.chemblink.com
Mexican wild yam
Dioscorea mexicana

31. Phenolic compounds
Benzene ring
Cyclohexane structure – three double bonds.
The basis of all ‘aromatic’ chemicals
Hydroxyl group (OH)
One or more attached to benzene ring
Functional groups (= aryl groups)
Methyl CH3
Methyoxy CH3O
Amino NH2
Carboxyl COOH
Lactone ring Coumarins
CO2H
OH
Salicylic acid

33. Phenols
 Phenols are often glycosides
 Simple Subclassification
• Flavanoids
• Tannins

34. Flavonoids
 Chemotaxonomically greatest diversity
 Many are pigments, located in fruit or flower
 Stress modifiers, antioxidants and vaso-protectants

35. Anthraquinones
 Phenols
 Flavanoids
 Anthroquinones red/purple
pigments
Cascara sagrada

36. Stillbenes
 Phenols
 Flavanoids
 Tannins
 Stilbenes
Vitis vinefera

38. Pyrones
 Phenols
 Flavanoids
 Kava pyrones
methysticin
Piper methysticum

39. Phenylpropanoids
Curcuminoids
Tumeric

40. Lignans
OH
OCH 3
OCH 3
OCH 3
OCH 3
H3CO
OCH 3
Schizandrin Schisandria chinensis - up to 30 lignans in seeds
• Hepatoprotective
• Inhibits lipid peroxidation

41. Echinacea Constituents
https://pubchem.ncbi.nlm.nih.gov
dodeca-2E,4E-dienoic acid
isobutylamide
cichoric acid echinocoside
Arabinogalactan
LaLone et. al. (2009) J. Agric Food Chem. 57(19): 8820-8830
Phenylpropanoid
Derivatives
Alkamides

42. Let’s Go a Little Deeper

43. Sandasi, M. et al. (2014) Hyperspectral imaging and chemometric modeling of Echinacea – A
novel approach in the quality control of herbal medicines. Molecules 19: 13104-13121.
Echinacea angustifolia
Echinacea pallida
Echinacea purpurea

44. Uncertainty with Production of
Echinacea Products
 Ethanol extracts produce higher levels of alkylamides and
phenolics
 Block inflammatory response, suppressing symptoms of with
infection
 More concentrated in roots
 Signatures?
 Echinacoside (phenolic) in E. angustifolia not E. purpurea.
 Echinacin (alkylamide) in E. angustifolia and E. pallida.

45. Uncertainty with Echinacea
 Water extracts contain polysaccharides and glycoproteins
(arabinorhamnogalactan)
 Enhance immunity by increasing production of cytokines
 Appear to be present in aerial parts

46. Phenylpropanoid Derivatives
 Cichoric acid - hydroxycinnamic acid
 Cynarin – hydroxycinnamic acid
 Chlorogenic acid - hydroxycinnamic acid, and an
intermediate in lignin biosynthesis
 Echinacoside - caffeic acid glycoside
 Verbascoside - caffeoyl phenylethanoid glycoside

47. Alkamides (Alkylamides)
 Most abundant in roots of E. purpurea and E.
angustifolia
 Much lower amounts in aerial parts E. purpurea
and E. angustifolia
 As a whole, much lower amounts in E. pallida
Mudge, E. et al. (2011) Analysis of alkylamides in Echinacea plant materials and
dietary supplements by UFLC with diode array and MS detection. J. Agri. Food
Chem. 59: 8086-8094.

48. E. purpurea
Perry, NB et al. (1997) Alkamide levels in Echinacea purpurea: a rapid analytical method
revealing differences among roots, rhizomes, stems, leaves and flowers. Planta Med. 63: 58-62

49. Root Tissue
1. cynarin
2. echinacoside
3. cichoric acid
4. echinacoside derivative
5. verbascoside
6. alkamide
7. alkamide
8. alkamide
9. alkamide
Sloley, DB et al. (2001) Comparison of chemical components and antioxidant capacity of
different Echinacea species. J Pharm. Pharmacol. 53:849-857

50. Mean alkamide levels (mg/g dry weight) in different parts of E.
purpurea followed by standard deviation. Bold significantly
different (P<0.01)

51. E. Purpurea and Quality Control
 Alkamide distribution flower heads important to
quality control
 13 polyacetylene artifacts formed during
storage, since they are found in dried but not
fresh roots of E. pallida.
 Second cut harvest contain cichoric acid no
alkamides
 Arabinogalactans - microbiological degradation

52. Cichoric Acid
 Degraded during processing and juice extraction
 This occurs with many plants – black tea
 Ascorbic acid (5mM) or EtOH (≥ 45%) inhibits
degradation
 short term during extraction
 longer term storage
Nusslein, B. et al. (2000). J. Nat. Prod. 63: 1615-1618.

53. E. purpurea Cultivar Screening
Trout Lake Farm
 Mechanical harvesting
 Flower heads, size and uniformity of flowering time
 Large smooth leaves (leaf hairs capture dirt)
 Deep purple color
 Intense tongue tingle
(Letchamo et al. 1999)

54.  Field of 2 million identified 420 optimal plants
 Used organoleptic and HPLC analysis to select 360
propagation lines
 20-30 of each line replanted in three different
locations
 Used phytochemical analysis on the aerial parts to
analyze at 4 stages of flower development

55. Cichoric acid
Isobutylamides

57. E. angustifolia
↑
aerial
roots
↑
Pairssameproduct
↑