Herbal Constituents

Supportive Science for Botanical Medicine© Lisa Ganora 2008

An Isolated Phytomolecule

• Isolated digitoxin is used in contemporary pharmacy

• Cardiac glycoside, extracted from Foxglove (Digitalis purpurea or D. lanata)

A Phytochemical in a MatrixThe ascorbic acid molecule is exactly the same in Oranges or Violets, but is embedded in very different chemical matrices

Functional Groups• Alcohol• Ketone• Aldehyde• Carboxylic acid • Ester• Ether• Amine• Amide• Sulfide• Sulfoxide• Methyl• Phenyl

R = any carbon backbone

Constituents: Major Categories

• Carbohydrates• Lipids• Amino acids &

derivatives• Phenolic

compounds• Terpenoids• Steroids• Alkaloids

• monosaccharides• oligosaccharides• polysaccharides• fatty acids• oils

(triacylglycerols)• waxes• alkamides

(including isobutylamides)

• sulfur compounds (Garlic)

• glucosinolates• cyanogenic

glycosides• 5-HTP• amines• enzymes

• simple phenols• phenolic acids• phenylpropanoids• coumarins• lignans• stilbenoids• xanthones• styrylpyrones• flavonoids• isoflavonoids• benzofurans• chromones• quinones• phloroglucinols

• monoterpenes• sesquiterpenes• essential oils• diterpenes• triterpenes & saponins• tetraterpenes (carotenoids)

• steroidal saponins • phytosterols• cardiac glycosides

• betalain alkaloids• diterpenoid alkaloids• indole alkaloids• isoquinoline alkaloids• methylxanthines• monoterpenoid alkaloids• peptide alkaloids• pyrrolidine alkaloids• piperidine alkaloids• pyrrolizidine alkaloids• quinoline alkaloids• quinolizidine alkaloids• tropane alkaloids

Immunomodulating Polysaccharides

• Stimulate non-specific immunity• Echinacea: glucuronoarabinoxylans

(glucuronic acid + arabinose + xylose) & arabinorhamnogalactans (arabinose + rhamnose + galactose) & arabinogalactans

• Others in Eleuthero, Baptisia, Calendula, Panax ginseng• Larix (Larch) has arabinogalactans

Baptisia

Fatty Acids: Omega Series

• Tells where the double bonds are in the molecule

• Omega 6’s & Omega 9’s common in diet

• Omega 3’s come from Flax & fish oils

Alpha-linolenic acid (ALA),from Flax seed oil: Omega 3

DHA – docosahexaenoic acid,from cold-water fish oils:Omega 3

EPA, eicosapentaenoic acid,from fish oils: Omega 3

Isobutylamides

• Isobutylamides are a type of alkamide • Echinacea purpurea & E. angustifolia

have the highest concentrations• Contribute to immunomodulating effect• Stimulate phagocytosis• COX-2 inhibitors

(anti-inflammatory)

Sulfur Compounds in Garlic• Alliin (major cysteine sulfoxide in Garlic)

+• Alliinase (an enzyme in fresh, whole

Garlic or correctly dried Garlic powders) Allicin, the active antibiotic

compound• Allicin sulfides, ajoene, dithiins, etc.

Alliinase

Alliin Allicin

Flavonoids• Largest class of polyphenols: ~ 4,000 kinds• Often responsible for yellow or

red/blue/purple colors in flowers, fruits, vegetables

• Serve as antioxidants for the plants during photosynthesis

• Includes antioxidant, anti-inflammatory, cancer-preventative, & cardioprotective compounds

–OH group at position 3 with double bond between carbons 2 & 3; next to =O at position 4 on ‘C’ ring–OH group at position 5 on ‘A’ ring next to =O and –OH on ‘C’ ring

Structures responsible for antioxidant activity include:

–OH groups at positions 3’ and 4’ on ‘B’ ring

Quercetin has all three features – an excellent antioxidant

Why are Flavonoids Good Antioxidants?

B

CA

Monoterpenes & Sesquiterpenes

• Monoterpenes: 10 carbons• Sesquiterpenes: 15 carbons

1 2

3

4

56

7

8

910

Menthol Nerolidol

1

2

3

4

5

6

7

8

9

10

11

12

131415

Antiseptic Monoterpenes• Cineole (1,8-cineole or eucalyptol) is the

major constituent of Eucalyptus oil (~ 70 – 85%)*

• Antiseptic, antibacterial, expectorant• Excreted through lungs: bronchitis• α-Pinene, a minor constituent (up to

14%) is toxic in very high doses

Cineole α-Pinene

Triterpenes & Steroids• Triterpenes• Saponins

– Triterpenoid– Steroidal

• Steroids– Misc. steroids– Phytosterols– Cardiac glycosides

• ~ 4,000 different structures known

• Triterpenes have 3 x 10 = 30 carbons

• Steroids are derived from them; lose 3 carbons to end up with 27

Triterpene skeleton

Steroid skeleton

Cardiac Glycosides in Lily of the Valley

• ~ 40 different glycosides based on several different aglycones; variable

• Convallatoxin highly active, but generally no more than 10% of the amount ingested can be absorbed

• Positive inotropic effect; used for mild cardiac insufficiency

Tetraterpenes: Carotenes & Xanthophylls

• Lycopene – parent compound of carotenoids

• Carotenes – alpha-, beta-, delta- & gamma-carotenes are closely related

• Xanthophylls – carotenoids with oxygen in their structures – include lutein, neoxanthin & violaxanthin; capsanthin & capsorubin; astaxanthin

Capsaicinoids: Pungent Principles in Capsicum Annuum

• Capsaicin & relatives are oil-soluble• Powerful topical analgesics: herpetic neuralgia,

arthritis• Diaphoretic, rubefacient, antiseptic

Betalain Alkaloids• Nitrogenous pigments found only in a

few plant families, where they replace anthocyanins

• Very potent antioxidants• Anticarcinogenic

Betanidin

Pyrrolizidine Alkaloids (PAs)

Symphytine, adiester

Necine rings are metabolized into toxic pyrroles in the liver cells

Necine rings

Lycopsamine, a monoester

Isoquinoline Alkaloids in Mahonia

Berberine

• Berberine & relatives predominate• Some palmatine & jatrorrhizine• Actions similar to Goldenseal

Herbs for the Immune System

Supportive Science for Traditional Herbal Medicine© Lisa Ganora 2008

Astragalus

• Stimulates non-specific immunity

• Deep immune system tonic

• Antioxidant• Adjunct therapy for

cancer• Astragaloside III is

one of many saponins in the root

Astragaloside III

Popular Healing Herbs

Supportive Science for Traditional Herbal Medicine© Lisa Ganora 2008

Cranberry• Cranberries are rich in anthocyanins:

– Cyanidin glycosides– Delphinidin glycosides– Peonidin glycosides

• Contain glycosides of quercetin• Lignans also present• Proanthocyanidins inhibit binding of bacteria to

urinary tract epithelium• Flavonoid extracts inhibit the growth of prostate

cancer cells• Many constituents are antioxidant

Hawthorn

• Hyperin, a glycoside of quercetin, is the main flavonoid in Hawthorn

• Also contains OPC’s• Helps heart muscle to work more

efficiently, strengthens contractions, stabilizes rhythm

• Enhances the utilization of oxygen in cells

• Contains many antioxidants• Antispasmodic, anti-inflammatory

Herbal Chemistry

Bonding in Phytochemicals

Oxygen can form a double bond with carbon

Acetone

Stereochemistry of Phytochemicals

Why isomerism matters: receptor specificity

X

Receptor binding site

X

Receptor binding site

R enantiomer S enantiomer

Ring Systems

Cyclohexane ring vs. benzene ring

pH Affects Solubility: Bases

To isolate basic compounds in the lab, first the whole plant is extracted with ethyl acetate or a similar solvent

Next the extract is mixed with a water solution that has been acidified with an inorganic acid like dilute HCl

And the ionized base, being water-soluble, partitions down into the aqueous layer