andrea lugli feverfew mar2010 final

8/9/2019 Andrea Lugli Feverfew Mar2010 Final

1/10

3/29/10

1

Pain relievingproperties of Feverfew

Tanacetum parthenium (L.) Sch. Bip.

Andrea Lugli BSc, (dott. Chim. Ind.), MCPP.

CPP Seminar 27 March 2010 -London

Tanacetum parthenium (L.) Sch.Bip.; Fam.: Asteraceae

(Syn.; Chrysanthemum Parthenium Bernh.,Matricaria parthenium L., Leucanthemum

parthenium (L.) Gren. Et Godr.)

A few Botanical Names

Some European Common Name

Italian: Amarella, Amareggiola, Erba amara vera,Camomilla bastarda, Matricale, Partenio.

German : Mutterkraut English : FeverfewFrench : Grande CamomilleSpanish : Yerba de Santa Maria

What our senses, tell us?

Strong Aromatic bitter!

Pleasent to taste, smell?


2/10

3/29/10

2

What we know from history,tradition, practice.3 Levels of Knowledge

Historical Traditional Modern-traditional

Historical

Dioscorides I century. AD

Dioscorides recommendedFeverfew for manycomplaints including all hotinflammations and hotswellings (AHP 2007)

Historical

Castore Durante (1529-1590)

Herbario Novo

Durante, talks about theemmenagogue actitivity of adecoction of the flowers with nutmeg in wine.

A decoction made with its flowers ,and nutmeg in wine, heat and caccia fuori i mestrui = isemmenagogue


3/10

3/29/10

3

HistoricalAccording to Berry (1984)

Fever, Headache, migraine

Difficulties in labour,Threatened miscariage,Regulation of menses

Relieve of stomachache,Toothache,Insect bite

Berry MI, 1984. Feverfew faces thefuture. Pharm J 232: 611-614.

HistoricalA brief historical outline, according to Jacques Fleurentin( President de la Socite FrancaisedEthonpharmacologie)

Greek Medicine : asthma and melanconie

Arabian Medicine : diuretic, emmenagogue

Middle Age (St. Hildegarde): febrifugeXIX sec .: stimulant, digestive, antispasmodic,emmenagogueFleurentin J. 2007. Les pantes qui nous soignent. Ouest-France.

TraditionalFeverfew flowers : they are used as asubtitute of Chamomile in case of dysmenorrhea , and disorder of femalecycle. Cataplams made with the infusion of flowers are used in case of contusion/bruise,and skin ulcers (Negri, 1979)

The flowers are the part used in case of aerophagia, headache, dysmenorrhea ,dispepsia...

Dosage : powder, 2-5 g/die; tincture,30-60gtt, 3-5 times daily (Palma 1964).

Traditional

LAntonelli (1941) says that all the plant is tonic, febrifuge,stimulant, antispasmodic, emmenagogue and antiflatulent , hesays that it was very well known to the old physicians. The flowers are used both fresh or dried, particularly in case of dysmenorrhea .

Dosage : herbal tea made with 4-16g /L, 3-4 glasses during the

morning, during the 4-5 days of the menstrual cycle.

Antonelli G 1941. Le Piante che ridanno la salute. EdizionePlanta Medica, copia anastatica della III edizione "Riveduta edaumentata" del 1941.


4/10

3/29/10

4

Traditional

Grieve (1973) An infusion of the flowers made with boiling water and alowed to becomecold, will allay any distressing sensitivenenssto pain in a higly nervous subject, and will afford relief to the face-ache or earache of adyspeptic or rheumatic person .

Fluid extract, dose: 3,5-7ml

Physiomedical American Tradition

- Physiomedical dispensatory of Cook (1869):

14g in around 1liter of boiling water, 250 ml(equivalent to 3-4g herb ), every 30 minutes or more frequently.

Traditional

American Indian Mahuna usedFeverfew internally asantirheumatic .Moermann (1998)

Modern-traditional(Experience Based Phytotherapy- EBP)

As a symptomatic theDosage is quite high

(around 2g/die of drug)

A. In prophylaxis of migraineB. As symptomatic antinflammatory/painkiller

2.

3.

Used in case of:Headache,

Dysmenorrhea,Rheumatic disorders

1.


5/10

3/29/10

5

Modern-traditional: a look at thedosage.

Two teaspoonfuls as herbal tea. 2-3 cups before meals, regularly for afew months.Wichtl M (ed.) 2004. Herbal Drugs and Phytopharmaceuticals. Handbook for a practice on a scientific basis.3rd edition. Stuttgart, medoharm Scientific publishers.

Up to 1800g/die (starting at the first sign of migraine)Mitchell WA. 2003. Plant medicine i n practice. Churchill Livingstone

higher doses of up to 2g/day may be required for acute treatment of migraine or for inflammatory conditions .Hoffmann D 2003. Medical Herbalism - The science and practice of herbal medicine. Healing Art Press.Rochester, Vermont.

About powder doses of 200mg bid are often recommended .Tincture 1:5 0,25-0,5ml tid (equivalent to max: 300mg)Trickey R, 1998. Women hormones and the menstrual cycle. Allen Unwin

1-3 ml/day of 1:5 tincture (equivalent to around 0,2-1 g/day of leaf).Bone K 2003. A clinical guide to blending liquid herbs. Churchill Livingstone.

Monographs : part used, indications,dosage

Monograph Part used Indications Dosage

ESCOP 2003 aerial parts prophylaxis of migraine 50-120 mg/die

American Herbal Pharmacopoeia (AHP)

leaves or aerialparts

prophylaxis of migraine(supported byclinical trial);others...(experiencedbased)

fresh leaves :1-3 l. daily;powder 100 mg daily;tincture (1:5) 10-40 gttevery 2-3 hrs asindicated

WHO vol.II (2002) leaves or aerialparts

prophylaxis of migraine(supported byclinical trial);others...(traditional/experiencedbased)

prevention of migraine : drug equivalent to 0,2-0,6 mgof parthenolide

Phytochemistry

Parthenolide

Apigenin

Santin

Costonulide

Centaureidin

Phytochemistry strongly dependenton

Variety Harvesting time


6/10

3/29/10

6

The Phytocomplex

FeverfewPhytocomplex

Sesquiterpenlactones(i.e. Parthenolide)

Flavonoids

Others:- Essential oil- Polyphenols (dicaffeoylchinicacids)

- Tannins, Melatonin (very low)

Phytochemistry

Part of the Plant Concentration of Parthenolide (%)

Flowers 1,38 Leaves 0,95

Stems 0,08Root 0,01Source: Heptinstall et al., 1992

Parthenolide distribution in the different parts of the plant

The content of Parthenolide in the flower maybe up to 4 times thatone in the leaves.

Germacranolide Parthenolide ,Costunolide, Artemorin,Crisantemomin

Guaianolide Artecanin, Crisatemin A eB, Crisantemolide,Partholide

Eudesmolide Magnolialide, Reinosin,Santamarin, 1- -hydroxi

arbuscolin, 5- -hydroxireinosin.

Sesquiterpenlactones in Feverfew: not only Parthenolide

The activity of Parthenolide is 1/24 of the activity of an extractobtained from a drug rich in flowers.

Costunolide is more active as antinflammatory than perthenolide.(Koo TH, Lee JH, et al., 2001. A sesquiterpene lactone, costunolide, from Magnolia grandiflora inhibits NF-kappa B by targeting I kappa Bphosphorylation. Planta Med. Mar;67(2):103-7; Kassuya CA, Cremoneze A, et al., 2009. Antipyretic and anti-inflammatory properties of theethanolic extract,dichloromethane fraction and costunolide from Magnolia ovata (Magnoliaceae).J Ethnopharmacol. Jul 30;124(3):369-76. Epub2009 Jun 12.

Leaf Disc Ligule

Flavonols

6-hydroxy kampferol

3,6-dimethyl ether + (+) -

3,6,4-trimethyl ether ( Santin ) +++ +++ ++

Quercetagetin

3,6-dimethylether + ++ - 3,6,3-trimethylether ( Jaceidin ) ++ +++ +

3,6,4 trimethylether ( Centaureidin ) ++ +++ +

Quantity: +++, major; ++, medium +, minor; (+), trace.

Source: modifided from Williams et al., 1999

Lypophilic flavonoids identified in different partof Feverfew 1/2


7/10

3/29/10

7

Leaf Disc Ligule Flavones

Apigenin (+) + +

Luteolin - ++ -

Chrysoeriol - (+) -

Apigenin 7-glucuronide +

Luteolin 7-glucuronide +

Quantity: +++, major; ++, medium +, minor; (+), trace.

Source: modifided from Williams et al., 1999

Lypophilic flavonoids identified in different partof Feverfew 2/2

Different profile also in the watersoluble flavonoids

Feverfew and inflammation

Parthenolide

- Hall IH et al., 1979. Antinflammatory activity of sesquiterpenlactones and relatedcompounds. J Pharm Sci 68:537-542.

NF-kB

iNOS(inducible nitric oxide

synthase

Inhibition of agrecan catabolism induced by TNF- .

(in vitro chondrocyteOsteoarthritis model)

(Zhonghua Yi Xue Za Zhi. 2008

Inhibition of synovialFibroblast proliferation(Parada-Turska et al., 2008)


Parthenolide

NF-kB

iNOS(inducible nitric oxide

synthase

Inhibition of agrecan catabolism induced by TNF- .

(in vitro chondrocyteOsteoarthritis model)

(Zhonghua Yi Xue Za Zhi. 2008

Flavonoids

Inhibition of synovialFibroblast proliferation(Parada-Turska et al., 2008)

Direct inhibitionOf COX-2 andLypoxygenase


Recently (Wu et al., 2007)indentified differentdicaffeoylchinic acids with elevated antioxidantaction .


8/10

3/29/10

8

Extracts Pharmacology An interesting study

An extract DEPLETED of parthenolide showedantinflammatory activity:

direct inhibition of lypoxygenase

inhibition of release of different

inflammatory mediators (PGE2, NO,TNF- , IL-2 etc. )

Sur R, Martin K, Liebel F, Lyte P, Shapiro S, Southall M. 2009. Anti-inflammatory activity of parthenolide-depletedFeverfew (Tanacetum parthenium). Inflammopharmacology. Feb;17(1):42-9.

The Original Sin

and the City of London

Going back to the origin of theEvidence Based Dosage (?!)

Johnson ES, Kadam NP et al., 1985. Efficacy of feverfew asprophylactic treatment of migraine . BMJ 291:569- 573.

RCT, double blind, placebo controlled 20 subjects (City of London Migraine Clinic) that were used to self

treating with feverfew fresh leaves.

COULD THEY HAVE USED THE FLOWERS?


9/10

3/29/10

9

The Beginning or Going back to thedosage

Each freeze dried leaf containing five leaflets weighed a mean of 25.7 mg.

The mean daily dose of feverfew used by patients before entry to thestudy was 2.44 leaves (roughly 60mg). We therefore decided that the dose of each capsule should be fixed at 25 mg and that each

patient should receive two capsules daily .

Today recommended dosage: powder: 50-120 mg/die

Roughly: 5-20 times lower than the traditional dosage

Modern-traditional Two teaspoonfuls as herbal tea. 2-3 cups before meals, regularly for a

few months.Wichtl M (ed.) 2004. Herbal Drugs and Phytopharmaceuticals. Handbook for a practice on a scientific basis.3rd edition. Stuttgart, medoharm Scientific publishers.

Up to 1800g/die (starting at the first sign of migraine)Mitchell WA. 2003. Plant medicine in practice. Churchill Livingstone

higher doses of up to 2g/day may be required for acute treatment of migraine or for inflammatory conditions .Hoffmann D 2003. Medical Herbalism - The science and practice of herbal medicine. Healing Art Press.Rochester, Vermont.

About powder doses of 200mg bid are often recommended .Tincture 1:5 0,25-0,5ml tid (equivalent to max: 300mg)Trickey R, 1998. Women hormones and the menstrual cycle. Allen Unwin

1-3 ml/day of 1:5 tincture (equivalent to around 0,2-1 g/day of leaf).Bone K 2003. A clinical guide to blending liquid herbs. Churchill Livingstone.

Summary of Pharmacological studies on aextract from Aerial part rich of flowers .

Foto Sara Mercati

Foto Sara Mercati


it is 3-30 times more active (in differentanimal models) than extracts from leaves or normal aerial parts).

it is 3 times more active than extracts fromleaves in a specific model of migraine (c-fos).

To test antinflammatory and pain reducingproperties in acute.


10/10

3/29/10

10


Content of parthenolide correlates withactivity only in the migraine model.

Content of total flavonoids, by itself, doesnot correlate with activity and does not explainthe difference in activity of different extracts.

CONCLUSION FROM Historical and traditional data and

information: leaves, aerial part, or flowers could be used. dosage can be quite high (specifically in acute

conditions)

The dosage supported by clinical trial in theprophylaxis of migraine

is not based on traditional use but on a very specificand unusual one. It is very low due to the fact that patients ate fresh

leaves. (They could very difficulty could ate other parts!)

CONCLUSION Phytochemistry shows that many active

constituents (es. different kind of sesquiterpenlactones or flavonoids) make thephytocomplex of flowers similar but not equal tothat one of leaves and standard aerial parts.

It would be possibile that extracts from a drug based or rich in flowers is more/the mostactive in acute conditions and at high dosage .

THE END

Thanks for your kind attention

andrea lugli feverfew mar2010 final

Documents