SENEGA --- Polygala senega L. (Polygalaceae) + +

 

HERBAL

MEDICINAL

PLANT

 

 

 

 

 

 

 

 

 

 

 

                                                                               

 

 

 

 

 

 

                                                                              

SENEGA

Polygala senega L. (Polygalaceae) + +

 

BY

 

RETTODWIKART THENU

 SENEGA 

(seh’ni-guh)  

 

Polygala senega L. (Polygalaceae) + +

 

 

SUMMARY AND PHARMACEUTICAL COMMENT

 

The chemistry and pharmacology of senega has been extensively investigated but only limited clinical data are available. The activity of the saponins in animals supports the herbal use for bronchitis. In view of the lack of toxicity data and uncertainty regarding the risk associated with chronic ingestion of haemolytic saponins, excessive use of senega, and use during pregnancy and lactation should be avoided.

 

OTHER COMMON NAMES

Milkwort, Mountain Flax, Northern Senega, Polygala Root, Rattlesnake Root, Seneca, Seneca Root, Seneca Snakeroot, Senega Root, Senega Snakeroot, Seneka

                                                    

 

DESCRIPTION

MEDICINAL PARTS: The medicinal part is the dried root.

FLOWER AND FRUIT: The raceme is 8 cm long and is smaller than the bracts. The petals are pale red, the wings are yellowish-white with green veins.

LEAVES, STEM AND ROOT: The plant is a perennial herb with up to 40 cm high stems, which sprout in the axils of the scalelike bracts of the previous year's growth. The leaves are 8 cm long and 3 cm wide, alternate, ovate-lanceolate to

lanceolate, acuminate and denticulate. The upper surface is rich green; the under surface somewhat paler. The root varies in color from pale yellowish-gray to brownish-gray. It is usually twisted or almost spiral and has a thick, irregular, gnarled crown.

HABITAT: Polygala senega is indigenous to the central and western U.S.

PRODUCTION: Seneca Snakeroot consists of the dried root with remains of aerial stems of Polygala senega and/or other closely related species or a mixture of Polygala species.

NOT TO BE CONFUSED WITH: The roots of other Polygala species.

 

 

SPECIES (FAMILY)

Polygala senega L. (Polygalaceae) and other closely related Polygala species cultivated in western Canada and Japan.

 

SYNONYM(S)

Northern Senega (Canada), Polygala, Polygala senega var. latifolia, Rattlesnake Root, Senega Root, Senega Snakeroot, Snake Root

 

ORIGIN

Senega is a perennial found in the United States and Canada.

 

PHARMACOPODIAL AND OTHER MONOGRAPHS

BHC 1992(G6)

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

ESCOP 2003(G76)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

LEGAL CATEGORY (LICENSED PRODUCTS)

 GSL(G37)

 

CONSTITUENTS

See Reference 1 and General References G2, G6, G20, G52, G59 and G62.

ACIDS Salicylic acid and its methyl ester 0.1–0.2%; hydroxycinnamic acids (e.g. caffeic acid, ferulic acid, sinapic acid) free or esterified with saponins.(2)

CARBOHYDRATES Arabinose, fructose, glucose, melibiose, raffinose, saccharose, stachyose, sucrose; 1,5-anhydro-D-glucitol and other D-glucitol derivatives;(3, 4) trisaccharides; mucilage, pectin. A series of oligosaccharide esters, senegoses A–O, containing acetic, benzoic, trans- and cis-ferulic acid moieties linked to glucose and fructose.(5, 6) Five acylated sucrose glycosides, tenuifolisides A–E, have been isolated from P. tenuifolia.(7, 8) The esterifying acids are 3,4,5-trimethoxycinnamic, p-hydroxybenzoic, sinapic and ferulic.

TERPENOIDS A complex mixture of bidesmosidic triterpene saponins (6–10%) based on the aglycone presenegin. The total saponin mixture may be referred to as senegin. The saponins of P. senega var. latifolia are 3-glucosides of presenegin with tetra-, penta- or hexa-glucosyl groups linked at C-28 and including 400- methoxycinnamoyl or 300,400-dimethoxycinnamoylfucosyl resulting in E- and Z-cinnamoyl isomers of each saponin.(9–11) Senegins I– IV were the first saponins to be characterised and were Eisomers.(12, 13) P. tenuifolia contains similar saponins named onjisaponins A–G.(14, 15)

XANTHONES A number of xanthones have been isolated from P. tenuifolia including 4-C-[b-D-apiofuranosyl-(1!6)-b-D-glucopyranosyl]-1,3,6-trihydroxy-7-methoxyxanthone.(8)

 

OTHER CONSTITUENTS Fat, resin, sterols and valeric acid ester.

 

OTHER POLYGALA SPECIES Polygala paniculata contains coumarins (aurapten, murrangatin, phebalosin and 7-methoxy-8-(1,4-dihydroxy-3-methyl-2-butenyl) coumarin,(16) pyranocoumarin).(17) Polygala chamaebuxus (European species) contains hydroxycinnamic acid esters involving acetic, ferulic and sinapic acids as the ester moieties, saponins, tenuifolin (prosapogenin), rutin (flavonoid glycoside), coniferin and syringen (phenolic glycosides).(2) Other European species (e.g. Polygala alpestris, Polygala comosa, Polygala vayredae) contain complex mixtures of bidesmosidic saponins, tenuifolin (prosapogenin), hydroxycinnimic acid esters similar to those reported for P. chamaebuxus.(18) Polygala triphylla contains B-ring oxygen-free trioxygenated- and glucosyloxy-xanthones.(19) Polygala polygama contains podophyllotoxin and demethylpodophyllotoxin (lignans).(20)

 

CHEMICAL COMPONENTS

 

COMPOUNDS: SNAKEROOT (SENEGA SPECIES)

Triterpene saponins (6-12%): chief components senegins II to IV, chief aglycone presenegin

Oligosaccharide esters: senegosene A-I

Xanthone derivatives

Methyl salicylate (traces) and its glucoside

 

COMPOUNDS: SNAKEROOT (TENUIFOLIA SPECIES)

Triterpene saponins (6-12%): chief components onjisaponine aglycone presenegenin

Oligosaccharide esters: tenuifolosen A-P

Polygalite (acerite, 1.5-anhydrosorbite) and its glycosides, for example polygalite-2-alpha-galactoside

 

 

USES

USES

Senega has widely varied uses, including treatment for snakebite, cough, bronchitis, asthma, croup, pharyngitis, and other respiratory conditions. It is also used to induce vomiting and to treat skin disorders.

 

FOOD USE

Senega is listed by the Council of Europe as a natural source of food flavouring (category N2). This category indicates that senega can be added to foodstuffs in small quantities, with a possible limitation of an active principle (as yet unspecified) in the final product.(G16)

 

HERBAL USE

Senega is stated to possess expectorant, diaphoretic, sialogogue and emetic properties. Traditionally, it has been used for bronchitic asthma, chronic bronchitis, as a gargle for pharyngitis, and specifically for chronic bronchitis.

 

 

 

 

 

Figure 1. Senega (Polygala senega).

 

 

Figure 2. Senega – dried drug substance (root).

 

ACTIONS

 

Hypoglycemic Action

The hypoglycemic action of senega results from the chemical component senegin, a saponin (Kako et al, 1996). The rhizomes appear to contain the chemical responsible for the hypoglycemic action.

Increased Immune Response

One study determined that the saponins in senega increase specific immune responses and act as vaccine adjuvants (Estrada et al, 2000).

Sedative Action

Sedative-like effects observed in laboratory animals may be due to the actions of the saponins found in senega (Carretero et al, 1986).

 

PHARMACOLOGICAL ACTIONS

IN VITRO AND ANIMAL STUDIES

Mucosal secretion Polygalic acid and senegin are stated to be irritant to the gastrointestinal mucosa, and to cause a reflex secretion of mucus in the bronchioles.(1, G6, G44, G52) A fluid extract of senega increased respiratory tract fluid secretion in guinea-pig, cat and dog, but not in rabbit.(G52) CNS-depressant activity CNS-depressant properties in mice (e.g. reduction in spontaneous activity, inhibition of amfetamine stimulation, potentiation of barbiturate-induced sleeping time, and decrease in rectal temperature) have been documented for Polygala microphylla.(21) Similar properties have been reported for Polygala tenuifolia and have been attributed to the saponin constituents. A methanolic extract of P. tenuifolia, various fractions and pure onjisaponins B, F and G prolonged hexobarbital sleeping time in mice.(G52) Onjisaponin F produced sleep times in mice of 33 and 35 minutes for doses of 5 and 20 mg/kg, respectively, compared with 24 minutes for control and 42 minutes for chlorpromazine hydrochloride (2 mg/kg).

Inhibition of alcohol absorption E,Z-senegin II and E,Zsenagasaponins a and b from P. senega var. latifolia have potent inhibitory effects on alcohol absorption in rats. E,Z-senegasaponins a or b (100 mg/kg) administered orally to rats 1 hour after 20% aqueous ethanol (5 mL/kg, orally) reduced blood alcohol concentrations after 1 hour from 0.5 mg/mL to 0.02 mg/mL.(10) Under similar test conditions, E,Z-senegin II administration led to a blood ethanol concentration of 0.09 mg/mL. Hypoglycaemic activity Senegin II and E,Z-senegasaponins a and b have significant hypoglycaemic effects in rodents.(22) Senegin II (2.5 mg/kg, intraperitoneally) reduced blood glucose concentrations in normal mice from 220 mg/dL to 131 mg/dL 4 hours after administration and also significantly lowered blood glucose concentrations in KK-Ay mice from 434 mg/dL to 142 mg/dL under similar test conditions (p < 0.001, compared with control, for both studies). In glucose tolerance tests in rats, administration of E,Z-senegasaponins a and b (100 mg/kg, orally) resulted in glucose concentrations of 107–123 mg/mL after 30 minutes compared with 156 mg/mL in control animals (p < 0.01).(11)

Hypolipidaemic activity Seven hours after administration of an n-butanol fraction of a methanolic extract of P. senega var. Latifolia containing senegin II (5 mg/kg, intraperitoneally), the mean (standard deviation) blood triglyceride concentration was 65 (9) mg/100 mL, compared with 152 (17) mg/mL in control animals (p < 0.05).(23) The blood triglyceride concentration in cholesterol-fed mice was also significantly reduced (p < 0.05) under the similar test conditions. Pure senegin II at a dose of 5 mg/kg was also reported to lower blood triglyceride concentrations in mice.(23)

Other Activities Guinea-pig serum taken two hours after administration of lyophilised aqueous extract of P. tenuifolia (600 mg, intraperitoneally) inhibited the growth of herpes simplex virus type 1 (HSV-1) in Vero cells.(G52) An unspecified senegin from P. senega produced a 34% inhibition of influenza virus (A2/ Japan 305) at a concentration of 12.5 mg/mL.(G52) An ethanolic extract of P. senega has been reported to inhibit growth of a range of fungi.(G52) Polygala erioptera and P. paniculata have exhibited molluscicidal activity, and P. paniculata is reported to possess antifungal activity.(17) A butanol extract of P. tanuifolia containing onjisaponins (100 mg/mL) inhibited cyclic adenosine monophosphate (cAMP) diesterase by 73%.(G52) Isolated onjisaponins E, F and G inhibited cAMP phosphodiasterase, with IC50 values of 3.1, 2.9, and 3.7 _ 10_5 mol/L, respectively, being similar in action to papaverine. A total saponin concentration of P. senega var. Latifolia increased rat plasma concentrations of adrenocorticotrophic hormone (ACTH), corticosterone and glucose 30 minutes after intraperitoneal administration (25 mg/kg). Single doses of a dried methanol (50%) extract of P. senega var. latifolia and P. tanuifolia administered orally (2 g/kg) to rats produced 62% and 100% inhibition, respectively, of congestive oedema.(G52) Under the same conditions, furosemide 100 mg/kg produced 100% inhibition of congestive oedema.

 

CLINICAL STUDIES

There is a lack of clinical research assessing the effects of senega and rigorous randomised clinical trials are required. The following observations and uses require assessment in welldesigned clinical studies.

A fluid extract of senega root was reported to reduce the viscosity of sputum in patients with bronchiectasis.(G52) A French patent has stated that a triterpenic acid extracted from senega possesses anti-inflammatory activity and is effective against graft rejection, eczema, psoriasis and multiple sclerosis.(24) These reports provide only a low level of clinical evidence and the observed effects cannot be attributed definitively to senega or its constituents.

 

 

ACTIVITIES

Antiinflammatory (1; APA); Antispasmodic (f; FAD); Depurative (f; DEM; TOM); Diaphoretic (f; APA; FAD; FEL; TOM); Diuretic (f; FAD; FEL); Emetic (1; APA; FAD; FEL); Emmenagogue (f; FEL; TOM); Expectorant (2; APA; FAD; KOM; PH2; PIP); Laxative (f; FAD; FEL; TOM); Secretagogue (f; FEL); Secretolytic (1; HHB; KOM; PH2); Sialagogue (1; CAN; FEL); Stimulant (f; TOM); Tonic (f; DEM).

 

INDICATIONS

Amenorrhea (f; FAD; MAD); Asthma (f; APA; CEB; FAD; MAD); Bleeding (f; DEM); Blepharosis (f; MAD); Bronchosis (2; APA; FAD; MAD; PH2; PHR); Cardiopathy (f; DEM; FAD); Cataract (f; MAD); Catarrh (2; FEL; KOM; MAD; PHR; PIP); Cold (f; APA; DEM; FAD; TOM); Congestion (f; PH2; TOM); Conjunctivosis (f; MAD); Constipation (f; FAD; FEL; TOM); Convulsion (f; DEM; FAD); Cough (2; PHR; PH2; TOM); Cramp (f; FAD); Croup (f; FAD; FEL; MAD; TOM); Cystosis (f; MAD); Dermatosis (f; FEL); Dropsy (f; MAD; TOM); Dysmenorrhea (f; MAD); Eczema (f; CEB); Emphysema (f; MAD); Enuresis (f; MAD); Fever (f; APA; FAD; FEL; TOM); Hemorrhoid (f; CEB); Hoarseness (f; FEL); Inflammation (1; APA; DEM); Laryngosis (f; MAD); Mucososis (f; TOM); Ophthalmia (f; MAD); Pain (1; FAD); Pertussis (f; MAD; TOM); Pharyngosis (1; CAN); Photophobia (f; MAD); Phthisis (f; MAD); Pleurisy (f; APA; FAD; MAD); Pneumonia (f; FAD; FEL; MAD; TOM); Pulmonosis (f; MAD); Respirosis (2; DEM; FAD; KOM; PH2; PIP); Rheumatism (1; DEM; FAD; MAD; TOM); Smallpox (f; TOM); Snakebite (f; APA; CEB; TOM); Sore Throat (f; FEL); Swelling (f; FAD); Syphilis (f; CEB); Toothache (f; DEM); Tracheosis (1; PHR; PH2); Tuberculosis (f; MAD); Typhoid (f; FEL); Water Retention (f; FAD; FEL); Wound (f; FEL).

 

INDICATIONS AND USAGE

Approved by Commission E:

• COUGH/BRONCHITIS

UNPROVEN USES: The drug is used for congestion of the respiratory tract, as an expectorant in cases of bronchitis with minor sputum output and tracheitis.

 

PRODUCT AVAILABILITY

Dried powdered root, extract, syrup, tea, tincture

PLANT PART USED: Dried root, Root, rootstock

 

DOSAGES

 

DOSAGES

Expectorant

·         Adult PO tea: 1 cup bid-tid

Other

·         Adult PO dried powdered root: 0.5-1 g tid

·         Adult PO extract: 0.3-1 ml q4hr prn

·         Adult PO syrup: 2 tbsp q4hr prn

·         Adult PO tincture: 2.5-5 ml q4hr prn

 

DOSAGES

Dosages for oral administration (adults) for traditional uses recommended in older and contemporary standard herbal and pharmaceutical reference texts are given below.

·         Dried root    0.5–1.0 g as an infusion three times daily.(G6, G7)

·         Senega Liquid Extract (BPC 1968)   0.3–1.0 mL.

·         Senega Tincture (BPC 1968)   2.5–5.0 mL.

 

DOSAGES

·         Root 3 ×/day (AHP; KOM); 0.5–2 g root, several ×/day (MAD); 1.5–3 g root (PIP); 0.5 g (ca. 1/5 tsp) root/cup tea/day, not to exceed 3 g/day (APA); 0.5 g root/cup (HHB); 0.5–1.0 g dry root, or in tea, 3 ×/day (CAN);

·         0.5–1 g powdered root (PNC); 2.5–5 ml concentrated root tea (PNC); 0.3–1 ml liquid root extract (CAN; PNC);

·         1.5–3 g fluid root extract (KOM; PIP); 2.5–7.5 g root tincture (KOM; PIP); 2.5–5 ml root tincture (CAN; PNC).

 

DOSAGES

MODE OF ADMINISTRATION: As a comminuted root for decoctions and other galenic preparations for internal use or as an extract. It is a component of various standardized antitussive preparations.

PREPARATION: To make an infusion, place 0.5 gm comminuted drug in cold water, heat to a simmer and strain after 10 minutes (1 teaspoonful = 2.5 gm drug).

DAILY DOSAGE: The daily dosage is 1.5 to 3.0 gm root or liquid extract (1:2) or 2.5 to 7.5 gm tincture (1:10). To use the infusion as an expectorant, drink 1 cup of tea 2 to 3 times daily. In serious cases, the tea can be taken every two hours if the patient is observed for side effects.

 

 

PRECAUTIONS AND ADVERSE REACTIONS

 

GENERAL: No health hazards or side effects are known in conjunction with the proper administration of designated therapeutic dosages. With prolonged use, gastrointestinal irritation can occur.

PREGNANCY: Not to be used during pregnancy.

 

OVERDOSAGE

Overdosage leads to nausea, diarrhea, gastric complaints and queasiness.

 

CONTRAINDICATIONS, INTERACTIONS, AND SIDE EFFECTS

CLASS 2B. Emmenagogue and uterotonic. Contraindicated in gastric ulcers and gastrosis; not for long-term use (AHP). Commission E reports root permitted for oral use. No contraindications, adverse effects, or interactions, except for GI irritation from continued or prolonged use (AEH; KOM). The Herbal HDR cautions that overdosage leads to diarrhea, gastric complaints, nausea, and queasiness (PHR). CAN cautions that saponins can irritate GI tract. Polygalic acid and senegin irritate the GI mucosa and may cause a reflex secretion of mucus in the bronchioles. Large doses may cause purging and vomiting (CAN).

 

 

CONTRA-INDICATIONS, WARNINGS

Senega may exacerbate existing gastrointestinal inflammation and excessive doses may cause vomiting. There is limited evidence from preclinical studies that constituents of senega have hypoglycaemic activity. The clinical relevance of this is not clear although, until further information is available, senega should not be used by patients with diabetes.

DRUG INTERACTIONS None documented. However, the potential for preparations of senega to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. There is limited evidence from preclinical studies that certain constituents of senega have hypoglycaemic activity. The clinical relevance of this, if any, is not clear; however, until further information is available, it is recommended that senega should not be used by patients receiving hypoglycaemic agents.

PREGNANCY AND LACTATION Limited information is available on the chemistry, pharmacology and toxicity of senega. In view of this, and the potential irritant properties of senega, its use during pregnancy and lactation should be avoided.

 

 

CONTRAINDICATIONS

Until more research is available, senega should not be used during pregnancy and breastfeeding. It should not be given to children. Senega should not be used by persons with hypersensitivity to this herb or salicylates. Clients with peptic or duodenal ulcers, central nervous system depression, or gastritis also should not use senega.

 

SIDE EFFECTS/ADVERSE REACTIONS

CNS: Dizziness, lethargy, anxiety

EENT: Blurred vision

GI: Nausea, vomiting, anorexia, abdominal pain, diarrhea

INTEG: Hypersensitivity reactions

 

INTERACTIONS

Drug

Anticoagulants (heparin, warfarin, salicylates): Senega may increase bleeding time when used with anticoagulants; avoid concurrent use.

Antidiabetics (insulin): Senega may decrease the effects of antidiabetics; avoid concurrent use.

INTERACTIONS—CONT’D

CNS depressants (alcohol, barbiturates, benzodiazepines, opiates, sedatives/hypnotics): Use of senega with CNS depressants may cause increased central nervous system effects; avoid concurrent use.

 

EFFECTS

The rhizome is secretolytic and works as an expectorant.

 

SIDE-EFFECTS, TOXICITY

There is a lack of clinical safety and toxicity data for senega and further investigation of these aspects is required. Saponins are generally regarded as irritant to the gastrointestinal mucosa, and irritant properties have been documented for senega and other Polygala species.(G51) Large doses of senega are reported to cause vomiting and purging.(G60)

The haemolytic index (HI) of senega saponins is stated to be between 2500 and 4500.(G62) Haemolytic saponins are toxic to mammals when administered intravenously, but have a low toxicity when given orally because they do not cross the gastrointestinal mucosa.(25) Contact with damaged mucosal areas may cause a problem. Toxicity associated with chronic exposure of the gastrointestinal mucosa to haemolytic saponins has not been established. It has been stated that the suitability of saponins for nutritional and pharmacological use requires further investigation free saponins in the gastrointestinal tract may interact with the mucosal cells, causing a transient increase in the permeability of the small intestine to intraluminal solutes and inhibiting active nutrient absorption.(25) This action may consequently facilitate the entry of antigens and biologically active food peptides into the blood circulation, with adverse systemic effects.(25) Aqueous and methanol extracts of P. senega and P. tenuifolia were negative in the rec-assay with Bacillus subtilis and in the reversion assay with Ames strains TA98 and TA100 of Salmonella typhimurium.(G52) A mixture of senegins given to rats (i.p.) gave an LD50 value of 3 mg/ kg and inhibited the growth of Walker carcinoma in rats with an ED50 value of 1.5 mg/kg.(G52) Cytotoxic lignans have been documented as constituents of a related species, P. polygama.(10)

 

CLIENT CONSIDERATIONS

ASSESS

·         Assess the reason the client is using goldenseal.

·         Assess for hypersensitivity reactions. If present, discontinue the use of senega and administer an antihistamine or other appropriate therapy.

·         Determine whether the client is taking anticoagulants, antidiabetics, or CNS depressants. Drugs in these classes should not be taken concurrently with this herb (see Interactions).

ADMINISTER

·         Instruct the client to store senega products in a cool, dry place, away from heat and moisture.

TEACH CLIENT/FAMILY

·         Caution the client not to use senega in children or those who are pregnant or breastfeeding until more research is available.

 

 

PREPARATIONS

 

PROPRIETARY MULTI-INGREDIENT PREPARATIONS

Argentina: Antitos; Hebert Caramelos; Ixana; Ixana; No-Tos Adultos; No-Tos Adultos; No-Tos Infantil; Pectobron. Australia: Senagar; Senega and Ammonia. Austria: Eicebaer; Tussimont. Belgium: Tux. Brazil: Expectomel; Pectal. Canada: Bronchial; Bronchozone; Sirop Cocillana Codeine; Wampole Bronchial Cough Syrup. Czech Republic: Stodal. France: Neo-Codion. Hong Kong: Coci-Fedra; Cocillana Christo; Cocillana Compound; Cocillana Compound; Mefedra-N; Mist Expect Stim. Portugal: Stodal. Russia: Neo-Codion Babies (Нео- Кодион Для Младенцев). South Africa: Borstol Cough Remedy. Spain: Broncovital; Pastillas Pectoral Kely; Pulmofasa. Sweden: Cocillana-Etyfin. Switzerland: Hederix; Makaphyt Gouttes antitussives; Makaphyt Sirop; Pectocalmine; Pectoral N; Phol-Tux. UK: Antibron; Chest Mixture; Chesty Cough Relief; Tickly Cough & Sore Throat Relief. Venezuela: Acetoben.

 

EXTRACTS

One antiinflammatory triterpenic acid is useful for eczema, graft rejection, multiple sclerosis, and psoriasis, according to a French patent mentioned by CAN. Looking at that suggests, to me, that the acid has immunosuppressant activity, which would be contraindicated in most diseases. Saponins can be hemolytic and a GI irritant (CAN). Hemolytic saponins are toxic when injected iv, but have low toxicity when given orally since they don’t cross GI mucosa (CAN). Free saponins in GI tract may react with mucosa, causing an increased permeability of small intestine to intraluminal solutes and inhibiting active nutrient absorption. This activity may facilitate entry of antigens and active food peptides into the blood circulation with adverse (and I also suppose good) side effects (CAN).

 

 

REFERENCE

 

 

Barnes, J., Anderson, L. A., and Phillipson, J. D. 2007. Herbal Medicines Third Edition. Pharmaceutical Press. Auckland and London.

 

Duke, J. A. with Mary Jo Bogenschutz-Godwin, Judi duCellier, Peggy-Ann K. Duke. 2002. Handbook of Medicinal Herbs 2nd Ed. CRC Press LLC. USA.

 

Gruenwald, J., Brendler, T., Jaenicke, Ch. 2000.  PDR for Herbal Medicines.  Medical Economics Company, Inc. at Montvale, NJ 07645-1742. USA

 

Linda S-Roth. 2010. Mosby’s Handbook Of Herbs & Natural Supplements, Fourth Edition. Mosby Elsevier. USA

 

 

Figure 3. Primary Chemical Components and Possible Actions

(Linda, S-R. 2010)