Wednesday, July 8, 2020

COWSLIP -- Primula veris L. (Primulaceae) ++

HERBAL

MEDICINAL

PLANT


 

 

 

 

 

 

 

 

 

 

 

                                                                          

   

   

 


COWSLIP

Primula veris  L. (Primulaceae) ++

 

 BY

 

RETTODWIKART THENU

Description: Primula veris - Wikipedia








COWSLIP  

(kow’slip)

 

Primula veris  L. (Primulaceae) ++

 

SUMMARY AND PHARMACEUTICAL COMMENT

The chemistry of cowslip is not well-documented and it is unclear whether saponins reported as constituents of the underground plant parts are also present in the flowers. Little pharmacological information has been documented to justify the herbal uses of cowslip. In view of the lack of toxicity data, excessive use of cowslip should be avoided.

 

 

TRADE NAMES

Comfrey (available from numerous manufacturers)

 

OTHER COMMON NAMES

Artetyke, Arthritica, Buckles, Crewel, Drelip, Fairy Cup, May Blob, Our Lady’s Keys, Paigle, Password, Peagle, Petty Mulleins, Plumrocks 

Oxlip, True Cowslip, English Cowslip, Butter Rose, Herb Peter Paigle, Key Flower, Key of Heaven, Fairy Caps. Palsywort, Plumrocks, Mayflower. Primrose.

 

DESCRIPTION

MEDICINAL PARTS: The medicinal parts are the roots and flowers.

FLOWER AND FRUIT: The flowers are in richly blossomed umbels with a short peduncle. The flowers are turned to one side and grow in clusters (up to 25) from the center of the leaf rosette. The calyx is cylindrical and appressed with a green margin. The remaining part of the calyx is yellow and it is 12 to 15 cm long. The corolla is odorless, usually sulfur yellow and has a tube with 5 triangular, orange spots. The fruit is an oval capsule with 1.5 to 2.5 mm-long brown, warty seeds.

LEAVES, STEM AND ROOT: This 10 cm high plant is a herbaceous perennial with a short sturdy rhizome. The green plant parts are covered in 2 mm long segmented hairs. The leaves are revolute in the bud. They are wrinkled, ovate or ovate oblong and are rounded at the base. They narrow quickly to the winged stems. During the flowering season they are irregularly dentate with blunt teeth. They are 3 to 6 cm long during the flowering season, but grow larger later. The upper side of the leaf is glabrous.

HABITAT: The plant is indigenous to all of Central Europe as far as the Southern European mountains. There are many subspecies.

PRODUCTION: Cowslip flower consists of the dried, whole flowers with calyx of Primula veris and/or Primula elatior as well as their preparations. Cowslip root consists of the dried  rhizome with roots of Primula veris and/or Primula elatior as well as their preparations. Cowslip root is harvested at best in the third year of growth.

 

SPECIES (FAMILY)

Primula veris L. (Primulaceae)

 

SYNONYM(S)

Paigle, Peagle, Primula, Primula officinalis (L.) Hill.

 

ORIGIN

Cowslip is found in the western region of the United States, Europe, and western Asia.

 

PHARMACOPODIAL AND OTHER MONOGRAPHS

BHP 1983(G7)

Complete German Commission E (Primrose flower)(G3)

ESCOP 1997(G52)

Martindale 35th edition(G85)

 

LEGAL CATEGORY (LICENSED PRODUCTS)

GSL  (external use only)(G37)

 

CONSTITUENTS

The following is compiled from several sources, including General References G2 and G59.

Carbohydrates Arabinose, galactose, galacturonic acid, glucose, rhamnose, xylose and water-soluble polysaccharide (6.2–6.6%).

Flavonoids Apigenin, gossypetin, isorhamnetin, kaempferol, luteolin and quercetin.(1)

Phenols Glycosides primulaveroside (primulaverin) and primveroside.

Quinones Primin and other quinone compounds.

Saponins Primula acid in sepals but saponins absent from other parts of the flower.

Tannins Condensed (e.g. proanthocyanidin B2), pseudotannins (e.g. epicatechin, epigallocatechin).(1)

Other Constituents Silicic acid and volatile oil (0.1–0.25%).

Other Plant Parts Saponins have been documented for the underground parts.(1) 'Primulic acid' is a collective term for the saponin mixture.(2) Primulic acid A glycoside (5–10%) yields primulagenin A as aglycone together with arabinose, galactose, glucose, glucuronic acid, rhamnose and xylose.(3, 4) The saponin content of the roots is stated to peak at two years.(5) After five years of storage the saponin content was reported to have decreased by 45%.

 

CHEMICAL COMPONENTS

 

COMPOUNDS: COWSLIP FLOWER

Flavonoids (3%): including rutin, kaempferol-3-O-rutinoside, isorhamnetin-3-O-glucoside; isorhamnetin rhamnosyl robinoside, isorhamnetin robinoside, isorhamnetin rutinoside, kaempferol robinoside, limocitrin-3-O-glucoside. Quercetin gentiobioside, quercetin-3-O-glucoside, quercetin robinoside

Primine

Triterpene saponins

 

COMPOUNDS: COWSLIP ROOT

Phenol glycosides (0.2 to 2.3%, high values in the Spring): primulaverin (3%, 2-hydroxy-5-methoxy- benzoic acid methyl ester-O-xyloglucoside) changing over during dehydration into the characteristic-smelling 5-methoxy-methyl salicylate

Triterpene saponins (5 to 10%): chief components primulic acid A (chief aglycone protoprimulagenin)

 

USES

USES

Cowslip is used to treat insomnia, anxiety, restlessness, and nervousness. The root is used for chronic cough.

 

FOOD USE

Cowslip is not commonly used in foods. A related species,

Primula eliator, is listed by the Council of Europe as a natural source of food flavouring (category N2). This category indicates that Primula eliator can be added to foodstuffs, provided that the concentration of coumarin does not exceed 2 mg/kg.(G16) Coumarins, however, are not documented as constituents of Primula veris, the subject of this monograph.

 

HERBAL USE

Cowslip is stated to possess sedative, antispasmodic, hypnotic, mild diuretic, expectorant and mild aperient properties. It has been used for insomnia, nervous excitability, hysteria and specifically for anxiety states associated with restlessness and irritability.(G2, G7,G64)

 

Figure 1. Cowslip (Primula veris).

 

 

Figure 2. Cowslip – dried drug substance (flowerhead).

 

ACTIONS

 

Respiratory Action

One study conducted in Europe evaluated the effect of pharmacotherapeutic options and herbal remedies for bronchitis. The herbal remedy Primula veris showed an effect equal to that of pharmacologic treatments (Ernst et al, 1997), as did several other combination herbal products with oil of eucalyptus, peppermint, anise, and ivy extract.

Other Actions

Older studies have identifi ed both hypotensive and hypertensive effects of saponins, chemical components in Primula veris. The saponin may be responsible for this action. Two fl avonoids, quercetin and apigenin, are responsible for the antiinfl ammatory and antispasmodic effects of cowslip. These effects are common in all herbs with these chemical components.

 

PHARMACOLOGICAL ACTIONS

 

IN VITRO AND ANIMAL STUDIES

The saponin fraction has been reported to cause an initial hypotension followed by a long-lasting hypertension in anaesthetised animals.(6) In vitro, the saponins have been documented to inhibit prostaglandin (PG) synthetase, but to a lesser extent than aspirin because of insignificant protein binding; to exhibit a slight antiinflammatory effect against carrageenan rat paw oedema; to contract isolated rabbit ileum; and to possess analgesic and antigranulation activity.(6) Flavonoid and tannin constituents have been documented for cowslip. A variety of activities has been reported for flavonoids including anti-inflammatory and antispasmodic effects. The tannins are known to be astringent.

 

CLINICAL STUDIES

There is a lack of clinical research assessing the effects of cowslip and rigorous randomised controlled clinical trials are required.

 

ACTIVITIES

Allergenic (1; PH2); Analgesic (1; APA; CAN); Antigranulation (1; APA; CAN); Antihistaminic (1; PNC); Antiinflammatory (1; APA; CAN); Antioxidant (1; PNC); Antiradicular (1; PNC); Antispasmodic (1; APA; CAN; HH2); Aperient (f; PNC); Astringent (1; APA; CAN); Candidicide (1; HH2); Cardiotonic (f; APA; HH2); Decongestant (1; APA); Diuretic (1; APA; HH2; PH2; PNC); Expectorant (2; HH2; KOM; PH2; PIP); Fungicide (1; HH2); Hemolytic (1; CAN); Hypertensive (1; APA; CAN); Hypnotic (f; CAN); Hypotensive (1; APA; CAN); Laxative (1; APA; HH2); Narcotic (f; MAD); Nervine (f; HH2); Neurotonic (f; PH2); Piscicide (1; HH2); Secretolytic (2; KOM; PIP); Sedative (f; APA; HH2; PNC); Vulnerary (1; APA).

 

INDICATIONS

Adenopathy (f; MAD); Anxiety (f; APA; CAN; PH2); Apoplexy (f; MAD); Arthrosis (f; HH2; MAD; PH2); Asthma (f; APA; MAD; PHR; PH2); Bronchosis (2; APA; MAD; PHR; PH2); Cancer (f; JLH); Cancer, liver (f; JLH); Cancer, spleen (f; JLH); Candida (1; HH2); Catarrh (2; HH2; KOM; MAD; PH2; PIP); Cold (1; APA); Congestion (1; APA); Conjunctivosis (f; MAD); Constipation (1; APA; HH2); Cough (2; MAD; PHR; PH2); Cramp (1; APA; CAN; HH2; PH2); Croup (f; MAD); Cystosis (f; HH2; MAD; PH2); Dermatosis (f; PH2); Dizziness (f; PH2); Dropsy (f; HH2); Exanthema (f; HH2); Fungus (1; HH2); Gastrosis (f; PH2); Gout (f; APA; MAD; PHR; PH2); Headache (f; HH2; PHR; PH2); Hepatosis (f; JLH); High Blood Pressure (1; APA; CAN); Hysteria (f; CAN; HH2); Induration (f; JLH); Infection (1; HH2); Inflammation (1; APA; CAN); Insomnia (f; APA; CAN; HH2; PH2; PNC); Low Blood Pressure (1; APA; CAN); Migraine (f; HH2; PH2); Mycosis (1; HH2); Myocardosis (f; HH2); Nephrosis (f; HH2; MAD; PH2); Neuralgia (f; APA; HH2; PHR; PH2); Nervousness (f; APA; CAN; HH2; PNC); Ophthalmia (f; JLH); Pain (1; APA; CAN); Palsy (f; PH2); Pertussis (f; APA; MAD; PHR; PH2); Pyelosis (f; MAD); Respirosis (2; APA; KOM; PH2; PIP); Rheumatism (f; MAD; PH2); Sore (f; MAD); Splenosis (f; JLH); Stomachache (f; HH2); Stomatosis (1; HH2); Stress (1; APA); Trachoma (f; MAD); Tremor (f; PHR; PH2); Vertigo (f; HH2; MAD; PHR; PH2); Water Retention (1; APA; HH2; PH2; PNC); Wound (f; MAD); Yeast (1; HH2).

 

INDICATIONS AND USAGE

COWSLIP FLOWER

Approved by Commission E:

• Cough/Bronchitis

Unproven Uses: Cowslip flower is used internally for catarrh of the respiratory tract. In folk medicine it is used for insomnia, anxiety states, as a cardiac tonic for feelings of dizziness and cardiac insufficiency. It is also used as a nerve tonic for shaking limbs, headaches and neuralgia.

Homeopathic Uses: Primula veris is used to treat headaches and skin rashes

 

COWSLIP ROOT

Approved by Commission E:

• Cough/Bronchitis

Unproven Uses: Cowslip root is used internally for catarrh of the respiratory tract. In folk medicine it is used internally for whooping cough, asthma, gout, rheumatic arthritis, bladder and kidney disease, migraine, dizziness, stomach cramps, scurvy and neuralgia. Externally it is used for headaches and skin impurities.

 

PRODUCT AVAILABILITY

Dried Herb, Fluid Extract

PLANT PART USED: Flowers

 

DOSAGES

 

DOSAGES

• Adult PO fluid extract: 1-2 ml tid (1:1 dilution in alcohol 25%)

• Adult PO infusion: 1-2 g dried herb, tid

 

DOSAGES

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

·         Dried Flowers   1–2 g as an infusion three times daily.(G7)

·         Liquid Extract   1–2mL (1 : 1 in 25% alcohol) three times daily.(G7)

 

DOSAGES

·         1 – 2 g flower as tea 3 ×/day (APA; CAN; HH2); 2 – 4 g flower (KOM; PH2; PIP);

·         1 – 2 ml liquid flower extract (1:1 in 25% ethanol) 3 ×/day (APA; CAN); 2.5 – 7.5 g flower tincture (KOM; PIP);

·         0.5 – 1.5 g root (KOM; PIP); 0.2 – 0.5 g finely cut root (PH2); 1.5 – 3 g root tincture (KOM; PIP).

 

DOSAGES

 

COWSLIP FLOWER

Mode of Administration: Cowslip preparations are available as solid and liquid pharmaceutical forms for oral intake and also available parenterally for homeopathic use.

 

Preparations: Tea: boiling water is poured over 2 to 4 gm drug and strained after 10 minutes (1 teaspoon corresponds to approximately 1.3 gm drug).

Liquid extract — drug 1:1 with 25% ethanol (V/V) (BHP83)

 

Daily Dosage: The average daily dose is 3 gm of drug. The single dose is 1 gm of drug.

Tea — 1 cup several times a day. As a bronchial tea, several cups a day, possibly sweetened with honey

Liquid extract — 1 to 2 ml 3 times a day

 

Homeopathic Dosage: 5 drops, 1 tablet or 10 globules every 30 to 60 minutes (acute) or 1 to 3 times daily (chronic); parenterally: i to 2 ml sc acute: 3 times daily; chronic: once a day (HAB34); different doses for children.

 

Storage: Should be protected from light and moisture.

 

COWSLIP ROOT

Preparations: Tea: 0.2 to 0.5 gm finely cut drug are added to cold water and brought to the boil, left to draw for 5 minutes and strained (1 teaspoon corresponds to approximately 3.5 gm drug).

Extract: Percolation with 50 parts water and 50 parts ethanol, then filtration and vacuum drying. The residue is dissolved in 60 parts ethanol and 40 parts water and neutralized with ammonia. It is then cooled for 24 hours and filtered again. It is finally dehydrated to produce a dry extract under low pressure. (OAB90)

Liquid extract: the Primula extract is dissolved in a mixture of ethanol (30 parts), glycerol 85% (20 parts) and water (20 parts) and filtered when cool. (OAB90)

Tincture: 20 parts root and 100 parts diluted ethanol are processed to a tincture in accordance with the OAB VII maceration procedure.

Syrup: 1.5 parts Cowslip are dissolved in 20 parts water while being heated. It is then mixed with 10 parts 85% glycerol and 68.5 parts simple syrup. (OAB90)

 

Daily Dosage: The average daily dose is 1 gm of drug. The single dose is 0.5 gm of drug.

Tincture: The daily dose is 7.5 gm.

Extract: The single dose is 0.1 to 0.2 gm.

Liquid extract: The single dose is 0.5 gm.

Tea: as an expectorant, 1 cup every 2 to 3 hours, sweetened with honey

 

Storage: Cowslip should be protected from light.

 

OVERDOSAGE

COWSLIP FLOWER

Overdose could lead to gastric complaints and nausea.

 

COWSLIP ROOT

Overdose could lead to queasiness, nausea, gastric complaints and diarrhea.

 

 

PRECAUTIONS AND ADVERSE REACTIONS

COWSLIP FLOWER

No health hazards or side effects are known in conjunction with the proper administration of designated therapeutic dosages. The epigeal organs of the Primula species possess a very high potential for sensitization due to the primine content. In the cases of Primula veris and P. elatior, the primine content is quite low, but sensitizations are nevertheless possible.

 

COWSLIP ROOT

No health hazards or side effects are known in conjunction with the proper administration of designated therapeutic dosages.

 

CONTRAINDICATIONS, INTERACTIONS, AND SIDE EFFECTS

CLASS 1 (AHP). Occasional GI distress and nausea recorded (AHP). “Hazards and/or side effects not known for proper therapeutic dosages” (PH2). Commission E reports for flower, contraindications: hypersensitivity; adverse effects: GI disturbances (occasionally). For root, GI disturbances (occasionally) (AEH; KOM). The Herbal PDR lists diarrhea, gastric discomfort, nausea, and queasiness as side effects of the root (PH2). CAN cautions the quinones are allergenic. May interfere with blood pressure therapy (CAN).

 

CONTRA-INDICATIONS, WARNINGS

Cowslip may cause an allergic reaction in sensitive individuals.

Drug Interactions None documented. However, the potential for preparations of cowslip 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 cowslip has hypo- and hypertensive activity.

Pregnancy And Lactation The safety of cowslip has not been established. In view of the lack of toxicity data, use of cowslip during pregnancy and lactation should be avoided.

 

CONTRAINDICATIONS

CLASS 1 HERB (FLOWER, ROOT).

Until more research is available, cowslip should not be used during pregnancy and breastfeeding. It should not be given to children. Cowslip should not be used by persons with hepatic disease, gastrointestinal conditions, or hypersensitivity to this herb.

 

SIDE EFFECTS/ADVERSE REACTIONS

CV: Hyper/hypotension

GI: Nausea, vomiting, anorexia, diarrhea, gastritis, hepatotoxicity

INTEG: Hypersensitivity reactions, contact dermatitis

SYST: Hypersensitivity

 

INTERACTIONS

Drug

Antihypertensives, diuretics: Cowslip may increase the effect of antihypertensives, diuretics.

CNS depressants: Cowslip may increase the effect of antianxiety agents and sedatives/hypnotics; do not use concurrently.

Lab Test

AST, ALT, alkaline phosphatase: Cowslip may increase these levels.

 

 

EFFECTS

EFFECTS: COWSLIP FLOWER

The drug has an expectorant effect, which is due to the flavonoid and saponin content. An increase of the volume of bronchial secretion has been demonstrated in animal experiments.

 

EFFECTS: COWSLIP ROOT

The saponin content gives the drug expectorant and diuretic effects. Recent studies on these effects are not available. The mode of action is postulated to be due to vagal stimulation.

 

SIDE-EFFECTS, TOXICITY

There is a lack of clinical safety and toxicity data for cowslip and further investigation of these aspects is required. Allergic contact reactions to related Primula species have been documented; quinone compounds are stated to be the allergenic principles with primin described as a strong contact allergen.(7)

Two positive patch test reactions to cowslip have been recorded, although allergenicity was not proven.(G51) An LD50 value (mice, intraperitoneal injection) for the saponin fraction is documented as 24.5 mg/kg body weight compared to a value of 9.5 mg/kg for reparil (aescin). Haemolytic activity has been reported for the saponins, and an aqueous extract of cowslip is stated to contain saponins that are toxic to fish. Saponins are stated to be irritant to the gastrointestinal tract.

The toxicity of cowslip seems to be associated with the saponin constituents. However, these compounds have only been documented for the underground plant parts, and not for the flowers which are the main plant parts used in the UK.

 

CLIENT CONSIDERATIONS

ASSESS

·         Assess the reason the client is using cowslip.

·         Assess for hypersensitivity reactions, including contact dermatitis. If present, discontinue use of cowslip and administer antihistamine or other appropriate therapy.

·         Assess for hepatotoxicity (increased AST, ALT, bilirubin levels; jaundice; claycolored stools; right upper-quadrant pain). If present, herb use should be discontinued and appropriate action taken.

·         Assess for the use of antihypertensives, antianxiety agents, diuretics, and sedative/ hypnotics (see Interactions).

Administer

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

Teach Client/Family

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

·         Inform the client that scientifi c research is lacking to support any of the uses for or actions of cowslip.

 

PREPARATIONS

PROPRIETARY MULTI-INGREDIENT PREPARATIONS

Argentina: Expectosan Hierbas y Miel. Austria: Bronchithym; Cardiodoron; Heumann's Bronchialtee; Krauter Hustensaft; Sinupret; Thymoval. Canada: Original Herb Cough Drops. Czech Republic: Biotussil; Bronchialtee N; Bronchicum Elixir; Bronchicum Hustensirup; Bronchicum Sekret-Loser; Sinupret. Germany: Bronchicum Elixir S; Bronchicum; Bronchipret; Brust- und Hustentee; Cardiodoron; Drosithym-N; Equisil N; Expectysat N; Harzer Hustenloser; Heumann Bronchialtee Solubifix T; Kinder Em-eukal Hustensaft; Phytobronchin; Sinuforton; Sinuforton; Sinupret; Solvopret; Tussiflorin Hustensaft; Tussiflorin Hustentropfen; TUSSinfant N. Hong Kong: Sinupret. Hungary: Sinupret. Netherlands: Bronchicum. Russia: Bronchicum (Бронхикум); Bronchicum Husten (Бронхикум Сироп от Кашля); Sinupret (Синупрет). South Africa: Cardiodoron. Singapore: Sinupret. Switzerland: Demo- Pectol; Kernosan Elixir; Pectoral N; Sinupret; Sirop pectoral contre la toux S; Sirop S contre la toux et la bronchite; Strath Gouttes contre la toux; Strath Gouttes pour les veines; Strath Gouttes Rhumatisme; Tisane pectorale pour les enfants. Thailand: Sinupret; Solvopret TP. UK: Bio-Strath Willow Formula; Onopordon Comp B.

 

 

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)

 

 

 

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