Tuesday, May 26, 2020

SQUILL, SEA ONION (Urginea maritima (L.) Baker) X (Asparagaceae) )


HERBAL
MEDICINAL
PLANT

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 SQUILL, SEA ONION













Urginea maritima  (L.) Baker) X
 (Asparagaceae)



BY




RETTODWIKART THENU
















SQUILL, SEA ONION !
(skwil)  

Urginea maritima  (L.) Baker) X    (Asparagaceae)



SUMMARY AND PHARMACEUTICAL COMMENT

Squill is characterised by its cardiac glycoside components and unusual flavonoid constituents. The reputed actions of
squill as an expectorant, emetic and cathartic can be attributed to the cardioactive components and squill has been used as an expectorant for many years. However, in view of the documented cardioactive and emetic properties of the aglycones, excessive use and use during pregnancy and lactation should be avoided. Red squill is primarily used as a rodenticide.

Red squill is distributed through the entire Mediterranean region and is sometimes cultivated in Germany. The cardiotonic effects of the plant have been known since ancient times.


DESCRIPTION

MEDICINAL PARTS: The medicinal parts come from the bulbs of the white latex variety collected after flowering and the fresh, fleshy bulb scales of the white variety and of the red variety.
FLOWER AND FRUIT: The flowering stem is erect and 50 to 150 cm high. It is often a washed purple color and glabrous. The flowers, which often number 100, are arranged in richly flowered, dense racemes up to 60 cm long. The bracts are membranous and pointed. They are shorter than the pedicles and drop early. The pedicles are up to 3 cm long, thin and smooth. The flowers are white, radial and star-shaped. The ovary is ovate to oblong triangular. The capsule is ovate to oblong, 3-valved, obtuse or almost pointed. Each chamber has 1 to 4 seeds, which are elongate, flattened, smooth, glossy and winged.
LEAVES, STEM AND ROOT: The plant is a perennial bulb plant. The bulbs are pear-shaped, about 15 to 30 cm in diameter. They are rarely sold whole commercially, as they tend to start growing. The fracture is short, tough and flexible.
CHARACTERISTICS: The taste is bitter and acrid.
HABITAT: Indigenous to the Mediterranean and is cultivated there too.
PRODUCTION: Squill consists of the sliced, dried, fleshy middle scales of the onion of the white variety of Urginea maritima, harvested during the flowering season. It is collected mostly from uncultivated regions.


SPECIES (FAMILY)
Drimia maritima (L.) Stearn (Asparagaceae),  Urginea maritima

SYNONYM(S)
Scilla, Sea Onion, Urginea, Urginea maritima (L.) Baker, Urginea scilla Steinh., White Squill
European squill, Indian squill, Mediterranean squill, red squill, sea squill,

Gruenwald cites this under Drimia maritima in edition 1, under this name in edition 2. HH2 maintains separate entries for U. indica (Roxb.) Kunth and U. maritima, a practice I follow, so far resisting the temptation to aggregate.

ORIGIN
Squill is found in Europe and Mediterranean regions.

PHARMACOPODIAL AND OTHER MONOGRAPHS
BHC 1992(G6)
BHP 1996(G9)
BP 2007(G84)
Complete German Commission E(G3)
Martindale 35th edition(G85)

LEGAL CATEGORY (LICENSED PRODUCTS)
GSL(G37)

CONSTITUENTS
See References 1 and 2 and General References G6 and G62.
Cardiac glycosides Scillaren A and proscillaridin A (major constituents); others include glucoscillaren A, scillaridin A, scillicyanoside, scilliglaucoside, scilliphaeoside, scillicoeloside, scillazuroside and scillicryptoside. Scillaren B represents a mixture of the squill glycosides.
Flavonoids Apigenin, dihydroquercetin, isovitexin, iso-orientin, luteolin, orientin, quercetin, taxifolin and vitexin.
Other constituents Stigmasterol, tannin, volatile and fixed oils.

USES
USES
Traditionally, squill has been used for its cardiac glycoside effect in the treatment of cardiac conditions such as congestive heart failure. It is also used to treat cough and to promote diuresis.

FOOD USE
The Food Additives and Contaminants Committee (FACC) recommended that squill be prohibited as a food flavouring.(G45)

HERBAL USE
Squill is stated to possess expectorant, cathartic, emetic, cardioactive and diuretic properties. Traditionally, it has been used for chronic bronchitis, asthma with bronchitis, whooping cough, and specifically for chronic bronchitis with scanty sputum.(G6, G7, G8,G64)


ACTIONS
ACTIONS
In North Africa, squill has been found to be poisonous to livestock, with ingestion of the plant leading to cardiac toxicity (El Bahri et al, 2000). Toxicity was also reported in a 55-year-old woman with Hashimoto thyroiditis who was taking squill to treat arthritis. Her symptoms were those of cardiac glycoside toxicity (Tuncok et al, 1995). Squill has exerted cardiac glycoside effects in humans but is considered to be milder than current cardiac glycoside prescription drugs (Stauch et al, 1977).

PHARMACOLOGICAL ACTIONS
The aglycone components of the cardiac glycoside constituents possess digitalis-like cardiotonic properties.(G41) However, the squill aglycones are poorly absorbed from the gastrointestinal tract and are less potent than digitalis cardiac glycosides.(1, 2) Expectorant, emetic and diuretic properties have been documented for white squill.(G41) Squill is reported to induce vomiting by both a central action and local gastric irritation.(1, 2) Subemetic or near-emetic doses of squill appear to exhibit an expectorant effect, causing an increase in the flow of gastric secretions.(1, 2)
Antiseborrhoeic properties have been documented for methanol extracts of red squill which have been employed as hair tonics for the treatment of chronic seborrhoea and dandruff.(G41) Squill extracts have been reported to exhibit peripheral vasodilatation and bradycardia in anaesthetised rabbits.(1, 2)

PHARMACOLOGY
·         HERB: Squill (Scillae bulbus). The herb consists of the dried, fleshy, central bulb sections of the white onion species Urginea maritima (L.) B., collected after the time of flowering and cut in to transverse or longitudinal strips, and preparations of the same.
·         IMPORTANT CONSTITUENTS: Steroid cardiac glycosides (bufadienolide, 1–3 %), glucoscillaren A, proscillaridin A, and scillaren A.
·         PHARMACOLOGICAL PROPERTIES: Squill has potent diuretic, positive inotropic and negative chronotropic effects. It also lowers left ventricular end diastolic pressure.

ACTIVITIES
Anticancer (1; CRC); Cardiotonic (f; CRC); Diuretic (f; CRC); Emetic (f; CRC); Expectorant (f; CRC); Hypotensive (2; KOM); Negative Chronotropic (2; KOM); Poison (f; CRC); Positive Inotropic (2; KOM); Rodenticide (1; CRC).

INDICATIONS
Adenopathy (f; CRC; JLH); Arrhythmia (2; CRC; PHR); Asthma (f; CRC); Bronchosis (f; CRC); Bruise (f; CRC); Burn (f; CRC); Callus (f; CRC); Cancer (1; CRC); Cancer, eye (f; CRC; JLH); Cancer, liver (f; CRC; JLH); Cancer, parotid (f; CRC; JLH); Cancer, spleen (f; CRC; JLH); Cardiac Insufficiency (2; KOM); Catarrh (f; CRC); Congestion (f; CRC); Corn (f; CRC); Cough (f; CRC); Croup (f; CRC); Dandruff (f; CRC); Edema (f; CRC); Felon (f; CRC); Gas (f; CRC); Heart (f; CRC); High Blood Pressure (2; KOM); Induration (f; CRC); Kidney Insufficiency (2; KOM); Nephrosis (f; CRC); Nervous Cardiopathy (2; PHR); Pertussis (f; CRC); Seborrhea (f; CRC); Sore (f; CRC); Stomachache (f; CRC); Tumor (f; CRC); Varicosis (2; PHR); Wart (f; CRC); Water Retention (f; CRC); Wound (f; CRC).

INDICATIONS AND USAGE
Approved by Commission E:
• Cardiac insufficiency NYHA  I and If
• Arrhythmia
• Nervous heart complaints
• Venous conditions
Unproven Uses: Squill is used for reduced kidney capacity. In folk medicine it is used for catarrhal conditions of the upper respiratory tract, bronchitis, asthma and whooping cough, also for wounds and fractures, back pain and hemorrhoids and for the disinfection of septic wounds.

Indications
– Heart failure (NYHA classes I and II)
– Cardiac arrhythmias
– Nervous heart disorders


PRODUCT AVAILABILITY
Dried bulb, extract, tincture
PLANT PART USED: Bulb


DOSAGES
DOSAGES
·         Adult PO decoction: pour 8 oz boiling water over 1 tsp dried bulb, let stand 15 min, allow to cool; may be taken tid
·         Adult PO tincture: 1⁄2-1 ml tid

DOSAGES
Dosages for oral administration (adults) for traditional uses recommended in older and contemporary standard herbal and pharmaceutical reference texts are given below.
·         Dried Bulb   60–200 mg as an infusion three times daily.(G6, G7)
·         Squill Liquid Extract (BPC 1973)   0.06–0.2 mL.
·         Squill Tincture (BPC 1973)   0.3–2.0 mL.
·         Squill Vinegar (BPC 1973)   0.6–2.0 mL.

DOSAGES
0.1–0.5 g StX sea onion powder (2; KOM).

DOSAGES
MODE OF ADMINISTRATION: Comminuted drug and other galenic preparations for internal use.
PREPARATION: Stabilized powder is standardized according to content, there are no more exact specifications in the
literature, standardization according to DABIO.
·         Squill Extract — Evaporated extract l :4; drug: diluted spirit of wine (EB6)
·         Acetum Scillae — drug: spirit of wine l:l (EB6)
·         Oxymel Scillae — 5 parts Acetum Scillae: 10 parts purified honey evaporated in a water bath to 10 parts
DAILY DOSAGE: Single dose: 60 to 200 mg; Daily dose: 180 to 200 mg; Average daily dosage: 0.1 to 0.5 gm of standardized sea onion powder.
·         Squill Extract: 1.0 gm; Liquid extract: 0.03 to 2.0 ml;
·         Tincture: 0.3 to 2.0 ml; Acetum Scillae: 1.0 gm; Acetic acid maceration: 0.6 to 2.0 ml
·         Oxymel Scillae: 2.5 gm
STORAGE: Squill should be protected from light and moisture at temperatures below 25 °C.

DOSAGE AND DURATION OF USE
– One dose equals 60–200 mg herb.
Daily dose: 180–200 mg herb.
Standardized powder: 0.1–0.5 g.
Extractum Scillae: 1.0 g.
Fluid extract: 0.03–2.0 mL.
Tincture: 0.3–2.0 mL.
Important: Because squill is so difficult to standardize, the isolated glycosides (e. g., proscillaridin A) should preferentially be used.

PRECAUTIONS AND ADVERSE REACTIONS
GENERAL: No health hazards are known in conjunction with the proper administration of designated therapeutic dosages. Because of the narrow therapeutic range of cardioactive steroid glycosides, side effects could appear even with therapeutic dosages. Side effects include tonus elevation of the gastrointestinal area, loss of appetite, vomiting, diarrhea, ' headache and irregular pulse. Contact with the juice of the fresh bulb can lead to skin inflammation (squill dermatitis). The administration of pure glycoside is preferable due to the difficulties of standardizing the drug (proscillaridin A).
DRUG INTERACTIONS: Increase of effectiveness and thus also of side effects is possible with concomitant administration of quinidine, calcium, saluretics, laxatives and extended therapy with glucocorticoids. Squill potentiates the positive inotropic and negative chronotropic effects of digoxin. The simultaneous administration of arrhythmogenic substances (sympathomimetics, methylxanthines, phosphodiesterase inhibitors, and quinidine) increases the risk of cardiac arrhythmias.

OVERDOSAGE
Besides the already-mentioned symptoms, overdosage can lead to cardiac rhythm disorders, life-threatening .ventricular tachycardia, atrial tachycardia with atrioventricular block, stupor, vision disorders, depression, confused states, hallucinations and psychosis. Fatal dosages lead to cardiac arrest or asphyxiation.
Treatment of poisoning includes gastric lavage and instillation of activated charcoal. All other measures are to be carried out according to the symptoms. In case of potassium loss, careful replenishment; for ectopic impulse formation in the ventricle, administration of phenytoin as antiarrhythmic drug; lidocaine for ventricular extrasystole; for pronounced bradycardia, atropine or orciprenaline. The prophylactic use of a pacemaker is recommended. Hemoperfusion for eliminating the glycosides or the administration of cholestyramine for interrupting the enterohepatic circulation are possible.

CONTRAINDICATIONS, INTERACTIONS, AND SIDE EFFECTS
Commission E reports contraindications: potassium deficiency, and therapy with digitalis glycosides; adverse effects: diarrhea, gastrosis, irregular pulse, nausea, and vomiting; and interactions with other drugs: potentiation of calcium, cardiac glycosides, extended glucocorticoid therapy, laxatives, quinidine, and saluretics (AEH; KOM). I thought that was a pretty big dose of Commission E, but here’s what Gruenwald has to say: Should not be used in 2nd or 3rd degree atrioventricular blocks, carotid sinus syndrome, hypercalcemia, hypokalemia, hypertropic cardiomyopathy, thoracic aortic aneurysm, ventricular tachycardia, and WPW Syndrome (PHR).

CONTRAINDICATIONS
Until more research is available, squill should not be used during pregnancy and breastfeeding. It should not be given to children. Squill should not be used by persons with hypokalemia, hypertropic cardiomyopathy, sick sinus syndrome, ventricular tachycardia, or second or third-degree heart block. Persons who are hypersensitive to squill should not use it.

CONTRAINDICATIONS:
Individuals with AV block classes II or III, hypercalcemia, hypokalemia, hypertrophic cardiomyopathy, carotid sinus syndrome, ventricular tachycardia, aneurysm of the thoracic aorta, or Wolff–Parkinson– White (WPW) syndrome should not use squill or glycosides isolated from it.

SIDE EFFECTS/ADVERSE REACTIONS
CNS: Anxiety, headache, tremors, central nervous system stimulation, seizures
CV: Arrhythmias, heart block, asystole
GI: Nausea, vomiting, anorexia
INTEG: Hypersensitivity reactions


INTERACTIONS
Drug
Cardiac agents (antiarrhythmics, beta-blockers, calcium channel blockers, cardiac glycosides): Squill may increase the effects of cardiac agents, causing life-threatening toxicity; do not use concurrently.

INTERACTIONS—CONT’D
CNS stimulants (amphetamines, cerebral stimulants), glucocorticoids, laxatives: Squill may increase the effects of central nervous system stimulants, glucocorticoids, laxatives; avoid concurrent use.
Iron salts: Squill may decrease the absorption of iron salts; separate by 2 hours.
Lab Test
Red blood cells: Squill may cause a decrease in red blood cells.

SIDE-EFFECTS, TOXICITY
CLINICAL DATA
Excessive use of squill is potentially toxic because of the cardiotonic constituents. However, squill is also a gastric irritant and large doses will stimulate a vomiting reflex.
PRECLINICAL DATA
Red squill is toxic to rats and is mainly used as a rodenticide, causing death by a centrally induced convulsant action.(1, 2) A squill soft mass (crude extract) has been stated to be toxic in guinea-pigs at a dose of 270 mg/kg body weight. A fatal dose for Indian squill (Urginea indica Kunth.) is documented as 36 mg/kg.

ADVERSE EFFECTS:
Because steroid cardiac glycosides have a narrow therapeutic range, therapeutic doses of these drugs can induce side effects in some individuals. These include increased muscle tone in the gastrointestinal region, lack of appetite, nausea, diarrhea, headaches, and irregular pulse.

CONTRA-INDICATIONS, WARNINGS
Squill may cause gastric irritation and should be avoided by individuals with a cardiac disorder. In view of the cardiotonic constituents, precautions applied to digoxin therapy should be considered for squill.
DRUG INTERACTIONS None documented. However, the potential for preparations of squill to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. Squill contains cardiac glycosides, and interactions listed for digoxin should be considered for squill.
PREGNANCY AND LACTATION Squill is reputed to be an abortifacient and to affect the menstrual cycle.(G30) In addition, cardioactive and gastrointestinal irritant properties have been documented. The use of squill during pregnancy and lactation should be avoided.

WARNING: Symptoms of overdose
·         Cardiac symptoms can range from cardiac arrhythmia to life-threatening tachycardia and/or atrial tachycardia with AV block.
·         CNS symptoms are stupor, impaired vision, depression, confusion, hallucination, and psychoses.
·         In lethal poisoning, the cause of death is cardiac arrest or asphyxia.
HERB–DRUG INTERACTIONS: The concomitant administration of arrhythmogenic substances such as sympathomimetics, methylxanthines, phosphodiesterase inhibitors, and quinidine increases the risk of cardiac arrhythmia.


CLIENT CONSIDERATIONS
ASSESS
·         Assess for hypersensitivity reactions. If present, discontinue the use of squill and administer an antihistamine or other appropriate therapy.
·         Assess cardiac status (blood pressure, pulse, possibly ECG) if the client is taking squill over an extended period of time.
·         Monitor electrolytes and watch for decreasing potassium levels.
·         Determine whether the client is taking other cardiac medications such as betablockers, calcium channel blockers, cardiac glycosides, and antidysrhythmics. This herb should not be used with these medications (see Interactions).
·         Assess for the use of central nervous system stimulants, glucocorticoids, and laxatives (see Interactions).
ADMINISTER
·          Instruct the client to store squill products in a cool, dry place, away from heat and moisture.
TEACH CLIENT/FAMILY
·         Caution the client not to use squill in children or those who are pregnant or breastfeeding until more research is available.
·         Advise the client that other, more mainstream agents are available and are preferred to squill.








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

Kraft, K and Hobbs, C. 2004 . Pocket Guide to Herbal Medicine. Thieme. Stuttgart New York.

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







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