Bulbus Allii Cepae Definition Bulbus Allii Cepae is the fresh or dried bulbs of Allium cepa L. (Liliaceae) or its varieties and cultivars. Synonyms Allium esculentum Salisb., Allium porrum cepa Rehb. (1). Selected vernacular names It is most commonly known as "onion". Basal, basl, cebolla, cebolla morada, cepa bulb, cepolla, cipolla, common onion, cu hanh, hom hua yai, hom khaao, hom yai, hu-t'sung, hu t'sung t'song, hua phak bhu, i-i-bsel, kesounni, khtim, Küchenzwiebel, l'oignon, loyon, Madras oignon, oignon, palandu, piyaj, piyaz, pyaz, pyaaz, ralu lunu, red globe onion, sibuyas, Spanish onion, tamanegi, umbi bawang merah, vengayan, yellow Bermuda onion, white globe onion, Zwiebel (1–5). Description A perennial herb, strong smelling when crushed; bulbs vary in size and shape from cultivar to cultivar, often depressed-globose and up to 20cm in diameter; outer tunics membranous. Stem up to 100cm tall and 30mm in diameter, tapering from inflated lower part. Leaves up to 40cm in height and 20mm in diameter, usually almost semicircular in section and slightly flattened on upper side; basal in first year, in second year their bases sheathing the lower sixth of the stem. Spathe often 3-valved, persistent, shorter than the umbel. Umbel 4– 9cm in diameter, subglobose or hemispherical, dense, many-flowered; pedicels up to 40mm, almost equal. Perianth stellate; segments 3–4.5 2–2.5mm, white, with green stripe, slightly unequal, the outer ovate, the inner oblong, obtuse or acute. Stamens exserted; filaments 4–5mm, the outer subulate, the inner with an expanded base up to 2mm wide and bearing short teeth on each side. Ovary whitish. Capsule about 5mm, 2n 16 (6). Plant material of interest: fresh or dried bulbs General appearance Macroscopically, Bulbus Allii Cepae varies in size and shape from cultivar to cultivar, 2–20cm in diameter; flattened, spherical or pear-shaped; white or coloured (7). WHO monographs on selected medicinal plants 6 Organoleptic properties Odor strong, characteristic alliaceous; taste strong; crushing or cutting the bulb stimulates lachrymation. Microscopic characteristics The external dried leaf scales of the bulbs show a large-celled epidermis with lightly spotted cell walls; the cells are elongated longitudinally. The underlying hypodermis runs perpendicular to the epidermis and contains large calcium oxalate crystals bordering the cell walls. The epidermis of the fleshy leaf scales resembles that of the dried leaf scales, and the epidermal cells on the dorsal side are distinctly longer and more elongated than the epidermal cells on the ventral side. Large calcium oxalate crystals are found in the hypodermis; stomata rare; large cell nuclei conspicuous; and spiral vessel elements occur in the leaf mesophyll (8). Powdered plant material Contains mainly thin-walled cells of the mesophyll with broken pieces of spiral vessel elements; cells containing calcium oxalate crystals are scarce (8). Geographical distribution Bulbus Allii Cepae ("onion") is probably indigenous to western Asia, but it is commercially cultivated worldwide, especially in regions of moderate climate (1). General identity tests Macroscopic inspection, microscopic characteristics and microchemical examination for organic sulfur compounds (9); and thin-layer chromatographic analysis for the presence of cysteine sulfoxides (10, 11). Purity tests Microbiology The test for Salmonella spp. in Bulbus Allii Cepae products should be negative. The maximum acceptable limits of other microorganisms are as follows (12– 14). Preparations for oral use: aerobic bacteria—not more than 105 /g or ml; fungi—not more than 104 /g or ml; enterobacteria and certain Gram-negative bacteria—not more than 103 /g or ml; Escherichia coli—0/g or ml. Total ash Not more than 6% (3). Bulbus Allii Cepae 7 Acid-insoluble ash Not more than 1.0% (3). Water-soluble extractive Not more than 5.0% (3). Alcohol-soluble extractive Not more than 4.0% (3). Pesticide residues To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin for Bulbus Allii Cepae is not more than 0.05mg/kg (14). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (12) and guidelines for predicting dietary intake of pesticide residues (15). Heavy metals Recommended lead and cadmium levels are no more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (12). Radioactive residues For analysis of strontium-90, iodine-131, caesium-134, caesium-137 and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (12). Other purity tests Chemical, foreign organic matter, and moisture tests to be established in accordance with national requirements. Chemical assays Assay for organic sulfur constituents, cysteine sulfoxides and sulfides by means of high-performance liquid chromatographic (16, 17) or gas–liquid chromatographic (18) methods, respectively. Quantitative levels to be established by appropriate national authority. Major chemical constituents Sulfur- and non-sulfur-containing chemical constituents have been isolated from Bulbus Allii Cepae; the sulfur compounds are the most characteristic (1, 4, 7). The organic sulfur compounds of Bulbus Allii Cepae, including the thiosulfinates, thiosulfonates, cepaenes, S-oxides, S,S-dioxides, monosulfides, WHO monographs on selected medicinal plants 8 disulfides, trisulfides, and zwiebelanes occur only as degradation products of the naturally occurring cysteine sulfoxides (e.g. (
)-S-propyl-L-cysteine sulfoxide). When the onion bulb is crushed, minced, or otherwise processed, the cysteine sulfoxides are released from compartments and contact the enzyme alliinase in adjacent vacuoles. Hydrolysis and immediate condensation of the reactive intermediate (sulfenic acids) form the compounds as indicated below (1). The odorous thiosulphonates occur (in low concentrations) only in freshly chopped onions, whereas the sulfides accumulate in stored extracts or steam distilled oils. Approximately 90% of the soluble organic-bound sulfur is present as γ-glutamylcysteine peptides, which are not acted on by alliinase. They function as storage reserve and contribute to the germination of seeds. However, on prolonged storage or during germination, these peptides are acted on by γ-glutamyl transpeptidase to form alk(en)yl-cysteine sulfoxides, which in turn give rise to other volatile sulfur compounds (1). Bulbus Allii Cepae 9 Dosage forms Fresh juice and 5% and 50% ethanol extracts have been used in clinical studies (1). A "soft" extract is marketed in France but is not recognized as a drug by French authorities (7). Dried Bulbus Allii Cepae products should be stored in well-closed containers, protected from light, moisture, and elevated temperature. Fresh bulbs and juice should be refrigerated (2–10°C). Medicinal uses supported by clinical data The principal use of Bulbus Allii Cepae today is to prevent age-dependent changes in the blood vessels, and loss of appetite (19). Uses described in pharmacopoeias and in traditional systems of medicine Treatment of bacterial infections such as dysentery, and as a diuretic (2, 7). The drug has also been used to treat ulcers, wounds, scars, keloids (3), and asthma (20, 21). Bulbus Allii Cepae has also been used as an adjuvant therapy for diabetes (4, 22, 23). Uses described in folk medicine, not supported by experimental or clinical data As an anthelminthic, aphrodisiac, carminative, emmenagogue, expectorant, and tonic (3), and for the treatment of bruises, bronchitis, cholera, colic, earache, fevers, high blood pressure, jaundice, pimples, and sores (3). Pharmacology Experimental pharmacology An aqueous extract or the juice of Bulbus Allii Cepae inhibited the in vitro growth of Escherichia coli, Serratia marcescens, Streptococcus species, Lactobacillus odontolyticus, Pseudomonas aeruginosa, and Salmonella typhosa (24–28). A petroleum ether extract of Bulbus Allii Cepae inhibited the in vitro growth of Clostridium paraputrificum and Staphylococcus aureus (24). The essential oil has activity against a variety of fungi including Aspergillus niger, Cladosporium werneckii, Candida albicans, Fusarium oxysporium, Saccharomyces cerevisiae, Geotrichum candidum, Brettanomyces anomalus, and Candida lipolytica (5, 29). The hypoglycaemic effects of Bulbus Allii Cepae have been demonstrated in vivo. Intragastric administration of the juice, a chloroform, ethanol, petroleum ether (0.25g/kg) or water extract (0.5ml), suppressed alloxan-, glucose- and epinephrine-induced hyperglycaemia in rabbits and mice (30–35). Inhibition of platelet aggregation by Bulbus Allii Cepae has been demonstrated both in vitro and in vivo. An aqueous extract inhibited adenosine diphosphate-, collagen-, epinephrine- and arachidonic acid-induced platelet WHO monographs on selected medicinal plants 10 aggregation in vitro (36, 37). Platelet aggregation was inhibited in rabbits after administration of the essential oil, or a butanol or chloroform extract of the drug (38–40). An ethanol, butanol or chloroform extract or the essential oil (10–60µg/ml) of the drug inhibited aggregation of human platelets in vitro (41, 42) by decreasing thromboxane synthesis (39). Both raw onions and the essential oil increased fibrinolysis in ex vivo studies on rabbits and humans (1). An increase in coagulation time was also observed in rabbits (1). Intragastric administration of the juice or an ether extract (100mg/kg) of the drug inhibited allergen- and platelet activating factor-induced allergic reactions, but not histamine- or acetylcholine-induced allergenic responses in guinea-pigs (43). A water extract of the drug was not active (43). A chloroform extract of Bulbus Allii Cepae (20–80mg/kg) inhibited allergen- and platelet aggregation factor-induced bronchial obstruction in guinea-pigs (44). The thiosulphinates and cepaenes appear to be the active constituents of Bulbus Allii Cepae (1). Both ethanol and methanol extracts of Bulbus Allii Cepae demonstrated diuretic activity in dogs and rats after intragastric administration (45, 46). Antihyperlipidaemic and anticholesterolaemic activities of the drug were observed after oral administration of minced bulbs, a water extract, the essential oil (100mg/kg), or the fixed oil to rabbits or rats (47–52). However, one study reported no significant changes in cholesterol or lipid levels of the eye in rabbits, after treatment of the animals for 6 months with an aqueous extract (20% of diet) (53). Oral administration of an ethanol extract of the drug to guinea-pigs inhibited smooth muscle contractions in the trachea induced by carbachol and inhibited histamine-, barium chloride-, serotonin-, and acetylcholine-induced contractions in the ileum (20). Topical application of an aqueous extract of Bulbus Allii Cepae (10% in a gel preparation) inhibited mouse ear edema induced by arachidonic acid (54). The active antiallergic and anti-inflammatory constituents of onion are the flavonoids (quercetin and kaempferol) (55). The flavonoids act as antiinflammatory agents because they inhibit the action of protein kinase, phospholipase A2, cyclooxygenase, and lipoxygenase (56), as well as the release of mediators of inflammation (e.g. histamine) from leukocytes (57). In vitro, an aqueous extract of Bulbus Allii Cepae inhibited fibroblast proliferation (58). A 0.5% aqueous extract of onion inhibited the growth of human fibroblasts and of keloidal fibroblasts (enzymically isolated from keloidal tissue) (59). In a comparative study, an aqueous extract of Bulbus Allii Cepae (1– 3%) inhibited the proliferation of fibroblasts of varying origin (scar, keloid, embryonic tissue). The strongest inhibition was observed with keloid fibroblasts (65–73%) as compared with the inhibition of scar and embryonic fibroblasts (up to 50%) (59). In human skin fibroblasts, both aqueous and chloroform onion extracts, as well as thiosulfinates, inhibited the platelet derived growth factor-stimulated chemotaxis and proliferation of these cells (60). In addition, a protein fraction isolated from an onion extract exhibited antimitotic activity (61). Bulbus Allii Cepae 11 Clinical pharmacology Oral administration of a butanol extract of Bulbus Allii Cepae (200mg) to subjects given a high-fat meal prior to testing suppressed platelet aggregation associated with a high-fat diet (62). Administration of a butanol extract to patients with alimentary lipaemia prevented an increase in the total serum cholesterol, -lipoprotein cholesterol, and -lipoprotein and serum triglycerides (63, 64). A saponin fraction (50mg) or the bulb (100mg) also decreased serum cholesterol and plasma fibrinogen levels (65, 66). However, fresh onion extract (50g) did not produce any significant effects on serum cholesterol, fibrinogen, or fibrinolytic activity in normal subjects (67, 68). Antihyperglycaemic activity of Bulbus Allii Cepae has been demonstrated in clinical studies. Administration of an aqueous extract (100mg) decreased glucose-induced hyperglycemia in human adults (69). The juice of the drug (50mg) administered orally to diabetic patients reduced blood glucose levels (22). Addition of raw onion to the diet of non-insulin-dependent diabetic subjects decreased the dose of antidiabetic medication required to control the disease (70). However, an aqueous extract of Bulbus Allii Cepae (200mg) was not active (71). The immediate and late cutaneous reactions induced by injection of rabbit anti-human IgE-antibodies into the volar side of the forearms of 12 healthy volunteers were reduced after pretreatment of the skin with a 50% ethanol onion extract (1). Immediate and late bronchial obstruction owing to allergen inhalation was markedly reduced after oral administration of a 5% ethanol onion extract 1 hour before exposure to the allergen (1). In one clinical trial in 12 adult subjects, topical application of a 45% ethanolic onion extract inhibited the allergic skin reactions induced by anti-IgE (72). Contraindications Allergies to the plant. The level of safety of Bulbus Allii Cepae is reflected by its worldwide use as a vegetable. Warnings No warnings have been reported. Precautions Carcinogenesis, mutagenesis, impairment of fertility Bulbus Allii Cepae is not mutagenic in vitro (73). Other precautions No general precautions have been reported, and no precautions have been reported concerning drug interactions, drug and laboratory test interactions, WHO monographs on selected medicinal plants 12 nursing mothers, pediatric use, or teratogenic or non-teratogenic effects on pregnancy. Adverse reactions Allergic reactions such as rhinoconjunctivitis and contact dermatitis have been reported (74). Posology Unless otherwise prescribed: a daily dosage is 50g of fresh onion or 20g of the dried drug; doses of preparations should be calculated accordingly (14).
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