Herba Ephedrae consists of the dried stem or aerial part of Ephedra sinica Stapf or other ephedrine-containing Ephedra species (Ephedraceae) (1–5).
Selected vernacular names
Amsania, budshur, chewa, Chinese ephedra, ephédra, horsetail, hum, huma, joint fir, khama, ma hoàng, ma huang, máhuáng, mao, maoh, maou, mao-kon, môc tac ma hoàng, mu-tsei-ma-huang, phok, san-ma-huang, shrubby, soma, song tuê ma hoàng, trung aa hoàng, tsao-ma-huang, tutgantha (4–10).
Erect or prostrate, green, almost leafless shrub, 20–90 cm high. Branches erect, short, glaucous green, somewhat flat, 1.0–1.5 mm in diameter, with small sparse longitudinal striae, fasciated at the nodes; nodes reddish brown; internode 2.5– 5.5 cm long × 2 mm in diameter. Small triangular leaves opposite, reduced to scales, barely 2mm. Flowers in summer, unisexual, dioecious; male flowers pedunculate or nearly sessile, grouped in catkins composed of 4 to 8 pairs of flowers with about 8 anthers; female flowers biflorous, pedunculate with 3 or 4 pairs of bracts, the naked ovule surrounded by an urn-shaped perianth sheath, fruiting with often fleshy red succulent bracts, 2-seeded (4, 7, 11).
Plant material of interest: stem or aerial part
Macroscopically, Herba Ephedrae occurs as thin cylindrical or ellipsoidal cylinder, 1–2 mm in diameter; 3.5–5.5cm in length of internode; light green to yellow-green; numerous parallel vertical furrows on the surface; scaly leaves at the node portion; leaves, 2–4 mm in length, light brown to brown in colour, usually opposite at every node, adhering at the base to form a tubular sheath around the stem. Under a magnifying glass, the transverse section of the stem appears as circle and ellipse, the outer portion greyish green to yellow-green in colour, and the centre filled with a red-purple substance or hollow. When fractured at an internode, the outer part is fibrous and easily split vertically (1).
Odour, slight; taste, slightly bitter and astringent, giving a slight sensation of numbness on the tongue (1).
The epidermal cells of the stem are covered with a moderately thick granular cuticle; the cells are polygonal or subrectangular, axially elongated, having straight anticlinal walls. The stomata are few and are of the ranunculaceous type with lignified appendages. The epidermis of the scaly leaf is covered with smooth (upper) or warty (lower) cuticle and consists of subrectangular to polygonal cells, having straight or sometimes slightly beaded anticlinal walls; few stomata are present resembling those of stem. The epidermis of the apical and marginal regions of the scaly leaf shows short papillae-like outgrowths. Chlorenchymatous palisade-like cells form the outer zone of the cortex; rounded ordinary parenchymatous cells form the inner zone of the cortex. Cortical parenchyma and pith cells contain an amorphous reddish brown substance. Non-lignified or lignified hypodermal and pericyclic fibres, which have thick walls, bear slit-like pits and blunt, slightly tapering, occasionally forked ends. The vessels of the secondary xylem of the stem are lignified with bordered pits, having rounded or oval apertures. The vessel segments have much inclined end walls, bearing foraminate perforation plates. The tracheids and fibrous tracheids of secondary xylem of the stem are lignified with bordered pits having oval or slit-like apertures. The fibres of the scaly leaf are lignified, usually irregular or nearly straight, having moderately thick walls and blunt or sometimes forked ends. Few, small, rounded, simple and compound starch granules with indistinct hilum are present in cortical parenchyma, pith, and medullary ray cells. Few, small prisms of calcium oxalate are present in the cortical parenchyma (4).
Powdered plant material
Powdered Herba Ephedrae is greyish green. Numerous thick fragments of cutinized outer walls of epidermis vary from colourless to varying shades of brown or red; numerous fragments of sclerenchyma fibres with extremely thickened, non-lignified to lignified walls, narrow, frequently indistinct lumina and sharp pointed ends; fragments of vascular tissue showing tracheids with bordered pores and occasional spiral and pitted tracheae; numerous chlorenchyma cells; starch grains simple, spheroidal to occasionally ovate, averaging up to 1.2µm but occasionally up to 20µm; fragments of epidermis with rectangular cells and granular contents, some with sunken elliptical stomata; fragments of lignified or non-lignified pith parenchyma, some of the cells showing mucilage sacs; papillae; granules of calcium oxalate (4, 6).
Ephedra species are found in Afghanistan, Central America, China, India, regions of the Mediterranean, Mongolia, and North America (4, 6–12).
General identity tests
Macroscopic and microscopic examinations and microchemical tests for the presence of alkaloids with Mayer's reagent (1–5, 7).
The test for Salmonella spp. in Herba Ephedrae products should be negative. The maximum acceptable limits for other microorganisms are as follows (13–15). For preparation of decoction: aerobic bacteria-not more than 107/g; fungi-not more than 105/g; Escherichia coli-not more than 102/g. Preparations for internal 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.
Foreign organic matter
Woody stems, not more than 5% (1). Does not contain stems of Equisetaceae or Gramineae plants, nor any other foreign matter (1).
Not more than 9% (3).
Not more than 2% (1).
Not more than 9% (3).
To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin for Herba Ephedrae is not more than 0.05 mg/kg (15). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (13) and guidelines for predicting dietary intake of pesticide residues (16).
Recommended lead and cadmium levels are no more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (13).
For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (13).
Other purity tests
Chemical, dilute ethanol-soluble extractive, and water-soluble extractive tests to be established in accordance with national requirements.
Contains not less than 0.7% total alkaloids, calculated as ephedrine by highperformance liquid chromatography in the Japanese pharmacopoeia; or not less than 0.8% of total alkaloids, calculated as ephedrine in the Chinese pharmacopoeia (1, 2).
Thin-layer (17), gas–liquid (18) or high-performance liquid (19) chromatographic analysis for ephedrine and related alkaloids are available.
Major chemical constituents
The major active principle found in Herba Ephedrae is (-)-ephedrine in concentrations of 40–90% of the total alkaloid fraction, accompanied by (+)-pseudoephedrine. Other trace alkaloids in the alkaloid complex include (-)-norephedrine, (+)-norpseudoephedrine, (-)-methylephedrine and (+)- methylpseudoephedrine. The total alkaloid content can exceed 2% depending on the species (20). Not all Ephedra species contain ephedrine or alkaloids.
Powdered plant material; extracts and other galenicals. Store in well closed, light-resistant containers.
Uses supported by clinical data
Herba Ephedrae preparations are used in the treatment of nasal congestion due to hay fever, allergic rhinitis, acute coryza, common cold, and sinusitis. The drug is further used as a bronchodilator in the treatment of bronchial asthma (4, 8, 10, 21–23).
Uses described in pharmacopoeias and in traditional systems of medicine
Herba Ephedrae has been used for the treatment of urticaria, enuresis, narcolepsy, myasthenia gravis, and chronic postural hypotension (4, 8, 22, 23).
Uses described in folk medicine, not supported by experimental or clinical data
Other medical uses claimed for Herba Ephedrae preparations include its use as an analgesic, an antiviral agent, an antitussive and expectorant, an antibacterial, and an immune stimulant (10, 24, 25).
Two of the main active constituents of Herba Ephedrae, ephedrine and pseudoephedrine, are potent sympathomimetic drugs that stimulate α-, β1- and β2- adrenoceptors (22, 23). Pseudoephedrine's activity is similar to ephedrine, but its hypertensive effects and stimulation of the central nervous system are somewhat weaker. Part of ephedrine's peripheral action is due to the release of norepinephrine, but the drug also directly affects receptors. Tachyphylaxis develops to its peripheral actions, and rapidly repeated doses become less effective owing to the depletion of norepinephrine stores (22).
Like epinephrine (adrenaline), ephedrine excites the sympathetic nervous system, causing vasoconstriction and cardiac stimulation. Ephedrine differs from epinephrine in that it is orally active, has a much longer duration of action, and has more pronounced activity in the central nervous system, but is much less potent (22, 23). The drug stimulates the heart rate, as well as cardiac output, and increases peripheral resistance, thereby producing a lasting rise in blood pressure. The cardiovascular effects of ephedrine persist up to ten times as long as those of epinephrine (22). Ephedrine elevates both the systolic and diastolic pressures and pulse pressure. Renal and splanchnic blood flows are decreased, while coronary, cerebral, and muscle blood flows are increased (22, 23).
Bronchodilator and nasal decongestant
Ephedrine, like epinephrine, relaxes bronchial muscles and is a potent bronchodilator owing to its activation of the β-adrenoceptors in the lungs (22, 23). Bronchial muscle relaxation is less pronounced but more sustained with ephedrine than with epinephrine. As a consequence, ephedrine should be used only in patients with mild cases of acute asthma and in chronic cases that require maintenance medication. Ephedrine, like other sympathomimetics with α-receptor activity, causes vasoconstriction and blanching when applied topically to nasal and pharyngeal mucosal surfaces (22, 23). Continued, prolonged use of these preparations (>3 days) may cause rebound congestion and chronic rhinitis (26). Both ephedrine and pseudoephedrine are useful orally as nasal decongestants in cases of allergic rhinitis, but they may not be very effective for the treatment of nasal congestion due to colds.
Central nervous system
Mydriasis occurs after local application of ephedrine (3–5%) to the eye, but the effect lasts for only a few hours (22). Ephedrine is of little value as a mydriatic in the presence of inflammation. The activity of the smooth muscles of the uterus is usually reduced by ephedrine; consequently, the drug has been used to relieve the pain of dysmenorrhoea (22).
Ephedrine is a potent stimulator of the central nervous system. The effects of the drug may last for several hours after oral administration (23). Thus, preparations containing Herba Ephedrae have been promoted for use in weight reduction and thermogenesis (fat burning) (27, 28). The safety and effectiveness of these preparations is currently an issue of debate and requires further investigation (29).
Ephedrine stimulates the α-adrenoceptors of the smooth muscle cells of the bladder base, which increases the resistance to the outflow of urine (23). Thus Herba Ephedrae has been used in the treatment of urinary incontinence and nocturnal enuresis.
Herba Ephedrae should not be administered to patients with coronary thrombosis, diabetes, glaucoma, heart disease, hypertension, thyroid disease, impaired circulation of the cerebrum, phaeochromocytoma, or enlarged prostate (10, 21, 23). Co-administration of Herba Ephedrae preparations with monoamine oxidase inhibitors is contraindicated as the combination may cause severe, possibly fatal, hypertension (23).
Dosage should be reduced or treatment discontinued if nervousness, tremor, sleeplessness, loss of appetite or nausea occurs. Not for children under 6 years of age. Keep out of the reach of children (30). Continued, prolonged use may cause dependency.
Insomnia may occur with continued use of Herba Ephedrae preparations (23).
In combination with cardiac glycosides or halothane, may cause heart rhythm disturbances (21); with guanethidine, may cause an enhancement of sympathomimetic effect (21); with monoamine oxidase inhibitors, can cause severe, possibly fatal, hypertension (26); with ergot alkaloid derivatives or oxytocin, may increase risk of high blood pressure (21).
Carcinogenesis, mutagenesis, impairment of fertility
Extracts of Ephedra sinica are not mutagenic in the Salmonella/microsome reversion assay (31).
Pregnancy: teratogenic effects
Ephedra sinica did not have any teratogenic effects in vivo (32).
Pregnancy: nonteratogenic effects
Ephedra sinica is not abortifacient in rats (32). Clinical studies in humans are not available; therefore, use of the drug during pregnancy is not generally recommended.
There are no reliable studies on this subject. Therefore, nursing mothers should not take Herba Ephedrae without consulting a physician.
Herba Ephedrae should not be administered to children under 6 years of age.
No information available concerning drug and laboratory test interactions.
In large doses Herba Ephedrae products can cause nervousness, headaches, insomnia, dizziness, palpitations, skin flushing and tingling, and vomiting (21). The principal adverse effects of ephedrine and Herba Ephedrae are stimulation of the central nervous system, nausea, tremors, tachycardia, and urine retention (24). Continued, prolonged use (>3 days) of topical preparations containing Herba Ephedrae, for the treatment of nasal congestion, may cause rebound congestion and chronic rhinitis (26). Continued prolonged use of oral preparations may cause dependency (21).
Crude plant material: 1–6g for decoction daily (8, 21). Liquid extract (1:1 in 45% alcohol): 1–3ml daily (21). Tincture (1:4 in 45% alcohol): 6–8ml daily (21).
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