Ephedra is a powerful plant used to support lung health. Molecules from it have been the basis for pharmaceuticals, and the plant is now only legally allowed to be prescribed by herbalists. This article explains the fascinating history behind the plant and its medicinal use.
Ma Huang is a plant used in Traditional Chinese Medicine (TCM) for a wide range of conditions and is most famous today as a treatment for asthma. The plant drug consists of the aerial parts â leaves, stems, flowers â of several species of Ephedra, particularly Ephedra sinica.
The isolated chemical ephedrine is popular as a drug to enhance athletic performance, promote weight loss, and relieve colds and flu. When it was first discovered its main use in pharmacy was as a bronchodilator to open up the airways of asthma sufferers.
The use of Ma Huang to suppress cough can be traced back to the oldest written record of Chinese medicinal plants. This article explores the history of the use of ephedrine and Ma Huang as a bronchodilator, and how the effects can be understood through both the lenses of chemistry and physiology, and traditional Chinese philosophies of healing.
The botany and chemistry of ephedra species
Ephedra species have been found in the fossil record going back 125 million years, when dinosaurs still walked the earth (1).There are around 71 species of ephedra recognised by current taxonomy, with a wide distribution through most of Asia and Europe, North Africa and the Horn of Africa, and the Western sides of South and North America (2). It is the only genus in the family Ephedraceae.
The botanical classification of this group of plants has been particularly difficult there are many close similarities in appearance between species. Ephedra species mostly grow as shrubs, consisting of long slender green stems that can photosynthesise. Their leaves appear as small scales on the stem and often turn brown and drop off.
Ephedra spp. have been confused with very ancient group of plants, the horsetails (Equisetum spp.) both historically and more recently in the herbal medicine trade (3).Market surveys today have found several species of Ephedra are sold as Ma Huang, sometimes differentiated as varieties of Ma Huang, but not always (4).
Ephedra sinica is the species most widely used for its medicinal properties. This species is found growing wild in Mongolia, Southern eastern provinces of Russia and in Northeastern China (5). While ephedrine is the most well known constituent, it contains 6 other structurally similar alkaloids in lesser concentrations with similar effects. Not all Ephedra species contain ephedrine type alkaloids (6).
The drug Ma Huanghas always been defined in Chinese Materia Medica texts as the aerial parts of several species of Ephedra. The less commonly used root of Ephedra spp. is known as Ma Huang Gen, which has long been seen as acting in opposition to the aerial parts; for example being prescribed âfor checking excessive perspiration of a weak patientâ (7). This traditional understanding has been corroborated by studies showing that chemicals that cause blood pressure to lower are only found in the root (8).
The discovery of ephedrine
Ma Huang has been traded from China to Japan from at least the 16th century, where it was incorporated into Japanese herbal medicine as a treatment for colds and flu in a combination with four to six other herbs known as Maoto, based on the Chinese formulation Ma Huang Tang (9).
The active chemicals of Ma Huangwere first isolated in 1887 by a professor at Tokyo University, Nagajosi Nagai. Of particular interest was a new chemical that was named after the plant as ephedrine. However, it was not until 1923 that researchers at Peking Union Medical College, K.K. Chen and Carl Schmidt, began investigating in detail how it could be used as a drug (10). They found that ephedrine acted in a very similar way to adrenaline, though with a milder, but longer lasting, effect (11).
Adrenaline, also known as epinephrine, is a hormone produced in the adrenal glands above the kidneys that acts as an essential messenger in the fight or flight response – this is how the body prepares itself to deal with a potentially dangerous situation. Adrenaline helps stimulate a range of changes including increased heart and breathing rate, slowing down digestion, releasing energy sources into the blood, dilation of blood vessels to the muscles, constriction of peripheral blood vessels, central nervous stimulation and bronchodilation. This response is coordinated by the sympathetic nervous system, that is why ephedrine is classed as a âsympathomimeticâ as it mimics the bodyâs natural messenger chemicals to activate receptors of this system.
Because of this effect ephedrine has become a popular drug for athletes to improve performance. It has also been used as a weight loss drug because it suppresses appetite and increases the rate that fat tissue uses and releases energy. It is also widely used in combination with caffeine in over the counter cold and flu remedies for opening nasal passages to relieve sinusitis (12).
However, care should be taken in dosage and duration of use, especially if taking any other medications that produce similar effects. It can lead to anxiety, restlessness, insomnia and a tolerance develops, and in extreme cases of improper use has caused heart attack and stroke. (13) Both Ephedra spp. and ephedrine should not be taken by people with hypertension, diabetes, hyperthyroidism orglaucoma (14). Because of these concerns there have been bans imposed on the use of ephedrine in sports and weight loss supplements by various regulatory bodies around the world.
Ephedrine as bronchodilator
Of particular interest for respiratory health is the bronchodilatory effect of ephedrine (15).When you breathe in air enters through the mouth and down the trachea, which divides into the left and right bronchi to enter the lungs, the bronchi further divide into many bronchioles, which then divide to join the many alveoli where gas exchange takes place. People suffering from asthma experience a tightening of the bronchioles causing coughing, wheezing and shortness of breath. The bronchi and bronchioles are lined with smooth muscle, which relaxes and opens up in response to adrenaline and ephedrine, this bronchodilatory effect relieves the symptoms of asthma.
While adrenaline had been used for treating asthma it had significant issues: it had to be injected, its effects were short lived, and it was chemically unstable. Ephedrine solved all these problems, leading to excitement amongst physicians in Europe and the USA, where it was widely adopted for treating asthma from 1926 the 1950s (16). Work on adrenaline led to the synthesis in the laboratory of several similar chemicals, one of which was salbutamol which became the next main treatment for asthma.
When used as an asthma treatment, and for Chronic Obstructive Pulmonary Disorder (COPD), ephedrine was commonly combined with two weaker bronchodilators: caffeine and theopylline, chemicals which were also isolated from a Chinese herbal medicine: tea (Camellia sinensis) (17).
The history of Ma Huang
According to legend, the mythological Chinese ruler Shennong (ç„ć) discovered the medicinal effects of tea when tea leaves from the twigs in his fire were carried up the hot air into his pot of boiling water. This was just one of the hundreds of herbs he tested on himself to identify their properties and taught people their uses, along with the practice of agriculture.
He is credited with writing The Shen Nong Ben Cao Jing (ç„ćæŹèç»), the oldest surviving written record of Chinese materia medica, thought to have been compiled in the 1st or 2nd Century CE. It is variously translated to English as The Divine Farmerâs Materia Medica, The Herbal Classic of the Divine Farmer, or Divine Husbandmanâs Classic of the Materia Medica (18,19,20).
This text has been continously referred to in texts on Chinese materia medica ever since, and many of the uses of herbs it describes are still employed today(22). It covers 365 herbs in total, corresponding to the natural cycle of days in a year, that are divided into three scrolls:
â120 âupperâ (shang) herbs, which can be taken daily to lengthen the lifespan; 120 âmiddleâ (zhong) herbs, which can be taken to prevent and hold back illness; and 125 âlowerâ (xia) herbs which treat illness, are mostly toxic and should not be taken for a long time(23)â.
Ma Huang appears on the âmiddle gradeâ scroll, which would match with the use of Ephedra spp. today â the use of ephedrine for acute infections only, and not longer term use for general health such as athletic training and weight loss.
The text describes Ma Huang as:
âbitter and warm. It is nontoxic, treating mainly wind stroke cold damage, headache, and warm malaria. It effuses the exterior [through] sweating, eliminates evil heat qi, suppresses cough and counterflow qi ascent, eliminates cold and heat, and breaks concretions and hardness, accumulations and gatherings. Its other name is Long Sha (Dragon Sand). It grows in rivers and valleys.â
The translator notes that a renowned scholar, known as âChancellor in the Mountainsâ, Tao Hong-jing (452-536 CE) later wrote, “Ephedra is the first choice in treating cold damage and resolving the muscles” and that, combined with âSinnamon Twig, Armeniaca, and Licoriceâ it âmay effect the cure of a tai yang pattern of wind cold in the exterior with pain and stiffness in the head and back of the neck, fever, generalized joint pain, a floating, tight pulse, absence of sweating, chest fullness, and pantingâ(24).
This is perhaps the first description of the Ma Huang Tangformulation that became so poular for respiratory infections, consisting of: Ma Huang (aerial parts of Ephedra spp.), Gui Zhi (twig of Cinnamomum spp.), Xing Ren (kernel of fruit of Prunus armeniaca) Can Gao (root of Glycyrrhiza spp.).
Writing 1,000 years after Tao Hong-jing, Li Shizhen (25) compiled a Compendium of Materia Medica, the Pentsâao Kang Mu, including 1,900 substances and referencing 900 previous works, critiquing them where necessary. Like his father and grandfather before him he travelled the countryside as a physician, both treating people and learning remedies from them. Ephedra is described and recommended for stimulating circulation, as a diaphoretic (to induce sweating) and antipyretic (to prevent or reduce fever). According to contemporary TCM herbalists Chen and Chen in the text âIt was also believed to be useful in the treatment of cough and as a result the stem became an important ingredient of many antitussive preparations.â (26).
Which they do themselves in their indications for Ma Huang: âRelieves Wheezing and Dyspnea, Stops Cough Wind-cold constriction of the Lung leading to Lung qi reversal: Ma Huang ventilates Lung qi and is useful in treatment of wheezing, dyspnea and cough characterized by wind-cold attacking the exterior that leads to abnornormal rising of Lung qi.â (27).
Approaching the use of Ma Huang, Ephedra spp. and ephedrine
As is so often the case, exploring the history of this herbal medicine indicates it has been used for a range of conditions on its own and in combination with other herbs, and that fully understanding these uses requires detailed knowledge of philosophies of healing of the time.
Seen through a contemporary biomedical lens, some connections can be made between these texts and the studied effects of ephedrine. The focus on sweating and treating cold and resolving the muscles can be linked to the increased blood flow to the muscles caused by ephedrine. From the mention of âsuppressing coughâ and curing âchest fullness and pantingâ in the The Herbal Classic of the Divine Farmer (Ben Cao Jing) we can assume it was used for treating conditions that we today would classify as asthma. This indication can be found throughout the history of writing on the materia medica of TCM, though it is important to note that it is normally accompanied by a detailed discussion of the cause of the disease and the particular manifestation in specific patients.
A full understanding of these aspects requires a detailed knowledge of the healing principles of TCM, from the concept of the flow Qi, generally translated as âlife forceâ, the elements and their relation to the organs, and the importance of the tastes of herbs, and how these combine. Asthma, cough and shortness of breath have many manifestations that will be caused by the interplay of environmental, internal, physical and emotional causes.
Based on research on ephedrine, a standard European reference on herbal medicines understands Ma Huang in biomedical terms as vasoconstricting, bronchodilating, and central [nervous system] stimulating properties (28).
However, like many herbal medicines the chemical constituents of the whole herb are not fully characterised or understood, and these may also aid in managing asthma, coughs and colds. For example research on Ephedra sinica shows it contains chemicals that have anti-inflammatory, anti-bacterial, anti-fungal, antioxidant and anti influenza effects that could explain other ways the herb extracts can work in treating respiratory infections (29,30).
Ephedra is just one example of a medicinal plant with rich history, thatâs traditional uses can now partially be explained by modern science. This plant can only be prepared and prescribed by licensed herbalists, due to its potential side effects. We really recommend seeing a herbalist for a personalised treatment plan for all sorts from respiratory health to other ailments. You can find one on our resources page here.
References
- Ickert-Bond, S.M., Rydin, C. and Renner, S.S., 2009. A fossilâcalibrated relaxed clock for Ephedra indicates an Oligocene age for the divergence of Asian and New World clades and Miocene dispersal into South America. Journal of Systematics and Evolution, 47(5), pp.444-456.
- Â Plants of the World Online. Facilitated by the Royal Botanic Gardens, Kew. Published on the Internet; https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:328160-2 Retrieved 02 Jan 2022.
- Yoshizawa, C., Kitade, M. and Mikage, M., 2005. Herbological studies on Chinese crude drug Ma-huang. Part 1-On the botanical origin of Ma-huang in ancient China and the origin of Japanese Ma-huang. Yakushigaku zasshi, 40(2), pp.107-116.
- Hu, S.Y., 1969. Ephedra (Ma-huang) in the new Chinese materia medica. Economic Botany, pp.346-351.
- Plants of the World Online. Facilitated by the Royal Botanic Gardens, Kew. Published on the Internet; https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:383460-1 Retrieved 02 Jan 2022
- Abourashed, E.A., ElâAlfy, A.T., Khan, I.A. and Walker, L., 2003. Ephedra in perspectiveâa current review. Phytotherapy research, 17(7), pp.703-712.
- Hu, S.Y., 1969. Ephedra (Ma-huang) in the new Chinese materia medica. Economic Botany, pp.346-351
- Tamada M, Endo K, Hikino H, Kabuto C. 1979. Structure of Ephedradine A, a hypotensive principle of Ephedra roots. Tetrahedron Lett 10: 873â876.
- Yoshino, T., Arita, R., Horiba, Y. and Watanabe, K., 2019. The use of maoto (Ma-Huang-Tang), a traditional Japanese Kampo medicine, to alleviate flu symptoms: a systematic review and meta-analysis. BMC complementary and alternative medicine, 19(1), pp.1-11.
- Lee, M.R., 2011. The history of Ephedra (ma-huang). JR Coll Physicians Edinb, 41(1), pp.78-84.
- Chen, K.K. and Schmidt, C.F., 1926. The action and clinical use of ephedrine: an alkaloid isolated from the Chinese drug Ma Huang. Journal of the American Medical Association, 87(11), pp.836-842.
- Abourashed, E.A., ElâAlfy, A.T., Khan, I.A. and Walker, L., 2003. Ephedra in perspectiveâa current review. Phytotherapy research, 17(7), pp.703-712.
- Lee, M.R., 2011. The history of Ephedra (ma-huang). JR Coll Physicians Edinb, 41(1), pp.78-84.
- Abourashed, E.A., ElâAlfy, A.T., Khan, I.A. and Walker, L., 2003. Ephedra in perspectiveâa current review. Phytotherapy research, 17(7), pp.703-712; Chen, J.K., Chen, T.T. and Crampton, L., 2004. Chinese medical herbology and pharmacology (Vol. 1267). City of Industry, CA: Art of Medicine Press.
- Barnes, J., Anderson, L.A. and Phillipson, J.D., 2003. Herbal medicines: a guide for healthcare professionals (No. Ed. 2). pharmaceutical press. p.244
- Lee, M.R., 2011. The history of Ephedra (ma-huang). JR Coll Physicians Edinb, 41(1), pp.78-84.
- SchultzeâWerninghaus, G. and MeierâSydow, J., 1982. The clinical and pharmacological history of theophylline: first report on the bronchospasmolytic action in man by SR Hirsch in Frankfurt (Main) 1922. Clinical & Experimental Allergy, 12(2), pp.211-215
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- Evans, L., 2017. Reading of the Divine Farmer’s Classic of Materia Medica: Shen Nong Ben Cao Jing Du. The Journal of Chinese Medicine, (114), pp.64-65.
- Shen Nung seated on a rock, wearing simple garments fashioned from leaves, holding a small plant; a selection of roots and plants are also shown on a ledge by his side. Watercolour, China, 1920?. Wellcome Collection. https://wellcomecollection.org/works/z5w9zzbf/images?id=z9szdx4b . Published 1920. Accessed January 6, 2022.
- Chen, J.K., Chen, T.T. and Crampton, L., 2004. Chinese medical herbology and pharmacology (Vol. 1267). City of Industry, CA: Art of Medicine Press.
- Nugent-Head, J., 2014. The First Materia Medica: The Shen Nong Ben Cao Jing. Journal of Chinese Medicine, (104). p.24
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- Chen, J.K., Chen, T.T. and Crampton, L., 2004. Chinese medical herbology and pharmacology (Vol. 1267). City of Industry, CA: Art of Medicine Press. p.14
- Chen, J.K., Chen, T.T. and Crampton, L., 2004. Chinese medical herbology and pharmacology (Vol. 1267). City of Industry, CA: Art of Medicine Press. p.36
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- Theory of diseases treated with ephedra decoction, Chinese. Wellcome Collection. https://wellcomecollection.org/works/pxhq48mb . Published 1833. Accessed January 6, 2022.
