Medical Attributes of Ephedra sp. – Ephedra /
Ma-huang
by Cassandra Cragle
Wilkes University
Wilkes-Barre, PA
July 2015
Ephedra spp., commonly known as Chinese ephedra or ma-huang,
are shrubby species of the genus Ephedra L. within the
Ephedraceae (ephedra family) (Bell & Bachman 2011). It is
native to Central Asia, including southern Siberia (Russian
Federation), Mongolia, and China (Bell & Bachman 2011). Ephedra
can also be found in the southwestern United States, temperate
tropical regions of North America and Mediterranean regions, Mexico,
South America (Ecuador to Patagonia and Argentina), southern Europe,
and northern Africa (Bell & Bachman 2011). Other common names
for Ephedra include Mormon-tea, jointfir, cañatilla,
popotillo, tepopote, as well as many others (FNA n.d., ITIS 2010).
While typically a shrub, Ephedra is occasionally a
clambering vine, which has jointed branches that are yellowish-green
to olive-green when young. The leaves are opposite or in whorls of 3
(FNA n.d.). It is terrestrial, found in arid areas and highlands, on
slopes, dry riverbeds, in sandy locations, or in fields on
mountainsides. Classified as a gymnosperm (Order Gnetales), Ephedra
produces cones and wind pollinates from March to June and sets seed
between June through September (Bell & Bachman 2011). The plants
are dioecious, female and male cones being produced on different
plants, and are wind-pollinated. All plants in a population tend to
reproduce in synchronization during a year with adequate rainfall,
and then not again for several years (Meyer 2015).
As an herbal remedy, the stems have shown anti-inflammatory
activity. It also possesses antitussive effects aiding in coughing,
cardiovascular effects and genetic effects that can mutate about 100
genes (Sigma-Aldrich 2015). Ephedra sinica extracts also
possess outstanding anti-bacterial activity (Dashtdar, et al. 2013).
It is also used to treat asthma, nose and lung congestion, and fever
with anhidrosis, which is the inability to sweat normally (Lee, et
al. 2000).
Ephedra contains alkaloids including ephedrine,
pseudoephedrine (isoephedrine), norpseudoephedrine (cathine),
norephedrine, methylephedrine, methylpseudoephedrine, tannins, and
other constituents (Sigma-Aldrich 2015). The alkaloids
ephedrine and pseudoephedrine are found in the leaves and stems.
They are structurally similar to amphetamines. They elicit effects
of central nervous system stimulation, bronchodilation,
hypertension, and chronotropic/inotropic effects. These alkaloids
are not present in the New World species of Ephedra (Caveney
et al. 2001). Tannins in Ephedra have astringent properties
and have long been used in topical preparations to treat oozing and
weeping of skin lesions, and also have been thought to possess some
renal protective agents (Dashtdar, et al. 2013). In a GC-MS
study, ephedrine was reported to be the major alkaloid in
ephedra. It is found primarily in the stem, with less in the
roots (Lv et al. 2015). Another analysis revealed that Ephedra
from Mongolia contained high amounts of five ephedrine alkaloids,
allowing it to be an effective supplemental resource (Kitani et al.
2009). The Ephedra population in southwestern Mongolia
showed a high likelihood of having hybrid origins. The plants in
this area were hard to identify based on external features, such as
having irregularly curved or twisted stems and several species were
involved. They were collected and treated as Ephedra sp.,
undergoing molecular analysis. It was determined that these were
species of Ephedra but showed a higher rate of nucleotide
variation (Kitani, et al. 2011).
A study by Song et al. (2012) conducted on mice fed high-fat diets
revealed that Ephedra sinica effectively reduced weight gain
and epididymal fat accumulation, improved glucose tolerance,
decreased triglycerides and increased high-density lipoprotein
cholesterol compared to control groups. Those results suggested that
Ephedra sinica may reduce obesity and hyperglycemia and could
possibly be used clinically to treat glucose intolerance obesity
(Song, et al. 2012).
Li et al. (2009) found that in rats with induced spinal cord
injuries, administering Ephedra sinica improved motor
function improvement after seven days in comparison to a control
group given water. Li, et al. (2009) concluded that Ephedra
sinica may help reduce inflammation and improve motor function
by inhibiting the complement system that causes the inflammation to
occur initially.
Conversely, Ephedra has well established adverse
effects. In the 1990s and early 2000s, Ephedra was
marketed for weight-loss and energy-enhancement in the United States
and were unregulated with no standardization of strength or
purity. There were no proven benefits except for minimal,
short-term weight loss. Research has linked Ephedra use with
hypertension, cardiac dysrhythmias, myocardial infarction, seizure,
stroke, and sudden death (Zell-Kanter, et al. 2015). Dietary
supplements containing Ma Huang (Ephedra alkaloids)
and guarana (caffeine) were widely marketed despite a lack of
research. The quantities of 35 commercial supplements were compared
with product labels. The results revealed the total Ephedra
alkaloid content ranged from 5.97mg to 29.3mg per serving. Of these
supplements, 31% contained greater than 110% of the total Ephedra
alkaloids listed on the labeling and 6% contained less than 90% of
the listed amount (Haller et.al. 2004).
A study was conducted on the relative toxicity of extracts from Ephedra
species under different conditions. Ephedra contains
0.5-2.5% total alkaloids by weight, and ephedrine makes up 30 to
90%. Using high performance liquid chromatography (HPLC), it was
determined that there were other chemicals present along with
ephedrine, which suggested that there were other unaccounted for
toxins present in the extract preparations (Lee, et al. 2000).
In April 2004, the FDA banned the sale of Ephedra-containing
products after receiving increasing evidence and more than 18,000
adverse-event reports. The number of calls related to Ephedra
use to poison control centers peaked at 10,326 in 2002 and declined
to 180 by the end of 2013. There is a direct relation between the
ban of Ephedra sales and a decline of adverse-event reports
by almost 98% since 2002, proving that the FDA ban on sales was very
effective (Zell-Kanter, et al. 2015).
In conclusion, Ephedra does have potential uses, as a
stimulant, for weight loss, to treat asthma, among others. However,
it does yield adverse reactions, such as hypertension, cardiac
dysrhythmias, myocardial infarction, seizure, stroke, and sudden
death. Ephedra is an effective plant, but is dangerous
without regulation and standardization of dosage. Until there is a
standard and the product is regulated when it is sold, it seems that
the ban is the best solution to prevent any future issues similar to
the ones that occurred in the past.
Caveney, S., D.A. Charlet, H. Freitag, M. Maier-Stolte, & A.N.
Starratt. 2001. New observations on the secondary
chemistry of world Ephedra (Ephedraceae). Am J Bot
88.7: 1199-208.
Dashtdar, M., M.R. Dashtdar, B. Dashtdar, M.K. Shirazi, & S.A.
Khan. 2013. In vitro, anti-bacterial activities of aqueous
extracts of Acacia catechu (L.F.) Willd, Castanea sativa,
Ephedra sinica Stapf. and Shilajita mumiyo against
Gram positive and Gram negative bacteria. J Pharmacopuncture
16.2: 15-22.
Haller, C. A., M. Duan, N.L. Benowitz, & P. Jacob 3rd.
2004. Concentrations of ephedra alkaloids and caffeine in
commercial dietary supplements. J Anal Toxicol 28.3: 145-51.
Kitani, Y., S. Zhu, T. Omote, K. Tanaka, J. Batkhuu, C. Sanchir, H.
Fushimi, M. Mikage, & K. Komatsu. 2009. Molecular
analysis and chemical evaluation of ephedra plants in Mongolia. Biol
Pharm Bull 32.7: 1235-43.
Kitani, Y., S. Zhu, J. Batkhuu, C. Sanchir, & K. Komatsu.
2011. Genetic diversity of Ephedra plants in Mongolia
inferred from internal transcribed spacer sequence of nuclear
ribosomal DNA. Biol Pharm Bull 34.5: 717-26.
Lee, M.K., B.W. Cheng, C.T. Che, & D.P. Hsieh. 2000.
Cytotoxicity assessment of mahuang (Ephedra) under different
conditions of preparation. Toxicol Sci 56.2: 424-30.
Li, L., J. Li, Y. Zhu, & G. Fan. 2009. Ephedra sinica
inhibits complement activation and improves the motor functions
after spinal cord injury in rats. Brain Res Bull.
16.78(4-5): 261-6.
Lv, M., J. Sun, M. Wang, W. Huang, H. Fan, F. Xu, & Z.
Zhang. 2015. GC-MS based metabolics study of stems and
roots of Ephedra sinica. J Pharm Biomed Anal.
114: 49-52.
Song, M.K., J.Y. Um, H.J. Jang, & B.C. Lee. 2012.
Beneficial effect of dietary Ephedra sinica on obesity and
glucose intolerance in high-fat diet-fed mice. Exp Ther Med
3.4: 707-12.
Zell-Kanter, M, M.A. Quigley, & J.B. Leikin. 2015. Reduction of
Ephedra poisonings after FDA ban. The New England
Journal of Medicine: 372:2172-74.
This paper was developed as part of the BIO 368 - Medical Botany
course offered at Wilkes University during the summer of 2015.
Course instructor was Kenneth M. Klemow, Ph.D. (kenneth.klemow@wilkes.edu).
The
information contained herein is based on published sources, and is
made available for academic purposes only. No warrantees, expressed
or implied, are made about the medical usefulness or dangers
associated with the plant species in question.