Article published online: 2024-02-29

Reviews

Ethnobotanical Uses and Pharmacological Activities

of Moroccan Ephedra Species

Authors
Mounia Chroho 1, Christian Bailly 2, 3, Latifa Bouissane 1

Affiliations Correspondence
1 Molecular Chemistry, Materials and Catalysis Laboratory, Prof. Dr. Christian Bailly
Faculty of Sciences and Technologies, Sultan Moulay Institute of Pharmaceutical Chemistry Albert Lespagnol (IC-

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Slimane University, Beni-Mellal, Morocco PAL), Faculty of Pharmacy, University of Lille
2 OncoWitan, Scientific Consulting Office, Lille, France 3 rue du Professeur Laguesse, BP-83, F-59006 Lille, France
3 Institute of Pharmaceutical Chemistry Albert Lespagnol, Phone: + 33 (0) 3 20 96 43 74, Fax: + 33 (0) 3 20 97 42 01
Faculty of Pharmacy, University of Lille, France christian.bailly@univ-lille.fr

Keywords AB STR AC T
Ephedra, Ephedrae herba, plants from Morocco, traditional Ephedra species are among the most popular herbs used in
uses, biological activities traditional medicine for a long time. The ancient Chinese
medical book “Treatise on Febrile Diseases” refers to the clas-
received September 24, 2023
sic traditional Chinese medicine prescription Ge Gen decoc-
accepted after revision February 1, 2024
tion, which consists of seven herbs, including an Ephedra spe-
published online February 29, 2024
cies. Ephedra species are utilized all over the world to treat
Bibliography symptoms of the common cold and coughs, and to combat
Planta Med 2024; 90: 336–352 major human diseases, such as asthma, cancers, diabetes,
DOI 10.1055/a-2269-2113 cardiovascular and digestive disorders, and microbial infec-
ISSN 0032‑0943 tions. This study aimed at identifying specific Ephedra species
© 2024. Thieme. All rights reserved. used traditionally in Morocco for therapeutic purposes. The
Georg Thieme Verlag KG, Rüdigerstraße 14, plant parts, their preparation process, and the treated pathol-
70469 Stuttgart, Germany ogies were identified and analyzed. The results revealed five
ethnobotanically important species of Ephedra: Ephedra alata
Correspondence Decne, Ephedra altissima Desf., Ephedra distachya L., Ephedra
Prof. Dr. Latifa Bouissane fragilis Desf., and Ephedra nebrodensis Tineo. These species
Molecular Chemistry, Materials and Catalysis Laboratory, Fac- are used traditionally in Morocco for treating people with dia-
ulty of Sciences and Technologies, Sultan Moulay Slimane betes, cancer, rheumatism, cold and asthma, hypertension,
University influenza virus infection, and respiratory ailments. In addition,
Campus Mghila, BP 523, 23000 Beni-Mellal, Morocco they are occasionally used as calefacient agents, to regulate
Phone: + 21 25 23 48 51 12, Fax: + 21 25 23 48 52 01 weight, or for capillary care. Few studies have underlined the
l.bouissane@usms.ma antibacterial and antioxidant activities of some of these Mo-
roccan Ephedra species, but little information is available re-
garding the natural products at the origin of the bioactivities.
Further phytochemical investigations and clinical data are en-
couraged to better support the use of these plants.

“Treatise on Febrile Diseases” refers to the classic traditional Chi-

Introduction nese medicine prescription Ge Gen decoction, which consists of
Ephedra plants are among the oldest and most popular herbs used seven herbs, including an Ephedra species [7], and a Latin textbook
in traditional medicine in China and Japan [1–3]. Ephedrae herba from the roman naturalist Pliny the Elder (Gaius Plinius Secundus,
has long been used as both medicine and food [4, 5]. It stands as AD 23–79) underlined the use of Ephedra as follows: “it is given
an efficient anti-stroke herbal medicine [6]. Its use as a folk phyto- from black austere wine, crushed, for coughs, sighs, convulsions,
medicine is mentioned in ancient medical books and traditional and drinking” [8]. For decades, Ephedra species have provided
prescriptions [3]. For example, the ancient Chinese medical book herbal remedies to treat human diseases [9, 10]. These medicinal

336 Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved.
 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
▶ Fig. 1 Illustrations of Ephedra species found in Morocco. a Ephedra alata, b Ephedra altissima, c Ephedra fragilis, and d Ephedra nebrodensis (by
Jean-Paul Peltier, licensed under CC BY‑NC 4.0.) e Ephedra distachya [32]. Their traditional medicinal uses are either well described (+), not reported
(−), or remains questionable (*in the case of E. distachya).

plants, largely distributed in arid and semiarid regions of the These undesirable reactions were generally related to the pres-
world, also carry ecological and economic values [11, 12]. ence of ephedrine-type alkaloids [21, 22]. The alkaloid ephedrine,
Over 60 Ephedra plants have been identified [4, 11]. The POWO often present in Ephedra herb extracts, mediates sustained excita-
database has listed 167 species, including 78 with accepted tory effects via activation of the α-2a adrenoceptor [23]. Over the
names (https://powo.science.kew.org/results?f = species_f% past 10 years, the development of an ephedrine alkaloid-free
2Caccepted_names&q=Ephedra). Ephedra species can be found Ephedra herb extract has been recommended for safer use by hu-
in Europe, southern and eastern Asia (notably in China and Japan), mans, with reduced side effects [21, 22, 24, 25]. Ephedrine-free
North America (southwestern United States and northern Mexi- Ephedra herb extract and derived products can be used to treat
co), the western part of South America, and in Africa, from North various diseases, including COVID-19, for example [2, 26].
Africa to the horn of Africa. Ephedra species grow in desert, arid, Ephedra species are used as medicinal plants in African and
and semiarid conditions, most often on dry, rocky, or sandy soil. Mediterranean countries. For example, the species Ephedra foemi-
They are often considered desert shrubs, but some species can nea Forssk is a traditional medicinal plant in the Eastern Mediter-
be found in riverbeds and grasslands [10, 13]. ranean region [27]. In Lebanon, this plant offers a popular remedy
In traditional medicine, the uses of Ephedra species are ex- to treat inflammation and bacterial infections [28]. The species
tremely diversified. They are utilized to treat respiratory affec- Ephedra nebrodensis Tineo growing in Algeria is largely used to
tions, such as cough, symptoms of the common cold and asthma, combat inflammatory and oxidative damage [29, 30]. The two
or as a deobstruent or emollient. These plants are also used to species Ephedra alata and Ephedra altissima growing in Tunisian
treat disorders of the cardiovascular and digestive systems, ail- arid zones are used traditionally to treat chills, coughs, fever, and
ments of the urinary tract, cancers, diabetes, as well as bacterial, bronchial asthma [31]. In the present work, we have identified the
viral, and fungal infections [14, 15]. Other studies mention the use Ephedra species used specifically in Morocco (▶ Fig. 1). We inven-
of Ephedra species for the treatment of edema, fever, and allergies toried their traditional medicinal uses by local populations and the
[1, 2, 16, 17]. Ephedra extracts are also considered as dietary sup- main bioactive products and associated pharmacological activ-
plements, notably for weight loss [18, 19]. However, it is impor- ities have been analyzed. The aim of this analysis is to highlight
tant to mention that despite the recognized benefits of Ephedra the use of Ephedra species in Morocco, to encourage further stud-
herbs on human health, adverse effects have occasionally been re- ies on the plantʼs pharmacological activities, and to try to provide
corded, such as excitation, agitation, palpitation, dysuria, arrhyth- a scientific rational for their medicinal usage.
mia, elevated blood pressure, dizziness, and insomnia [2, 20, 21].

Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved. 337
 Reviews

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
▶ Fig. 2 Distribution of the five species of Ephedra around the world (maps defined from the Global Biodiversity Information Facility [gbif.org]) [33,
42, 47, 54, 57].

Ephedra species found in Morocco and

Results their medicinal uses
Several ethnobotanical surveys and floristic studies have been
Ephedra species around the world performed in different regions of Morocco to take inventory of
Ephedra species are dispersed in arid and semiarid areas of Asia, the flora species of the country. For example, recent studies refer
Europe, Northern Africa, southern North America, and South to the medicinal plants used traditionally in the Safi and Sefrou
America [11]. The five species discussed in this paper are mainly provinces [62, 63] or the Ksar Elkebir [64] and Tafilalet regions
present in North Africa and Eurasia (▶ Fig. 2). E. alata is located in [65]. Toxic plants found in northeastern Morocco have been in-
North Africa and West Asia (▶ Fig. 2 a) [33], and was cited among ventoried as well [20]. Other studies cover different local areas or
the flora of Morocco [34–36], Algeria [37], Tunisia [38, 39], and they are concerned with specific pathology or disorders, such as
Palestine [40]. E. altissima is limited to North Africa and the south the Moroccan plants used to treat cancers [14, 66], skin affections
of Europe [41] (▶ Fig. 2 b) [42], including countries such as Austria [67], kidney diseases [68], or cardiovascular diseases [69]. Some
(botanical garden) [43] and Morocco [44–46]. Ephedra distachya is Moroccan plants have been largely studied, such as the endemic
the most abundant of these species and belongs to the extreme argan [Argania spinosa (L.) Skeels], which is well known for its fa-
north of Africa and Eurasia (▶ Fig. 2 c) [47]. Samples from China mous oil extracted from argan seeds [70]. However, there is no
[48], Morocco [49, 50], Greece [51], Spain [52], Ukraine [53], study focused on Moroccan Ephedra species and their medicinal
and Austria [43] have been reported. Ephedra fragilis is distributed uses. We performed this specific analysis.
in North Africa and Europe (▶ Fig. 2 d) [54] as well as in Morocco We identified five medicinal Ephedra species present in Moroc-
[44, 55] and Austria [43]. Finally, Ephedra nebrodensis, which has co, namely, E. alata, E. altissima, E. distachya, E. fragilis, and E. ne-
the lowest distribution, can be found in North Africa [56], Europe brodensis (▶ Fig. 1 and Table 1). They are essentially located in
(▶ Fig. 2 e) [57], including Italy [58, 59] and Spain [52], Morocco the southern part of the country, but also in the Middle and High
[60], and Algeria [61]. Here, we will focus on Moroccan Ephedra Atlas Mountains. The ethnobotanical information on Moroccan
species. Ephedra is limited, probably because the density of the population
is low in south Morocco and because of the aridity of the region.
Ephedra species are not abundant compared to other plants. For
example, Abouri and coworkers identified 163 plant species re-

338 Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved.
 or inhaled to treat respiratory ailments. There is also a mention of
▶ Table 1 Ephedra species of Morocco and their locations.
massage using a decoction to treat rheumatoid arthritis [34]. De-
coctions made from the aerial parts of E. altissima are used to treat
Ephedra Location in Morocco Reference
species diabetes and cancer. However, this product should be used with
care because it can induce neurological damages, notably dizzi-
Ephedra Laâyoune Sakia El Hamra region [35]
alata
ness or vertigo [20]. E. alata is perhaps a safer species, with no ma-
Tarfaya Province [36] jor toxicity reported, in particular, no hallucinogenic effect when a
Tata Province [34] plant decoction is used for oral treatment of diabetes in the Za-
gora region of Morocco [76]. However, caution is required be-
Ephedra Atlas Mountains, Imouzzer re- [44–46]
altissima gion cause Ephedra preparations containing the alkaloid ephedrine
may cause hypotension and spontaneous abortion in pregnant
Ephedra Southern Morocco [71, 72]
fragilis
women [77].
Oulad Teima, Taroudant [44, 55]
Souss-Massa region Pharmacological activities of Ephedra extracts

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Ephedra Central Middle Atlas [15] and associated bioactive products
nebrodensis Experimental studies performed with plant extracts made from
High Atlas [60]
Moroccan Ephedra are rare, but there are a few useful reports
Tichoukt Mountain, Middle Atlas [56]
(▶ Table 3) that can be completed with studies using the same
Ephedra Southern Morocco [49, 50] species collected from other countries. Thereafter, the plant ex-
distachya
tract activities are discussed in turn.

Ephedra alata Decne

The dried aerial parts of a sample of E. alata collected from the
presenting 134 genera in the Tata province (south-eastern Moroc- Laâyoune Sakia El Hamra region (Morocco) have been used to pre-
co) but only one Ephedra species, E. alata Decne. (known locally as pare a plant extract via an ultrasound-assisted extraction process
Tamatrt), which is used traditionally mainly to treat colds and res- with the objective of optimizing the yield of the main active ingre-
piratory ailments. Ephedracea appeared to be rare in this part of dient from the extract, the flavonoid glycoside isoquercetin [35].
the country, in contrast to Lamiaceae and Asteraceae, which are The process afforded more than 1 mg of isoquercetin per gram of
much more abundant [34]. The situation is a little more favorable extract. The isoquercetin-enriched extract was shown to display
in the Middle and High Atlas Range, with a more frequent pres- higher antioxidant and enzymatic effects than a classical extract
ence of Ephedra species, such as E. nebrodensis Guss. found on obtained with a conventional Soxhlet extraction. The enriched ex-
the rocky ecosystem (from 2200 meters) [56]. tract showed a higher inhibitory efficiency against different en-
The five Ephedra species present in Morocco are used tradition- zymes, such as elastase and collagenase implicated in skin aging,
ally to treat different diseases (▶ Table 2). Four of them are well tyrosinase involved in hyperpigmentation, α-amylase playing a
referenced, but there is no published information on the local role in diabetes, hyaluronidase involved in inflammation pro-
(Moroccan) use of E. distachya L. to treat human diseases. Howev- cesses, and cholinesterase implicated in some neurodegenerative
er, this plant is cited as a medicinal plant in other countries, owing disorders. The content of isoquercetin was largely enhanced and
to its content of catechins and other polyphenolic compounds the associated bioactivities reinforced [35]. Isoquercetin (querce-
with antioxidant and anti-inflammatory properties [73, 74]. We tin 3-glucoside, also called isoquercitrin) (▶ Fig. 3) is a major con-
choose to maintain this species in our analysis because the pres- stituent of E. alata and a well-known flavonoid found in a variety of
ence of the plant in Morocco has been clearly mentioned [49, 50] plants, with anti-neuroinflammatory and anticancer activities
and practitioners have cited this species also. Two other Ephedra [84–87]. Recently, this compound has been characterized as a
species are present in Morocco, Ephedra foliata Boiss. ex C. A.Mey. promising molecule for the treatment of osteoporosis [88].
and Ephedra major Host, but we did not identify any study pertain- E. alata is one of the medicinal plants used to treat cancer in
ing to the traditional medicinal use of these species. For this rea- Morocco [14, 66] and in other countries, such as Algeria and Pal-
son, we did not consider them in our study (▶ Fig. 1). The most estine (East Jerusalem) [89, 90]. Methanolic or ethanolic extracts
frequently cited species is E. alata Decne. followed by E. altissima made from the plant have revealed marked inhibitory effects on
Desf., E. fragilis Desf., and then E. nebrodensis Tineo. This latter the proliferation of breast cancer cell lines in vitro. The activity
species can be commonly found in other Mediterranean countries has been associated with the presence of diverse flavonoids, phe-
such as Algeria and Italy [29, 58] and more rarely in other parts of nolic acids, and proanthocyanidins [37, 91–93]. A recent study
the word, such as Pakistan [75]. Altogether, they are used locally evidenced the induction of tumor cell apoptosis in a p53-depen-
to treat a variety of human diseases, such as asthma, rheumatism, dent manner by an ethanolic extract of E. alata (with a specimen
hypertension, diabetes, cancer, and other pathologies or condi- from Algeria) [94]. Isoquercetin contributes to the anticancer ef-
tions (▶ Table 2). The aerial parts of the plants are used to make fects in conjunction with other glycosylated flavonoids, such as lu-
decoctions from the leaves or stems. E. alata is the most fre- teolin-7-O-glucuronide and myricetin-3-rhamnoside, which have
quently used Ephedra species in the form of decoction (powdered been characterized in a sample of a wild E. alata plant [40]. Other
branches) or infusion (leaves) and the preparations are used orally bioactivities have been characterized with E. alata extracts, includ-

Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved. 339
 Reviews

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
▶ Fig. 3 E. alata with the extraction and purification process developed to efficiently extract isoquercetin [35] (photo of the plant from POWO
[https://powo.science.kew.org]).

▶ Table 2 Medicinal traditional uses of Ephedra species from Morocco.

Ephedra Local vernac- Therapeutic tradi- Part of the Method of Moroccan study Refer-
species ular name tional uses plant used preparation area ences

Ephedra Timitrte Antidiabetic Leaves Leaf decoction as- Central Middle At- [15]
nebrodensis sociated with Apium las region
graveolens and Pet-
roselinum sativum

Ephedra Daghmous Cancer Leaves, stems Decoction (oral Greater Casablanca [14]
alata Elaalnda administration)

Chdida Rheumatism, colds Leaves, stems Oral powder Tarfaya Province [36]

Andla Cancer Leaves Infusion, powder [66]

for internal or ex-
ternal uses

Amater Asthma, arthritis/ Stems Decoction (oral/ [78]

rheumatoid ointment)

Tamatrt To gain weight, cale- Leaves, Oral, inhalation, Tata Province [34]
facient, diabetes, branches massage
asthma, hyperten-
sion, colds, influenza,
respiratory ailments,
rheumatoid arthritis

Diabetes Leaves Decoction powder/ Zagora [76]

oral

Ephedra Tougel argan Diabetes Stems, leaves, Decoction/oral Chtouka Ait Baha [79]
altissima and whole and Tiznit (West-
plant ern Anti-Atlas)

Laâlenda Abortion Stems [80]

Laâlenda Cancer Aerial part Internal uses Northeastern [20]

Morocco

Ephedra Azrm Hair care and diabetes Aerial part Decoction Northeastern [81]
fragilis Amater Leafy stems Morocco

Amater Diabetes Leafy stems Decoction/oral Taroudant [82]

Province

340 Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved.
 ▶ Table 3 Studies about Ephedra species from Morocco.

Ephedra Plant part and Main activity studied Results Refer-

species preparation used ences

Ephedra Aerial parts, etha- Enzyme inhibitory and Antioxidant and inhibitory activities against diverse enzymes [35]
alata nol extract antioxidant activities; (acetyl- and butyryl-cholinesterase, α-amylase, elastase, hya-
extraction of isoquerce- luronidase). Optimization of the extraction process for iso-
tin quercetin (recovery: 1034 µg/g of extract using optimized pa-
rameters: EtOH concentration, liquid-solid ratio, extraction
time, extraction temperature, and ultrasonic power).

Ephedra Roots, methanolic Anti-staphylococcal ac- Antibacterial activities of the extract, notably against Staphylo- [45]
altissima extract tivity coccus epidermidis and two strains of Staphylococcus aureus.

Roots, methanolic Antileishmanial activity The alcoholic extract was found active against Leishmania in- [46]
extract fantum (IC50 = 490.8 µg/mL).

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Ephedra Aerial parts, sev- Antioxidant, anti-glyca- Marked antioxidant activity of the ethyl acetate fraction. Iden- [55]
fragilis eral organic ex- tion activities; chemical tification of rutin, quercetin, caffeic, ferulic acid, gallic acid,
tracts composition and vanillic acid.

Aerial parts, ethyl Cytoprotective effect Protection of Tetrahymena pyriformis cells from oxidative stress [83]
acetate extract induced by hydrogen peroxide.

ing antioxidant and anti-inflammatory effects [16], notably asso- ity of the plant against type 2 diabetes [101]. The activity has
ciated with the presence of glycosylated flavonoids such as iso- been associated with the presence of flavone glycosides, such as
rhamnetin-3-O-rutinoside, isoschaftoside, and kaempferol-3-O- isovitexin-2-O-rhamnoside, kaempferol-3-O-rhamnoside, and
rhamnoside [95]. There is also mention of antidiabetic and anti- quercetin-3-O-rhamnoside found in the ethyl acetate extract
bacterial activities with this plant [96–99]. Aqueous extracts of E. [102]. The flavonoid content is higher in E. altissima compared to
alata contain diverse flavonoids but also alkaloids, phenolic com- E. alata. This has been evidenced when comparing the seeds of
pounds, and steroids useful to improve wound healing [100]. the two plants (both collected in Southern Tunisia). The former
contained significantly more flavonoids but also more polyphe-
Ephedra altissima Desf. nols and more condensed tannins than the latter species. As a re-
This Ephedra species is native to the north of Africa (Morocco, Al- sult, the antioxidant potential of an E. altissima seed extract was
geria, Tunisia, Libya, and Mauritania), the Canary Islands, and found to be markedly higher than that of an E. alata seed extract.
Chad. A plant sample collected in the Atlas Mountains in the Im- The predominant bioactive natural products were gallic acid,
ouzzer region of Morocco has been used to prepare both aqueous quercetin, epicatechin, naringin, and the atypical flavone cirsiliol
and methanolic extracts of E. altissima that were then tested for (3′,4′,5-trihydroxy-6,7-dimethoxyflavone) [31] (▶ Fig. 4 a). Cirsi-
their antibacterial activities. The aqueous extracts were found in- liol is an interesting compound regulator of mitophagy in cancer
active, whereas methanolic extracts made from the plant roots re- cells [103], apparently acting as an inhibitor of tyrosine kinase
vealed a modest activity against Staphylococcus aureus [strain TYK2 (KD = 0.8 µM) in cancer cells and tumors [104]. Its anticancer
ATCC 29 213, which is a classical methicillin-resistant (MRSA) effects have been well evidenced using different cell lines and tu-
strain]. The antibacterial activity was noticeable but weak com- mor models in recent years [105, 106]. It is also a potent antioxi-
pared to that measured with other Moroccan plants, such as Ber- dant molecule capable of binding to the enzyme F1Fo-ATP syn-
beris hispanica, for example [45]. The authors also evaluated the thase [107] and a compound that can mitigate amyloid-β (Aβ) ag-
capacity of the plant extracts to inhibit the growth of the promas- gregation, therefore being of potential interest to treat neurode-
tigote forms of Leishmania parasites, responsible for cutaneous generative disorders [108]. This compound is probably a major
leishmaniasis. The extract from E. altissima revealed a modest ac- contributor to the bioactivities of E. altissima.
tivity against Leishmania infantum (IC50 = 490.8 µg/mL) [46]. The plant contains many other compounds, including alka-
These are the only studies performed with samples of E. altissima loids, tannins, saponins, and cardiac glycosides, identified after
collected in Morocco. extraction with various organic solvents, notably with the plant
Other studies have evaluated the bioactivities of E. altissima ex- leaves extracted with ethanol [109]. Phenols, sterols, saponins,
tracts but with plant specimens collected from other countries. In tannins, terpenoids, flavonoids, and alkaloids have also been iden-
particular, a recent work evidenced the antibacterial effects of an tified in an E. altissima stem methanolic extract, and this extract
ethyl acetate extract from an Algerian sample of the plant (col- was found to affect male mice reproductive functions [110]. The
lected in Bouhmama County). It revealed inhibitory activities same methanolic extract was found to exhibit a dose-dependent
against the two enzymes, α-amylase (IC50 = 8.07 µg/mL) and pan- (500–3000 mg/kg) central nervous system depression and a mild
creatic lipase (IC50 = 289.1 µg/mL), coupled with an anti-inflam- antipsychotic activity without anxiolytic-like effects in mice [111].
matory effect (IC50 = 126.4 µg/mL), possibly explaining the activ- It is interesting to note that the fresh stems of this species contain

Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved. 341
 Reviews

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
▶ Fig. 4 E. altissima with the extraction process used to extract various natural products from the seeds, including the flavonoid cirsiliol or the
glutamate uptake inhibitor L‑CCG III (cis-α-(carboxycyclopropyl) glycine) from the fresh stems of the plant (photo of the plant from https://www.
teline.fr; photo credit: Jean-Claude Thiaudière).

neither ephedrine nor pseudoephedrine, but they contain sub- E. nebrodensis, notably a marked dose-dependent capacity to re-
stantial amounts of the two cis-diastereoisomers of the L-gluta- duce croton oil-induced ear edema in mice. The antioxidant effect
mate analogue (2S,3S,4R)-2-carboxycyclopropyl)-glycine (L- has been correlated to the high content of polyphenolics, flavo-
CCGIII) and (2S,3R,4S)-2-(carboxycyclopropyl) glycine (L-CCGIV) noids, and tannins [30, 61]. Cell protective effects were also ob-
(▶ Fig. 4 b). These two rare 2-(carboxycyclopropyl)-glycine (CCG) served. A 1 : 1 ethanolic : acetone extract from the aerial parts of
derivatives (which constitute about 1 % of the stem dry weight in the plant (collected from Arzana Province, Sardinia, Italy) has
the plant) alter neurotransmission. They selectively activate sub- shown a protective effect against cardiovascular damages in-
groups of glutamate receptors depending on stereochemistry. In duced by the anticancer drug doxorubicin in rats. The level of the
mammalian neurons, L-CCGIII potentiates responsiveness to L- antioxidant defense enzymes (GSH and SOD) was increased and
glutamate and L-CCGIV activates the N-methyl D-aspartate lipid peroxidation was reduced [115]. A phytochemical analysis
(NMDA) subtype of the L-glutamate receptor [112]. These com- performed using an essential oil from the related species E. nebro-
pounds provided the foundation for the design of novel modula- densis Tineo ex Guss. subsp. nebrodensis (from Italy) has shown the
tors of NMDA receptors [113]. presence of numerous volatile sesquiterpene hydrocarbons (citro-
nellol, β-patchoulene, etc.) [116, 117]. Much the same type of ter-
Ephedra nebrodensis Tineo (ex Guss.). penes have been found in other Ephedra-based volatile oils, such
This Ephedra species is a Mediterranean medicinal plant well dis- as (E)-phytol (10.1 % in the oil of E. fragilis), and benzaldehyde
tributed in Morocco and Algeria and is also found in Italy. It is a and cis-calamenene (8.0 and 3.6 %, respectively, in the oil of E. dis-
Macaronesian-Mediterranean nanophanerophyte growing in dry tachya) [118]. Two phenolic glycosides designated nebrodensides
and rocky places [114]. A 1 : 1 ethanolic : acetone crude extract A and B (▶ Fig. 5) have been isolated from the aerial parts of this
prepared from the aerial parts of a plant sample collected in Urzu- plant, together with (−)-epicatechin and (−)-ephedrine. The two
lei (Sardinia, Italy) has shown antioxidant and hypotensive effects, compounds were found inactive against proliferation of Madin-
as well as antinociceptive and anti-inflammatory activities. The Darby canine kidney (MDCK) cells and the influenza A virus [58].
presence of ephredrine-type alkaloids was suspected [59]. The Nebrodenside A has been found in Dodonaea viscosa (L.) (Spinda-
presence of ephedrine and pseudoephedrine (▶ Fig. 5) was evi- cea) and shown to exert anti-inflammatory and analgesic proper-
denced later when Hamoudi and coworkers performed a phyto- ties [119]. The compound has been isolated from the herb Leonto-
chemical screening of the same plant (aerial parts) collected in Al- podium leontopodioides (Willd.) Beauv. (Asteraceae) and charac-
geria. They identified the alkaloids together with phenolic com- terized as a modest inhibitor of lipase and α-glucosidase enzymes
pounds and a large fraction of flavonoids with antioxidant proper- (IC50 = 12.3 and 6.1 µM, respectively) [120]. The same product
ties [29, 61]. They further characterized the antioxidant, anti-in- was isolated from the aerial parts of Phagnalons ordidum L. (also
flammatory, and analgesic effects of a hydroalcoholic extract of Asteraceae) and shown to exert antioxidant activity [121]. Re-

342 Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved.
 This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
▶ Fig. 5 E. nebrodensis and the chemical structures of alkaloids ephedrine and pseudoephedrine and the two phenolic glycosides nebrodensides A–
B (photo of the plant from https://www.teline.fr; photo credit: Jean-Paul Peltier).

▶ Fig. 6 E. fragilis (stems) with a representation of the frugivorous lizard Podarcis lilfordi, which consumes the plant seeds and importantly contrib-
utes to their dispersion. The phenolic compound gallic acid (isolated from the stems) contributes to the antioxidant properties of the extract
through interaction with the receptor for advanced glycation end products (RAGE; molecular structure from PDB: 2MOV) (photo of the plant from
https://www.teline.fr; photo credit: Jean-Paul Peltier).

cently, a computational study has suggested that this compound tors to the dispersion of the plant seeds, such as the frugivorous
could be used as an inhibitor of severe acute respiratory syndrome Balearic lizard Podarcis lilfordi Günter (Lacertidae) [123, 124].
coronavirus 2 (SARS‑CoV‑2) responsible for COVID-19, owing to Through its intense frugivorous activity, this lizard plays a more
its capacity to bind to the receptor-binding domain of the virus important role than insects in pollination and seed dispersal
Spike glycoprotein [122]. [125] (▶ Fig. 6).
In Morocco, the plant can be found in the Souss-Massa region
Ephedra fragilis Desf. (Taroudant Province). An authenticated sample collected in the
The evergreen species E. fragilis (vernacular name: joint pine) is a city of Oulad Teima, near Taroudant, has led to the preparation
fleshy-fruited tall scrambling shrub (up to 1.8 m) growing essen- of an ethanolic extract further fractionated using ethyl acetate
tially on rocky hills and stone walls. It is native to the eastern Med- (EA). This EA fraction has revealed a high content of phenolic and
iterranean region of southern Europe and Northern Africa, and flavonoid compounds and strong antioxidant activity. The fraction
from Madeira and the Canary Islands (Spain). It grows primarily protected cultured cells (from Tetrahymena pyriformis) against ox-
in the subtropical biome. Small animals are important contribu- idative stress injury induced by hydrogen peroxide, protecting

Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved. 343
 Reviews

ported with caffeic acid [132]. It is therefore not surprising to ob-

serve that a plant extract containing the same type of phenolic
compounds and alkaloids (with α-adrenoceptor activity) can also
affect lymphocyte activities. Ephedrine has been shown to atten-
uate oxidative damages in epithelial cells, through regulation of
endoplasmic reticulum (ER) stress [133].
Several studies have underlined the anti-inflammatory action
of ephedrine and ephedrine-containing extracts from various
Ephedra species [16, 134–136]. An extract of E. fragilis made from
a Tunisian specimen revealed dose-dependent anti-inflammatory
effects, with inhibition of the production of nitric oxide (NO) in li-
popolysaccharide-stimulated RAW 264.7 macrophages. The etha-
▶ Fig. 7 E. distachya (stems) from which the polysaccharides ephe- nolic extract contained high levels of both caffeic acid and hydrox-
ycinnamic acid [137]. This latter compound notoriously exerts

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
drans A–E can be isolated. These water-soluble polymers exhibit
antioxidant and hypoglycemic properties [35] (photo of the plant antioxidant activity and modulates proinflammatory cytokines
from https://inpn.mnhn.fr; photo credit: P. Rouveyrol). [138].

Ephedra distachya L.
This shrub species (also known as Ephedra vulgaris Rich. or sea
these cells from DNA damage and metabolic oxidation. The ex- grape) is a major component of desert vegetation. It can be found
tract showed potent antioxidant activities [55]. The extraction in North Africa (Morocco, Algeria) but also in sand dunes of tem-
process has been optimized and several bioactive compounds perate deserts, such as the Gurbantünggüt desert in the Junggar
were isolated from the modified EA fraction, notably four phenolic Basin (northwestern China), and in Central Asia, for example [139,
compounds (caffeic acid, ferulic acid, gallic acid, and vanillic acid) 140]. It can be found as well in clay steppes of the Ulyanovsk re-
and two conventional flavonoids (rutin and quercetin). The phe- gion in Russia [141], the Balkan Peninsula in Serbia [142], and the
nolic derivatives were characterized as the main components re- dunes of Letea in Romania [143, 144].
sponsible for both antioxidant and antiglycation activities of the From a phytochemical viewpoint, this species has been less in-
extract [83]. A complementary molecular modeling analysis (in sil- vestigated than the other aforementioned species. This herb is
ico) suggested that gallic acid can form stable complexes with the rich in catechins, which possess antioxidant activities [145], and
receptor for advanced glycation end product (RAGE) [83] also contains large amounts of pseudoephedrine (1.25–1.59 % of
(▶ Fig. 6). This is not surprising because these phenolic derivatives dry weight), a sympathomimetic used to treat symptoms of the
present high affinities for the different proteins of the HMGB1/ common cold and flu, sinusitis, asthma, and bronchitis [74]. The
RAGE/NF-κB signaling pathway and gallic acid is known to reduce subspecies E. distachya subsp. helvetica (from Vienna, Austria)
the risk of AGE-mediated cellular complications, preventing fibro- was shown to contain 20.8 mg of (pseudo)ephedrine per gram of
sis induced by advanced glycation end products [126–128]. dry weight, which is less than the content in E. fragilis (27.1 mg/g)
Total organic carbon (TOC) is particularly high in E. fragilis com- [43]. However, the ephedrine content may vary substantially from
pared to other plants growing on semiarid Mediterranean soils one plant to another because another study indicated that ephe-
[129]. Nevertheless, this species contains many less phenolic drine was not detected in the species E. distachya subsp. helvetica
compounds than the other studied Ephedra species (notably 8- [146]. Its content in phenolic and flavonoid compounds is not par-
fold less phenols than E. alata) and less flavonoids as well, but a ticularly high (largely inferior to that found in E. alata, for exam-
high content in ephedrine alkaloids [43]. The main characteristic ple), but this species does present a high content of total alkaloids
of E. fragilis is the presence of the two alkaloids, pseudoephedrine (15.8 mg/g compared to 0.2 mg/g in E. fragilis) [43]. These alka-
and ephedrine, in the different parts of the plants. Pseudoephe- loids have not been characterized formally but the phylogenetic
drine is a stereoisomer of ephedrine (▶ Fig. 5) that is commonly similarities between E. distachya and the well-studied analogous
used as a nasal decongestant in combination with other anti-in- species Ephedra sinica [147] suggest that it may contain similar al-
flammatory drugs for the symptomatic treatment of some com- kaloids such as the ephedrannins largely present in E. sinica [148].
mon pathologies such as the common cold. The alkaloid content Cell suspension cultures (callus) of E. distachya have been devel-
is very high in E. fragilis flowers, which contain both alkaloids oped and used to elicit the production of phytoalexin p-coumar-
(1.86 %) whereas the seeds essentially contain pseudoephedrine oylamino acids by the addition of a yeast extract to the culture
(0.62 %) and the branches a little quantity of ephedrine (0.054 %), [149–151].
as determined with a specimen of E. fragilis from Malta [130]. A characteristic of E. distachya is the content in glycans called
Ephedrine and pseudoephedrine can exert immunomodulatory ephedrans A, B, C, D, and E, with hypoglycemic and antioxidant
activities. Notably, pseudoephedrine has been shown to modulate activities [48] (▶ Fig. 7). They have a different molecular mass
T cell activation, via the inhibition of interleukin-2 (IL-2) and TNF-α (from 6.6 × 103 to 1.5 × 106 Da) and varied monosaccharide com-
gene transcription in stimulated Jurkat T cells, thereby inhibiting positions, with the presence of trehalose and xylose in ephedrans
the transcriptional activity of proteins JNK and AP-1 (activator pro- A and B, and various proportion of rhamnose and arabinose [148].
tein-1) [131]. Similar T cell deactivation effects have been re- These polysaccharides also display anti-inflammatory activity

344 Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved.
[152]. Similar polysaccharides with antihypertensive and antioxi- tory action of isoschaftoside found in E. alata, for example [95].
dant activities have been characterized in other species, such as This compound is a potent antioxidant and an anti-inflammatory
E. alata [153]. agent with an anti-steatosis activity useful to combat metabolic
liver disease [165, 166]. Other flavonol glycosides, such as iso-
Clinical trials with Ephedra-based products rhamnetin-3-O-rutinoside, contribute similarly to the antioxidant
Medicinal products containing Ephedra extracts or ephedrine are and anti-inflammatory effects [16]. This compound is also a pro-
not frequently used nowadays due to the adverse effects reported apoptotic agent, useful to limit the growth of cancer cells [167]. It
with Ephedra preparations in the past (see Discussion below). would be interesting to apply network pharmacology approaches
However, there are rare clinical trials that concern Ephedra, nota- to determine how these different metabolites participate and co-
bly with Chinese medicines containing Mahuang (Ephedrae her- operate to promote the activity of the plant extract. This type of
ba). For example, trial NCT03733873 has evaluated the Ephedra- approach has proved useful to predict the combinatorial effects of
containing Chinese medicine Suoquan for the treatment of noc- Ephedrae herba components [162, 168–170].
turnal enuresis [154]. Trial NCT00432991 evaluated the effect of Evidently, alkaloids are essential components of the extracts,
intramuscular ephedrine on the incidence of nausea and vomiting most of them containing either ephedrine and/or pseudoephe-

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
in women during and after a Cesarean section. The objective was drine. Their content varies from one Ephedra species to another,
to reduce or prevent hypotension [155]. Ephedrine and phenyl- depending on diverse plant growth parameters, such as altitude.
ephrine can be safely used to counteract hypotension after spinal It has been observed recently with another species (Ephedra saxa-
anesthesia in obstetric patients, but the safety of the product ad- tilis) that the ephedrine content increased as the altitude gradient
ministration requires careful monitoring [156, 157]. We will not increased, and pseudoephedrine decreased as the altitude gra-
discuss further ephedrine-based trials so as to maintain a focus dient decreased [171]. There is also a seasonal variation of the al-
on Ephedra plants and extracts. kaloid content [161]. Their concentrations vary greatly according
to plant species, the collection location, and cultivation conditions
[172, 173]. Both ephedrine and pseudoephedrine are key medici-
Discussion nal components of almost all Ephedra, and their contents in Ephe-
Plants of the Ephedraceae family and Ephedra species in particular dra formulations can be precisely estimated from the compound-
are used in many countries all over the world to treat human dis- ing amount of the starting Ephedra plant [160]. They are useful
eases. One of the most popular Ephedra-based medicinal herbs is medications to prevent or treat hypotension, for example, owing
the one called Mahuang in Chinese, which corresponds to the her- to their indirect sympathomimetic pharmacodynamic properties
baceous stem of E. sinica Stapf, Ephedra intermedia Schrenk et C. A. [174] but their use remains controversial, because they can also
Mey., and Ephedra equisetina Bge. [158]. Mahuang decoctions induce cardiovascular side effects, including stroke and heart at-
(Ephedrae herba) are largely used in China to treat asthma, liver tack [175, 176]. Pseudoephedrine was considered potentially
disease, skin disease, and other diseases [4, 5]. Ephedrae herba more useful than ephedrine due to its anorexigenic effect and its
(Maoto) is also used in traditional Japanese medicine (Kampo) capacity to influence lipolysis and thermogenesis. But the use of
[159, 160], based notably on the cultivation of E. sinica [161]. The this product is also associated with effects on the cardiovascular
same species is also used in the Republic of Korea, notably to com- and central nervous systems. Its prescription to obese patients is
bat obesity [162, 163]. Ephedra species can be found on all conti- not at all recommended [177]. These considerations have
nents and many of them are associated with traditional medicinal prompted the development of ephedrine alkaloid-free Ephedra
usage. The bracts of Ephedra cones have played a crucial role in herb extracts [21, 24, 178]. Beyond flavonoids and alkaloids, Ephe-
long-distance seed dispersal that is responsible for a wide distribu- dra extracts also contain useful terpenoids, carboxylic acids, tan-
tion of the genus in semiarid and arid areas of Eurasia, North Afri- nins, and other types of constituents such as unsaturated fatty ac-
ca, North America, and South America [164]. Ephedra species are ids [55, 97, 179, 180]. The polysaccharides found in the stems of E.
commonly exploited for their anti-inflammatory, anticancer, anti- alata are particularly interesting products due to their contribu-
bacterial, antioxidant, hepatoprotective, anti-obesity, antiviral, tion to the antihypertensive and antioxidant activities of the ex-
and diuretic activities [11, 148]. To our knowledge, seven Ephedra tracts [153]. Ephedra polysaccharides warrant further considera-
species are present in Morocco, including five used traditionally to tion to improve their identification and contribution to extract ac-
treat diverse symptoms and/or pathologies (Fig. ▶ 1). Four species tivities [181, 182].
are clearly listed as being used to treat inflammatory diseases Ephedrine was well recognized as a dependable asthma treat-
(such as rheumatism) or other pathologies: E. alata (the most fre- ment in the Western world by the mid-1930 s. Primitive inhalers
quently used species), E. altissima, E. fragilis, and E. nebrodensis. were created to provide ephedrine alkaloids, and they become
The ethnobotanical use of E. distachya in Morocco is very likely, the main oral asthma medications in the 1940 s and 1950 s [3].
but firm evidence is lacking. Nevertheless, this species is with no Ephedrine was widely used and readily available, but over time, it
doubt a medicinal plant used in the surrounding Mediterranean was realized that the alkaloid was more toxic than initially
area. thought.
The medicinal activities of Moroccan Ephedra extracts can be Ephedra was appointed as a weight-loss and energy-en-
linked to the presence of diverse bioactive products, in particular hancement supplement in the US in the 1990 s and early 2000 s.
ephedrine-type alkaloids and glycosylated flavonoids. Among the It was categorized as an herbal supplement under the Dietary
many beneficial flavonoids, one can underline the anti-inflamma- Supplement Health and Education 1994 [183, 184]. No evidence

Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved. 345
 Reviews

proved Ephedra’s effectiveness other than short-term weight loss. constituents and their mechanism of action. The validated names
However, the number of reported adverse events increased [185]. of the different Ephedra species have been checked (http://www.
In 2004, the Food and Drug Administration (FDA) in the United worldfloraonline.org, accessed on September 10, 2023).
States received over 18 000 reports of harmful events associated
with Ephedra, and banned dietary supplements with ephedrine al-
kaloids [4, 185]. The same ban of Ephedra was imposed in the
Conclusion and Outlook
European Union by the European Commission in 2015. Among Five medicinal Ephedra species present in Morocco were identi-
the toxic responses to Ephedra use are increased blood pressure, fied, namely, E. alata, E. altissima, E. distachya, E. fragilis, and E. ne-
excitement, sweating, and dysuria, in addition to more serious brodensis. They are used locally in the Moroccan traditional phar-
events like arrhythmia, nephritis, gallstones, and possibly death macopeia to treat a variety of human diseases, such as asthma,
due to myocardial infarction and stroke or respiratory failure [4, rheumatism, hypertension, diabetes, cancer, and other patholo-
183, 184]. gies. The pharmacological evidence necessary to support their
Altogether, our analysis identified the Ephedra species used tra- clinical use remains somewhat insufficient at present for these
ditionally in Morocco and provided useful information to establish Moroccan species. Further studies are encouraged to better sup-

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
links between the pharmacological effects observed with the port the medicinal use of these plants.
plant extracts and the nature of bioactive natural products identi-
fied in those preparations. Moroccan Ephedra plants, notably the Contributorsʼ Statement
two most frequently used regional species E. alata and E. altissima, Data collection: M. Chroho; Design of the study: C. Bailly, L. Bouis-
represent key medicinal plants for the country. Their traditional sane; Drafting the manuscript: M. Chroho, C. Bailly, L. Bouissane;
use can be encouraged, but always with caution due the presence Investigation: C. Bailly, L. Bouissane; Visualization: C. Bailly, L.
of potentially harmful ephedrine-type alkaloids [18, 183, 185]. Bouissane; Revision and editing of the manuscript: L. Bouissane;
Their use should be accompanied with health information when- Supervision of the final version of the manuscript: C. Bailly, L.
ever possible. In this respect, the danger of using Arabic YouTube Bouissane.
videos regarding herbal cancer treatment has been pointed out
recently [186]. There is no reason to ban the traditional use of Mo- Funding Information
roccan Ephedra extracts to treat some human infections, notably
inflammatory symptoms, making profit of the abundance, relative This research did not receive any specific grant from funding agencies in
safety, and beneficial functional attributes of the products. But it the public, commercial, or not-for-profit sectors.
would be useful to assess the toxicological profile of such extracts
in parallel, so as to better understand the efficacy, safety, and Acknowledgements
quality of the available products.
Finally, beyond the health benefits, it is interesting to note that The authors are thankful to Sultan Moulay Slimane University, Morocco,
for partial support.
the same type of Moroccan Ephedra extracts can be used in the
field of green chemistry. An aqueous plant extract of E. alata has
Conflict of Interest
proved efficient when used as a reducing and capping agent for
the synthesis of copper oxide nanoparticles [187]. Similarly, other
The authors declare that they have no conflict of interest.
Ephedra extracts have been used to prepare various types of com-
posite nanoparticles [187–190]. A bright future may be antici-
References
pated in front of Ephedra plant extracts in medicine, green chem-
istry, and the food industry.
[1] Guo L, Gao Y, He P, He Y, Meng F. Modeling for predicting the potential
geographical distribution of three Ephedra herbs in China. Plants 2023;
12: 787
Materials and Methods
[2] Uema M, Hyuga M, Yonemitsu K, Hyuga S, Amakura Y, Uchiyama N, Miz-
The scientific literature pertaining to Ephedra species found in Mo- oguchi K, Odaguchi H, Goda Y. Antiviral effect of ephedrine alkaloids-
rocco was searched through the databases of PubMed Central, free ephedra herb extract against SARS‑CoV‑2 in vitro. Microorganisms
2023; 11: 534
Web of Science, and Google Scholar. The article search was per-
formed essentially from January to September 2023, using indi- [3] Lee MR. The history of Ephedra (ma-huang). J R Coll Physicians Edinb
2011; 41: 78–84
vidual key words (Ephedra, Ephedrae herba, ephedrine, Ephedra al-
[4] Tang S, Ren J, Kong L, Yan G, Liu C, Han Y, Sun H, Wang XJ. Ephedrae
kaloids) and combinations to cover all scientific data reported
herba: A review of its phytochemistry, pharmacology, clinical applica-
thus far on the plant family. Databases from various publishers, tion, and alkaloid toxicity. Molecules 2023; 28: 663
such as ScienceDirect, Springer, Wiley, and others were also con-
[5] Zheng Q, Mu X, Pan S, Luan R, Zhao P. Ephedrae herba: A comprehensive
sulted. About 250 publications were reviewed and priority was review of its traditional uses, phytochemistry, pharmacology, and toxi-
given to the most recent studies. Publications (mostly in the Eng- cology. J Ethnopharmacol 2023; 307: 116153
lish language) and written information (including those in Arabic [6] Zhang J, Li Y, Chen X, Pan Y, Zhang S, Wang Y. Systems pharmacology
language) providing a precise location of the plant were taken in- dissection of multi-scale mechanisms of action for herbal medicines in
to consideration. Other studies not specifying the geographical stroke treatment and prevention. PLoS One 2014; 9: e102506

origin of the plant were only considered for analysis of the phyto-

346 Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved.
[7] Liu X, Ke S, Wang X, Li Y, Lyu J, Liu Y, Geng Z. Interpretation of the anti- Ephedra Herb extract administered orally to mice. J Ethnopharmacol
influenza active ingredients and potential mechanisms of Ge Gen De- 2023; 301: 115827
coction based on spectrum-effect relationships and network analysis. [24] Odaguchi H, Sekine M, Hyuga S, Hanawa T, Hoshi K, Sasaki Y, Aso M,
J Ethnopharmacol 2024; 319: 117290 Yang J, Hyuga M, Kobayashi Y, Hakamatsuka T, Goda Y, Kumagai Y. A
[8] Pliny the Elder. Natural History: Book XXVI: Chapter XX. Translation by H. double-blind, randomized, crossover comparative study for evaluating
Rackham. London: Loeb Classical Library; 1952 the clinical safety of ephedrine alkaloids-free Ephedra Herb Extract
[9] Abourashed EA, El-Alfy AT, Khan IA, Walker L. Ephedra in perspective – A (EFE). Evid Based Complement Alternat Med 2018; 2018: e4625358
current review. Phytother Res 2003; 17: 703–712 [25] Yoshimura M, Amakura Y, Hyuga S, Hyuga M, Nakamori S, Maruyama T,
[10] Ismail S, Gaglione R, Masi M, Padhi S, Rai AK, Omar G, Cimmino A, Arciel- Oshima N, Uchiyama N, Yang J, Oka H, Ito H, Kobayashi Y, Odaguchi H,
lo A. Ephedra foeminea as a novel source of antimicrobial and anti-biofilm Hakamatsuka T, Hanawa T, Goda Y. Quality evaluation and characteriza-
compounds to fight multidrug resistance phenotype. Int J Mol Sci 2023; tion of fractions with biological activity from Ephedra Herb extract and
24: 3284 ephedrine alkaloids-free ephedra herb extract. Chem Pharm Bull (Tokyo)
2020; 68: 140–149
[11] González-Juárez DE, Escobedo-Moratilla A, Flores J, Hidalgo-Figueroa S,
Martínez-Tagüeña N, Morales-Jiménez J, Muñiz-Ramírez A, Pastor-Pala- [26] Sadeghi Dousari A, Karimian Amroabadi M, Soofi Neyestani Z, Taati
cios G, Pérez-Miranda S, Ramírez-Hernández A, Trujillo J, Bautista E. A re- Moghadam M, Satarzadeh N. The use of Ephedra herbs in the treatment

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
view of the Ephedra genus: Distribution, ecology, ethnobotany, phyto- of COVID‑19. Avicenna J Phytomed 2023; 13: 231–239
chemistry and pharmacological properties. Molecules 2020; 25: 3283 [27] Al-Nemi R, Makki AA, Sawalha K, Hajjar D, Jaremko M. Untargeted me-
[12] Ma XH, Lu YY, Huang DD, Zhu TT, Lv PL, Jin L. [Ecology suitability study of tabolomic profiling and antioxidant capacities of different solvent crude
Ephedra intermedia. Zhongguo Zhong Yao Za Zhi 2017; 42: 2068–2071 extracts of Ephedra foeminea. Metabolites 2022; 12: 451

[13] Elhadef K, Smaoui S, Fourati M, Ben Hlima H, Chakchouk Mtibaa A, Sell- [28] Khalil M, Khalifeh H, Saad F, Serale N, Salis A, Damonte G, Lupidi G, Daher
em I, Ennouri K, Mellouli L. A review on worldwide Ephedra history and A, Vergani L. Protective effects of extracts from Ephedra foeminea Forssk
story: From fossils to natural products mass spectroscopy characteriza- fruits against oxidative injury in human endothelial cells.
tion and biopharmacotherapy potential. Evid Based Complement Alter- J Ethnopharmacol 2020; 260: 112976
nat Med 2020; 2020: e1540638 [29] Hamoudi M, Amroun D, Boutefnouchet S, Bensouici C, Kaoula S, Harzal-
[14] Bourhia M, Abdelaziz Shahat A, Mohammed Almarfadi O, Ali Naser F, lah D, Khennouf S, Dahamna S. Phytochemical screening, in vitro antiox-
Mostafa Abdelmageed W, Ait Haj Said A, El Gueddari F, Naamane A, Ben- idant and enzyme inhibitory properties, and acute toxicity of extracts
bacer L, Khlil N. Ethnopharmacological survey of herbal remedies used from the aerial parts of Ephedra nebrodensis, a source of bioactive com-
for the treatment of cancer in the greater Casablanca-Morocco. Evid pounds. Comb Chem High Throughput Screen 2022; 25: 1058–1071
Based Complement Alternat Med 2019; 2019: 1–9 [30] Hamoudi M, Amroun D, Baghiani A, Khennouf S, Dahamna S. Antioxi-
[15] Hachi M, Hachi T, Essabiri H, Ainane T, Yaakoubi AE, Zidane L. Floristic dant, anti-inflammatory, and analgesic activities of alcoholic extracts of
analysis of the medicinal flora used by the population of the Central Mid- Ephedra nebrodensis from Eastern Algeria. Turk J Pharm Sci 2021; 18:
dle Atlas (Morocco). IOP Conf Ser Earth Environ Sci 2022; 1090: 012025 574–580

[16] Mufti A, Contreras MDM, Gómez-Cruz I, Alshamrani A, Nahdi S, Mansour [31] Mahmoudi M, Boughalleb F, Maaloul S, Mabrouk M, Abdellaoui R. Phyto-
L, Alwasel S, Harrath AH, Tlili N. Ephedra alata Subsp. alenda as a novel chemical screening, antioxidant potential, and LC–ESI–MS profiling of
source of bioactive phytochemicals: Characterization based on the mass Ephedra alata and Ephedra altissima seeds naturally growing in Tunisia.
spectrometry and profiling of antioxidant and anti-inflammatory prop- Appl Biochem Biotechnol 2023; 195: 5903–5915
erties. Life (Basel) 2023; 13: 323 [32] Ghavam M, Soleimaninejad Z. An overview of the various uses of Ephedra
[17] Rahhal B, Jaradat N, Shraim WBM, Zyoud A, Hattab S. The diuretic activ- distachya L. from the past to the present. Avicenna J Pharm Res 2020; 1:
ity of Ephedra alata and Plumbago europaea in mice using an aqueous ex- 82–86
tract. Moroc J Chem 2018; 6: 569–576 [33] Global Biodiversity Information Facility. Ephedra alata. Accessed Novem-
[18] Lai S, Yu C, Dennehy CE, Tsourounis C, Lee KP. Online marketing of Ephe- ber 16, 2023 at: https://www.gbif.org/species/2653286
dra weight loss supplements: Labeling and marketing compliance with [34] Abouri M, Mousadik AE, Msanda F, Boubaker H, Saadi B, Cherifi K. An eth-
the U.S. food and drug administration ban on ephedra. J Altern Comple- nobotanical survey of medicinal plants used in the Tata Province, Moroc-
ment Med 2021; 27: 796–802 co. Int J Med Plant Res 2012; 1: 99–123
[19] Lee E, Yoon SH, Kim H, Kim YD, Leem J, Park J. Ephedrae Herba in combi- [35] El Maaiden E, Qarah N, Ezzariai A, Mazar A, Nasser B, Moustaid K, Bouk-
nation with herbal medicine (Zhizichi decoction and Phellodendri Cor- cim H, Hirich A, Kouisni L, El Kharrassi Y. Ultrasound-assisted extraction
tex) for weight reduction: A case series. Integr Med Res 2020; 9: 100408 of isoquercetin from Ephedra alata (Decne): Optimization using response
[20] Kharchoufa L, Bouhrim M, Bencheikh N, Addi M, Hano C, Mechchate H, surface methodology and in vitro bioactivities. Antioxidants (Basel)
Elachouri M. Potential toxicity of medicinal plants inventoried in North- 2023; 12: 725
eastern Morocco: An ethnobotanical approach. Plants 2021; 10: 1108 [36] Idmʼhand E, Msanda F, Cherifi K. Ethnobotanical study and biodiversity
[21] Takemoto H, Takahashi J, Hyuga S, Odaguchi H, Uchiyama N, Maruyama of medicinal plants used in the Tarfaya Province, Morocco. Acta Ecol Sin
T, Yamashita T, Hyuga M, Oshima N, Amakura Y, Hakamatsuka T, Goda 2020; 40: 134–144
Y, Hanawa T, Kobayashi Y. Ephedrine alkaloids-free ephedra herb ex- [37] Ziani BEC, Heleno SA, Bachari K, Dias MI, Alves MJ, Barros L, Ferreira ICFR.
tract, EFE, has no adverse effects such as excitation, insomnia, and ar- Phenolic compounds characterization by LC‑DAD- ESI/MSn and bioactive
rhythmias. Biol Pharm Bull 2018; 41: 247–253 properties of Thymus algeriensis Boiss. & Reut. and Ephedra alata Decne.
[22] Hyuga S, Hyuga M, Oshima N, Maruyama T, Kamakura H, Yamashita T, Food Res Int 2019; 116: 312–319
Yoshimura M, Amakura Y, Hakamatsuka T, Odaguchi H, Goda Y, Hanawa [38] Benabderrahim MA, Yahia Y, Bettaieb I, Elfalleh W, Nagaz K. Antioxidant
T. Ephedrine alkaloids-free Ephedra Herb extract: A safer alternative to activity and phenolic profile of a collection of medicinal plants from Tu-
ephedra with comparable analgesic, anticancer, and anti-influenza activ- nisian arid and Saharan regions. Ind Crops Prod 2019; 138: 111427
ities. J Nat Med 2016; 70: 571–583 [39] Mighri H, Akrout A, Bennour N, Eljeni H, Zammouri T, Neffati M. LC/MS
[23] Huang X, Hyuga S, Amakura Y, Hyuga M, Uchiyama N, Hakamatsuka T, method development for the determination of the phenolic compounds
Goda Y, Odaguchi H, Hanawa T, Kobayashi Y. Overlooked switch from of Tunisian Ephedra alata hydro-methanolic extract and its fractions and
transient sedation to sustained excitement in the Biphasic effects of evaluation of their antioxidant activities. South Afr J Bot 2019; 124: 102–
110

Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved. 347
 Reviews

[40] Al-Rimawi F, Abu-Lafi S, Abbadi J, Alamarneh AAA, Sawahreh RA, Odeh I. [60] Sekiewicz K, Sekiewicz M, Romo A, Didukh Y, Fennane M, Boratynski A.
Analysis of phenolic and flavonoids of wild Ephedra alata plant extracts Chorological and conservation status of the endemic cypress, Cupressus
by LC/PDA and LC/MS and their antioxidant activity. Afr J Tradit Comple- atlantica Gaussen, in the High Atlas (Morocco). Dendrobiology 2014; 71:
ment Altern Med 2017; 14: 130–141 3–13
[41] Rydin C, Pedersen KR, Friis EM. On the evolutionary history of Ephedra: [61] Hamoudi M, Amroun D, Khennouf S, Dahamna S. Antioxidant evaluation
Cretaceous fossils and extant molecules. Proc Natl Acad Sci U S A 2004; and polyphenol contents of hydro ethanolic extractʼs fractions from
101: 16571–16576 Ephedra nebrodensis. J Drug Deliv Ther 2020; 10: 314–319
[42] Global Biodiversity Information Facility. Ephedra altissima Desf. Accessed [62] Lemhadri A, Achtak H, Lamraouhi A, Louidani N, Benali T, Dahbi A,
November 16, 2023 at: https://www.gbif.org/species/2653284 Bouyahya A, Khouchlaa A, Shariati MA, Hano C, Lorenzo JM, Chen JT,
[43] Ibragic S, Sofić E. Chemical composition of various Ephedra species. Bosn Lyoussi B. Diversity of medicinal plants used by the local communities
J Basic Med Sci 2015; 15: 21–27 of the coastal plateau of Safi province (Morocco). Front Biosci (Schol
Ed) 2023; 15: 1
[44] Rydin C, Korall P. Evolutionary relationships in Ephedra (Gnetales), with
implications for seed plant phylogeny. Int J Plant Sci 2009; 170: 1031– [63] Lyoussi B, Bakour M, Cherkaoui-Tangi K, El-Hilaly J, Hano C. Ethnobotan-
1043 ical survey and pharmacological screening of medicinal plants used as
antihypertensive in Sefrou province (middle-north of Morocco): Benefits
[45] Zeouk I, Balouiri M, Bekhti K. Antistaphylococcal activity and phyto-

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
and challenges. Front Biosci (Schol Ed) 2023; 15: 4
chemical analysis of crude extracts of five medicinal plants used in the
center of Morocco against dermatitis. Int J Microbiol 2019; 2019: 1–7 [64] Hinad I, Sʼhih Y, Elhessni A, Mesfioui A, Ouahidi ML. Medicinal plants
used in the traditional treatment of diabetes in Ksar Elkebir Region
[46] Zeouk I, Et-Touys A, Balouiri M, Fellah H, Lalami AEO, Bekhti K. Leishma-
(North-Western Morocco). Pan Afr Med J 2022; 42: 319
nicidal activity of plant extracts from Sefrou, a Moroccan focus of leish-
maniasis, against various leishmania parasites in the promastigote stage. [65] Eddouks M, Ajebli M, Hebi M. Ethnopharmacological survey of medicinal
Phytothérapie 2019; 17: 83–89 plants used in Daraa-Tafilalet region (Province of Errachidia), Morocco.
J Ethnopharmacol 2017; 198: 516–530
[47] Global Biodiversity Information Facility. Ephedra distachya L. Accessed
November 16, 2023 at: https://www.gbif.org/species/2653321 [66] El Hachlafi N, Benkhaira N, Ferioun M, Kandsi F, Jeddi M, Chebat A, Addi
M, Hano C, Fikri-Benbrahim K. Moroccan medicinal plants used to treat
[48] Konno C, Mizuno T, Hikino H. Isolation and hypoglycemic activity of
cancer: Ethnomedicinal study and insights into pharmacological evi-
ephedrans A, B, C, D and E, glycans of Ephedra distachya herbs. Planta
dence. Evid Based Complement Alternat Med 2022; 2022: 1–19
Med 1985; 51: 162–163
[67] Ajjoun M, Kharchoufa L, Alami Merrouni I, Elachouri M. Moroccan medic-
[49] McGregor HV, Dupont L, Stuut JBW, Kuhlmann H. Vegetation change,
inal plants traditionally used for the treatment of skin diseases: From
goats, and religion: A 2000-year history of land use in southern Morocco.
ethnobotany to clinical trials. J Ethnopharmacol 2022; 297: 115532
Quat Sci Rev 2009; 28: 1434–1448
[68] Bencheikh N, Elbouzidi A, Kharchoufa L, Ouassou H, Alami Merrouni I,
[50] Cheddadi R, Palmisano A, López-Sáez JA, Nourelbait M, Zielhofer C, Tabel
Mechchate H, Es-Safi I, Hano C, Addi M, Bouhrim M, Eto B, Elachouri M.
J, Rhoujjati A, Khater C, Woodbridge J, Lucarini G, Broodbank C, Fletcher
Inventory of medicinal plants used traditionally to manage kidney dis-
WJ, Roberts CN. Human demography changes in Morocco and environ-
eases in north-eastern Morocco: ethnobotanical fieldwork and pharma-
mental imprint during the Holocene. The Holocene 2019; 29: 816–829
cological evidence. Plants 2021; 10: 1966
[51] Bolinder K, Humphreys AM, Ehrlén J, Alexandersson R, Ickert-Bond SM,
[69] Chaachouay N, Azeroual A, Bencharki B, Zidane L. Herbal medicine used
Rydin C. From near extinction to diversification by means of a shift in
in the treatment of cardiovascular diseases in the Rif, North of Morocco.
pollination mechanism in the gymnosperm relict Ephedra (Ephedraceae,
Front Pharmacol 2022; 13: 921918
Gnetales). Bot J Linn Soc 2016; 180: 461–477
[70] Barkaoui M, Msanda F, Boubaker H, El-Boullani R, Asri OE, Chokri A, El-
[52] Askew RR, Nieves-Aldrey JL. Eupelmidae (hymenoptera, chalcidoidea) of
Yaagoubi M, Koutaya A, Eloirdi A, Arifi K, Chahboune M. Ethnobotany,
Iberia and the Canary Islands: An annotated checklist with descriptions
traditional knowledge, and nutritional value of Argan (Argania spinosa
of some previously unrecognised males and a new species of calosota
(L.) Skeels) in Western Anti-Atlas of Morocco. Braz J Biol 2022; 84:
curtis, 1836. Graellsia 2017; 73: e065
e260477
[53] Patra B, Bera S, Molchanoff S, Wang Y, Yang J, Li C. Morpho-anatomy of
[71] Heleno SA, Martins A, Queiroz MJRP, Ferreira ICFR. Bioactivity of phenolic
Xerephedromiya ustjurtensis (Diptera: Cecidomyiidae) induced galls and
acids: Metabolites versus parent compounds: A review. Food Chem
intersexual variation of gall density in Ephedra distachya L. (Ephedraceae)
2015; 173: 501–513
from Ukraine. Acta Bot Hung 2012; 54: 377–389
[72] Zhao X, Dupont L, Cheddadi R, Kölling M, Reddad H, Groeneveld J, Ain-
[54] Global Biodiversity Information Facility. Ephedra fragilis Desf. Accessed
Lhout FZ, Bouimetarhan I. Recent climatic and anthropogenic impacts
November 16, 2023 at: https://www.gbif.org/species/2653414
on endemic species in southwestern Morocco. Quat Sci Rev 2019; 221:
[55] Guenaou I, Nait Irahal I, Errami A, Lahlou FA, Hmimid F, Bourhim N. Bio- 105889
active compounds from Ephedra fragilis: Extraction optimization, chemi-
[73] Kakiuchi N. [Phylogenic analysis and evaluation of ephedra plants and
cal characterization, antioxidant and antiglycation activities. Molecules
aconites for medicinal use.] Yakugaku Zasshi 2017; 137: 1193–1200
2021; 26: 5998
[74] Minami M, Taichi F, Honda Y, Ueno K, Shinozaki J, Itoh S, Takano A, Ber-
[56] Taleb MS, Fennane M. Flora of the biological and ecological interest site
diyar J, Maltsev II, Nakane T. Environmental and soil characteristics in
(BEIS) of Tichoukt mountain (middle atlas, Morocco). Nat Technol C‑Sci
Ephedra habitats of Uzbekistan. J Nat Med 2021; 75: 246–258
Environ 2016; 1: 2–9
[75] Qazilbash NA. Pakistan ephedra. II. comparative study of Ephedra nebro-
[57] Global Biodiversity Information Facility. Ephedra nebrodensis Tineo. Ac-
densis and Ephedra gerardiana. Pharm Weekbl 1971; 106: 373–382
cessed November 16, 2023 at: https://www.gbif.org/species/2653437
[76] Boufous H, Marhoume F, Chait A, Bagri A. Ethnopharmacological survey
[58] Cottiglia F, Bonsignore L, Casu L, Deidda D, Pompei R, Casu M, Floris C.
of medicinal plants with hallucinogenic effect and used against pain, in-
Phenolic constituents from Ephedra nebrodensis. Nat Prod Res 2005; 19:
flammatory diseases, diabetes and urinary lithiasis in Zagora “Morocco”.
117–123
J Intercult Ethnopharmacol 2017; 6: 342–350
[59] Ballero M, Foddis C, Sanna C, Scartezzini P, Poli F, Petitto V, Serafini M,
[77] Howards PP, Hertz-Picciotto I, Bech BH, Nohr EA, Andersen AMN, Poole
Stanzione A, Bianco A, Serilli AM, Spina L, Longoni R, Kasture S. Pharma-
C, Olsen J. Spontaneous abortion and a diet drug containing caffeine and
cological activities on Ephedra nebrodensis Tineo. Nat Prod Res 2010; 24:
1115–1124

348 Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved.
 ephedrine: A study within the Danish national birth cohort. PLoS One [95] Mufti A, Tir M, Zarei A, Contreras MM, Gómez-Cruz I, Feriani A, Gha-
2012; 7: e50372 zouani L, Saadaoui E, Allagui M, Harrath AH, Ramazani A, Tlili N. Phyto-
[78] Youbi AEL, Ouahidi I, Mansouri LEL, Daoudi A, Bousta D. Ethnopharma- chemical profiling of Ephedra alata subsp. alenda Seeds by High-Per-
cological survey of plants used for immunological diseases in four re- formance Liquid Chromatography–Electrospray Ionization–Quadru-
gions of Morocco. Eur J Med Plants 2016; 13: 1–24 pole-Time-of-Flight-Mass Spectrometry (HPLC‑ESI-QTOF‑MS), molec-
ular docking, and antioxidant, anti-diabetic, and acetylcholinesterase
[79] Barkaoui M, Katiri A, Boubaker H, Msanda F. Ethnobotanical survey of
inhibition. Anal Lett 2022; 55: 2450–2466
medicinal plants used in the traditional treatment of diabetes in Chtouka
Ait Baha and Tiznit (Western Anti-Atlas), Morocco. J Ethnopharmacol [96] Ben Lamine J, Boujbiha MA, Dahane S, Cherifa AB, Khlifi A, Chahdoura
2017; 198: 338–350 H, Yakoubi MT, Ferchichi S, El Ayeb N, Achour L. α-Amylase and α-glu-
cosidase inhibitor effects and pancreatic response to diabetes mellitus
[80] Balahbib A, El Omari N, Sadak A, Bakri Y, Bouyahaya A. Antileishmanial
on Wistar rats of Ephedra alata areal part decoction with immunohisto-
properties of Moroccan medicinal plants and mechanism insights of
chemical analyses. Environ Sci Pollut Res Int 2019; 26: 9739–9754
their main compounds. Biointerface Res Appl Chem 2020; 10: 7162–
7176 [97] Dbeibia A, Taheur FB, Altammar KA, Haddaji N, Mahdhi A, Amri Z,
Mzoughi R, Jabeur C. Control of Staphylococcus aureus methicillin re-
[81] Merrouni IA, Kharchoufa L, Bencheikh N, Elachouri M. Ethnobotanical
sistant isolated from auricular infections using aqueous and metha-
profile of medicinal plants used by people of North-eastern Morocco:
nolic extracts of Ephedra alata. Saudi J Biol Sci 2022; 29: 1021–1028

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
Cross-cultural and Historical approach (Part I). Ethnobot Res Appl 2021;
21: 1–45 [98] Palici IF, Liktor-Busa E, Zupkó I, Touzard B, Chaieb M, Urbán E, Hoh-
mann J. Study of in vitro antimicrobial and antiproliferative activities
[82] Katiri A, Barkaoui M, Msanda F, Boubaker H. Ethnobotanical survey of
of selected Saharan plants. Acta Biol Hung 2015; 66: 385–394
medicinal plants used for the treatment of diabetes in the Tizi n’ test re-
gion (Taroudant Province, Morocco). J Pharmacogn Nat Prod 2017; 3: [99] Saidi SA, Al-Shaikh TM, Alghamdi OA, Hamden K. Ephedra alata subsp.
2472–0992 alenda (Ephedraceae) leaf extracts: Phytochemical screening, anti-dia-
betic, anti-obesity and anti-toxic activities on diabetic-induced liver-
[83] Guenaou I, Hmimid F, Lahlou FA, Errami A, Irahal IN, Fahde S, Ouafik ʼ,
kidney-testes toxicities and inhibition of α-amylase and lipase en-
Bourhim N. Cytoprotective effect of ethyl acetate fraction from Ephedra
zymes. Heliyon 2022; 8: e11954
fragilis on H2O2-induced oxidative damage in Tetrahymena pyriformis.
Comp Biochem Physiol Part C Toxicol Pharmacol 2021; 239: 108899 [100] Kittana N, Abu-Rass H, Sabra R, Manasra L, Hanany H, Jaradat N, Hus-
sein F, Zaid AN. Topical aqueous extract of Ephedra alata can improve
[84] Liu J, Hui A, Wang J, Hu Q, Li S, Chen Y, Wu Z, Zhang W. Discovery of
wound healing in an animal model. Chin J Traumatol 2017; 20: 108–
acylated isoquercitrin derivatives as potent anti-neuroinflammatory
113
agents in vitro and in vivo. Chem Biol Interact 2023; 383: 110675
[101] Bouafia W, Mouffouk S, Haba H. Quantification of total bioactive con-
[85] Mbikay M, Chrétien M. Isoquercetin as an Anti-Covid-19 medication: A
tents and evaluation of the antioxidant and antibacterial activities of
potential to realize. Front Pharmacol 2022; 13: 830205
crude extracts from Ephedra altissima Desf. Acta Sci Biol Sci 2021; 43:
[86] Orfali GC, Duarte AC, Bonadio V, Martinez NP, de Araújo ME, Priviero FB, e52123
Carvalho PO, Priolli DG. Review of anticancer mechanisms of isoquerci-
[102] Bouafia W, Hamdi A, Mouffouk S, Rodríguez Arcos R, Jiménez A,
tin. World J Clin Oncol 2016; 7: 189–199
Guillen R, Haba H. Phenolic composition, in vitro alpha-amylase and
[87] Zhang W, Yin Z, Guo Q, Chen L, Zhang J. Ionic liquid-based ultrasonic-as- pancreatic lipase inhibitory effects, anti-inflammatory and antioxidant
sisted extraction coupled with HPLC to analyze isoquercitrin, trifolin and activities of Ephedra altissima. Indian J Pharm Sci 2022; 84: 890–901
afzelin in Amygdalus persica L. flowers. BMC Chem 2023; 17: 102
[103] Jiang T, Peng L, Wang Q, Huang B, Peng D, Men L, Jiang Y, Zhu M,
[88] Wu M, Qin M, Wang X. Therapeutic effects of isoquercetin on ovariecto- Wang M, Lin L, Lv J, Li S. Cirsiliol regulates mitophagy in colon cancer
my-induced osteoporosis in mice. Nat Prod Bioprospect 2023; 13: 20 cells via STAT3 signaling. Cancer Cell Int 2022; 22: 304
[89] Bouhaous L, Miara MD, Bendif H, Souilah N. Medicinal plants used by pa- [104] Jia X, Huang C, Hu Y, Wu Q, Liu F, Nie W, Chen H, Li X, Dong Z, Liu K.
tients to fight cancer in northwestern Algeria. Bull Cancer 2022; 109: Cirsiliol targets tyrosine kinase 2 to inhibit esophageal squamous cell
296–306 carcinoma growth in vitro and in vivo. J Exp Clin Cancer Res 2021; 40:
[90] Jaradat NA, Al-Ramahi R, Zaid AN, Ayesh OI, Eid AM. Ethnopharmacolog- 105
ical survey of herbal remedies used for treatment of various types of can- [105] Lim HJ, Jang HJ, Bak SG, Lee S, Lee SW, Lee KM, Lee SJ, Rho MC. In vitro
cer and their methods of preparations in the West Bank-Palestine. BMC inhibitory effects of cirsiliol on IL‑6-induced STAT3 activation through
Complement Altern Med 2016; 16: 93 anti-inflammatory activity. Bioorg Med Chem Lett 2019; 29: 1586–
[91] Danciu C, Muntean D, Alexa E, Farcas C, Oprean C, Zupko I, Bor A, Minda 1592
D, Proks M, Buda V, Hancianu M, Cioanca O, Soica C, Popescu S, Dehe- [106] Prasad P, Vasas A, Hohmann J, Bishayee A, Sinha D. Cirsiliol suppressed
lean CA. Phytochemical characterization and evaluation of the antimi- epithelial to mesenchymal transition in B16F10 malignant melanoma
crobial, antiproliferative and pro-apoptotic potential of Ephedra alata cells through alteration of the PI3K/Akt/NF-κB signaling pathway. Int
decne. Hydroalcoholic extract against the MCF‑7 breast cancer cell line. J Mol Sci 2019; 20: 608
Molecules 2019; 24: 13
[107] Carlini L, Tancreda G, Iobbi V, Caicci F, Bruno S, Esposito A, Calzia D,
[92] Sioud F, Dhouafi Z, Lahmar A, Elgueder D, Chekir-Ghedira L. A novel anti- Benini S, Bisio A, Manni L, Schito A, Traverso CE, Ravera S, Panfoli I.
cancer effect of Ephedra alata decne in breast cancer cells. Nutr Cancer The flavone cirsiliol from Salvia x jamensis binds the F1 moiety of ATP
2022; 74: 3403–3412 synthase, modulating free radical production. Cells 2022; 11: 3169
[93] Sioud F, Amor S, Toumia IB, Lahmar A, Aires V, Chekir-Ghedira L, Delmas [108] Hu H, Du W, Zhang W, Fang J. Cirsiliol mitigates Aβ fibrillation and
D. A new highlight of Ephedra alata decne properties as potential adju- underlying membrane-leakage associated neurotoxicity: A possible
vant in combination with cisplatin to induce cell death of 4 T1 breast implication in the treatment of neurodegenerative disease. Int J Biol
cancer cells in vitro and in vivo. Cells 2020; 9: 362 Macromol 2022; 213: 915–922
[94] Bensam M, Rechreche H, Abdelwahab AE, Abu-Serie MM, Ali SM. The [109] Edrah SM, Aljenkawi A, Omeman A, Alafid F. Qualitative and quantities
role of Algerian Ephedra alata ethanolic extract in inhibiting the growth analysis of phytochemicals of various extract for Ephedra altissima from
of breast cancer cells by inducing apoptosis in a p 53-dependent path- Libya. J Med Plants Stud 2016; 4: 119–121
way. Saudi J Biol Sci 2023; 30: 103650
[110] Mezogi J, Abusaida H, El Jaafari H, Shibani N, Dali A, Abuelkhair K, Sha-
labi S, Aburawi S. Effect of sub toxic dose of Ephedra Altissima metha-

Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved. 349
 Reviews

nolic extract on reproductive system of male albino mice. Alq J Med under woody vegetation patches in semi-arid Mediterranean soils. Sci
App Sci 2020; 3: 13–22 Total Environ 2016; 553: 340–348
[111] Aburawi SM, Mezogi JS, Abuelkhair KF. Effect of Ephedra altissima stems [130] Attard E, Vella K. Effects of ephedrine and Ephedra fragilis crude ex-
extract on behavior in the mouse. Mediterr J Pharm Pharm Sci 2021; 1: tracts on human peripheral lymphocytes. Pharmacogn Res 2009; 1:
23–31 38–42
[112] Caveney S, Starratt A. Glutamatergic signals in Ephedra. Nature 1994; [131] Fiebich BL, Collado JA, Stratz C, Valina C, Hochholzer W, Muñoz E, Bel-
372: 509–509 lido LM. Pseudoephedrine inhibits T-cell activation by targeting NF-κB,
[113] Maolanon A, Papangelis A, Kawiecki D, Mou TC, Syrenne JT, Yi F, Han- NFAT and AP‑1 signaling pathways. Immunopharmacol Immunotoxicol
sen KB, Clausen RP. Stereoselective synthesis of novel 2′-(S)-CCG‑IV 2012; 34: 98–106
analogues as potent NMDA receptor agonists. Eur J Med Chem 2021; [132] Márquez N, Sancho R, Macho A, Calzado MA, Fiebich BL, Muñoz E. Caf-
212: 113099 feic acid phenethyl ester inhibits T-cell activation by targeting both nu-
[114] Del Guacchio E, Cambria S, Brullo S. Typification of the name Ephedra clear factor of activated T-cells and NF-κB transcription factors.
nebrodensis (Ephedraceae). Phytotaxa 2021; 496: 90–92 J Pharmacol Exp Ther 2004; 308: 993–1001

[115] Shah S, Mohan MM, Kasture S, Sanna C, Maxia A. Protective effect of [133] Wang HL, Chen FQ, Wu LJ. Ephedrine ameliorates chronic obstructive
Ephedra nebrodensis on Doxorubicin induced cardiotoxicity in rats. Iran pulmonary disease (COPD) through restraining endoplasmic reticulum

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
J Pharmacol Ther 2009; 8: 61–66 (ER) stress in vitro and in vivo. Int Immunopharmacol 2022; 103:
107842
[116] Maggi F, Nicoletti M, Petitto V, Sagratini G, Papa F, Vittori S. Solid-
Phase Microextraction (SPME) analysis of six Italian populations of [134] He W, Ma J, Chen Y, Jiang X, Wang Y, Shi T, Zhang Q, Yang Y, Jiang X,
Ephedra nebrodensis Tineo ex Guss. subsp. nebrodensis. Chem Biodivers Yin S, Zheng A, Lu J, Zheng Y. Ephedrine hydrochloride protects mice
2011; 8: 95–114 from staphylococcus aureus-induced peritonitis. Am J Transl Res 2018;
10: 670–683
[117] Maggi F, Lucarini D, Tirillini B, Vittori S, Sagratini G, Papa F. Essential oil
composition of Ephedra nebrodensis Tineo ex Guss. subsp. nebrodensis [135] Khattabi L, Boudiar T, Bouhenna MM, Chettoum A, Chebrouk F, Chader
from Central Italy. J Essent Oil Res 2010; 22: 354–357 H, Lozano-Sánchez J, Segura-Carretero A, Nieto G, Akkal S. RP-HPLC‑E-
SI-QTOF‑MS qualitative profiling, antioxidant, anti-enzymatic, anti-in-
[118] Kobaisy M, Tellez MR, Khan IA, Schaneberg BT. Essential oil composi-
flammatory, and non-cytotoxic properties of Ephedra alata Monjauzea-
tion of three Italian species of Ephedra. J Essent Oil Res 2005; 17:
na. Foods 2022; 11: 145
542–546
[136] Oshima N, Yamashita T, Uchiyama N, Hyuga S, Hyuga M, Yang J, Haka-
[119] Khan K, Rasool S, Khan K, Badshah SL, Ahmad N, Jan MT, Hizbullah SM,
matsuka T, Hanawa T, Goda Y. Non-alkaloidal composition of Ephedra
Khan I, Ullah A, Muhammad A. Computational evaluation and anti-in-
Herb is influenced by differences in habitats. J Nat Med 2019; 73: 303–
flammatory and analgesic activities of nebrodenside a isolated from
311
Dodonaea viscosa. Nat Prod Commun 2019; 14: 1–5
[137] Soumaya B, Yosra E, Rim BM, Sarra D, Sawsen S, Sarra B, Kamel M, Wis-
[120] Gou P, Xiao Y, Lv L, Xie H. Hydroquinone and terpene glucosides from
sem AW, Isoda H, Wided MK. Preliminary phytochemical analysis, anti-
Leontopodium leontopodioides and their lipase inhibitory activity. Fito-
oxidant, anti-inflammatory and anticancer activities of two Tunisian
terapia 2018; 130: 89–93
Ephedra species: Ephedra alata and Ephedra fragilis. South Afr J Bot
[121] Cherchar H, Faraone I, DʼAmbola M, Sinisgalli C, Piaz FD, Oliva P, Ka- 2020; 135: 421–428
bouche A, Kabouche Z, Milella L, Vassallo A. Phytochemistry and anti-
[138] Wang ZY, Yin Y, Li DN, Zhao DY, Huang JQ. Biological activities of p-
oxidant activity of aerial parts of Phagnalon sordidum L. Planta Med
hydroxycinnamic acids in maintaining gut barrier integrity and func-
2019; 85: 1008–1015
tion. Foods 2023; 12: 2636
[122] Rashid HU, Ahmad N, Abdalla M, Khan K, Martines MAU, Shabana S.
[139] Tao Y, Wu GL, Zhang YM. Dune-scale distribution pattern of herba-
Molecular docking and dynamic simulations of Cefixime, Etoposide
ceous plants and their relationship with environmental factors in a sa-
and Nebrodenside A against the pathogenic proteins of SARS‑CoV‑2.
line–alkali desert in Central Asia. Sci Total Environ 2017; 576: 473–480
J Mol Struct 2022; 1247: 131296
[140] Tao Y, Zhang YM, Downing A. Similarity and difference in vegetation
[123] Neghme C, Santamaría L, Calviño-Cancela M. Strong dependence of a
structure of three desert shrub communities under the same temper-
pioneer shrub on seed dispersal services provided by an endemic en-
ate climate but with different microhabitats. Bot Stud 2013; 54: 59
dangered lizard in a Mediterranean island ecosystem. PLoS One 2017;
12: e0183072 [141] Sachkov SA, Zolotuhin VV. Ypsolopha admirandella sp. n. (Lepidoptera:
Ypsolophidae), a new European species from the steppes of Russia.
[124] Rodríguez-Pérez J, Larrinaga AR, Santamaría L. Effects of frugivore
Zootaxa 2020; 4822: zootaxa-4822
preferences and habitat heterogeneity on seed rain: a multi-scale anal-
ysis. PLoS One 2012; 7: e33246 [142] Niketić M. The first record of Ephedra Distachya L. (Ephedraceae, Gne-
tophyta) in Serbia–Biogeography, coenology, and conservation. Bot
[125] Fuster F, Traveset A. Evidence for a double mutualistic interaction be-
Serbica 2018; 42: 123–138
tween a lizard and a Mediterranean gymnosperm, Ephedra fragilis. AoB
Plants 2019; 11: plz001 [143] Frink JP, Szabó A. Distribution of Ephedra distachya L. Subsp. Distachya
in Transylvania (Romania) with special regards to new occurrences. Ka-
[126] Umadevi S, Gopi V, Elangovan V. Regulatory mechanism of gallic acid
nitzia J Bot 2008; 16: 119–132
against advanced glycation end products induced cardiac remodeling
in experimental rats. Chem Biol Interact 2014; 208: 28–36 [144] Schneider-Binder E, Kuhlke F. Habitats with sea grape (Ephedra dista-
chya) on the dunes of Letea (Danube Delta, Romania). Transylv Rev
[127] Umadevi S, Gopi V, Vellaichamy E. Inhibitory effect of gallic acid on ad-
Syst Ecol Res 2015; 17: 45–56
vanced glycation end products induced up-regulation of inflammatory
cytokines and matrix proteins in H9C2 (2-1) cells. Cardiovasc Toxicol [145] Osmic N, Culum D, Ibragic S. Catechins and other phenolic com-
2013; 13: 396–405 pounds in herb of eight Ephedra species in comparison to Camellia si-
nensis. Nat Prod Res 2022; Nov 23: 1–6
[128] Zou C, Liu L, Huang C, Hu S. Baiying qingmai formulation ameliorates
thromboangiitis obliterans by inhibiting HMGB1/RAGE/NF-κB signal- [146] Kim HK, Choi YH, Erkelens C, Lefeber AWM, Verpoorte R. Metabolic fin-
ing pathways. Front Pharmacol 2022; 13: 1018438 gerprinting of Ephedra species using 1H‑NMR spectroscopy and princi-
pal component analysis. Chem Pharm Bull (Tokyo) 2005; 53: 105–109
[129] Cerdán M, Sánchez-Sánchez A, Jordá JD, Amat B, Cortina J, Ruiz-Vicedo
N, El-Khattabi M. Characterization of water dissolved organic matter

350 Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved.
[147] Ni S, Matsumoto M, Shimoyama Y, Allain N, Coskun M, Yllmaz T, [164] Yang Y, Wang Q. The earliest fleshy cone of Ephedra from the early cre-
Mlkage M. Anatomical, chemical, and molecular genetic studies of taceous Yixian Formation of Northeast China. PLoS One 2013; 8:
Ephedra distachya. J Jpn Bot 2013; 88: 144–155 e53652
[148] Zhang BM, Wang ZB, Xin P, Wang QH, Bu H, Kuang HX. Phytochemistry [165] Guan S, Sun L, Wang X, Huang X, Luo T. Isoschaftoside inhibits lipo-
and pharmacology of genus Ephedra. Chin J Nat Med 2018; 16: 811– polysaccharide-induced inflammation in microglia through regulation
828 of HIF‑1α-mediated metabolic reprogramming. Evid Based Comple-
[149] Song KS. Exogenous D‑Ala enhances the accumulation ofp-coumaroy- ment Alternat Med 2022; 2022: e5227335
lamino acids inEphedra distachya cultures. Arch Pharm Res 1995; 18: [166] Su Y, Kang Y, Yi J, Lin Q, Zhang C, Lin Z, Yan Z, Qu J, Liu J. Isoschaftoside
336–339 reverses nonalcoholic fatty liver disease via activating autophagy in
[150] Song KS, Tomoda M, Shimizu N, Sankawa U, Ebizuka Y. Mannan glyco- vivo and in vitro. Evid Based Complement Alternat Med 2022; 2022:
peptide elicits p-coumaroylamino acids in Ephedra distachya cultures. e2122563
Phytochemistry 1995; 38: 95–102 [167] Amrati FE, Elmadbouh OHM, Chebaibi M, Soufi B, Conte R, Slighoua M,
[151] Song KS, Ebizuka Y. Elicitor-induced phenylalanine-ammonia lyase, cin- Saleh A, Al Kamaly O, Drioiche A, Zair T, Edderkaoui M, Bousta D. Eval-
namic acid 4-hydroxylase andp-coumaroyl transferase activity in Ephe- uation of the toxicity of Caralluma europaea (C.E) extracts and their ef-
dra distachya cultures. Arch Pharm Res 1996; 19: 219–222 fects on apoptosis and chemoresistance in pancreatic cancer cells.

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
J Biomol Struct Dyn 2023; 41: 8517–8534
[152] Zhang B, Zeng M, Zhang Q, Wang R, Jia J, Cao B, Liu M, Guo P, Zhang Y,
Zheng X, Feng W. Ephedrae Herba polysaccharides inhibit the inflam- [168] Jang D, Lee MJ, Kim KS, Kim CE, Jung JH, Cho M, Hong BH, Park SJ, Kang
mation of ovalbumin induced asthma by regulating Th1/Th2 and KS. Network pharmacological analysis on the herbal combinations for
Th17/Treg cell immune imbalance. Mol Immunol 2022; 152: 14–26 mitigating inflammation in respiratory tracts and experimental evalua-
tion. Health Care (Don Mills) 2023; 11: 143
[153] Soua L, Koubaa M, Barba FJ, Fakhfakh J, Ghamgui HK, Chaabouni S.
Water-soluble polysaccharides from Ephedra alata stems: Structural [169] Li H, Guo L, Ding X, An Q, Wang L, Hao S, Li W, Wang T, Gao Z, Zheng
characterization, functional properties, and antioxidant activity. Mole- Y, Zhang D. Molecular networking, network pharmacology, and mo-
cules 2020; 25: 2210 lecular docking approaches employed to investigate the changes in
Ephedrae Herba before and after honey-processing. Molecules 2022;
[154] Lee YB, Ah Lee J, Soobin Jang, Lim Lee H. Herbal medicine (Suoquan)
27: 4057
for treating nocturnal enuresis: A protocol for a systemic review of ran-
domized controlled trials. Medicine (Baltimore) 2018; 97: e0391 [170] Yao T, Wang Q, Han S, Lu Y, Xu Y, Wang Y. Potential molecular mecha-
nisms of Ephedra Herb in the treatment of nephrotic syndrome based
[155] Griffiths JD, Gyte GM, Popham PA, Williams K, Paranjothy S, Broughton
on network pharmacology and molecular docking. Biomed Res Int
HK, Brown HC, Thomas J. Interventions for preventing nausea and
2022; 2022: e9214589
vomiting in women undergoing regional anaesthesia for caesarean
section. Cochrane Database Syst Rev 2021; 5: CD007579 [171] Lu M, Zhang Y, Wang S, Wang X, Zhang S, De J. Ephedrine and pseu-
doephedrine in Ephedra saxatilis on the vertical altitude gradient
[156] Dusitkasem S, Herndon BH, Somjit M, Stahl DL, Bitticker E, Coffman JC.
changed in southern Tibet Plateau, China. PLoS One 2023; 18:
Comparison of phenylephrine and ephedrine in treatment of spinal-in-
e0290696
duced hypotension in high-risk pregnancies: A narrative review. Front
Med 2017; 4: 2 [172] Fuchino H, Anjiki N, Murase S, Matsuo H, Hayashi S, Kawahara N, Yosh-
imatsu K. Effect of cultivation conditions on components of Ephedra
[157] Hu LJ, Mei Z, Shen YP, Sun HT, Sheng ZM, Chen XZ, Qian XW. Compar-
sp. using liquid chromatography-mass spectrometry and multivariate
ative dose-response study of phenylephrine bolus for the treatment of
analysis. Chem Pharm Bull (Tokyo) 2022; 70: 848–858
the first episode of spinal anesthesia-induced hypotension for cesarean
delivery in severe preeclamptic versus normotensive parturients. Drug [173] Li YC, Wu CH, Le TH, Yuan Q, Huang L, Chen GF, Yang ML, Lam SH,
Des Devel Ther 2022; 16: 2189–2198 Hung HY, Sun H, Wu YH, Kuo PC, Wu TS. A modified 1H‑NMR quantifi-
cation method of ephedrine alkaloids in Ephedrae Herba samples. Int
[158] Tian NN, Yang XH, Zhu YX, Zeng XS, Yuan JY, Yang JL, Jia WW, Li C. Ma-
J Mol Sci 2023; 24: 11272
huang (herbaceous stem of Ephedra spp.): chemistry, pharmacody-
namics, and pharmacokinetics. Zhongguo Zhong Yao Za Zhi 2022; [174] Xue X, Lv X, Ma X, Zhou Y, Yu N, Yang Z. Prevention of spinal hypoten-
47: 3409–3424 sion during cesarean section: A systematic review and Bayesian net-
work meta-analysis based on ephedrine, phenylephrine, and norepi-
[159] Kakimoto M, Nomura T, Nazmul T, Kitagawa H, Kanno K, Ogawa-
nephrine. J Obstet Gynaecol Res 2023; 49: 1651–1662
Ochiai K, Ohge H, Ito M, Sakaguchi T. In vitro suppression of SAR-
S‑CoV‑2 infection by existing kampo formulas and crude constituent [175] Gad MZ, Azab SS, Khattab AR, Farag MA. Over a century since ephe-
drugs used for treatment of common cold respiratory symptoms. drine discovery: an updated revisit to its pharmacological aspects,
Front Pharmacol 2022; 13: 804103 functionality and toxicity in comparison to its herbal extracts. Food
Funct 2021; 12: 9563–9582
[160] Nose M, Kobayashi R, Tada M, Hisaka S, Masada S, Homma M, Haka-
matsuka T. Comparison of ephedrine and pseudoephedrine contents [176] Yoo HJ, Yoon HY, Yee J, Gwak HS. Effects of ephedrine-containing
in 34 Kampo extracts containing Ephedrae Herba used clinically in Ja- products on weight loss and lipid profiles: A systematic review and
pan. J Nat Med 2023; 77: 476–488 meta-analysis of randomized controlled trials. Pharmaceuticals (Basel)
2021; 14: 1198
[161] Kudo Y, Umemoto K, Obata T, Kaneda A, Ni S, Mikage M, Sasaki Y, An-
do H. Seasonal variation of alkaloids and polyphenol in Ephedra sinica [177] Munafò A, Frara S, Perico N, Di Mauro R, Cortinovis M, Burgaletto C,
cultivated in Japan and controlling factors. J Nat Med 2023; 77: 137– Cantarella G, Remuzzi G, Giustina A, Bernardini R. In search of an ideal
151 drug for safer treatment of obesity: The false promise of pseudoephe-
drine. Rev Endocr Metab Disord 2021; 22: 1013–1025
[162] Lim DW, Yu GR, Kim JE, Park WH. Network pharmacology predicts
combinational effect of novel herbal pair consist of Ephedrae herba [178] Goda Y. Regulatory science of natural products. J Nat Med 2022; 76:
and Coicis semen on adipogenesis in 3 T3-L1 cells. PLoS One 2023; 732–747
18: e0282875 [179] He M, Yan J, Cao D, Liu S, Zhao C, Liang Y, Li Y, Zhang Z. Identification
[163] Song EJ, Shin NR, Jeon S, Nam YD, Kim H. Impact of the herbal medi- of terpenoids from Ephedra combining with accurate mass and in-silico
cine, Ephedra sinica stapf, on gut microbiota and body weight in a diet- retention indices. Talanta 2013; 103: 116–122
induced obesity model. Front Pharmacol 2022; 13: 1042833

Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved. 351
 Reviews

[180] Miao SM, Zhang Q, Bi XB, Cui JL, Wang ML. A review of the phytochem- [186] Kharbat FF, Abu Daabes A. Assessing Arabic youtube videos on herbal
istry and pharmacological activities of Ephedra herb. Chin J Nat Med cancer treatment: Absence of health information quality. Health Infor-
2020; 18: 321–344 matics J 2023; 29: 14604582231198022
[181] Wang B, Yan L, Guo S, Wen L, Yu M, Feng L, Jia X. Structural elucidation, [187] Atri A, Echabaane M, Bouzidi A, Harabi I, Soucase BM, Ben Chaâbane R.
modification, and structure-activity relationship of polysaccharides in Green synthesis of copper oxide nanoparticles using Ephedra Alata
chinese herbs: A review. Front Nutr 2022; 9: 908175 plant extract and a study of their antifungal, antibacterial activity and
[182] Xia YG, Wang TL, Sun LM, Liang J, Yang BY, Kuang HX. A new UPLC‑MS/ photocatalytic performance under sunlight. Heliyon 2023; 9: e13484
MS method for the characterization and discrimination of polysaccha- [188] El-Zayat MM, Eraqi MM, Alrefai H, El-Khateeb AY, Ibrahim MA, Aljohani
rides from genus Ephedra based on enzymatic digestions. Molecules HM, Aljohani MM, Elshaer MM. The antimicrobial, antioxidant, and
2017; 22: 1992 anticancer activity of greenly synthesized selenium and zinc composite
[183] Rao N, Spiller HA, Hodges NL, Chounthirath T, Casavant MJ, Kamboj nanoparticles using Ephedra aphylla extract. Biomolecules 2021; 11:
AK, Smith GA. An increase in dietary supplement exposures reported 470
to US poison control centers. J Med Toxicol 2017; 13: 227–237 [189] Nasar MQ, Khalil AT, Ali M, Shah M, Ayaz M, Shinwari ZK. Phytochemi-
[184] Cheng E, Hsiao R, Feliciano Z, Betancourt J, Han JK. Taken to heart–ar- cal analysis, Ephedra Procera C. A. mey. mediated green synthesis of sil-
rhythmic potential of heart-leaf sida, a banned ephedrine alkaloid: A ver nanoparticles, their cytotoxic and antimicrobial potentials. Medici-

This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
case report. Eur Heart J Case Rep 2022; 6: ytac023 na (Mex) 2019; 55: 369

[185] Zell-Kanter M, Quigley MA, Leikin JB. Reduction in ephedra poisonings [190] Shnoudeh AJ, Qadumii L, Zihlif M, Al-Ameer HJ, Salou RA, Jaber AY,
after FDA ban. N Engl J Med 2015; 372: 2172–2174 Hamad I. Green synthesis of gold, iron and selenium nanoparticles us-
ing phytoconstituents: Preliminary evaluation of antioxidant and bio-
compatibility potential. Molecules 2022; 27: 1334

352 Chroho M et al. Ethnobotanical Uses and … Planta Med 2024; 90: 336–352 | © 2024. Thieme. All rights reserved.