TYPE Review

PUBLISHED 19 April 2023

DOI 10.3389/fphar.2023.1170145

Ethnobotanical uses,
OPEN ACCESS phytochemistry and biological
EDITED BY
François Chassagne,
IRD UMR152 Pharmacochimie et Biologie
activity of the genus Euclea: A
Pour le Développement (PHARMADEV),
France review
REVIEWED BY
Smith B. Babiaka,
University of Buea, Cameroon
Abebe Dagne Taye 1, Gizachew Kassahun Bizuneh 2* and
Latifa Bouissane, Asmamaw Emagn Kasahun 3
Université Sultan Moulay Slimane,
Morocco 1
Department of Pharmacy, College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia,
2
Department of Pharmacognosy, School of Pharmacy, College of Medicine and Health Sciences,
*CORRESPONDENCE
University of Gondar, Gondar, Ethiopia, 3Department of Pharmaceutics, School of Pharmacy, College of
Gizachew Kassahun Bizuneh,
Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
gizachewkassahun4@gmail.com

RECEIVED 20 February 2023

ACCEPTED 05 April 2023
PUBLISHED 19 April 2023
Euclea (Ebenaceae) is a genus of flowering shrubs and trees widely distributed in
CITATION
Taye AD, Bizuneh GK and Kasahun AE Africa, the Comoro Islands, and Arabia. This review aimed to evaluate the
(2023), Ethnobotanical uses, ethnobotanical uses, phytochemistry, and biological activities of the genus
phytochemistry and biological activity of
Euclea on available research reports. This was achieved through PubMed,
the genus Euclea: A review.
Front. Pharmacol. 14:1170145. Medline, Google Scholar, Science Direct, Taylor and Francis Online, Wiley
doi: 10.3389/fphar.2023.1170145 Online Library which provides access to scientific and medical research. The
COPYRIGHT extensive literature survey revealed that plants that belong to this genus are used
© 2023 Taye, Bizuneh and Kasahun. This as folkloric medicine for the treatment of diabetes mellitus, toothache, diarrhea,
is an open-access article distributed
cancer, malaria, leprosy, and genital and oral diseases in the case of HIV/AIDS-
under the terms of the Creative
Commons Attribution License (CC BY). related diseases. To date, more than 40 secondary metabolites have been
The use, distribution or reproduction in isolated and identified from these plants, especially from E natalensis and E.
other forums is permitted, provided the
divinorum. Among these, naphthoquinones, terpenes, and flavonoids are
original author(s) and the copyright
owner(s) are credited and that the original potential secondary metabolites with profound biological activities. Euclea
publication in this journal is cited, in plant extracts and their bioactive compounds possess outstanding
accordance with accepted academic
pharmacological properties, especially antimalarial, antidiabetic, anticancer,
practice. No use, distribution or
reproduction is permitted which does not antimicrobial, and antioxidant properties.
comply with these terms.

KEYWORDS

Euclea, naphtoquinones, phytochemistry, ethnobotanical use, pharmacological activity

Introduction
The word “Euclea” comes from a Greek word “eukleia”, “eu” meaning “good”, and
“kleios”meaning report (Maroyi, 2017). The genus Euclea belongs to the family Ebenaceae
and is composed of 16 accepted species (Dhayalan et al., 2015; Botha, 2016).
The genus Euclea is distributed in the tropical and subtropical regions of the world.
However, it is most abundant in Eastern and Southern Africa (Mebe et al., 1998) and South-
East Asia (Botha, 2016). Euclea divinorum is distributed in Botswana, South Africa, Namibia,
Swaziland, Zimbabwe, Tanzania, Uganda (Shumba, 2018), Sudan, Kenya, and Ethiopia
(Woldemedhin et al., 2017). Euclea natalensis is widely found along the eastern coast of
southern Africa (Johanna, 2007). Euclea latideus is well presented in the lowlands of the
tropical and to a lesser extent, in subtropical regions of the world (Philip et al., 2018). A
versatile medicinal plant in Ethiopia from this genus is Euclea divinorum. Traditionally it is
used for the treatment of skin inflammation, scabies, cancer, hepatitis, urinary inconsistency,

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FIGURE 1
(A) Euclea divinorum (B) Euclea natalensis (C) Euclea undulate.

chest pain, pneumonia, gonorrhea, constipation, edema, abdominal

and chest pain (Feyissa et al., 2013; Woldemedhin et al., 2017;
Mekonnen et al., 2018).

Botanical profile and taxonomy of Euclea

Most of the plants are trees, shrubs, and sub-shrubs, usually

evergreen with alternate, opposite to sub-opposite, or in pseudo-
whorls and diamond leaved (Figure 1A). Inflorescences: dioecious,
axillary, or less frequently in branched pseudo-racemes, or flowers
occasionally solitary (Figure 1B). Calyx: 4-5-lobed, usually
polysepalous, not accrescent on fruits. Corolla: urceolate to
subglobose, 5 - 8-lobed or campanulate and deeply 4-5-lobed.
Stamens: 10-30; anthers dehiscing by large ellipsoidal apical
pores, hairy or glabrous, oblong or lanceolate, 2-celled; filaments
short, usually slender and glabrous. Staminodes: usually absent,
glabrous; styles 2 (or 1, bifid), usually glabrous; stigmas bifid at apex.
Ovary: ovoid or globular, hairy or glabrous, usually 4-celled; ovules
4, pendulous. Fruit: usually globose, 1-seeded berry (Halim et al.,
2014), edible, spherical and one-seeded berries (Figure 1C) FIGURE 2
(Dhayalan et al., 2015). Many members of this genus are Flowchart of reviews included and excluded.
traditionally used to treat different diseases. Some are
scientifically investigated for various biological activities and
phytoconstituents. Previously, reviews that focus on single Methodology
species, E undulata Thunb (Maroyi, 2017) and E. divinorum
Hiern (Omara et al., 2020) have been conducted. To the authors’ This review aims to critically evaluate available research reports
knowledge, no study reviewed the ethnopharmacological use, on the genus and systematically organize and present the results.
phytochemistry, and biological activities of the whole genus. The review summarizes the existing knowledge on the

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TABLE 1 Traditional uses of members of the genus Euclea.

Species Part Indication Country References

used
E. crispa R cough South Africa Schmidt et al. (2002)

R constipation South Africa Chinsamy and Koitsiwe (2016)

Swaziland Long (2005)

B, F, L, R Diabetes South Africa, Palmer and Pitman (1972)

Swaziland, Zimbabwe Chinsamy and Koitsiwe, 2016; Schmidt
et al., 2002; Masoga, 2020

L Dysmenorrhoea South Africa Steenkamp (2003)

R convulsions and epilepsy Zimbabwe Stafford et al. (2008)

E. coriacea B Constipation, Stomach pains South africa Kose et al. (2015)

R, L and S Gonorrhea Lesotho Mugomeri et al., 2014

E. R HIV/AIDS-related diseases Zambia Chinsembu (2016)

divinorum
R urine retention Ethiopia Woldemedhin et al. (2017)

L malaria, leprosy, gonorrhea, syphilis and tapeworm Ethiopia Geyid et al., 2005; Nanyingi et al., 2008

R induce labour Kenya Kaingu et al. (2012)

F abdominal upsets, skin, kidney and respiratory disorders Kenya Kigen et al. (2017)

R convulsions Zimbabwe Sobiecki (2002)

R schistosomiasis South African Sparg et al. (2000)

E. kellau B splenic pain Tanzania Orzalesi et al. (1970)

R Ancylostomiasis Tanzania Orzalesi et al. (1970)

L snake-bite Orzalesi et al. (1970)

E. R Diabetes South Africa; Kenya Deutschländer M. S. et al., 2009; Keter

natalensis and Mutiso, 2012

R Epilepsy South Africa Van Wyk and Gericke (2000)

L Antidote for poisoning, snake bite Malawi Morris and Msonthi (1996)

B Prostate cancer Uganda Omara et al. (2020)

R Leprosy, syphilis, toothache South Africa Oosthuizen and Lall (2020)

Sh and B chest pains, bronchitis, pleurisy, and asthma South Africa Oosthuizen and Lall (2020)

R Herpes simplex virus 1 South Africa Lall et al. (2005a)

Tuberculosis South Africa Lall and Meyer (2001)

B schistosomiasis South Africa Sparg et al. (2000)

E. racemosa R Warts of the rectum, Constipation Ethiopia D’avigdor et al., 2014; Ayele et al., 2023

RB Cancer Ethiopia Wube et al. (2005)

RB toothache and malaria Uganda Neuwinger (2000)

R cancer, abdominal pain and convulsive dysmenorrhoea Tanzania Neuwinger (2000)

RB, L, Diabetes Kenya Keter and Mutiso (2012)

S, Br

E. schimper L gonorrhea, eczema and constipation, snake biting, scabies, leprosy, Tinea Ethiopia Gelahun, 1989; Abebe and Ayehu, 1993;
capitis, acne, warts, rheumatic pain and elephantiasis Mekonnen et al., 2018

R febrile disease (fever, headache and sweating) Ethiopia Giday et al. (2003)

B Dysmenorrhoea South Africa Steenkamp (2003)

(Continued on following page)

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TABLE 1 (Continued) Traditional uses of members of the genus Euclea.

Species Part Indication Country References

used
E. undulata RB Diabetes South Africa Deutschländer M. et al., 2009;
Deutschlander, 2010

B, R Toothache Botswana Palmer and Pitman, 1972; Motlhanka and

Nthoiwa, 2013

L Diarrhoea South Africa Deutschländer M. S. et al. (2009)

S Chewing stick Zimbabwe Joshua et al., 2013

AP, aerial part; B, bark; Br, Branch; F, flower; Fr, Fruit, L, leaf; R, root; RB, root bark; Sh, shoot; S, stem; Sd, Seed; WP, whole plant.

ethnobotanical use, phytochemistry, and pharmacological activity of used as enemata or as an ingredient of inembe (herbal medication
species belonging to the genus Euclea to bring the reader up to date regularly taken during pregnancy to ensure trouble-free
with the current literature. Articles on the species of the genus Euclea confinement). Emesis or purgation is induced with root
that reported ethnobotanical uses, biological activities, and isolation preparations (Deutschländer M. et al., 2009).
and identification of compounds were included. It is attempted to The Zulu people use E. natalensis as a purgative (Lall and
include articles published from 1975–2023 while some articles Meyer, 2001; Weigenand et al., 2004) and for abdominal
published before 1975 were also included by considering their complaints in the form of infusion (Deutschländer M. S. et al.,
importance. In this review articles where the full text was not 2009; Deutschländer, 2010). Its charred and powdered root is
available in the database or even after contacting the author by used treat leprosy, urinary tract infections, venereal diseases,
email were excluded (Figure 2). dysmenorrhea, and ancylostomiasis among Shangaan people
This review excluded unpublished results and publications (Lall & Meyer, 2000; Lall and Meyer, 2001); Kooy et al., 2006;
unavailable online, articles written in languages other than Deutschländer, 2010) while its root bark infusions for sores and
English, and articles whose titles and abstracts did not contain wounds in South Africa (Lall and Meyer, 2001). Within the
the search terms. Chemical structures of only isolated and Tonga people, the same part of this plant exhibits toothache
characterized compounds were provided, while structures of and headache relief (Deutschländer M. et al., 2009; Babiaka et al.,
compounds identified from essential oils and other chemical 2015; Dhayalan et al., 2015).
analyses were not. Different databases, including PubMed, In Swaziland, the stem bark decoction of E. divinorum is a
Google Scholar, Scopus, and Medline, were employed to search folk medicine for constipation (Amusan et al., 2007). The root
literature using “keywords such as “Euclea”, “ethnobotanical use”, bark is used for diarrhea, convulsions, cancer, and skin diseases
“phytochemistry”, and “pharmacological activity” dated up to (Mebe et al., 1998; Babiaka et al., 2015). In Kenya, the root of this
December 2023.” plant is a remedy for chest pain, pneumonia, and internal body
swelling (Woldemedhin et al., 2017). In Ethiopia, the roots and
leaves of this plant are used for treating urinary retention,
Ethno pharmacological uses malaria, leprosy, gonorrhea, syphilis, and tapeworm (Feyissa
et al., 2013; Woldemedhin et al., 2017). E. schimperi is
Ethnomedicinal claims on the genus Euclea to treat several traditionally prescribed for managing wounds, teeth infection,
ailments are illustrated in Table 1. The genus Euclea is used to eye disorder, headache, gonorrhea, eczema, skin disorder, snake
treat hypnosis, toothache, headache (Bapela et al., 2008; Babula biting, scabies, leprosy, and elephantiasis in Ethiopia (Mekonnen
et al., 2009), chest complaints, bronchitis, pleurisy, chronic et al., 2018).
asthma, urinary tract infections, and venereal diseases (Lall &
Meyer, 2000; Lall and Meyer, 2001; Weigenand et al., 2004; Kooy
et al., 2006; Johanna, 2007; Bapela et al., 2008). An infusion of the Phytochemistry
roots of E. ceispa possesses antiepileptic activity (Dhayalan et al.,
2015). The root bark of E. undulata is reported to be used for the Euclea is a good source of naphthoquinones, pentacyclic
management of body pains, diabetes, headache, and toothache triterpenes (Dagne et al., 1993; Joubert et al., 2006; Kwon
while an infusion of its leaves is used for stomach problems or et al., 2011; Dhayalan et al., 2015), flavonoids, naphthols
diarrhea, and leaf decoction for tonsillitis (Deutschländer M. (Dagne et al., 1993) and diosindigo (Dhayalan et al., 2015).
et al., 2009; Dhayalan et al., 2015; Maroyi, 2017). This plant is a Members of the genus Euclea contain primarily
folk medicine for diabetes in the Venda area, Limpopo Province naphtoquinones and the root/root bark of the plant is the
(Deutschländer M. S. et al., 2009; Babiaka et al., 2015; Maroyi, main source of the naphtoquinones. Phytochemical screening
2017). In the Western Cape, the root infusion of E. undulata is revealed that the leaf of E. schimperi contains saponins,

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TABLE 2 Naphthoquinones isolated from Euclea species.

No. Name of the compound Species Plant Structure References

part

1. 2-methylnaphthazarin E. pseudebenus R Ferreira et al., 1973; Dhayalan et al.,

2015

2. 7-methyl-juglone E. undulata R Deutschländer M. et al., 2009;

Mbaveng & Kuete, 2014; Botha, 2016

3E.natalensis R Mbaveng & Kuete, 2014;

Deutschländer M. S. et al., 2009; Babula
et al., 2009

4E. natalensis S, R Lall et al., 2005b; Joubert et al., 2006;

and Sd Johanna, 2007; Bapela et al., 2008;
Babiaka et al., 2015; Kooy et al., 2006

5E. divinorum Us Mebe et al., 1998; Babula et al., 2009

6E. divinorum R Al-fatimi (2019)

7E. pseudebenus R Ferreira et al. (1973)

8E. racemosa R Wube et al. (2005)

ssp. schimperi

9E. lanceolata RB Ferreira et al. (1974)

3. 8,8’-dihyd roxy-4,4’-dimethoxy-6, 6’- E. lanceolata RB Ferreira et al. (1974)

dimethyl-2,2’- binaphthyl-l,l’- quinone

4. 8’-hydroxydiospyrin E. lanceolata RB Ferreira et al. (1974)

5. biramentaceone E. pseudebenus R Ferreira et al. (1973)

6. diospyrin E. undulata R Deutschländer M. et al. (2009)

E. crispa var crispa R,Fr Botha (2016)

E. undulata Fr Botha (2016)

E. natalensis S, R Lall et al., 2005a; Joubert et al., 2006;

and Sd Johanna, 2007; Bapela et al., 2008;
Babiaka et al., 2015

E. pseudebenus Us Dhayalan et al. (2015)

E. divinorum R Al-fatimi (2019)

E. natalensis Us Deutschländer M. S. et al. (2009)

(Continued on following page)

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TABLE 2 (Continued) Naphthoquinones isolated from Euclea species.

No. Name of the compound Species Plant Structure References

part

7. eucleanal E. divinorum L Ng’ang’a et al., 2012

8. eucleanal B E. divinorum L Mwihaki Ng’ang’a et al., 2012

9. eucleanal A E. divinorum L Mwihaki Ng’ang’a et al., 2012

10. euclein (3, 6’-dimer of 7-methyljuglone.) E.pseudebenus R Ferreira et al. (1973)

11. isodiospyrin E. undulata Fr Deutschländer M. et al., 2009; Botha,

2016

E. crispa Fr Botha (2016)

E. natalensis Us Kooy et al., 2006; Wube et al., 2005

E. racemosa R Wube et al., 2005; Al-fatimi, 2019

ssp. schimperi

12. mamegakinone E. natalensis Us Kooy et al., 2006

E. natalensis Us Deutschländer M. S. et al. (2009)

E. pseudebenus R Ferreira et al., 197

E. racemosa R Wube et al. (2005)

ssp. schimperi

E. natalensis, E. cripsa, Us Dhayalan et al. (2015)

and E. schimperi

E. divinorum R Al-fatimi (2019)

E. lanceolata RB Ferreira et al. (1974)

13. natalonone E. crispa subsp. Crispa Us Kwon et al. (2011)

(Continued on following page)

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TABLE 2 (Continued) Naphthoquinones isolated from Euclea species.

No. Name of the compound Species Plant Structure References

part

14. neodiospyrin E. natalensis S, R Joubert et al., 2006; Johanna, 2007;

and Sd Bapela et al., 2008; Babiaka et al., 2015

15E. racemosa R Wube et al. (2005)

ssp. schimperi

15. octahydroeuclein E. natalensis RB Weigenand et al., 2004; Lall et al., 2006

16. shinanolone E. natalensis RB Weigenand et al., 2004; Kooy et al.,

2006; Lall et al., 2006

18E. natalensis S, R Joubert et al., 2006; Johanna, 2007;

and Sd Bapela et al., 2008

19E. divinorum Us Mebe et al. (1998)

20E.racemosa R Wube et al. (2005)

ssp. schimperi

21E. natalensis Us Kooy et al., 2006

B, bark; F, flower; Fr, Fruit; R, root; RB, root bark; S, shoot; Sd, Seed; Us, Unspecified.

terpenoids, tannins, steroids, polyphenols, and flavonoids after Kuete, 2014; Botha, 2016). They were mainly detected from the root
extraction with methanol and chloroform (Mekonnen et al., barks of the genus Euclea (Khan, 1985). Naphthoquinone isolated
2018). Aqueous and 80% methanol root extract of E. from the genus Euclea is presented in Table 2.
divinorum had shown to contain saponins, flavonoids,
glycosides, steroids, tannins, and terpenoids (Woldemedhin
et al., 2017; Al-fatimi, 2019) but alkaloids and anthraquinones Flavonoids
were absent (Woldemedhin et al., 2017). On the other hand, the
root bark of this plant produces alkaloids, terpenoids, flavonoids, Flavonoids are phenolic compounds having two benzene rings
tannins, and saponins (Shumba, 2018). Methanol leaf and stem linked through a heterocyclic pyrane ring (Shumba, 2018).
extracts of E. undulata contained alkaloids, diterpenes, Quercetin, kaempferol (Al-fatimi, 2019), new aromadendrin-3-O-
glycosides, phytosterols, reducing sugars, saponins, and β-L-arabinopyranoside (17), and known flavonoids such as catechin
tannins (Maroyi, 2017). Essential oils, saponins, terpenoid (Dagne et al., 1993; Mebe et al., 1998), myricetin-3-O-α-
derivatives, alkaloids, and flavonoids are the constituents of E. L–rhamnopyranoside (21) and quercetin-3-O-α-L-
crispa subsp. crispa (Kwon et al., 2011). rhamnopyranoside (22) were isolated from the extract of ethanol
aerial part of E. divinorum (Dagne et al., 1993), (Table 3). Acetone
leaves extract of E. racemosa ssp. Schimperi yields quercetrin,
Naphthoquinone myricitrin, myricetin-3-O-arabinopyranoside (20) and rutin (23),
(Asres et al., 2006).
Quinones are one of the plant-derived secondary metabolites. HPLC detects large amounts of myricitrin and small amounts of
Based on the number of benzene rings in the structural fused and isoquercitrin and quercitrin in E. schimperi (Mueller-harvey et al.,
skeleton, they are mainly classified as naphthoquinone, 1987). Root bark extracts of E. undulata (acetone) (Deutschländer,
phenanthrenequinone, anthraquinone, and benzoquinone (Demir, 2010; Babiaka et al., 2015; Botha, 2016), E. divinorum (chloroform)
2020). Naphthoquinones are phenolic compounds derived from and E. undulata (acetone) resulted in the isolation of epicatechin
naphthalene occurring in plants (common) and fungi (Mbaveng & (19) and catechin (18) respectively (Babiaka et al., 2015).

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TABLE 3 Flavonoids isolated from Euclea species.

No. Name of the compound Species Plant part Structure References

17 aromadendrin-3-O-β-L E. divinorum A Dagne et al., 1993

arabinopyranoside

18 catechin E. divinorum RB Babiaka et al. (2015)

19 epicatechin E. undulate RB Deutschländer, 2010; Babiaka et al., 2015; Botha,

2016

20 myricetin-3-O-arabinopyranoside E. racemosa L Asres et al. (2006)

21 myricetin-3-O-α-L –rhamnopyranoside E. divinorum A Dagne et al., 1993

22 quercetin-3-O-α-L-rhamnopyranoside E. divinorum A Dagne et al., 1993

(Continued on following page)

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TABLE 3 (Continued) Flavonoids isolated from Euclea species.

No. Name of the compound Species Plant part Structure References

23 rutin E. racemosa L Asres et al. (2006)

A, arial; RB, root bark; L, leaf.

Hyperoside, quercitrin, epicatechin, catechins and gallocatechin antimicrobial effect. Diospyrin and 7-methyljuglone were more
were isolated from the leaves of E. crispa subsp. Crispa effective against Gram-positive bacteria than Gram-negative
(Rademana et al., 2019). bacteria.
Shinanolone, 7-methyljuglone, diospyrin, isodiospyrin and
neodiospyrin in the genus Euclea especially E. natalensis are
Terpenoids potent for the treatment of both drug-sensitive and resistant
tuberculosis (Joubert et al., 2006; Johanna, 2007; Bapela et al.,
Triterpenes are a group of natural products, derived from 2008; Babula et al., 2009; Babiaka et al., 2015). On the other hand,
isoprene units. In nature, triterpenoids are often existed as tetra- diospyrin, lupeol, betulin and 7-methyl juglone presented in E.
or penta-cyclic structures but some acyclic, mono-, bi-, tri- and hexa natalensis has inhibitory activity against drug-sensitive M.
acyclic. As described in Table 4, Lupeol, lupine, botulin and tuberculosis at MIC of 8.0 and 0.5 mg/mL respectively
oleanolic acid are some examples of pentacyclic triterpenoids (Maroyi, 2017). The intracellular and extracellular inhibition
(Furtado et al., 2017). Triterpenoids were detected from root and of the latter compound is greater than that of the anti-
stem barks of E. natalensis (Khan, 1985). Phytol (0.66%) and tuberculosis drugs streptomycin and ethambutol (Lall et al.,
squalene (5.85%) were detected from hexane extract of E. crispa 2005b; Mcgaw et al., 2008).
using GC-MS (Palanisamy & Ashafa, 2018). 7-methyl juglone and mamegakinone are effective against M.
tuberculosis (Kooy et al., 2006), Neisseria gonorrhoeae, Shigella
dysenteriae and Shigella flexneri. Aqueous and acetone extracts of
Miscellaneous the roots of E. natalensis inhibited the growth of Mycobacterium
tuberculosis at MIC value of 0.5 mg/mL while MIC values for B.
The following bioactive compounds with their composition cereus, B. pumilus, B. subtilis, M. kristinae and S. aureus ranged from
were identified from hexane extract of E. crispa using GC-MS: 0.1–6.0 mg/mL (Lall & Meyer, 2000; Lall and Meyer, 2001). 7-
tetracosane (14.98%), dodecane (10.76%), 2-ethyl-1-decanol methyl juglone is also effective against Saccharomyces cerevisiae,
(8.00%), tridecane (7.53%), diphenyl vinyl phosphine (6.38%), M. bovis, M. smegmatis and M. fortuitum (Mbaveng & Kuete, 2014).
triacontane (5.27%), 2,6-dimethylheptadec-ane (5.02%), docosane Due to Shinanolone, E. natalensis inhibits the growth of Gram-
(3.68%), tetradecane (3.59%), 1-hepten-3-ol (2.63%), orthotolidine positive bacterial strains and a drug-sensitive strain of M.
(2.31%), Phenyl glucuronide (2.25%), 5-tridecy-lbenzene-1,3-diol tuberculosis at a concentration of 0.1 mg/mL (Weigenand et al.,
(1.90%), and Pentadec-ane (1.68%) (Palanisamy & Ashafa, 2018). 2004).
Vitamin E, fatty acid methyl esters such as saturated (C14, C20) and Ethanolic extract of E. crispa leaves elicit antimicrobial activity with
unsaturated (C16, C18:1, C18:2, and C18:3 were isolated from twigs and maximum inhibition zone against Staphylococcus aureus, Streptococcus
leaves of E. undulate (Maroyi, 2017). VTLC identified gallic and aureus, Escherichia coli, Klebsiella pneumonia, Aspergillus niger and
ellagic acid esters in E. schimperi (Mueller-harvey et al., 1987). Aspergillus terreus (Palanisamy et al., 2019). Previous literatures
demonstrated that E. lanceolata, E. undulata and E. multiflora
possess antifungal activity due to the presence of lawsone, juglone
Biological activities and 7-methyljuglone (Lall & Meyer, 2000; Lall and Meyer, 2001). Euclea
natalensis comprises β-sitosterol (Lall et al., 2006; Moosavi et al., 2020),
Antimicrobial activity 20 (29)-lupine-3β-isoferulic and shinanolone that have inhibitory
The acetone and aqueous extract of E. natalensis inhibited the activity against Aspergillus niger at 0.01 mg/mL. The former
growth of Bacillus cereus, B. pumilus, B. subtilis, Micrococcus compound and octahydro euclein significantly show fungistatic
kristinae, and Staphylococcus aureus at concentrations ranging activity against C. cladosporioides at 0.01 mg/mL. Besides this,
between 0.1 and 6.0 mg/mL (Lall and Meyer, 2000). Isolated octahydro euclein present in this plant is very effective for
compounds from the root extract also demonstrated a significant Phytophthora sp. at 0.1 mg/mL (Lall et al., 2006).

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TABLE 4 Terpenoids isolated from Euclea species.

No Name of the compound Species Plant Structure References

part

24 20 (29)-lupene-3α-isoferulate E. natalensis RB Weigenand et al. (2004)

25 20 (29)-lupene-3β-isoferulate E. natalensis RB Lall et al. (2006)

26 3-oxo-oleanolic acid E. crispa Us Kwon et al. (2011)

subsp. crispa

27 3β-(5-hydroxyferuloyl)lup-20 E. crispa Us Kwon et al. (2011)

(30)-ene subsp. crispa

(Continued on following page)

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TABLE 4 (Continued) Terpenoids isolated from Euclea species.

No Name of the compound Species Plant Structure References

part

28 α-amyrin E. kellau L Orzalesi et al. (1970)

29 α-amyrin-3O-ß-(5-hydroxy) ferulic E. undulate RB Deutschländer, 2010; Botha, 2016

acid

30 betulin E. natalensis RB Weigenand et al., 2004; Lall et al., 2005b; Lall

et al., 2006

E. divinorum RB Mebe et al., 1998; Al-fatimi, 2019

E. kellau Br Orzalesi et al. (1970)

E. latideus R Philip et al. (2018)

E. undulata RB Deutschländer, 2010

E. crispa RB Rademana et al. (2019)

subsp. crispa

31 farnesol E. crispa L Palanisamy et al. (2020)

(Continued on following page)

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TABLE 4 (Continued) Terpenoids isolated from Euclea species.

No Name of the compound Species Plant Structure References

part

32 germanicol E. divinorum RB Kilonzo et al. (2019)

33 lupene E. divinorum RB Mebe et al., 1998; Al-fatimi, 2019

34 lupeol E. natalensis RB Weigenand et al., 2004; Lall et al., 2005a; Lall

et al., 2006

E. divinorum RB Mebe et al., 1998; Al-fatimi, 2019

E. kellau Br Orzalesi et al. (1970)

E. latideus R Philip et al. (2018)

E. undulata RB Deutschländer, 2010; Botha, 2016

(Continued on following page)

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TABLE 4 (Continued) Terpenoids isolated from Euclea species.

No Name of the compound Species Plant Structure References

part

35 ursolic acid E. kellau Br, L Orzalesi et al. (1970)

36 ursolic acid lactone E. kellau Br, L Orzalesi et al. (1970)

37 uvaol E. kellau L Orzalesi et al. (1970)

38 β-sitosterol E. natalensis RB Lall et al., 2006; Moosavi et al., 2020

39 γ-sitosterol E. divinorum RB Kilonzo et al. (2019)

Br, Branch; L, leaf; R, root; RB, root bark; Us, Unspecified.

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Ethyl acetate root extract of E. divinorum has inhibitory activity can be achieved with acetone root bark extracts of E. undulata by
against Gram-negative bacteria like E. coli but is ineffective for S. displaying a glucose uptake of 162.2% by changing liver cells at
aureus. Alkaloids and terpenoids in this plant contribute to this kind 50 mg/mL (Maroyi, 2017). E. coriacea contains phytosterols that
of antibacterial activity (Shumba, 2018). The MIC values of the possess antidiabetic activity (Mugomeri et al., 2014). Acetone
extracts of E. divinorum against bacterial activity for root bark ethyl root bark extracts of E. undulata effectively reduced fasting
acetate and leaf aqueous ranges from 0.048-0.871 mg/mL and 0.781- blood glucose levels, raised cholesterol, and triglyceride levels
1.562 mg/mL respectively. The first extract is very effective against S. to close to normal without causing weight gain in an in vivo
typhi followed by stem bark aqueous and root bark petroleum ether model of streptozotocin-nicotinamide-induced type-2 diabetes
extract against S. aureus (Kilonzo et al., 2019). (Deutschländer et al., 2012).
The non-polar dichloromethane root extract of E. divinorum
root bark has better antifungal activity than the nystatin for Antioxidant activity
Absidia corymbifera, Aspergillus fumigatus, Candida krusei, Ethanolic root bark and leaf extracts of E. crispa have radical
Microsporum gypseum, Mucor sp. and Trichophyton scavenging activity because of flavonoids, phenolics (Tinevimbo,
mentagrophytes. This activity is maintained with lupeol, 2017) and (6E, 10E)-2, 6, 24-trimethylpentane cosa-2, 6, 10-
lupine, botulin, 7-methyl juglone, diospyrin, iso diospyrin and triene isolated from the leaves of E. crispa exhibited potent
shinalone (Al-fatimi, 2019). antioxidant activity (Palanisamy et al., 2019). The leaves of E.
crispa were tested for antioxidant activity and showed
Antiviral activity IC50 values of 113.79, 109.59, and 116.65 μg/mL for DPPH,
The acetone extract of E. natalensis demonstrated moderate hydroxyl and nitric oxide radical scavenging assays. Farnesol
antiviral activity against HSV-1, at concentrations of 0.1–0.02 mg contributes to such activity (Palanisamy et al., 2020). At a
ml−1 (Lall et al., 2005a). In a study conducted by Tshikalange et al. 2000 mg/mL concentration, E. divinorum inhibits DPPH by
(2007) 7-methyljuglone (potent), diospyrin, neodiospyrin, 82.5%, 74.5% and 62.5% for the methanol fraction, aqueous
isodiospyrin, and 6-methyljuglone isolated from that E. natalensis fraction and crude extract, respectively (Feyissa et al., 2013).
exhibited HIV-1 reverse transcriptase activity at the concentrations Fatty acids, flavonoids, and phenolics of E. undulata showed
ranging from 25 to 50 μg/mL. The leaf extract of E. schimperi showed antioxidant activity using the DPPH, ABTS and FRAP assays
good antiviral activity against Influenza A virus and herpes simplex (Maroyi, 2017). The free radical scavenging effect of methanol
virus (HSV-1) with IC50 values of 6.22 6 μg/mL and 67.5 μg/mL, and chloroform leaf extracts of E. schimperi was demonstrated.
respectively (Gebre-Mariam et al., 2006). The methanol and chloroform extracts were able to scavenge the
DPPH radical with a percentage scavenging activity of 85.4% and
Antimalarial activity 58.5% at the concentration of 40 μg/mL, respectively (Mekonnen
Aqueous, dichloromethane, and methanol leaf and twig et al., 2018).
extracts of E. undulata have shown antimalarial activity
against Plasmodium falciparum using the parasite lactate Anticancer activity
dehydrogenase assay (Maroyi, 2017). E. latideus is also The leaves of E. crispa subsp. crispa extract exhibited anti-
effective against P. falciparum especially for the chloroquine proliferative activity on human breast adenocarcinoma (MCF-7)
resistant strain of P. falciparum due to the presence of lupeol, and human epidermoid carcinoma (A431) cell lines with IC 50
betulin, and 3β-(5-hydroxy feruloyl) lup-20 (30)-ene (Philip values of 45.7 μg/mL and 41.8 μg/mL, respectively (Rademana
et al., 2018). The dichloromethane and methanol (1:1) root et al., 2019). 7-methyl juglone and 3β-(5-hydroxy feruloyl) lup-
and leaf extracts of E. natalensis demonstrated promising 20 (30)-ene, which are the main constituents of E. divinorum,
activity in a research by Clarkson et al. (2004) employing the showed anticancer effects against human breast cancer, colon
parasite lactate dehydrogenase assay, with (IC 50) values of cancer, fibrosarcoma, nasopharyngeal carcinoma, lung cancer,
5.1 and 5.3 mg/mL, respectively, against P. falciparum. A and human melanoma (Mebe et al., 1998). Diterpenes isolated
study done by Philip et al. (2018) indicated that the extracts from E. coriacea has been reported to possess an anticancer effect
and isolated compounds from E. latideus demonstrated in human cells (Mugomeri et al., 2014). 7-Methyl juglone
antiplasmodial activity against chloroquine sensitive and isolated from E. racemosa ssp. schimperi has been described to
chloroquine resistant strains of P. falciparum. The leaves of E. possess significant cytotoxic properties against human colon
natalensis also showed antiplasmodial activity with an IC50 of carcinoma cells (Wube et al., 2005). Euclea natalensis also
25.6 μg/mL (Tajuddeen et al., 2022). The in vivo antimalarial contains this compound that has anticancer activity on several
assay of the aqueous root extract of E. divinorum possessed cancer cell lines, such as KB, Lu1, and LNCaP (Mbaveng & Kuete,
significant parasitemia suppression (Girmaw and Engidawork, 2014).
2022).

Antidiabetic activity Other activities

E. undulata containing α-amyrin-3-O-β-(5-hydroxy) ferulic
acid inhibits α-glucosidase and epicatechin lowers glucose levels E. coriacea contains phytosterols that possess anti-
in the blood (Botha, 2016). Phenolic acids and flavonoids of E. inflammatory and anti-pain activity (Mugomeri et al., 2014). A
crispa inhibit alpha amylase with IC 50 values of 1.001 mg/mL study showed that E. natalensis shoot extract has in vivo
and 1.65 mg/mL (Tinevimbo, 2017). Lowering of blood glucose hepatoprotective activity by reducing the level of alanine

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Taye et al. 10.3389/fphar.2023.1170145

transaminase liver enzyme by 15% (50 mg/kg) and 40% Conclusion

(100 mg/kg). This plant also provides an immunomodulatory
activity by increasing T-helper 1 cell cytokines such as The genus Euclea is well known for its use in the treatment of
Interleukin 2, Interleukin 12, and Interferon α by 12 fold and diabetic and body pain manifestations. The traditional claims
decreasing the T-helper 2 cell cytokine, interleukin 10 by 4 fold were justified by different biological evaluations. The genus
when compared to baseline cytokine production (Lall et al., 2016). Euclea is known to be a source of biologically active
The in vivo evaluation of the antidiuretic activity of E. divinorum compounds. More than 40 compounds were isolated from the
revealed that the aqueous and methanol root extract of the plant genus and naphthoquinones, pentacyclic triterpenes and
possessed a significant diuretic activity by increasing urine volume flavonoids are the most abundant bioactive secondary
and electrolyte excretion (Woldemedhin et al., 2017). Feyissa et al. metabolites which are responsible for the observed biological
(2013) demonstrated that the crude extract and solvent fractions of activity. Most of these secondary metabolites are found in the
E. divinorum leaves restored gentamicin-induced nephrotoxicity by roots and root bark while some in fruit, seeds, leaves and shoots.
decreasing tubular necrosis, serum and oxidant markers and by According to the present review, it has been noted that the
increasing in antioxidant molecules. The methanol fraction potential uses of the species in the treatment of viral infections
provided the most renoprotection, implying that semi-polar and nerve-related diseases have not been scientifically explored.
antioxidant principles may be involved. We believe the scientific community researching on the genus
will benefit from the material compiled in this review.

Acute toxicity, gentotoxicity and cytotoxiciy

Author contributions
Acute toxicity studies of the crude and methanolic extract of E.
divinorum leaves indicated that it was safe when administered orally AT designed the study, conducted the literature review,
at 2000 mg/kg (Feyissa et al., 2013; Woldemedhin et al., 2017). After extracted relevant information to the study, write the
a period of 72 h, the animals tolerated the administered dose, and manuscript. AK and GB contributed in writing, editing and
there were no appreciable changes in behavior such as motor revising the manuscript. All authors read and approved the
activity, diarrhoea, breathing, alertness, restlessness, convulsions, manuscript.
coma and appearance. Since no mortality was recorded within
14 days, the lethal dose (LD50) was indicated to be more than
2000 mg/kg. Shauli, (2023) evaluated the acute and sub-acute oral Conflict of interest
toxicity of E. natalensis and the results demonstrate that no treatment
related deaths or toxic signs were observed. Another study done by The authors declare that they no conflict of financial interests or
Ayele et al. (2023) revealed that E. racemosa was safe after oral toxicity personal relationships that could have appeared to influence the
study with LD50 greater than 2000 mg/kg. E. latideus is considered as a work reported in this review.
non-toxic plant since acute toxicity studies showed that crude extracts
had LD50 > 5,000 mg/kg (Kodi et al., 2018).
Taylor et al. (2003) investigated genotoxicity in human Publisher’s note
peripheral blood lymphocytes of South African medicinal plants.
The results reported that the dichloromethane root extract of E. All claims expressed in this article are solely those of the authors
divinorum induced DNA damage (more cells with high tail DNA and do not necessarily represent those of their affiliated
content), which was however lower than that of the positive control organizations, or those of the publisher, the editors and the
(1 mM potassium bichromate). However, the bark extract of E. reviewers. Any product that may be evaluated in this article, or
natalensis showed positive results for genotoxicity in the claim that may be made by its manufacturer, is not guaranteed or
micronucleus test. endorsed by the publisher.

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