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Review of Ethnomedicinal Uses, Phytochemistry and Pharmacological Properties of Euclea natalensis A.DC.

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Euclea natalensis is traditionally used as herbal medicine for several human diseases and ailments in tropical Africa. This study reviews information on ethnomedicinal uses, botany, phytochemical constituents, pharmacology and toxicity of E. natalensis. Results of this study are based on literature search from several sources including electronic databases, books, book chapters, websites, theses and conference proceedings. This study showed that E. natalensis is used as traditional medicine in 57.1% of the countries where it is indigenous. Euclea natalensis has a high degree of consensus on abdominal pains, antidote for snake bites, diabetes, diarrhoea, malaria, roundworms, stomach problems, toothache, venereal diseases and wounds. Several ethnopharmacological studies have shown that crude extracts and chemical compounds from E. natalensis demonstrated many biological activities both in vitro and in vivo, which included antibacterial, antidiabetic, antifungal, antimycobacterial, antiviral, antioxidant, antiplasmodial, larvicidal, antischistosomal, molluscicidal, dentin permeability and hepatoprotective activities. Future studies should focus on the mechanism of biological activities of both crude extracts and chemical compounds from the species, as well as structure–function relationships of bioactive constituents of the species.
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molecules
Review
Review of Ethnomedicinal Uses, Phytochemistry and
Pharmacological Properties of Euclea natalensis A.DC.
Alfred Maroyi ID
Medicinal Plants and Economic Development (MPED) Research Center, Department of Botany,
University of Fort Hare, Private Bag X1314, Alice 5700, South Africa; amaroyi@ufh.ac.za; Tel.: +27-719600326
Received: 1 November 2017; Accepted: 30 November 2017; Published: 2 December 2017
Abstract:
Euclea natalensis is traditionally used as herbal medicine for several human diseases
and ailments in tropical Africa. This study reviews information on ethnomedicinal uses, botany,
phytochemical constituents, pharmacology and toxicity of E. natalensis. Results of this study are
based on literature search from several sources including electronic databases, books, book chapters,
websites, theses and conference proceedings. This study showed that E. natalensis is used as traditional
medicine in 57.1% of the countries where it is indigenous. Euclea natalensis has a high degree of
consensus on abdominal pains, antidote for snake bites, diabetes, diarrhoea, malaria, roundworms,
stomach problems, toothache, venereal diseases and wounds. Several ethnopharmacological studies
have shown that crude extracts and chemical compounds from E. natalensis demonstrated many
biological activities both
in vitro
and
in vivo
, which included antibacterial, antidiabetic, antifungal,
antimycobacterial, antiviral, antioxidant, antiplasmodial, larvicidal, antischistosomal, molluscicidal,
dentin permeability and hepatoprotective activities. Future studies should focus on the mechanism
of biological activities of both crude extracts and chemical compounds from the species, as well as
structure–function relationships of bioactive constituents of the species.
Keywords: ethnopharmacology; Euclea natalensis; herbal medicine; traditional uses; tropical Africa
1. Introduction
Euclea natalensis A.DC. (family Ebenaceae) is traditionally used as herbal medicine to treat several
human diseases and ailments in tropical Africa. The wide usage of the species as herbal medicine in
tropical Africa has resulted in a major resurgence in interest in the ethnopharmacological properties of
E. natalensis, a plant species characterized by several uses which are recognized culturally, medicinally
and commercially. According to Van Wyk [
1
,
2
], the roots of E. natalensis have commercial potential
as remedies for chest ailments, toothache, bronchitis, pleurisy, asthma, headache, and urinary tract
infections, as well as mouth rinses or toothbrush sticks that may be developed into pharmaceutical
drugs and health promoting products. The twigs and roots of E. natalensis are traditionally used as
chewing sticks, toothbrushes and mouthwash for oral hygiene, for cleaning teeth and the gums in
the belief that these plant parts benefit the health of the mouth and teeth [
3
]. In southern Africa, the
root or twig of E. natalensis is peeled from the end of a small root or twig and the end is chewed to
a fibrous brush, with the root changing in colour from white to yellow as it is chewed, imparting
a pungent and refreshing taste to the mouth [
4
]. In East Africa, the twigs are used as toothbrushes
and roots of E. natalensis are also chewed by women to impart a red colour to their mouths [
5
].
Research by
Van Wyk and Gericke [4]
showed that, in southern Africa, the root bark of E. natalensis is
moistened and applied to the lips as a yellow-brown cosmetic by women. Research by Cunningham [
6
]
revealed that roots of E. natalensis are sold as herbal medicines in herbal medicine informal markets in
Mozambique and South Africa. Similarly, leaves of E. natalensis are sold as herbal medicines in herbal
medicine informal markets in Tanzania [7].
Molecules 2017,22, 2128; doi:10.3390/molecules22122128 www.mdpi.com/journal/molecules
Molecules 2017,22, 2128 2 of 16
Euclea natalensis is a widely used as herbal medicine in South Africa and the species is an ingredient
of a commercial herbal concoction or formula called imbiza [
8
]. The imbiza formula or prescription is
in clinical use, sold in informal markets, medicinal herbal markets and pharmacies in South Africa.
Imbiza is a general term for a class of purgative medicines which affect internal cleansing system,
often administered as a vaginal douche, a drink or an emetic [
9
]. Imbiza has also gained popularity
in South Africa as an immune booster and as a tonic used to treat and manage various minor and
chronic illnesses [
10
]. Imbiza is used as herbal concoction for ailments such as colds, chest infections,
skin infections, diabetes, tuberculosis, cancer and symptoms of human immunodeficiency virus (HIV)
and acquired immunodeficiency syndrome (AIDS) [
11
]. Traditional healers in South Africa prescribe
imbiza for women’s fertility problems, as a blood purifier, scrofula and for chest complaints [
8
,
9
].
Imbiza is also traditionally used to facilitate pregnancy by preparing the uterus to accept a fetus [
9
].
Apart from E. natalensis,imbiza also contain roots of Polygala fruticosa P. J. Bergius, Raphionacme spp.,
bulbous roots of Crinum spp. and Cyrtanthus obliquus (L. f.) Aiton and the root barks of Zanthoxylum
capense (Thunb.) Harv., Capparis tomentosa Lam. and Rauvolfia caffra Sond. [
8
]. While the cultural,
medicinal and ethnopharmacological values of E. natalensis have received considerable attention in the
last 50 years [
1
4
,
8
,
12
21
], no attempt has been made to review literature on the medicinal potential,
phytochemistry and ethnopharmacological properties. Therefore, the aim of the current review is to
comprehensively document information on the botany, medicinal uses, phytochemistry and biological
activities of E. natalensis to understand its ethnopharmacological value as traditional herbal medicine.
2. Research Methodology
To identify relevant information on the botany, medicinal uses, phytochemistry and biological
activities of E. natalensis, a review was compiled based on scientific literature from various sources
including Google Scholar, Web of Science, SciFinder, Scopus, Science Direct, PubMed, Scielo,
Springerlink, Google Patents, Espacenet, BioMed Central (BMC) and Medline. The keywords
used for identification of relevant data included different scientific name and synonyms, common
English names, and the terms: biological activities, medicinal uses, ethnobotany, ethnopharmacology,
medicinal, pharmacology, phytochemistry and therapeutic value, Euclea natalensis, Euclea multiflora,
Royena macrophylla, Natal guarri, Natal ebony and large-leaved guarri. Other relevant scientific
publications were obtained from the University of Fort Hare library, Alice campus in South Africa.
3. Ethnomedicinal Uses of E. natalensis
The different uses of E. natalensis are summarized in Table 1, including data about herbal
preparation and countries where such practices are applied. Information on phytochemicals
is summarized in Table 2and associated pharmacological properties are discussed separately.
Ethnomedicinal uses of E. natalensis in Table 1are validated by bibliography shown in Table 2and
pharmacological properties of the species discussed in Section 5of the manuscript.
Euclea natalensis has been recorded in Angola, Botswana, the Democratic Republic of Congo,
Ethiopia, Kenya, Malawi, Mozambique, Namibia, Somalia, South Africa, Swaziland, Tanzania, Zambia
and Zimbabwe. The species is found in arid and rocky habitats, termite mounds, dune bush, open
grassveld, thickets, forests, forest margins, river banks and swamps, with altitude ranging from sea
level to about 1600 m above sea level [
5
,
22
,
23
]. It is a shrub or small to medium-sized dioecious tree.
The roots, bark, twigs and leaves of E. natalensis exhibit several medicinal applications and used to treat
or manage various human diseases and ailments throughout the distributional range of the species
(Table 1). The roots were the most used plant parts (83.3%), followed by bark and leaves with 6.7%
each, leaf sap (3.3%) and twigs (1.7%). A total of 51 ethnomedicinal uses of E. natalensis are documented
in the literature (Table 1) from eight countries in tropical Africa. The country with the highest number
of ethnomedicinal uses is South Africa with 30 ethnomedicinal uses based on 11 literature records,
followed by Tanzania with 15 uses and six literature records, Kenya with 11 uses and five literature
records, Mozambique with five uses and five literature records and Malawi with five uses and one
Molecules 2017,22, 2128 3 of 16
literature record (Table 1). Literature records show high degree of consensus for at least 12 major
diseases and ailments, which include abdominal pains, antidote for snake bites, chewing sticks or
toothbrush, diabetes, diarrhoea, malaria, mouthwash, purgative, roundworms, stomach problems,
toothache and venereal diseases (Table 1). In some cases, different parts of E. natalensis are mixed with
plant parts of other species forming an herbal concoction or formula. For example, in South Africa,
roots of E. natalensis are boiled with roots of Capparis tomentosa and thorns of Gymnosporia heterophylla
and Phoenix reclinata and tied to a sharp instrument which is then stabbed into the chest of a patient
suffering from pleurisy and pleurodynia [
8
,
14
]. In South Africa, E. natalensis is an ingredient of herbal
concoction called imbiza also containing roots of Polygala fruticosa, Raphionacme spp., bulbous roots of
Crinum spp. and Cyrtanthus obliquus and root barks of Zanthoxylum capense, Capparis tomentosa and
Rauvolfia caffra used to purify the blood [
8
]. Research by Chauke et al. [
24
] revealed that root decoction
of E. natalensis is taken orally mixed with roots of Grewia hexamita and Pappea capensis as remedies for
stomach complaints and reproductive problems in women such as infertility and painful menstruation.
In Tanzania, root decoction of E. natalensis is mixed with other plant species such as Acacia brevispica,
Acacia hockii, Acacia robusta, Aloe secundiflora, Asparagus flagellaris, Capparis fascicularis, Carrisa spinarum,
Clerodendrum myricoides, Cymbopogon citratus, Dichrostachys cinerea, Eucalyptus spp., Gomphocarpus
fruticosus, Harrisonia abyssinica, Kedrostis foetidissima, Mangifera indica, Pennisetum purpureum, Psidium
guajava, Punica granatum, Musa spp., Sansevieria ehlenbergii, Withania somnifera, Ximenia caffra and
Zanthoxylum chalybeum as herbal medicine for amoebic dysentery, opportunistic infections and venereal
diseases [25].
Table 1. Medicinal uses of Euclea natalensis based on ailment categories proposed by Cook [26].
Monotherapeutic Applications Plant Parts Used Country References
Categories/subcategories
Blood system disorders
Blood purification Root infusion taken orally South Africa [27]
Digestive system disorders
Constipation, diarrhoea, enema,
purgative, stomach problems Root infusion taken orally Kenya, Tanzania, Malawi,
Mozambique, South Africa [7,23,2831]
Genitourinary system disorders
Sexual stimulation, urinary tract
infections, vaginal discharge Bark, root infusion taken orally South Africa,
Swaziland, Kenya [8,30,32,33]
Infections or infestations
Anthelminthic, asthma, bronchitis,
chewing sticks, gonorrhoea,
hookworm, malaria, mouthwash,
rabies, schistosomiasis, scrofulous
swellings, sexually transmitted
infections (STIs), syphilis,
toothache, tuberculosis, venereal
diseases, yellow fever
Charred and powdered root, leaf
sap applied topically or leaf, root
decoction taken orally. Roots or
twigs used as chewing sticks,
mouthwash or toothbrush.
Tanzania, Ethiopia,
Mozambique, Kenya,
Zimbabwe, South Africa,
Malawi, Swaziland
[4,5,7,8,1320,23,24,28,30,
32,3440]
Injuries
Burns, leprosy sores, sores,
wounds
Root bark decoction or powder
applied topically East Africa, South Africa [8,13,14,16,23,41]
Metabolic system disorders
Diabetes Root decoction taken orally Kenya; South Africa [24,42,43]
Nervous system disorders
Epilepsy, hypnotic Root decoction taken orally or root
smoke inhaled South Africa [4,44]
Pain
Abdominal pains, earache,
headache, splenic swellings, ulcers
Root infusion taken orally or
applied topically
Kenya, Malawi, South
Africa, Swaziland, Tanzania [8,13,16,23,28,30,32,40]
Molecules 2017,22, 2128 4 of 16
Table 1. Cont.
Monotherapeutic Applications Plant Parts Used Country References
Poisoning
Antidote for poisoning, snake bite
Powdered leaf applied topically or
root decoction taken orally Kenya, Malawi [28,29]
Pregnancy/birth/puerperium
disorders
Abortifacient, infertility,
menstrual problems, puerperium Root decoction taken orally Mozambique, South Africa [41,44,45]
Respiratory system disorders
Chest complaints Root decoction applied topically South Africa [1,2,8]
Skin, subcutaneous cellular
tissue disorders
Skin care Root infusion applied topically South Africa [38]
Miscellaneous
Bad dreams, protective charms Bark infusions applied topically or
leaf decoction taken orally South Africa, Tanzania [7,8,41]
Multi-therapeutic applications
Amoebic dysentery
Root infusion taken orally mixed
with roots of Carissa spinarum L.,
Harrisonia abyssinica Oliv. and
Ximenia caffra Sond.
Tanzania [25]
Infertility
Root infusion taken orally mixed
with roots of Grewia hexamita Burret
and Pappea capensis Sond. & Harv.
South Africa [24]
Menstrual problems
Root infusion taken orally mixed
with roots of Grewia hexamita and
Pappea capensis
South Africa [24]
Opportunistic infections
Root infusion taken orally mixed
with roots of Acacia hockii De Wild.,
Acacia robusta Burch., Clerodendrum
myricoides R. Br., Cymbopogon citratus
(DC.) Stapf, Dichrostachys cinerea (L.)
Wight & Arn., Eucalyptus spp.,
Kedrostis foetidissima (Jacq.) Cogn.,
Mangifera indica L.,
Pennisetum purpureum Schumach.,
Psidium guajava L.,
Punica granatum L., Musa spp.,
Withania somnifera (L.) Dunal and
Ximenia caffra
Tanzania [25]
Root infusion taken orally mixed
with roots of Asparagus flagellaris
(Kunth) Baker, Capparis fascicularis
DC., Harrisonia abyssinica, Sansevieria
ehrenbergii Schweinf. ex Baker and
Ximenia caffra
Root infusion taken orally mixed
with roots of Acacia brevispica Harms,
Aloe secundiflora Engl., Carissa
spinarum,Dichrostachys cinerea,
Harrisonia abyssinica, Ximenia caffra
Root infusion taken orally mixed
with roots of Carissa spinarum,
Harrisonia abyssinica,Withania
somnifera,Ximenia caffra and
Zanthoxylum chalybeum Engl.
Root infusion taken orally mixed
with roots of Carissa spinarum,
Harrisonia abyssinica and
Ximenia caffra
Pleurisy
Root infusion taken orally mixed
with roots of Capparis tomentosa and
thorns of Gymnosporia heterophylla
and Phoenix reclinata
South Africa [14]
Molecules 2017,22, 2128 5 of 16
Table 1. Cont.
Monotherapeutic Applications Plant Parts Used Country References
Pleurodynia
Root infusion taken orally mixed
with roots of Capparis tomentosa and
thorns of Gymnosporia heterophylla
and Phoenix reclinata
South Africa [14]
Stomach problems
Root infusion taken orally mixed
with roots of Grewia hexamita and
Pappea capensis
South Africa [24]
Venereal diseases
Root decoction mixed with roots of
Zanthoxylum chalybeum
Tanzania [25]
Root decoction mixed with roots of
Aloe secundiflora,Gomphocarpus
fructicosus (L.) W. T. Aiton and
Harrisonia abyssinica,
Root decoction mixed with roots of
Carissa spinarum,
Harrisonia abyssinica, Ximenia caffra
4. Phytochemistry
Various chemical constituents have been isolated from E. natalensis, mainly compounds
belonging to naphthoquinone and pentacyclic terpenoids classes (Table 2). Lopes and Paul [
46
]
isolated two pentacyclic terpenoids, betulin
1
and lupeol
2
from the root bark of E. natalensis,
while Tannock [47]
isolated naphthoquinones, namely isodiospyrin
3
and mamegakinone
4
from
the same species (Table 2). King et al. [
48
] isolated natalenone
5
from the root bark of E. natalensis,
while Ferreira et al. [49]
isolated natalenone
5
, 8
0
-hydroxydiospyrin
6
, euclanone
7
, galpinone
8
,
methylnaphthazarin
9
and neodiospyrin
10
from the same species (Table 2). Khan et al. [
50
]
isolated lupeol
2
, mamegakinone
4
, diospyrin
11
and 7-methyljuglone
12
from the root bark of
E. natalensis while Khan [
51
] isolated 4,8-dihydroxy-6-methyl-1-tetralone (shinanolone
13
) from
the same species (Table 2). Weigenand et al. [
52
] isolated betulin
1
, lupeol
2
, shinanolone
13
, 20(29)-lupene-3
β
-isoferulate
14
and octahydroeuclein
15
from the root bark of E. natalensis.
Similarly, Lall et al. [
53
] isolated betulin
1
, lupeol
2
, shinanolone
13
, 20(29)-lupene-3
β
-isoferulate
14
,
octahydroeuclein
15
and
β
-sitosterol
16
from the root bark of E. natalensis (Table 2).
Van der Kooy [54]
isolated isodiospyrin
3
, mamegakinone
4
, neodiospyrin
10
, diospyrin
11
, 7-methyljuglone
12
,
shinanolone
13
and 5-hydroxy-4-methoxy-2-nathaldehyde
17
from the root bark of E. natalensis.
Van der Kooy et al. [
55
] isolated isodiospyrin
3
, mamegakinone
4
, neodiospyrin
10
, diospyrin
11
,
7-Methyljuglone
12
and shinanolone
13
from root bark of E. natalensis (Table 2). Bapela et al. [
56
]
assessed the correlation between plant growth and accumulation of diospyrin
11
, 7-methyljuglone
12
and shinanolone
13
in seeds and seedlings of E. natalensis, but the compounds accumulated
at variable rates and no trend could be established between their synthesis and seedling growth.
Bapela et al. [
57
] assessed seasonal variation of isodiospyrin
3
and neodiospyrin
10
, diospyrin
11
,
7-methyljuglone
12
and shinanolone
13
from wild plants of E. natalensis but no defining pattern
was established in the synthesis and accumulation of levels of these compounds within the species.
Bapela et al. [
58
] assessed effect of nitrogen, phosphorus and potassium fertilizers on accumulation of
isodiospyrin
3
, neodiospyrin
10
, diospyrin
11
, 7-methyljuglone
12
and shinanolone
13
. A significantly
positive correlation was established between the concentration of isodiospyrin
3
, neodiospyrin
10
,
diospyrin
11
, 7-methyljuglone
12
and shinanolone
13
with fertilization from field-grown seedlings [
58
].
Joubert et al. [59]
used high performance liquid chromatography (HPLC) to quantify the concentration
of diospyrin
11
and 7-methyljuglone
12
in roots of E. natalensis. The concentration of diospyrin
11
was
higher (about 2750 mg/kg) than the concentration of 7-methyljuglone
12
which was about 450 mg/kg.
Joubert et al. [
59
] argued that the observed variation in naphthoquinones concentration could be
due to the age of the roots harvested, wound and environmental or other stress factors. Cooper
and Owen-Smith [
60
] showed that E. natalensis leaves contain >5% condensed tannins and therefore
Molecules 2017,22, 2128 6 of 16
impalas and kudus avoided grazing the species due to high tannin content while the leaves of the
species were accepted by goats.
Table 2. Chemical compounds isolated and characterized from Euclea natalensis root bark.
No. Chemical Compound Chemical Formula References
Pentacyclic terpenoids
1Betulin CH30H50 O2[46,52,53]
2Lupeol C30H50 O [46,50,52,53]
14 20(29)-lupene-3β-isoferulate C40H58 O4[52,53]
16 β-sitosterol C29H50O [53]
Naphthoquinone
3Isodiospyrin C22H14 O6[47,54,55]
4Mamegakinone C22H14 O6[47,50,54,55]
5Natalenone C22H16 O6[48,49]
680-hydroxydiospyrin C22H14O7[49]
7Euclanone C22H14 O7[49]
8Galpinone C33H20 O9[49]
9Methylnaphthazarin C11H8O4[49]
10 Neodiospyrin C22H14 O6[49,54,55]
11 Diospyrin C22H14 O6[50,54,55]
12 7-methyljuglone C11H8O3[50,54,55]
13 Shinanolone C11H12 O3[5255]
15 Octahydroeuclein C22H22O6[52,53]
17 5-hydroxy-4-methoxy-2-nathaldehyde C12H10O3[54]
5. Pharmacological Properties
Extracts from Euclea natalensis possess a wide spectrum of pharmacological properties, including
antibacterial [
25
,
35
,
40
,
50
,
52
,
61
63
], antimycobacterial [
17
,
39
,
52
,
54
,
55
,
64
70
],
antifungal [51,57]
,
antiviral [
18
,
71
], antidiabetic [
72
], antioxidant [
67
,
72
], antiplasmodial [
73
], larvicidal [
74
],
antischistosomal [
75
], molluscicidal [
76
], dentin permeability [
77
,
78
], hepatoprotective [
79
],
cytotoxicity [
17
,
18
,
35
,
67
,
80
] and toxicity [
19
] activities as outlined below. Some of the documented
pharmacological properties of crude extracts and compounds isolated from the species may be
responsible for the ethnomedicinal uses of the species indicated in Table 1. However, assessment of
the ethnomedicinal uses and documented pharmacological effects of the species show that there is
not enough systematic data on phytochemistry and pharmacological effects for the majority of the
ethnomedicinal applications of the species.
5.1. Antimicrobial Activities
Euclea natalensis is widely used as herbal medicine for a wide range of infectious diseases
caused by microorganisms. Such diseases or ailments include amoebic dysentery, bronchitis, chest
complaints, diarrhoea, sexually transmitted infections, sores, syphilis, toothache, tuberculosis, urinary
tract infections, venereal diseases and wounds [
7
,
8
,
13
,
16
,
21
,
24
,
25
,
29
,
30
,
38
,
39
,
41
]. Such wide use of
E. natalensis against bacterial, fungal and viral infections in traditional medicine prompted several
researchers to assess antibacterial, antifungal, antimycobacterial and antiviral activities of crude
extracts and compounds isolated from the species. The antibacterial, antifungal, antimycobacterial
and antiviral investigations reported mixed results as highlighted in the relevant sub-sections below.
5.1.1. Antibacterial Activity
Khan and Nkunya [
40
] evaluated antibacterial activities of E. natalensis root bark extract against
Escherichia coli and Staphylococcus aureus. The extract was active against Staphylococcus aureus exhibiting
15–20 mm inhibition zone. Khan and Nkunya [
40
] evaluated antibacterial activities of the compounds
mamegakinone
4
, diospyrin
11
and 7-methyljuglone
12
isolated from E. natalensis roots against
Molecules 2017,22, 2128 7 of 16
Bacillus anthracis, Bacillus cereus, Clostridium perfringens, Corynebacterium diphtheriae, Escherichia coli,
Haemophilus influenzae, Klebsiella aerogenes, Neisseria gonorrhoeae, Pseudomonas aureginosa, Salmonella
Heidelberg, Shigella dysenteriae, Shigella flexnerii and Staphylococcus aureus. The compounds were active
against most of the bacteria except Escherichia coli and Pseudomonas aureginosa, with inhibition zone
demonstrated by the pathogens ranging from 8 mm to 24 mm [
40
]. A preliminary antibacterial
assay showed that the petroleum ether and chloroform extracts of E. natalensis root bark gave an
inhibitory zone of 15 mm, at an extract concentration of 0.3 mg/mL against Staphylococcus aureus [
50
].
Lall and Meyer [61]
evaluated antibacterial activities of water and acetone root extracts of E. natalensis
against Bacillus cereus,Bacillus pumilus,Bacillus subtilis,Enterobacter aerogenes,Enterobacter cloacae,
Escherichia coli,Klebsiella pneumoniae,Micrococcus kristinae,Pseudomonas aeruginosa, Serratia marcescens
and Staphylococcus aureus. The water and acetone extracts inhibited the growth of Bacillus cereus,
Bacillus pumilus,Bacillus subtilis,Micrococcus kristinae and Staphylococcus aureus at concentrations
ranging between 0.1 mg/mL and 6.0 mg/mL. The water extract did not exert any inhibitory action
on Gram-negative bacteria, while the acetone extract showed inhibitory activity at a concentration of
5.0 mg/mL against all the Gram-negative bacteria investigated [
61
]. Weigenand et al. [
52
] evaluated
antibacterial activities of betulin
1
, lupeol
2
, shinanolone
13
, 20(29)-lupene-3
β
-isoferulate
14
and
octahydroeuclein
15
compounds isolated from root bark of E. natalensis against Bacillus cereus,Bacillus
pumilus,Bacillus subtilis,Enterobacter cloacae,Escherichia coli,Klebsiella pneumoniae, Pantoea agglomerans,
Pseudomonas aeruginosa,Serratia marcescens,Staphylococcus aureus and Streptococcus faecalis using the
agar plate method with streptomycin sulphate as control. The compound shinanolone
13
showed
inhibitory activity against Gram-positive bacterial strains at a concentration of 0.1 mg/mL and
20(29)-lupene-3
β
-isoferulate
14
showed inhibitory activity against Bacillus pumilus at a concentration
of 0.1 mg/mL [
52
]. More et al. [
35
] evaluated antimicrobial activities of ethanol leaf extracts of
E. natalensis against oral pathogens, namely Actinobacillus actinomycetemcomitans,Actinomyces naeslundii,
Actinomyces israelii,Porphyromonas gingivalis,Prevotella intermedia and Streptococcus mutans, using the
disk diffusion method. The extracts were active against the tested bacteria with both minimal inhibitory
concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 1.6 mg/mL
to 25 mg/mL [
35
]. Van Vuuren and Naidoo [
62
] evaluated antibacterial activities of aqueous and a
mixture of methanol and dichloromethane (1:1) leaf extracts of E. natalensis against bacterial pathogens
associated with urogenital or sexually transmitted infections which included Gardnerella vaginalis,
Neisseria gonorrhoeae, Oligella ureolytica and Ureaplasma urealyticum. All methanol and dichloromethane
extracts exhibited noteworthy activities with MIC values ranging from 1.5 mg/mL to 2.0 mg/mL
against all tested pathogens. The exhibited antibacterial activities validate the ethnobotanical use of
E. natalensis as herbal medicine against vaginal discharge in Kenya [
30
], sexually transmitted infections
and syphilis in South Africa [
8
,
13
,
24
,
38
] and venereal diseases in South Africa and Tanzania [
8
,
13
,
25
].
Sharma and Lall [
63
] evaluated antimicrobial activities of leaf and root ethanol extracts of E. natalensis
against pathogenic bacteria, Propionibacterium acnes using the broth dilution method with tetracycline
as positive control. The extracts showed weak activities with MIC value of 250
µ
g/mL in comparison
to MIC value of 3.1 µg/mL demonstrated by tetracycline, the positive control.
Otieno et al. [
25
] evaluated antimicrobial activities of root ethanol extracts of E. natalensis, and
extracts of E. natalensis mixed with root extracts of Carissa spinarum,Ximenia caffra and Harrisonia
abyssinica against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi,
Staphylococcus aureus and Streptococcus faecalis using the disc diffusion assay with ampicillin and
dimethylsulphoxide (DMSO) as positive and negative controls, respectively. The multi-plant extracts
of E. natalensis mixed with Carissa spinarum,Ximenia caffra and Harrisonia abyssinica were more active
against all tested microbes with inhibition zones ranging from 18 to 22 mm, MIC values ranging
8.3 ±0.6 µg/mL
to 55
±
2.6
µ
g/mL and MBC values ranging from 0.02 mg/mL to 0.335 mg/mL [
25
].
The single extract of E. natalensis showed some activity against Staphylococcus aureus only with inhibition
zone of 14 mm and MIC value of 55
±
4.4
µ
g/mL. These results support use and preference of
Molecules 2017,22, 2128 8 of 16
E. natelensis mixed with other plant species as remedy for stomach complaints in South Africa [
14
,
24
],
amoebic dysentery, opportunistic infections and venereal diseases in Tanzania [25].
5.1.2. Antimycobacterial Activity
Lall and Meyer [
39
] evaluated antimycobacterial activities of acetone and water root extracts
of E. natalensis against drug-resistant and drug-sensitive strains of Mycobacterium tuberculosis H37Rv
using the agar plate method. Acetone and water extracts inhibited the growth of Mycobacterium
tuberculosis at a concentration of 0.5 mg/mL. Lall and Meyer [
39
] evaluated the acetone and water
extracts using a rapid radiometric method against Mycobacterium tuberculosis and obtained a MIC
value of 0.1 mg/mL against the strains. In 2001, Lall and Meyer [64] evaluated the antimycobacterial
activities of diospyrin
11
isolated from E. natalensis against the drug-sensitive and drug-resistant
strains of Mycobacterium tuberculosis using the radiometric respiratory BACTEC assay. The compound
diospyrin
11
was active against Mycobacterium tuberculosis with MIC value of 100
µ
g/mL for all strains.
Weigenand et al. [
52
] evaluated antimycobacterial activities of betulin
1
, lupeol
2
, shinanolone
13
,
20(29)-lupene-3
β
-isoferulate
14
and octahydroeuclein
15
compounds isolated from root bark of E.
natalensis against a drug-sensitive strain of Mycobacterium tuberculosis H37Rv using a rapid radiometric
method with TB drugs, streptomycin and ethambutol as controls. The compound shinanolone
13
showed inhibitory activity against a drug sensitive strain of Mycobacterium tuberculosis at a
concentration of 0.1 mg/mL [
52
]. Lall et al. [
17
] evaluated antimycobacterial activities of crude
extracts, the compounds betulin
1
, lupeol
2
, diospyrin
11
and 7-methyljuglone
12
isolated from the
roots of E. natalensis against Mycobacterium tuberculosis both in axenic medium and in a macrophage
cell line. Crude extract, diospyrin
11
and 7-methyljuglone
12
isolated from the plant exhibited MIC
values of 8.0, 8.0 and 0.5
µ
g/mL, respectively, against Mycobacterium tuberculosis while betulin
1
and
lupeol
2
were inactive. The MIC value of 7-methyljuglone
12
against a panel of clinical pan-sensitive
and drug-resistant strains of Mycobacterium tuberculosis ranged from 0.32 to 1.25
µ
g/mL [
17
]. Similarly,
Van der Kooy et al. [
52
] evaluated antimycobacterial activities of isodiospyrin
3
, mamegakinone
4
,
neodiospyrin
10
, diospyrin
11
, 7-methyljuglone
12
and shinanolone
13
isolated from root extracts of E.
natalensis against Mycobacterium tuberculosis using the radiometric respiratory BACTEC assay. The MIC
values of isodiospyrin
3
(10.0
µ
g/mL), neodiospyrin
10
(10.0
µ
g/mL), diospyrin
11 (8.0 µg/mL)
and 7-methyljuglone
12
(0.5
µ
g/mL) compared well to those of the known antimycobacterial drugs
ethambutol, isoniazid and rifampicin [
55
]. McGaw et al. [
65
] evaluated antimycobacterial activities
of root extracts of E. natalensis and the compound diospyrin
11
isolated from the species against
Mycobacterium bovis, Mycobacterium fortuitum and Mycobacterium smegmatis using a twofold serial
dilution assay with anti-TB drug isoniazid as positive control. The root extracts showed some activities
with MIC values ranging from 5.7
µ
g/mL to 16.3
µ
g/mL against the tested organisms, and the
compound diospyrin
11
also showed some activities with MIC values ranging from 15.6
µ
g/mL
to 62.5
µ
g/mL against the tested organisms [
65
]. McGaw et al. [
66
] evaluated antimycobacterial
activities of acetone, chloroform and methanol root extracts of E. natalensis and the compounds
lupeol
2
, neodiospyrin
10
, diospyrin
11
, 7-methyljuglone
12
and shinanolone
13
isolated from the
species against Mycobacterium bovis, Mycobacterium fortuitum and Mycobacterium smegmatis using a
twofold serial dilution assay with anti-TB drug isoniazid as positive control. The plant extracts
demonstrated activity with MIC values ranging from 5.7 to 664.1
µ
g/mL against Mycobacterium
bovis, Mycobacterium fortuitum and Mycobacterium smegmatis [
66
]. The MBC values were relatively
high, ranging from 625 to > 2 500
µ
g/mL against Mycobacterium bovis, Mycobacterium fortuitum and
Mycobacterium smegmatis [
66
]. Compound lupeol
2
was inactive against all tested pathogens while
neodiospyrin
10
, diospyrin
11
, 7-methyljuglone
12
and shinanolone
13
demonstrated activities with
MIC values ranging from 1.6 to 166.7
µ
g/mL and MBC values ranging from 15.6 to 250.0
µ
g/mL against
Mycobacterium bovis, Mycobacterium fortuitum and Mycobacterium smegmatis [
66
]. Lall et al. [
67
] evaluated
in vitro
antimycobacterial activities of ethanolic shoot extracts of E. natalensis against Mycobacterium
tuberculosis H37Rv using a 96-well microtitre to determine the minimum inhibitory concentration
Molecules 2017,22, 2128 9 of 16
of the extract. The E. natalensis extracts were also evaluated for
in vivo
antimycobacterial activities
in Mycobacterium tuberculosis H37Rv infected mice. The MIC value of the extract was found to be
125
µ
g/mL against Mycobacterium tuberculosis compared to MIC value of 0.25
µ
g/mL exhibited by
the positive control isoniazid. The antimycobacterial activities of E. natalensis extracts evaluated on
Mycobacterium tuberculosis (H37Rv) infected Balb/c mice showed substantial decrease in bacterial
loads when comparing the infected control group to the treatment groups, showing a decrease in lung
homogenate colony forming units from 1.5 ×106(control) to 7.1 ×103(drug control) [67]. Therefore,
the traditional use of E.natalensis extract against sores, purulent lesions and skin infections, cough
could possibly be attributed to the activities of compounds such as of isodiospyrin
3
, neodiospyrin
10
,
diospyrin
11
, 7-methyljuglone
12
and shinanolone
14
against Mycobacterium tuberculosis. Evaluation of
antimycobacterial activities of naphthoquinone compounds isolated from E.natalensis [
54
,
68
70
] seem
to suggest that 7-methyljuglone 12 and diospyrin 11 are the most active constituents.
5.1.3. Antifungal Activity
Lall et al. [
53
] evaluated antifungal activities of the compounds betulin
1
, lupeol
2
, shinanolone
13
, 20(29)-lupene-3
β
-isoferulate
14
, octahydroeuclein
15
and
β
-sitosterol
16
isolated from the root bark
of E. natalensis against Aspergillus flavus, Aspergillus niger, Cladosporium cladosporioides and Phytophthora
spp. Aspergillus niger was significantly inhibited by shinanolone
13
, 20(29)-lupene-3
β
-isoferulate
14
and
β
-sitosterol
16
at 0.01 mg/mL. Of all the compounds tested, only octahydroeuclein
15
was found to be significantly effective against Phytophthora spp. at 0.1 mg/mL. The compounds
octahydroeuclein
15
and
β
-sitosterol
16
significantly inhibited the growth of Cladosporium cladosporioides
at 0.01 mg/mL [
53
]. None of the isolated compounds exhibited significant activities against Aspergillus
flavus at 0.01 mg/mL [
53
]. Van Vuuren and Naidoo [
62
] evaluated antifungal activities of aqueous
and a mixture of methanol and dichloromethane (1:1) leaf extracts of E. natalensis against Candida
albicans, a pathogen associated with genital candidiasis or thrush. The aqueous and a mixture of
methanol and dichloromethane extracts exhibited noteworthy activities with MIC values of 0.5 mg/mL
and 3.0 mg/mL against Candida albicans, respectively. The exhibited anticandidal activities validates
the ethnobotanical use of E. natalensis as herbal medicine against vaginal discharge in Kenya [
30
],
sexually transmitted infections in South Africa [
24
,
38
] and venereal diseases in South Africa and
Tanzania [8,13,25].
5.1.4. Antiviral Activities
Lall et al. [
18
] evaluated antiviral activities of acetone and water extracts of E. natalensis and
the compound diospyrin
11
isolated from this species against herpes simplex virus Type 1 (HSV-1).
The acetone extract of E. natalensis showed moderate antiviral activity against HSV-1, at concentrations
of 0.1 to 0.02 mg/mL as shown by the reduction of virus-induced cytopathogenic effects and the
protection of cells in a cell viability assay. The compound diospyrin
11
exhibited no inhibitory effects
while water extracts exhibited weak activity at a concentration of 0.2 mg/mL which corresponded to a
42% cytopathic effect [
18
]. Mahapatra et al. [
71
] evaluated the HIV-1 reverse transcriptase inhibition
activities of the compound 7-methyljuglone
12
isolated from the roots of E. natalensis and its synthetic
derivatives against recombinant HIV-1 enzyme using non-radioactive HIV-RT colorimetric assay.
The compound 7-methyljuglone
12
and synthesized compounds exhibited potent inhibitory activities
ranging from 70% to 100% at 100
µ
g/mL [
71
]. These findings will provide baseline data to future
research focusing on correlating the traditional use of E. natalensis as herbal medicine for viral infections
and the antiviral properties of the species.
5.2. Antidiabetic Activities
Nkobole et al. [
72
] evaluated antidiabetic activities of acetone root extracts of E. natalensis by
assessing
in vitro α
-glucosidase and
α
-amylase enzyme assays. The plant extract demonstrated
inhibition of 92.6
±
0.04% and 74.5
±
0.04% at 0.2 mg/mL on
α
-glucosidase and
α
-amylase, respectively.
Molecules 2017,22, 2128 10 of 16
The compounds lupeol
2
and
β
-sitosterol
16
isolated from the stem bark of Terminalia sericea Burch. ex
DC. stem bark were evaluated for antidiabetic activities using
α
-glucosidase and
α
-amylase enzyme
assays. Compounds lupeol
2
and
β
-sitosterol
16
inhibitory activities on
α
-glucosidase with 50%
maximal inhibitory concentration (IC
50
) values of 66.5
µ
M and 66.5
µ
M, respectively [
72
]. Against
α
-amylase, the compounds lupeol and
β
-sitosterol exhibited moderate activities with IC
50
values of
140.7
µ
M and 216.0
µ
M, respectively. These findings validate the traditional use of E. natalensis as
herbal medicine for diabetes in Kenya [43] and South Africa [24,42].
5.3. Antioxidant Activities
Nkobole et al. [
72
] evaluated antioxidant activities of acetone root extracts of E. natalensis using
2,2-diphenyl-1-picrylhydrazyl radical (DPPH) free radical assay. The DPPH scavenging activity
of the plant extract was 94.4
±
0.01% which was comparable to 95.8
±
0.01% demonstrated by
the control, Vitamin C. Nkobole et al. [
72
] also evaluated antioxidant activities of the compounds
lupeol
2
and
β
-sitosterol
16
isolated from the stem bark of Terminalia sericea using DPPH free radical
assay. The compound lupeol
2
demonstrated high radical activity, exhibiting half maximal effective
concentration (EC
50
) values of 3.66
µ
M, which was comparable to the EC
50
values of 2.52
µ
M
demonstrated by the control, Vitamin C [
72
]. Lall et al. [
67
] evaluated antioxidant activities of
E. natalensis ethanolic shoot extracts using theDPPH free radical assay. The IC
50
value of the extracts
against DPPH free radical was found to be 22.55
±
2.93
µ
g/mL against 4.34
±
0.48
µ
g/mL exhibited
by the control, ascorbic acid [
67
]. These results obtained by Lall et al. [
67
] and Nkobole et al. [
72
] are
important as intake of antioxidant rich herbal medicines scavenge free radicals and modulate oxidative
stress-related degenerative effects.
5.4. Antiplasmodial and Larvicidal Activities
Clarkson et al. [
73
] evaluated antiplasmodial activities of aqueous, dichloromethane,
dichloromethane and methanol (1:1) root and stem extracts of E. natalensis against Plasmodium falciparum
using the parasite lactate dehydrogenase assay. Euclea natalensis dichloromethane and methanol (1:1)
root and leaf extracts showed promising activities with IC
50
values of 5.1
µ
g/mL and 5.3
µ
g/mL,
respectively [
73
]. The antiplasmodial properties demonstrated by E. natalensis imply that the species
could be a promising candidate for further investigation as plant-based antimalarial agent. Historically,
some of the antimalarial drugs have been derived from herbal medicines or from structures modelled
on medicinal plant lead compounds and these include the quinoline-based antimalarials as well as
artemisinin and its derivatives. Maharaj et al. [
74
] evaluated larvicidal activities of roots and stem
dichloromethane extracts of E. natalensis by exposing the third instar Anopheles arabiensis larvae to
the extracts with acetone and distilled water as controls. The root and stem extracts exhibited 100%
mortality after 48 and 96 h of exposure, respectively [
74
]. These results provide a scientific basis to the
traditional uses of E. natalensis as herbal medicine for malaria in East Africa [
16
], Mozambique [
15
],
Tanzania [7,19] and Zimbabwe [20].
5.5. Antischistosomal and Molluscicidal Activities
Sparg et al. [
75
] evaluated antischistosomal properties of crude extracts of E. natalensis against
the schistosomula of Schistosoma haematobium with praziquantel and a culture medium blank as
controls. The schistosomula were placed into a culture medium to which the plant extracts were added.
Euclea natalensis was active, killing 66.7% of the schistosomula worms at a concentration of 3.13 mg/mL.
The schistosomula worms that were placed in the culture medium blank survived between 12 and 24 h
of exposure while the praziquantel MIC value was 1
µ
g/mL [
75
]. Ojewole [
76
] evaluated molluscicidal
activities of E. natalensis by exposing adult Bulinus africanus and Biomphalaria pfeifferi to sublethal and
lethal doses of crude and aqueous bark, leaf and twig extracts of the species for a period of 24 h using
niclosamide (Bayluscide
®
) (Coating Place Inc., Washington DC, WA, US) as reference molluscicide
for comparison. The extracts demonstrated moderate to strong molluscicidal activity with lethal dose
Molecules 2017,22, 2128 11 of 16
90% (LD
90
) value of 50–100 ppm compared to the positive control, niclosamide (Bayluscide
®
) which
killed all the snails at a dose of 1 ppm [
76
]. These pharmacological evaluations are of importance in
the traditional use of E. natalensis as remedy for schistosomiasis in South Africa [
8
,
13
] and remedy for
intestinal worms in East Africa [5,16] and Malawi [28] and South Africa [13,14].
5.6. Dental Health
Sales-Peres et al. [
77
] evaluated the effect of an experimental gel containing E. natalensis extract
on dentin permeability. The study assessed the
in vitro
variations in hydraulic conductance of dentin
after treatment with E. natalensis gel and acidified fluorophosphate gel. The acidified fluorophosphate
gel was worse for preventing dentin permeability (90.8%), followed by the control gel (77.1%), and the
E. natalensis extract was the most effective (66.0%). Therefore, E. natalensis presented the most effective
action to reduce dentin permeability. Sales-Peres et al. [
77
] revealed that E. natalensis gel not only
reduced dentin permeability, but also resisted posttreatment citric acid challenge without changing its
permeability. This effect can be attributed to the naphthoquinone compounds present in twigs and
roots of E. natalensis as the compounds result in the dentin tubule obliteration due to the formation of
a protective layer on the teeth [
77
]. Similarly, Sales-Peres et al. [
78
] evaluated the effect of E. natalensis
gel on the reduction of erosive wear with or without abrasion, in enamel and dentin. The authors
carried out five-day experimental crossover phases with volunteers wearing palatal devices containing
human enamel and dentin blocks. The E. natalensis gel was applied in a thin layer in the experimental
group and was not applied in the control group. The E. natalensis gel caused less wear in enamel in the
experimental group than in the control group and a statistically significant value was found for erosion
and erosion and abrasion in dentin. Therefore, E. natalensis may play a role in the prevention of dentin
loss under mild erosive and abrasive conditions [
78
]. Based on the research findings of Sales-Peres
et al. [
77
,
78
], E. natalensis extracts may be an alternative health product to protect oral health and
prevent dental caries, tooth wear and dentinal sensitivity. These findings support the traditional
use of the twigs and roots of E. natalensis as chewing sticks, toothbrush, mouthwash and remedy
for toothache in Kenya [
5
,
30
], Mozambique [
34
,
35
], South Africa [
4
,
8
,
13
,
35
,
38
], Swaziland [
32
] and
Tanzania [
5
,
7
,
21
]. The regular use of E. natalensis as chewing sticks, mouthwash or toothbrush might
control the formation and activity of dental plaque and therefore reduce the incidence of gingivitis
and possibly of dental caries [
31
]. These findings corroborate the wide application of the twigs and
roots of E. natalensis as chewing sticks, toothbrush, mouthwash and remedy for toothache in Kenya,
Mozambique, South Africa, Swaziland and Tanzania [4,5,7,21,30,32,38].
5.7. Hepatoprotective Effects
Lall et al. [
67
] evaluated
in vitro
hepatoprotective activities of E. natalensis ethanolic shoot extracts
on human HepG2 cells. The hepatoprotective activities of E. natalensis extracts were tested
in vivo
using a rat model of isoniazid- and rifampicin-induced hepatotoxicity. Euclea natalensis showed a
hepatoprotective effect (50% at 12.5
µ
g/mL) and the ability to increase T-helper 1 cell cytokines
Interleukin 12, Interleukin 2 and Interferon
α
by up to 12-fold and the ability to decrease the
T-helper 2 cell cytokine Interleukin 10 fourfold when compared to baseline cytokine production [
67
].
These findings provide a further scientific basis to the invention relating to the ethanolic extracts from
the shoots of E. natalensis exhibiting immune stimulatory activity and hepatoprotective activity
in vitro
and
in vivo
studies [
79
]. The ethanolic extract of E. natalensis provides an immune stimulatory effect
on peripheral blood mononuclear cells, selecting a Th1 immune response over a Th2 immune response.
Research by [
79
] showed that ethanolic shoot extract of E. natalensis showed significant
in vitro
hepatoprotective activities against D-galactosamine and
in vivo
studies, the extract was nontoxic,
acting as hepatoprotectant against the toxic effect of some of the first line drugs.
Molecules 2017,22, 2128 12 of 16
5.8. Cytotoxicity and Toxicity
Lall et al. [
17
] evaluated cytotoxicity of crude chloroform extract of the roots of E. natalensis,
diospyrin
11
and 7-methyljuglone
12
by exposing different concentrations of samples to green monkey
kidney cells (Vero) and a mouse macrophage cell line, J774A.1. Cytotoxicity results for the Vero
cell line showed that the crude extract and diospyrin
11
had 50% maximal inhibitory concentration
(IC
50
) values of 64.87 and 17.78
µ
g/mL, respectively. The concentration of 7-methyljuglone
12
that
effected a 90% reduction of growth of Mycobacterium tuberculosis Erdman within J774.1 macrophages
was 0.57
µ
g/mL [
17
]. Similarly, Lall et al. [
18
] evaluated cell toxicity of root extracts of E. natalensis
by determining the effect of the crude extracts and diospyrin
11
on the monolayers of primary
vervet monkey kidney (VK) cells. The dose of the plant samples that inhibited 50% cell growth
(ID
50
) after the incubation period was 0.1 mg/mL and 0.2 mg/mL for acetone and water extracts,
respectively. The compound diospyrin
11
exhibited an ID
50
value of 0.02 mg/mL on VK cells.
The water extract from the roots of the plant was the least toxic to cell cultures and inhibited
the replication of HSV-1 moderately at a concentration of 0.2 mg/mL [
18
]. More et al. [
31
]
evaluated cytotoxicity of ethanol leaf extracts of E. natalensis using the XTT (sodium 3
0
-[1-(phenyl
amino-carbonyl)-3,4-tetrazolium]-bis-[4-methoxy-6-nitro) benzene sulphonic acid hydrate) assay
method. The extracts showed cytotoxicity activity on the Vero cell line with IC50 value of
285.1 ±4.9 µg/mL [31]
. Mahapatra et al. [
71
] evaluated cytotoxicity activities of the compound
7-methyljuglone 12 isolated from the roots of E. natalensis and its synthetic derivatives using the XTT
assay method. Cytotoxicity results for the Vero cell line showed that the compound 7-methyljuglone
12
and synthesized compounds had EC
50
values ranging from 2.5
µ
g/mL to 36.1
µ
g/mL [
71
].
Kishore et al. [80]
evaluated cytotoxicity activities of 7-methyljuglone
12
isolated from the root extract
of E. natalensis and a series of its derivatives on MCF-7, HeLa, SNO and DU145 human cancer cell lines
using the XTT method. Most of the 7-methyljuglone derivatives exhibited significant toxicity on HeLa
and DU145 cell lines with IC
50
values ranging from 5.3
µ
M to 10.1
µ
M [
80
]. Lall et al. [
67
] evaluated
in vitro
cell cytotoxicity using cell lines (primary peripheral blood mononuclear cells, U937 monocytes
and Chang liver cells), acute and sub-acute toxicity were carried out on eight-week-old female Balb/c
mice by administering ethanolic shoot extracts of E. natalensis orally. During the study conducted
on the cytotoxic effect of E. natalensis on peripheral blood mononuclear cells, U937 monocytes and
Chang liver cells, E. natalensis extract showed no cellular toxicity with IC
50
values ranging from
131.3 ±1.67 µ
g/mL to 208.9
±
10.3
µ
g/mL. An IC
50
value below 50
µ
g/mL has been considered to
be moderately toxic and samples with a toxicity value higher than 100
µ
g/mL have been considered
to be non-toxic [
67
]. During mechanistic studies, the extract showed a 50% inhibition of mycothiol
reductase activity at 38.62
µ
g/mL. During the acute and sub-acute studies, E. natalensis exhibited no
toxic effect and the 50% lethal dose (LD
50
) was established to be above 2000 mg/kg. The extract was
able to reduce the mycobacterial load (1.5-fold reduction) in infected mice. Isoniazid and rifampicin
caused significant hepatic damage in rats, and the extract was able to reduce the toxicity by 15% and
40% at 50 mg/kg and 150 mg/kg respectively [67].
Moshi et al. [
19
] evaluated toxicity of ethanol roots and stem extracts of E. natalensis using the
brine shrimp lethality test. The extracts were toxic with LC
50
value of 19.33
µ
g/mL. These results
obtained by Moshi et al. [
19
] indicate the possibility that E. natalensis may be toxic calls for assessment
of target-organ toxicity studies.
6. Conclusions
Euclea natalensis is an important and frequently used herbal medicines in tropical Africa.
The species is widely used for human diseases and ailments such as abdominal pains, antidote
for snake bites, diabetes, diarrhoea, malaria, roundworms, stomach problems, toothache and venereal
diseases. Recent research on E. natalensis focused primarily on antimicrobial properties of the crude
extracts of the species, naphthoquinone and pentacyclic terpenoid compounds isolated from the
species. Literature studies revealed that naphthoquinone and pentacyclic terpenoid compounds
Molecules 2017,22, 2128 13 of 16
isolated from E. natalensis such as shinanolone
13
exhibited antibacterial effects [
50
], shinanolone
13
, 20(29)-lupene-3
β
-isoferulate
14
, octahydroeuclein
15
and
β
-sitosterol
16
exhibited antifungal
effects [
53
], isodiospyrin
3
, neodiospyrin
10
, diospyrin
11
, 7-methyljuglone
12
and shinanolone
13
exhibited antimycobacterial effects [
17
,
39
,
52
,
55
,
65
,
66
], diospyrin
11
and 7-methyljuglone
12
exhibited cytotoxic effects [
17
]. The compound 7-methyljuglone
12
appears to be the most efficient
antimycobacterial of all the compounds that have been isolated from E. natalensis so far. Any future
research on E. natalensis should consolidate its ethnomedicinal usage with its phytochemistry and
pharmacological effects if ethnopharmacological potential of the species is to be fully realized.
Such further research should assess mechanisms of actions, clinical effectiveness and proper dosage
for the documented ethnomedicinal uses and associated pharmacological activities. Based on current
information, the ethnomedicinal uses and documented pharmacological effects of the species show that
there is not enough systematic data on phytochemistry and pharmacological effects for the majority
of the ethnomedicinal applications of the species. There is still need for research on phytochemical,
bioactive compounds and other medicinal ingredients and minerals that can be used to explain the
wide use of E. natalensis as herbal medicine in tropical Africa. Future studies should also focus on the
mechanism of biological activities and structure–function relationships of bioactive constituents of
the species. Likewise, animal studies and clinical studies are to a large degree missing and should be
carried out to determine the potential of this plant to be used in human medicine.
Acknowledgments:
Research reported in this publication was supported by the National Research Foundation
(NRF) and Govan Mbeki Research and Development Centre (GMRDC), University of Fort Hare. The views and
opinions expressed are not those of the NRF or GMRDC but of the author of the material published.
Conflicts of Interest: The author declares no conflict of interest.
References
1.
Van Wyk, B.-E. A broad review of commercially important southern African medicinal plants.
J. Ethnopharmacol. 2008,119, 342–355. [CrossRef] [PubMed]
2.
Van Wyk, B.-E. The potential of South African plants in the development of new food and beverage products.
S. Afr. J. Bot. 2011,77, 812–829. [CrossRef]
3.
Stander, I.; Van Wyk, C.W. Toothbrushing with the root of Euclea natalensis.J. Biol. Buccale
1991
,19, 167–172.
[PubMed]
4.
Van Wyk, B.; Gericke, N. People’s Plants: A Guide to Useful Plants of Southern Africa; Briza Publications: Pretoria,
South Africa, 2007.
5.
White, F.; Verdcourt, B. Ebenaceae. In Flora of Tropical East Africa; Polhill, R.M., Ed.; A.A. Balkema: Rotterdam,
The Netherlands, 1996; pp. 43–49.
6.
Cunningham, A.B. African Medicinal Plants: Setting Priorities at the Interface between Conservation and Primary
Health Care; People and Plants Working paper 1; UNESCO: Paris, France, 1993.
7.
Posthouwer, C. Medicinal Plants of Kariakoo Market, Dar es Salaam, Tanzania. MSc Dissertation, Leiden
University, Leiden, The Netherlands, 2015.
8.
Hutchings, A.; Scott, A.H.; Lewis, G.; Cunningham, A. Zulu Medicinal Plants. An Inventory; University of
Natal Press: Scottsville, South Africa, 1996.
9.
Varga, C.A.; Veale, D.J.H. Isihlambezo: Utilization patterns and potential health effects of pregnancy-related
traditional herbal medicine. Soc. Sci. Med. 1997,44, 911–924. [CrossRef]
10.
Maroyi, A. Lippia javanica (Burm. f.) Spreng: Traditional and commercial uses, phytochemical and
pharmacological significance. Evid.-Based Complement. Altern. Med.
2017
,2017, 6746071. [CrossRef]
[PubMed]
11.
Mahlangeni, N.T.; Moodley, R.; Jonnalagadda, S.B. Elemental composition of Cyrtanthus obliquus and
Lippia javanica used in South African herbal tonic, Imbiza. Arabian J. Chem.
2014
. Available online: http:
//dx.doi.org/10.1016/j.arabjc.2014.07.007 (accessed on 5 August 2017). [CrossRef]
12. Williamson, J. Useful Plants of Nyasaland; The Government Printer: Zomba, Malawi, 1955.
13.
Watt, J.M.; Breyer-Brandwijk, M.G. The Medicinal and Poisonous Plants of Southern and Eastern Africa; E. and S.
Livingstone: London, UK, 1962.
Molecules 2017,22, 2128 14 of 16
14. Bryant, A.T. Zulu Medicine and Medicine Men; Struik: Cape Town, South Africa, 1966.
15.
Bandeira, S.O.; Gaspar, F.; Pagula, F.P. African ethnobotany and healthcare: Emphasis on Mozambique.
Pharm. Biol. 2001,39, 70–73. [PubMed]
16. Kokwaro, J.O. Medicinal Plants of East Africa; Kenya Literature Bureau: Nairobi, Kenya, 1993.
17.
Lall, N.; Meyer, J.J.M.; Wang, Y.; Bapela, N.B.; van Rensburg, C.E.J.; Fourie, B.; Franzblau, S.G.
Characterization of intracellular activity of antitubercular constituents from the roots of Euclea natalensis.
Pharm. Biol. 2005,43, 353–357. [CrossRef] [PubMed]
18.
Lall, N.; Meyer, J.J.M.; Taylor, M.B. Anti-HSV-1 activity of Euclea natalensis.S. Afr. J. Bot.
2005
,71, 444–446.
[CrossRef]
19.
Moshi, M.J.; Mbwambo, Z.H.; Nondo, R.S.O.; Masimba, P.J.; Kamuhabwa, A.; Kapingu, M.C.; Thomas, P.;
Richard, M. Evaluation of ethnomedical claims and brine shrimp toxicity of some plants used in Tanzania as
traditional medicines. Afr. J. Trad. Complement. Altern. Med. 2006,3, 48–58.
20.
Ngarivhume, T.; van’t Klooster, C.I.E.A.; de Jong, J.T.V.M.; Westhuizen, J.H. Medicinal plants used by
traditional healers for the treatment of malaria in the Chipinge district in Zimbabwe. J. Ethnopharmacol.
2015
,
159, 224–237. [CrossRef] [PubMed]
21.
Ngowi, N.J. Ethnobotanical study of medicinal plants in Kondoa eroded area of central Tanzania. Int. J. Sci.
Basic Appl. Res. 2015,21, 223–233.
22.
Notten, A. Euclea natalensis A. DC.; Kirstenbosch National Botanical Garden: Cape Town, South Africa, 2010.
Available online: http://pza.sanbi.org/euclea-natalensis (accessed on 9 August 2017).
23.
Palmer, E.; Pitman, P. Trees of Southern Africa Covering all Known Indigenous Species in the Republic of South
Africa, South West Africa, Botswana, Lesotho and Swaziland; A.A. Balkema: Cape Town, South Africa, 1972.
24.
Chauke, M.A.; Shai, L.J.; Mogale, M.A.; Tshisikhawe, M.P.; Mokgotho, M.P. medicinal plant use of villagers in the
Mopani district, Limpopo province, South Africa. Afr. J. Trad. Complement. Altern. Med.
2015
,12, 9–26. [CrossRef]
25.
Otieno, J.N.; Hosea, K.M.M.; Lyaruu, H.V.; Mahunnah, R.L.A. Multi-plant or single-plant extracts, which is the
most effective for local healing in Tanzania? Afr. J. Trad. Complement. Altern. Med. 2008,5, 165–172. [CrossRef]
26.
Cook, F. Economic Botany Data Collection Standard; Prepared for the International Working Group on
Taxonomic Databases for Plant Sciences (TDWG); Royal Botanic Gardens, Kew: London, UK, 1995.
27.
De Wet, H.; Ngubane, S.C. Traditional herbal remedies used by women in a rural community in northern
Maputaland (South Africa) for the treatment of gynaecology and obstetric complaints. S. Afr. J. Bot.
2014
,
94, 129–139. [CrossRef]
28.
Morris, B. Chewa Medical Botany: A Study of Herbalism in Southern Malawi; International African Institute,
Lit Verlag: Hamburg, Germany, 1996.
29.
Pakia, M.; Cooke, J.A. The ethnobotany of the Midzichenda tribes of the coastal forest areas in Kenya: 2.
Medicinal plant uses. S. Afr. J. Bot. 2003,69, 382–395. [CrossRef]
30.
Maunguja, A.B. Assessment of Plant Diversity and Utilization of Wild Medicinal Species by Households
Proximate to Arabuko Sokoke Forest in Kilifi County of Kenya. MSc Dissertation, University of Nairobi,
Nairobi, Kenya, 2016.
31.
Bruschi, P.; Morganti, M.; Mancini, M.; Signorini, M.A. Traditional healers and laypeople: A qualitative and
quantitative approach to local knowledge on medicinal plants in Muda (Mozambique). J. Ethnopharmacol.
2011,138, 543–563. [CrossRef] [PubMed]
32.
Long, C. Swaziland’s Flora: siSwati Names and Uses; Swaziland National Trust Commission: Mbambane,
Swaziland, 2005; Available online: http://www.sntc.org.sz/index.asp (accessed on 19 August 2017).
33.
Amusan, O.O.G. Ethical and environmental issues in bioprospecting for drugs through traditional medicine:
The case for Swaziland. Afr. J. Plant Sci. Biotechnol. 2008,2, 1–9.
34.
Filipe, M.; Gomes, E.T.; Serrano, R.; Silva, O. Caracterização farmacognóstica da raiz de Euclea natalensis.
Plantas Medicinais e Fitoterapêuticas nos Trópicos. IICT /CCCM, 29, 30 e 31 de Outubro de 2008. Available
online: http://www2.iict.pt/archive/doc/M_Filipe_wrkshp_plts_medic.pdf. (accessed on 21 July 2017).
35.
More, G.; Tshikalange, T.E.; Lall, N.; Botha, F.; Meyer, J.J.M. Antimicrobial activity of medicinal plants against
oral microorganisms. J. Ethnopharmacol. 2008,119, 473–477. [CrossRef] [PubMed]
36.
Yirga, G. Assessment of traditional medicinal plants in Endrta district, south-eastern Tigray, northern
Ethiopia. Afr. J. Pl. Sci. 2010,4, 255–260.
37.
Yirga, G.; Teferi, M.; Kasaye, M. Survey of medicinal plants used to treat human ailments in Hawzen district,
northern Ethiopia. Int. J. Biodiv. Cons. 2011,3, 709–714.
Molecules 2017,22, 2128 15 of 16
38.
Tshikalange, T.E.; Mophuting, B.C.; Mahore, J.; Winterboer, S.; Lall, N. An ethnobotanical study of medicinal
plants used in villages under Jongilanga tribal council, Mpumalanga, South Africa. Afr. J. Trad. Complem.
Altern. Med. 2016,13, 83–89. [CrossRef] [PubMed]
39.
Lall, N.; Meyer, J.M.M.
In vitro
inhibition of drug-resistant and drug-sensitive strains of Mycobacterium
tuberculosis by ethnobotanically selected South African plants. J. Ethnopharmacol.
1999
,66, 347–354. [CrossRef]
40.
Khan, M.R.; Nkunya, M.H.H. Antimicrobial activity of Tanzanian traditional medicinal plants.
In Proceedings of the International Conference on Traditional Medicinal Plants, Arusha, Tanzania,
18–23 February 1990
; Mshigeni, K.E., Nkunya, M.H.H., Fupi, V., Mahunnah, R.L.A., Mshiu, E.N., Eds.;
Dar es Salaam University Press: Dar es Salaam, Tanzania, 1991; pp. 48–63.
41.
Pujol, J. Natur Africa: The Herbalist Handbook; Jean Pujol Natural Healers Foundation: Durban, South Africa, 1990.
42.
Deutschländer, M.S.; Lall, N.; van de Venter, M. Plant species used in the treatment of diabetes by South
African traditional healers: An inventory. Pharm. Biol. 2009,47, 348–365. [CrossRef]
43.
Keter, L.K.; Mutiso, P.C. Ethnobotanical studies of medicinal plants used by Traditional Health Practitioners
in the management of diabetes in Lower Eastern Province, Kenya. J. Ethnopharmacol.
2012
,139, 74–80.
[CrossRef] [PubMed]
44.
Arnold, H.-J.; Gulumian, M. Pharmacopoeia of traditional medicine in Venda. J. Ethnopharmacol.
1984
,
12, 35–74. [CrossRef]
45.
Conde, P.; Figueia, R.; Saraiva, S.; Catarino, L.; Romeiras, M.; Duarte, M.C. The botanic mission to
Mozambique (1942–1948): Contributions to the knowledge of the medicinal flora of Mozambique. Hist. Ciênc.
Saúde Manguinhos Rio de Janeiro 2014,21, 2.
46.
Lopes, M.H.; Paul, I.M. Triterpenóides pentacíclicos de Euclea natalensis eEuclea divinorum.Revista Portuguesa
de Química 1973,15, 213–217.
47.
Tannock, J. Naphthoquinones from Diospyros and Euclea species. Phytochem
1973
,12, 2066–2067. [CrossRef]
48.
King, T.J.; Ferreira, M.A.; Alves, A.C. Thomson, R.H. Natalenone, a novel quinone dimer from Euclea
natalensis.J. Chem. Soc. Chem. Commun. 1976,7, 241–242. [CrossRef]
49.
Ferreira, M.A.; Alves, A.C.; Costa, M.A.C.; Paul, M.I. Naphthoquinone dimers and trimers from Euclea
natalensis.Phytochemistry 1977,16, 117–120. [CrossRef]
50.
Khan, M.R.; Mutasa, S.L.; Ndaalio, G.; Wevers, H. Antibiotic action of constituents of the roots of Euclea
natalensis A.DC. Pak. J. Sci. Ind. Res. 1978,21, 197–199.
51.
Khan, M.R. Isolation of 4,8-dihydroxy-6-methyl-1-tetralone from the root bark of Euclea natalensis.Planta Med.
1985,5, 356. [CrossRef] [PubMed]
52.
Weigenand, O.; Hussein, A.A.; Lall, N.; Meyer, J.J.M. Antibacterial activity of naphthoquinones and
triterpenoids from Euclea natalensis root bark. J. Nat. Prod. 2004,67, 1936–1938. [CrossRef] [PubMed]
53.
Lall, N.; Weiganand, O.; Hussein, A.A.; Meyer, J.J.M. Antifungal activity of naphthoquinones and triterpenes
isolated from the root bark of Euclea natalensis.S. Afr. J. Bot. 2006,72, 579–583. [CrossRef]
54.
Van der Kooy, F. Characterisation, Synthesis and Antimycobacterial Activity of Naphthoquinones Isolated
from Euclea natalensis. MSc Dissertation, University of Pretoria, Pretoria, South Africa, 2004.
55.
Van der Kooy, F.; Meyer, J.J.M.; Lall, N. Antimycobacterial activity and possible mode of action of newly isolated
neodiospyrin and other naphthoquinones from Euclea natalensis.S. Afr. J. Bot. 2006,72, 349–352. [CrossRef]
56.
Bapela, M.J.; Lall, N.; Isaza-Martinez, J.H.; Regnier, T.; Meyer, J.J.M. Variation in the content of
naphthoquinones in seeds and seedlings of Euclea natalensis.S. Afr. J. Bot. 2007,73, 606–610. [CrossRef]
57.
Bapela, M.J.; Lall, N.; Meyer, J.J.M. Seasonal variation of naphthoquinones in Euclea natalensis subspecies
natalensis.S. Afr. J. Bot. 2008,74, 218–224. [CrossRef]
58.
Bapela, M.J.; Kuete, V.; Du Toit, E.; Meyer, J.J.M.; Lall, N. Fertilization-induced changes in growth parameters
and antimycobacterial activity of Euclea natalensis (Ebenaceae). S. Afr. J. Bot. 2008,74, 244–250. [CrossRef]
59.
Joubert, A.; van der Kooy, F.; Meyer, J.J.M.; Lall, N. HPLC in the comparative study of the content
of naphthoquinones (quinonoid constituents) in Euclea species of South Africa. Chromatographia
2006
,
64, 399–403. [CrossRef]
60.
Cooper, S.M.; Owen-Smith, N. Condensed tannins deter feeding by browsing ruminants is a South African
savanna. Oecologia 1985,67, 142–146. [CrossRef] [PubMed]
61.
Lall, N.; Meyer, J.J.M. Antibacterial activity of water and acetone extracts of the roots of Euclea natalensis.
J. Ethnopharmacol. 2000,72, 313–316. [CrossRef]
Molecules 2017,22, 2128 16 of 16
62.
Van Vuuren, S.F.; Naidoo, D. An antimicrobial investigation of plants used traditionally in southern Africa
to treat sexually transmitted infections. J. Ethnopharmacol. 2010,130, 552–558. [CrossRef] [PubMed]
63.
Sharma, R.; Lall, N. Antibacterial, antioxidant activities and cytotoxicity of plants against Propionibacterium
acnes.S. Afr. J. Sci. 2014,110. [CrossRef]
64.
Lall, N.; Meyer, J.J.M. Inhibition of drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis by
diospyrin, isolated from Euclea natalensis.J. Ethnopharmacol. 2001,78, 213–216. [CrossRef]
65.
McGaw, L.J.; Lall, N.; Hlokwe, T.M.; Michel, A.L.; Meyer, J.J.M.; Eloff, J.N. Bovine tuberculosis: A zoonotic
target for medicinal plants. Planta Med. 2007,73, P186. [CrossRef]
66.
McGaw, L.J.; Lall, N.; Hlokwe, T.M.; Michel, A.L.; Meyer, J.J.M.; Eloff, J.N. Purified compounds and
extracts from Euclea species with antimycobacterial activity against Mycobacterium bovis and fast-growing
mycobacteria. Biol. Pharm. Bull. 2008,31, 1429–1433. [CrossRef] [PubMed]
67.
Lall, N.; Kumar, V.; Meyer, D.; Gasa, N.; Hamilton, C.; Matsabisa, M.; Oosthuizen, C.
In vitro
and
in vivo
antimycobacterial, hepatoprotective and immunomodulatory activity of Euclea natalensis and its mode of
action. J. Ethnopharmacol. 2016,194, 740–748. [CrossRef] [PubMed]
68.
Lall, N. Isolation and Identification of Naphthoquinones from Euclea natalensis with Activity against
Mycobacterium tuberculosis, Other Pathogenic Bacteria and Herpes simplex Virus. Ph.D. Thesis,
University of Pretoria, Pretoria, South Africa, 2001.
69.
Van der Kooy, F. The Medicinal and Chemical Aspects of Naphthoquinones Isolated from Euclea natalensis
A. DC. on Mycobacterium tuberculosis. Ph.D. Thesis, University of Pretoria, Pretoria, South Africa, 2007.
70.
Mahapatra, A.; Mativandlela, S.P.N.; Binneman, B.; Fourie, B.P.; Hamilton, C.J.; Meyer, J.J.M.;
van der Kooy, F.; Houghon, P.; Lall, N. Activity of 7-methyljuglone derivatives against Mycobacterium
tuberculosis and as subversive substrate for mycothiol disulfide reductase. Bioorg. Med. Chem.
2007
,
15, 7638–7646. [CrossRef] [PubMed]
71.
Mahapatra, A.; Tshikalange, T.E.; Meyer, J.J.M.; Lall, N. Synthesis and HIV-1 reverse transcriptase inhibition
activity of 1,4-naphthoquinone derivatives. Chem. Nat. Compd. 2012,47, 883–887. [CrossRef]
72.
Nkobole, N.; Houghton, P.J.; Hussein, A.; Lall, N. Antidiabetic activity of Terminalia sericea constituents.
Chem. Nat. Compd. 2011,6, 1585–1588.
73.
Clarkson, C.; Maharaj, V.J.; Crouch, N.R.; Grace, O.M.; Pillay, P.; Matsabisa, M.G.; Bhagwandin, N.; Smith, P.J.;
Folb, P.I.
In vitro
antiplasmodial activity of medicinal plants native to or naturalised in South Africa.
J. Ethnopharmacol. 2004,92, 177–191. [CrossRef] [PubMed]
74.
Maharaj, R.; Maharaj, V.; Crouch, N.R.; Bhagwandin, N.; Folb, P.I.; Pillay, P.; Gayaram, R. Screening of
selected ethnomedicinal plants from South Africa for larvicidal activity against the mosquito Anopheles
arabiensis.Malar. J. 2012,11, 320. [CrossRef] [PubMed]
75.
Sparg, S.G.; Van Staden, J.; Jäger, A.K. Efficiency of traditionally used South African plants against
schistosomiasis. J. Ethnopharmacol. 2000,73, 209–214. [CrossRef]
76.
Ojewole, O.J.A. Indigenous plants and schistosomiasis control in south africa:molluscicidal activity of some
Zulu medicinal plants. Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas 2004,3, 8–22.
77.
Sales-Peres, S.H.C.; Brianezzi, L.F.F.; Marsicano, J.A.; Forim, M.R.; da Silva, M.F.G.F.; Sales-Peres, A.
Evaluation of an experimental gel containing Euclea natalensis: An
in vitro
study. Evid.-Based Complement.
Altern. Med. 2012,2012, 184346. [CrossRef] [PubMed]
78.
Sales-Peres, S.H.C.; Xavier, C.N.H.; Mapengo, M.A.A.; Forim, M.R.; Silva, M.F.; and Sales-Peres, A.
Erosion and abrasion-inhibiting in situ effect of the Euclea natalensis plant of African regions. Braz. Oral Res.
2016,30, e85. [CrossRef] [PubMed]
79.
Oosthuizen, C.B.; Lall, N. Shoot Extracts and Compositions of Euclea natalensis for Immune Modulation
and Hepatoprotection. Int Pat Appl WO 2015049643A1. 2015. Available online: https://www.google.com/
patents/WO2015049643A1?cl=en (accessed on 16 November 2017).
80.
Kishore, N.; Binneman, B.; Mahapatra, A.; van de Venter, M.; du Plessis-Stoman, D.; Boukes, G.; Houghton, P.;
Meyer, J.J.M.; Lall, N. Cytotoxicity of synthesized 1,4-naphthoquinone analogues on selected human cancer
cell lines. Bioorg. Med. Chem. 2014,22, 5013–5019. [CrossRef] [PubMed]
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2017 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
... Euclea natalensis is an evergreen woody plant belonging to the Ebenaceae family, widely distributed in the forests of South Africa, Botswana, and other African nations. It has been extensively studied for its medicinal properties (17). The selection of this plant for the current study is based on its documented ethnopharmacological uses across various countries (17). ...
... It has been extensively studied for its medicinal properties (17). The selection of this plant for the current study is based on its documented ethnopharmacological uses across various countries (17). E. natalensis is frequently employed in traditional medicine for the management of various conditions, including headaches, sexually transmitted infections, tuberculosis, skin infections, and diabetes mellitus (17)(18)(19). ...
... The selection of this plant for the current study is based on its documented ethnopharmacological uses across various countries (17). E. natalensis is frequently employed in traditional medicine for the management of various conditions, including headaches, sexually transmitted infections, tuberculosis, skin infections, and diabetes mellitus (17)(18)(19). Previous investigations have explored the antioxidant potential of the acetone root bark extract and ethanolic shoots extract. ...
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Diabetes, a chronic metabolic disorder with increasing global prevalence, poses a significant public health concern, necessitating the development of safe and effective drugs. This study specifically assessed the inhibitory effects of Euclea natalensis leaf extracts on alpha-amylase through in vitro, in vivo, and in silico methods. The extracts were sequentially obtained using solvents of graded polarity. alpha-amylase inhibition studies were conducted through spectrophotometric methods, while in vivo assessments were performed using a starch tolerance test on rats. Molecular docking was carried out using Autodock 4.2.6, and SwissADME, along with ADMETlab 2.0, were employed to determine the drug-likeness and toxicity properties of the literature-mined compounds. The extracts demonstrated significant in vitro inhibition of alpha-amylase, with the methanol extract exhibiting the highest percentage of inhibition at 27% ± 4.2, followed by hexane and aqueous extracts at 18% ± 2.5 and 18% ± 3.7, respectively. In vivo, the extracts lowered blood glucose levels, with acarbose reducing peak blood glucose levels by 42%, while both the aqueous and methanol extracts reduced it by 19% each after 30 min. The overall glucose-lowering effect, based on the area under the starch tolerance curve, ranked as follows: acarbose > methanol > aqueous > hexane > dichloromethane extract. Molecular docking identified 20(29)-lupene-3 beta-isoferulate C3 as the most promising compound with the lowest binding energy of -11.4 kcal/mol. Molecular dynamics revealed that C3 loses stability as it diverges from the active site. Additionally, while all other compounds passed the Lipinski drug-likeness criteria, 20(29)-lupene-3 beta-isoferulate C3 did not. Therefore, the present study suggests that E. natalensis exhibits antidiabetic properties through the inhibition of alpha-amylase and may serve as a source of potential antidiabetic drug molecules.
... Euclea natalensis A. DC, locally known as Motlhakola in Botswana, is a woody plant in the EBENACEACE (ebony) family that is traditionally used for the treatment of many conditions, including headaches, sexually transmitted infections, tuberculosis, skin infections, and diabetes [11]. It has evergreen leaves and small spherical red berries which turn black when ripe. ...
... It has evergreen leaves and small spherical red berries which turn black when ripe. Extracts from the plant have been shown to have antidiabetic effects by inhibiting α-amylase and αglucosidase activities [11][12][13]. Extracts of Euclea natalensis are rich in naphthoquinones and pentacyclic tannins [14]. ...
... Extracts of Euclea natalensis are rich in naphthoquinones and pentacyclic tannins [14]. Through scientific research, Euclea natalensis was found to possess antibacterial [14], anti-inflammatory [11], antifungal [15], antioxidant [16], antidiabetic [16,17] and hepatoprotective effects [13]. However, the in vivo effect of the plant on diabetes has not yet been explored. ...
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Euclea natalensis is a commonly used plant in traditional African medicinefor treating several diseases, including diabetes. The objective of thepresent study was to evaluate the antidiabetic effects of the leaf extractsof Euclea natalensis and elucidate some of its mechanisms of action.High-fat diet – low Streptozotocin-induced diabetic Sprague Dawley ratswere orally treated with the methanol and dichloromethane extracts (100 and 200 mg/kg bw), and their fasting blood glucose levels, body weights,and food and water intake were measured every seven days for 21 days.Biomarkers of oxidative stress, lipid profile, gluconeogenic enzyme activ-ities, glucose transporter 4 (GLUT 4) protein expression, and AMP-activated protein kinase (AMPK) gene expression were also determined.The 200 mg/kg bw of methanol extracts significantly reduced fastingplasma glucose, glycated hemoglobin (HbAc1), triglycerides, and low-density lipoprotein levels. The extract increased insulin sensitivity andhepatic glycogen synthesis, decreased hepatic glucose output, andincreased the activities of antioxidant enzymes in diabetic animals after21 days of treatment. The methanol extract also significantly upregulatedthe relative expression of GLUT 4 protein via the promoted expression ofskeletal muscle and hepatic AMPK. Histological investigation showedameliorated pancreatic degeneration and expedited regeneration of isletsof Langerhans in diabetic rats treated with the methanol extract com-pared with the dichloromethane extract. The findings demonstrated thatEuclea natalensis has beneficial effects on the biochemical and cellabnormalities of type 2 diabetes, partly via the modulation of theAMPK – GLUT 4 pathway.
... a high-quality predictor Web Server for Small Molecule pKa Prediction that uses a Graph-Convolutional Neural Network. Briefly, secondary metabolites from Euclea natalensis root were selected in previous works [18]. Naphtoquinones were considered for prediction because these compounds are sensitive to pH variations [19]. ...
... This result corroborates with previous studies by Orsavová and colleagues [23], where low quantities of about 1.71 g COG kg −1 of TMAC were obtained in Lednice berries. Therefore, this low quantity was expected, as most studies with Euclea natalensis report the presence of naphthoquinones [15,17,18,21,22,24,25], which are the potential compounds that change color according to the pH of the medium. Figure 3 shows the FTIR and UV-VIS spectra of the Euclea natalensis extract. ...
... This value is comparable with some naphthoquinones identified by previous works. Euclea natalensis root are rich in several compounds [18]; however, they are considered naphthoquinones for acid-base application because they were described in the literature as potential acid-base indicators [19]. MolGpKa was used to determine the pKa values of the main naphthoquinones identified in Euclea natalensis Figure 6, shows that the pK a value of naphthoquinones that occur in Euclea natalensis varies from 4.8 to 11.8. ...
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This work presents Euclea natalensis root extracts as a Green acid-base indicator, focusing on the application in titration and determination of pKa. The Euclea natalensis root extracts were obtained by heating the biomass in water at 60 °C for 1 h. The obtained extracts were applied for acid-base titration, and the pKa value was determined and compared to bromothymol blue and methyl orange, conventional acid-base indicators. Furthermore, the pKa of some naphthoquinones that occur in Euclea natalensis root were predicted using MolG pKa web server and compared with experimental pKa value. The results showed that the Euclea natalensis extract presented a titration performance comparable to common synthetic acid-based indicators (bromothymol blue-NaOH/HCl, required volume-11.8 ± 0.1 mL and Euclea natalensis, NaOH/HCl, required volume 11,6 ± 0.1 mL). Euclea natalensis root extracts presented a pKa of 7.01, corroborating the predicted pKa values of two main candidate compounds in Euclea natalensis root. These two compounds may cause color changes in Euclea natalensis root extracts in acidic media and basic solutions. These results showed that the Euclea natalensis root extracts are potential green and locally available acid-base indicators. However, additional work is still necessary to understand the stability and which compound or compounds are the core for color change.
... Euclea natalensis is an evergreen woody plant of the Ebenaceace family and is found abundantly in African countries, including Botswana and South Africa. The root, bark, and leaf extracts of Euclea natalensis are used for blood purification and treatment of diseases, such as headache, sexually transmitted infections, tuberculosis, skin infections, and diabetes mellitus [10]. Previous studies have assessed and reported the antioxidant [11,12], antibacterial [13] and antidiabetic effects [12] of various parts of Euclea natalensis. ...
... Previous studies have assessed and reported the antioxidant [11,12], antibacterial [13] and antidiabetic effects [12] of various parts of Euclea natalensis. Phytochemical studies have shown that the plant is rich in phytocompounds, such as naphthoquinones, tannins, and pentacyclic terpenoids [10,11,14]. Due to its ethnopharmacological uses, Euclea natalenisis has received considerable scientific attention, making it one of the herbal plants of economic importance and worth scientific exploration of its antidiabetic potential. ...
... As shown in Fig. (1), it was deduced that the extracts have compounds in the groups of phenols, terpenoids, esters, proteins, carbohydrates, and lipids, as also summarized in Table 2 (supplementary data). Previous phytochemical studies on the Euclea natalensis plant have demonstrated the presence of bioactive phytochemicals, such as phenols, flavonoids, saponins, terpenoids, and steroids [10,13,14], of which these FTIR peaks indicated their presence. The presence of such compounds makes Euclea natalensis a useful source of bioactive compounds for medicinal purposes. ...
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Background: Postprandial hyperglycemia is a key factor in type 2 diabetes, and its management is critical in alleviating the deleterious consequences of diabetes and its associated micro and macrovascular complications. Objective: The current study aims to determine the effect of Euclea natalensis leaf extracts on α- glucosidase inhibition in vitro and postprandial hyperglycemia in vivo in rats. Methods: Sequentially extracted leaf extracts of Euclea natalensis were evaluated for their inhibitory effects on α-glucosidase in vitro and the suppression of postprandial hyperglycemia in normoglycemic rats. The extracts were fingerprinted using a Fourier-transform infrared spectrophotometer (FTIR), and the bioactive compounds were evaluated by molecular docking for their interaction with α-glucosidase. Results: FTIR fingerprinting of the extracts showed that they contain functional groups of important bioactive phytochemicals. The extracts inhibited α-glucosidase in vitro, with the methanol extract (1 mg/mL) showing the highest inhibitory effect of 93.52 ± 1.50% compared to 69.62% ± 1.45 of the standard drug acarbose (0.05 mg/mL). The extracts also reduced postprandial hyperglycemia in rats in a sucrose tolerance test, where the hexane and methanol extracts performed similarly to Acarbose. Molecular docking studies showed that 20(29)-lupene-3β- isoferulate 3 is the most potent α-glucosidase inhibitor with the lowest binding energy of -10.79 kcal/mol, 2 hydrogen bonds with residues ASP1526 and ASP1157, and numerous Van der Waal interactions with amino acids in the binding pocket of α-glucosidase. Conclusion: Euclea natalensis leaf extracts were found to suppress postprandial hyperglycemia by inhibiting α-glucosidase activity; thus, it has a promising potential for use as an antidiabetic agent.
... Indigenous people throughout Southern Africa, particularly in the East and South Coast regions extending outward up to Mozambique, Swaziland, and Ethiopia, have been using this deciduous tree for the treatment of respiratory and dermato-logical ailments [22,23]. Euclea natalensis is traditionally employed as a medicine in 57% of the countries where it is indigenous [24]. In a study conducted by Lall et al. (2016), the ethanolic shoot extract of E. natalensis exhibited a minimum inhibitory concentration (MIC) value of 125 µg/mL, indicating moderate antimycobacterial ability [22]. ...
... In literature, leaves are generally removed from the aerial parts since the leaves are not used by the indigenous communities for the treatment of TB. There is currently no literature that suggests that other plant parts of E. natalensis have any significant antimycobacterial activity [24,34]. This can potentially place pressure on the current Euclea populations due to the roots being the most bioactive plant part identified and the plant part where 7-MJ is predominantly found. ...
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7-Methyljuglone (7-MJ) is a pure compound isolated from the roots of Euclea natalensis A. DC., a shrub indigenous to South Africa. It exhibits significant promise as a potential treatment for the highly communicable disease tuberculosis (TB), owing to its effective antimycobacterial activity against Mycobacterium tuberculosis. Despite its potential therapeutic benefits, 7-MJ has demonstrated in vitro cytotoxicity against various cancerous and non-cancerous cell lines, raising concerns about its safety for consumption by TB patients. Therefore, this review focuses on exploring the potential of poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as a delivery system, which has been shown to decrease in vitro cytotoxicity, and 7-MJ as an effective antimycobacterial compound.
... Similarly, in South Africa, the stem bark of P. capensis is mixed with the roots of Euclea natalensis A.DC. subsp. angustifolia F.White (Ebenaceae) and Grewia hexamita Burret (Malvaceae) as traditional medicines against infertility and menstrual problems (Chauke et al. 2015, Maroyi 2017 Watt & Breyer-Brandwijk 1962, Gelfand et al. 1985, Mabogo 1990, Mulaudzi et al. 2011, Muthee et al. 2011, Makule et al. 2014 Gelfand et al. 1985, Mabogo 1990, Palgrave, 2002, Hankey 2004, Mulaudzi et al. 2011, Pendota et al. 2017 ...
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This study evaluated the effect of Euclea natalensis gel on the reduction of erosive wear with or without abrasion, in enamel and dentin. During two five-day experimental crossover phases, volunteers (n = 10) wore palatal devices containing human enamel and dentin blocks (E = 8 and D = 8). The gel was applied in a thin layer in the experimental group, and was not applied in the control group. In the intraoral phase, volunteers used the palatal appliance for 12 h before the gel treatment, and were instructed to start the erosive challenges 6 h after the gel application. Erosion was performed with Coca-Cola® (for 5 min) 4 times/day. The appliance was then put back into the mouth and was brushed after 30 minutes. After intraoral exposure, the appliances were removed and the specimens were analyzed using profilometry (mean ± SD, μm). The Euclea natalensis gel caused less wear in enamel in the experimental group (EROS = 12.86 ± 1.75 µm; EROS + ABRAS = 12.13 ± 2.12 µm) than in the control group (EROS = 14.12 ± 7.66 µm; EROS + ABRAS = 16.29 ± 10.72 µm); however, the groups did not differ from each other significantly. A statistically significant value was found for erosion and eros + abrasion in dentin (p = 0.001). Euclea natalensis may play a role in the prevention of dentin loss under mild erosive and abrasive conditions. A clinical trial is required to confirm these promising results in a clinical situation.
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The present invention relates to shoot extracts from Euclea natalensis for use in modulating immune responses in a subject and/or providing hepatoprotection in a subject. The invention also provides for pharmaceutical compositions contain the extract and to the use of medicaments contain the extract.
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