molecules
Review
Review of the Traditional Uses, Phytochemistry, and
Pharmacological Activities of Rhoicissus Species (Vitaceae)
Nondumiso P. Dube 1 , Xavier Siwe-Noundou 2, *, Rui W. M. Krause 2 , Douglas Kemboi 1 ,
Vuyelwa Jacqueline Tembu 1, * and Amanda-Lee Manicum 1, *
1
2
*
Citation: Dube, N.P.; Siwe-Noundou,
X.; Krause, R.W.M.; Kemboi, D.;
Tembu, V.J.; Manicum, A.-L. Review
of the Traditional Uses, Phytochemistry,
and Pharmacological Activities of
Rhoicissus Species (Vitaceae). Molecules
2021, 26, 2306. https://doi.org/
10.3390/molecules26082306
Academic Editors: Deok-Chun Yang,
Farid Chemat, Lorenzo Di Cesare
Mannelli and Ramya Mathiyalagan
Received: 18 February 2021
Department of Chemistry, Tshwane University of Technology, 175 Nelson Mandela Drive, Private Bag X680,
Pretoria 0001, South Africa; DlaminiNP2@tut.ac.za (N.P.D.); kemboidouglas01@gmail.com (D.K.)
Department of Chemistry, Rhodes University, P.O. Box 94, Grahamstown 6140, South Africa;
r.krause@ru.ac.za
Correspondence: X.siwenoundou@ru.ac.za (X.S.-N.); TembuVJ@tut.ac.za (V.J.T.);
ManicumAE@tut.ac.za (A.-L.M.); Tel.: +27-(012)-382-6309 (A.-L.M.)
Abstract: Species within the genus Rhoicissus (Vitaceae) are commonly used in South African traditional medicine. The current review discusses the occurrence, distribution, traditional uses, phytochemistry, and pharmacological properties of Rhoicissus species covering the period 1981–2020. The
data reported were systematically collected, read, and analysed from scientific electronic databases
including Scopus, Scifinder, Pubmed, and Google Scholar. Reported evidence indicates that species
in this genus are used for the treatment of gastrointestinal complaints, sexually transmitted infections (STIs), and infertility, as well as to tone the uterus during pregnancy and to facilitate
delivery. Pharmacological studies have further shown that members of the Rhoicissus genus display
antidiabetic, uterotonic, ascaricidal, hepatoprotective, antioxidant, antimicrobial, anticancer, and
anti-inflammatory properties. They are linked to the presence of bioactive compounds isolated
from the genus. Hence, Rhoicissus species can potentially be an alternative therapeutic strategy to
treat diseases and develop safer and more potent drugs to combat diseases. Plant species of this
genus have valuable medicinal benefits due to their significant pharmacological potential. However,
scientific investigation and information of the therapeutic potential of Rhoicissus remain limited as
most of the species in the genus have not been fully exploited. Therefore, there is a need for further
investigations to exploit the therapeutic potential of the genus Rhoicissus. Future studies should
evaluate the phytochemical, pharmacological, and toxicological activities, as well as the mode of
action, of Rhoicissus crude extracts and secondary compounds isolated from the species.
Keywords: botany; cuneifolia; pharmacology; phytochemistry; Rhoicissus; Vitaceae
Accepted: 25 March 2021
Published: 16 April 2021
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1. Introduction
For centuries, herbal medicines have been used worldwide to treat and prevent various
ailments, particularly in developing countries where infectious diseases are endemic [1–3].
The World Health Organization estimates that approximately 80% of the world population
uses traditional treatment methods for their primary healthcare system [4–6]. This is due to
the increasing costs of conventional treatments, difficult access to modern health facilities,
exhaustion of conventional therapies, lack of effective drugs for a serious illness, evolution
of multidrug-resistant microorganisms, belief that natural products are better or safer, and
cultural or spiritual preference [1,4–8]. This has drawn scientific and research interest
toward naturally derived compounds. These are considered safe, effective, affordable,
and biologically friendly, having fewer toxic side-effects than synthetic drugs [2,9–11].
Furthermore, the interest in natural products has yielded numerous impressive results, including the discovery of diversely sourced products with antimicrobial, anti-inflammatory,
antihelminthic, antidiabetic, and anticancer activity, leading to pharmaceutical companies’
4.0/).
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acceptance of natural products as a part of the modern and effective tools for new drugs
and new drug leads [11,12].
Traditionally, Rhoicissus species are mainly used to enhance fertility and to facilitate
delivery during pregnancy. Decoctions are taken orally to treat impotence and infertility.
Women take them in the last trimester of pregnancy to ensure the good health of the mother
and fetus by preventing long and complicated labour [13–15]. Species from this genus
are also used for the treatment of cattle disease, gastrointestinal complaints, and cuts,
swollen glands through warming of the roots in fire and pressing them against the glands,
diarrhoea, broken bones, cuts, epilepsy, menorrhagia, renal complaints, sprained ankles,
stomach ailments, and sores, in addition to as an antiemetic in children and as a general
pain reliever [14,16–19].
The species from the genus Rhoicissus have also been reported to contain numerous
secondary metabolites such as alkaloids, terpenoids, and flavonoids which display various
biological effects such as anti-inflammatory, anticancer, and antioxidant activities [14].
Phytochemical investigations of Rhoicissus species have revealed the presence of bioactive
compounds responsible for these activities. As a successful example, proanthocyanidin
monomers and dimers, as well as gallic acid, isolated from Rhoicissus tridentata were
found to stimulate smooth muscle contraction in isolated rat uterine tissue [15]. Lupenone
isolated from Rhoicissus species has also been reported to possess antibiotic and antioxidant
activity [15]. However, despite the medicinal application of this genus and the bioactive
compounds isolated and identified from them, there exists no consolidation on previous
and latest scientific information on the phytochemistry and biological activities of genus
Rhoicissus. Hence, the current report presents a comprehensive literature review from 1981
to 2020. It includes the botany, geographical distribution, traditional uses, phytochemistry,
and pharmacological properties of Rhoicissus species.
2. Literature Survey Databases
The data reported were systematically collected, read, and analysed from scientific
electronic databases including Scopus, Elsevier, Scifinder, Research gate, ScienceDirect, and
Google Scholar. Keywords such as Vitaceae, Rhoicissus, and traditional use were submitted
during the search. Additional information on the botany, geographical distribution, traditional uses, phytochemistry, and pharmacological properties of Rhoicissus species was
gathered from references in journal articles, book chapters, books, journal articles, and encyclopedias. The information thus obtained was critically analysed to obtain new insights
and possible knowledge gaps for future research opportunities about Rhoicissus species.
3. Family Vitaceae
Vitaceae, also known as the grape family, are a medium-sized plant family with about
950 species belonging to 16 genera primarily distributed in the tropics, subtropics, and
the north and south temperate zones [20–25]. It is reported that Vitaceae have a largely
pantropical distribution in Asia, Africa, Australia, the neotropics, and the Pacific islands,
with only a few genera in temperate regions [23,26,27]. The family is well known for
containing one of the most economically important fruit crops, the grape (Vitis vinifera L.),
as the source of wine, sultanas, currants, and raisins [24,26].
This known group of flowering plants usually features erect, prostrate, woody climbers,
often with swollen or jointed nodes and herbaceous vines, or small succulent trees [21,24,28,29].
Vitaceae are readily distinguished from other angiosperm families by their unique seed morphology, inflorescences as cyme, corymb, or panicle, and leaf-opposed tendrils, enabling
the family to be the most successful climbers in tropical and temperate forests [23,25,29,30].
The stomata apertures in the epidermis are bounded by two guard cells which primarily
allow the rapid movement of carbon dioxide, water vapour, and oxygen in and out of the
leaf [29]. The flowers are small, greenish, and inconspicuous, with a ring-like or lobed
disc [28,31].
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According to the phylogenic and morphological evidence, the new classification places
the 950 species and 16 genera into five tribes: (i) tribe Ampelopsideae J. Wen & Z. L. Nie,
trib. nov. (47 species in four genera: Ampelopsis, Nekemias, Rhoicissus, and Clematicissus);
(ii) tribe Cisseae Rchb. (300 species in one genus: Cissus); (iii) tribe Cayratiaea J. Wen & L. M.
Lu, trib. nov. (370 species in seven genera: Cayratia, Causonis, Afrocayratia, Pseudocayratia,
Acareosperma, Cyphostemma, and Tetrastigma); (iv) tribe Parthenocisseae J. Wen & Z. D.
Chen, trib. nov (16 species in two genera: Parthenocissus and Yua); (v) tribe Viteae Dumort
(190 species in two genera: Ampelocissus and Vitis). The largest genera in this family are
Cissus L. and Cyphostemma (Planch) [23,25,26,30]. A taxonomy of the Vitaceae family is
summarised in Table 1.
Table 1. Taxonomy of the Vitaceae family.
Taxonomic Hierarchy
Classification
Reference
Kingdom
Subkingdom
Super division
Division
Class
Subclass
Order
Family
Plantae—plants
Tracheobionta—vascular plants
Spermatophyta—seed plants
Magnoliophyta—flowering plants
Magnoliopsida—dicotyledons
Rosidae
Rhamnales
Vitaceae—grape family
[23,25,26,30]
[23,25,26,30]
[23,25,26,30]
[23,25,26,30]
[23,25,26,30]
[23,25,26,30]
[23,25,26,30]
[23,25,26,30]
4. Genus Rhoicissus
4.1. Occurance, Distribution, and Botanical Description
The genus Rhoicissus Planch. is one of the smallest genera in the family [26]. Approximately 12 species represent it, namely, Rhoicissus tridentata, R. digitata, R. rhomboidea,
R. tomentosa, R. revoilli, R. sessilifolia, R. microphylla, R. kougabergensis, R. laetans, R. capensis, R. erythrodes, and R. sekhukhuniensis, which are endemic to tropical and southern
Africa [26,27,32]. Rhoicissus species are distributed in the Afrotropical zone of Africa, to
the south of the Sahara Desert, in the southern and eastern parts of the Arabian Peninsula,
Madagascar, southwestern Pakistan, and the Islands of the Western Indian Ocean [26,30].
Rhoicissus species are described as climbing shrubs or woody vines, with tendrils
opposite the leaves and more or less swollen nodes. The leaves are different, simple, or
palmately compound. They are often rusty, with inflorescences borne opposite the leaves
with 5–7 merous flowers that are small, greenish, and inconspicuous, with a ring-like or
lobed disc. The stamens are equal in number to the petals and opposite to them [31,32]. The
flower buds are globose in outline, while the floral disc is annular, entire, and thick [33].
Furthermore, they usually have 5–6 fleshy petals per flower. The genus can be distinguished from other genera of the tribe by its distinctly rugose seeds with linear chalaza
and divergent ventral in folds [25]. The summary of phytochemistry, ethnomedicinal and
biological studies reported for Rhoicissus species is illustrated in Table 2.
Table 2. Summary of phytochemistry, ethnomedicinal, and biological studies reported for Rhoicissus species.
Plant Name
Botanical Description
Traditional Uses
Biological
Activity
Phytochemistry
R. capensis
Not reported
Not reported
Not evaluated
Not evaluated
R. digitata
Reported
Reported
Evaluated
Evaluated
R. erythrodes
Not reported
Not reported
Not evaluated
Not evaluated
R. kougabergensis
Not reported
Not reported
Not evaluated
Not evaluated
R. laetans
Reported
Not reported
Not evaluated
Not evaluated
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Table 2. Cont.
Plant Name
Botanical Description
Traditional Uses
Biological
Activity
Phytochemistry
R. microphylla
Reported
Not reported
Not evaluated
Not evaluated
R. revoilli
Reported
Reported
Evaluated
Evaluated
R. rhomboidea
Reported
Reported
Evaluated
Not evaluated
R. sekhukhuniensis
Not reported
Not reported
Not evaluated
Not evaluated
R. sessilifolia
Not reported
Not reported
Not evaluated
Not evaluated
R. tomentosa
Reported
Reported
Evaluated
Evaluated
R. tridentata
Reported
Reported
Evaluated
Evaluated
4.2. Rhoicissus digitata
Rhoicissus digitata (L.f.) Gilg & Brandt can grow and reach 15 m in length, is usually
found in riparian fringing vegetation, and is reportedly from Natal, Transvaal (South Africa)
and Mozambique [34]. This species is a vigorous, evergreen vine, climbing by leaf-opposed
tendrils. Leaves are compound, usually trifoliate, although palmate compound leaves
with four or five leaflets are not uncommon. Tendrils and axillary buds are present at
every node and unbranched. Inflorescences are leaf-opposed and cymose, with sparsely
compound dichasia on which a small number of flowers are produced. Fruits form in small
clusters; they are green when unripe and turn dark purple when ripe, and they ripen from
September through to December (Figure 1A) [34,35]. It is well known as baboon grape and
dune grape (in English), isinwazi (in isiZulu), and vyfvingerdruif (in Afrikaans), and they
are used for medicinal purposes [35].
Figure 1. Rhoicissus species: (A) R. digitata; (B) R. laetans; (C) R. microphylla; (D) R. revoilii; (E) R. rhomboidea; (F) R. tomentosa; (G) R. tridentata.
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4.3. Rhoicissus laetans
Rhoicissus laetans (Turcz.) Gilg & Brandt is a shrub up to 1.5 m high, sometimes
scrambling with simple, petiolate leaves and absent tendrils [33]. Its berries are 12 mm in
diameter. Classification of this species in the genus Rhoicissus is supported by the shape of
its flower buds, structure of the floral disc, and inflorescence morphology [33]. R. laetans is
distinguished from all the other members of the genus by its shrubby habit and simple,
glabrous, glaucous green leaves (Figure 1B) [33]. R. laetans is endemic to the northeastern
Transvaal escarpment, where it occurs in a small area. The species is found in mountain
grassland with stunted shrub vegetation or steep, densely wooded kloof slopes with mixed
bushveld vegetation. Occasionally, it occurs in riverine forest. The species grows on
soils derived from quartzite and sandstone, and it flowers from at least November till
February [33].
4.4. Rhoicissus microphylla
Rhoicissus microphylla (Turcz.) Gilg & Brandt is a small shrub which has ovate leaves
with the lamina’s undersurface covered with reddish-brown hairs (Figure 1C). It occurs in
the Eastern Cape, South Africa [33].
4.5. Rhoicissus revoilii
Rhoicissus revoilii Planch., commonly known as bushveld grape or warty grape, is
a woody climber with tendrils about 1–10 m in height [18]. It is a shrub, robust woody
climber, or a creeper in mid- to high-altitude forests, forest margins, bushveld, riverine
shrubs, or woodlands [36]. This species has glossy dark green trifoliate leaves with entire
margins, looping lateral veins, and domatia on lateral vein axils of the abaxial surface
(Figure 1D). The leaflets are elliptic, and the laterals of this species are asymmetrical,
glabrous, or hairy [36]. Their fruits are reddish to black, two-lobed, round in shape and
edible [31]. It is distributed in eastern Africa from Ethiopia and Sudan to the Democratic
Republic of Congo, Zambia, Zimbabwe, Mozambique, and eastern South Africa (Transvaal,
Natal, Swaziland), as well as in Ghana, Comoro Islands, Saudi Arabia, and Yemen [37].
4.6. Rhoicissus rhomboidea
Rhoicissus rhomboidea (E. Mey. ex Harv.) Planch. is a canopy climber that can grow
and reach 20 m [36]. It is usually referred to as bastard forest grape or rope wood grape
and is distributed in Eastern South Africa (Transvaal, Natal, Swaziland, Cape Province),
Mozambique [37]. This species is found in forests, forest margins, and thickets. The leaves
are always made up of rhomboid leaflets (asymmetrical rhomboid for lateral leaflets) and
almost always with six dentitions along the margin. It has a globose bud shape with thick
spreading petals. The leaflets are shortly stalked, 1–4 mm long. It has trifoliate leaves and
russet hairs on both surfaces of the leaflets. The leaves are leathery, glossy, and dark green
on the adaxial surface and without hair when fully grown (Figure 1E) [36].
4.7. Rhoicissus tomentosa
Rhoicissus tomentosa (Lam.) Wild & Drummond is commonly known as an evergreen
grape in English, idiliya in Xhosa, and isiNwazi in Zulu, and it is distributed in southern
Africa (Transvaal, Natal, Swaziland, Cape Province) [37]. R. tomentosa can either be a
scrambling shrub or a canopy climber that can reach up to 20 m in height. It is found
on the fringes of forests or gaps in closed forests and on riverine bushes [36]. The leaves
of R. tomentosa are broadly transversely elliptic to reniform [33]. The leaves have lobes
along the margin, simple in form, and three-nerved at the base. They are dark green on
the adaxial surface and covered with rusty velvet hairs on the abaxial surface (Figure 1F).
Rusty velvety hairs are also found covering young stems and tendrils but are later lost on
stems as they mature and are replaced by raised dots known as lenticels [36]. Their flowers
in dense axillary heads are small and yellowish-green. The fruit is edible, globose, about
20 mm in diameter, and red to purplish-black [31].
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4.8. Rhoicissus tridentata
Rhoicissus tridentata is a polymorphic species with numerous nomenclature revisions
over the last two centuries [38]. Originally, this species was divided and classified as
several species in the genus Rhus. It was later reclassified in the genus Cissus. Later, Wild
and Drummond in 1963 combined three different species, R. cuneifolia, R. erythrodes, and
R. cirrhiflora and classified them as R. tridentata [20]. Urton then combined five different
species in 1986, R. cuneifolia, R. erythrodes, R. cirrhiflora, R. pauciflora, and R. dimidiata, and
classified them as R. tridentata but divided the species into two subspecies, being subspecies
tridentata and subspecies cuneifolia [20,38]. Cissus dimidiate was noted as being a mere form
of Rhoicissus sericea. They considered R. sericea to be conspecific with the plant named
Cissus dimidiata by Ecklon and Zeyher, 1835 and correctly applied the name Rhoicissus
dimidiata to them [20].
The subspecies are divided according to the number of indentations on the leaflet
margins [38]. If the leaflets have no dentations or crenations on the leaflet margins or if the
number of dentations is four or less, they are classified as subspecies tridentata. If the leaflet
has more than four dentations, then it is classified as cuneifolia. The subspecies cuneifolia
is more prevalent, having a wider distribution, extending from the Eastern Cape to the
northern portion of South Africa. In contrast, subspecies tridentata occurs from Riversdale
district eastward to Port St Johns and then extends inland in the Southeastern Cape to the
Karoo of South Africa [20].
R. tridentata (L.f) Wild & Drumm. subsp. cuneifolia (Eckl. & Zehr.), N.R. Urton is a
deciduous shrubby creeper in the Vitaceae family. It is commonly known as wild grape
(English), isinwazi (Zulu), and umnxeba (isiXhosa) [39]. This subspecies occurs in various
habitats but is primarily found in forests along forest margins or grows as an erect shrub
of up to 2 m or more in open grassy woodlands [20]. R. tridentata has tendrils and can
grow up to 3 m high, spreading up to 1.5 m. The leaves are trifoliate with wedge-shaped
leaflets, each having a serrated margin (Figure 1G). The plant bears small inconspicuous
yellowish-green flowers followed by small brownish-red berries [39]. Lignotubers ranging
in size from 5 to 30 cm in diameter are attached to the roots [20].
5. Ethnomedicinal Uses of Rhoicissus Species
Species of the Rhoicissus genus are widely used in traditional medicines in African
medicinal systems to treat various diseased conditions. According to several reports,
they are common medicinal herbs used by the Zulus and Xhosas of South Africa. They
are used to treat cattle diseases, high blood pressure and acute headaches, as well as for
blood purification and intestinal cleansing, increasing fertility, relieving menstruation pain,
managing helminthiasis and venereal diseases, treating bloody constipation, increasing
milk production in lactating mothers, wound and ringworm healing, anaesthetic properties,
and facilitating delivery during pregnancy, among others [14,40–43], as summarised in
Table 3. However, no particular class of compound has been identified or linked to a
particular medicinal application. Furthermore, even though most of the Rhoicissus species
are used in African traditional medicine, their prescription, mechanisms and mode of
actions, associated side-effects, and/or proven efficacy are not clear. A more detailed study
is needed to establish their mode of action, side-effects, and safety.
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Table 3. Traditional medicinal uses reported for Rhoicissus species.
Plant Name
R. digitata
R. rhomboidea
R. tomentosa
Ethnic Name
(Z—Zulu; X—Xhosa)
Isinwazi (Z);
Uchititibhunga (X,Z);
umNangwazi (Z);
umPhambane (Z);
iTangalehlathi (Z);
umThwazi (Z)
Isinwazi (Z)
Isinwazi
Idiliya (X);
Impindabamshaye (X);
UmPhambane (Z)
Part
Traditional Use
Reference
Leaf
During pregnancy, to facilitate delivery,
isihlambezo and inembe, which is taken as an
abortifacient.
[14]
It is used to treat cattle diseases.
[40]
An infusion of the tuber is taken for high blood
pressure and acute headaches;
It is used to treat goats and sheep with
paratyphoid.
[41]
Bulbs
Enema for blood purification and intestinal
cleansing;
Used to treat gastrointestinal complaints;
Used as an amulet that destroys gossip;
The plant is also used to increase fertility;
Used to treat painful menstruation;
Used as a general pain reliever.
[42,43]
Roots
Used in the preparation of stomach medicine.
[16,44]
Roots
Used during pregnancy to facilitate delivery.
[14]
Leaf/
stem
Anthelminthic for calves,
during pregnancy to ensure a safe delivery,
and dysmenorrhoea.
[14]
Bark
Used for heartwater in livestock by crushing
and boiling in water and used with Kedrostis
africana to treat 3 day stiff sickness.
[45]
Crushed and boiled in milk for young calves to
treat or manage helminthiasis.
[45]
The boiled roots fusion are used to enhance
fertility.
[42,44,46]
To treat goats and sheep with paratyphoid.
[41]
A root decoction is taken as a remedy for
venereal diseases and bloody constipation.
[18]
Decoctions are given to breastfeeding mothers
and cows to increase milk production.
[47]
Sap from the stem is applied to cuts, burns, and
sores.
[18]
They are externally rubbed onto infected skin to
hasten wound and ringworm healing.
Decoctions are orally taken to treat intestinal
worms, including hookworms.
Decoctions are also externally applied to boils
to ensure faster healing.
[47]
Used as an antiseptic.
[18]
Fresh leaf and stem squeezed together with
water and given orally and also nasally for
livestock to treat leech infection.
[48]
Tubers
Roots
Roots
Stem
R. revoilii
Isinwazi (Z)
Leaves
(crushed)
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Table 3. Cont.
Plant Name
R. tridentata
Ethnic Name
(Z—Zulu; X—Xhosa)
Isinwazi (Z)
Part
Roots
Traditional Use
Reference
Used as herbal oxytocics.
[15]
Used with Clivia miniate, Agapanthus africanus,
Pentanisia prunelloides, and Gunnera perpensa to
prepare isihlambezo (that which cleans)
decoctions used by women in the last trimester
of pregnancy.
[13,15,49–51]
Ease of ingestion by use of juice from the roots
extracted through chewing,
care of abdominal pain during menstruation,
treatment of swollen glands through warming
of the roots in fire and pressing them against the
glands, antiemetics in children, broken bones,
cuts, epilepsy, menorrhagia, eye infections,
sexually transmitted infections (STIs), sprained
ankles, stomach ailments, and sores.
[14,17,19,52]
Used in the protection of liver damage, also
known as hepatoprotective effects.
[53]
Its sap is reported to have healing and
anaesthetic properties, and tuberous roots are
boiled and fed to young animals, especially
those that have lost their mothers.
[19]
Used for the treatment of helminth diseases in
cattle and the tick-borne cattle disease,
babesiosis.
[54,55]
Used to treat erectile dysfunction.
[56]
Heartburn, peptic ulcers, diarrhoea, renal
disorders, and infertility in women.
[57]
Heartwater, redwater, internal parasites,
general ailments, and abortion.
[58]
6. Biological Studies of Rhoicissus Species
6.1. Anti-Inflammatory Activity
The research reported on the anti-inflammatory potential of methanolic extracts of
R. digitata (leaf), R. romboidea (root), R. tomentosa (leaf/stem), and R. tridentata (root) indicated significant inhibition of cyclooxygenase (COX-1) [59,60]. COX-1 is a prostaglandinproducing enzyme that promotes inflammation, pain, and fever, activates platelets, and protects the stomach and intestinal lining. An ethanol indomethacin standard solution (20 µM
in the assay) was assayed together with the samples (13.3 mg for each sample residue) to
verify the sensitivity of the assay [59]. The extracts of R. digitata and R. rhomboidea exhibited
the highest inhibition of prostaglandin synthesis with 53% and 56% inhibition, respectively,
compared to 89% inhibition by the indomethacin standard, suggesting their potential to be
used as anti-inflammatory agents [59,60]. It was reported that none of the aqueous extracts
showed any significant anti-inflammatory activity [59]. Furthermore, R. tridentata was
investigated with the anti-inflammatory enzyme 15-lipoxygenase (15-LOX). The enzyme
(15-LOX) was made up to a final concentration of 200 units/mL in 2 M borate buffer
(pH 9), and a volume of 12.5 µL of each plant sample and control was added to 487.5 µL
of 15-LOX [52]. R. tridentata showed a half maximal inhibitory concentration (IC50 ) of
87.39 µg/mL against the 15-LOX enzyme [52]. The results suggested that members of the
genus Rhoicissus have the potential to be used as anti-inflammatory agents.
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6.2. Antimicrobial Activity
The antimicrobial activities against Gram-positive and Gram-negative microorganisms
of the methanolic extracts of R. digitata, R. rhomboidea, R. tomentosa, and R. tridentata were investigated [59]. Standard antibiotics, penicillin G (10 IU·disc−1 ), tetracycline (30 µg·disc−1 ),
and chloramphenicol (30 µg·disc−1 ), were used to eliminate variations between plates [59].
It was found that all extracts showed some degree of antimicrobial activity, with R. rhomboidea (root) demonstrating the highest inhibitory activity against different microorganisms.
The crude methanolic extracts of R. tridentata and R. digitata mainly inhibited Gram-positive
and Gram-negative microorganisms. Most of the extracts showed insufficient inhibitory
activity towards Salmonella sp. including S. Typhimurium and Shigella sp. (S. boydii and
S. flexneri). None of the extracts inhibited Escherichia coli or showed activity against S.
flexneri. R. digitata (leaf) extract indicated a >10.00 mm inhibition zone diameter against
S. boydii compared to the standard chloramphenicol that showed a 7.00 mm inhibition
zone diameter. Tetracycline showed no activity against S. boydii [59] as a standard. R.
rhomboidei stem extract and the standards chloramphenicol and tetracycline all indicated a
>10.00 mm inhibition zone diameter against Salmonella sp. [59]. It was also reported that the
plant extracts inhibited the Gram-positive microorganisms more than the Gram-negative
ones [59].
The antifungal activity of Rhoicissus species was tested using Candida albicans and
Saccharomyces cerevisiae [59]. Methanolic extracts of R. digitata (leaf) and R. romboidea (root)
exhibited the highest antifungal activity against C. albicans with an inhibition zone diameter
of >10.00 mm. A methanol extract of R. tridentata exhibited antifungal activity against C.
albicans with an inhibition zone diameter of 7.00 mm [59].
A study conducted to screen 14 medicinal plants used by the Venda community
for infectious diseases supported the antibacterial activities of the methanol extracts of
the roots and tubers of R. tridentata [61]. Experiments were conducted using 10 µL of a
50 mg/mL gentamycin solution as a positive control and 15 µL (6%) of dimethyl sulfoxide
(DMSO) as a negative control [61]. The extracts of R. tridentata showed activities against
all the organisms tested with minimum inhibitory concentrations (MICs) varying from
0.75 mg/mL against Bacillus cereus to 6.00 mg/mL against Bacillus subtilis, Enterobacter
cloacae, and Pseudomonas aeruginosa. The minimum inhibitory concentration of gentamycin
was 0.008 mg/mL against most of the organisms tested and 0.017 mg/mL for P. aeruginosa
and Serratia marcescens [61]. Fruit extracts were not as active as the underground parts and
exhibited MICs of more than 12.00 mg/mL [61].
Antimicrobial properties of the methanol root and leaf extracts of R. revoilli were also
studied. The extracts were active against three microorganisms: Gram-positive Streptococcus
pyogenes, Gram-negative Salmonella typhi, and the fungal pathogen Aspergillus niger [47].
First, 3 g of the filtered and dried plant extract was constituted with 10 mL of 100%
cyclohexane to prepare a stock solution. The control had cyclohexane alone without any
extract to cancel the effect of the solvent on the test organisms [47]. The growth inhibition
diameter was 4.68 mm for S. pyogenes, 5.08 mm for S. typhi, and 4.27 mm for A. niger.
The root extract showed more significant microbial growth inhibition in comparison to
leaf extracts [47]. R. revoilli also displayed inhibitory activity against Staphylococcus aureus
at high dilution levels with a 9.00 mm inhibition zone diameter and showed minimal
inhibitory activity against Escherichia coli (8.00 mm inhibition zone diameter) [62]. The
standard, Dettol, showed higher inhibitory activity against E. coli (20.00 mm inhibition
zone diameter) but only at low dilution levels, and inhibitory activity against S. aureus was
lower than in the case of E. coli with a 12.00 mm inhibition zone diameter [62]. The ethanol
extract of R. revoilii rhizomes displayed inhibition zone diameters of 12.82 mm against E.
coli and 17.50 mm against C. albicans [63]. Standard concentrations of 0.12 mg/mL nystatin
and 0.3 mg/mL chloramphenicol were used as positive controls. About 500 mg of the
ethanol extract was triturated with 1 mL of DMSO and then made up to 5 mL in distilled
water to give a test solution of 100 µg/µL concentration for each fraction [63]. These results
support the traditional antimicrobial use of R. revoilli.
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Different medicinal plants were tested for antifungal activities against five Fusarium
species using the whole-plate diffusion method [64]. Sterile dimethyl sulfoxide (DMSO)
was used as a negative control, and nystatin was used as a positive control [64]. The
methanol extract (roots) of R. tridentata was active against Fusarium graminearum with an
inhibition zone diameter of 15.00 mm compared to an inhibition zone diameter of 20.00 mm
for nystatin [64]. The acetone extract (tubers) showed high activities with MIC values
ranging between 0.95 and 3.75 mg/mL against the five Fusarium species tested [64].
Methanol/chloroform (50/50, v/v) and ethyl acetate (100%) extracts of the rhizomes of
R. tomentosa were tested against 14 bacterial strains using the disc diffusion and microdilution assay methods [46]. Bacteria most susceptible to rhizome extracts were Staphylococcus
aureus (MIC of 0.06 mg/mL) and Bacillus subtilis (MIC of 0.13 mg/mL) [46]. The results
showed that the rhizome extracts of R. tomentosa have good antibacterial activity against
Gram-positive organisms such as S. aureus, B. subtilis, Enterococcus faecalis (2.00 mg/mL),
Mycobacterium smegmatis (0.06 mg/mL), Bacillus cereus (0.50 mg/mL), and Staphylococcus
epidermidis (2.00 mg/mL). In contrast, only the Gram-negative organisms Proteus vulgaris
(8.00 mg/mL) and Proteus mirabilis (16.00 mg/mL) displayed sensitivity to the extracts [46].
Extracts of selected plant species used to treat sexually transmitted infections (STIs) in
southern Africa were investigated for antimicrobial properties and anti-human immunodeficiency virus (HIV) activity against the recombinant HIV-1 enzyme [52]. Doxorubicin at
100 µg/mL was used as the positive control. For the negative control, only the lysis buffer
and reaction mixture were added [52]. R. tridentata demonstrated the best antimicrobial
activity against Neisseria gonorrhoeae with the lowest MIC value of 0.40 mg/mL. C. albicans
and Gardnerella vaginalis had MIC values of 0.80 mg/mL and Oligella ureolytica had an MIC
value of 1.60 mg/mL [52]. R. tridentata also had the best HIV-1 RT inhibition activity of
75.50% compared to that of the positive control doxorubicin (96.50%) at 100.00 µg/mL [52].
The observed activities may lead to new multitarget drugs against STIs.
R. tridentata (ethanol extract) also displayed activity against C. albicans, E. coli, and
S. aureus with an MIC of 0.80 mg/mL compared to the positive control ciprofloxacin with
an MIC of 0.1 mg/mL [65].
In a related study, traditional medicinal plants used in South Africa to treat urinary
tract infections caused by microorganisms were investigated [66]. Ciprofloxacin was used
as the positive control at a final concentration of 0.063 mg/mL, while 100 µL of 1.0% DMSO
(instead of plant extract) was used as the negative control [66]. The methanol extract
of R. tridentata displayed the highest activity against Serratia marcescens with an MIC of
0.13 mg/mL [66]. The positive control ciprofloxacin presented an MIC of <0.063 mg/mL.
The polar extracts of R. tridentata were able to reduce the initial cell attachment of S.
aureus, P. mirabilis, and Serratia marcescens by approximately 50% [66]. The quantitative antiquorum sensing assay indicated that the methanol extract of R. tridentata inhibited violacein
production by C. violaceum by more than 50%, with an IC50 of 2.58 mg/mL [66]. The positive
control eugenol was 1.73 mg/mL [66]. The results validate the use of R. tridentata to treat
urinary tract infections (UTIs) and indicate that this plant may be a suitable source of
antipathogenic drugs to treat UTIs [66].
6.3. Antiproliferative Activity
Aqueous and methanol extracts of R. digitata, R. rhomboidea, R. tomentosa, and R.
tridentata were screened to determine their therapeutic potentials as anticancer agents [14].
The antiproliferative activity in vitro against HepG2 cells, a human liver cancer cell line,
was determined. The aqueous root extract of R. tridentata subsp. cuneifolia displayed the
highest antiproliferative activity, with a 96.27% inhibition of proliferation compared with
the other crude plant extracts [14]. The methanol extract of R. tridentata also presented a
more potent inhibition of 87.01%. The crude root extract of R. tomentosa exhibited 70.40%
inhibition of proliferation [14]. The results from this study demonstrated that all the
Rhoicissus species screened have potential antineoplastic activity against the HepG2 cell
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line, and the root extracts demonstrated stronger inhibitory activities compared with the
leaf and stem extracts [14].
6.4. Antioxidant Activity
The antioxidant activity of R. tridentata was 0.06 µg/mL, lower than that of vitamin C
(IC50 of 1.44 µg/mL) [65]. In this study, 2 mg plant samples were tested at concentrations
ranging from 500–3.91 µg/mL. Ascorbic acid (vitamin C) was used as a positive control,
and ethanol was used as a solvent control (blank) [65].
Methanol extracts of the roots, stems, and leaves of four Rhoicissus species (R. digitate,
R. rhomboidea, R. tomentosa, and R. tridentata) were tested for antioxidant activity [67].
Commercial antioxidants vitamin E, butylated hydroxytoluene (BHT), and hydroxyanisole
(BHA) were used as standards [67]. The extracts of R. rhomboidea and R. tridentata revealed
more than 50% antioxidant activity compared with values obtained for the commercial
antioxidants. The commercial antioxidants gave the following results vitamin E, 63%;
butylated hydroxytoluene (BHT), 50.10%; butylated hydroxyanisole (BHA), 42.50% [67]. R.
rhomboidea and R. tridentata inhibited the 1, 1′ -diphenyl-2-picrylhydrazyl free radical with
approximately 98% radical scavenging activity. Xanthine oxidase was inhibited by 88.20%
by the root extract of R. rhomboidei. The stem of R. tridentata exhibited an inhibitory effect
above 70% against xanthine oxidase. It also prevented the production of thiobarbituric
acid-reactive substances and free radical-mediated DNA sugar damage (catechin showed
an 85.40% inhibitory effect) [67].
The four Rhoicissus extracts had a strong chelating effect on Fe2+ ions, especially the
leaves of R. tridentata [67]. R. digitata and R. tomentosa extracts possessed pro-oxidative
properties at high concentrations (2.50 mg/100 mL) due to the presence of the plant
phenolics [67]. The results indicate that the four Rhoicissus species have a protective action
against the overproduction of free radicals. One of the mechanisms of action suggests
that R. rhomboidea and R. tridentata contain compounds (polyphenols) with strong radicalscavenging and antiradical-generating effects.
6.5. Uterotonic Activity
Pharmacological investigation of crude aqueous extracts of R. tridentata roots displayed direct contractile responses in isolated rat uterus and ileum [68]. The muscarinic
receptor system and the produced cyclooxygenase metabolites facilitated the contractile
response to the extract [68]. The results provide evidence justifying the ethnomedical use
of this plant to promote quick and uncomplicated labour. The potential exists for the plant
decoctions to cause birth complications caused by increased uterine contractility [68]. It
was also confirmed that the contractile activity of R. tridentata extracts varies seasonally
to different plant parts [51]. The activity of the plant extracts from plants harvested in
summer and autumn were 4–5-fold higher than extracts from plants harvested in winter or
spring. The lignotubers stimulated the most significant number of contractions, followed
by the stems, roots, and leaves [51].
Aqueous extracts of the roots of R. tridentata revealed notable in vitro activity on
isolated rat uterine smooth muscle tissue [15]. Extracts with the highest activity also
contained proanthocyanidin monomers, dimers, gallic acid, and 74% polymeric proanthocyanidins [15]. Glucose and a hydrogel of glucose extracted from the methanol root extract
also greatly stimulated uterine muscle contraction [15]. β-Sitosterol and its glucoside,
sitosterolin, exhibited only slight oestrogenic activity, increasing the response of the uterus
by about 2% at concentrations of acetylcholine below 10−7 M and 10−5 M, respectively, and
inhibiting this response at higher acetylcholine concentrations [15].
Furthermore, the chloroform and ethanol extracts of the root bark of R. tridentata were
investigated for their in vitro activity on the contraction of corpus cavernosum smooth
muscle of white New Zealand rabbits [56]. The extracts stimulated dose-dependent
relaxation in the muscle at concentrations of 13.00 and 6.50 mg/mL [56]. At an extract concentration of 13.00 mg/mL, the relaxation induced was significantly higher
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(p < 0.01, 30.70 ± 3.3 chloroform extract and 43.00 ± 9.4 ethanol extract) than that seen
with 3.2 × 10−5 mg/mL of the positive control Viagra [56]. This study indicated that R.
tridentata is a promising candidate for the treatment of erectile dysfunction.
6.6. Cytotoxicity
The ethanol extract of R. tridentata showed moderate toxicity with a half maximal
effective concentration (EC50 ) of 88.50 ± 0.09 µg/mL, whereas actinomycin D exhibited
an IC50 value of 0.00932 µg/mL [65]. Actinomycin D ranging from 400–3.13 and 0.013 to
0.0001 µg/mL was used as a positive control for the cytotoxicity assay. The toxicity effects
of the samples were determined using 50 µL of XTT reagent (1 mg/mL 2,3-bis-(2-methoxy4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) with 0.383 mg/mL N-methyl
dibenzopyrazine methyl sulphate (PMS)) [65].
The cytotoxicity of the aqueous extracts from R. tridentata was studied using monkey
Vero cells and human fibroblasts [50]. The threshold for zero cell deaths was 8.00 µg/mL for
monkey Vero cells. At this concentration, 100% of human fibroblast cells also survived [50].
The estimated concentration in the bloodstream was 6.10 µg/mL, taking dilutions into
account. It was then concluded that R. tridentata is not toxic at a cellular level since the
estimated cell concentrations were below the thresholds for zero cell death for monkey Vero
cells, which is 8.00 µg/mL [50]. The nontoxic nature of this species was also demonstrated
using human hepatoma, kidney epithelial, histiocytoma, and mouse Leydig cells [15].
6.7. Hepatoprotective Activity
The identity of catechins and the in vitro antioxidative properties of R. tridentata
motivated a study to investigate the in vivo hepatoprotective effects of R. tridentata against
CCl4 -induced acute liver injury in rats [53,55,67]. The variables investigated were the
alanine aminotransferase (ALT), aspartate aminotransferase (ASP), glucose-6-phosphatase
(G-6-Pase), and lipid peroxide (LPO) levels of liver homogenates. Liver microsomal
fractions were investigated as malondialdehyde (MDA) levels [53]. The results displayed a
decrease in the concentration of ALT, ASP, and LPO (p < 0.05) after the administration of
the plant extract to the CCl4 -intoxicated rats. In contrast, the G-6-Pase concentration was
elevated (p < 0.05) in the plant extract-treated rats, and this shows that R. tridentata has
components with hepatoprotective properties [53].
6.8. Ascaricidal Activity
The in vitro anthelmintic activity of the extracts of R. tridentata was tested, and the
median effective dose (ED50 ) values of the extracts were determined using the Ascaris
model [54]. The ED50 of R. tridentata was found to be 4.36 mg/mL [54]. The highest dose of
10.00 mg/mL first showed activity at 12 h, achieving a maximum response of 100% at 24 h.
Doses of 4.00, 6.00, and 8.00 mg/mL first showed activity at 12 h. The maximum response
was achieved at 48 h for doses of 4.00 and 6.00 mg/mL. After 36 h, the maximum response
was achieved for 8.00 mg/mL. The lowest dose of 2.00 mg/mL started a response at 24 h
and only achieved a 90% response at 48 h [54]. These results show that R. tridentata can be
used for the treatment of helminth diseases in cattle.
A study to determine in vitro ascaricidal activity of ethanolic and water extract of roottuber R. tridentata against adult nematodes was conducted [69]. The in vitro adult motility
inhibition assay revealed that the two extracts exhibited motility inhibition, and the ethanolic extract was more potent [69]. The ascaricidal single-dose effect increased with increasing
concentration of the extract. The highest concentrations of 64.00 and 128.00 mg/mL for
ethanol and water extracts gave a maximum mean percentage ascaricidal activity by 48 h as
80.00 ± 10.0% and 90.00 ± 0.6%, respectively [69]. The crude extract’s potential to control
gastrointestinal nematodes was indicated by the low ED50 of 25.00 mg/mL [69].
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6.9. Antidiabetic Activity
A study was designed to evaluate the antidiabetic potential of aqueous leaf extracts of
R. tridentata in alloxan-induced diabetic mice [19]. The aqueous leaf extracts showed antidiabetic activity. Intraperitoneally and orally administered aqueous whole-stem extracts of R.
tridentata decreased the blood glucose levels at all four doses of 50.00, 100.00, 200.00, and
300.00 mg/kg body weight, from the first hour to the sixth hour in a dose-independent
manner [19]. The intraperitoneal route of herbal extract administration was more effective
than the oral route [19].
7. Phytochemistry of Some Species of the Rhoicissus Genus
The study of chemical compounds found in plants is essential for drug discovery
and for developing novel therapeutic agents against significant diseases as they are biologically active. Different species of the Rhoicissus genus have been shown to possess
bioactive compounds such as coumarins, flavonoids, phytosterols, essential oils, saponins,
terpenoids, alkaloids, reducing sugars, and tannins, which are the reason for their use
in traditional medicine. The phytochemical screening carried out on the rhizomes of R.
tomentosa revealed the presence of many known groups of bioactive compounds: alkaloids,
flavonoids, saponins, steroids, reducing sugars, and tannins [46].
While there have been many investigations on the pharmacological activities of this
genus, little has been achieved concerning the isolation and identification of bioactive
compounds. It is established that few chemical constituents have been isolated from these
species within the review period, as most of the chemical constituents have been profiled
from the crude extracts. This limits further studies aimed at advancing the bioactive
constituents to clinical trials.
Among the identified compounds, essential oils and other phenolic acids (1–14) were
predominant. Other compounds included triterpenoids such as 12,13-dehydrolupeol
(21), 3β-taraxerol (23), and stigmasterol (24), as well as flavonoids such as quercetin (22),
quercetrin (25), and aromadendrin-7-O-β-glucopyranoside (26), among others, as illustrated in Tables 4 and 5 and Figures 2–4.
Table 4. Compounds identified in R. tomentosa rhizomes and their biological activities.
Compound
Number
Name of Compound
Biological Activity
Reference
1
2
3
D -Asparagine
L -Arginine
Glycyl-L-valine
Immuno-stimulant, antibacterial, anti-infective, and analgestic activities.
Anti-inflammatory, immunostimulant, and antihypertensive activities.
Analgesic, antipyretic, antioxidant, and anti-inflammatory activities.
Neuroprotective activity, pyrimidine metabolism, antidepressant, and
antiepileptic actions.
Antipruritic, antifungal, anti-infective, and antioxidant activities.
Antioxidant, antibacterial, anthelmintic, and antifungal activities.
Antifungal, antitumor, antibacterial, and antioxidant activities
Anti-abortifacient, antioxidant, antibacterial, analgesic, and antipyretic
activities.
Antipruritic, antioxidant, and anaesthetic activities
Antibacterial activity.
Antispasmodial, antioxidant, and antiabortifacient activities.
Analgesic, antipyretic, antibacterial, antifungal, and anti-inflammatory
activities.
Antioxidant, anti-inflammatory, antitumor, antispasmodial, and
antimicrobial activities.
Antifungal, cytotoxicity, antiasthmatic, and antidepressant activities.
[70]
[71]
[72]
4
Uridine
5
6
7
Tetradecanoic acid
Hexadecanoic acid
Octadecanoic acid
8
Eicosanoic acid
9
10
11
Docosanoic acid
Tetracosanoic acid
Hexadecanoic acid, methyl ester
12
Decanoic acid, 2-propenyl ester
13
cis-9-Octadecenoic acid
14
9-Octadecynoic acid
[73]
[74]
[75]
[76]
[77]
[78]
[79]
[80]
[81]
[82]
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Figure 2. Chemical structures of acids isolated from the genus Rhoicissus.
Organic acids (malic (15), succinic (16), and fumaric acids (17)) (Figure 2) were also
detected in the free phenolic fraction and malonoic and propanoic acids were detected
in the hydrolysable fraction of R. tridentata [17]. Homovanillyl alcohol was found in the
free phenolic fraction, and gallic (18), vanillic (19), and ferulic acids (20) (Figure 2) were
confirmed in the bound phenolic fraction [17]. Qualitative and quantitative phytochemical
screening of the aqueous leaf extracts of R. tridentata also indicated the presence of phenols,
alkaloids, flavonoids, tannins, and saponins [19]. R. tridentata is known to contain a
high concentration of polyphenolic compounds [55,67]. The phytochemical screening of
R. revoilli revealed active compounds such as flavonoids, alkaloids, saponins, steroids,
and anthraquinones. Aldehydes were detected in the leaf extract [47]. However, these
compounds were not structurally elucidated.
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Figure 3. Chemical structures of triterpenoids, flavonoids, alkaloid, and carotenoid isolated from the genus Rhoicissus.
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Figure 4. Structures of proanthocyanidin monomers and dimers from genus Rhoicissus.
A phytochemical investigation of the roots and fruits of R. digitata led to the isolation
of triterpenes and flavonoids [44]. From the roots, leaves, and fruits of R. tomentosa,
terpenoids, flavonoids, an alkaloid, and a carotenoid were isolated, as illustrated in Table 5
and Figure 3 [44]. Moreover, the leaf extracts of R. tomentosa tested positive for coumarins,
flavonoids, phytosterols, essential oils, saponins, terpenoids, and resveratrol, and the
hexane and ethyl acetate/hexane (1:4) extracts of R. tomentosa were submitted for GC–MS
analysis [83].
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Table 5. Compounds isolated from Rhoicissus species.
Plant Name
Class
Triterpenoids
Number
Name
Biological Activity
Reference
21
12,13Dehydrolupeol
Anti-inflammatory, antitumor,
chemopreventive, hepatoprotective,
cardioprotective, and antiarthritic
[44,84]
β-Sitosterol
Antidiabetic, neuroprotective,
chemoprotective agent, antioxidant,
anti-inflammatory,
hypocholesterolemic, inducing
apoptosis, angiogenic, anthelminthic,
and immunomodulatory
[44,85]
31
Oleanolic acid
Anticancer, antiosteoporosis,
antiobesity, antidiabetic, lipid-lowering,
anti-inflammatory, antioxidant,
immune-regulatory, and
hepatoprotective effects
[44,86]
34
(+)-Catechin
Antioxidant, antimicrobial,
antimutagenic, anticarcinogenic, and
cardioprotective
[44,87]
22
Quercetin
Antioxidant (peroxonitrite (ONOO− )
half maximal inhibitory concentration
(IC50 ) = 8.6 µM;
2,2-diphenyl-1-picrylhydrazyl (DPPH)
IC50 = 27.6 µM), anti-inflammation,
antiviral, antiobesity, and
antidepressant, as well as preventing
cancer, diabetes, asthma, hypertension,
and cardiovascular diseases
[44,88]
23
3β-Taraxerol
Antidiabetic, anti-inflammatory
[44,89]
24
Stigmasterol
Antiosteoarthritic,
antihypercholestrolemic, cytotoxicity,
antitumor, hypoglycaemic,
antimutagenic, antioxidant,
anti-inflammatory, and central nervous
system (CNS) effects
[44,90]
25
Oleanolic acid
[44]
32
β-Sistosterol
[44]
32
R. digitata
Flavonoids
Terpenoids
R. tomentosa
25
Quercetrin
[44]
34
(+)-Catechin
[44]
26
Aromadendrin-7O-βglucopyranoside
[44]
27
Pheophytin
Neuroprotective,
antimutagenic, anti-inflammatory
[44,91]
Lutein
Antioxidant, antiarthritis,
anti-inflammatory, hepatoprotective,
cardioprotective, anticataract,
antidiabetic, anticancer, and bone
remodelling activities
[44,92]
Flavonoids
Alkaloid
Carotenoid
28
Previously undescribed compounds from the species were isolated from the extracts
of R. tridentata [15]. The proanthocyanidin monomers and dimers from the methanol root
extract were identified as follows using HPLC: catechin (34), gallocatechin (35), fisetinidol
(36) mollisacacidin (37), epicatechin (38), epigallocatechin (39), epicatechin-3-O-gallate (40),
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procyanidin B3 (41), procyanidin B4 (42), fisetinidol (4α-8) (43), fisetinidol (4β-8), catechin
(44) (Figure 4), andgallic acid (18) (Figure 2).
Glucose and a partially identified hydrogel of glucose were also isolated from the
methanol root extract. Oleanolic acid (31) was isolated from a chloroform extract. The
nonpolar fraction yielded two further triterpenoids, 20(29)-lupen-3-one (29) and 20-epi-ψtaraxastananol (30), as well as γ-sitosterol (33), which were identified by gas chromatography–
mass spectrometry (Figure 3). From the extract of branches, the plant growth hormone
triacontanol was purified [15].
Most of the isolated compounds have documented health-promoting properties. It
supports their use by traditional healers to promote good health during pregnancy. Proanthocyanidins are potent antioxidants beneficial for the heart, cardiovascular, and immune
systems (Figure 4). Lupenone (29) has antibiotic and antioxidant activity [93]. Triacontanol has cholesterol-lowering properties, and the triterpenoids such as oleanolic acid
(31), lupenone (29), and taraxastananol (30) are well known for their anti-inflammatory
properties [15,94].
8. Conclusions
R. tridentata is used to treat various ailments including erectile dysfunction, pains,
swelling, cuts, wounds, kidney and bladder complications, stomach ailments, and livestock
diseases, as well as for gynaecological purposes. Compounds isolated from R. tridentata
include proanthocyanidin monomers and dimers, phenols, alkaloids, flavonoids, tannins,
saponins, organic acids, and triterpenoids. Pharmacological studies indicated that Rhoicissus species exhibited antitumor, antispasmodic, antipruritic, anaesthetic, neuroprotective,
analgesic, antipyretic, antidepressant, antiepileptic, anthelmintic, antiasthmatic, antidiabetic, uterotonic, ascaricidal, hepatoprotective, antibacterial, antidiabetic, antioxidant,
antimicrobial, antifungal, anticancer, and anti-inflammatory properties. These results are
encouraging and indicate that Rhoicissus is an essential source of many pharmacologically
and medicinally important compounds. Hence, this plant has the potential as an alternative
therapeutic strategy to treat diseases and can be used as part of a template for developing
safer and powerful drugs to combat diseases. The observed biological activities of the members of Rhoicissus support the medicinal use of these plants by traditional healers. However,
no specific compound class has been identified or linked to a particular ethnomedicinal application of these species. Their prescription, mechanisms, associated side-effects, and/or
proven efficacy are also not clear. Thus, there is a need for more detailed studies to establish
the missing information.
While many investigations into the pharmacological activities of the genus Rhoicissus
have been done, little has been achieved concerning the isolation and identification of
bioactive compounds. Only a few chemical constituents have been isolated from these
species within the review period. This limits further studies aimed at advancing the
bioactive constituents to clinical trials. Studies focusing on the biological activities of
Rhoicissus have been conducted in vitro, and little data are available on the biological
activities of compounds isolated from the species. There is a need for further studies
focusing on the phytochemistry, pharmacological, and toxicological properties, as well as
in vivo studies involving the crude extracts and chemical compounds isolated from the
species. New techniques such as high-throughput screening, molecular docking studies,
and metabolomics should be advanced, especially for complex plant matrices.
Author Contributions: N.P.D. conceptualised, read, reviewed, and wrote the original draft of the
manuscript; X.S.-N., R.W.M.K., D.K., V.J.T. and A.-L.M. read, reviewed, corrected, and provided
insights into the occurrence, distribution, traditional uses, phytochemistry, and pharmacological
properties of Rhoicissus species. All authors have read and agreed to the published version of
the manuscript.
Funding: This research was funded by the National Research Foundation, grant number 121119, and
Tshwane University of Technology, Pretoria, South Africa.
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Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Acknowledgments: The authors are grateful to Leonie Goosen for proofreading the manuscript.
Conflicts of Interest: The authors declare no conflict of interest. Funders had no role in the design of
the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in
the decision to publish the results.
Abbreviations
ANOVA
ALT
ASP
ATP
BHA
BHT
CCl4
COX
DMSO
DNA
G-6-Pase
LOX
LPO
MIC
STI
TGF-β1
UTI
one-way analysis of variance
alanine amino transferase
aspartate amino transferase
adenoside triphosphate
butylated hydroxyanisole
butylated hydroxy toluene
carbon tetrachloride
cyclooxygenase
dimethyl sulfoxide
deoxyribonucleic acid
glucose-6-phosphate
lipo-oxygenase
lipid peroxide
minimum inhibitory concentration
sexually transmitted infection
transforming growth factor-β1
urinary tract infection
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