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Received: 4 June 2022 Revised: 6 July 2022 Accepted: 6 July 2022
DOI: 10.1002/fft2.170
REVIEW ARTICLE
Desmodium adscendens (Sw.) DC.: A magnificent plant with
biological and pharmacological properties
Maria Giulia Manzione1Jesús Herrera-Bravo2,3Javad Sharifi-Rad4
Dorota Kregiel5Mustafa Sevindik6Emre Sevindik7Zeliha Salamoglu8
Wissam Zam9Sara Vitalini10,11 Christophe Hano12 Wirginia Kukula-Koch13
Wojciech Koch14 Raffaele Pezzani1,15
1Phytotherapy Lab, Endocrinology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy
2Departamento de Ciencias Básicas, Facultad de Ciencias, Universidad Santo Tomas, Santiago, Chile
3Center of Molecular Biology and Pharmacogenetics, Scientific and TechnologicalBioresource Nucleus, Universidad de La Frontera, Temuco, Chile
4Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador
5Department of Environmental Biotechnology, Lodz University of Technology, Lodz, Poland
6Department of Food Processing, Bahçe VocationalSchool, Osmaniye Korkut Ata University, Osmaniye, Turkey
7Department of Agricultural Biotechnology, Facultyof Agriculture, Adnan Menderes University, Aydin, Turkey
8Department of Medical Biology, Faculty of Medicine, Nigde Omer Halisdemir University, Nigde, Turkey
9Department of Analytical and Food Chemistry,Faculty of Pharmacy, Al-Andalus University for Medical Sciences, Tartous, Syria
10Department of Agricultural and Environmental Sciences, Università degli Studi di Milano, Milan, Italy
11Phytochem Lab, Department of Agricultural and Environmental Sciences, Università degli Studi di Milano, Milan, Italy
12Laboratoire de Biologie Des Ligneux Et Des Grandes Cultures (LBLGC), INRA USC1328 Université d’Orléans, Orléans Cedex 2, France
13Department of Pharmacognosy with Medicinal Plants Garden, Medical University of Lublin, Lublin, Poland
14Department of Food and Nutrition, Medical University of Lublin, 4a Chodźki Str., Lublin 20-093, Poland
15AIROB, Associazione Italiana per la Ricerca Oncologica di Base, Padova, Italy
Correspondence
Javad Sharifi-Rad, Facultad de Medicina,
Universidad del Azuay,Cuenca, Ecuador.
Email: javad.sharifirad@gmail.com
Sara Vitalini, Department of Agricultural and
Environmental Sciences, Università degli Studi
di Milano, Via G. Celoria 2, 20133, Milan, Italy.
Email: sara.vitalini@unimi.it
Christophe Hano, Laboratoire de Biologie Des
Ligneux Et Des Grandes Cultures (LBLGC),
INRA USC1328 Université d’Orléans, 45067
Orléans Cedex2, France.
Email: hano.christophe@gmail.com
Abstract
Desmodium adscendens (Sw.) DC. is a plant of the Fabaceae family especially rich in
flavonoids but also in alkaloids, terpenoids, steroids, phenols, phenylpropanoids, gly-
cosides, and volatiles. This herb has been traditionally used in numerous countries all
over the world for its pharmacological and biological properties (i.e., it has been used
for the treatment of diarrheas, fever, epilepsy, asthma, leishmaniasis, gastroduode-
nal ulcer, diabetes, hepatic diseases, etc.). Given the wide uses of D. adscendens,this
review summarizes all recent data on D. adscendens evaluating its phytochemistry as
well as its ethno-traditional and pharmacological properties. In addition, an association
between the phytocompounds of this plant and its potential mechanism of action in cell
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial- NoDerivs License, which permits use and distribution in any
medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2022 The Authors. Food Frontiers published by John Wiley & Sons Australia, Ltd and Nanchang University, Northwest University, Jiangsu University, Zhejiang
University, FujianAgriculture and Forestry University.
Food Frontiers. 2022;3:677–688. wileyonlinelibrary.com/journal/fft2 677
678 MANZIONE ET AL.
Raffaele Pezzani, Phytotherapy Lab,
Endocrinology Unit, Department of Medicine
(DIMED), University of Padova, via Ospedale
105, Padova, 35128, Italy.
Email: raffaele.pezzani@unipd.it
Sara Vitalini and Raffaele Pezzani are co-last
authors.
and animal models has been investigated, focusing with a special emphasis on human
experiments.
KEYWORDS
clinical trial, Desmodium adscendens, pharmacological properties, phytochemistry, preclinical
studies
1INTRODUCTION
According to World Health Organization https://www.who.int/health-
topics/traditional-complementary-and-integrative-medicine,the
term “traditional medicine” is defined as the sum of knowledge, skills,
and practices based on different culture-specific theories, beliefs,
and experiences to protect and improve health. The use of traditional
medicine since ancient times is shared in different countries, and its
knowledge has been transmitted for generations (Leonti, 2011). Plants
(fruits, vegetables, herbs) can contain many active ingredients, such as
vitamins, terpenoids, phenolic compounds, nitrogen compounds (alka-
loids, amines, and betalains), and other metabolites with interesting
antioxidant potential (Muanda et al., 2011; Serafini & Peluso, 2016;
Traka & Mithen, 2011). Desmodium adscendens (Sw.) DC., abbreviated
“DA”, is a perennial medicinal plant from the Fabaceae family found in
tropical and subtropical areas of the world which contains numerous
bioactive compounds (Magielse et al., 2013). This herbaceous plant
(Figure 1) is used since ancient times for different diseases, including
muscle cramps, tendinitis, spinal pain, epilepsy, jaundice, hepatitis,
bronchitis, asthma, allergic reactions, and eczema. It has also anti-
spasmodic and antihypertensive properties (Seriki et al., 2019). Of
note that diverse ethnotraditional medicines in the world used DA
for the treatment of different diseases. For example, in the American
continent, it is valued for the treatment of gonorrhea, diarrheas, body
aches, excessive urination, ovarian inflammations, fever, and epilepsy,
while in Africa it cures smooth muscle contraction and asthma (Taylor,
2005; Gyamfi et al., 1999). In India, D. adscendens has been reported
to possess antileishmanial, antioxidant, immunomodulatory, antiulcer,
cardio-protective, antidiabetic, anti-amnesia, antiviral, and hepato-
protective activities (Ma et al., 2011; Rastogi et al., 2011). In Europe,
the plant is commonly used as a food health supplement for its hep-
atoprotective action even if EFSA (European Food Safety Authority,
the agency of the European Union that provides scientific information
on potential risks associated with the food chain and botanicals) still
needs to confirm this supposed effect (Botanicals On-hold – EFSA
https://www.efsa.europa.eu ›sites ›default ›files 371, M-2008-1061,
EFSA-Q-2008-3268, 2535 – Desmodium).
The nonflowering aerial parts including leaves and stems are the
medicinal parts that have been extensively studied over the past few
decades (Ma, Zheng, Hu, Rahman & Qin, 2011; Rastogi, Pandey &
Rawat, 2011). These organs contain flavonoids, isoflavonoids, alka-
loids, terpenoids, steroids, phenols, phenylpropanoids, glycosides, and
volatile molecules (Ma et al., 2011). In vitro and in vivo works based
on crude extracts, fractions, or isolated components of DA have been
shown to provide scientific evidence for their conventional uses. The
aim of this review is to provide comprehensive information on botany,
phytochemistry, traditional uses, preclinical and clinical pharmacolog-
ical research, and the toxicology of DA and to explore its therapeutic
potential and future perspectives. This work was prepared by research-
ing articles, papers, and books from different databases (Embase-
Elsevier, Google Scholar, Ovid, PubMed, Science Direct, Scopus, Web
of Science) using a combination of different keywords, that is, Desmod-
ium,Desmodium adscendens, pharmacology, ethnopharmacology, phy-
tochemicals, antioxidant, antimicrobial, anti-asthmatic, immunomodu-
latory, antiulcer, cardioprotective, antidiabetic, anti-amnesia, antiviral,
hepatoprotective. Only sources written in English from any country
were included.
2PHYLOGENY, BIOGEOGRAPHY, AND
CHARACTER EVOLUTION
Fabaceae (Leguminosae), the third largest family within the
Angiosperms, includes 946 genera and over 24,500 accepted species
(The Plant List, http://www.theplantlist.org/browse/A/Leguminosae/).
There are commonly three subfamilies—Caesalpinioideae,
Mimosoideae, and Papilionoideae—that have been recently split into
six subfamilies, namely Caesalpinioideae, Cercidoideae, Detarioideae,
Dialioideae, Duparquetioideae, and Papilionoideae. The Legume
Phylogeny Working Group (LPWG) provided key and taxonomic
descriptions to exemplify the diversity of flowers and fruits in these
subfamilies (Azani et al., 2017). The Phaseoloid clade is one lineage
within Papilionoideae, which comprises the Phaseoleae sensu lato (s.l.)
clade, Desmodieae, and Psoraleeae. The clade shows a multifaceted
phylogenetic association among and within tribes. Indeed Desmodieae
and Psoraleeae can be considered monophyletic groups that are
nested within the paraphyletic Phaseoleae s.l. group (Jin et al., 2019).
The tribe Desmodieae (Benth.) Hutchinson comprises 32 genera and
ca. 530 species used for medicine and forage (Jabbour et al., 2018).
They largely grow in warm-temperate regions, even if a small group
has adapted to cool-temperate and boreal regions of North Amer-
ica. This tribe is commonly represented by herbs or shrubs, while not
often by trees. Legumes or loments (a single carpel that disarticu-
lates into single-seeded segments when ripe) are the classical forms of
fruits. Bryinae, Desmodiinae, and Lespedezinae are the three subtribes
of Desmodieae. Of note that Desmodiinae possesses great generic
diversity in tropical South and South-East Asia, while species of the
subtribe Lespedezinae are found in temperate East Asia and North
America. The tribe was further circumscribed into three groups based
on an analysis of the chloroplast gene rbcL: the Lespedeza group (three
MANZIONE ET AL.679
FIGURE 1 Flowering stem and developing seedpods of
Desmodium adscendens (Sw.) DC. plant
genera) corresponding to the Lespedezinae subtribe, the Phyllodium
(12 genera), and Desmodium (17 genera) groups, together correspond-
ing to the Desmodiinae subtribe (Jabbour et al., 2018; Jin et al., 2019).
Jabbour et al. obtained chloroplast (rbcL, psbA-trnH) and nuclear
(ITS-1) DNA sequences to evaluate the molecular phylogeny and his-
torical biogeography of Desmodieae (Jabbour et al., 2018). The results
obtained from wide molecular analysis suggested that the hypothetical
common ancestor of Desmodieae was dated to the Middle Oligocene
and was likely an Asian shrub or tree producing indehiscent loments.
While America has been suggested to be colonized once, with the
development of Desmodium intortum (Mill.) Urb. and Desmodium adscen-
dens (Sw.) DC., Oceania, and Africa were populated several times.
Jin and co-workers investigated the plastome evolution and analyzed
phylogenetic signaling by sequencing six complete plastomes from rep-
resentative members of Desmodieae (Jin et al., 2019). The phylogenetic
analysis showed that the tribe Desmodieae was probably a mono-
phyletic group nested within the paraphyletic Phaseoleae, as reported
in former works.
Desmodium is a genus with more than 46 species and is consid-
ered a curative plant in Africa (Central African Republic, Gabon, Ghana,
Cameroon, Congo, Ivory Coast, Equatorial Guinea, Senegal, Sierra
Leone, Benin, and Togo), in South America (Peru, Bolivia, Ecuador,
Brazil, Venezuela, Guyana, Guyana, Nicaragua), in Southeast Asia
(Japan, Burma, Indonesia, Malaysia, Philippines, Cambodia, Vietnam),
India, Indian Ocean (Rodrigues, Mauritius), in Pacific (Vanuatu, New
Caledonia, Guadalcanal, Salomon, Palau), Taiwan, and China (Farid
et al., 2018) and North-East America (Parker et al., 2015).
3PHYTOCHEMISTRY OF DESMODIUM SPECIES
Different parts of Desmodium species possess mixed groups of
bioactive compounds. They are rich in flavonoids (flavones, 7, 8-
prenyl-lactone flavonoids, flavonols, flavan-3-ols, and flavanonols) and
especially isoflavonoids (isoflavones, isoflavanones, pterocarpans, and
coumaronochromones) (Figure 2a,b). Indole alkaloids, phenylethy-
FIGURE 2 Chemical structures of flavonoids (a) and isoflavonoids
(b). Chemical structure of isovitexin-2″-O-xyloside. (c) Chemical
structure of quercitrin dehydrate (d)
lamine alkaloids, pyrrolidine alkaloids, amide alkaloids, and simple
alkylamine were the main alkaloids found in Desmodium. In addition,
numerous terpenoids, steroids, phenols, phenylpropanoids, glycosides,
and volatile oils have been isolated and characterized in the genus (Ma
et al., 2011).
Some studies evaluated methanolic crude extracts of DA reporting
the presence of polyphenols and particularly flavonoids, found mainly
in the leaves rather than in stems (Konan et al., 2012; Mamyrbékova-
Békro et al., 2008). In the past decade, Baiocchi and collaborators
were able to quantify saponins and alkaloids using high-resolution
mass spectrometry (Baiocchi et al., 2013). Of note that plants grown
in Africa were quantified for flavonoids by high-performance liquid
chromatography (HPLC) with a diode array detector, mass spec-
trometry, and multidimensional nuclear magnetic resonance spec-
troscopy (Zielinska-Pisklak et al., 2015). Chemical characterization of
DA plant material identified the isovetixin-2″-O-xyloside (flavone C-
glycosides) (Figure 2c) as the main compound in an ethanol extract
(Muanda et al., 2011). Munda and collaborators isolated and identi-
fied five main phenolic compounds from DA leaves, namely caffeic
acid, quercetin, p-coumaric acid, epicatechin, and rutin as well as
other compounds such as phenylethylamines, indole-3-alkyl amines,
tetrahydroiso-quinolones, and triterpenoid saponins (Muanda et al.,
2011).
The volatiles extracted from the leaves included phytone
(14.72%), caryophyllene oxide (11.32%), eudesma (7.41%), geran-
iol (5.42%), linalool (5.33%), palmitic acid (5.06%), α-caryophyllene
(4.76%), scytalone (3.83%), β-ionone (3.47%), 2,2-dimethyl-hexanale
(3.37%), pelargonaldehyde (3.26%), hyperforine (3.27%), 2-pentyl
furan (2.71%), oleic acid (2.68%), and 4-azidoheptane (2.02%) (Ayoola
et al., 2018) In another study, phytochemical investigation of a DA
680 MANZIONE ET AL.
decoction resulted in the identification of flavonoids such as vicenin-2,
isoschaftoside, schaftoside, 2″-O-xylosylvitexin, 2″-O-pentosyl-
chexosylapigenin, and an O-hexosyl-C-hexosyl-apigenin, tentatively
identified as 2″-O-glucosyl-vitexin (van Dooren et al., 2018). In addi-
tion, DA decoction possessed vitexin and isovitexin glycosides at high
concentration: vitexin and the C-glycosides thereof were investigated
for their interaction at the gastrointestinal level (with simulation test)
reporting the stability of the molecules (van Dooren et al., 2018).
Muanda et al. evaluated the total phenolic profile in DA leaves which
were found to be a rich source of flavonoids with 12.8 mg of catechin
equivalent (CE)/g dry weight (dw) (Muanda et al., 2011). The amount
of total polyphenols was 11.1 mg of gallic acid equivalent (GAE)/g
dw while that of total anthocyanin and total tannin compounds was
not elevated, equal to 0.0182 mg CE/g dw and 0.39 mg CE/g dw,
respectively. Finally, HPLC analyses revealed that the main phenolic
compound identified in the methanol–water extract was quercetin
dihydrate (2.11 mg/mL) (Figure 2d). The compounds identified in DA
are listed in Table 1. Recently, also seeds of D. gangeticum (L.) DC. were
evaluated and their content (oil and fatty acids) was examined. The
yield of crude oil was found to be 4.39%. Among the identified fatty
acids, oleic acid (38.7%), linoleic acid (35.4%), palmitic acid (11.2%),
behenic acid (8.0%), and stearic acid (4.5%) were the main constituents
(Manivel et al., 2018).
4 TRADITIONAL USE OF GENUS DESMODIUM
Ethnobotany describes relationships between humans and plants and
searches for traditional botanical knowledge. Ethnobotanical studies
explore the profound interaction between plant diversity, social, and
cultural systems to understand and develop knowledge of valuable
region-specific plants (Amjad et al., 2017; Baydoun et al., 2015). Among
these, Desmodium spp. were frequently reported as ethnomedicinal
plants. In particular, DA is the most known and used plant, also called
beggar-lice, beggar weed, tick clover, or tick trefoil (Rastogi et al.,
2011). The simple use of DA by decoction (the act of placing a plant
or its part in hot water and the possibility to be administered orally or
topically) led to the wide diffusion of this plant (Baydoun et al., 2015).
In Brazil, this species is without difficulty collected in the Northeast,
Center West, and Southeast regions (Rastogi et al., 2011). In Mato
Grosso, the plant is known as “amores do campo” or “carrapichinho”
and in São Paulo and Rio Grande do Sul as “pega-pega” (Santos et al.,
2013). Its leaves are commonly collected to treat leucorrhea, gonor-
rhea, diarrheas, body aches, excessiveurination, hepatic infections, and
ovarian inflammations (Rastogi et al., 2011). In France and Belgium, this
plant is traditionally used as a food health supplement for its hepato-
protective effects (Muanda et al., 2011). DA is a woody stem climbing
plant that also grows in fallow land on the west coast of Africa, fre-
quently found in Nigeria, Cameroon, and Zimbabwe. This perennial
herb produces numerous light-purple flowers and green fruits in small,
beanlike pods (Adeniyi et al., 2013). It is a solitary hedgerow grow-
ing in humid lands, and it is widespread in savannas and forests (Azani
et al., 2017). In Africa, plants of the Desmodium genus are extensively
used to heal asthma and smooth muscle spasms (Muanda et al., 2011).
In China, the use of Desmodium spp. for ethnomedicinal purposes
dates back as far as 3000 years ago. They were mainly used to treat
fever, block pain, restore blood circulation, counteract toxins, remove
cough, and relieve dyspnea. Ethnopharmacological studies on DA in
India showed a broad spectrum of activities including antileishmanial,
antiviral, antioxidant, immunomodulatory, antiulcer, cardio-protective,
antidiabetic, and anti-amnesia, and hepatoprotective (Rastogi et al.,
2011). Currently, in Chinese and Indian medicines, Desmodium species
are used to approach with fever, rheumatism, hemoptysis, abscess,
common cold, wounds, icteric hepatitis, pharyngitis, infantile malnutri-
tion, dysentery, urinary diseases, parotitis, cholecystitis, malaria, and
epidemic encephalitis (Ma et al., 2011; Rastogi et al., 2011).
D. gangeticum, another recognized and used plant of the same genus
commonly known as ‘Salpan’, ‘Salpani’ in Hindi and ‘Shalparni’ in San-
skrit, is used in Ayurveda, Siddha, and Unani systems of medicine either
as a single drug or in combination with other drugs. D. gangeticum is
an accepted source of Shaliparni as per the Ayurvedic Pharmacopeia
of India (Vaghela et al., 2012). This plant with bitter tonic, febrifuge,
digestive, anticatarrhal, and antiemetic properties, is used in inflam-
matory conditions of the chest and other cases due to “vata” disorder
(in Ayurveda, vata is one of the three principles of energy associated
with movement). The roots have been used as an expectorant and in
snake bites and scorpion stings. It is an ingredient of Ayurvedic prepa-
rations like “Dashmoolarishta” and “Dashmoolakwaath” recommended
for postnatal care to avoid secondary complications (Rastogi et al.,
2011).
Desmodium species that form a nitrogen-fixing symbiosis with rhi-
zobia play an important role in sustainable agriculture (Delamuta
et al., 2015; Xu et al., 2016). They are very effective in suppressing
weeds while improving soil fertility. In addition, these plants provide
high-value animal fodder and forage, inducing milk production and
expanding farmers’ income sources (Khan et al., 2014; Thomas & Sum-
berg, 1995). In general, soil microedges provide an ecological niche
for Desmodium spp. (Kowalski & Henry, 2019). Furthermore, DA has
been used as a ground cover in post-mining lands. It was documented
that this plant is an important instrument in soil conservation and
rehabilitation, especially in degraded soils (Tambunan et al., 2017).
In addition, a very recent work analyzed the effects of DA and
Arachis repens as cover crops on banana plantations (Reine Kosso Boka
et al., 2022). The authors showed that only Arachis repens (and not DA)
were able to enrich the biological soil fertility because it increased
arbuscular mycorrhizal fungal spores at a different time of analysis (6
and 12 months).
5PHARMACOLOGICAL PROPERTIES OF
DESMODIUM ADSCENDENS
The pharmacological properties of DA have been widely explored dur-
ing the past decades (Rastogi et al., 2011). In the following sections, we
summarize the scientific evidence of the therapeutic potential of DA
obtained from preclinical experiments and clinical trials (Table 2).
MANZIONE ET AL.681
TAB L E 1 Chemical compounds from leaves of D. adscendens
Source Compounds References
Alkaloids
Aqueous extract,
ethanol 70%
Dimethyltryptamine, dimethyoxyphenylethylamine,
salsoline, hordenine, tyramine, gramine
Baiocchi et al. (2013),
Addy and Schwartzman
(1995)
Flavonoids
Decoction,
ethanol 70%,
methanol 50%,
methanol 70%
6C,8C-Dihexosyl-kaempferol, 5-O-hexosyl-apigenin,
6-C,8-C-dihexosyl-apigenin, 6-C-pentosyl-8-C-hexosyl-kaempferol,
6-C-hexosyl-8-C-pentosyl-kaempferol, 5-O-hexosyl-kaempferol,
6-C-hexosyl-8-C-pentosyl-diosmetin,
6-C-pentosyl-8-C-hexosyl-kaempferol,
6-C-pentosyl-8-C-hexosyl-apigenin, 8-C-hexosyl-kaempferol,
6-C-pentosyl-8-C-hexosyl-kaempferol,
6-C-pentosyl-8-C-hexosyl-apigenin,
6-C-hexosyl-8-C-rhamnosyl-kaempferol,
6-C-hexosyl-8-C-pentosyl-apigenin,
5-O-pentosyl-1,6-rhamnosyl-kaempferol, saponarin
(6-C-hexosyl-7-O-hexosyl-apigenine),
7-O-pentosyl-1,6-rhamnosyl-kaempferol,
6-C-hexosyl-8-C-pentosyl-apigenin, vitexin(8-C-hexosyl-apigenin),
5-O-rhamnosyl-(1-6)-hexosyl-apigenin,
5-O-pentosyl-(1-6)-hexosyl-apigenin,
6-C-hexosyl-8-C-pentosyl-kaempferol, astragalin
(3-O-hexosyl-kaempferol), 6-C-hexosyl-8-C-rhamnosyl-apigenin,
5-O-pentosyl-(1,6)-hexosyl-diosmetin, 6-C-hexosyl-8-C-pentosyl-apigenin,
6-C-rhamnosyl-8-C-hexosyl-apigenin,
6-C-hexosyl-7-O-rhamnosyl-apigenin, 7-O-rhamnosil-quercetin,
6-C-rhamnosyl-8-C-hexosyl-apigenin, 7-O-hexosyl-kaempfero,
1,6-rhamnosyl-7-O-hexosyl-7-apigenin, 7-O-hexosyl-apigenin,
7-O-pentosyl-1,6-hexosyl-diosmetin, isovitexin 2″-O-xyloside, vitexin
2″-O-xyloside, vitexin, isovitexin, 2″-O-glucosyl-vitexin, vicenin-2,
schaftoside, isoschaftoside, 2″-O-xylosylvitexin, 2″-O-pentosyl-C-hexosyl
apigenin, epicatechin, rutin, quercetin, quercetin glucosyl, quercetin
dehydrate
Muanda et al. (2011),
Baiocchi et al. (2013),
Zielinska-Pisklak et al.
(2015)
Van dooren et al. (2018)
Phenolic acids
Methanol 50%,
methanol 70%
Caffeic acid, p-coumaric acid, gallic acid,
protocatechuic acid, chlorogenic acid, cinnamic acid
Muanda et al. (2011)
Saponins
Ethanol 70% Soyasaponin I, soyasaponin III,
dehydrosoyasaponin I, and soyasapogenol B and E
Baiocchi et al. (2013)
Terpenoids
Essential oil α-Terpinene, α-terpinolene, linalool, geraniol
α-caryophyllene, caryophyllene oxide, epoxide II humulene eudesma
Muanda et al. (2011)
Fatty acids
Essential oil Margaric acid, oleic acid, palmitic acid Muanda et al. (2011)
Others
Essential oil 2-Pentyl furan, 1-methyl silabenzène, azido-4 heptane, 2-(N-methyl
pyrrolidine) methenamine, 3-hexen-1-ol,2,2- dimethyl-hexanal, 3-octenol,
pelargonaldehyde, methyl benzoate, perillardehyde, mandelic acid,
b-ionone, ol-13 8-cedrene, 3-(2-pentyl) 1,2,4- cyclopentanetrione, oleic
acid, phytone, scytalone, hyperforin, palmitic acid, margaric acid,
α-isomethyl ionone, linoleic acid, 4,6,9- nonadecatriene, cetanole
Muanda et al. (2011)
682 MANZIONE ET AL.
TAB L E 2 Preclinical and clinical pharmacological properties of D. adscendens
Types of samples
administrated Results References
Aqueous or alcoholic extracts
of DA
Decrease in the anaphylactic contraction of ileal pieces from sensitized guinea
pigs
Addy and Awumey (1984)
Oral administration of the
extracts
Reduction in the sensitivity of trachea-bronchial smooth muscle to histamine
and decreased the amount of muscle stimulating substances released from
the lungs
Addy (1992)
DHS-I purified from crude
extracts of DA
Activation of maxi-K which regulates bronchospasms McManus et al. (1993)
n-butanol fraction of DA Increase in prostaglandin synthesis Addy and Schwartzman (1995)
Intraperitoneal administration
of the plant extract
Hypothermia, a reduction of acetic acid-induced writhes and climbing activities,
analgesic properties, and a delay in the onset of clonic PTZ convulsion
N’Gouemo et al. (1996),
Amoateng et al. (2017)
Leaf extracts Antioxidant and antiradical activities Muanda et al. (2011)
Hydroalcoholic extract of DA Cytoprotective effects in human kidney LLC-PK1 François et al. (2015)
D-pinitol isolated from aqueous
decoction of DA
Hepatoprotective properties Magielse et al. (2013)
Lisosan® Reduction Hypocholesterolemic and hepatoprotective effects Russo et al. (2019)
Hexane/methanol extract of DA Antimicrobial effects against Staphylococcus aureus SA1199 and Candida
albicans ATCC 90029 strains
Adeniyi et al. (2013)
Silver nanoparticles Antimicrobial effects against Escherichia coli Thirunavoukkarasu et al.
(2013)
DA decoction Vitexin and C-glycosides were stable during their passage in the
gastrointestinal tract, while the O-glycosidic bonds of O-glycosides of vitexin
were metabolized by the colon bacteria. The flavonoid fraction and D-pinitol
were both stable.
Van Dooren et al. (2018)
DA combined with
Lithotamnium calcareum
Patients with head and neck cancer were concomitantly treated with standard
chemotherapy.ECOG and GPS scores were found to be stable throughout
the study. Moreover, both pain and fatigue significantly improved at a later
stage of the therapy.
Imperatori et al. (2018)
5.1 Preclinical experiments
5.1.1 Anti-asthmatic properties
In 1984, Addy and Awumey performed the first preclinical study to
evaluate the effects of DA extracts on anaphylaxis in guinea pigs
(M. E. Addy & Awumey, 1984). For this purpose, animals were sensi-
tized with egg albumin (antigen) to provoke an allergic reaction and
bronchial smooth muscle contractions. Guinea pigs were then divided
into three groups. One group was treated with water (control), one
with aqueous, and one with alcoholic extract of DA (DAE). Extracts
were administered orally. Anaphylaxis was assessed by determining
the contractions of the ileal pieces. The study revealed that animals
receiving an aqueous or alcoholic extract of DA had less than 50%
bronchial contractions compared to control animals. Histamine con-
tent of lung tissues of guinea pigs treated with plant extracts was
reduced by more than 50% compared to animals treated with water.
The authors proposed that DAE probably interfered with the release
of inflammatory mediators. Nevertheless, they did not isolate the
active components responsible for the anti-inflammatory action and
the work did not compare the use of DA with standard pharmaco-
logical therapy (i.e., prednisolone, chlorpheniramine, ketotifen, etc.)
for anaphylaxis in experimental models. Subsequent studies identified
triterpenoid saponins, β-phenylethylamines, and tetrahydroisoquino-
lines in DA as the main effectors of the potential anti-asthmatic
activity of DA (M. E. Addy & Schwartzman, 1995). In vitro experiments
using microsomes from the human kidney, cortex showed that two
phenylethylamines found in DA, tyramine,and hordenine, activated the
NADPH-dependent cytochrome P450 monooxygenase and increased
the levels of prostaglandin E2 (PGE2). Salsoline, a tetrahydroisoquino-
line derivative found in DA, inhibited P450 monooxygenase and
decreased the levels of PGE2 (M. E. Addy, 1992). In 1993, McManus
et al. (1993) purified dehydrosoyasaponin I (DHS-I), a triterpene
glycoside, from crude extracts of DA. When applied to bovine tra-
cheal smooth muscle membranes, DHS-I could activate reversibly and,
with high-affinity, calcium-dependent potassium channels (maxi-K) by
partially inhibiting the binding of monoiodotyrosine charybdotoxin
(125I-ChTX) to receptor sites (Ki=120 nM, 62% maximum inhibition)
(McManus et al., 1993). Maxi-K channels regulate the muscle tone of
lung airways and the release of substances that causes bronchocon-
striction and inflammation. These results suggest that different classes
of bioactive molecules found in DA may haveanti-asthmatic properties.
However, in vivo studies are needed to compare the beneficial effects
of the phytochemicals found in DA with the effects of chemically
MANZIONE ET AL.683
related molecules found in other natural sources. For example, soya
saponins extracted from soya beans have promisinganti-inflammatory
activities in mice (Kang et al., 2005). Saponins content of soya beans
is also higher compared to the percentage of soyasaponins found in
DA (0.43–0.76% in soya beans compare to 0.003–0.03% in DA) (M.
E. Addy, 1992), and, therefore, it should be carefully evaluated which
plant source is more convenient to use for future therapeutic applica-
tion. Moreover,a comparison with a standard therapy would be helpful
to uncover the alleged benefits of DA or other medicinal plants.
5.1.2 Neurological effects
In 1996, the neuropharmacological profile of DAE in rodents was
examined (N’Gouemo et al., 1996). Intraperitoneal administration of
the plant extract at doses of 1000 mg/kg caused abdominal contrac-
tions, decreased spontaneous motor activity, and exploratory behavior.
Moreover, administration of DAE (300 mg/kg) caused a significant fall
in body temperature (p<0.05) compared to untreated animals. Injec-
tion of 109.89 mg/kg of DA inhibited acetic acid-induced writhes by
50% compared with injection of the vehicle. In addition, pretreatment
with 300 mg/kg DAE inhibited tonic pentylenetetrazole (PTZ) induced
convulsions and significantly (p<0.05) postponed the onset of clonic
PTZ convulsion (N’Gouemo et al., 1996). The authors suggested that
DA at 300 mg/kg could have depressant activity on the central ner-
vous system, together with anticonvulsant and analgesic effects in
mice. More recently, a similar study investigated the antipsychotic-
like properties of DAE in mice (Amoateng et al., 2017). Animals were
orally pretreated with 30, 100, 300, 1000, and 3000 mg/kg DAE or
vehicle. The effects on spontaneous motor activity and general anes-
thetic effects (Irwin’s test) were measured for 3 h after treatment.
Doses up to 300 mg/kg did not cause detectable neurological effects
in agreement with the previous observation (N’Gouemo et al., 1996).
However,mice pretreated for 15–30 min with 1000–3000 mg/kg of DA
were sedated. Locomotor behavior was also evaluated by comparing
mice treated with 1000 mg/kg DAE or with 1 mg/kg chlorpromazine,
a well-known antipsychotic agent, or water (negative control). The
frequency of rearing in mice treated with DAE was significantly
decreased (p≤0.001) by ∼50% compared to control animals (water).
Apomorphine-induced cage climbing was decreased after pretreat-
ment with 300–1000 mg/kg of DAE although the effects were less
potent compared to treatment with haloperidol (HAL). The total dura-
tion of HAL-induced catalepsy in mice was significantly increased
(p≤0.01) after pretreatment with 1000 mg/kg DA. Overall, these stud-
ies suggest that DAE used at 1000 mg/kg has potential sedative and
analgesic effects, that need to be further investigated in human stud-
ies. Moreover, the authors proposed that the antipsychotic effects
were probably due to the presence of flavonoids acting on choliner-
gic or serotonergic mechanisms. More recently, a survey from Goma
city in the Democratic Republic of Congo reported that people from
this region made use of different plant extracts including DA for the
treatment of different mental disorders (i.e., depression, anxiety, post-
traumatic stress disorder, schizophrenia, etc.) (Kyolo et al., 2022). Even
if the work investigated the ethnopharmacological use of DA, it has
not been possible to conclude the real benefit of DA in these diseases,
both of the anecdotic uses and lack of standardization. Clinical trials
are necessary to pursue the matter.
In other studies, it has been shown that salsolinol (a tetrahydroiso-
quinoline derivative), found in DA and other natural sources, showed
both neuroprotective and neurotoxic activities in mice (Kurnik-Lucka
et al., 2018). Interestingly, salsolinol is also produced endogenously
from dopamine, indeed it was first detected in the urine of Parkinsonian
patients on therapy with L-DOPA (L-dihydroxyphenylalanine) (Sandler
et al., 1973). This suggested a role in Parkinson’s pathogenesis as a neu-
rotoxin that can induce apoptosis of dopaminergic neurons due to its
structural similarity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP) (CNS Neurol Disord Drug Targets, 2020). However, salsolinol
can be found in numerous plants and protein-derived foods, that is,
bananas, cheese, cocoa, eggs, flour, etc. (Deng et al., 1997)andeven
if potentially implicated in the disease, up to now it is not possible to
determine a clear positive or negative impact of salsolinol on human
health. What emerges from different studies is that it colocalizes with
dopamine-rich regions not only in the brain but also in the enteric
nervous system and gut microbiota (CNS Neurol Disord Drug Targets,
2020). Different aspects of the pharmacological and biological profile
of salsolinol still need to be established, but it is tempting to specu-
late that this molecule can be probably responsible for the neurological
effects of DA or can act to enhance the effect of endogenous salsolinol
in animal models.
5.1.3 Antioxidant properties
Muanda and collaborators evaluated the antioxidant properties of DA
leaves by measuring the levels of intracellular radical oxygen species
(ROS) in mouse granulocytes exposed to hydrogen peroxide (H2O2)
and treated with DA extracts (Muanda et al., 2011). ROS levels were
evaluated by flow cytometry. The results showed that treatment with
25 mg/mL of DA reduced the level of intracellular of 83.2 ±6.21%
of ROS level generated by exogenous H2O2. Moreover, HPLC anal-
ysis of DAE showed a significant content of phenolic, flavonoids,
anthocyanins, and tannins with known antioxidant properties. In a sub-
sequent study, it was shown that treatment of pig kidney (LLC-PK1)
cells with 1 mg/mL of DAE significantly improved the viability of LLC-
PK1 cells exposed to glucose-induced oxidative stress (Francois et al.,
2015). The protective effect of DAE was not dose-dependent since
treatment with 30 mg/mL did not restore cell proliferation. These data
suggest that DA extract may have antioxidant activity at least in in
vitro experiments (Francois, Fares, Baiocchi & Maixent, 2015). Addi-
tional in vivo studies are needed to confirm the protective effects
of DA in comparison with well-known natural antioxidants such as
quercetin, resveratrol, and curcumin (Simioni et al., 2018). Of note that
ROS cell levels were decreased by DA leaf aqueous extract, suggest-
ing a scavenging activity capacity of the plant (Muanda et al., 2011).
A straight association between phenolic compounds and antioxidant
activity (R2=0.96) was found, with a concentration-response curve for
684 MANZIONE ET AL.
reduction of ROS generated by exogenous H2O2in blood cells derived
from mice. The author concluded that DA possessed pharmacologi-
cal activity to be potentially tested in clinical trials; however, no other
work followed this suggestion. Consequently,the supposed antioxidant
properties of DA are justified only in a preclinical setting and need to be
confirmed in human experiments.
5.1.4 Hepatoprotective properties of D-pinitol
isolated from DA
The work of Magielse and collaborators evaluated the protective
effect of D-pinitol (or 3-O-methyl-D-chiro-inositol) isolated from
aqueous decoction of DA against acute liver damage induced by
D-galactosamine and chronic ethanol-induced liver damage in rats
(Magielse et al., 2013). The authors compared the effects of several
dosages of D-pinitol with that of silymarin, a natural compound with
known hepatoprotective activity in vivo (Baradaran et al., 2019;Fre-
itag et al., 2015). Oral administration of 5 mg/kg D-pinitol significantly
reduced aspartate transaminase (AST) and alanine transaminase (ALT)
levels (biomarkers for liver damage) 48 h after galactosamine injection
at least in the acute liver damage model. Similar results were obtained
with 20 mg/kg of silymarin. However, DA decoction nor pure D-pinitol
at doses of 10–20 mg/kg had no hepatocurative effects on the chronic
hepatotoxicity model. Thus, it is conceivable that the potential hep-
atoprotective activity of DA is fundamental in an acute setting, while
in the chronic model the plant shows a limiting effect. In addition,
the authors used a limited number of animals in ethanol-induced liver
damage with a modest increase in serum AST and ALT. Such experi-
mental constraints could distort the real effect of DA in the chronic
model and will force the researchers to further deepen the supposed
hepatoprotective activity of DA in new experiments.
5.1.5 Hepatoprotective properties of DA
More recently, the beneficial effects of Lisosan® Reduction, a combi-
nation of medicinal plant extracts, were tested in mice high-fat diet
(HFD)-fed mice (Russo et al., 2019). The plant mixture, produced from a
powder of fermented DA, Triticum aestivum,Malus domestica,Picrorhiza
kurroa,andHordeum vulgare, has a polyphenol profile composed of
syringic acid, trans-sinapic acid, and neochlorogenic acid, followed by
vitexin, trans-p-coumaric acid, and trans ferulic acid. The study showed
that administration of Lisosan® Reduction (60 mg/kg) had hypoc-
holesterolemic and hepatoprotective effects in HFD mice by restoring
the levels of total cholesterol, serum triglycerides, and glucose with
no toxic effect (ALT and AST levels resulted unaffected by the for-
mulation). Nevertheless, the beneficial effects of Lisosan® Reduction
cannot be directly related to the presence of DA, which represented
20% of the total mixture. Among the four most abundant constituents
of Lisosan® Reduction, syringic acid (284.69 ±0.77 mg/kg), trans-
sinapic acid (117.39 ±1.07 mg/kg), neochlorogenic acid (115.88 ±
0.28 mg/kg), and vitexin (60.40 ±1.24 mg/kg), only the last has been
identified in DA so far (van Dooren et al., 2018; Zielinska-Pisklak
et al., 2015). Syringic acid and trans-sinapic are found in T. aestivum
(Wu et al., 2001), which represents 64% of Lisosan® Reduction while
neochlorogenic acid is one of the main polyphenolic compounds in
M. domestica (Crozier et al., 2006) (10% of Lisosan mixture). Conse-
quently, the real activity of DA in the product Lisosan® Reduction is
probably limited and restricted, even if the product showed hypoc-
holesterolemic and hepatoprotective in a mouse model. As mentioned
in the previous section, DA still needs to be deeply studied to uncover
its hepatoprotective properties.
5.1.6 Antimicrobial properties
In the study conducted by Adeniyi et al. different concentrations of
DA hexane/methanol extract showed a significant antimicrobial effect
on Staphylococcus aureus SA1199 and Candida albicans ATCC 90029
strains (Adeniyi et al., 2013). At the concentration of 0.25 mg/mL,
the percentage of S. aureus cells death was approximately 100%
within 120 min. Comparable results were obtained for C. albicans.It
has been shown that silver nanoparticles have antimicrobial effects
(Cho et al., 2005). Different research groups used the leaf aqueous
extract of Desmodium gangeticum (L) DC. (abbreviated DG) to synthe-
size silver nanoparticles (AgNPs) with sizes ranging from 18 to 39 nm
(Thirunavoukkarasu et al., 2013; Vasanth & Kurian, 2017). The antibac-
terial property of the DG-based AgNPs was tested against S. aureus
(ATCC strain) and Escherichia coli (ATCC strain). At a concentration
of 2500–5000 μg/mL DG-based AgNPs were highly toxic against E.
coli, thus suggesting the potential use of D. gangeticum in the produc-
tion of antimicrobials of a new generation. However, another study
showed that oral administration of 100 mg/kg, DG-based AgNPs in
rats-induced alterations in renal architecture. Moreover, cytotoxicity
was observed in LLC PK1 cells when treated for 24 h with 1 mg/mL
nanoparticles (Vasanth & Kurian, 2017). These outcomes using DG can
be used as a model for future experimentation of DA since the two
species belong to the same genus and partially share the antimicrobial
effect. Although nanoparticles are known for their easy permeability in
tissues and most relevant studies were performed on the DG plant, it
is important to optimize the antimicrobial in vitro and in vivo effects of
DA for a future and safer administration in higher organisms.
5.2 Clinical data
DA possesses numerous pharmacological properties, and it is popular
as herbal tea. Nevertheless, only a few studies investigated the phar-
macological properties and/or toxicities of DA in humans. In 2018, van
Dooren and collaborators used the in vitro gastrointestinal dialysis
model combined with HPLC to investigate the biotransformation of D-
pinitol, vitexin, and the flavonoid fraction of DA decoction (van Dooren
et al., 2018). The authors found that vitexin and C-glycosides were sta-
ble during their passage in the gastrointestinal dialysis model, while
the O-glycosidic bonds of O-glycosides of vitexin were metabolized by
MANZIONE ET AL.685
the colon bacteria. The flavonoid fraction was stable since no biotrans-
formation occurred in the colon phase. D-pinitol was also very stable
during passage through the gastric, small intestine, and colonic phases.
Nevertheless, the in vitro model used in this study did not give infor-
mation about the absorption or the enzymatic reactions occurring in
the intestine. Thus, it will be interesting to evaluate these processes in
the future, as the DA metabolism is understudied in humans.
In 2019, a single-arm study investigated the therapeutic poten-
tial of Desmovit®, a medical device containing 300 mg of DA leaves
and 50 mg of Lithotamnium calcareum (a red marine algae rich in cal-
cium and magnesium) in patients with head and neck cancer treated
with standard chemotherapy (paclitaxel 75 mg/m2plus carboplatin
or methotrexate 40 mg/m2) (Imperatori et al., 2018). Twelve patients
received an intravenous infusion of paclitaxel or methotrexate and
a medical device containing 300 mg of DA leaves and 50 mg of L.
calcareum. Patients were monitored for 12 weeks byassessing the Glas-
gow Prognostic Score (GPS), a prognostic score that evaluates the
plasma level of C-reactive protein and albumin levels, and by exam-
ining the Eastern Cooperative Oncology Group (ECOG) performance
status, (used to determine how patients tolerate the therapy) (Oken
et al., 1982). Pain and fatigue were also examined. Patients treated
with Desmovit® had stable GPS scores throughout the 10 weeks-study
with ECOG scores that slightly increased at week 10. Moreover, both
pain and fatigue significantly improved at a later stage of the therapy
(weeks 8–10). The study could not conclude that the potential ben-
eficial events are exclusively imputable to DA because concomitant
administration of L. calcareum and/or standard chemotherapy could
have played a role. Even if nonexhaustive and preliminary, this clinical
trial shed new light on the therapeutic potential of this plant. Undoubt-
edly, more comprehensive studies and clinical evidence are necessary
to expand the use of DA in other human diseases.
6TOXICITY
The first in vivo example of acute toxicity was observed after intraperi-
toneal administration of DA extract in mice (N’Gouemo et al., 1996).
Only 25% of mice receiving 300 mg/kg of plant extract showed abdom-
inal contractions, while a dose of 1000 mg/kg was associated with
more severe neurological symptoms, such as reduced spontaneous
motor activity and exploratory behavior. In 2015, François et al. (2015)
evaluated the safety and the protective effect of a hydro-alcoholic
extract of DA on the human liver (HepG2) and pig kidney (LLC-PK1)
cells (Francois et al., 2015). The authors performed cell viability assays
using different concentrations of plant extract (1, 10, or 100 mg/mL).
The results showed that treatment of LLC PK1 and HepG2 cells with
100 mg/mL of DA for 24 h reduced cell proliferation by ∼35% and
∼50%, respectively, compared with control (dimethyl sulfoxide). No
toxicity was observed at dosages of 1 and 10 mg/mL. In a topical work,
Quaye et al. investigated the effect of DA leaf extract on liver and kid-
ney function in rats (Quaye et al., 2017). The authors recorded the
animal mortality after oral administration of various doses of plant
extract or 5 mL of standard saline solution as control (acute toxicity
study). The mean doses that induced 50% lethality (LD50) were cal-
culated and used for subchronic toxicity studies. The results showed
that doses higher than 1122 mg/kg (LD50) caused severe signs such
as piloerection of both the fur and the whiskers, shiny eyes, agitation,
and diarrhea. On autopsy treated rats had wrinkled lungs, darker-
colored liver, and dark spots in kidneys. Biomarkers of liver damage
(ALT and AST enzymes) and direct bilirubin concentration were also
increased after administration of DA, while other biomarkers (serum
creatinine concentration, γ-glutamyltransferase, protein concentra-
tion, total bilirubin, and blood urea nitrogen) were not altered. Thus,
the authors suggested that low dosages of DA (1–100 mg/kg) could be
safely used in animal models, similar to another study in which treat-
ment with 300 mg/kg did not cause significant side effects (Amoateng
et al., 2017). Furthermore, even if D. gangeticum was used and not
DA, administration of DG-based silver nanoparticles in rats altered
renal architecture, even though behavioral or physiological changes
were absent (Vasanth & Kurian, 2017). Moreover, treatment with DG-
based nanoparticles also caused cytotoxicity (cell death augmentation)
and mitotoxicity (oxidative stress increase) in LLC PK1 cells as above
reported (Vasanth & Kurian, 2017). We can assume that the same
effects could be seen with DA, but certainly only in vitro and in vivo
data can answer such a hypothesis.
7FUTURE PERSPECTIVE AND CONCLUSIONS
In developing countries, plants have been always part of an ethnophar-
macological use, given the economic straits of people living in such
countries. Recently, it has been observed an increasing trend in con-
suming plant-derived compounds (supplements, foods, homemade
preparations), especially in Western countries. Leaving aside the rea-
sons why humans are paying more interest toward plants, it is undeni-
able that in the past decade the use of plant extracts or plant-derived
compounds has grown exponentially. On the one hand, this fact is
certainly positive because it turns attention towards a world away
from the spotlight; on the other hand, it favors the use of plants or
their derived compounds for which a scientific rational study is not
always available. For DA, different studies have been conducted pro-
viding evidence of its medical use, essentially derived and based on
ethnobotanical use in Africa and India. Rational evidence originates
from different preclinical in vitro and in vivo research on DA (Ma et al.,
2011; Rastogi et al., 2011) and one clinical trial (Imperatori et al., 2018).
These proofs, although of a certain value, cannot clearly and definitely
justify the use of DA in humans, lacking a large, randomized, placebo-
controlled study. Thus, a well-prepared clinical trial is urgently needed
to assess the effectiveness and safety of DA.
ACKNOWLEDGMENTS
We thank dr. Mauricio Mercadante for providing images of Figure 1
and dr. Susi Barollo for her help with the English language. This work
received no specific grant from any funding agency in the public,
commercial, or not-for-profit sectors.
686 MANZIONE ET AL.
CONFLICT OF INTERESTS
The authors declare that they have no conflict of interest.
ORCID
Javad Sharifi-Rad https://orcid.org/0000-0002-7301-8151
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How to cite this article: Manzione, M. G., Herrera-Bravo, J.,
Sharifi-Rad, J., Kregiel, D., Sevindik, M., Sevindik, E., Salamoglu,
Z., Zam, W., Vitalini, S., Hano, C., Kukula-Koch, W., Koch, W., &
Pezzani, R. (2022). Desmodium adscendens (Sw.) DC.: A
magnificent plant with biological and pharmacological
properties. Food Frontiers,3, 677–688.
https://doi.org/10.1002/fft2.170
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