ABSTRACT

Euphorbia hirta is a common medicinal plant in folk and traditional medicine systems. This plant has shown
promising effects against several human ailments and infectious diseases. Therefore, it is important to summarize the
medicinal activities and value of Euphorbia hirta. The main intent of this literature review was to summarize the
phytochemical content and pharmacological applications of Euphorbia hirta. The literature review about the
pharmacology and phytochemistry of Euphorbia hirta was collected from different global platforms, such as Scopus,
ERIC, PubMed, and Web of Science. E. hirta has a rich phytochemistry and exhibits remarkable activity against
respira- tory diseases, gastrointestinal disorders and venereal diseases. Different extracts of this plant have shown
significant preclinical anticancer propensity against an array of different cancer cell lines. It acts as a highly active
antiviral agent and has shown pronounced activity against coxsackievirus, human immunodeficiency virus, dengue
virus, poliovirus and simian immunodeficiency virus. A clinical study showed its inhibitory responses against flu
and fever in dengue patients. Most im- portantly, the plant possesses remarkable inhibitory action on ACE, which
aids SARS-CoV-2 entry into host cells. The multidimensional role of Euphorbiahirta as a potential antiviral agent
suggests its possible application to control COVID-19 along with modern and Western medicinal strategies. In
conclusion, the literature review regarding Euphorbia hirta showed its strong pharmacological applications, such as
antimicrobial, antimalarial, anti-asthmatic, antioxidant, antiviral and anticancer activities. Further in-depth research is
necessary to monitor its role in the management of viral diseases, especially COVID-19.

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 INTRODUCTION
Euphorbia hirta is frequently known as “Asthma plant” in English and “Dudhi” in Hindi. The
plant is widely distributed throughout the globe, and in Asia, it is mainly found in Yemen, Oman,
Palestine, Tai- wan, Syria, Lebanon, India, Bhutan, Pakistan, Nepal, Myanmar, Thailand, Sri Lanka,
Indonesia, Malaysia, Papua New Guinea and the Philippines (Patel, et. al., 2019). The plant belongs to
the genus Euphorbia family of Euphor-biaceae. The morphological features of Euphorbia hirta include a
slender stem with hair development and many branches arising from it from base to top. The plant is
annual purple or reddish in color and attains a height of approximately 40 cm. The leaves of the plant grow
oppositely and are elliptical-oblong to oblong- lanceolate in shape. The leaves measure up to 1 – 2.5 cm
in length with green color on the top side and pale color on the bottom side. The fruits are three- celled,
yellow, keeled capsules, hairy, 1 - 2 mm in diameter, containing four-sided, three brown, wrinkled,
angular, seeds (Hazra, et. al., 2019).
The plant Euphorbia hirta has long served humanity in the form of traditional and folk medicine.
In addition to Euphorbia hirta, other species of the genus Euphorbia also show medicinal importance
and are being used in traditional medicine. A milky juice comes out of all the species of Euphorbia upon
breaking, and this juice is considered to be more/less toxic and hence was used on arrows for hunting
purposes in old times (Gupta, et.al., 2018). Euphorbia hirta is a high-value medicinal plant possessing
significant antimalarial, antifungal, antifertility, antispasmodic, sedative, anti-asthmatic, anthelmintic and
antibacterial properties. Additionally, the plant has been found to have significant anticancer effects
against a variety of aggressive cancer cells .

This review aims to summarize the phytochemical compositions and pharmacological activities of
Euphorbia hirta and tries to bridge the possible role of Euphorbia hirta in the management of COVID-
19, a going on global pandemic. Respiratory tract exposure to the external environment leads to high
communicability of the disease. SARS-CoV-2 patients differ in clinical symptoms some show evident
symptoms, and some remain asymptotic (Hazra, et. al., 2019). Asymptomatic patients with SARS-CoV-2
viral loads are the most active transporters leading to the fast spread of the disease because these patients
are not aware of the disease until advanced stages. The initial clinical symptoms involve chills, fever,
fatigue, cough, diarrhea, shortness of breath and respiratory symptoms. The generation of potential
vaccines or capable drugs against SARS-CoV-2 infection is the global emergency right now.
Unfortunately, the development of vaccines or potential drugs may take a longer time. Therefore,
intermediate treatment methodologies are needed to address this global health issue. The government of
the Republic of China is currently emphasizing Traditional Chinese Medicine (TCM) in controlling SARS-
CoV-2 infection (Xu, and Zhang, 2020)
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 Several clinical trials have already been initiated to study the efficiency of TCM against SARS-
CoV-2 infection. In certain cases, patients along with Western medicine were sidewise supplied with TCM.
The results showed that TCM induced synergistic effects with Western medicine against SARS-CoV-2 (Ni,
Chen, Huang, Han, Xu, and Zhang, 2020). Treatments with medicinal plants and herbs are mostly
symptoms and sign based. Herbal medicines with potential efficacy against specified targets against viruses
could be evaluated for their activity against SARS-CoV-2, reliant on signs and symptoms (Ang, Lee, Choi,
Zhang, and Lee, 2020). The prime focus of this review was to summarize the phytochemical constituents
and pharmacological and medicinal importance of Euphorbia hirta along with assessing its possibility to
be used against COVID-19.

EUPHORBIA HIRTA

3
 Euphorbia Hirta
Euphorbia hirta Linn. (Figure 1) is a small annual, branched herb that can grow to 70 cm in

height, purple or red dish in color with copious amounts of latex, and covered with sprout hairs.

Leaves: The leaves are opposite, biculate and simple, the stipules are linear, the leaf blade is lanceolate,

oblong serrate, long elliptic, tapering, 3 – 4 cm long and 1 – 1.4 cm wide, and its margin is smoothly

serrated.

Flowers: The monoecious inflorescence, an axillary or terminal cluster of flowers, is known as a

cyathium, in which several cyathia are arranged in a cyme. The male and female flowers are in a pod and

both appellation. The flowers are unisexual, male flowers are sessile, prophylls are linear, fringed, perianth

absent and have a stamen, female flowers have a small peduncle, the perianth is fringed, the ovary is

covered with tiny hairs above, 3-celled, has 3 - Styles, small and the tip is double. The flowering period

is usually year round.

Fruit: The fruit is allomorphic, pistillate, elongated, 3-lobed, obtuse base covered with shoot hairs.

Seeds: Seeds are oblong, 4-sided prismatic, wrinkled and brownish pink in color, capsule 3-seeded,

green and covered with fleshy spines, seeds smooth, hard mottled crustal skin with a white caruncle at

the top enclosing oily endosperm (Chen, Er, Mohamed, and Chen. 2018).

Roots: The root is a distinct and developed primary root (taproot system).

Classification: E. hirta Linn. belongs to the Euphorbiaceae family, known as the Spurge family. It is the

largest family, consisting of almost 300 genera and 5000 species. Euphorbia is the largest genus of the

Euphorbiaceae family and includes approximately 1600 species.

MEDICINAL PROPERTY OF EUPHORBIA HIRTA

Different parts of Euphorbia hirta have shown numerous pharmacological and biological

properties. The high bio- logical value of the plant is primarily attributed to its high diversity in

phytochemical content. Some of the biological activities are represent Ho, Chan, Chung, and Leung.

(2020).
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Ethnopharmacology

Euphorbia hirta has a very high medicinal value. Ethnophar- macologically, Euphorbia hirta is

used to cure respiratory and bronchial disorders (hay fever, bronchitis and asthma), conjunctivitis and

gastrointestinal diseases such as intestinal parasitosis, dysentery and diarrhea. Furthermore, Euphorbia

hirta shows significant tonic and hypotensive properties (Hazra, Dutta, Ghosal, Paria, and Rao 2 0 1 9 ) . Stem

sap of Euphorbia hirta is used to cure eyelid styes caused by bacterial infection, and leaves are used

against boils and swellings by making their poultice. The plant as a whole is used by humans against

different diseases, such as fresh herb decoction in the treatment of thrush by gargling, dry decoction to

cure skin disorders and decoction of roots, which is implemented in snake bites and for milk production in

nursing mothers. Antispas modic and antiamoebic activities have been shown for polyphenolic extracts of

the plant (Gyuris, Szlávik, Minárovits, Vasas, Molnár, and Hohmann, 2019). Furthermore, the Euphorbia hirta-

isolated compound quercitrin has been reported to have remarkable antidiarrheal potential. It shows

reflexive effects on cardiovascular systems in humans, such as the respiratory system (Huang, Chen, and

Yang, 2020). The Euphorbia hirta plant alcoholic extracts show tranquilizing effects on the genitor-

urinary tract and report hypoglycemic effects in rats. The isolated compounds and solvent extracts of

Euphorbia hirta demon- strated substantial anticancer activities. Euphorbia hirta ex- tracts exhibit

inhibitory effects on prostaglandin re- lease, including D2, E2 and I2. It has also been re- ported to

produce protective effects against contami- nation caused by aflatoxin in mustard, rice, maize and wheat

crops (Khursheed, and Jain 2021). Methanolic extracts of Euphorbia hirta leaves have been shown to have

strong antibacterial and antifungal properties. Itchy soles are treated by pounding, warming and rubbing

the leaves of Euphorbia hirta with coconut oil and turmeric. Plant latex is used to cure eye sores by

applying it to the surma on the lower eye- lids. A number of the ethnopharmacological uses of Euphorbia

hirta are listed in Table 1.

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 Figure 4: Biological activity profile of Euphorbia hirta.

Antibacterial activity

Ethanolic extraction from Euphorbia hirta leaves has been tested for its antibacterial activities

against Salmonella typhi, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and

Escherichia coli. The extract showed strong inhibition of all these bacteria except Salmonella typhi. The

minimum inhibitory values were calculated to be 74.61, 57.64, 22.55 and 54.09 mg/ml for Bacillus subtilis,

Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli, respectively (Kumari, and Pandey.

2017). Unlike solvent extractions from the stem, bud and leaves of Euphorbia hirta, their antimicrobial

effects against Staphylococcus aureus were evaluated using the disc-diffusion method. The methanolic

extract from leaves and bud exhibited very strong activity against S. aureus , with a zone of inhibition

score of 20 mm and a zone of inhibition area score of 471.00 mm2. Chloroform and aqueous fractions of

Euphorbia hirta L. leaves have been reported to possess noncytotoxic but antibacterial effects against

Klebsiella pneumonia (Liu, Murakami, Ji, Abreu, and Zhang, 2017).

Anti-inflammatory activity

The medicinal herb Euphorbia hirta has been reported to have remarkable anti-inflammatory

effects. In a study, the aqueous and ethanolic extracts of Euphorbia hirta were evaluated for their anti-

inflammatory activity against carrageenan-induced inflammation in rats. It has been shown that both

extracts produced substantial anti-inflammatory effects against the reference drug diclofenac sodium (50
6
mg/kg) (Martinez, Mariano, Teresa, Lazcano, and Bye. 2019).. In a similar study, the lyophilized aqueous

extract from Euphorbia hirta has been reported to suppress inflammation in carrageenan- induced rats

starting from the concentrations of 100 mg/kg of body weight. Furthermore, n-hexane ex- tracts from

Euphorbia hirta have been shown to inhibit inflammation in mouse models of phorbol acetate-induced ear

inflammation. The anti-inflammatory effects were found to be concentration-dependent. In another study,

fractionated Euphorbia hirta aqueous extract showed in vitro anti-inflammatory activity on rabbit synovial

fibroblasts (Mir, Khurshid, and Aftab, 2022).

Table 1: Pharmacological activities of E. hirta

No Activity Action

1 Anti-allergic activity The ethanolic fraction of E. hirta induces inhibitive effects on the discharge of IL-6
and TNF-α in anti-DNP-HAS activated rat peritoneal mast cells.

2 Antibacterial activity Different solvent extracts from E. hirta were evaluated for antibacterial ef-
fects Bacillus subtilis, Pseudomonas. aeruginosa, Staphylococcus aureus, and Es-
cherichia coli. The results demonstrated outstanding antibacterial property of E.
hirta against these pathogen bacteria.

3 Anti-diabetic activity The solvent extracts of stem, flower and leaf of E. hirta showed lowering effects on
overall blood glucose levels on administration to streptozotocin induced diabetic
mice.

4 Anti-diarrheal activity The leaves of E. hirta are rich in flavonoids content especially the quercitin
molecule has been shown to exhibit anti-diarrheal effects through enhancement
in the absorption of colonic fluid in presence of secretagogue compounds.

7
5 Antioxidant activity Antioxidant activity of E. hirta was shown by performing FRAP and DPPH as-
say and outcomes demonstrated remarkable antioxidant potential of methanolic
extract of E. hirta by acting against oxidative damage to protein.

6 Antitumor activity Research has shown that the methanolic extract of E. hirta induce antiprolifer-
ative effects in Hep-2 cells isolated from human epithelioma of larynx. Hence,
predicting antitumor potency of E. hirta.

7 Anxiolytic and seda- The antagonists of the GABAA receptor-benzodiazepine receptor-Cl channel
tive activity complex with E. hirta were used together, and anxiety in the EPM showed marked
anti-anxiety activity in chronic immobilization stress

8 Diuretic activity The E. hirta ethanolic extract on administration to rats augmented the total urine
excretion thus improving diuresis.

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Antioxidant activity

Euphorbia hirta possesses strong antioxidant activities in both animal models and in vitro. It

has been shown to have strong free radical scavenging potency in various experimental models

using hydroxyl radical scavenging, ABTS, and DPPH assays. The free-radical scavenging ability of

the methanolic extract of Euphorbia hirta was investigated Sytar, Brestic, Hajihashemi, Skalicky, Kubeš,

and Lamilla- Tamayo. (2012). The results reported that the methanolic fraction of Euphorbia hirta leaf

extract produced a tremendous DPPH inhibition of 71.96±0.78%. The increasing order of DPPH

scavenging activity of Euphorbia hirta was stems (44.42±0.94%) < roots (48.59±0.97%) < flow- ers

(52.45±0.66%) < leaves. The IC50 values calculated for stems, roots, flowers and leaves were 1.358,

0.989, 0.972 and 0.803 mg/mL, respectively Ni, Chen, Huang, Han, Xu, and Zhang. (2020). Another

study carried out by S. Asha and coworkers reported significant antioxidant activity for Euphorbia

hirta. They showed antioxidant activities for three types of extractions from Euphorbia hirta

through superoxide, DPPH and hydroxyl radical scavenging assays. Out of the three extracts

(ethanolic, methanolic and aqueous), the ethanolic extract exhibited the highest antioxidant

propensity with a significant IC50 value compared to the methanolic and aqueous extracts.

Furthermore, a significant relationship was obtained between the phenolic content of the extracts

and antioxidant activity, and the ethanolic extract showed a high phenolic content Ogunlesi, Okiei,

Ofor, and Osibote. (2019). Euphorbia hirta showed maximum free radical scavenging and antioxidant

activities at approxi- mately 0.25 mg/ml.

Anticancer activity

Several traditionally used medicinal plants are thought to have preventive effects against

different human malignancies, including cancer Srivastava, and Soni,. (2019). These plants are rich

in chemical contents that show modulatory effects on different physiological functions and target

the proliferation of cancer cells. Euphorbia hirta has been reported to produce significant

anticancer effects in vitro against acute myeloid leukemia HL-60 cells. Furthermore, extracts from
Euphorbia hirta have revealed anticancer effects against squamous cell carcinoma, Hep-2 and

malignant melanoma. Shao-Ming Chi et al., 2012 isolated (1’R,5’R)-5- (5’carboxylmethyl-2’-

oxocyclopentyl)-3Z-pentenyl acetate, a cyclopentanone derivative from Euphorbia hirta. The

ethanolic extract was examined for cytotoxicity against the K562 and A549 cell lines.

The outcome of the study revealed weak cytotoxicity against A549 cells (15.02 ± 11.60%) and

remained almost inactive against K562 cells. Sandeep et al. in 2011 evaluated the antitumor

properties of Euphorbia. hirta. Aerial parts of Euphorbia hirta were extracted using different solvents,

including chloroform, ethanol and petroleum ether, and showed positive results for the presence of

alkaloids, tannins, saponins, and flavonoids. The ethanol and chloroform extracts were reported to

maximize the mean survival and inhibit the growth of solid tumors in administered mice. This

antitumor activity was attributed to the manifestation of flavonoids.

Antimalarial and anti-asthmatic activities

Euphorbia hirta has been reported to contain a pool of active phytochemicals that raise the

medicinal value of the plant Sandeep, and Chandrakant. (2021). Euphorbia hirta has been termed an

“Asthma plant”. It shows depressant effects on the respiratory system and reflexive effects on

brochial tubes. Additionally, methanolic extraction from aerial parts of Euphorbia hirta by bioassay-

guided fractionation has been evaluated for antiparasitic activity against P. falciparum. The key

chromatographic fraction has been reported to show over 90% inhibition at 5 µg/ml against P.

falciparum Patel, Naikwade, Magdum. (2019) .

 Table 1. List of Plants Used in Treatment and Management Asthma in FCT and its Environs
S/N Family Scientific Local Habit UVI Ethnomedicinal use/ Some chemical References
Name Name Pharmacological uses constituent/isolated
compound(s)
1 Amaryllidaceae Crinum Isumeri (Y), Herb 0.02 Used in treatment of Lycorine, β-sitosterol, [68]
glaucum Albasar infectious diseases ambelline
A.Chev Kwa’adi (H) including cough and
sexually transmitted
infections /Antimicrobial
2 Amaryllidaceae Crinum jagus Ogede odo Herb 0.03 Used in treatment of Gigantellinine, [69,70]
(J. Thomps.) (Y), Albasa tuberculosis /Anti- gigancrine
Dandy (H) tuberculosis
3 Amaryllidaceae Allium Alubosa Herb 0.03 Used in treatment of Ascalonisoide A and B [71,72,73]
ascalonicum elewe (Y), gastroduodenal
L. Ramuza disorder/Antimicrobial
(H)
4 Amaryllidaceae Allium cepa L. Alubosa Herb 0.02 Used to relieve stomach Cysteine, Methionine [74,75]
funfun (Y), upset, congestion /Anti-
Albasa (H) inflammatory
5 Amaryllidaceae Allium sativum Alubosa Herb 0.06 Used to cure systemic fungal alliin, allicin, ajoenes, [76,77,78]
L. ayuu (Y), infections/Antimicrobial vinyldithiins
Tafarnuwa
(H)

6 Anacardiaceae Mangifera Mangoro Tree 0.02 Used in treatment of Galic acid, Mangiferin, [79,80]
indica L. (H, Y) dysentery, ophthalmia, Kampferol, Quercetin,
constipation /Antidiabetic, Ascorbic acid
Antidiarrheal
7 Anarcardiaceae Sclerocarya Daniya (H) Tree 0.02 Used in treatment of Auronol,Davidigenin, [81-83]
birrea diarrhea /Antidiarrheal, naringenin, hesperetin
(A.Rich.)Hochst Antihypertensive, anti-
. inflammatory
8 Annonaceae Annona Abo (Y), Shrub 0.02 Used in treatment of N-cerotoyltryptamine, [84,85]
senegalensis Gwadan daaji epilepsy/ lacceroic acid,
Pers. (H) Anticonvulsant, stigmasterol glycoside
anti-inflammatory
9 Asphodelaceae Aloe vera (L.) Eti erin (Y), Shrub 0.02 Used in treatment of Veracylglucan A, [86,87]
Burm.F. Kathala (H) constipation, skin aloenin aglycone, 7-
diseases, worm hydroxy-5-
 infection/ Antimicrobial (hydroxymethyl)-2-
methylchromone
10 Asteraceae Acanthospermu Danguro Herb 0.03 Used in treatment of Flavanone, [88,89]
m hispidum DC. gogoro (Y), jaundice, malaria, Stigmasterol, Quercetin
Kashi yawo convulsion/ Antiviral,
(H) Antimicrobial
11 Bignoniaceae Newbouldia Akoko (Y), Tree 0.10 Used in treatment of Apigenin, Ursolic acid, [90-92]
laevis (P. Aduruku (H) diabetes mellitus/ Stigmasterol, Canthic
Beauv.) Seem. Antihyperglycemic acid
ex Bureau
12 Burseraceae Boswellia Ewe epa (Y), Tree 0.02 Used in treatment of Incensole, incensole [93,94]
dalzielii Hutch. Hano / convulsion/ acetate
Harrabi (H) Anticonvulsant

13 Caricaceae Carica papaya Ibepe (Y), Tree 0.03 Used in treatment of Ferulic acid, Choline, [95,96]
L. Gwanda (H) urogenital disorders/ Quercetin, p – coumaric
Antimicrobial, acid, papain
Antifungal
14 Chrysobalanaceae Parinari spp. Abere (Y), Tree 0.02 Used in treatment of oral Betulinic acid, [97,98]
Aubl. Gwandangi da diseases/ Antimicrobial Oleanolic acid
(H)

15 Combretaceae Anogeissus Ayin (Y), Tree 0.10 Used as an antifungal/ Chebulic acid, gallic [99,100]
leocarpus DC. Marke (H) Antifungal acid, elaagic acid,
castalagin

16 Combretaceae Terminalia Idi (Y), Tree 0.03 Used in treatment of Arjunolic acid, α- [101,102]
avicennioides Baushe (H) tuberculosis/ Anti- amyrin, olean-12-ene
Guill. & Perr. tuberculosis

17 Combretaceae Combretum Ogan bule Shrub 0.02 Used in management of β-sitosterol, picatechin [103,104]
micranthum (Y), Geeza hypertension/ Anti -
G.Don (H) hypertension
 FUTURE PROSPECTS

It is essential and needed of this era to continue the expansion of drug development and
therapeutics based on plants and their chemical composition. Drugs and therapeutics based on
plants are economical (cost effective) and are believed to be less toxic than synthetics. Cancer is a
global health problem, making it difficult for scientists and researchers to overcome this ailment.
Plants have assisted humanity against several malignancies in the past, and they are believed to do
so currently and in the future as well. There are several drugs based on plants that have been ap-
proved for cancer chemotherapy, such as Taxol and paclitaxel. Euphorbia hirta has a substantial
potential to inhibit different cancers in humans due to its rich phytochemistry and active
constituents. This plant bears a unique class of compounds called euphorbins, and they are
complex in structure and active in nature. Therefore, it is believed to possess remarkable phar
macological potential, which needs to be explored.

Figure 5: Target site for possible inhibition of SARS-CoV-2 entrance to host human cells. Adapted from
Brown et al. 2021
 It is highly recommended to push on progress in the field of potential antiviral therapeutics
designed on natural products and their synthetic derivatives. Moreover, to look for therapeutics
against coron- aviruses, natural products have been the leading sources that have assisted human
civilization in over- coming health hazards since the ages. The thera- peutics designed on natural
products have significant benefits over the synthetic ones, such as their cost ef- fectiveness and
miniscule or lack of side effects. De- spite noteworthy developments in the field of vaccine
development in this modern era, we lag behind in terms of developing breakthrough vaccines for
sev- eral viruses, including SARS-CoV-2. Therefore, it seems to be a very difficult job to develop a
poten- tial treatment methodology for the management of such infectious viral diseases. However,
plants such as Euphorbia hirta and their bioactive phytochemicals have tremendous potential to serve
humanity in over- coming these infectious diseases. Based on docking studies and the antiviral
properties of phytochemicals, E. hirta could also prove advantageous against coro- naviruses. The
rapid genomic mutations in SARS- CoV-2, HIV and HSV are the key drawbacks of an- tiviral
therapeutics in targeting specific proteins and genes. The plant Euphorbia hirta has huge poten- tial
against COVID-19, as it showed against different viruses, such as malaria, HSV and dengue. The
plant has a strong antiviral property and has significant po- tential to target key sites, enzymes and
replication of SARS-COV-2. Therefore, we recommend clinical in vestigations of Euphorbia hirta
against this lethal dis- ease.

Conclusions

Euphorbia hirta is a valuable medicinal plant used globally in different traditional systems of

medicines. It has been reported to have various bioactivities against a wide array of human disorders.

Most importantly, the plant as a whole bears a huge variety of chemical entities that enhance its

therapeutic potential. The plant as a whole has been shown to have remarkable antiviral potential

against HIV, DANV, HSV, etc. and enhancing immune responses against pathogens. It has great

potency for free radical scavenging and ACE inhibition. Therefore, these features of Euphorbia hirta

may play an advantageous role throughout the management of highly infectious and deadly viral

diseases such as COVID-19.

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