A comprehensive literature review on Pharmacological effects of Euphorbia milii

(Crown of Thorns)

A COMPREHENSIVE INVESTIGATION OF THE MULTIPLE USES OF

EUPHORIA MILLI (CROWN OF THORNS)

, ANBARASU MAHENDIRAN*, NAVEENA GOPAL, NIVEDHA DURAISAMY AND

RAJESWARI RAJAMANI

Department of Pharmacology, Vellalar College Of Pharmacy, Erode- 638012, Tamilnadu

Running title: Pharmacology of Euphorbia milii

*Address for correspondence:

E-mail: raji2185@gmail.com
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Abstract
The review was conducted to go into great detail regarding the pharmacological properties of
Euphorbia milii. various literature collections about this plant and collections of its medicinal
effects were used. Euphorbia milii contains the phytoconstituents alkaloids, flavonoids, terpenoids,
cardiac glycosides, steroids (phytosterols), protease, anthocyanin, proteins, tannins, and phenolic
compounds. Various pharmacological actions of Euphorbia milii were assessed in this review.
According to literature collections, Euphorbia milii possessed anti-cancer, anti-oxidant,
hepatoprotective, muscle-relaxing, antinociceptive, sedative, molluscicidal, anti-trypanosomal,
proteolytic, lectinic, antileishmanial, ovicidal, catalytic, inhibitory, nematicidal, insecticidal,
amoebicidal, anti-gout, wound healing, larvicidal, antiviral, and antimicrobial properties. This
review came to the conclusion that subsequent research on the Euphorbia milii plant should utilize
the pharmaceutical literature.

Keywords: Euphorbia milii, Euphorbiaceae, crown of thorns, folk medicines

Introduction
The intricacy of diseases and the negative side effects of using synthetic medications have led to a

significant increase in the use of medicinal plants and herbal products worldwide. The

pharmacological effects of natural compounds, such as cytotoxicity, antioxidants, antidiabetic,

antibacterial, and anti-inflammatory properties, have been evaluated and confirmed. In a similar

vein, it has been found that the likelihood of major health problems like cancer, cardiovascular

diseases, and type 2 diabetes is inversely connected to the larger use of natural goods worldwide. In

light of this, the scientific community has given the discovery of bioactive products derived from

natural sources, such as medicinal plants, a great deal of recognition (Saleem et al., 2019)[1]. One of

the common genera of medicinal plants found in the tropical areas of Pakistan, India, and China is

the genus Euphorbia. Different varieties of Euphorbia have historically been used as folk medicines

for treating a variety of illnesses due to their significant therapeutic potential. The seasonal bloom

Euphorbia milii (E. milii), commonly known as "the crown of thorns" or "the Christ plant," is one

of the most well-known medicinal plants in this genus due to its folkloric use as a treatment for liver

disease, cancer, and skin diseases (Chohan et al., 2020)[2]. These pharmacological properties of the

plant are attributed to the presence of secondary metabolites such as tannins, flavonoids, saponins,

phenols, etc. The plant is native to Madagascar but primarily found in the South Asian region [3].
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Synonyms:

Euphorbia splendens var. bojer (Hook.) Costantin and Gallaud

Euphorbia splendens subsp. bojer (Hook.) Denis

Euphorbia bojeri Klotzsch

Euphorbia bojeri Hook

Euphorbia breonii var. mucronulata Ram. Goyena

Euphorbia milii var. milii

Scientific classification:

Domain: Eukaryota

Kingdom: Plantae

Phylum: Spermatophyta

Subphylum: Angiospermae

Class: Dicotyledonae

Order: Euphorbiales

Family: Euphorbiaceae

Genus: Euphorbia

Species: Euphorbia milii

Vernacular names:

International (English): Siamese Lucky Plant, Christ's plant, Christ plant, Crown-of-thorns, Christ’s

thorn.

India: Ainkona kalli (Tamil), Kanta Mukut (Bangla)

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Chinese: Wàn nián cì, Tiě hǎi táng, Fān zǐ cì,

Italian: Corona di spine, Spina di Cristo

Spanish: Corona de Cristo, Gracia de Dios, Tu-y-yo, Espinas de Cristo

Swedish: Kristi tornekrona

Indonesia: Mahkota duri

Traditional Uses:

According to studies, over 5% of the species of Euphorbia are used medicinally. Folk medicine

regularly employs Euphorbia milii Des Moul to cure trichiasis, hepatitis, cancer, and warts (in

southern Brazil). The seeds are used as a laxative for kids, the leaves are used to treat ringworm and

snake bites, and the whole plant paste is used to treat broken animal bones. To treat asthma, oral

doses of 500 mg three times per day and 250–500 mg twice per day of Euphorbia milii Des Moul

flower powder and whole plant ash are used, respectively. Numerous other medical conditions can

be treated using Euphorbia species, including sensory impairments, blood disorders, genitourinary

syndromes, microbial infections, scorpion stings, and pregnancies and puerperium. In addition to its

disinfecting, antiseptic, and emollient properties, the formulations are used as skin remedies to treat

warts, itching, hair loss, dermatitis, acne, sunburn, boils, rashes, and irritation. Undiluted latex from

Euphorbia milii Des Moul was shown to irritate mammal eyes and skin. While some ingenol

diterpene esters are effective skin irritants, they don't have the same tumor-promoting capabilities as

other closely related ingenol and phorbol derivatives. It was discovered that milli amines made from

Euphorbia milii Des Moul latex were extremely molluscicidal.

Chemical constituents of Euphorbia milii:

There have been numerous studies on the chemical makeup of Euphorbia species. The outcomes

showed that various chemical substances were present. The phytochemicals anthocyanin, -cyanin,

alkaloids, phenolic compounds, carbohydrates, amino acids, cardiac glycosides, steroids,

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anthraquinone, tannins, phlorotannins, reducing sugar, saponins, coumarin, triterpenes, and

flavonoids (a name which terpenes and flavonoids) are the most frequently found in Euphorbia milii

Des Moul. The ethanolic extract of Euphorbia milii Des Moul's thorn part and stem part both

included alkaloids, as well as amino acids, proteins, and cardiac glycosides, respectively, according

to qualitative phytochemical studies[4]. The goal of this literature review is to examine the

pharmacological therapeutic properties of Euphorbia milii.

PHARMACOLOGICAL STUDIES OF EUPHORBIA MILII

The pharmacological activities of Euphorbia milii are assessed using various in vivo and in vitro

screening techniques. The pharmacological properties of this plant include hepatoprotective, anti-

cancer, antioxidant, antinociceptive, muscle-relaxing, sedative, and antimicrobial properties.

Antimicrobial activity:

Pradyutha and Rao Uma Maheswara Rao V et al.(2015) assessed the Antibacterial activity of leaves

of the Euphorbia milii plant. Hexane, chloroform, ethyl acetate, acetone, ethyl alcohol, methanol,

and water were used to make leaf extracts of E. milii. The resultant extracts of the plants were

screened for antibacterial activity against Micrococcus luteus MTCC 106, Arthrobacter

protophormiae MTCC 2682, Rhodococcus rhodochrous MTCC 265, Alcaligens faecalis MTCC

126, Proteus mirabilis MTCC 425, Enterobacter aerogenes MTCC 10208, Proteus vulgaris MTCC

426, Bacillus megaterium MTCC 428, Enterococcus faecalis MTCC 439, Streptococcus mutans

MTCC 497, Salmonella enterica MTCC 3858, Staphylococcus aureus MTCC 737, Pseudomonas

aeruginosa MTCC 1688, and Bacillus subtilis MTCC 441. E. milii extracts in ethyl alcohol and

ethyl acetate showed excellent antibacterial activity against both Gram-positive and Gram-negative

microorganisms. The MIC and MBC of the extracts that showed antibacterial activity were then

determined using various concentrations. The MBC values varied from 50 to 100 mg/ml, and the

MIC values ranged from 25 to 75 mg/ml. The antibacterial ability of the E. milii leaf material was

demonstrated by the study's findings (Pradyutha and Rao, 2015)[5].

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Uma Maheswara V Rao evaluated the antimicrobial Antimicrobial potential of various solvents

extracts of the E. milii stem using. Hexane, chloroform, ethyl acetate, acetone, methanol, ethyl

alcohol, and water were used to extract the stem of the E. milii plantstudied. The agar-well diffusion

method was used to test the antimicrobial activity of bacteria and fungi. By using the broth dilution

method, the MIC, MBC, and MFC were assessed. In comparison to the positive control

(Streptomycin) and other solvent extracts, methanol extract was shown to have greater potential and

exhibit excellent antibacterial activity. MBC values ranged from 25 mg/ml to 100 mg/ml, and MIC

values were found to be between 12.5 mg/ml and 75 mg/ml. The antifungal activity of E. milii stem

extracts in methanol and aqueous form was higher than that of the positive control fluconazole

against all of the investigated fungi, with MIC values ranging from 6.25 to 25 mg/ml and MFC

values from 12.5 to 50 mg/ml[6].

NyeinMyint w et al. (199) tested Extracts of 41 plants including Euphorbia milii for antibacterial

activity by using 18 species of bacteria. Escherichia coli (5 strains), Shigella spp. (4 strains), Vibrios

spp. (3 strains), and one strain each of Klebsiella aerogenes, Plesiomonas shigelloides, Proteus

morganii, Pseudomonas pyocyanea, Salmonella typhi, and Staphylococcus aureus are among the

microorganisms that were tested. One of the plants that has been discovered to have antibacterial

action is Euphorbia milii[7].

Rathee R et al. investigated the antimicrobial activity of five species of traditionally used medicinal

plants namely Adhatoda vasica, Artemisia annua, Cordia oblique, Croton bonplandianum, and

Euphorbia milii against different strains of bacteria and fungi which are known to cause various

types of infectious diseases. Methods: Dry leaves of these plants were used to make organic

extracts, and tests on their antimicrobial sensitivity against different bacterial and fungal strains

using the disc diffusion assay method and the Resazurin-based Microtitre Dilution Assay method

were conducted on these extracts. Adhatoda vasica, Artemisia annua, Cordia oblique, Croton

bonplandianum, and Euphorbia milii were all studied plants in this study, and all of them

6
demonstrated antimicrobial activity against at least one strain of bacteria and fungus. This could

support its alleged applications in the management of numerous infectious illnesses [8].

B Pokhrel et al. carried out the green synthesis of stable silver nanoparticles using Euphorbia milii

extract and studied its antimicrobial activity against Escherichia coli. With the use of a natural

reducing agent derived from an extract of the Euphorbia milii plant, simple heating at 900 C was

used to successfully complete a single-step green synthesis of stable silver nanoparticles from silver

nitrate solution. Transmission electron microscopy and UV-visible spectroscopy were used to

characterize the nanoparticles. The virtually spherical nanoparticles were discovered to have

diameters between 6 and 50 nm, with an average particle size of close to 23 nm. The zone inhibition

test was used to examine the antibacterial activity of silver nanoparticles against the pathogenic

strain of E. coli, and it revealed a considerable inhibition of the bacterial strain [9].

Abur Rauf investigated the antimicrobial activity of Euphorbia milii. Its chloroform and methanol

fractions showed good antibacterial effectiveness against Klebsiella pneumonia and Staph

epidermis in well diffusion assay tests for susceptibility. Significant antibacterial activity was also

shown by the ethyl acetate fraction of the roots against the majority of the pathogens tested [10].

Kingsley and Abraham analyzed the antimicrobial compounds from Euphorbia milii. Calculating

the minimal inhibitory concentration against the pathogens Pseudomonas aeruginosa, Escherichia

coli, Salmonella typhimurium, Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella

pneumoniae, and Shigella dysenteriae allowed researchers to assess the antibacterial impact. The

plant extract's active metabolites had a strong antibacterial action. Penicillin-binding proteins were

docked against the isolated active metabolites using the in silico analysis program iGemdock.

Except for Shigella dysenteriae, Hexamethlyl-Cyclotrisiloxane/Tolmetin appeared as the most

effective active metabolite in the docking score against all pathogens. The ideal solution was N-

hexadecanoic acid[11].

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Kamel H Shaker et al. examined the antibacterial properties of Euphorbia milii extract and its sub-

fractions against Gram-negative, and Gram-positive bacteria, unicellular yeast, and two filamentous

fungi, and the lowest inhibitory doses were established. The most notable antibacterial activity was

shown by the ethyl acetate fraction (EAf) against the five pathogenic microorganisms that were

examined[12].

Shahbaz Aman et al. created copper nanoparticles that are biocompatible and non-toxic by using an

extract of Euphorbia milii des moul and tested these nanoparticles' bactericidal efficacy against

MDR strains of Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter

baumannii. The biogenic G-CuNPs were characterized using UV-Vis spectroscopy, dynamic light

scattering, X-ray diffraction, Fourier transforms infrared spectroscopy, transmission electron

microscopy, and scanning electron microscopy methods. It was discovered that G-CuNPs had a

charge density of 21.52 mV, an average diameter of 40 nm, and a spherical shape. After three hours

of incubation at a dosage of 2 mg/ml, the G-CuNPs completely eliminated the MDR strains. The G-

CuNPs effectively damaged the DNA and ruptured the cell membrane by producing more reactive

oxygen species, according to mechanistic analyses[13].

Ogah C et al. evaluated the antimicrobial activity of the leaf extract of Euphorbia milii.var

splendens in vitro, against selected microorganisms. The E. milii leaves were gathered, cleaned,

allowed to air dry, and then milled into a coarse powder. The ethanol and aqueous extracts of the

powder were produced by cold maceration in ethanol and sterile distilled water, respectively.

Similarly to this, sterile distilled water was used to create an aqueous extract from the plant's fresh

leaves. Using the agar well diffusion method, tests for antibacterial activity were conducted.

Reference antibacterial and antifungal medications were Levofloxacin and Bifonazole, respectively.

While the aqueous dry leaf extract was exclusively effective against Bacillus subtilis, the ethanol

dry leaf extract was effective against both Staphylococcus aureus and Bacillus subtilis. No bacterial

test organism was susceptible to aqueous fresh leaf extract. The study's fungal samples, Aspergillus

niger, Aspergillus flavus, Aspergillus fumigatus, Trichophyton rubrum, and Mycobacterium

8
globose, did not exhibit any growth inhibition in response to any of the three extracts. For S. aureus

and B. subtilis, the ethanol dry leaf extract's minimum inhibitory concentration (MIC) was 50 and

75 mg/mL, respectively[14].

Walaa A Negm et al. evaluated the antibacterial potential of electrospray PVA/PLGA nanoparticles

loaded with chlorogenic acid isolated from Euphorbia milii for the management of Pseudomonas

aeruginosa lung infection. They discovered chlorogenic acid (CGA) for the first time and clarified

the phytochemical profile of Euphorbia milii flowers. CGA nanoparticles were prepared in a

polyvinyl alcohol (PVA)/PLGA polymeric matrix using the electrospraying process. Particle size,

polydispersity index (PDI), zeta potential, loading efficiency (LE), scanning electron microscopy,

and an in vitro release study were all fully characterized. The best formula (F2) was chosen for

future experiments. It has the following parameters: particle size (454.36 36.74 nm), surface charge

(-4.56 0.84 mV), percent LE (80.23 5.74), initial burst (29.46 4.79), and percent cumulative release

(97.42 4.72). PVA/PLGA NPs loaded with CGA (F2) showed in vivo antibacterial efficacy against

Pseudomonas aeruginosa in the mouse lung infection model. The incorporation of CGA into

electrospray PVA or PLGA NPs was found to be a potential method for creating antibacterial

agents[15].

Winatra I M Y et al. determined the effect of giwang fern cactus leaf extract (Euphorbia milii) on

the number of fibroblasts in burnt white rats infected with Pseudomonas aeruginosa. An

experimental study with a control group utilizing three groups of rats employs a randomized post-

test research design. The results of the data were statistically analyzed using a parametric test using

one-way ANOVA. On Windows, SPSS version 20.0 was used to analyze the data. According to this

study, the P1 group (25%) and control (23.31.86) groups had lower average numbers of fibroblasts

than the 50% giwang fern cactus leaf (Euphorbia milli) extract (38.38.77). It is known that there is a

significant comparison between the groups (p 0.05) based on the analytical test. After the

administration of the extract from the giwang fern cactus leaf (Euphorbia milii), it was determined

that there was a substantial variation in the number of fibroblast cells among the groups [16].
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Molluscicidal activity:

De Souza et al. evaluated the molluscicidal activity of Crown of Christ (Euphorbia splendens var.

HislopII) latex on snails acting as intermediate hosts of Schistosoma mansoni and Schistosoma

haematobium. It was also assessed how the latex affected the egg masses and embryos of B.

glabrata. They measured a 90% fatal dosage (LD90) for plant-derived molluscicides using the

World Health Organisation's standardized technique. The LD90 ranged from 0.13 ppm for B.

glabrata exposed to lyophilized latex to 4.0 ppm for B. pfeifferi tested with natural latex. This

substance is among the most effective and targeted plant molluscicides yet found[17].

Suvajeejarun T et al. observed the molluscicidal activities of some Euphorbia milii hybrids against

the snail Indoplanorbis exustus. For its molluscicidal properties, latex from 12 different E. milii

hybrids was tested. Mortality rates of Indoplanorbis exustus exposed for 24 and 48 hours at varied

latex concentrations between 6 and 25 ppm were recorded. Eight latex hybrids worked well. The six

most potent hybrids killed all snails within 24 hours of exposure: E. milii Dang-udom, E. milii

Arunroong, E. milii Raweechotchuong, E. milii Srisompote, E. milii Sri-umporn, and E. milii

Tongnopakun. 50% of the snails were killed by the latex of E. milii Dowpraket and E. milii

Promsatid under the same circumstances. These outcomes suggest that these six hybrids have the

potential as organic molluscicidal substances[18].

EC Oliveira-Filho et al. examined the effects of biotic (snail size and food availability) and abiotic

(temperature, water hardness, and organic material content) parameters on the molluscicidal action

of Euphorbia milii latex. Snail lethality was assessed after 24 and 48 hours of exposure to

lyophilized latex solutions in bioassays using 10 B. glabrata snails per concentration. In the test,

neither the amount of water hardness nor the availability of food had an impact on latex-induced

snail death. Small differences in snail lethality caused by E. milii and snail size were observed.

Younger (3–8 mm) and newly hatched (shell diameter 1mm) snails were slightly more prone to

harm than older (10–25 mm) mollusks. The molluscicidal effect of E. milii latex, on the other hand,

10
was altered by environmental factors such as temperature (i.e., the LC50 and LC90 values were cut

in half for every 10°C rise in temperature) and concentration of organic materials in the water (i.e.,

the higher the concentration of organic matter, the higher the LC50 value). Water temperature,

organic material concentration, and to a lesser extent snail size can all affect how effective E. milii

latex is as a molluscicide[19].

Lima MG evaluated the metabolic changes in Biomphalaria glabrata infected with Schistosoma

mansoni exposed to latex of Euphorbia milii solution. This study aimed to screen the effects of latex

exposure from 24 hours until 35 days after exposure to the latex solution in order to check how long

the solution exhibits adverse effects on the carbohydrate metabolism and on the nitrogen excretion

products of molluscs. This was done to determine how long after the first application of the latex of

Euphorbia milii it remains active on the metabolic pathways of the mollusc's host. The effect was

strongest in the groups exposed up to 14 days after solution preparation, and it included a reduction

in the levels of glycogen in the tissues examined as well as changes in nitrogen excretion patterns

and the concentration of total proteins in the hemolymph. However, there were still statistically

significant differences even if the glycogen levels and nitrogen excretion products in both cases

were only gradually restored to levels similar to those in the control groups after 21 days. The

formulation of protocols for the control of schistosomiasis is aided by these results, which also

optimize the use of this substance as a molluscicide of natural origin[20].

Coelho et al. evaluated the in vitro molluscicidal activity of Euphorbia milii var splendens latex in

the control of Biomphalaria tenagophila. Adult mollusks of the species B. tenagophila were divided

into groups of ten for the molluscicide test, and they were immersed in latex for 24 hours at

concentrations of 2.5 ppm, 1.25 ppm, 0.625 ppm, and 0.3125 ppm. At the various quantities tested,

E. milii var. splendens latex was found to have significant molluscicidal action. This illustrates the

potential of employing latex from E. milii var. splendens to manage populations of B. tenagophila

species.

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Toxicological effect:

Coelho et al. evaluated the latex toxicity of Euphorbia milii var. splendens. The toxicity of latex at a

concentration of 0.3125 ppm was assessed using the Artemia salina test to gauge mortality and the

Allium cepa test to gauge growth inhibition and root weight. In the toxicity test with A. cepa and

against A. salina nauplii, it was also able to detect mild toxicity. The A. cepa test showed no change

in the parameters assessed in comparison to the control group, indicating environmental safety [21].

Antitrypanosomal activity:

Amin E et al. carried out the anti-trypanosomal activity of the crude extract of 15 Euphorbia species

including Euphorbia milii against Trypanosoma brucei brucei. Results: After 48 and 72 hours of

incubation, the anti-trypanosomal activity of the 15 species of Euphorbia showed that E.

officinarum L. and E. milii Des Moul. had the maximum activity against Trypanosoma brucei

brucei[22].

Proteolytic activity:

Mahajan R et al. evaluated twenty-five Euphorbian garden plants including Euphorbia milii for

their proteolytic activities using casein as a substrate. One of the good enzyme sources discovered

in this investigation is Euphorbia milii. Cysteine and serine proteases are produced by this plant. In

addition to cheese production specifically, these proteases may be employed for a variety of

industrial purposes in general[23].

MV Jagannadham et al. evaluated the proteolytic activity of the medicinal plant Euphorbia milii.

The latex of the Euphorbia milii plant was used to purify a serine protease known as "Milin" to

homogeneity. The enzyme had a molecular mass of 51 kDa, an ideal pH of 8.0, and a temperature

range of 60 °C (SDS-PAGE). With casein and azo albumin as substrates, milin maintains full

proteolytic activity over a broad pH (5.5–12) and temperature range (up to 65 °C). Serine protease

inhibitors like PMSF, APMSF, and DFP, but not other protease inhibitors like E-64 and PCMB,

12
decrease the activity of Milin. Milin was not inhibited by the proteinaceous inhibitor soybean

trypsin inhibitor (SBTI), which is found naturally in plants, like the other serine proteases from the

genus Euphorbia, even at very high doses. It was discovered that the enzyme's specific extinction

coefficient, molar extinction coefficient (am), and isoelectric point were 29, 152,500 M1 cm1, pH

7.2, and, respectively. The activity of the enzyme depends on a detectable carbohydrate moiety (7-

8%) in the glycoprotein that makes up the enzyme. Chemical calculations indicate that there are 23,

14, and 14 tryptophan, tyrosine, and cysteine residues in the sequence of Milin, respectively. Twelve

of the 14 cysteine residues were 6-disulfide linkages, while the other two were free cysteines. The

first 12 amino acid residues of the N-terminal sequence, which was determined, do not match any

sequence of other known plant serine proteases. The enzyme's great stability is further revealed by

perturbation experiments by temperature, pH, and chaotropes, as evidenced by CD, fluorescence,

and proteolytic activity. It has been noted that the latex of the medicinal plant Euphorbia milii

exhibits proteolytic action[24].

Lectinic activity:

Ifejirika-Ugboaja EC et al. assessed sixteen (16) species of some tropical Euphorbiaceae plants for

the presence of Lectins. The leaves of Euphorbia milii were the source of the lectins. Direct

haemagglutination was performed by E. milii on pooled, washed human ABO cells in saline. Using

the Biuret protein assay method, the protein content of the crude extracts of the sixteen (16) species

was also determined. The results showed that there is no correlation or link between the amount of

protein content and the agglutination patterns of the extracts. The goal of this study was to identify

the presence of lectinic properties in certain tropical Euphorbiaceae extracts, including E. milii[25]

Antileishmanial activity:

Mohammad B carried out the Antileishmanial effects of traditional herbal extracts against cutaneous

leishmaniosis in vivo. The southwest Iranian province of Ilam sits near the border with Iraq, which

has been at war for more than eight years straight. In this region, leishmaniasis has spread to

13
become an endemic illness that affects both locals and soldiers. Out of 552 referral-positive patients

to diagnostic centers, 150 cases of leishmaniasis were chosen for this trial; group I included 110

patients receiving glucantime, and group II included 40 patients receiving a treatment regimen that

included Euphorbia milii, Aloe vera juice, animal fat, and turmeric. Health centers in urban and

rural areas assisted in the study's completion. Results showed that patients treated with a

combination of plant extractions had significantly better clinical outcomes and fewer parasites than

those treated with glucantime. In less than 100 days following the onset of the disease, the majority

of patients recovered from the lesion; nevertheless, 7.5% of these patients' wounds went untreated

during the same duration of treatment. Results for patients who received glucantime showed that

32.7% of wounds healed between 63 and 76 days and 61.8% within 90 and 120 days; only 5.5% of

these patients' wounds did not heal during this time. Utilizing the current plant combination resulted

in a more effective therapy that caused the tissue to soften, turn pink, and heal lesions [26] .

Antioxidant activity:

Hammad Saleem et al. investigated and compared the biological activities and chemical

composition of dichloromethane (DCM) and methanol (MeOH) solvent extracts of Euphorbia

milii Des Moul aerial and root parts. Six distinct techniques (FRAP, CUPRAC,

Phosphomolybdenum, DPPH, ABTS, and ferrous chelation) were used to test antioxidant potential.

The largest concentrations of phenolic and flavonoid compounds were found in methanolic extracts

of the aerial and root sections. These compounds tend to have considerable DPPH, ABTS (radical

scavenging), FRAP, and CUPRAC (reducing power) potentials. It turned out that the root extracts

were a more reliable source of bioactive antioxidant compounds. According to the findings, E. milii

represents a possible lead source for natural antioxidant chemicals[1].

Tahir Ali Chohan et al. investigated the antioxidant potential of Euphorbia milii. To study

antioxidant capability, the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) was used. The

DPPH radical was scavenged by the various fractions of the Em-MeOH extract in the following

14
order: Em-C > Em-EA > Em-D > Em-B > Em-H > Em-W fractions. The findings showed that

among all six fractions, the Em-C fraction's IC50 value was closest to quercetin's (IC50: 1.69 0.14

g/ml), at 6.41 0.99 g/ml. While the remaining fractions showed no discernible antioxidant activity,

the Em-D and Em-EA fractions only showed modest antioxidant activity (IC50: 9.12 and 7.48 1.2

g/ml, respectively) in comparison to the standard. The aerial section of E. milii has good to

moderate antioxidant activity overall, and the scavenging activity of the various components rises in

a concentration-dependent[2].

Uma Maheswara V Rao assessed the antioxidant potential of various solvent of stem of E. milii.

Hexane, acetone, methanol, ethyl alcohol, chloroform, ethyl acetate, and water were used to extract

the stem of the E. milii plant. By using the DPPH (2,2-dyphenyl-1-picrylhydrazyl) assay,

antioxidant activity was examined. The highest levels of antioxidant activity were seen in ethanol,

methanol, and aqueous extracts[6].

Abdur Rauf investigated the antioxidant activity of Euphorbia milii. When several E. milii fractions

were tested for their antioxidant capability using the DPPH radical scavenging assay at various

doses, the chloroform fraction demonstrated strong scavenging activity. The existence of OH,

saturated CH stretching, C=C, C=O, NOsub>2/sub>, C-N, Ar-O, C-O, and R-O stretching were all

detected using IR spectroscopy of the different extracts/fractions[10].

Ravneet Kaur et al. investigated the antioxidant activity of the methanolic flower extract

of Euphorbia milii using various phytopharmacological and advanced computational techniques. It

was discovered that the DPPH assay had a higher scavenging activity (19.65 0.545 g/ml) than the

H2O2 assay (14.66 0.185 g/ml), proving that E. milii floral extracts have a large amount of

antioxidant potential. It is concluded that the antioxidant effects of the E. milii floral extracts may

perhaps be due to the phytoconstituents present in these extracts[19].

Dheer P et al. studied the antioxidant potential of Euphorbia milii, Euphorbia hirta, and Euphorbia

pulcherrima belonging to the Euphorbia genus. Estimates for the phenolic, flavonoid, and tannin

15
content were made using conventional techniques once the whole antioxidant profile was

completed. E. milii has a total antioxidant activity of 74.594 0.137 g/ml. When the reducing power

was examined using FRAP, E. milii (157.1610.195 g/ml) showed maximum efficiency[27].

Ronnie L Besagas et al. identified the free radical scavenging activity of leaf extracts of Euphorbia

milii Des Moul. The plant samples' capacity to scavenge free radicals was assessed using the DPPH

test. The methanolic leaf extracts of E. milii had the highest DPPH radical scavenging activity

(74.37%). This plant seemed to be an excellent source of antioxidants and a potentially useful

source of treatments for a variety of chronic and degenerative disorders brought on by oxidative

stress[28].

Ashfaq et al. examined the antioxidant prospects of Euphorbia milii. The organic extracts were

made by extracting the dried plant in its entirety with n-hexane, dichloromethane, and methanol.

The DPPH radical scavenging assay was used to quantify the antioxidant activity. The methanol

extract demonstrated significant (P = 0.04) antioxidant potential, showing 78.8% inhibition with an

IC50 value of 35.71 g/mL. The study discovered that Euphorbia milii possesses significant

antioxidant capabilities[29].

Haleshappa R et al. evaluated the antioxidant properties of Euphorbia milii extracts. E. milii's thorn

and stem portions were extracted with a chosen solvent using ethanol in a continuous, hot Soxhlet

process. To determine the functional group of the crude extract, researchers evaluated the total

antioxidant capacity, DPPH free radical scavenging activity, and infrared (IR) spectroscopy. Ethanol

extracts of E. milii's thorn and stem showed IC50 values of 187.91 and 138.44, respectively. The

existence of OH, saturated CH stretching, C=C, C=O, NO2, C-N, Ar-O, C-O, and R-O stretching is

confirmed by the IR spectroscopy of the E. milii extracts. The biological activity and antioxidant

qualities of ethanol extracts from the plant's thorn and stem portions suggested that E. milii might be

a suitable medication ingredient in traditional remedies[30].

Ovicidal and Toxicological effects:

16
De Ftima Kieko Ozaki T et al. assessed the ovicidal efficacy and toxicity of hydroalcoholic extracts

obtained by percolation of three plants: Tagetes minuta L., Euphorbia milii var splendens (Bojer ex

Hook.) Ursch & Leandri and Synadenium carinatum Boiss, against Ancylostoma spp. All of the

analyzed plant species' hydroalcoholic extracts were found to elicit mild ovicide activity at every

concentration tested. Additionally, the toxicity of these extracts was examined in tests on Artemia

salina L. and Allium cepa L. at various concentrations. When compared to the other species

examined, it was found that E. milii was the only species of plant that showed considerably low

toxicity at a concentration of 12.5 L/mL[31].

Antinociceptive activity:

Qaisar M et al. tested the crude methanolic extract of aerial parts of Euphorbia milii for its

antinociceptive property. Utilizing a chemically produced pain paradigm (acetic acid), the

antinociceptive impact was assessed. The crude methanolic extract considerably reduced the

writhing caused by acetic acid. At the tested doses of 50, 100, and 150 mg/kg, respectively, the

mean number of writhing decreases of the crude methanolic extract was 12.34, 32.54, and 71.44%.

The tested sample was closest to the diclofenac sodium percent impact, which was 82.34%. The

effect of the crude methanolic extract was dosage and time-dependent[32].

Antinociceptive, Muscle relaxant and Sedative activity:

Nazar Ul Islam et al. evaluated the antinociceptive, sedative and muscle relaxant activity of gold

nanoparticles generated by the methanolic extract of Euphorbia milii. Without employing any

external reducing agents, a 1 mM warm trihydrated tetrachloroaurate solution was stirred with E.

milii methanolic extract to create Au-EM. By using atomic force microscopy, scanning electron

microscopy, ultraviolet-visible spectroscopy, and infrared spectrophotometry to characterize the

gold nanoparticles, their stability was assessed against changes in pH and various concentrations of

sodium chloride (NaCl). Testing of Au-EM's metal detection capabilities included cobalt, copper,

lead, mercury, and nickel. In comparison to the crude E. milii methanolic extract, the

17
antinociceptive, sedative and muscle relaxant efficacy of Au-EM was tested in BALB/c mice at

doses of 10 and 20 mg/kg. In various NaCl and pH solutions, Au-EM demonstrated remarkably

high stability. At doses of 10 and 20 mg/kg, Au-EM demonstrated a substantial (P 0.01)

antinociceptive effect, sedative effect in an open-field test (P 0.05) and muscle relaxant effect in the

rotarod test at 10 mg/kg (P 0.05) and 20 mg/kg (P 0.01) after 30, 60, and 90 min in comparison to

the unrefined E. milii methanolic extract. According to these findings, the gold nanoparticles

significantly increased the efficacy of the methanolic extract of E. milii and demonstrated

considerable analgesic, strong sedative and muscle relaxing properties[33].

Chengling Li et al. evaluated the Euphorbia milii extract-mediated zinc oxide nanoparticles and

their muscle relaxant, antinociceptive and sedative activity for pain management in pediatric

children. Zinc oxide nanoparticles (ZnO NPs-EM) made with Euphorbia milii aqueous extract have

been created, identified, and tested for their ability to relax muscles, antinociceptive efficacy and

sedative actions. In an open-field experiment, at dosages of 10 and 20 mg/kg, ZnO NPs clearly had

a significant muscle-relaxing, antinociceptive and sedative effect(P 0.05) compared to the aqueous

extract of E. milii. These results suggested that the ZnO NPs had significant muscle relaxing,

analgesic and sedative properties and improved the efficacy of the E. milii aqueous sample[34].

Hepatoprotective activity:

Kasireddy Paul Babu and P Shanmugasundaram evaluated the effect of Euphorbia milii extract on

hepatoprotective activity against paracetamol-induced hepatic damage in Wistar rats. Wister rats of

either sex (M or F) and age of two months were used in the experimental study. Prior to oral

administration, the paracetamol (PCM) was diluted with saline (vehicle). Food was withheld 12

hours prior to PCM injection to increase acute liver damage in mice from groups II, III, IV, V, and

VI. 24 hours after PCM injection, animals were slaughtered. Retro-orbital plexus punctures were

used to obtain blood samples, which were then allowed to coagulate for 30 minutes at 37°C.

Different biochemical parameters were examined in the serum after centrifugation at 2500 rpm for

18
15 minutes at 37°C. The protective benefits of AEEM against PCM-induced liver damage were

confirmed in the pre-treatment of rats with AEEM (alcoholic extract Euphorbia milii) and

silymarin, which inhibited the paracetamol-induced rise in serum levels of transaminases and total

serum bilirubin. The hepatoprotective activity of conventional silymarin (100mg/kg) and AEEM

(500mg/kg) was compared. The test extract and silymarin had no impact on the elevation of serum

alkaline phosphatase levels, though. The rate of metabolism and other substrates for hepatic

microsomal enzymes are decreased in the presence of extensive liver damage caused by

paracetamol itself. PCM-induced toxicity requires the induction of cytochrome P450 or the

reduction of hepatic glutathione. Through PCM, the AEEM decreased all of the biochemical

parameters' high stages. The protective effect of AEEM against experimentally produced liver

injury in rats has been demonstrated by the considerable inhibition of PCM-induced hepatic

necrosis. The tests used to diagnose liver illnesses that are the most sensitive include ALT, AST,

ALP, and SB. According to the results of this experiment, AEEM has hepatoprotective properties [35].

Catalytic activity:

Mahmoud Nasrollahzadeh et al. biosynthesized the palladium/sodium borosilicate nanocomposite

using Euphorbia milii extract and evaluated its catalytic activity in the reduction of chromium (VI),

nitro compounds, and organic dyes. Several instrumental analyses, including X-ray diffraction

(XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM),

energy dispersive X-ray spectroscopy (EDS), EDS elemental dot maps, and transmission electron

microscopy (TEM), were used to confirm the immobilization of Pd NPs on the surface of the

sodium borosilicate glass. The green nanocatalyst was successfully used to reduce chromium (VI),

nitro compounds such as 2,4-dinitrophenylhydrazine and 4-nitrophenol, and certain organic dyes

like Congo red (CR), methyl orange (MO), and methylene blue (MB). The heterogeneous catalyst

that was produced by biosynthesis was easily recovered and reused for at least five consecutive

reactions without losing any of its effectiveness. Result: By reducing PdII ions with an aqueous

19
extract of the leaves of Euphorbia milii, an effective, quick, biocompatible, and convenient

approach is established for producing Pd/sodium borosilicate nanocomposite [36].

Anticancer activity:

Tahir Ali Chohan et al. investigated the anticancer potential of Euphorbia milii (E. milii) using an

exquisite combination of phytopharmacological and advanced computational techniques. When

compared to the standard drug 5-fluorouracil (5-FU), the chloroform fraction (Em-C) of the E. milii

methanol extract demonstrated much greater cytotoxicity (IC50: 11.2 0.8 g/ml) against the HepG2

hepatocarcinoma cell line. However, when compared to 5-FU (IC50: 6.87 0.5 g/ml), Em-C showed

no statistically significant change in cytotoxicity (22.1 0.8 g/ml) in a human cervical cancer cell line

(HeLa). Furthermore, HepG2 cells were suppressed as a result of a sharp decline in CDK2 and

E2F1 protein expression, according to Western blot and qRT-PCR analyses. Cyclobarbital (CBT)

and benzodioxole derivative (BAN) were specifically detected in Em-C's GC-MS study as being

two of its main ingredients. Additionally, the molecules BAN, CBT, and MBT were molecularly

docked into the binding sites of many molecular targets, including CDK2, thymidylate synthase

(TS), caspase 3, BCL2, and topoisomerase II. Astonishing binding affinity has been shown for

CDK2 and thymidylate synthase by the compounds BAN and CBT, respectively. The results of the

docking study have been further supported by molecular dynamic simulation studies, which indicate

that CDK2 and TS may be suitable targets for BAN and CBT, respectively. It was determined that

these phytoconstituents of E. milii (BAN and CBT) are probably what is causing the anti-invasive

activity against HepG2 cells[2].

Ashfaq et al. examined the cytotoxic prospects of Euphorbia milii. The organic extracts were made

by extracting the dried plant in its entirety with n-hexane, dichloromethane, and methanol. The

brine shrimp lethality test was used to determine the total amount of cytotoxic substances. In the

brine shrimp lethality test, methanol extract demonstrated substantial cytotoxicity at the highest

20
dose level, with an LD50 of 471.05 g/mL. The study discovered that Euphorbia milii has significant

cytotoxic characteristics[29].

FJR Paumgartten et al. verified the Absence of tumor-promoting activity of Euphorbia milii latex

on the mouse back skin. Male and female DBA/2 mice received a single dosage of the starting drug

DMBA (400 nmol) administered to their rear skin. Ten days following the experiment's start, testing

for tumor-promoting activities began. Two times each week for 20 weeks, mouse back skin was

treated with acetone, lyophilized latex (20, 60, or 200 g per mouse), or tetradecanoyl phorbol

acetate (TPA) (5 nmol, positive control). Papillomas were first noticed in TPA-treated mice during

the 11th week, and by the 17th week, all animals had skin tumors. Both mice exposed to latex and

mice treated with the solvent alone did not develop tumors. Because of this, the mouse back skin

experiment did not reveal any tumor-promoting effects of E. milii crude latex[37].

Inhibitory activity:

Hammad Saleem et al. studied and compared the biological functions and chemical makeup of

solvent extracts of the aerial and root sections of Euphorbia milii Des Moul in dichloromethane

(DCM) and methanol (MeOH). The studied extracts were assessed for their ability to inhibit the

enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE), glucosidase, amylase, and

tyrosinase. The highest concentrations of phenolic and flavonoid compounds were found in

methanolic extracts from the aerial and root sections. These compounds' considerable DPPH, ABTS

(radical scavenging), FRAP, CUPRAC (reducing power), and glucosidase inhibition potentials seem

to coincide with these concentrations. The phosphomolybdenum assay, cholinesterases, and

tyrosinase inhibition were all carried out using the two DCM extracts with the lowest bioactive

levels. According to the findings, E. milii is a potentially valuable lead source for naturally

occurring bioactive enzyme inhibitory chemicals[1].

Zha-Jun Zhan et al. evaluated the diverse diterpenoids with α-glucosidase and β-glucuronidase

inhibitory activities from Euphorbia milii. From the complete plants of Euphorbia milii Des Moul.,

21
four unidentified regular rosane-type diterpenoids, euphominoids M–P, and three unidentified

rearranged rosane-type diterpenoids, euphomilones C–E, were isolated, together with nine other

recognized chemicals. Their structures were clarified by meticulously interpreting the mass

spectroscopy and NMR data. By performing single-crystal X-ray diffraction tests and comparing

theoretical and experimental ECD spectra, the absolute configurations were established. While

euphomilones C–E had 7/5/6 or 5/7/6 fused ring systems, which were uncommon among rosane-

type diterpenoids, euphomminoid M had a highly oxygenated ring A and a unique four-membered

oxygen ring. Euphominoid C revealed a considerable inhibitory effect against both -glucosidase and

-glucuronidase, while 19-norrosa-1,3,5(10),15-tetraene-2,3-diol and antiquarian showed more

strong -glucosidase inhibitory activity than the positive control acarbose in the in vitro bioassays.

The discovery of Rosane-type diterpenoids as glucuronidase inhibitors was a first[38].

Nematicidal activity:

Jose Humberto de Queiroz et al. tested the protease enzyme's nematicidal activity in latex from

Euphorbia milii. With a reduction of 65.59% after 24 hours and a reduction of 96.46% after 48

hours, the treatment of Panagrellus redivivus larvae with partly purified proteases demonstrates the

remarkable efficacy of E. milii latex proteases in nematode control[39].

Insecticidal activity:

Okonkwo CO and Ohaeri OC evaluated the insecticidal activity of essential oils from the leaves of

Euphorbia milii through disruption in the ionic composition. From Periplaneta americana and

Tettigonia virridisima that had been subjected for 24 hours to 600mg of essential oil extracted using

a soxhlet device and hexane from the leaves of Euphorbia milii, fat bodies, and hemolymph were

removed using conventional techniques. The biochemical analysis of fat bodies and hemolymph

was done to determine the potential modes of the oil's insecticidal effect. In the fat body, changes in

the concentrations of the ions Mn2+, Mg2+, Na2+, K2+, and Ca2+ were examined. In the

hemolymph, potential changes in the activity of the metabolic enzymes acetylcholinesterase,

22
catalase, and glutathione-S-transferase were also assessed. Magnesium ion levels in the fat bodies

of P. americana exposed to E. milii oil significantly decreased (p 0.05) when compared to the

negative control, while sodium ion levels significantly increased when compared to the positive

control. The ionic composition of T. virridissima, as well as the biochemical parameters examined

in the hemolymph of both insects, did not alter significantly (p 0.05) as a result of the oil when

compared to the control groups. Overall, the results of this investigation offer compelling evidence

that the insecticidal activity of essential oils from E. milii may result from physiological disturbance

of ionic composition; as a result, they may be classified as members of the organo-chlorine class of

insecticides[40].

Antiviral activity:

Walaa A Negm et al. evaluated the Antiviral potential of electrospray PVA/PLGA nanoparticles

loaded with chlorogenic acid isolated from Euphorbia milii for the management of coronavirus.

They discovered chlorogenic acid (CGA) for the first time and clarified the phytochemical profile

of Euphorbia milii flowers. CGA nanoparticles were prepared in a polyvinyl alcohol (PVA)/PLGA

polymeric matrix using the electrospraying process. Particle size, polydispersity index (PDI), zeta

potential, loading efficiency (LE), scanning electron microscopy, and an in vitro release study were

all fully characterized in vitro. The best formula (F2) was chosen for future experiments. It has the

following parameters: particle size (454.36 36.74 nm), surface charge (-4.56 0.84 mV), percent LE

(80.23 5.74), initial burst (29.46 4.79), and percent cumulative release (97.42 4.72). The in vitro

antiviral activity was examined using a plaque assay. The Middle East respiratory syndrome

coronavirus (MERS-CoV), NRCEHKU270, and the coronavirus HCV-229E were both resistant to

F2. F2 had an IC50 of 170 1.1 and 223 0.88 g/mL against HCoV-229E and MERS-CoV,

respectively. In comparison to free CGA, the values of the IC50 for F2 were significantly lower

(p.05). A promising approach exhibiting a notable improvement in CGA antiviral efficacy against

MERS-CoV and the low pathogenic human coronavirus (HCoV-229E) is the fabrication of CGA

into an ideal PVA or PLGA nano delivery backdrop through electrospraying[15].

23
Sadia Chaman et al. determined the antiviral potentials of Euphorbia milii var. splendens leaf

against Peste des petits ruminants virus (PPRV). Using the Vero cell line and the 3-(4,5-

dimethylthiazol-2-yl)-2, diphenyltetrazolium bromide (MTT) assay, the methanol extract, as well as

the n-hexane, chloroform, ethyl acetate, and n-butanol fractions of E. milii leaves, were screened for

antiviral activity against PPRV. Cell survival rates (CSP) greater than 50% at non-cytotoxic

concentrations were regarded as virucidal. At all test doses, the effects of methanol extract and

fractions against PPRV were significant (p 0.05). Ethyl acetate, n-hexane, and n-butanol fractions

were non-virucidal in antiviral assays at all test concentrations ranging from 1.56 to 800 g/mL; even

at these concentrations, they did not exhibit antiviral activity. The methanol extract and its

chloroform fractions, on the other hand, had significant (p 0.05) virucidal potential. The findings

suggested that additional antiviral ingredient extraction from the fractions may open up new

avenues for the creation of novel antiviral medicines[41].

Amoebicidal activity:

Satish V Patil et al. evaluated the amoebicidal activity of photosynthesized nanoparticles using

Euphorbia milii and two other plants. Silver nanoparticles (AgNPs) that were relatively stable were

created using a plant extract from the Euphorbia milii species. The vitality of Acanthamoeba

castellanii trophozoites was not significantly affected by the amoebicidal activity of E. milii leaf

extracts. When tested against A. castellanii trophozoites, the activity of the E. milii extract at 50 g

mL1 exhibited 3% mortality, but AgNPs synthesized from the same extract at 50 g mL1 showed 5%

inhibition. AgNPs produced by plants have more amoebic activity[42].

Anti-gout activity:

Nurul Huda Abdul Wahab et al. evaluated the anti-gout properties of Euphorbia milii. Euphorbia

milii was selected as the sample because it has been found to have several secondary metabolites

that may be useful in the treatment of gout. The crude extracts of Malaysian E. milii were subjected

to quantitative analysis of total phenolic content and xanthine oxidase inhibitory assay, followed by

24
IC50 to determine the concentration required to suppress 50% of uric acid generation. As a result of

having the greatest total phenolic content (0.77 0.02 mg QAE/g of the sample), the methanol leaf

extract of E. milii was shown to be a powerful uric acid inhibitor (IC50 = 0.0864 mM). By 65.6%,

this value greatly decreased the generation of uric acid. As a result, the crude extract contained

methanolic leaf extract that was tested using GC-MS and hexadecanoic acid and exhibits anti-gout

effects. In conclusion, it is possible to create a novel medicine from the Malaysian E. milii plant that

could be useful in the treatment of gout[43].

Wound healing activity:

Rong-Ye Wang et al. evaluated the wound-healing activity of silver nanoparticles synthesized using

Euphorbia milii leaf extract. Euphorbia milii leaf extract effectively produces silver nanoparticles.

The synthesis of AgNPs was studied using UV-visible spectra, and it was discovered that as the

reaction time increased, the peak's shape changed, increasing the number of silver nanoparticles

produced by the reduction of silver ions in the aqueous solution. The biphasic nature of the

biosynthesized silver nanoparticles was validated by the X-ray diffraction technique and associated

XRD patterns. While SAED diffraction patterns revealed the crystalline structure of the AgNPs,

low-magnification TEM pictures showed monodispersed AgNPs with sizes ranging from 20 to 30

nm. Additionally, the excision wound model was used to examine the wound-healing activity of

AgNPs. The rate of wound closure was measured, and Group II (treated with 10% Ointment base

with biosynthesized AgNPs) showed significantly greater wound healing activity than the control

group and Group I (treated with Standard Nitrofurazone ointment) in Albino rats[44].

Atherosclerosis:

Ni Made Linawati et al. determined the role of a combination of tea from E. milii flowers and

propolis (EMP) in preventing atherosclerosis through VEGF-β and MMP-8 pathways. 28 male

Wistar rats, each weighing 100–200 grams (g), were split into four groups for the experiment: K0,

P1, P2, and P3. Following a week of acclimatization, K0 received standard feed, P1 received

25
standard feed and EMP tea 40 mg/100 g/day, P2 received a high-fat diet (HFD) of 2 g/200 g/day,

and P3 received an HFD of 2 g/200 g/day and EMP tea 40 mg/100 g/day. Treatment lasted for 30

days, and on the 31st day, total cholesterol and MMP-8 and VEGF-B blood levels were measured

using the Erba XL 100 method and ELISA, respectively. Results revealed decreased levels of

MMP-8 secretion and total cholesterol (17.450.91 ng/dl and 77.836.55 mg/dl) in the group

receiving the HFD and EMP tea, but not VEGF-secretion (p > 0.05). It was determined that rats

administered HFD were able to lower their MMP-8 and total cholesterol secretion by administering

the EMP combo tea at a dose of 40 mg/100 g bw for 30 days[45].

Larvicidal activity:

Eusseph A Federico et al. evaluated the larvicidal activity of Euphorbia milii stem extract using an

Aedes Aegypti mosquito. He developed natural alternatives that could kill mosquito larvae. For the

first formulation, the stem of the crown-of-thorns plant (Euphorbia milii) was pounded with a

mortar and pestle before being soaked in 120 mL of distilled water. For the second formulation, the

stem was simply soaked in 120 mL of water. 10 mL and 20 mL of each of these two formulations

were divided into distinct concentrations. 48 hours were given for both formulations to settle. These

remedies were then used on various containers containing 10 mosquito larvae each. A positive

control (cooking oil) and a negative control (acetone) were also applied to mosquito larvae in

addition to the treatments. It took 24 hours to calculate the fatality rate. The findings demonstrated

that the treatments had a 0–50% mortality rate for mosquito larvae. The majority of deaths are

caused by Culex quinquefasciatus. The control groups, however, had a death rate of 100%. At the

0.05 significance level, there was also a significant difference between the experimental and control

groups (P =.0008). As a result, it was discovered that Euphorbia milii stem extracts were only

marginally efficient against mosquito larvae[46].

Antitubercular activity:

26
Ni Made Linawati et al. evaluated the influence of Euphorbia milii flower extract in increasing the

activity of Th17 cells through IL-17 secretion in Mycobacterium tuberculosis-infected mice. The

control group for this experiment was the post-test alone group. Six treatment groups of 24 male

BalbC were formed, and the first and third weeks of the treatments were evaluated. P1 and P3

received OAT and were infected with M. tb, whereas P2 and P4 received infected M. tb along with

OAT and EM. Groups K1 and K2 serve as negative controls. The first week saw the termination of

K1, P1, and P2, while the third week saw the termination of K2, P3, and P4. For an ELISA IL-17

analysis, pulmonary organs were removed. The results showed that the average IL-17 levels in K1,

P1, P2, K2, P3, and P4 were 81.18, 90.00, 88.65, 87.53, 75.45, and 87.53 pg/ml, respectively. The

concentration of IL-17 was somewhat higher in the group that received EM extracts in the third

week than in the group that did not, but the difference was not statistically significant. It presumably

occurred as a result of a variety of variables that influence the stability of IL-17 and, therefore, the

result. To reduce the influence of these factors, more study is required to understand how IL-17's

mRNA expression occurs[47].

CONCLUSIONS

One of the decorative plants with a variety of therapeutic benefits is Euphorbia milii. The

antibacterial, molluscicidal, antioxidant, antinociceptive, muscle relaxant, sedative,

hepatoprotective, anticancer, and antiviral properties of this plant are beneficial. These activities

occur due to the presence of many chemical constituents like β-amyrin acetate, β-sitosterol,

cycloartenol, lupeol, euphol, alkaloids, phenolic compounds, carbohydrates, anthocyanin, β-cyanin,

proteins, amino acids, cardiac glycosides, steroids, anthraquinone, tannins, phlorotannins, reducing

sugar, saponins, coumarin, triterpenes, and flavonoids. This review came to the conclusion that the

diverse literature on pharmacological activity is helpful for a quick search of the pharmacological

activities of Euphorbia milii.

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27
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