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Chaudhary, P.; Singh, D.; Swapnil, P.; Meena, M.; Janmeda, P. Phytochemical of Euphorbia neriifolia. Encyclopedia. Available online: https://encyclopedia.pub/entry/50659 (accessed on 04 September 2024).
Chaudhary P, Singh D, Swapnil P, Meena M, Janmeda P. Phytochemical of Euphorbia neriifolia. Encyclopedia. Available at: https://encyclopedia.pub/entry/50659. Accessed September 04, 2024.
Chaudhary, Priya, Devendra Singh, Prashant Swapnil, Mukesh Meena, Pracheta Janmeda. "Phytochemical of Euphorbia neriifolia" Encyclopedia, https://encyclopedia.pub/entry/50659 (accessed September 04, 2024).
Chaudhary, P., Singh, D., Swapnil, P., Meena, M., & Janmeda, P. (2023, October 23). Phytochemical of Euphorbia neriifolia. In Encyclopedia. https://encyclopedia.pub/entry/50659
Chaudhary, Priya, et al. "Phytochemical of Euphorbia neriifolia." Encyclopedia. Web. 23 October, 2023.
Phytochemical of Euphorbia neriifolia
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This entry is adapted from the peer-reviewed paper 10.3390/su15021225

In the Indian subcontinents, Euphorbia neriifolia Linn. (EN) is one of the valuable plants from the big family of Euphorbiaceae, which is usually found in rocky and hilly areas. E. neriifolia was found to be useful in curing tumors, abdominal swelling, bronchial infection, hydrophobia, earache, cough and cold, asthma, leprosy, gonorrhea, spleen enlargement, leucoderma, snake bites, scorpion stings, and causing appetite improvement, etc. Different in vitro and in vivo experimental studies were performed to determine the antioxidant, anti-diabetic, immunomodulatory, anti-inflammatory, anti-arthritic, wound healing, anti-atherosclerosis, radioprotective, anti-anxiety, anti-convulsant, anti-psychotic, anti-thrombotic, dermal irritation, hemolytic, analgesic, anti-fertility, diuretic, anti-microbial, anti-diarrheal, and anti-carcinogenic activities of the various parts of EN. Several bioactive compounds, such as euphol, nerifoliol, taraxerol, euphonerins A–G, lectin, etc., were isolated from E. neriifolia and need to be investigated further for various biological activities (cardiovascular and neuronal diseases). In the pharmaceutical sector, E. neriifolia was selected for the development of new drugs due to its broad pharmacological activities. 

Euphorbia neriifolia diseases triterpenes

1. Introduction

Since ancient times, people have searched for drugs in nature to cure their illnesses. There was no information concerning the cause of the disease or the medicinal plants, such as how to use them for treatment; everything was based on experience alone [1]. Many plants species from different parts of the world have been proposed for medicinal use as they are composed of various types of chemical compounds, such as secondary metabolites with different biochemical activities [2]. According to the World Health Organization (WHO) [3], almost 80% of the global population is still dependent upon the traditional system (Ayurvedic, Sidha, Tibetan, Unani, Rigpa, Sowa, Folk, Homeopathic, and Chinese) of medicines for the betterment and well-being of their lives. Most of the treatments include active components and extracts from the medicinal plants [4]. The difficulty in the formation of chemical-based drugs, along with increasing costs and health-related side effects, has led researchers to focus on medicinal plants [5]. The demand for naturally derived drugs has gained significant attention in both developed and developing countries because of their accessibility, preventive nature, diversity, affordability, and the safety of natural bioactive agents present in the plants [6].
Traditional medicinal systems have created a base of early medicines with chemical, pharmacological, and subsequent studies. Some of the well-known examples to date include salicin derived from the bark of Salix alba L., morphine isolated from Papaver somniferum, quinine isolated from Cinchona succirubra bark, pilocarpine derived from Pilocarpus jaborandi, etc., for the treatment of inflammation, congestive heart failure, fever, and chronic and acute glaucoma [7]. To hold a better position in both traditional and modern systems of medicine across the globe, the Euphorbia neriifolia Linn. plant needs to be characterized and its use standardized in terms of diversity and pharmacological activities [8]. The family Euphorbiaceae consists of approximately 800 species, 317 genera, and 49 tribes. A large number of species from the genus Euphorbia are under the snuk name and its synonym. Euphorbia neriifolia is a deciduous, large succulent medicinal plant with stipular thorns that is usually found throughout the Orissa and Deccan Peninsula in India [9]. This plant is widely known for its therapeutic activities, such as anti-viral, anti-convulsant, radioprotective, anti-arthritic, anti-asthmatic, anti-fertility, anti-diarrheal, and anti-ulcer activities [10]. Different types of diterpenoids with variable skeleton, such as eurifoloids A–R, eupnerias G–I, and eupnerias J–M, were isolated from E. neriifolia plants. Anti-HIV and cytotoxic activity against HepG2/Adr cell lines are the related pharmacological activities that were reported for these diterpenoids [11]. Some triterpenoidal compounds, such as neritroterpenols A–B, C, and D–G; turucallane triterpenes; and euphane from the stem of E. neriifolia are reported to have anti-proliferative and anti-inflammatory activities, respectively [12]. The research into natural compounds is relevant, and there are compounds used in clinical practice from natural sources. Furthermore, since plants have been used in treating various pathologies since ancient times, it is essential to validate these traditional applications and simultaneously study new compounds with relevant biological potential.

2. Medicinal Uses of Different Parts of Euphorbia neriifolia

Classically, E. neriifolia is divided into the vagbhata, susruta, and caraka categories. The caraka exhibits the properties of rasa with tikta and katu actions, and susruta shows properties of virya with the action of usna. Guna expresses snigdha, tiksna, and laghu actions. Vipaka shows the action of katu, and karma exhibits recana, dipana, and kapha-vatahara actions. The caraka displays medoroga, kusta, arsas, sotha, sula, udara, gulma, and vatavyadhi indications [13][14].
The leaves are used for carminative, stomachic, and expectorant purposes [15][16]. Flavonoids isolated from E. neriifolia leaf are also utilized to treat various chronic diseases, whereas oil extracted from E. neriifolia and sesame is utilized to treat joint pain [17]. Coronavirus disease-2019 (COVID-19) has affected the health of a large population of people all across the world. This disease has different clinical presentations. Although different medicines have been repurposed to treat COVID-19, none of them were found to be particularly effective in the perspective of the global population. Thus, there is always a need to discover novel strategies to deal with this virus. A total of 60 patients in groups of four were analyzed properly. Approximately 66.66% of patients were below 40 years of age and approximately 68.33% were males. The patients complained of various symptoms at the commencement of therapy, such as diarrhea, red eye, loss of taste, headache, skin rash, chest pain, running nose, sore throat, difficult breathing, cough, body aches and pains, and weakness. The leaves of E. neriifolia were utilized for moderate and mild COVID-19 patients. The results showed the beneficent effect of E. neriifolia in the management of COVID-19, especially in resource-constrained and developing countries. In 15 mild COVID-19 patients, the p-value of the RBC variable was 0.5000 to 1.0000 from 1–7 days and 0.4493 to 0.8986 from 7–14 days; the WBC p-value varied from 0.0002 to 0.0004 from 1–7 days and 0.1976 to 0.3953 from 7–14 days; the neutrophil p-value varied from 0.0000 from 1–7 days and 0.0128 to 0.0257 on 7–14 days; the hemoglobin p-value varied from 0.0042 to 0.0085 from 1–7 days and 0.1032 to 0.2063 from 7–14 days; the platelet p-value varied from 0.0789 to 0.1578 from 1–7 days and 0.2380 to 0.4760 from 7–14 days; the d-dimer p-value varied from 0.0053 to 0.0105 from 1–7 days and 0.0067–0.0134 from 7–14 days; and the p-value of S-ferritin and oxygen saturation varied from 0.000 to 0.000 from 1–14 days. The discharge criterion was containment of COVID-19-associated symptoms so that the person can manage their health at home after being discharged from the hospital. A conclusion could not be made due to small sampling size. This plant is pertinent in the conditions of the spread of COVID-19, as the overload of CoV in infected individuals may be treated with the help of this plant without the need of hospitalization if direct connection is maintained between the physicians and the patients [18].
The latex of E. neriifolia is purgative, acrid, and results in dermatitis [19]. Burkill and Haniff [20] stated that E. neriifolia latex is a diuretic and vermifuge. The tribal people of Chattishgarh utilized the latex of E. neriifolia as an aphrodisiac mixture, and they treated cracks in their foot soles by boiling latex with castor oil, along with salt [21]. A chymotrypsin-like serine protease, neriifolin, was obtained from the E. neriifolia latex by gel filtration, cation exchange chromatography, and ammonium sulfate precipitation. The enzyme has an isoelectric point of pH 5.7 and a molecular mass of 35.24 kDa. A high ratio of proteolytic activity and stability against detergent additives, oxidizing agents, surfactants, temperature, and pH make neriifolin a suitable candidate for different applications related to industry [22]. Euphorbia neriifolia latex was utilized as an effective drug for rheumatism [23][24]. It was found to be useful in the treatment of the gaseous distension of the abdomen, paralysis, gout, and sciatica [24][25][26]. The bark was considered to be a poor stomach poison and good contact poison [9]. Other medicinal uses of E. neriifolia are listed in Table 1.
Table 1. The medicinal uses of Euphorbia neriifolia.
Plant Parts Used in Applications References
Whole plant Anemia, fever, ulcer, inflammation, loss of consciousness, piles, delirium, bronchitis, and tumor Whole plant juice as alexipharmic, carminative, and laxative [9]
Vata-dosha disorders such as constipation, neuroglia, bloating, paralysis, induction of severe purgation, and for improving the strength of digestion Whole plant [19]
Anal fistula Whole plant as rubefacient and aphrodisiac [19]
Anorexia, fatigue, vomiting, weakness, spree syndrome, arthritis, and digestive tract disorder Whole plant as one of the components of Dashmoolarishtam [19]
Insecticide As a spray to kill insects [27]
For fencing As it is covered with spines [27]
Leaves Asthma Succus administration comprising leaf juice and simple syrup in a minimum dosage of 10–20 mL three times a day [9]
Earache Leaf juice [9]
Wound healing Steamed leaves paste on the affected area for 4–5 days [9][16]
Arthritis, skin wart Leaf juice [17]
Bleeding piles, ano-rectal fistula, bronchitis, cold, and cough As a diuretic and aphrodisiac [28]
Stem Direct expectoration of phlegm Stem juice at a small dosage with honey and borax [28]
Hydrophobia Pulp of the stem mixed with fresh ginger [28]
Piles and fistula Stem juice [28]
Chronic respiratory problem Stem juice with black pepper [27]
Latex Drastic cathartic condition Latex juice [15]
Piles Latex juice with turmeric [15]
Warts Latex juice [20]
Skin warts, arthritis, and earache. Latex juice [16]
Opthalmia Milky juice in combination with shoot [15][16][29]
Rheumatic infection Milky juice in combination with margosa oil [15][16][29]
Unhealthy ulcer, glandular swelling, and scabies EN latex juice with fresh butter [15][16][21][29]
Cracks in their foot soles Boiling latex with castor oil and salt [15][16][29]
Wounds and burns Milk of E. neriifolia latex [15][16][29]
Reduce swelling in piles, pain, and itching Lukewarm extract [15][16][29]
Asthma Five drops of latex juice containing gokaran root, agaba root, and madar flower with honey [9]
Vitiligo, fistula, and syphilis Latex juice [15][25][26][30]
Leprosy, general anasarca, dropsy, syphilis, spleen and liver enlargement Trivit root, chebulic myrobalans, long-peppers, clove soaked in latex juice for a month and then dried to form pills [9]
Ascites, anasarea, and tympanitis Latex juice with chebulic myrobalan, trivit root, and long pepper [15]
Protection against herbivorous insects Latex [31]
Bark Semen passing with urine Mixture of bark and leaves of Piper betle L. [32]
Roots Snake bites and scorpion stings Root of E. neriifolia in combination with black pepper [9][15][32]
Blood pressure A small dosage may increase blood pressure and a high dosage may decrease blood pressure [9][15][32]
Dropsy Boiled mixture of root-bark in water [9][15]

3. Phytochemical Composition

EN yielded different types of bioactive compounds that possess several biological activities. These compounds are steroidal saponins, triterpenoidal saponins, anthocyanins, alkaloids, flavonoids, several triterpenes, and sugars [15][33]. The phytochemistry of the genus Euphorbia is quite complex with different types of chemical compounds of various classes, as shown in Table 2.

3.1. Terpenes

The diversity of cyclic triterpenes in terms of their structure is incredible. Approximately 130 different types of triterpenoids have been isolated so far from the various species of Euphorbia. According to reports, tertracyclic triterpenoids are one of the major triterpenoids in the Euphorbia species and were divided into four classes: cycloartanes (40–84), lanostane (85–94), euphane (20–39), and tirucallane (1–19). Specifically, 9,19-cyclolanostanes (cycloartanes) are the main triterpenes that contain a cyclopropane ring and a characteristic side chain. These are the key intermediates in the biosynthesis of phytosterols and can be utilized as chemotaxic markers in the genus Euphorbia [34]. Thus, significant efforts were made in the isolation, characterization, and identification of novel flavonoids from the whole plant extract, stem bark, seeds, stems, roots, aerial parts, and latex of Euphorbia species [35]. Different types of triterpenoids, such as β-amyrin, taraxerol, Glut-5(10)-en-1-one, and Glut-5-en-3β-ol, were isolated from the leaves and stem of E. neriifolia [36].
Yeoh et al. [37] reported the enzyme profile of E. neriifolia latex and it was found to be different from the other latex containing plants. Therefore, this characteristic feature can be utilized for the identification of E. neriifolia from the other species of latex bearing plants. The partial purification and characterization of lectin was performed by Seshaginrao and Prasad [38], whereas a tetracyclic triterpene was isolated by Mallavadhani et al. [39]. E. neriifolia latex and its isolated compounds are reported to have anti-arthritic, anti-inflammatory, mitogenic, cytotoxic, pesticidal, and molluscicidal activities. The phytocompounds most related to toxicity and significant pharmacological activities in Euphorbia are diterpenes with ingenane, tigliane, and abietane skeletons. Latex consists of 12-deoxyphorbol esters and diterpene esters of ingenol and phorbol which are widely known to act as tumor promoting agents and highly active cocarcinogenic agents [40].

3.2. Flavonoids

Flavonoids are the other dominant phytocompound of Euphorbia species after triterpenoids and macrocyclic diterpenes. Flavonoids mostly present as anthocyanidins, flavanol, flavanonol, flavanone, flavonols, chalcones, neoflavonoids, and isoflavonoids. These compounds are biogenetically and structurally associated as they have chalcone as a common precursor. They are reported to have promising pharmacological activities and various therapeutic potentials. Apart from providing protection against herbivores and other pathogenic microorganisms, they act as a stress-protecting agent and are also responsible for various pharmacological activities in humans. As per different studies on Euphorbia species, flavonoids exhibit anti-cancer, anti-proliferative, anti-angiogenic, anti-inflammatory, anti-diabetic, anti-microbial, anti-depressant, and anti-ulcer activities in vitro. Flavonoids are still not considered as nutrients but their consumption is found to be significant for the health of a human being. They are also utilized as natural dyes and in skin-care, and cosmetic products [41]. Several studies reported the role of flavonoids in the thyroid hormone metabolism; they are also known as vitamin P and are found to be important to deal with hemorrhage. They are considered a functional food for the prevention of diseases and promotion of good health [35].

3.3. Saponins

Saponins are functionally and structurally the biggest group of phytocompounds, commonly formed in plants, and play a very significant role in the defense mechanism of the plant. Due to their ability to produce foam when mixing with water, they are named saponin, which means “soap”. Chemically, they consist of steroidal or triterpenoidal aglycones, which are associated with the different moieties of oligosaccharides. Based on the structure of aglycones, saponins are differentiated into three groups, (1) steroidal glycoalkaloids, (2) steroids, and (3) triterpenoids. Among them, triterpenes are immensely formed in licorice [42]. Crude saponin, euphol, was isolated from the hydroalcoholic extract of E. neriifolia and was evaluated further for various in vitro pharmacological properties. Crude saponin was reported to have a better antioxidant capacity compared to silymarin along with greater value of bitterness index. Their antioxidant ability was evaluated against hydroxyl and superoxide radicals, lipid peroxidation, reducing power, and hydrogen donating ability. The crude saponin does not show protective activity against bacteria up to 10 mg/mL of concentration, but the saponin fraction of E. neriifolia is found to be useful to treat inflammation, diabetes, cardiovascular diseases, and cancer [43]. The saponin fraction of E. neriifolia possesses hepatoprotective activity against carbon tetrachloride, aflatoxin, galactosamine, ter-butyl hydroperoxide, and cadmium, and this is because of the presence of bioactive compounds that prevent alteration in the plasma membrane of the liver and promotes repair in liver cells [44]. Other bioactive constituents that are obtained from different parts of E. neriifolia are shown in Table 2.
Table 2. Bioactive compounds obtained from the different parts of Euphorbia neriifolia.
Plant part Extracts Secondary Metabolite Types Structure Pharmacological Activity References
Whole plant Methanol extract Diterpenoids
  • Eupnerias G–I (1– 3),
  • Ent-16α,17-dihydroxyatisan-3-one (4),
  • Eurifoloid R (5),
  • Ent-atisane-3α,16α,17-triol (6),
  • Ent-atisane-3β,16α,17-triol (7),
  • Ent-atisane-1β,16α,17-triol (8),
  • 4,13β-Dihydroxy-14-oxo-3,4-secoatis-16-en-3-oic acid methyl ester (9),
  • Eurifoloid M (10),
  • Ent-3S-hydroxyatis-16(17)-en-1,14-dione (11),
  • Ent-3α,13S-dihydroxyatis-16-en-14-one (12),
  • Ent-3β,13S-dihydroxyatis-16-en-14-one (13),
  • Ent-13S-hydroxyatis-16-ene-3,14-dione (14),
  • (4R,5S,8S,9R,10S,13R,16S)-Ent-16α,17-dihydroxy-19-tigloyloxykauran-3-one (15)
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Eupnerias G
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Eupnerias H
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Eupnerias I, ent-16α,17-dihydroxyatisan-3-one, Eurifoloid R
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Ent-atisane-3α,16α,17-triol, Ent-atisane-3β,16α,17-triol, Ent-atisane-1β,16α,17-triol
Sustainability 15 01225 i005
4,13β-Dihydroxy-14-oxo-3,4-secoatis-16-en-3-oic acid methyl ester
Sustainability 15 01225 i006
Eurifoloid M
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Ent-3S-hydroxyatis-16(17)-en-1,14-dione
Sustainability 15 01225 i008
Ent-3α,13S-dihydroxyatis-16-en-14-one, Ent-3β,13S-dihydroxyatis-16-en-14-one, Ent-13S-hydroxyatis-16-ene-3,14-dione
Sustainability 15 01225 i009
(4R,5S,8S,9R,10S,13R,16S)-Ent-16α,17-dihydroxy-19-tigloyloxykauran-3-one		 Anti-HIV effect was shown by compound 4 and 5 with EC50 values of 6.6 ± 3.2 and 6.4 ± 2.5 μg/mL,
Moderate cytotoxic activity was exhibited by compound 1 and 6 against HepG2/Adr and HepG2 cells with IC50 values of 13.70 and 15.57 μM, and compound 15 was reported to exhibit cytotoxic activity (IC50 = 0.01µM) against HepG2 but not against HepG2/Adr cell line		 [11]
Whole plant Hexane extract Triterpene and Triterpene alcohol
  • Taraxerol, and
  • β-Amyrin
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Taraxerol
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β-Amyrin		 Taraxerol exhibits anti-cancer activity via Nf-kB signalling pathway inhibition or by induction of apoptosis in case of middle ear epithelial cholesteatoma cells [45][46]
Leaves Hydroethanolic extract Flavonoids
  • 2-(3,4-Dihydroxy-5-methoxy-phenyl)-3,5-dihydroxy-6,7-dimethoxychromen-4-one (C18H18O9)
 Sustainability 15 01225 i012
2-(3,4-dihydroxy-5-methoxy-phenyl)-3,5-dihydroxy-6,7-dimethoxychromen-4-one (C18H18O9)		 Exhibits anti-cancer activity due to its ability to scavenge reactive oxygen species and to inhibit lipid peroxidation [41]
Leaves Ethanolic extract
  • Glycosides
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Glycosides		 Inhibits the proliferation of Plamodium falciparum with IC50 values of 5.4, 4.1, and 1.1 µg/mL, and shows cytotoxic activity against KN3-1 human epidermoid cancer cells [47]
Leaves Ethanolic extract Triterpenoids
  • (1–4) friedelane
  • (5–7) glutinane
  • (8) Lupane
  • (9–11) Taraxerane
  • (12,13) Oleanane
  • (14) Dammarane
  • (15) Ocotillone
  • (16,17) Simiarenane
  • (18–20) Cycloartane
  • (21 & 22) Cycloeucalane
  • 3β-Friedelanol (1),
  • 3α-Friedelanol (2),
  • 3β-Acetoxy fridelane (3),
  • Friedelin (4),
  • Glutinone (5),
  • Glutin-5-en-3β-ol (6),
  • Glutinol acetate (7),
  • Lupenone (8),
  • Epitaraxerol (9),
  • Epitaraxeryl acetate (10),
  • Taraxeryl acetate (11),
  • β-amyrin (12),
  • β-amyrin acetate (13),
  • Dammarenediol II acetate (14),
  • Cabraleadiol monoacetate (15),
  • 3β-Simiarenol (16),
  • Simiarenone (17),
  • Cycloartenol (18),
  • 24-Oxocycloart-25-en-3β-ol (19),
  • (23Z)-Cycloart-23-ene-3β,25-diol (20),
  • Cycloeucalenol (21),
  • 29-Norcycloartanol (22), and
  • Afzelin (23)
 Sustainability 15 01225 i014
3β-Friedelanol, 3α-Friedelanol, 3β-Acetoxy fridelane, Friedelin
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Glutinone, Glutin-5-en-3β-ol, Glutinol acetate
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Lupenone
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Epitaraxerol, Epitaraxeryl acetate, Taraxeryl acetate
Sustainability 15 01225 i018
β-Amyrin, β-Amyrin acetate
Sustainability 15 01225 i019
Dammarenediol II acetate
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Cabraleadiol monoacetate
Sustainability 15 01225 i021
3β-Simiarenol, Simiarenone
Sustainability 15 01225 i022
Cycloartenol
Sustainability 15 01225 i023
24-Oxocycloart-25-en-3β-ol
Sustainability 15 01225 i024
(23Z)-Cycloart-23-ene-3β,25-diol
Sustainability 15 01225 i025
29-Norcycloartanol
Sustainability 15 01225 i026
Afzelin		 Triterpenoids showed anti-viral activity in comparison to actinomycin D, Found to be effective against the herpes virus and inhibits replication of SARS-COV by binding to its 3CL pro proteases [27][36][47]
Leaves Aqueous extract Flavonoid
  • Kaempferol
 Sustainability 15 01225 i027
Kaempferol		 Kaempferol modulates metastasis, inflammation, angiogenesis, and apoptosis, and provides protection against chronic diseases by activating the body antioxidant defense mechanism against free reactive species [48][49]
Leaves Ethyl acetate extract Diterpenoids (Eurifoloids A–R)
  • Ingenane (1&2),
  • Abietane (3–7),
  • Isopimarane (8–12), and
  • ent-atisane (13–18)
 Sustainability 15 01225 i028
Ingenane (1&2)
Sustainability 15 01225 i029
Abietane
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Isopimarane
Sustainability 15 01225 i031
Ent-atisane		 Various diterpenoids such as ingenanae, abietane, isopimarane, and ent-atisane exhibit anti-HIV activity [50]
Leaves Methanol extract Cycloartane terpenoids
  • Neriifolins A–C
 Sustainability 15 01225 i032 Sustainability 15 01225 i033
Neriifolins A, Neriifolins B
Sustainability 15 01225 i034
Neriifolins C		 Neriifolins A–C showed cytotoxicity against MCF breast cancer cell line with IC50 value of 9.50, 7.12, and 13.14 µM [51]
Leaves Methanol extract Pachypodol
  • 5,40-Dihydroxy-3,7,30-trimethoxyflavone
 Sustainability 15 01225 i035
5,40-Dihydroxy-3,7,30-trimethoxyflavone		 Inhibits the proliferation of Psudomonas aeruginosa, Escherichia coli, Streptococcus faecalis, Streptococcus aureus, Bacillus subtilis, Candida glabrata, Candida krusei, and Candida albicans [27]
Leaf Chloroform and ethanol extract  
  • Saponin (Sapogenin),
  • Rutin, and
  • Quercetin
 Sustainability 15 01225 i036
Saponin

Sustainability 15 01225 i037
Rutin

Sustainability 15 01225 i038
Quercetin		 Saponin shows anti-microbial activity against Staphylococcus aeruginosa, Escherichia coli, and Pseudomonas aeruginosa;
Rutin inhibits the activity of Cryptococcus gattii, and Cryptococcus neoformans; and
Quercetin found to be effective against Candida albicans		 [9][27][44][52][53]
Leaves _ Diterpenoids
  • Phorneroids A–M, and three known compounds
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Phorneroids A
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Phorneroids B
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Phorneroids C

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Phorneroids D
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Phorneroids E, F
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Phorneroids G
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Phorneroids H, I

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Phorneroids J, K, L
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Phorneroids M

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Compound I

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Compound II

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Compound III		 Phorneroids A–M, and three known compounds exhibit moderate cytotoxic activity against HL-60 and A549 cancer cell line [54]
Leaves _ Ingenane and ingol diterpenoids
  • Phonerilins A–K, and five known analogues
 Sustainability 15 01225 i051
Phonerilins A
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Phonerilins B, Phonerilins C, Phonerilins D, Phonerilins E, Phonerilins F, Phonerilins G, and 2 analogues

Sustainability 15 01225 i053
Phonerilins G, Phonerilins H, Phonerilins I, Phonerilins J, Phonerilins K, and three analogues		 Phonerilins A–K, and five known analogues exhibit moderate cytotoxic activity against HL-60 and A549 cancer cell line [55]
Stem Ethanolic extract Euphane and tirucallane triterpenes
  • Neritriterpenols A–G, and four known triterpene
 Sustainability 15 01225 i054
Neritriterpenols A, Neritriterpenols B
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Neritriterpenols C
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Neritriterpenols D
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Neritriterpenols E
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Neritriterpenols F Sustainability 15 01225 i059
Neritriterpenols G
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Triterpene
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Triterpenes
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Triterpenes		 Neritriterpenols A–G, and four known triterpene exhibit anti-proliferative and anti-inflammatory activities [12]
Stem bark Ethyl acetate extract Ingenane-type diterpenoids
  • Eurifoloid E, and
  • Euphorneroid A
 Sustainability 15 01225 i063
Eurifoloid E
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Euphorneroid A		 Eurifoloid E
and Euphorneroid A inhibit pro-inflammatory mediators such as iNOS, IL-6, IL-1β, and NO in cases of LPS-induced RAW264.7 macrophage		 [56]
Stem bark Methanol extract Diterpenes
  • Ent-3-oxoatis-16α,17-acetonide (4),
 Sustainability 15 01225 i065
Ent-3-oxoatis-16α,17-acetonide		 Exhibits anti-HIV activity with EC50 value of 8.7 µg/mL [57]
Stem and Bark Methanol extract Diterpenes
  • Ent-3-oxoatisan-16α, 17-acetonide, and
  • Euphorneroid D
 Sustainability 15 01225 i066
Ent-3-oxoatisan-16α, 17-acetonide
Sustainability 15 01225 i067
Euphorneroid D		 Ent-3-oxoatisan-16α, 17-acetonide and Euphorneroid D exhibit anti-HIV activity with EC50 value of 24 and 34 mM [58]
Stem and Bark Ethanol and petroleum ether extract Anthocyanin
  • Tulipanin, and
  • Pelargonin
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Tulipanin
Sustainability 15 01225 i069
Pelargonin		 Tulipanin inhibits the proliferation of Bacillus subtilis, E. coli, P. aeruginosa, and Staphylococcus aureus [27][45]
Stem and Bark Methanol extract Triterpene alcohol
  • Euphol
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Euphol		 Euphol exhibits an anti-nociceptive effect in neuropathic pain and inflammatory conditions [45][59]
Stem barks Ethyl acetate extract Ent-isopimarane diterpenoids
  • Eupneria J,
  • Eurifoloid H, and
  • Ent-isopimara-8(14),15-dien-3β,12β-diol
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Eupneria J
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Eurifoloid H
Sustainability 15 01225 i073
Ent-isopimara-8(14),15-dien-3β,12β-diol		 Eupneria J, Eurifoloid H, and ent-isopimara-8(14),15-dien-3β,12β-diol exhibit anti-HIV activity with an IC50 value of 6.70 and 0.31 µg/mL and anti-influenza activity with an IC50 value of 3.86 µg/mL [60]
Stem bark Ethyl acetate extract Ent-abietane diterpenoids
  • Eupnerias A–F
 Sustainability 15 01225 i074
Eupnerias A–E
Sustainability 15 01225 i075
Eupnerias F		 Exhibit anti-influenza and anti-inflammatory activities [61]
Bark Petroleum ether extract Diterpenes
  • Pelargonin-3,5-diglucoside,
  • n-Hexacosanol, and
  • Euphorbol
 Sustainability 15 01225 i076
Pelargonin-3,5-diglucoside
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n-Hexacosanol
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Euphorbol		 n-Hexacosanol was found to be effective to treat diabetic ileum by ameliorating the overexpression of M(3) and M(2) mRNA receptor [45][62]
Fresh Latex from stem Crude extract  
  • Neriifolin-S
 Sustainability 15 01225 i079
Neriifolin-S		 Neriifolin-S exhibits milk clotting activity [22]
Dried Latex Methanol extract Triterpene and Triterpene alcohol
  • Cycloartenol (C10H50O),
  • Nerifolione [9,19-cyclolanost-20(21)-en-24-ol-3-one], and
  • Nerifoliol
 Sustainability 15 01225 i080
Cycloartenol
Sustainability 15 01225 i081
Nerifolione
Sustainability 15 01225 i082
Nerifoliol		 Cycloartenol, Nerifolione, and Nerifoliol
inhibit p38 MAP kinase phosphorylation and migration of glioma cells		 [33][45][63]
Root Petroleum ether extract Diterpenes
  • Delphin, and
  • Tulipanin
 Sustainability 15 01225 i083
Delphin
Sustainability 15 01225 i084
Tulipanin		 Delphinidin 3,5-O-diglucoside and Tulipanin exhibit antioxidant activity by suppressing the formation of reactive oxygen species from lacrimal gland tissue that preserves tear secretion [45][64][65]
Root Ethanol
extract		 Triterpene alcohol
  • Cycloartenol, and
  • Euphorbol
 Sustainability 15 01225 i085
Cycloartenol
Sustainability 15 01225 i086
Euphorbol		 Cycloartenol exhibits antioxidant activity [45][66]
Root Methanolic extract Diterpenes
  • 12-Deoxyphorbhol-13, 20-diacetate, and
  • Ingenol triacetate
 Sustainability 15 01225 i087
12-Deoxyphorbhol-13, 20-diacetate
Sustainability 15 01225 i088
Ingenol triacetate		 12-Deoxyphorbhol-13, 20-diacetate and Ingenol triacetate exhibit anti-HIV activity in the case of MT-4 cells at 0.65 and 0.051 mM concentration, and are useful to treat the skin condition, actinic keratosis [45][67][68]
Fresh Root Protease fraction Diterpenes
  • Neriifolene [(C20H30O3), and
  • Atisine diterpene anti-quorin (C20H28O3)
 Sustainability 15 01225 i089
Neriifolene
Sustainability 15 01225 i090
Atisine diterpene anti-quorin		 Atisine diterpene anti-quorin exhibits wound healing activity by inducing the intercellular signaling and aggregation of platelets vis PAR-1 [45][69]

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Priya Chaudhary
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Devendra Singh
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Mukesh Meena
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Pracheta Janmeda
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