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A review on phytochemical constituents and pharmacological potential of Calotropis procera

Barkha Darra Wadhwani a, Deepak Mali a, Pooja Vyas a, Rashmy Nair b and Poonam Khandelwal *a
aDepartment of Chemistry, Mohanlal Sukhadia University, Udaipur-313001, India. E-mail: poonamkhandelwal@mlsu.ac.in
bDepartment of Chemistry, S.S. Jain Subodh P.G. College, Jaipur-302004, India

Received 6th September 2021 , Accepted 25th October 2021

First published on 4th November 2021


Abstract

Calotropis procera is locally known as Aak or Madar in Hindi, milk weed in English and belongs to the family Apocynaceae and subfamily Asclepiadoideae. Although a wasteland plant, it is of sacred use as its flowers are offered for worshipping Lord Shiva, a Hindu God. Tribes all over the world use the plant in treatment of various diseases like snake bite, body pain, asthma, epilepsy, cancer, sexual disorders, skin diseases and many more. This plant contains various phytoconstituents such as flavonoids, terpenoids, cardenolides, steroids oxypregnanes etc. Though literature searches reveal many reviews about ethnomedicinal uses, chemical composition and pharmacological activities, no recent papers are available that provide an overview of the therapeutic potential and toxicity of Calotropis procera. Hence, the insight of this review is to provide a systemic summary of phytochemistry, pharmacology, toxicology and therapeutic potential of Calotropis procera and to highlight the gaps in the knowledge so as to offer inspiration for future research.


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Barkha Darra Wadhwani

Ms Barkha Darra Wadhwani did her Master's in Organic Chemistry from Bhupal Nobles University, Udaipur, Rajasthan in 2015 and Bachelor's from Guru Nanak Girls PG College, Udaipur, Rajasthan in 2007. Presently, she is pursuing PhD from Mohanlal Sukhadia University, Udaipur, Rajasthan. Her research interests include isolation and characterization of bioactive constituents from plants and synthetic methodology.

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Deepak Mali

Mr Deepak Mali did his Master's in Organic Chemistry from Mohanlal Sukhadia University, Udaipur, Rajasthan in the year 2016 and Bachelor’s from Seth Mathuradas Binani Government PG College, Nathdwara, Rajasthan in 2014. Presently, he is pursuing PhD from Mohanlal Sukhadia University, Udaipur. His research interests include natural product isolation and synthesis of heterocyclic moieties.

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Pooja Vyas

Dr Pooja Vyas served as Assistant Professor at Mehsana Urban Institute of Science, Ganpat University, Mehsana, Gujarat in 2019–2020. Dr Vyas completed her Master's degree from the Department of Chemistry, Mohanlal Sukhadia University, Udaipur, Rajasthan in 2014. She received her doctoral degree in 2018 from Mohanlal Sukhadia University, Udaipur. Her areas of research interest include natural product isolation and organic synthesis.

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Rashmy Nair

Dr Rashmy Nair is Associate Professor of Organic Chemistry at S.S. Jain Subodh P.G. College, Jaipur, Rajasthan, India. Her academic interests include organic synthesis, green chemistry, spectroscopy and natural product chemistry. Dr Nair completed her Master's degree from Department of Chemistry, University of Rajasthan, Jaipur in the year 1999. She received her doctoral degree in the year 2004 from University of Rajasthan, Jaipur, India. Her areas of research interest include natural products, synthetic methodology, nanocatalysis, multicomponent reactions and materials science.

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Poonam Khandelwal

Dr Poonam Khandelwal is Assistant Professor of Chemistry at Mohanlal Sukhadia University, Udaipur, Rajasthan, India. Dr Khandelwal completed her Master's degree from the Department of Chemistry, University of Rajasthan, Jaipur in 2004. She received her doctoral degree in 2008 from the University of Rajasthan, Jaipur. She had worked as Visiting Scientist at School of Agriculture, Meiji University, Kawasaki, Japan in 2017 for two months. She worked as INSA Visiting Scientist at CSIR-Indian Institute of Chemical Technology, Hyderabad in 2019 for two months. Her areas of research interest include natural product isolation and characterization, synthetic methodology and nanocatalysis.


1. Introduction

Calotropis belongs to the Apocynaceae family, which is commonly known as milkweed or Aak. Plants of this genus are known as milkweeds due to the exudation of white and sticky latex from different plant parts. Genus Calotropis has two common species viz. Calotropis procera (Rakta arka) and Calotropis gigantea (Sweata arka), which are described as possessing vital pharmacological properties in Ayurvedic toxicology and therapeutics. Other species are C. sussuela and C. acia.

Calotropis procera (Aiton) W. T. Aiton is an erect, soft wooded, evergreen perennial shrub and commonly known as ‘Sodom apple’ or ‘Madar shrub’. In Bengali, it is known as ‘Akanda’ and in Hindi as ‘Aak’. It manifests its wide utilization in Indian, Arabic and Sudanese traditional medicinal systems for healing global range of diseases.

The Dangas tribe in Gujarat,1 Singhum tribe in Bihar,2 tribes of Ghatigaon forest in Gwalior,3 tribes of Andhra Pradesh4 have been using this plant in the treatment of various disorders such as ear pain, cough, fever, abdominal pain, dysentery and elephantiasis.

Calotropis procera is more toxic than Calotropis gigantea and assumed to be even more poisonous than cobra venom. It is interesting that the cobra and other poisonous snakes cannot even bear its smell; hence snake charmers of Bengal use this plant for controlling or taming cobras.5

Earlier reviews6–16 have discussed on phytochemistry, ethnobotany and pharmacological potential of Calotropis procera. Review on Calotropis species17–20 comparing procera and gigantea have deliberated their therapeutic importance. The present review summarizes the phytochemistry, pharmacology, commercial aspects, traditional medicinal uses, toxicology and recent studies on Calotropis procera. The future scope of Calotropis procera has also been affirmed with a view to establish its multiple biological activities and mode of action.

2. Unique properties of Calotropis procera

2.1 Toxicity

C. procera finds its widespread distribution over many regions of the globe. What makes its phytochemistry interesting is the exudation of milky and toxic latex from all the plant parts. The latex is referred to as vegetable mercury as it shows mercury like effects on human body.21

Every part of this plant is toxic, but stem (latex) and roots are more poisonous than leaves. The leaves of this plant have three toxic glycosides calotropin, calotoxin and uscharin, whereas its latex contains calotropin, calotoxin and calactin, which are caustic and considered poisonous in nature. Besides this, the concentration of calactin, which is a toxic glycoside, gets increased as defense mechanism on encounter of grasshopper or insect attack and this is the rationale behind the plant not being consumed by cattles or other grazing animals.22 Other than this, osmotin, a laticifer protein purified from latex also provides protection to plant against phytopathogens.23 Its milk is irritant, neurotoxic and has anticholinergic activity, which causes toxicity and fatal complications. Madar juice and latex has bitter taste and a burning pain which causes salivation, stomatitis, vomiting, diarrhoea, dilated pupils, titanic convulsion, collapse and death. The fatal period varies from half an hour to eight hours.24 If latex enters into the eye, it causes kerato-conjunctivitis, corneal edema and dimness of vision without any pain.25–27 Some cases showed permanent endothelial cell damage, which was evident after three weeks.5,28 C. procera was found toxic at the dose of 100 mg kg−1 to chick embryo. Its toxicity caused hepatocellular degeneration in liver, brain congestion, dilation of central veins, sinusoids, underdeveloped lung and kidneys.29 Hence, bearing in mind the toxic effects of certain extracts and glycosides, further studies should be focused to explain toxicity and safe use of C. procera.

2.2 Ability to survive under extreme climatic conditions

Another interesting aspect of this plant is its ability to tolerate adverse environmental conditions like scarcity of water, arid environment or any kind of harsh climate. To understand this, Akhkha30 studied the effect of stress caused due to water scarcity and found that photosynthetic machinery remained uninfluenced, infact rate of photosynthesis gets raised at mild water regime (50%) which can be considered as a compensatory mechanism. Further Ramadana et al.31 studied the influence of light and irrigation on cumulation of β-sitosterol in C. procera. They hypothesized that β-sitosterol biosynthesis pathway supported the plant to bear drought and light intensity stress.

2.3 Commercial prospective

2.3.1 As biofuel. C. procera is rich in hydrocarbons and contains biologically degradable materials similar to that found in other agricultural crops. Traore32 conducted fermentation experiments and found that it is a good substrate for biogas synthesis. Barbosa et al.33 found that oil composition of its seeds varies from 19.7 to 24.0% which proves its future potential as biodiesel, specially in those areas where people rely mainly on wood as source of energy production.
2.3.2 As biopesticide. Laticifer proteins (LP) from Calotropis procera were assayed for insecticidal activity against different crop pests to assess the biological role of latex. Diets containing 4% latex led to decreased weight gain (ED50 = 3.07%) and affected survival (LD50 = 4.61%) of third instars of Ceratitis capitata.34 The crude flavonoid fraction (Cf), the latex protein fraction (LP) and the leaf methanolic extract showed significant insecticidal activity.35 These studies suggest that it can be developed as natural biopesticidal agent.

2.4 Industrial prospective

2.4.1 Cheese making agent. In West Africa, crude aqueous extract of C. procera is used as milk clotting enzyme in traditional method of cheese production.36 It displayed an optimum activity at a temperature of 75 °C, which is essential for cheese production.37 Calotropain enzyme found in the plant is more efficient than papain, ficin and bromelin, moreover it can lead to milk coagulation, digestion of meat, casein and gelatin.38,39 These studies supported its traditional use as cheese making agent.
2.4.2 As surfactant. C. procera milk latex was used as a surfactant for facile synthesis of Eu3+ activated La(OH)3 and La2O3 nanophosphors through green mediated hydrothermal route. The latex reflected good capping potency for controlling the morphology and phase of the nanophosphor.40 Hence its latex can be a good source of natural surfactant.
2.4.3 As corrosion inhibitor. Extract of C. procera was studied for its corrosion inhibition action by weight loss, electrochemical, SEM and UV methods, significant corrosion inhibitive effect in sulphuric acid medium on mild steel was observed.41 Hence, it can be used as green corrosion inhibitor.
2.4.4 As dehairing agent of leather. Latex peptidases of C. procera when assayed against skin representative substrates, revealed complete dehairing process, while no changes in leather structure were observed. Thus, it can be an appropriate environment friendly dehairing agent as compared to toxic sodium sulphite treatment for tanneries.42

3. Ethnomedicinal uses

An insight into Ayurveda, Unani and folk uses of different parts of C. procera and C. gigantea to cure various ailments was compiled by Misra et al.43 Ethnomedicinal uses of plant parts of C. procera in curing various diseases have been summarized in Table 1.
Table 1 Ethnomedicinal applications of C. procera
Plant part Disease Preparation/administration References
Root/root bark Amoebic dysentery Paste with/without opium taken orally 44–46
Cholera Powder orally taken or paste along with black pepper and ginger juice 44
Dysentery Powder orally taken 47
Elephantiasis and hydrocele Paste mixed with fermented rice water applied on the affected area 48–50
Epilepsy Grounded with goat milk and used as nasal drops 46
Indigestion Powder orally taken 47
Jaundice Taken with rice in grounded form 51
Neuritis Orally administered with cow butter 46
Rheumatism Powder taken with milk and sugar 48
Snake bite Powder orally taken. Paste applied on wounds and internally taken with ghee 47 and 52
Spider and insect bite Powdered and taken with vinegar 48
Syphilis Root bark powder taken orally 46
Latex Boils Applied externally 46
Black scar on the face Applied along with turmeric paste 44
Ascites Applied externally 47
Liver and spleen disorder Taken after dilution 47
Leprosy Applied on the affected area 47
Migraine Applied on the affected side vein of forehead 44
Piles (haemorrhoids) Applied externally 44
Dog/jackal bite Applied on wound 44 and 48
Ring worm Applied externally 46
Scabies Applied externally 46
Snake bite Applied on wounds or taken orally (20–30 drops for adults and 15–20 for infants) 46
Five drops with 50 drops of distilled water injected hypodermally 46
Syphilis, leprosy and odema Applied externally with sesame oil 48 and 50
Tooth ache Applied on affected tooth 48 and 50
Vertigo Applied on affected parts 53
Leaf Cold, cough, asthma and bronchitis Warmed along with ghee and bandaged on the chest of infants 44
Calculus, liver and spleen disorder Powder taken orally 48
Ear ache or ear troubles Juice along with fermented boiled rice water used as ear drops 50
Eczema and skin eruptions Applied externally along with turmeric and sesame oil 48, 50 and 53
Enlargement of abdominal viscera and spleen Oral administration of powder 48 and 51
Gonorrhoea Decoction used for washing and taken orally 51
Inflammatory swellings Covered on affected part after warming 51
Joint pain Powder taken 47
Malaria and intermittent fever Oral administration of fresh juice 46, 49 and 51
Body pain Paste applied after warming 51
Paralysis and sciatica Massaged after preparing decoction with sesame oil 47
Snake bite Oral administration of fresh juice 50
Ulcers, wounds, sores Powder orally administered or external application 47, 49 and 51
Flowers Health tonic Oral administration of powder 47
Cough Burnt to produce ash, then taken with honey 44
Rat bite Oral administration of powder 47 and 49
Dog/jackal bite (rabies) Seven tepals chewed with fine rice on seventh day of biting, continued for seven days decreasing one tepal everyday 44
Feet pain Decoction used for fomentation 46
Epilepsy Oral administration of paste with black pepper 46
Asthma and bronchitis Fruit taken with jaggery 3
Liver and spleen disorder Administered along with milk 46
Fruit Eye disorder Decanted ash water applied on eye lids 44
Anemia Mixed with same quantity of red chilli, mineral salt and taken with milk. 46
Whole plant Rheumatic pain and hyperacidity Paste directly taken 44
Young twigs Purgative Juice taken 54


4. Major milestone of Calotropis phytochemistry

Phytochemistry of Calotropis procera has always attracted the attention of researchers because despite its toxicity, it employs wide applications in traditional medicinal system till date. Dating back to 1936, Hesse et al.55 identified calotropin as the first compound from this plant. Further Hesse and his coworkers56,57 isolated heart poisons or cardiac glycosides namely calotropin, calotoxin, calactin, uscharin, voruscharin and uscharidin.58 Root powder of this plant is used in tribes to induce abortion in women and as an uterotonic since ancient period. Later it was found that it was due to the compound calotropin. Gupta et al.59 administered calotropin to gerbils and rabbits and observed reduction in spermatids count by 65% and 94% respectively.

In 1955, Rajagopalan et al.60 identified chemical constituents of seed viz. coroglaucigenin, corotoxigenin and frugoside (cardenolides). Later Bruschweiler et al.61 identified three additional cardenolides viz. uzarigenin, syriogenin and procerosid. A novel cardenolide, 2′′-oxovoruscharin was isolated from the root bark by Quaquebeke et al.62 and modified into its semisynthetic derivative, i.e., UNBS1450. Akhtar and Malik63 isolated a new cardenolide named proceragenin from the hexane-insoluble fraction of C. procera.

A fascinating feature of the plant is its potential to curb Alzheimer's disease (AD), the most predominant root cause of dementia, a neurodegenerative disease. Its dried latex showed attenuation of β-amyloid deposition in mouse brain and cerebral protective activities.64 Hence, it is imperative to evaluate the mechanism of metabolites, so that it can lead to promising direction to search new scaffolds for AD treatment. In 2015, Mohamed et al. isolated three non-glycosidic cardenolides namely calactoprocin, procegenin A and procegenin B from the latex.65

A patent claimed that polar extract of C. procera showed anti-ulcerative colitis activity in dose-dependent manner in a subject mammal and was found to be more effective than the standard drug Prednisolone.66

5. Pharmacology

Over the last many years, researchers have carried out numerable pharmacological activities, which are summarized in Table 2.
Table 2 Brief summary of the pharmacological properties
S. no. Pharmacological activities Parts/extracts/possible chemical constituents References
1 Wound healing potential Latex: aqueous extract 67
Latex 68
Bark: ethanolic extract 69
Leaves: aqueous extract 70
Bark: aqueous extract 71
2 Anticoccidial activity Dried leaves powder 72
3 Toxicity activity Leaves: aqueous extract 73 and 74
Leaves and stem bark extracts 75
Leaves and stem: ethanolic extract 29
Leaves: ethanolic extract 79
4 Biopesticidal/insecticidal activity Leaves: extract 80 and 81
Leaves: methanolic extract, latex protein fraction, flavonoids (quercetin-3-O-rutinoside) 35
5 Antimycoplasmal activity Leaves: acetone extract 82
6 Hepatoprotective activity Root bark: methanolic extract 83
Flowers: hydroethanolic extract 84
Roots: chloroform extract 85
7 Antimicrobial/antibacterial activity Leaves: methanolic extract, flavonoids (quercetin-3-O-rutinoside) 86
Leaves and latex: ethanol, aqueous, and chloroform extract 87
Leaves and stem: aqueous, ethanolic, methanolic extract 88 and 89
Endophytic fungi of C. procera 90
Seeds: chloroform extract 91
Root: pet. ether, methanolic extract 92
Flowers: ethanolic extract 93
Latex 94
Leaves: methanolic extract 95
Leaves, flower, root bark: ethanolic extract 96
Leaves and latex: aqueous, ethanolic extract 97 and 98
Leaves: aqueous, methanolic extract 99
Latex: aqueous extract 78
8 Central nervous system activity Latex proteins 100
9 Antioxidant activity Leaves, flower, fruit, latex 101
Leaves: aqueous, methanolic extract, quercetin and its derivatives 76
Leaves: aqueous and methanolic extract 102
Leaves, flowers and fruits: methanolic extract 103
Bark: ethanolic extract 69
10 Antinociceptive activity Latex protein 104
11 Antihelmintic activity Flowers: crude powder, aqueous and methanolic extract 105
Latex: fresh, dried aqueous extract 106 and 107
12 Antiinflammatory activity Dry latex 108 and 109
Stem bark: chloroform and hydro-alcoholic extract 110
Latex: hexane, dichloromethane, ethyl acetate, n-butanol and aqueous extract 77
Latex: pet. ether, acetone, methanol extract 111
Leaves: aqueous extract 112
Flowers: ethanolic extract 93
13 Antidiarroheal activity Bark: Arkamula Tvarka (Ayurvedic preparation) 45
Latex 113
14 Antifungal activity Aqueous bark extract 114
Leaves: aqueous, methanol, acetone and ethanol extract 115
Root bark 116
Antimycotic activity against dermatophytes Latex 117
Antimycofloral activity (fungi in wheat) Fresh latex 118
15 Larvicidal activity Crude latex and ethanolic extract of leaf 119
Leaves: ethanolic extract 120
Leaves: aqueous extract 121
Flower, young bud, mature leaves and stems: ethanolic extract 122
Flowers: aqueous extract 123
16 Tobacco mosaic virus (TMV) inhibitor activity Latex 124
17 Antifertility activity Ethanolic extract of roots 125
Leaves: ethanolic extract 79
Roots (calotropin) 59
Abortifacient activity Latex 126
Antisperm activity Root: chloroform extract 127
Oestrogenic/antiovulatory activity Roots: ethanolic and aqueous extract 128
18 Plasma clotting activity Protein fraction isolated from fresh latex 129
19 Antiplasmodial activity Different plant parts: ethyl acetate, ethanolic and acetone extract 130
Leaves extract 131
20 Antipyretic activity Dry latex: aqueous extract 132
Flowers: ethanolic extract 93
21 Antiasthmatic activity Flowers 133
22 Anticonvulsant activity Root extracts 134
23 Cytotoxic activity Root (2′′-oxovoruscharin) 62
Laticifer proteins (LP) recovered from latex 135
Root: methanolic, aqueous, ethyl acetate, hexane extracts 136
Plant: methanolic extract 137
Stems: uzarigenin 138
Root bark: calotroprocerol A 139
Root: alcoholic, hydro-aqueous and aqueous 140
Leaf: ethanolic extract 149
24 Analgesic activity Flowers: Ethanolic extract 93
25. Antihyperglycemic activity Leaves: pet ether, methanol and aqueous extracts 141
26 Antiarthritis activity Latex 142
Protein sub fraction of latex 143
27 Antimolluscicidal activity Latex: 95% aqueous ethanol (uscharin) 144
28 Antitermites activity Latex 145
29 Antimigraine activity Dried terminal leaves 146
30 Anti-ulcer activity Root: chloroform extract 147
Plant: 50% ethanolic extract 148
Leaf: ethanolic extract 149
Stem bark: chloroform and hydroalcoholic extract 110
31 Spasmolytic activity Plant: aqueous extract 150
32 Allelopathic activity Leaves: aqueous extract 151
33 Anti-keloidal activity Latex 68
34 Anti-hyperbilirubinemic activity Leaves: aqueous extract 70
35 Antiapoptotic activity Latex 152


The details enumerated in the Table 2 is indicative of the fact that the different plant parts demonstrate large number of pharmacological activities. Moreover, maximum number of activities were conducted at extract level, therefore horizons for further research is still bright, wherein the active principle constituents responsible for the activities may be identified. Here some of the very vital biological activites are being discussed in detail.

5.1 Cytotoxic potential

Various phytoconstituents and plant extracts were examined for their in vitro anticancer potential on various cancer cell lines, and showed significant cytotoxic activities as summarized in Table 3.
Table 3 Summary of cytotoxic studies of C. procera
C. procera: plant part/chemical constituent Cancer cell lines/model Method of analysis/assay Mechanism of action/investigation Observation References
Uscharin and its derivatives Lung cancer (A549) MTT colorimetric assay, intraperitoneal (ip) injection-related toxicity Na+/K+-ATPase inhibition activity Cardenolides derived from 2′′-oxovoruscharin exhibited significant in vitro antitumor activity and high in vivo tolerance 62
2′′-Oxovoruscharin and its derivatives Two glioblastoma (Hs683, U373) and two colon cancer (HCT-15 and LoVo)
Laticifer proteins (LP) recovered from latex HL60 (promoyelocytic leukemia), HCT-8 (colon), MDA-MB-435(breast), SF-295(brain) 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide MTT LP is a target for DNA topoisomerase I triggering apoptosis in cancer cell lines IC50 values for LP ranged from 0.42 to 1.36 μg mL−1 to SF-295, MDA-MB-435 respectively 135
Root: methanolic, aqueous, ethyl acetate, hexane extracts (1, 5, 10, 25 μg mL−1) Human Hep 2 Tetrazolium bromide (MTT), colorimetry Treatment initiated apoptotic mechanism by blocking the cell cycle at S-phase and thus preventing cells from entering proliferative (G2/M) phase Ethyl acetate extract showed strongest cytotoxic effect 136
Plant: methanolic extract (0, 5, 10, 20 and 40 μg mL−1) Human skin melanoma cells (SK-MEL-2) Annexin-V FITC flow cytometry method, MTS assay Methanolic extract induced apoptosis as shown by the accumulation of cells in the G2/M phase and the decrease of cell percentage in the G0/G1 phase At 40 μg mL−1 late apoptotic cell percentage was increased up to 80%. C. procera exerted cytotoxic potential 137
5-Hydroxy-3,7-dimethoxyflavone-4-O-β-glucopyranoside; uzarigenin; β-anhydroepidigitoxigenin; 2β,19-epoxy-3β,14β-dihydroxy-19-methoxy-5α-card-20(22)-enolide; β-anhydroepidigitoxigenin-3β-O-glucopyranoside HT 29, HepG2 (human cancer cell lines), NIH-3T3 (mouse fibroblast cell line) CellTiter-Blue® cell viability assay Uzarigenin showed moderate cytotoxicity 138
Calotroprocerol A; calotroproceryl acetate A; calotroprocerone A, B; pseudo-taraxasterol acetate; taraxasterol; calotropursenyl acetate B; stigmasterol; (E)-octadec-7-enoic acid A549 non-small cell lung cancer (NSCLC), the U373 glioblastoma (GBM) and the PC-3 prostate cancer cell lines 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay Growth inhibition action Calotroprocerol A exhibited in vitro growth inhibitory activity in all the three cancer cell lines with effects comparable to those of cisplatin and carboplatin 139
Calotroposide H; calotroposide I; calotroposide J; calotroposide K; Calotroposide L; calotroposide M; calotroposide N A549 non-small cell lung cancer (NSCLC), U373 glioblastoma (GBM), and PC-3 prostate cancer cell lines MTT colorimetric assay Calotroposide K and M exhibited subnanomolar growth inhibition activity with IC50 ranging from 0.5 to 0.7 μM against U373 glioblastoma (GBM) and PC-3 prostate cancer cell lines C. procera exhibited cytotoxic potential 153
Calotroposide S PC-3 prostate cancer, A549 non-small cell lung cancer (NSCLC), and U373 glioblastoma (GBM) cell lines MTT colorimetric assay Calotroposide S showed potent anti proliferative activity C. procera exerted anti-proliferative activity 154
Latex: hexane, chloroform, ethyl acetate and aqueous extract. Calactin; 15β-hydroxy calactin; afroside; uscharin; 15β-hydroxy uscharin; calotoxin; 12β-hydroxycoroglaucigenin; afrogenin; calactoprocin; procegenin A; procegenin B A549 (lung) and hela (cervix) cancer cell lines using cisplatin as a positive control MTT colorimetric assay Growth inhibition action Highest cytotoxic activity was displayed by chloroform extract. Amongst isolated compounds, calactin displayed highest cytotoxic activity 65
Root: alcoholic, hydro-aqueous and aqueous extracts(10 μg mL−1, 30 μg mL−1, 100 μg mL−1) Human oral (KB) and central nervous system (SNB-78) cancer cell lines Sulforhodamine-B (SRB) assay Alcoholic extract showed significant growth inhibition action C. procera roots exhibited in vitro cytotoxicity against oral and CNS human cancer cell lines 140


Over past decade, cytotoxic activities of various extracts and chemical constituents of C. procera have been carried out. Majority of studies were conducted on various cancer cell line models in vitro, except the one conducted using UNBS1450. UNBS1450, a semi-synthesized cardenolide was compared to reference anticancer agents and classic cardenolides in prostate cancer cell line in vitro and in vivo following s.c. (subcutaneous) and orthotopic prostate cancer cell grafting into mice; it was found to be more effective than tested reference compounds, such as mitoxantrone, taxol, oxaliplatin, irinotecan and temozolomide and less toxic than cardenolides.155,156 Mechanism of UNBS1450 was studied and proven to be a potent sodium pump inhibitor as it inhibits NF-kB transactivation and triggers apoptosis by recruitment of pro-apoptotic Bak and Bax protein thereby leading to cell death.157,158 Carrying out further in vivo studies will play a crucial role in ascertaining the safer use of UNBS1450. Therefore, further studies are necessary to obtain the clinically important lead molecules for the development of potent anticancer drugs.

5.2 Wound healing potential

C. procera has folk medicinal reputation as a wound healing agent. In vivo studies proved its wound healing potential as summarized in Table 4.
Table 4 Summary of in vivo studies of wound healing potential of C. procera
Model C. procera extract/dose/duration Negative control Investigation Result References
Guinea pigs 20 mL of 1.0% sterile solution of the latex twice daily for 7 days Excision wounds Wounds exhibited marked dryness, no visual sign of inflammation Significant prohealing property 67
Male albino-Wistar rats Ethanolic extract of bark (50 mg per wound) Incision and excision wounds Extract demonstrated wound healing effect by accelerating wound closure and epithelialization Excellent dermal wound healing potential 69
Wistar rats Aqueous extract of C. procera (25 mg and 50 mg kg−1) Incision and excision wounds Significant (P < 0.05) increase in breaking strength and percentage wound contractions with decreased epithelization period was observed Significant wound healing property 70


These data strongly support its ethnomedicinal use in wound healing potential and skin problems. In vivo screening showed considerable results in dose-dependent manner when compared to positive controls. A future perspective of studying the side effects and toxicity of the extracts at the dose level can also be unravelled.

5.3 Anti-inflammatory potential

Anti-inflammatory potential of extracts from C. procera have been summarized in Table 5.
Table 5 Summary of in vivo anti-inflammatory potential of C. procera
Model C. procera extract/dose/duration Negative control Investigation Result References
Male albino rats and albino guinea pigs 50 mg, 200 mg 500 mg and 1 g kg−1 dry latex Carrageenan-induced oedema test, cotton pellet granuloma and vascular permeability etc. Dry latex suppressed fluid exudation, due to its influence on vascular permeability and also delayed the onset and intensity of UV induced erythema Significant anti-inflammatory potential 108
Male albino rats Dry latex Carrageenin and formalin-induced pedal oedema test At dose 5 mg per rat, showed 71% inhibition in the case of the carrageenin-induced oedema (P < 0.005) and 32% inhibition for the formalin-induced oedema (P < 0.05). At higher dose (50 mg per rat), 96% and 98%, for carrageenin- and formalin-induced oedema groups respectively Potent anti-inflam-matory activity 109
Albino rats of either sex Stem bark: chloroform and hydro-alcoholic extract Carrageenan-induced paw oedema Significant reduction in the inflammation at 100, 200 and 400 mg kg−1 displayed by chloroform extract Significant anti-inflammatory potential 110
Male Wistar rats Dry latex: petroleum ether, acetone, methanol and aqueous extracts (50 mg per rat) Carrageenan induced paw oedema Maximum anti-inflammatory effect (59% and 53% inhibition) by the aqueous and acetone extracts respectively compared to (63%) inhibition exhibited by phenylbutazone Latex of C. procera exerted anti-inflammatory property 111
Male Wistar rats Crude latex: hexane, dichloromethane, ethyl acetate, n-butanol and aqueous fractions (1.0, 5.0 or 10.0 mg kg−1 and 0.2 mL) Carrageenan-induced peritonitis Dichloromethane, ethyl acetate, and aqueous fractions inhibited carrageenan-induced neutrophil migration in rats at the ratios 67%, 56%, and 72%, respectively Latex of C. procera possess anti-inflammatory property 77


On the basis of studies mentioned in Table 5, it can be concluded that the anti-inflammatory effect of dry latex needs to be further characterized as well as the nature of active principle leads responsible for anti-inflammatory activity remains to be identified.

5.4 Larvicidal/insecticidal potential

Aqueous and ethanolic extracts of leaves and other parts of C. procera showed significant larvicidal activities against various vector species as summarized in Table 6.
Table 6 Summary of larvicidal potential of C. procera
Vector species C. procera extract/dose/duration Observation Result References
Culex quinquefasciatus 3rd instar larvae Crude latex and ethanolic extract of leaves 100% larval mortality at 300 ppm concentration of latex and at 1000 ppm concentration of ethanolic leaf extract. LC50 values of the latex and ethanolic leaves extract were 57.3 and 388.7 ppm respectively Crude latex exerted stronger larvicidal potential than ethanolic extract 119
Musca domestica 3rd instar larvae Ethanolic extract of leaves (500 mg L−1) 100% mortality at 500 ppm. LC50 value of the extract 282.5 ppm Leaves exerted insecticidal potential 120
Anopheles arabiensis and Culex quinquefasciatus 2nd, 3rd, 4th instar larvae Aqueous extract of leaves (1000, 500, 200 ppm) LC50 value 273.53, 366.44, 454.99 ppm for 2nd, 3rd and 4th instar larvae Leaves showed oviposition deterrent, larvicidal and adult emergence activity 121
Anopheles stephansi 3rd instar larvae Ethanolic extracts of different parts viz. flower, young bud, mature leaves and stems (100 to 5000 ppm) Mature leaves extract exhibited 100% mortality at 2000 ppm after 48 hours of incubation Mature leaves showed high larvicidal activity against tested larvae 122
Culex species 4th instar Aqueous extract of flowers (1%, 2.5% and 5%)/24 h At 1% concentration, the mortality rate was 0%, 60% and 100% and at 2.5% concentration, mortality rate was 20%, 80% and 100% at the end of 1, 3 and 4 days of exposure, and at 5% concentration, 100% mortality was recorded at the end of third day Flowers exhibited remarkable larvicidal properties against the pupae and late 4th instar larvae of Culex sp. 123


Above studies indicated that aqueous and ethanolic extracts of leaves of C. procera possessed phenomenal oviposition deterrent and larvicidal effect, thus it can be developed as environment friendly alternative for the synthetic insecticides for mosquito control.

5.5 Anthelmintic potential

C. procera is used as an anthelmintic by ruminant farmers as proved by activities summarized in Table 7.
Table 7 Summary of in vivo and in vitro studies of anthelmintic potential of C. procera
Model C. procera extract/dose Compared with drug Observation Result References
In vivo: sheep infected with mixed species of nematodes in vitro: Haemonchus contortus Crude powder (CP), crude aqueous (CAE) and crude methanolic extracts (CME) Levamisole 88.4%, 77.8% and 20.9% reduction in egg count percent for CAE, CP and CME respectively Aqueous extract of C. procera has good anthelmintic potential 105
Earthworms Aqueous extract of dry latex (5, 10, 50 and 100 mg mL−1) and fresh latex (1.45, 7.25, 29, 72.5 and 145 mg mL−1) Piperazine At 5 to 10 mg mL−1 concentration paralysis at 90 min, at 100 mg mL−1 death within 60 min. Fresh latex also showed dose-dependent paralysis Latex showed wormicidal activity, hence can be used as an anthelmintic agent 106


5.6 Antioxidant potential

Leaves of C. procera displayed highest antiradical activity as evident from activities summarized in Table 8.
Table 8 Summary of in vitro studies of antioxidant potential of C. procera
C. procera part Extract/dose/duration Investigation Result References
Leaves, fruits, flowers and latex Methanolic solution of dried extract DPPH radical scavenging assay Leaves exhibited maximum DPPH radical scavenging activity with IC50 = 0.18 mg mL−1, whereas latex showed minimum activity with IC50 = 0.42 mg mL−1 101
Leaves Aqueous and methanolic extract (1, 5, 10, 50, 100 and 500 μg mL−1) DPPH radical scavenging assay IC50 of the methanol extract was 110.25 μg mL−1, the aqueous extract showed mild antioxidant activity 102
Leaves 2–100 mg mL−1 for quercetin in methanol and 20–100 mg mL−1 for AME and quercetin derivatives with different methoxy substitution DPPH radical scavenging assay Varying degrees of antioxidant activity was exerted by quercetin derivatives, but quercetin was found to be most active 76
Leaves, flowers and fruits Methanolic extracts of the samples of different concentrations (100–1000 ppm) DPPH radical scavenging assay IC50 values in leaves, fruits and flowers were 16.08, 16.06 and 10.31 μg mL−1 respectively, showing strong antioxidant activity of C. procera 103


Above activities proved that quercetin, aqueous and methanolic extracts of leaves of C. procera possessed remarkable antiradical activity. Evaluation of the in vivo antioxidant potential would be indispensable, so that it can be used as natural antioxidant ingredients in food and drug industries.

5.7 Antiplasmodial potential

Traditional practitioners use C. procera as antimalarial agent. Activity summarized in Table 9.
Table 9 Summary of in vitro schizontocidal activity of C. procera
Model C. procera extract/dose Investigation Result References
Chloroquine sensitive strain, MRC 20 and a chloroquine resistant strain, MRC 76 of Plasmodium falciparum Ethyl acetate, acetone, methanol fractions of flower, bud, root: (62–125 mg mL−1) Percentage inhibition varied from 7.51 to 61.38% between the various fractions against MRC 20 and for MRC 76, percentage inhibition varied from 3.437 to 41.08% between the various fractions At the lower dose range, the root extracts of C. procera found to be the most effective for both P. falciparum MRC 20 and MRC 76. Hence, C. procera exerted antiplasmodial potential 130


Over past decades, reduction in efficiency of chloroquine has been observed, thus resistivity to antimalarial drugs can be a threat to control malaria. The hunt for analogues with reduced toxicity and improved antimalarial activity still prevails. The possibilities of finding active compounds and correlating with specific dose effective antimalarial activity, from those parts of the plant, which are used separately or together could be further pursued.

5.8 Hepatoprotective activity

In vivo experimental study proves that C. procera has hepatoprotective potential as summarized in Table 10.
Table 10 Summary of in vivo hepatoprotective potential of C. procera
Model C. procera extract/dose Negative control Investigation Result References
Albino rats of either sex Methanol extract (MCP) of root and its sub fractions viz. hexane (HCP), ethyl acetate (ECP) and chloroform (CCP) (200 mg kg−1) Carbon tetra chloride MCP and its sub fractions HCP, ECP displayed hepatoprotective effect by reducing the elevated serum levels of, serum glutamic pyruvic transaminase, alkaline phosphatase and serum glutamic oxaloacetic transaminase, it increased high density lipoprotein. CCP does not show effective results C. procera exerted hepatoprotective potential 83
Wistar rats of either sex Hydro-ethanolic extract of C. procera flowers (200 mg kg−1 and 400 mg kg−1) Paracetamol-induced hepatitis Improvement in the hepatic architecture was observed C. procera flowers have hepatoprotective effect 84


5.9 Miscellaneous activities

Antiapoptotic activity of latex of C. procera was carried out by Sayed et al. (2016) on catfishes exposed to (100 μg L−1) 4-nonylphenol as chemical pollutant. Significant (P < 0.05) decrease in apoptotic cells, enzymes (superoxidase dismutase, acetylcholinesterase cortisol etc.) and ions validified antiapoptotic activity of the crude latex against the toxicity of 4-nonylphenol.152 Hence, crude latex exerted antiapoptotic activities against the toxicity of 4-nonylphenol.

Anti-hyperbilirubinemic activity of leaves was evaluated using phenylhydrazine and paracetamol induced Wistar rats. Significant (P < 0.05) decrease in concentrations of serum total bilirubin in hyperbilirubinemic rats proved bilirubin lowering activity of aqueous extracts of C. procera.70

Recent studies indicated that C. procera has significantly broader range of beneficial effects as it contains bioactive phytochemicals with therapeutic potential. By far only cytotoxic studies on cancer cell lines have been well established in clinical trials, whereas other activities have been evidenced by basic studies. Most of the studies are limited to in vitro studies which lack exploration of molecular mechanism of action. Therefore, mechanism based in vitro and in vivo studies should be carried out, which can lead to understanding of underlying mechanism related to traditional uses.

6. Phytochemistry

C. procera contains cardenolides, flavonoids, sterols, oxypregnanes triterpenoids, glycosides and other constituents as elaborated in Table 11.7 Flavonoid and its glycosides (Fig. 1) are the major compounds isolated from the leaves of C. procera. Steroids (Fig. 2) and cardenolides (Fig. 3) are the major secondary metabolites found in the latex. Cardenolides have also been reported from other plant genera of the family Apocynaceae or Asclepiadaceae like Strophanthus, Cerbera, Apocynum, Nerium, and Thevetia.159 Traditionally they are employed in curing of congestive heart failure.160 Cardenolides are C23 steroids with steroid nucleus having a glycoside moiety at C-3 and a lactone moiety at C-17.6 Cardiac glycosides can be novel antineoplastic agents as cancer cells are more prone to these compounds.159 Terpenoids (ursane, olenane type and pentacyclic triterpenes etc.) (Fig. 4) have been isolated from flowers, root bark and latex. Oxypregnane glycosides (Fig. 5) have recently been reported from root bark of this plant.153,154 They have steroidal skeleton containing a 2-deoxy sugar moiety. These oxypregnanes have benzoyl moiety at C-12 and a straight 5–7 units sugar chain connected to C-3 of the aglycone.6 Some glycosides (Fig. 6), lignan glycosides (Fig. 7), terpene glycosides (Fig. 8) and caffeic acid derivatives (Fig. 9) have also been isolated from this plant.
image file: d1ra06703f-f1.tif
Fig. 1 Chemical structures of flavonoids.

image file: d1ra06703f-f2.tif
Fig. 2 Chemical structures of steroids.

image file: d1ra06703f-f3.tif
Fig. 3 Chemical structures of cardenolides.

image file: d1ra06703f-f4.tif
Fig. 4 Chemical structures of terpenoids.

image file: d1ra06703f-f5.tif
Fig. 5 Chemical structures of oxypregnanes.

image file: d1ra06703f-f6.tif
Fig. 6 Chemical structures of glycosides.

image file: d1ra06703f-f7.tif
Fig. 7 Chemical structures of lignan glycosides.

image file: d1ra06703f-f8.tif
Fig. 8 Chemical structures of terpene glycosides.

image file: d1ra06703f-f9.tif
Fig. 9 Chemical structures of caffeic acid derivatives.

A number of hydrocarbons, saturated and unsaturated fatty acids were also identified from C. procera extract by GC-MS.161,162 Similarly fatty acid ester, phthalate derivatives, and pentacyclic triterpenes were identified from chloroform extract of roots of Calotropis procera.163

Table 11 Compounds isolated from Calotropis procera
S. No. Compound name (molecular formula) Extract/fraction Eluent Plant part & references
Flavonoids
1 5-Hydroxy-3,7-dimethoxyflavone-4′-O-β-glucopyranoside (C23H24O11) Ethanolic extract Benzene-chloroform Stem138
2 Isorhamnetin 3-O-β-D-rutinoside (C28H32O16) 85% methanolic extract 10–40% methanol Leaves76,164
3 Isorhamnetin 3-O-β-D-robinoside (C28H32O16) 85% methanolic extract 10–40% methanol Leaves76,164
4 Isoquercitrin (C21H20O12) 85% methanolic extract 70% methanol Leaves76
5 Quercetagetin-6-methyl ether 3-O-β-D-4C1-galacturonopyranoside (C22H20O14) 85% methanolic extract 40–60% methanol Leaves76
6 Quercetin (C15H10O7) 85% methanolic extract 80% methanol Leaves76
7 Isorhamnetin (C16H12O7) 85% methanolic extract 80% methanol Leaves76
8 Azaleatin (C16H12O7) 85% methanolic extract 80% methanol Leaves76
9 3,3′-Dimethoxy quercetin (C17H14O7) 85% methanolic extract 50–60% ethyl acetate Leaves76
10 3,6,3′,4′-Tetramethoxy quercetin (C18H16O7) 85% methanolic extract 50–60% ethyl acetate Leaves76
11 3,6,7,3′,4′-Pentamethoxy quercetin (C19H18O7) 85% methanolic extract 60–100% ethyl acetate Leaves76
12 Kaempferol-3-O-rutinoside (C27H30O15) Methanolic extract Ethyl acetate[thin space (1/6-em)]:[thin space (1/6-em)]water[thin space (1/6-em)]:[thin space (1/6-em)]formic acid[thin space (1/6-em)]:[thin space (1/6-em)]glacial acetic acid (100[thin space (1/6-em)]:[thin space (1/6-em)]26[thin space (1/6-em)]:[thin space (1/6-em)]11[thin space (1/6-em)]:[thin space (1/6-em)]11, v/v) Leaves86
13 Quercetin-3-O-rutinoside (C27H30O16) Methanolic extract Ethyl acetate[thin space (1/6-em)]:[thin space (1/6-em)]water[thin space (1/6-em)]:[thin space (1/6-em)]formic acid[thin space (1/6-em)]:[thin space (1/6-em)]glacial acetic acid (100[thin space (1/6-em)]:[thin space (1/6-em)]26[thin space (1/6-em)]:[thin space (1/6-em)]11[thin space (1/6-em)]:[thin space (1/6-em)]11, v/v) Leaves86
14 Luteolin (C15H10O6) Ethanol–water extract (60[thin space (1/6-em)]:[thin space (1/6-em)]40)/butanol fraction n-Hexane–acetone (70[thin space (1/6-em)]:[thin space (1/6-em)]30) Stem bark165
15 Epicatechin (C15H14O6) Ethanol–water extract (60[thin space (1/6-em)]:[thin space (1/6-em)]40)/butanol fraction n-Hexane–acetone (60[thin space (1/6-em)]:[thin space (1/6-em)]40) Stem bark165
16 Kaempferol 3-O-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (C27H30O15) Ethanolic extract Water–methanol (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Fruits149
[thin space (1/6-em)]
Steroids
17 Stigmasterol (C29H48O) Methanolic extract/hexane fraction Hexane–ethyl acetate Flowers,166 root bark,139 latex167
18 β-Sitosterol (C29H50O) Ethanolic extract/chloroform fraction Hexane–ethyl acetate Flowers,166 latex,167 aerial part168
19 Daucosterol or β-sitosterol glucoside (C35H60O6) Ethanolic extract/chloroform fraction 10% aq. methanol and hexane Latex, aerial part,168 roots169
20 Benzoyllineolone (C28H36O6) Ether extract/chloroform fraction Benzene–chloroform Root bark170
21 Benzoylisolineolone (C28H36O6) Ether extract/chloroform fraction Benzene–chloroform Root bark170
22 Lineolone (C21H32O5) Ether extract Root bark170
23 Isolineolone (C21H32O5) Ether extract Root bark170
24 Cyclosadol (C31H52O) Methanolic extract Flowers166
25 β-Sitost-4-en-3-one (C29H48O) Methanolic extract n-Hexane–ethyl acetate (95[thin space (1/6-em)]:[thin space (1/6-em)]5) Flowers166
[thin space (1/6-em)]
Steroids[thin space (1/6-em)]:[thin space (1/6-em)]cardenolides
26 Calactin (C29H40O9) Ethanolic extract/chloroform fraction 10% aq. methanol and hexane Roots,62 latex,65 aerial part168
27 15β-Hydroxycalactin (C29H40O10) Ethanolic extract/chloroform fraction Latex65
28 Calactoprocin or 14β,15β-dihydroxy-19-oxo-2α,3β-[(2S,3S:4R,6R)-tetrahydro-3-hydroxy-4-methoxy-6-methyl-2H-pyran-2,3-diyl]bis(oxy)-5α-card-20(22)-enolide (3′β-methoxy-15β-hydroxy calactin) (C30H42O10) Ethanolic extract/chloroform fraction Latex65
29 Afroside (C29H42O9) Ethanolic extract/chloroform fraction Latex65
30 Calotoxin (C29H40O10) Ethanolic extract/chloroform fraction Aerial part,168 latex65
31 Calotropin (C29H40O9) Ethanolic extract/chloroform fraction Root bark,62 latex and aerial part168
32 12β-Hydroxycoroglaucigenin (C23H34O6) Ethanolic extract/chloroform fraction Latex65
33 Procegenin A or 3α,12β,14β-trihydroxy-19-hydroxymethyl-5α-card-20(22)-enolide or 3-epi,12β-hydroxycoroglaucigenin (C23H34O6) Ethanolic extract/chloroform fraction Latex65
34 Procegenin B or 3α,12β,14β-trihydroxy-19-oxo-5α-card-20 (22)-enolide or 12β-hydroxy carpogenin (C23H32O6) Ethanolic extract/chloroform fraction Latex65
35 Afrogenin (C23H34O6) Ethanolic extract/chloroform fraction Latex65
36 Desglucouzarin (C29H44O9) Ethanolic extract/chloroform[thin space (1/6-em)]:[thin space (1/6-em)]ethyl acetate fraction Chloroform–methanol (9[thin space (1/6-em)]:[thin space (1/6-em)]1) Stem171
37 Frugoside (C29H44O9) Ethanolic extract/chloroform[thin space (1/6-em)]:[thin space (1/6-em)]ethyl acetate fraction Chloroform–methanol (9[thin space (1/6-em)]:[thin space (1/6-em)]1) Seeds,60 stem,171 root bark172
38 Uzarigenin (C23H34O4) Ethanolic extract/chloroform[thin space (1/6-em)]:[thin space (1/6-em)]ethyl acetate fraction Chloroform–methanol (9.5[thin space (1/6-em)]:[thin space (1/6-em)]0.5) Latex61
Stem168,171,173
39 Uzarigenone (C23H32O4) Ethanolic extract/benzene Chloroform–methanol (9.5[thin space (1/6-em)]:[thin space (1/6-em)]0.5) Stem171
40 β-Anhydroepidigitoxigenin-3β-O-glucopyranoside (C29H42O8) Ethanolic extract/benzene[thin space (1/6-em)]:[thin space (1/6-em)]chloroform Chloroform–methanol (9[thin space (1/6-em)]:[thin space (1/6-em)]1) Stem138
41 β-Anhydroepidigitoxigenin or 3β-hydroxy-5α-carda-14(15),20(22)-dienolide (C23H32O3) Ethanolic extract → benzene[thin space (1/6-em)]:[thin space (1/6-em)]chloroform Chloroform–methanol (9[thin space (1/6-em)]:[thin space (1/6-em)]2) Stem138
42 Calotropagenin (C23H32O6) Chloroform extract Hexane–diethyl ether (9[thin space (1/6-em)]:[thin space (1/6-em)]11) Aerial part174
43 Ischarin (C31H41NO8S) Ethanolic extract Chloroform Aerial part168
44 Ischaridin (C29H42O8) Ethanolic extract/10% aq. methanol and hexane fraction Chloroform–methanol (98[thin space (1/6-em)]:[thin space (1/6-em)]2) Aerial part168
45 2′′-Oxovoruscharin (C31H41NO9S) Methanolic extract Dichloromethane–methanol (98[thin space (1/6-em)]:[thin space (1/6-em)]2) Root bark62
46 Proceraside A (C31H44O10) Methanolic extract/ethyl acetate fraction Chloroform–methanol Root bark172
47 Syriogenin (C23H34O5) Methanolic extract Water–methanol Latex61
48 Proceroside (C29H40O10) Methanolic extract Water–methanol Latex61
49 Uscharidin (C29H38O9) Ethanolic extract Aerial part56
50 Voruscharin (C31H43NO8S) Methanolic extract Acetone–methanol (8[thin space (1/6-em)]:[thin space (1/6-em)]2) Roots62
51 Coroglaucigenin (C23H34O5) Chloroform extract Seeds60
52 Corotoxigenin (C23H32O5) Ether extract Seeds60
53 3-[β-(4-O-β-D-Glucopyranosyl-β-D-6-desoxyallopyranosyl)oxy]uzarigenin (C35H54O13) 70% ethanolic extract/benzene[thin space (1/6-em)]:[thin space (1/6-em)]chloroform Chloroform–methanol (9[thin space (1/6-em)]:[thin space (1/6-em)]1.5) Stem173
54 Uzarin or 3-[β-(2-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy] uzarigenin (C35H54O14) 70% ethanolic extract/benzene[thin space (1/6-em)]:[thin space (1/6-em)]chloroform Chloroform–methanol (9[thin space (1/6-em)]:[thin space (1/6-em)]2) Stem173
55 15β-Hydroxyuscharin (C31H41NO9S) Ethanolic extract Chloroform Latex65
56 Uscharin (C31H41NO8S) Methanolic extract Chloroform–methanol (70[thin space (1/6-em)]:[thin space (1/6-em)]30) Aerial part,168 latex65,168
57 Proceragenin or 7β,14β-dihydroxy-5α-card-20(22)-enolide (C23H34O4) Methanolic extract/chloroform fraction Hexane–chloroform (1[thin space (1/6-em)]:[thin space (1/6-em)]9) Aerial part63
58 2β,19-Epoxy-3β,14β-dihydroxy-19-methoxy-5-α-card-20(22)-enolide (C24H34O6) Ethanolic extract/benzene[thin space (1/6-em)]:[thin space (1/6-em)]chloroform fraction Chloroform–methanol (9[thin space (1/6-em)]:[thin space (1/6-em)]2) Stem138
59 Procesterol or (24S)-24-ethyl-stigmast-4-en-6α-ol-3-one (C29H48O2) Ethanolic extract/chloroform fraction Hexane–chloroform (3[thin space (1/6-em)]:[thin space (1/6-em)]2) Fresh and undried flowers176
[thin space (1/6-em)]
Terpenes/terpenoids
60 α-Amyrin (C30H50O) Methanolic extract/hexane[thin space (1/6-em)]:[thin space (1/6-em)]ethyl acetate gradients Dichloromethane–methanol (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Flowers176
61 β-Amyrin (C30H50O) Methanolic extract/hexane[thin space (1/6-em)]:[thin space (1/6-em)]ethyl acetate gradients Dichloromethane–methanol (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Flowers176
62 α-Amyrin acetate (C32H52O2) Methanolic extract Pet. ether–chloroform (1[thin space (1/6-em)]:[thin space (1/6-em)]9) Roots169
63 Procerursenyl acetate or urs-18α-H-12,20(30)-diene-3β-yl acetate (C32H50O2) Methanolic extract Pet. ether–chloroform (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots177
64 Calotropenyl acetate or urs-19(29)-3β-yl acetate (C32H52O2) Chloroform extract Benzene–hexane (60[thin space (1/6-em)]:[thin space (1/6-em)]40) Flower,175 latex and aerial part168
65 Calotropoleanyl ester or olean-13(18)-en-3β-yl acetate (C32H52O2) Ethanolic extract Pet. ether Root bark178
66 Calotroprocerol A or ursa-5,12,20(30)-trien-18αH-3β-ol (C30H46O) Methanolic extract n-Hexane–ethyl acetate Root bark139
67 Calotroproceryl acetate A or ursa-5,12,20(30)-trien-18αH-3β-yl acetate (C32H48O2) Methanolic extract n-Hexane–ethyl acetate Root bark139
68 Calotroprocerone A or ursa-5,12,20(30)-trien-18αH-3-one (C30H44O) Methanolic extract n-Hexane–ethyl acetate Root bark139
69 Calotroproceryl acetate B or ursa-5,12,20-trien-18αH-3β-yl acetate (C32H48O2) Methanolic extract n-Hexane–ethyl acetate Root bark139
70 Calotropursenyl acetate B or urs-12,19(29)-diene-3β-yl acetate (C32H50O2) Methanolic extract n-Hexane–ethyl acetate Root bark139,180
71 Pseudo-taraxasterol acetate (C32H52O2) Methanolic extract n-Hexane–ethyl acetate Root bark139
72 Taraxasterol (C30H50O) Methanolic extract n-Hexane–ethyl acetate Root bark139
73 Proceroleanenol A or olean-13(18)-en- 9α-ol (C30H50O) Ethanolic extract Benzene–chloroform Root bark178
74 Proceroleanenol B or olean-5,13(18)-dien-3α-ol (C30H48O) Ethanolic extract Benzene–chloroform (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Root bark178
75 Cycloart-23-ene-3β,25-diol (C30H50O2) Ethyl acetate extract Hexane–ethyl acetate (2[thin space (1/6-em)]:[thin space (1/6-em)]1) Flowers166
76 Lupeol (C30H50O) Ethanolic extract Latex179
77 3-epi-Moretenol (C30H50O) Ethanolic extract Latex179
78 Multiflorenol (C30H50O) Pet. ether fraction Chloroform–ethyl acetate (3[thin space (1/6-em)]:[thin space (1/6-em)]2) Flowers,166 latex167
79 Urs-19(29)-en-3-β-ol (C30H50O) Acetone fraction Pet. ether–acetone (8[thin space (1/6-em)]:[thin space (1/6-em)]2) Latex167
80 Calotropenyl acetate or urs-19(29)-en-3-yl acetate (C32H52O2) Pet. ether fraction Chloroform–ethyl acetate (3[thin space (1/6-em)]:[thin space (1/6-em)]5) Latex167
81 3β,27-Dihydroxy-urs-18-en-13,28-olide (C30H46O4) Ethyl acetate fraction Benzene–ethyl acetate (8[thin space (1/6-em)]:[thin space (1/6-em)]2) Latex167
82 Calotropfriedelenyl acetate or friedelin-1-ene-3 β-yl acetate (C32H52O2) Ethanolic extract Root bark180
83 Calotropterpenyl ester or 6,10,14-trimethylpentadec-6-enyl-2′,4′,8′,12′,16′-pentamethyl nonadecane ester (C42H82O2) Ethanolic extract Root bark180
84 Phytyl iso-octyl ether or 3,7,11,15-tetramethyl hexadecanyl-6′-methyl hept-5′-enyl ether (C28H56O) Methanolic extract Pet. ether–chloroform (1[thin space (1/6-em)]:[thin space (1/6-em)]3) Roots181
85 Dihydrophytoyl tetraglucoside or 3,7,11,15 tetramethylhexadecanoyl-β-D-glucopyranosyl-(2 → 1)-β-D-glucopyranosyl-(2 → 1)-β-D-glucopyranosyl (2 → 1)-β-D-glucofuranoside (C44H80O22) Methanolic extract Chloroform–methanol (3[thin space (1/6-em)]:[thin space (1/6-em)]2) Roots181
86 Procerasesterterpenoyl triglucoside or 2,6,10,14,18-pentamethylnonadecanoyl-β-D-glucopyranosyl-(2 → 1)-β-D-glucopyranosyl-(2 → 1)-β-D-glucopyranoside (C42H78O17) Methanolic extract Chloroform–methanol (3[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots181
87 Oleanolic acid (C30H48O3) Chloroform extract/butanol fraction Benzene–ethyl acetate (10[thin space (1/6-em)]:[thin space (1/6-em)]1–1[thin space (1/6-em)]:[thin space (1/6-em)]10) Stem bark165
88 Lupeol-3-O-acetate (C32H52O2) Ethanolic extract Chloroform–methanol (9.3[thin space (1/6-em)]:[thin space (1/6-em)]0.7) Leaves149
89 Proceraursenolide or 18-αH-urs-12-en-3,25-olide (C30H46O2) Ethanolic extract Pet. ether–chloroform (1[thin space (1/6-em)]:[thin space (1/6-em)]3) Roots183
[thin space (1/6-em)]
Oxypregnane oligoglycosides
90 Calotroposide H or 12-O-benzoylisolineolon-3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl (C63H96O21) Methanolic extract/n-butanol fraction Chloroform–methanol (85[thin space (1/6-em)]:[thin space (1/6-em)]15) Root bark153
91 Calotroposide I or 12-O-benzoylisolineolon-3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranosyl (C63H96O21) Methanolic extract/n-butanol fraction Chloroform–methanol (85[thin space (1/6-em)]:[thin space (1/6-em)]15) Root bark153
92 Calotroposide J or 12-O-benzoylisolineolon-3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranosyl-( 1 → 4)-β-D-cymaropyranosyl-(1 → 4)-(6-O-acetyl)-β-D- glucopyranoside (C71H108O27) Methanolic extract/n-butanol fraction Chloroform–methanol (85[thin space (1/6-em)]:[thin space (1/6-em)]15) Root bark153
93 Calotroposide K or 12-O-benzoylisolineolon-3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D- glucopyranoside (C69H106O26) Methanolic extract/n-butanol fraction Chloroform–methanol (85[thin space (1/6-em)]:[thin space (1/6-em)]15) Root bark153
94 Calotroposide L or 12-O-benzoylisolineolon-3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 4)-β-D-glucopyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranoside (C68H104O28) Methanolic extract/n-butanol fraction Chloroform–methanol (85[thin space (1/6-em)]:[thin space (1/6-em)]15) Root bark153
95 Calotroposide M or 12-O-benzoylisolineolon-3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranoside-(1 → 4)-(6-O-acetyl)-β-D-glucopyranoside (C78H120O30) Methanolic extract/n-butanol fraction Chloroform–methanol (85[thin space (1/6-em)]:[thin space (1/6-em)]15) Root bark153
96 Calotroposide N or 12-O-benzoylisolineolon-3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D- oleandropyranosyl-(1 → 4)-β-D-glucopyranoside-(1 → 4)-β-D-gluopyranoside (C75H116O31) Methanolic extract/n-butanol fraction Chloroform–methanol (85[thin space (1/6-em)]:[thin space (1/6-em)]15) Root bark153
97 Calotroposide S or 12-benzoylisolineolon-3-O-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-oleandropyranosyl-(1 → 4)-β-D-oleandro-pyranosyl-(1 → 4)-β-D-oleandropyranoside (C84H132O30) Methanolic extract/n-butanol fraction Chloroform–methanol (85[thin space (1/6-em)]:[thin space (1/6-em)]15) Root bark154
[thin space (1/6-em)]
Aliphatic and phenolic glycoside
98 Methyl resorcinyl triglycoside or O-methyl resorcinyl-β-D-glucuronopyranosyl (2 → 1)-β-D-glucopyranosyl-(2 → 1)-β-D-glucopyranoside (C25H36O18) (phenolic glycoside) Methanolic extract Chloroform–methanol (3[thin space (1/6-em)]:[thin space (1/6-em)]2) Roots169
99 Butanediol diglucuronoside or (n-butan-1,4-diol-1,4-β-D-diglucuronopyranoside) (C16H26O14) (aliphatic glycoside) Methanolic extract Chloroform–methanol (4[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots169
100 (E)-3-(4-Methoxyphenyl-2-O-β-D-4C1-glucopyranoside)-methyl propenoate (C17H22O9) 85% methanolic extract 40–60% aqueous methanol Leaves76
101 Methyl 4-O-β-D-glucopyranosyl ferulate (C17H22O9) Ethanolic extract Water–methanol (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Flowers149
[thin space (1/6-em)]
Lignan glycoside
102 7′-Methoxy-3′-O-demethyl-tanegool-9-O-β-D-glucopyranoside (C26H34O12) Ethanolic extract Water–methanol (6[thin space (1/6-em)]:[thin space (1/6-em)]4) Flowers149
103 Pinoresinol-4-O-glucoside (C26H32O11) Ethanolic extract Water–methanol (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Flowers149
104 Syringaresinol-4-O-glucoside (C28H36O13) Ethanolic extract Water–methanol (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Fruits149
[thin space (1/6-em)]
Terpene glycoside
105 Labdan-18-ol-β-D-galactofuranoside (C26H48O6) Methanolic extract Chloroform–methanol (9[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots182
106 Proceralabdanoside/labdan-3β-ol-11,15-olide-18,20-dioic acid-3β-D-galactofuranoside (C26H40O12) Methanolic extract Chloroform–methanol (9[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots182
[thin space (1/6-em)]
Caffeic acid derivatives
107 Methyl caffeate (C10H10O4) 85% methanolic extract 30–50% aqueous methanol Leaves76
108 Caffeic acid (C9H8O4) 85% methanolic extract 30–50% aqueous methanol Leaves76
109 Rosmarinic acid (C18H16O8) Ethanolic extract Chloroform–methanol (8.5[thin space (1/6-em)]:[thin space (1/6-em)]1.5) Flowers149
110 Methyl rosmarinate (C19H18O8) Ethanolic extract Chloroform–methanol (8.5[thin space (1/6-em)]:[thin space (1/6-em)]1.5) Flowers149
[thin space (1/6-em)]
Others
111 2-Propenyl-2Z-hydroxyethyl carbonate Leaves186
112 Glyceryl mono-oleolyl-2-phosphate (C21H41O7P) Methanolic extract Pet. ether–chloroform (1[thin space (1/6-em)]:[thin space (1/6-em)]3) Roots177
113 Methyl behenate (C23H46O2) Methanolic extract Chloroform–methanol (99[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots177
114 N-Dotriacont-6-ene (C32H64) Methanolic extract Pet. ether–chloroform (3[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots177
115 Methyl myrisate (C15H30O2) Methanolic extract Chloroform Roots177
116 Glyceryl-1,2-dicapriate-3-phosphate (C23H45O8P) Methanolic extract Chloroform–methanol (97[thin space (1/6-em)]:[thin space (1/6-em)]3) Roots177
117 (E)-Octadec-7-enoic acid (C18H34O2) Methanolic extract/n-hexane fraction n-Hexane–ethyl acetate Root bark139
118 Proceranol or n-triacontan-10β-ol (C30H62O) Methanolic extract Chloroform–methanol (99[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots177
119 Methyl ferulate Methanolic extract Chloroform–methanol (8.5[thin space (1/6-em)]:[thin space (1/6-em)]1.5) Flowers149
120 1,2-Dihexadecanoyl-3-phosphatyl glycerol (C35H69O8P) Methanolic extract Chloroform–methanol (99[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots181
121 n-Tetradecanyl palmitoleate/n-tetradecanyl n-hexadec-9-enoate (C30H58O2) Methanolic extract Pet. ether–chloroform (1[thin space (1/6-em)]:[thin space (1/6-em)]3) Roots183
122 Tricapryl glyceride (C33H62O6) Methanolic extract Pet. ether Roots183
123 Oleodipalmityl glyceride (C53H100O6) Methanolic extract Pet. ether–chloroform (9[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots183
124 Tribehenyl glyceride (C69H134O6) Methanolic extract Pet. ether–chloroform (1[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots183
125 Capryl glucoside/n-decanoyl-β-D-glucopyranoside (C16H31O7) Methanolic extract Chloroform–methanol (49[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots182
126 Palmityl glucoside/n-hexacosanoyl- β-D-glucopyranoside (C22H43O6) Methanolic extract Chloroform–methanol (19[thin space (1/6-em)]:[thin space (1/6-em)]1) Roots182
127 Stearyl glucoside/n-octadecanoyl-β-D-glucopyranoside (C24H47O7) Methanolic extract Chloroform–methanol (93[thin space (1/6-em)]:[thin space (1/6-em)]7) Roots182
128 n-Heptanoate/heptylate (C8H16O2) Ethanolic extract Hexane–chloroform Aerial part162
129 n-Octanoate/caprylate (C9H18O2) Ethanolic extract Hexane–chloroform Aerial part162
130 n-Nonanoate (C10H20O2) Ethanolic extract Hexane–chloroform Aerial part162
131 n-Tridecanoate/tridecylat (C14H28O2) Ethanolic extract Hexane–chloroform Aerial part162
132 n-Pentadecanoate/pantadecylate (C16H32O2) Ethanolic extract Hexane–chloroform Aerial part162
133 n-Hexadecanoate/palmitate (C16H34O2) Ethanolic extract Hexane–chloroform Aerial part162
134 n-Heptadecanoate/margorate (C18H36O2) Ethanolic extract Hexane–chloroform Aerial part162
135 Methyl nonanotetracnoate (C10H12O2) Ethanolic extract Hexane–chloroform Aerial part162
136 n-Decenoic acid (C10H18O2) Ethanolic extract Hexane–chloroform Aerial part162
137 9-Decenoate (C11H20O2) Ethanolic extract Hexane–chloroform Aerial part162
138 Undecadienoate (C12H20O2) Ethanolic extract Hexane–chloroform Aerial part162
139 9-Dodecenoate (C13H24O2) Ethanolic extract Hexane–chloroform Aerial part162
140 Tridecatrienoate (C14H22O2) Ethanolic extract Hexane–chloroform Aerial part162
141 2,4,5-Tetradecatrienoate (C15H24O2) Ethanolic extract Hexane–chloroform Aerial part162
142 Hiragonate (C17H28O2) Ethanolic extract Hexane–chloroform Aerial part162
143 Heptadecadienoate (C18H22O2) Ethanolic extract Hexane–chloroform Aerial part162
144 Heptadecenoate (C18H38O2) Ethanolic extract Hexane–chloroform Aerial part162
145 9-Eicosenoate/gadoleate (C21H40O2) Ethanolic extract Hexane–chloroform Aerial part162
146 Gallic acid (C7H6O5) Ethanolic extract HPLC analysis Aerial part184
147 Ferulic acid (C10H10O4) Ethanolic extract HPLC analysis Aerial part184
148 p-Coumaric acid (C9H8O3) Ethanolic extract HPLC analysis Aerial part184
149 Vanillic acid (C8H8O4) Ethanolic extract HPLC analysis Aerial part184
150 Rutin (C27H30O16) Ethanolic extract HPLC analysis Aerial part184
151 4-Hydroxy-4-methylpentan-2-one (C6H12O2) Acetone extract GC-MS analysis Latex161
152 2,3,4-Trimethylhexane (C9H20) Acetone extract GC-MS analysis Latex161
153 Decane (C10H22) Acetone extract GC-MS analysis Latex161
154 n-Pentadecane (C15H32) Acetone extract GC-MS analysis Latex161
155 2,6-Dimethyl tetra-1,5-decaene (C16H28) Acetone extract GC-MS analysis Latex161
156 n-Eicosane (C20H42) Acetone extract GC-MS analysis Latex161
157 3,7,11-Trimethyl-2,6,10,12-pentadecatrien-1-ol (C18H30O) Acetone extract GC-MS analysis Latex161
158 2,6,10,15,19,23-Hexamethyl-2,6,10,14,18,22-tetracosahexaene (C30H50) Acetone extract GC-MS analysis Latex161
159 1,3,5-Tri-isopropylbenzene (C15H24) Acetone extract GC-MS analysis Latex161
160 6,10,14-Trimethyl-pentadecanone-2 (C18H36O) Hexane extract GC-MS analysis Leaves185
161 9-Octadecenoic acid (Z)-(C18H34O) Hexane extract GC-MS analysis Leaves185
162 (6Z,9Z)-Pentadecadien-1-ol (C15H28O) Hexane extract GC-MS analysis Leaves185
163 Farnesol isomer (C15H26O) Hexane extract GC-MS analysis Leaves185
164 Tetratetracontane (C44H90) Hexane extract GC-MS analysis Leaves185
165 Ergost-5-en-3-ol (C28H48O) Hexane extract GC-MS analysis Leaves185


Apart from the compounds mentioned in Table 11, terpenoids named α-calotropeol and β-calotropeol have been isolated from ethanolic extract of latex.179 A cardenolide named 19-dihydrocalotropagenin and flavonoid named 3′-O-methyl-quercetin-3-O-rutinoside have also been reported from ethanolic extract of aerial parts.168

7. Conclusion, discussion and future perspectives

In the present review, the research progress in phytochemistry and pharmacology of C. procera have been summarized. There have been acquirements in the research; still some gaps came across our studies which are as follows:

(1) Folks and tribes have been using C. procera since ancient times; still investigations can be carried out on inception time of traditional uses of C. procera.

(2) Secondary metabolites of plant vary according to several factors like region, environment, quality of soil, age of plant etc. Moreover, latex and root bark seem to be exhaustively investigated for phytoconstituents, not much research on flowers, pods and seeds for phyoconstituentsis have been conducted. Further exploring these parts can lead to discovery of new phytoconsituents of interest.

(3) The plant can be employed commercially as scientific studies have proved its use as cheese making agent, dehairing of leather, natural surfactant, biopesticide and corrosion inhibitor.

(4) Numerous activities on validation of its cytotoxic and anti-inflammatory potential have been conducted. A few have been carried out on its antimigraine, antiplasmodial and anticonvulsant effects. Carrying out further scientific studies in these fields can provide medical science with effective and promising new drugs.

(5) Most of the cytotoxic activities conducted are in vitro except the one conducted on UNBS1450; a semi-synthesized cardenolide. Further studies should be carried out to examine its in vivo potential.

(6) Right route and right dose can convert a dreadful toxicant into an outstanding drug whereas even a drug in lack of proper dosage and route can become a fatal poison. Folk practitioners have been employing C. procera as antifertility and uterotonic agent. Further studies using positive controls, study of toxicity and side effects can lead to discovery of effective and natural contraceptive drugs.

(7) Active principles behind many of the activities are unknown, except the one known for cytotoxic, antibacterial, antifertility, antimolluscicidal and insecticidal activity. More research can be carried out to know the active principles so that potent drugs can be made.

(8) Replicable and environment benign sources of energy are the need of hour, Calotropis procera being rich source of various hydrocarbons, thus can prove to be a promising biofuel agent.

Overall, the pharmacology, toxicology, traditional uses, use of secondary metabolites, clinical trials and quality control has been reviewed in this paper. However, there seems to be a good correspondence between pharmacological activities and traditional uses. Further research in this field is essential to determine the active principles and the underlying mechanisms.

Author contributions

Barkha Darra Wadhwani: literature collection, evaluation and draft manuscript preparation. Deepak Mali and Pooja Vyas: literature collection: pharmacological activity and analyses of chemicals constituents of C. procera. Rashmy Nair: reviewing and editing. Poonam Khandelwal: concept development; idea generation; manuscript preparation; reviewing and editing.

Conflicts of interest

The authors confirm that this article content has no conflict of interest.

Acknowledgements

One of the authors (Barkha Darra Wadhwani) is thankful to DST, India for providing WOS-A project sanction no. SR/WOS-A/CS-24/2019(G).

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