INTRODUCTION

The Euphorbiaceae family, which includes more than 300 genera and 8000 species of flowering plants, includes the one Codiaeum variegatum (L.). Most of this family are herbs, shrubs, or trees that are generally found in tropical regions^1,2. This species of plant is indigenous to the tropical rainforests of the Philippines, Papua New Guinea, Australia, and the Moluccan Islands of Indonesia^3,4. Since it grows readily in many tropical and warm climates, Codiaeum variegatum has been introduced there⁵. Although it was initially brought to England in 1804, hybrids were primarily created in Belgium and France during the 1800s.

Because of its varied leaf patterns and colours, it has drawn a lot of interest from breeders, landscapers, horticulturists, and gardeners, leading to the development of several cultivars for commercial production. With more than 300 types available in the decorative horticulture market, Crotons are well-liked tropical ornamental plants in both Europe and the US. This plant is native to tropical rainforests in places like the Philippines, Papua New Guinea, Australia, and the Indonesian Moluccan Islands. It has been successfully introduced to other warm, tropical locations. First grown in England in 1804, crotons underwent significant hybridization in Belgium and France in the 1800s. The United States, especially South Florida, contributed to the development of several hybrids throughout the 1920s and 1930s.

Growing for its eye-catching foliage, Codiaeum variegatum, is a popular houseplant. It is not to be confused with Croton, another genus of more than 700 species in the same family, in which, it was previously mistakenly classified as Croton variegatum. It is one of six species of broadleaf evergreen perennials, shrubs, and small trees in this genus that are native to tropical Asia and the western Pacific region. The colour and design of the leaves on this evergreen shrub or small tree vary greatly, and several varieties have been created. Tender perennial, it is only hardy in zones 11–12. They are widely employed as landscape shrubs for striking hedges, eye-catching focal points in gardens, or potted specimens around in subtropical and tropical regions.

Although croton grows upto 10 feet tall in its natural habitat, houseplants often have considerably smaller branches than the wild species. The big, variable-length, leathery, thick leaves range in size from 2 to 12 inches. The glossy, alternating leaves can range in shape from linear to oval, with some having a wavy or spiral shape and others having a smooth or lobed edge that is occasionally severely cut to the midrib. As the leaves age, the colour of the foliage can vary, ranging from green to various combinations of white, pink, orange, red, yellow, or purple variegated with green. Markings can be blotches on any area of the leaf blade in a regular or haphazard pattern, or they can follow the main veins.

It seldom blossoms when houseplants are cultivated. It has tiny blooms in long axillary racemes in the spring when it grows in the ground in frost-free regions. Unlike the yellowish, petal fewer female flowers, the white male flowers have five tiny petals and 20–30 stamens that resemble a starburst. These blooms are produced on different inflorescences.

Fruits, a tiny tripartite capsule with three tiny seeds within that is approximately a third of an inch in diameter, follow pollinated female flowers. Usually sold as an indoor plant, croton may also be used outdoors in mixed decorative or annual plantings, or as a seasonal accent plant in pots. If cultivating in pots—either inside or outdoors—consider selecting a pot colour that complements the foliage's colour, either by contrasting with the predominant hue or by reflecting one of the leaf colours. Consider growing croton with other tropical annuals like orange-flowering lantana, yellow golden shrimp plant, or red pentas, whose blooms echo the colour(s) of the leaves. Alternatively go for a plant with purple blooms, such mealy cup sage or Angelonia, to contrast with a croton cultivar that has orange and red leaves.

Rich, wet soil that drains well is ideal for cacti growth. When cultivated indoors, they require bright, indirect light. When relocated from inside, they must initially adjust to full sun, but they perform well in partial shade outside and may withstand full sun in colder climes if kept wet. Increased light causes the leaves to have a more vivid colour and makes the plant smaller. Insufficient light can cause the vibrant leaves to turn back to shades of green, while excessive exposure to bright sunlight turns the leaves bland and grey. Watering these plants should only occur when the top half-inch to an inch of soil dries up because they have modest water demands. Cut back on wintertime irrigation. If a plant has prolonged periods of wetness or dryness, it will shed its leaves.

Croton prefers temperatures between 60- and 85-degrees Fahrenheit; if it stays below 50 degrees, it frequently has leaf drop. Keep them safe from harsh temperature changes and drafts. Plants that experience abrupt environmental changes may become shocked and lose leaves. During the growing season, fertilize once or twice, or more frequently if you desire rapid growth. When the plant outgrows its container, repot it in a pot that is only 1-2 inches bigger. If plants become lanky, they can be severely trimmed in the early spring before new growth starts to encourage branching and new development. Other than the typical insects that frequently infest houseplants, croton has minimal pest concerns.

Once temperatures are regularly above 50ºF, container-grown plants can be placed outside for the growth season. They should be progressively acclimated to the varying light levels outdoors before being brought back inside in the fall before temperatures dip below 50ºF, as this can result in leaf loss. In the fall, you can lift and pot up plants that were intended to be seasonal and planted in the ground. Softwood cuttings taken in the summer or air layering in the spring are two simple ways to grow this plant. It can be produced from seed, but the progeny will not look like the parents. Therefore, the only means of preserving certain cultivars is by asexual propagation.

DESCRIPTION OF CODIAEUM VARIEGATUM⁶

Scientific name: Codiaeum variegatum

Common name: Croton

Family: Euphorbiaceae

Plant type: Shrub

Planting month for zone 10 and 11: Year round

Uses: Hedge; border; mass planting; container or above-ground planter; suitable for growing indoors; accent; screen; attracts butterflies

Availability: Generally available in many areas within its hardiness range

The Euphorbiaceae, often known as purges, are woody, blooming, broadleaf evergreen shrubs that may grow up to 8 feet tall in their natural environment, which is limited to Malaysia, the Pacific islands, and northern Australia. These plants are more frequently cultivated indoors, where they may reach a height of three feet. The cultivated variations, called var. pictum, are grown for their beautiful, variegated foliage, although the wild form has glossy, green leaves. Depending on which of the many cultivars is cultivated, crotons' leaves can have a range of sizes, shapes, and colours. The Latinized form of the Ternate colloquial word, kodiho, is where the genus name originates. The term variegatum refers to the colour of the leaf; it implies variegated.

Crotons require well-drained, humus soil that is periodically dry, low to medium relative humidity, and full sun or moderate shade. Water them often in the spring and infrequently in the fall. If at all feasible, mist departs on a daily basis. In USDA Zones 11 and 12, they are easy to cultivate as an accent plant outside or as a houseplant inside in winter-hardy locations. For optimal leaf colour, the plants require strong light and some direct sunlight; excessive shadow might cause the lower leaves to drop off. When inside, consider standing the plant on a bed of damp stones to satisfy its humidity needs. Crotons benefit from a resting time from fall to late winter with less watering, but they do not require winter dormancy.

This evergreen shrub may reach a height of three meters when grown outdoors in its native habitat. As a result, it makes beautiful border plantings in gardens, similar to bushes or hedges. Indoors, they make an intriguing container plant that brightens a space when you can keep them at the right temperatures and humidity levels. However, the space must be well-lit and exposed to sunshine.

Appearance of Codiaeum variegatum⁷:

As previously said, variegated croton is cultivated mostly for its leaves rather than its blooms, which are considered too unappealing and unimportant. Depending on the cultivar, the leathery type leaves might vary in size and colour, but a grower can always expect intriguing hues to appear—they frequently change from green to a deep purple. The veins are clearly visible in these leaves.

Figure 1: Croton Plant (Codiaeum variegatum)

Flowering:

In its native habitat, the flowers bloom in little clusters of white and yellow blooms along a stem at different periods of the year. However, they are less likely to flower indoors.

Figure 2: Croton Plant Flowering)

Displaying:

Due of its size and requirement for intense light, croton is frequently cultivated within a greenhouse or conservatory. If you give it the right growing conditions—a lot of water, a windowsill facing east or west, a location free from drafts and with high humidity—it may also thrive elsewhere in your house.

Figure 3: Croton Plant

Poisonous:

This plant produces poisonous milky sap. There are several symptoms that can occur if children, dogs, or cats consume any components of this plant, including as nausea, vomiting, and diarrhoea. Wearing gloves is advised while handling the plant since the sap can irritate skin.

Figure 4: Milky white sap in Croton Plant

Botanical Profile^9,10,11:

A member of the Euphorbiaceae family is Codiaeum. It's a typical decorative plant that grows well in tropical and warm weather. This plant has several leaf types with variegation patterns that show sections, gradations, or shades of various colours, including pink, lavender, red, green, orange, yellow, and black. These leaves of Codiaeum variegatum vary even in their shape and colour. Also, they may vary from oval to linear. They can be twisted or wavy (Fig. 5).

The cultivars of C. variegatum were categorized into nine classes by the Croton society: small, extremely thin, recurved, interrupted, oak leaf, wide, spiral, semi-oak, narrow, tiny, and tiny leaf. To distinguish between these cultivars, a solid scientific foundation has to take into account a number of factors. Croton cultivars may be accurately defined using the leaf index, which is obtained by dividing leaf length by leaf index.

Variations in the tissue-level concentration of red pigment and chlorophyll can also be linked to changes in leaf colour and variegation patterns. Anthocyanidin, for instance, is a pigment that distinguishes red croton cultivars from green or yellow cultivars, suggesting possible variations in phytochemical content depending on leaf colour.

Furthermore, it is highly recommended that croton cultivars be accurately classified using genetic or molecular markers, as spontaneous somatic mutations may occur even within the same variety of C. variegatum. The wide, leathery leaves exhibit a considerable degree of variety in length, ranging from 2 to 12 inches.

The glossy leaves are placed in an alternating pattern and can be linear, round, or have smooth or lobed borders. Occasionally, they are even deeply sliced all the way down to the midrib. Some leaves have margins that are spiralling or wavy. Shades of green, white, pink, orange, red, yellow, and purple are among the possible leaf colours; these colours are frequently combined. As they become older, the leaves' colour may shift. Blooms are rare when the plant is grown indoors. When planted in the ground, it produces tiny blooms in long axillary racemes in April in areas without cold. In contrast to the male flowers, which have five little petals and 20–30 stamens, giving the impression of a starburst, the female flowers are yellowish and produced on distinct inflorescences.

Cultivation of Codiaeum variegatum:

Numerous techniques, including cuttings, grafting, seeds, and air layering, can be used to cultivate Codiaeum variegatum (Nasib et al., 2008). Cuttings from mature, healthy plants with at least three sets of leaves are the most popular way to propagate C. variegatum (Chen and Stamps, 2006). However, utilizing recently generated shoot tips, a quicker and more convenient form of propagation was created in vitro, and this method is known to increase plant production.

Ethanopharmacological uses^2,12,13,14:

The leaves of the Codiaeum species were used locally to treat cancer, diabetes, hypercholesterolemia, intestinal worms, constipation, diarrhoea, external wounds, inflammation, fever, ulcers, discomfort, and weight loss. The C. variegatum plant's leaves are used as a tonic, while the fruits, seeds, and flowers are used as purgatives, fruits for dysmenorrhea, and flowers for flatworms. While the roots are used to treat diarrhoea, the bark is utilized to treat dyspepsia. The bark is also used to treat persistent liver enlargement and recurring fevers. In the past, individuals with stomach problems such diarrhoea, gastroenteritis, and gastric ulcers were treated with extracts prepared by boiling fresh or dried leaves.

Additionally, this plant has been utilized to treat skin conditions including bacterial and fungal infections, skin allergies, and gastrointestinal irritation in nations like Malaysia, India, the Fiji Islands, and Papua New Guinea (Fig. 6). Ointments containing C. variegatum latex, leaf extract, or root extract were applied to the afflicted regions. As seen by examples reported in Bangladesh, the use of C. variegatum latex on wounds has been linked to adverse reactions such dermatitis and allergic reactions. Due to its therapeutic qualities, several C. variegatum cultivars are significant and have been utilized in traditional medicine around the world, particularly in Asian nations where the plant is indigenous. Other cultivars of C. variegatum are descended from this species, which is the wild variety native to the Moluccan Islands of Indonesia, sometimes known as cv. Mollucanum.

Figure6. Pharmacological uses of Codiaeum variegatum.

Phytoconstituents^{12,15,16,17,18}:

Quantitative estimation revealed that phytochemicals are in between the following range alkaloids in between the range of (4.66 -10.2%), flavonoids (33.1-37.63%), saponins (11.36-13.76%), phenolics (35.43-39.76%), tannins (10.5-18.5%), terpenoids (27.56-30.3%). Essential oils obtained by hydro distillation of the air-dried leaves of four varieties of Codiaeum variegatum were analysed by GC and GC-MS. The main constituents of C. variegatum (L.) Blume f. lobatum cv. Disraeli were caryophyllene oxide (58.2 %) and (Z)-β-farnesene (19.6 %). All the four compounds present in C. variegatum var. pictum ‘Congo’ namely linalool (39.3 %), 1,2,4-trimethylbenzene (21.0 %), β-pinene (21.6 %) and α-pinene (17.9 %) were present in significant amounts. Phytol (17.8 %), β-bisabolene (9.6 %) and linalool (8.9 %) were the major components of C. variegatum (L.) Blume f. taeniosum cv. Gold Sun, while, C. variegatum (L.) ‘Dreadlocks’ was dominated by β-ionone epoxide (29.7 %), γ-muurolene (20.5 %), naphthalene (16.3 %) and (E)- α-ionone (14.8 %). The chemical constituents of the studied essential oils were being reported for the first time. The essential oil displayed mortality (fumigant toxicity) against Sitophilus zeamais adults at tested concentration with lethal concentrations (LC50) of 72.07, 73.50, 47.43 and 44.04 μg/mL air respectively. The chemical constituents and insecticidal activity of essential oils of C. variegatum were being reported for the first time.

Some factors that determine the range of phytochemical substances found in Codiaeum variegatum include the kind of plant and its origin. This helps explain the differences between cultivars and their different medicinal uses. To fully understand the roles that certain cultivars, play in traditional medicine, further investigation into the structural characterization of chemical components present in plant extracts is necessary. Qualitative analysis was used to identify compound classes such as coumarins, saponins, anthraquinones, and cardenolides.

The methanol extract of C. variegatum leaf included ent-trachyloban-18‑hydroxy-trachyloban-3-one, ent-trachyloban-3-one, alpha-amyrin, beta-sitosterol, and ent-trachyloban-3-one. After being separated from the petroleum extract of C. variegatum stem bark by silica gel column chromatography, the structure of taraxerol was determined utilizing methods such as IR and NMR spectroscopy. The hydroethanolic leaf extract (50:50, v/v) of C. variegatum contained terpenoids, while the stem bark did not. "Gold dust," gathered in Ghana's Accra. Analogous investigations conducted in the Lal Bagh Botanical Garden in Bangalore, India, concentrated on extracts from the roots, leaves, and stems of many C. variegatum cultivars and found notable amounts of terpenoid compounds, namely between 27 and 30 percent. C. variegatum ethanol extract obtained in Bangladesh was studied by Saffron et al. (2014). HPLC-DAD was only able to identify four of the eleven primary phenolic compounds: epicatechin, rutin, ellagic acid, and p-coumaric acid. The investigation found eleven noteworthy phenolic compounds. Among the other chemicals discovered, ellagic acid was the most abundant, at around 200 mg/100 g dry weight. Furthermore, a leaf extract containing 80% methanol was studied, which resulted in the separation of two phenolic acids, p-coumaric acid and caffeic acid, as well as five flavonoids: isovitexin, vice-2, orientin, vitexin, and apigenin. These compounds were separated using Sephadex LH-20 column chromatography, and their individual structures were determined by 1H and 13C NMR spectroscopy and mass spectrometry, respectively. Another study discovered eleven volatile chemicals in the leaves of C. variegatum from Bogor, West Java, Indonesia. (6Z, 9Z)−6,9-pentadecadiene-1-ol, 2,3-dihydro-3,5-dihydroxy-6-methyl-4pyran-4-one (11 %), and hexadecanoic acid (21 %) were the main constituents.

Table 2: List of Phytochemical compounds present in Codiaeum variegatum^19,20,21

Class of Compounds	Chemical constituents
Flavonoids	Rutin, Ellagic acid, Vicenin, Orientin, Epicatechin, Apigenin, Vitexin
Terpenoids	Ent- trachyloban-3-one, Ent- 18‑hydroxy trachyloban-3-one, Taraxerol, α- amyrin, Caryophyllene, β-franesene-ene, Linalool, 1,2,4- tri-methyl benzene, β- pinene, α- pinene, β- bisabolene Linalool
Alkaloids	Glaucine, Oxaglaucine, Hemiargyrine
Phenolic acid	Chlorogenic acid, Caffeic acid, Proto-catechunic acid, p-hydroxy benzoic acid, Vanillic acid
Essential oil	Hexadecenoic acid, 2,3 di hydro-3,5-di‑hydroxy-6-methyl-4 pyran-4-one

The novel latex of C. variegatum included a cyanoglucoside that was identified as 2-(3,4,5)-trihydroxy-6-hydroxymethyltetrahydropyran-2-yloxymethyl acrylonitrile. X-ray diffraction, NMR, and MS were used to establish the structure of this molecule. Ultimately, it was found that oxygenated sesquiterpenes, specifically sesquiterpene hydrocarbons (33%) and caryophyllene oxide (58%) and (Z)-farnesene (20%), were the primary constituents of C. variegatum. Significant components were linalool (39%), alpha-pinene (22%), 1, 2, 4-trimethylbenzene (21%), phytol (18%), alpha-pinene (18%), beta-bisabolene (10%), and linalool (9%).

Phytochemistry:

Very little is known about the structural elucidation of particular compounds, and the majority of phytochemical research on C. variegatum documented the qualitative identification or quantification of groups of chemicals present in different variations. The phytochemical composition of C. variegatum was shown to be correlated with the plant's variety and provenance, which may account for the variations across cultivars and their various therapeutic applications.

Pharmacological Properties:

Among the articles that were chosen, 34.83% documented the biological activity of C. variegatum variants in vitro, and in vivo. There hasn't been single clinical research on C. variegatum -based products discovered yet. The primary biological characteristics of C. variegatum were its antibacterial, cytotoxic, anti-amoebic, and antiviral activities. These characteristics were shown to be associated with the traditional therapeutic use of each variety.

Wound healing activity^22,23:

By adding extracts to a basic ointment base B.P. (British Pharmacopoeia) at concentrations of 2% and 4% w/w, the healing capacity of C. variegatum root was examined. To measure wound healing activity, the study used burn, excision, and incision wound models in rats. The results concerning the capacity to contract wounds, the length of time it took to close wounds, and the tensile strength were similar to those of nitrofurazone, a medication that is often used. According to statistical analysis, wounds treated with an ointment containing 4% w/w alcoholic extract showed considerably improved wound healing and longer epithelization times (P < 0.001). The ointment formulations with a weight percentage of 2% and 4% showed notable tensile strength. The results of the excision and burn wound models were corroborated by the histology investigation.

Anti-bacterial activity^25,
26,27,28:

Natural substances produced from plants have long been important in traditional African medicine, acting as cures for a range of illnesses, including infections.

Many communities have been impacted by the frequency of infectious diseases brought on by pathogenic bacteria, and in certain situations, treating these illnesses has become more difficult due to the presence of antibiotic-resistant strains. It is commonly known that phytochemicals taken from medicinal plants have the ability to treat bacterial infections. A thorough analysis has been conducted on the antibacterial properties of C. variegatum ethanol and water leaf extracts. The modified Kirby-Bauer disc diffusion technique was employed to analyse the antibacterial characteristics of these crude extracts, and the resultant zone of inhibition was evaluated. To investigate the extracts' possible antibacterial properties, Gram-positive bacteria (Bacillus subtilis) and Gram-negative bacteria (Serratia marcescens) were employed. Crude extracts of C. variegatum leaves in ethanol and water demonstrated substantial inhibitory zones of 20 mm and 12 mm against Bacillus subtilis and Serratia marcescens, respectively, as compared to the control group. This suggests that the medicinal qualities of plants may yield standardized, reasonably priced, and secure herbal remedies. Moreover, these extracts could include novel chemical components that could be used to create broad-spectrum antibiotics.

Anti-inflammatory activity^29,30:

On macrophages, the effects of extracts/fractions from C. variegatum were studied, with an emphasis on blocking the activities of 5-lipoxygenase, TNF-α, and NO (nitric oxide). Various quantities (0.1, 1, 10, and 100 g/ml) were used, and during the incubation time, no discernible effect on cell viability was seen at the recorded values. The extracts and fractions showed concentration-dependent decreases in 5-lipoxygenase activity, as well as improved anti-inflammatory activity as a consequence of fractionation and generation of TNF-α and NO by live primary murine macrophages. Out of all the fractions, HEF2 (Human oesophageal tissue), HEF3, HEF5, EEF1 (Fibroblast cell line), EEF3, and EEF5 showed the most anti-inflammatory efficacy. Both the extracts and fractions of C. variegatum demonstrated a much greater anti-inflammatory capacity, mainly through the inhibition of pro-inflammatory mediators including 5-lipoxygenase, TNF-α (tumour necrosis factor), and NO.

Anti-oxidant activity^31,32,33:

The anti-oxidant properties of the aqueous, hydroethanolic 70/30 (v/v), and ethanolic extracts of C. variegatum were assessed by the use of lipid LPO inhibitory tests, ferric iron-reducing anti-oxidant power, and DPPH (2,2-diphenyl-1-picrylhydrazyl) investigations (Fig. 2). In terms of DPPH (IC50, 50% deadly concentration of 00.77 g/ml of DPPH), FRAP (fluorescently-labelled molecules) (EC50, 50% efficient concentration of 00.543.6 g/ml), and its capacity to stop lipid peroxidation (IC50 00.21.52 g/ml), the ethanolic extract demonstrated the strongest anti-oxidant activity. It's important to remember that this activity was still far lower than that of ascorbic acid. A significant amount (p < 0.05) was found by statistical analysis between the extracts and ascorbic acid. Phenolic molecules were found in these extracts after phytochemical examination, and these chemicals may be the cause of the reported antioxidant effects.

Cytotoxic activity^34,35,36,37:

It has been investigated how well phenolic compounds made from C. variegatum work as chemo preventives to counteract the cytotoxic and genotoxic effects of mitomycin C. Samples were collected 24 hours after giving male Swiss albino mice an extract or treatment with mitomycin. We assessed DNA damage, cell viability, and chromosomal abnormalities in spermatocytes and bone marrow cells (using the comet test). According to reports, no cytotoxic nor genotoxic effects were seen by the extract at its greatest concentration on mouse somatic and germ cells. On the other hand, mitomycin C significantly decreased cell growth and increased chromosomal aberrations and DNA damage. Moreover, if mice were given the phenolic substance obtained from Codiaeum two hours before Mitomycin C, Mitomycin C's cytotoxicity and genotoxicity were avoided.

Anti-amoebic activity³⁸:

The leaves of C. variegatum are used by local populations in Cameroon as a remedy for bloody diarrhoea. Under the direction of bioassays, the aqueous leaf extracts of C. variegatum and other fractions were tested against trophozoites of Entamoeba histolytic axenic culture. By undermining Gal/GalNAc lectin, a protein that is frequently present on the surface of parasites, the sub-fraction SF9B caused possible morphological defects in E. histolytica trophozoites, which ultimately resulted in the death of the parasite. Furthermore, a transcriptome study based on RNA sequencing shows that treatment with active sub-fraction causes the overexpression of the gene that produces ceramide synthase, which is crucial for cell differentiation and death.

Anticonvulsant activity^39,40:

Medicinal plants like C. variegatum are among the medication's identified therapeutic ingredients and its source. It has been investigated how effective an ethanol extract of C. variegatum is as an anti-convulsant. Necrosis and cellular adaption changes defined by sparse cell population, inflammation, hypertrophy, and neurosis were seen in the brain stroma. There were noticeable differences between the treatment groups that received dosages of 200 mg/kg, 400 mg/kg, and 600 mg/kg and the control group that received 0.1 ml of normal saline. It is commonly known that glia cells—in particular, astrocytes—maintain neurons, which are the specialized basic units of the central nervous system.

Antipyretic activity⁴¹:

The presence of bioactive compounds with various pharmacological actions, such as abortifacient, anti-amoebic, antibacterial, anticancer, and antifungal properties, in C. variegatum is widely recognized. Research has shown that plant leaf extract in ethanol has antipyretic properties.

Toxicity profile^{21, 42}^:

The presence of poisonous chemicals in the sap, which is created when the plant's above-ground sections sustain mechanical injury, is linked to C. variegatum's dangerous characteristics. Conversely, the safety of other types may be associated with the variety of phytochemicals found in different cultivars or the lower extraction of toxic ingredients during decoction, the traditional way of making therapeutic recipes. Three distinct species of C. variegatum-Aureo-maculatum, Pictum, and Punctatum—were discovered to be potentially toxic, although Mollucanum and Spirale variants were shown to be harmless. The literature review states that C. variegatum aqueous extract did not produce any harmful effects when administered to rats and mice of both sexes at dosages of up to 200 mg/kg b.w. in a sub-chronic study and up to 24 g/kg b.w. in an acute toxicity experiment. This opinion holds that C. variegatum poses little danger and may be utilized therapeutically in traditional healthcare settings without having any noticeable negative effects.

Safety evaluation and toxic potential of Codiaeum variegatum⁴³:

Whereas Mollucanum and Spirale variations of C. variegatum were determined to be harmless, other varieties (Aureo-maculatum, Pictum, Punctatum) were reported to have a hazardous potential. Because poisonous chemicals are released into the sap when the plant's aerial parts are mechanically injured, C. variegatum has a potentially hazardous potential.

CONCLUSION^{44,45,46,47,48}:

Many of the ornamental plants are also reported to have significant biological activities. Some of them belongs to the family Euphorbiaceae. Typically, they are used to treat a variety of illnesses. This review found that the most common uses of C. variegatum in folk medicine for treating a wide range of ailments are its leaves and aqueous extracts. The truth is that ancient methods of preparing medicinal substances ought to be encouraged as they may extract advantageous ingredients while omitting dangerous ones. Furthermore, quality control may be achieved by using the dangerous compounds (5-deoxyingenol and phorbol esters) discovered in the conventionally used C. variegatum. Furthermore, all the relevant data that will be required for further research investigation is included in the current literature evaluation. The molecular mechanisms of the secondary metabolites that show specific therapeutic benefits should be the subject of further research. The clinical potency and toxicological studies conducted on C. variegatum must be examined and documented. Therefore, it is essential to accurately identify and describe the secondary metabolites included in the extract using the existing approaches. Investigating the complex links involved in herb-drug and food-drug interactions requires this. Nevertheless, more complex experimental techniques like DNA microarrays and other sophisticated instruments should be used to significantly expand the pool of possible candidates for natural therapies.

ACKNOWLEDGEMENTS:

The authors are thankful to RGUHS, Karnataka for providing the research grant and also we express our gratitude to the Management of RR College of Pharmacy, for providing the facilities to publish this work.

CONFLICT OF INTEREST:

No conflict of interest.

REFERENCES:

1. Mwine, Julius, Van D, Patrick. Why do Euphorbiaceae tick as medicinal Plants? A review of Euphorbiaceae family and its medicinal features. Journal of Medicinal Plants Research. 2011; 5: 652-662.

2. Mfotie N, Emmanuel, Moundipa, Paul, Niedermeyer, Timo. Codiaeum variegatum (L.) Rumph. ex A. Juss. (Euphorbiaceae): An overview of its botanical diversity, traditional uses, phytochemistry, pharmacological effects and perspectives towards developing its plant-based products. Journal of Ethnopharmacology. 2011.

3. Brown B F. A Codiaeum encyclopedia: crotons of the world Valkaria Tropical Garden Valkaria. 1995.

4. Deng M, Chen J, Henny R J, Li Q. Genetic relationships of Codiaeum variegatum cultivars analyzed by amplified fragment length polymorphism markers. Hort. Science. 2010; 45(6): 868-874.

5. Govaerts R. World checklist and bibliography of euphorbiaceae. kew: the royal botanic gardens. 2000.

6. Croton Plant Care: Everything You Need to Know (thespruce.com)

7. How to Grow Croton Plants (Codiaeum variegatum) - Gardening Channel

8. Croton Plant: Care and Growing Guide of Codiaeum Variegatum (leafyplace.com)

9. Croton, Codiaeum variegatum – Wisconsin Horticulture

10. Asniawati M D, Purwantoro A. Genetic diversity of Croton (Codiaeum variegatum (l.) rumph. ex a. juss) and its offspring based on RAPD markers. Ilmu Pertan. (Agric. Sci.). 2019; 4: 52-58.

11. Rahman A H, Akter M. Taxonomy and medicinal uses of Euphorbiaceae (Spurge) family of Rajshahi, Bangladesh Res. Plant Sci. 2013; 1.

12. Moundipa PF, Flore KG, Bilong CF, Bruchhaus I. In vitro amoebicidal activity of some medicinal plants of the Bamun region (Cameroon). Afr. J. Tradit. Complement Altern. Med. 2005; 2: 113-121, 10.4314/ajtcam.v2i2.31109

13. Rahmatullah M, Ferdausi D, Mollik M A, Azam M N, Rahman M T, Jahan R. Ethnomedicinal survey of Bheramara area in Kushtia District, Bangladesh. 2009; 3; 534-541.

14. Shah S, Bhat J A. Ethnomedicinal knowledge of indigenous communities and pharmaceutical potential of rainforest ecosystems in Fiji Islands J. Integr. Med. 2019; 17.

15. https://www.selinawamucii.com/plants/euphorbiaceae/codiaeum-variegatum/

16. Muell, Arg, Sangha R. Bijekar1 M C, Gayatri, Rajanna L. Phytochemical profile of Baliospermum montanum (Wild). International Journal of Innovation and Scientific Research. 2014. Vol 12; 37-42.

17. Lawal, Oladipupo A, Isiaka A O, Faith S G, Adeleke A. K, Andy R O. Chemical Composition and Insecticidal Activity of Essential Oils of Four Varieties of Codiaeum variegatum (L.) from Nigeria. Journal of Essential Oil-Bearing Plants. 2018; 21; 840 - 847.

18. Babatunde E E, Banji A F, Foluke O, Ayandiran A D, Fatima K. Comparative study of leaf morphology, phytochemical, mineral and proximate analysis of Codiaeum variegatum (L.) A. Juss. (Malpighiales: euphorbiaceae) and its stable mutant Braz. J. Biol. Sci. 2017; 4.

19. Aragão G F, Carneiro L M, Rota Junior A P, Bandeira P N, Lemos T L, Viana G S. Alterations in brain amino acid metabolism and inhibitory effects on PKC are possibly correlated with anticonvulsant effects of the isomeric mixture of α-and β-amyrin from Protium heptaphyllum. Pharm. Biol. 2015; 53: 407-413.

20. Bijekar S R, Gayatri M C. Phytochemical profile of Codiaeum variegatum (L.) Bl. Int. J. Pharm. Pharm. Sci.2014. Vol 2; 22-31.

21. Pandey, Swapnil and Singh, Sonia. Exploring Phytoconstituents and Pharmacological Profile of Codiaeum variegatum (L.), Garden Croton. Pharmacological Research - Modern Chinese Medicine. 2023; 9: 100327. 10.1016/j.prmcm.2023.100327.

22. Sangeetha G, Mohan K L, Aruna G, Sekar B M, Balammal G. Study on wound healing activity of root of Codiaeum variegatum. International Journal of Innovative Drug Discovery. 2011; 1: 19-23.

23. Nitu V. Madan, Mahesh S. Sahu, Yogeshwari T. Jambhulkar, Atreyee S. Mamidwar, Nilesh T. Hingawe, Amit N. Maliye. A Review on Euphorbiaceae plants for peptic ulcer. Res. J. Pharmacognosy and Phytochem. 2018; 10(4): 336-339.

24. Fapohunda S O, Esan E B, Ogunwenmo K O, Adedayo A. Report of Fusarium oxysporum on Codiaeum variegatum (L.) Blume (Euphorbiaceae) cultivars in Nigeria. Journal of Life & Physical Sciences, acta SATECH. 2005; 2: 40-41.

25. Anyasor G N, Esiaba I O, Ogunwenmo K O, Esan E B, Olajuyigbe O O, Ikpeoha N S, Onyishi C C, Bright O C. Biochemical and antimicrobial effects of aqueous and alcoholic extracts of Codiaeum variegatum (L.) Blume cv. ovalifolium (Euphorbiaceae). In: Proceedings of the 3rd International e-Conference on Agricultural Biosciences [3rd International e-Conference on Agricultural BioSciences]. 2010; 35-36.

26. Mohamed N E, El-Masry R A, Awad A E, Badr H A. Chemical composition and antibacterial activity of codiaeum variegatum leaves Zagazig J. Agric. Res. 2019; 46: 1133-1140.

27. Bhot M, Saha M, Phatak A, Chandra N. Antimicrobial activity of leaf extracts of Codiaeum variegatum (l.) Blume. International Journal of Pharmacology and Biological Sciences. 2010; 4(1): 17.

28. Pechangou SN, Enang BE, Ngohoba VS, Njoya EM, Njayou FN, Moundipa PF. Crude Extracts of Codiaeum variegatum Stem Exhibit Potent Antioxidant and Anti-inflammatory Activities in Vitro. J Explor Res Pharmacol. 2023; 8(1): 25-35. doi: 10.14218/JERP.2022.00039.

29. Bijekar, Sangha and Gayatri M, Rajanna L. Evaluation of antiinflammatory activity of flavonoid fractions from euphorbiaceae members on raw 264.7 cell lines. 2015; 16.

30. Nsangou S P, Mandou C N, Fondjou C M, Ngohoba V S, Enang E B, Njingou I, Joya E M N, Njayou F N, Fewou P M. Codiaeum variegatum hydro alcoholic leaf extracts and their fractions inhibit pro-inflammatory mediators in vitro. J. Biosci. Med. 2023; 11: 40-54.

31. Hassan, Emad, Rasmia, El-Toumy, Sayed, Mohamed, Samy and Omer, Elsayed. Phenolic Metaboloites and Antioxidant Activity of Codiaeum variegatum CV. spirale. Journal of Pharmacy Research. 2014; 88: 619-623.

32. Hassan, Emad, Rasmia, El-Toumy, Sayed, Mohamed, Samy and Omer, Elsayed. Phenolic Metaboloites and Antioxidant Activity of Codiaeum variegatum CV. spirale. Journal of Pharmacy Research. 2014; 88: 619-623.

33. Pechangou, Nsangou, Sylvain, Enang II, Brice, Ngohoba, Vigny, Mfotie, Njoya, Emmanuel, Frederic Nico, Njayou and Moundipa, Paul. Crude Extracts of Codiaeum variegatum Stem Exhibit Potent Antioxidant and Anti-inflammatory Activities in Vitro. Journal of Exploratory Research in Pharmacology. 2022.

34. Saffoon, Nadia, Alam, Md, Uddin, Golam, Mezbah. Phytochemical and Cytotoxic Investigation of Codiaeum variegatum Linn. Leaf. Stamford Journal of Pharmaceutical Sciences. 2010; 3: 51-53.

35. Abo-Zeid M A, Farghaly A A, Hassan E M, Abdel-Samie N S. Phenolic compounds of Codiaeum variegatum spirale lessened cytotoxic and genotoxic effects of mitomycin C in mice somatic and germ cells. Cytol. Genet. 2019; 53: 494-501.

36. Anim, Mathias Tawiah, Christopher Larbie, Regina Appiah-Opong, Isaac Tuffour, Kofi B A Owusu and Abigail Aning. Extracts of Codiaeum variegatum (L.) A. Juss is Cytotoxic on Human Leukemic, Breast and Prostate Cancer Cell Lines. Journal of Applied Pharmaceutical Science. 2016; 6: 87-93.

37. Fahmy M A, Farghaly AA, Hassan E E, Hassan Z M, Abd-Alla H I. Protective role of Codiaeum variegatum against genotoxicity induced by carmustine in somatic and germ cells of male mice. 2022.

38. Labu Z K, Laboni F R, Mamun M M, Howlader M S. Antidiarrhoeal activity and total tannin content of ethanolic leaf extract of Codiaeum variegatum Dhaka Univ. J. Pharm. Sci. 2015; 14.

39. Moshi M J, Kagashe G A. A study of the effect of extracts of Codiaeum Variegatum (L.) A. Juss on Picrotoxin-induced convulsions in mice. Tanzania Medical Journal. 2004; 1.

40. Finbarrs-Bello E, Egwu O, Atuadu V, Egwu E. Histological effects of ethanolic leaf extract of Codiaeum variegatum on the cerebrum of adult Wistar rats J. Exp. Clin. Anat. 2016; 15.

41. Kanedi M, Setiawan W A, Handayani K, Febriyanti V. Antipyretic effect of ethanol extract of plant leaves of garden croton (Codiaeum variegatum) in male mice GSC Biol. Pharm. Sci. 2021; 14: 202-206.

42. Abhay Deep Johnson, Ajay Singh. Toxic effect of biologically active compound Rutin extracted from Euphorbious plant Codiaeum variegatum against mosquito Culex quinquefasciatus (Diptera: Culicidae) larvae. Research J. Science and Tech. 2017; 9(3): 301-307.

43. Emmanuel, Mfotie, Njoya, Melanie, Flore, Gondam, Kamini, Wilfred, Angie, Abia, Sylvain, Nsangou, Pechangou, Fréderic N, Njayou, Angèle, Nkouatchoua T, Paul F, Moundipa. Acute and sub-chronic toxicity evaluation of the aqueous extract of Codiaeum variegatum leaves on Wistar albino rodents of both sexes. Journal of complementary medicine research. 2018; 7: 108–114.

44. Shivani Sharma, Hitesh K. Dhamija, Bharat Parashar. Jatropha curcas: A Review. Asian J. Res. Pharm. Sci. 2012; 2(3): 107-111.

45. Akshada Kakade, Indrayani Raut, Sandeep Kane, Rahul Adnaik, C. S. Magdum, S. K. Mohite. Anti-inflammatory Activity of Aqueous and DCM Extracts of Jatropha gossypifolia Linn in Albino Rats. Research J. Pharmacognosy and Phytochemistry 2011; 3(4): 148-150.

46. Kadiri Sunil Kumar, H Padmalatha, Surayya Farheen, Kalakonda Rajesh. Mood Elevating Activity of Plant Chrozophora plicata (Euphorbiaceae). Research Journal of Pharmacology and Pharmacodynamics. 2014; 6(2): 75-78.

47. Gayathri Segaran, Lokesh Ravi, Mythili Sathiavelu. Bioactivity guided extraction of PDHC [3,3’-(propane-2,2-diyl)bis (3,4,5,6,7,8- hexahydro-1h-isochromene)]: A Novel antibacterial compound from an ornamental plant Polyalthia longifolia. Research Journal of Pharmacy and Technology. 2021; 14(4): 2101-7.

48. Sathish M, Nandhini V, Suresh R. In vitro Alpha amylase and Alpha glucosidase enzyme inhibition of leaf extracts of Jatropha glandulifera Roxb. Research Journal of Pharmacy and Technology. 2022; 15(6): 2493-7.

Received on 07.05.2024 Modified on 06.06.2024

Asian J. Research Chem. 2024; 17(3):159-168.

DOI: 10.52711/0974-4150.2024.00030

Temperature:	The optimal temperature range is 65-80ºF (18-27ºC), with a minimum temperature of 60ºF (15ºC). Steer clear of chilly drafts near doors and windows.
Light:	As previously indicated, for the croton to continue looking healthy, it needs lots of light.
Watering:	From April until the end of summer, irrigate the soil slightly to keep it wet. Wintertime will require far less watering.
Soil:	It works well to add perlite or sand (1 part) to potting mixtures based on peat (2 parts) or other good-draining varieties.
Fertilizer:	For best results, feed this plant every two weeks with a diluted fertilizer during the growing season ( spring – fall).
Re-Potting:	Every two to three years, repot. Even though the plant like its roots to be congested, only once it has outgrown its pot should you adjust it to a size larger.
Humidity:	Since croton plants prefer high humidity, try using a humidifier to increase the room's humidity or setting the plant on a tray with water and stones.
Propagation:	Using stem cuttings, they may be propagated rather easily in the spring. Apply rooting hormone to the stem tips, plant in potting soil, and, if you can, keep the bottom of the containers warm.
Pruning:	These plants often get too big and bushy for some interior spaces as they mature. In the spring, you can trim stems back to the proper size.

S. No	Geographical source	Local names	Part used	Traditional uses
1	Indonesia	Katomas, Silastom	Leaves	Decoction used to relieve intestinal constipation; juice used to treat affected areas with eczema treatment.
2	India	Garden croton	Root	A concoction of alcoholic roots and an ointment used to heal wounds, prevent secondary infections, and manage skin eruptions.
3	Malaysia	Bunga mas	Leaves	Decoction used to relieve constipation; leaf extract ointment used to wound and cuts.
4	Panama	Marmara	Leaves	Extract used to treat rashes and acne in infants.
5	Thailand	Kila	Leaves	Decoction with antimicrobial properties.
6	Bangladesh	Pata- bahar	Leaves	Used as massage oil.

Pharmacological activities	Part of the plant	Extract used	Experimental model	Observation analysis
Anti-diarrhoeal	Leaf	Ethanol	Castor oil-induced diarrhoea in Swiss albino mice	Reduced intestinal inflammation
Anti-amoebic	Leaf	Aqueous	Axenic and polyxenic culture of Entamoeba histolytica	Significant effect
Anti-inflammatory	Leaf	Methanol	NO inhibitory assay	NO production inhibition
Antiviral	Latex	Fresh latex	Influenza virus	Potential effect
Wound healing	Roots	Methanol	Excision, incision model Burn wound model in albino rats	Pro-healing activity
Anti-microbial	Leaf	Methanol	Escherichia coli, Staphylococcus epidermidis, Staphylococcus. aureus	Increased the permeability of cell membrane; increased synergetic impact along with antibiotics
Anti-bacterial	Leaf	Chloroform	Pseudomonas aeruginosa, E. coli, Staphylococcus aureus, Bacillus subtilis	Potential effect
Antioxidant	Leaf	Methanol	DPPH scavenging activity, NO scavenging activity	ROS (Reactive oxygen species) detoxification
Antiviral	Leaf	Ethanol	Herpes simplex type-1	Antiviral activity against Simplex virus
Cytotoxic	Leaf, root, stem	Methanol	MTT, 3-(4,5-dimethylthiazol-2-yl) −2,5-diphenyltetrazolium bromide assay, cell lines (MCF7, PC3, HepG2, HCT116)	Strong inhibitory impact on cell lines as compared to leaf extract
Antifungal	Leaf	Ethanol	Agar diffusion method	Against Fusarium oxysporum, Alternaria alternate