INTRODUCTION:

Calotropis gigantea, also referred to as milk weed (Asclepiadaceae), is a common wasteland weed that grows wild throughout India and is resistant to salt and drought. It's one of the odd plants that grazing animals don't eat.

The phytochemicals that have been found in this plant include giganteol, usharin, α and β-calotropeol, β-amyrin, fatty acids, hydrocarbons, sterols, and a variety of tetracyclic triterpene substances (Murti and Seshadri, 1943, 1945a, b). Cardenolide, calotropin (Kupchan et al., 1964), α-amyrin, β-amyrin, taraxasterol, β-sitosterol, α-amyrin methylbutazone, β-amyrin methylbutazone, α-amyrin acetate, β-amyrin acetate, taraxasteryl acetate, gigantursenyl acetate B (Sen et al., 1992; Habib et al., 2007), flavonol glycoside, akundarol, uscharidin, calotropin, frugoside¹.

In numerous regions of the world, including India, plants, animals, and other natural items have had a significant impact on human culture and civilization since prehistoric times. Plants have been worshipped by humans since the dawn of civilization. These plants are kept as genetic resources and are used for food, fuel, fodder, fiber, fertilizer, febrifuge, and many more purposes. Calotropis gigantea is one such plant. The herb Calotropis gigantea is referred to as "Sweta Arka" and Caotropis procera as "Raktha Arka" in traditional Ayurvedic medicine. Both of them share many botanical characteristics and exhibit comparable pharmacological actions².

The ethanol extract of C. gigantea's roots demonstrated cytotoxic activity towards human chronic myelogenous leukemia (K562) and human gastric cancer (SGC-7901) cell lines in vitro by the MTT method during our screening for cytotoxic agents from tropical medicinal plants, with IC50 values of 9.7μg/mL and 6.7μg/mL, respectively. From the ethanol extract of C. gigantea, a novel pregnanone called calotropone and one known cardiac glycoside, gofruside (2), were isolated via bioassay-guided fractionation. Their structures were clarified through the use of spectrum methods, particularly 1D and 2D NMR spectroscopy. Compounds 1 and 2 both shown notable cytotoxicity³.

In Bangladesh (Kitagawa et al., 1992) and Indonesia (Kiuchi et al., 1998), Calotropis gigantea is used as medicine. From the aerial sections of C. gigantea, isorhamnetin-3-O-rutinoside, isorhamnetin-3-O glucopyronoside, taraxasterol acetate, and flavonol trisaccharide were separated and identified. Calotropis gigantea roots contain two novel oxiopregnane oligoglycosides called Calotropis A and B, whose chemical structures have been determined (Kitagawa et al., 1992). The cytotoxic properties of 4-O-beta-d-glucopyranosyl frugoside, cardenolide glycosides, calotropin frugoside, and "Akond mul" (a root of Calotropis gigantea) were also discovered (Kiuchi et al., 1998). Four novel chemical ingredients have recently been identified from the roots: sucrose, calotropinnaphthalene (a naphthalene derivative), calotropis sesquiterpenol (a terpene derivative), and calotropbenzofuranon (a terpene derivative) (Gupta and Ali, 2000).In Indian traditional medicine, the roots of C. gigantea have been used to treat lep rosy, eczema, syphilis, elephantiasis, ulceration, and cough (Kartikar and Basu, 1984)⁴.

The entire plant, including the roots, bark, leaves, and flowers, is used to cure a variety of illnesses and anomalies in people. Additionally, Oudhia and Tripathi and Oudhia et al. revealed that extracts of several plant parts, including the Calotropis root, stem, leaf, and stem + leaf, have an impact on the germination and vigor of seedlings of a variety of agricultural crops. Its utility in biomethanation is highlighted by its latex content and natural availability. Biogas could be the most popular domestic energy source in a nation like India with a large cattle population⁵.

TAXONOMICAL CLASSIFICATION:

· Kingdom: Planatae

· Subkingdom: Tracheobionta

· Class: Dicotyledones

· Sub class: Asteridae

· Order: Gentianales

· Family: Apocynaceae

· Subfamily: Asclepidiaceae

· Genus: Calotropis

· Species: Calotropis gigantean.

COMMON NAME:

English: Madar, Giant Milk-weed, Roostertree, Mudar plant

Sanskrit: Alarka, Rajaarka, Shvetarka, Asuka, Madaar, Bhasvanmuula, Dinesh, Prabhakar

Unani: Madaar, Aak

Siddha: Erukku

French: Calotrope, Pomme de Sodome

German: WahreMudarpflanzer, Gomeiner

Italian: Calotropo

Bengali: Aaknad

Telugu: Jilledu, Mandaram

Punjabi: Ak

Arab: Ushar

Persian: Kharak.

BOTINICAL DESCRIPTION:

Botanical description of Calotropis Includes following part:

· Bark and Branches: The branches have a white fur-like covering called tomentum, and the bark is thick, rough, and corky with a yellow-brown color. The twigs are green and meaty.

· Leaves: The leaves are simple, oblong to obovate, opposite-decussate, and fairly big, measuring approximately 30 by 25 cm. They have an acute apex, a sessile (nearly

· decurrent) base, and four to six pairs of subopposite nerves that are noticeable on the abaxial surface.

· Inflorescences: From the base of the leaves, pedunculate (about 7 cm) cymes containing three to twenty inflorescences emerge.

· Flowers: Five thick, ovate petals measuring one centimeter by one centimeter, with white at the base and purple points, five thin, dirty white sepals, and five purple-tipped stamens surround a white stigma with five lobes.

· Fruits: Fruits are made up of green, ovoid, spongy fruits, or follicles, that can grow to be up to 15 cm long and 10 cm wide. The seeds are light brown, plumed, and have a pappus of white filaments that can reach a length of 6 cm on one side when they split open. March to October would be the principal blossoming time.

· Root: Across the board, the root is present. With rootlets that vary in diameter, the bark is separated from the wood by 0.5 to 2.0cm. between two and five centimeters. Externally, it is whitish-grey in color, wrinkled when still new, and scratches or lesions in the bark readily release whitish latex. It's not a full fracture.

· Calyx: Five oblong-shaped lobes with tiny, fleshy glands inside that resemble teeth at the base.

· Corolla:Subcordate to widely subcampanulate, regular, gamopetalous, pale rose-purple or Liliac, with five broad, ovate, lanceolate, valvate, spreading lobes and a short tube.

· Leaf: Simple, opposite, sub-sessile, slightly thick, fleshy, coriaceous, 10–15 cm long and 4.5–6.5 cm broad, broadly cuneate, obovate or obovate oblong, slightly cordate, and auricled at base with tuft of short, simple hairs on the top side close to the petiole attachment point. Ashy gray pubescence envelops the delicate leaves. Mature leaves are pale green and almost smooth, or even glabrous.

· Flowers: Regular, bisexual, pale rose or liliac, purple or light greenish-yellow, with a subtle scent At the tips of lateral or interpetiolar peduncles that emerge from the opposite sides of the nodes, they are grouped in simple or sometimes compound cymose corymbs. Each cluster is surrounded by an involucre of many tiny, pointy, scaly caducous bracts. The flower buds have an ovoid shape. regular, gamopetalous, pale rose-purple or liliac corolla.

· Stamens: Five stamens are placed at the base of the coro The stamina cold formed by the union of filaments is completely akin to the column, only somewhat shorter. Less than half the length of the column, the appendages are slender. The appendages have pale color and are squishy.

· Root bark: The remaining section of the tap roots is spirally twisted, having noticeable tops with rounded heads. When the bark is broken, these hardy roots, which are grayish white in color, release sap. There are fissures in the bark of the elder roots. The exterior of the bark is yellowish-grey, while the interior is white ⁶.

Fig 1: Plant of Giant Calotropis.

PHYTOCHEMISTRY OF GIANT CALOTROPIS:

Cardenolides from the latex and leaves of the plants, 9, triterpenoids, 10, anthocyanins from the flowers, 11, and hydrocarbons, 12, have all been studied phytochemically. Cardiovascular glycosides were discovered in Calotropis gigantea leaves and latex; several glycosides were isolated and studied. The active principle "mudarine" was extracted from C. gigantean leaves. Adjacent to this, there was also a yellow, bitter acid and resin. Calotropogenjn (1), Calotropin (2), Uscharin (3), Calotoxin (4), and Calactin (5) were found to be the cardiac glycosides 10, 14. Three glycosjdgs cardenolide. Coroglaucigennae (6), 45 befaglucopyranosylfrugoside (8) and 70 frugoside (7) were identified as the cytotoxic components of "akond mul" (Calotropis gigontea L. roots). It was determined whether these substances were cytotoxic to different human and mouse cell lines.

A new flavonol trisaccharide was isolated from the aerial parts of C. gigantea in addition to the isolation and characterization of isorhamnetin-3-O-rutinoside (11), isorhamnetin glucopyranoside (12), and taraxasteryl acetate. Its structure was determined to be isorhamnetin-3-0-(2-0-beta-D-galactopyranosyl-6O-alpha-L-rhamnopyranosyl)-beta-D-glucopyranoside (13) using a combination of fast atom bombardment mass spectroscopy, 'H and "C NMR spectra, and some chemical degradations. A methanol extract of Catotropis gigantea's root bark yielded giganticine, a novel non-protein amino acid, whose structure

was determined using spectroscopic techniques. It has noteworthy antifeedant properties against the nymphs of Schistocerca gregaria, a desert locust. Calotropin-FI and calotropin-FII are two proteinases that include carbohydrates that were isolated from Calotropis gigantea latex using CM-Sephadex C-50 chromatography. Chromatography revealed that calotropain-FI and Fll were both homogenous ⁷.

PHARMACOLOGICAL ACTIVITY:

Antitumor action:

Cardenolides are specific secondary metabolites that are produced by Calotropis gigantea and have antimalarial and anticancer effects. In his study, GM Hoopes created a superior de novo assembly for C. gigantea, representing 157, 284, 427 BP with a N50 scaffold size of 805, 959 BP. Quality evaluations indicated that this assembly nearly perfectly represented the genic space. Gene expression atlas generation and annotation were aided by the creation of transcriptome data in the form of RNA-sequencing libraries from a developmental tissue series. This treatment also reduced the number of viable tumor cells and body weight gain, changed hematological (Hb, RBC, and WBC), and biochemical parameters, returning them almost entirely to normal.

CNS Activity:

The ethanolic extract of C. gigantea was given orally to lab animals at doses of 100, 200, and 500mg/kg bodyweight. The anticonvulsant effects were examined on a maximal electroshock test and a strychnine-induced convulsions model. The skeletal muscle relaxant and sedative properties were tested with a rota rod and an actophotometer, respectively. This extract only prevented seizures brought on by strychnine; it had little to no effect on seizures brought on by electroshock. Both motor coordination and locomotor activity were shown to be decreased in mice. In the acute toxicity sample, the extract was determined to be safe up to a level of 2000 mg/kg. At dosages of 250 and 500mg/kg bodyweight, the central nervous system (CNS) activity of an alcoholic extract of peeled Calotropis gigantea R.Br.

Antiviral activity:

A novel lignan glycoside called (+)-pinoresinol 4-O-[60-Ovanilloyl] was discovered from Calotropis gigantea latex. -b-Dglucopyranoside (1), two recognized phenolic compounds, 69-O-vanilloyltachioside (2) and 69-O-vanilloylisotachioside (3), and one genuine compound, (+) pinoresinol 4-O-b-Dglucopyranoside, were examined using the cytopathic effect to determine their ability to inhibit A/PR/8/34 (H1N1) in MDCK cells. Compound 1 inhibited the H1N1 virus A/PR/8/34. Its in vitro inhibitory efficacy against a range of avian and human influenza viruses was assessed using the CPE inhibition assay. Subsequent investigation showed that 1 successfully stopped the influenza virus's transcription factor NF-kB from moving to the nucleus and from exporting viral ribonucleoproteins⁸.

Inflammatory activity:

Rats with pedal oedema and air pouch models of inflammation were used to investigate the inflammatory responses of latex from Calotropis procera. Significant inflammation was generated by subcutaneously injecting an aqueous solution (0.1ml of 1% dry latex, DL) into the plantar surface of the paw. One hour after the injection, the maximum inflammatory reaction was reached, and it remained that way for an additional hour. Vascular permeability increased in conjunction with the inflammatory response and peaked in 15 minutes. Additionally, a 2.5% DL solution was injected into the 6-day-old rat air pouch to cause inflammation. Conversely, in the air pouch model, prednisolone inhibited inflammation more effectively than phenylbutazone. Therefore, anti-inflammatory medication evaluation might be based on the DL-induced inflammation in several models⁹.

Wound healing activity:

The current study's findings demonstrated that Calotropis gigantea has a distinct prohealing activity. The plant Calotropis gigantea's alcoholic root bark extract significantly increased the percentage of excision wound closure in the excision wound healing model through improved epithelization. Alkaloids, tannins, flavonoids, and triterpenoids were found in the Calotropis gigantea root bark extract according to a preliminary phytochemical investigation. The wound-healing effect of Calotropis gigantea may be attributed to any one of the identified phytochemical ingredients. It is well known that infections can exacerbate wounds from surgery. Previous research has demonstrated that a variety of plants' antibacterial properties promotes wound healing. Additionally, the plant's antibacterial activity has been assessed by earlier researchers (Ashraful et al., 2008); as a result, the current study validates the plant's traditional claims regarding wound healing¹⁰.

Vasodilatation effect:

The current investigation predicts that the latex has a notable vasodilatation impact at concentration dependent levels. The research that is now available suggests that alterations in the cation (Ca2+/Na+) permeability of the corresponding membrane are the primary mechanism by which latex affects the cardiovascular system. As a result, it is believed that C. gigantea latex acts similarly to C. magus by increasing coronary flow and excitability of Ca2+ channels in cardiac muscle. According to Freeman and Turner (1972), the release of Ca2+ from the membrane binding site into the mesoplasm may be the cause of the increased isotonic contractility of the isolated guinea pig heart. According to Paes de Carvalho et al. (1969), Ca2+ is crucial for the creation of pacemaker potentials ¹¹

Hypoglycemic Effect:

Thus, the goal of the current study was to assess C. gigantea's potential anti-diabetic effects in diabetic rats by utilizing a chloroform extract of the plant's leaves and flowers, as well as to ascertain whether the oral glucose tolerance test (OGTT) had improved glucose tolerance. Regarding the mode of action, it is possible that the extract's anti-diabetic properties enhance glucose absorption 33 or that they are partially mediated by inhibiting the gluconeogenic enzymes glucose-6-phosphatase. 35 However, before specific recommendations for drug development can be given, the mechanism (s) and site (s) of activity as well as the active constituent (s) of chloroform extracts of C. gigantea leaves and flowers as well as their toxicological effects must be identified¹².

Antifungal activity:

The yield of C. gigantea latex in the ethanolic extract was 15.5% in this investigation. The antifungal efficacy of C. gigantea latex ethanolic extract against eight distinct fungus species is displayed in Table 1. The presence or absence of inhibitory zones and zone widths (mm) were used to assess the antifungal efficacy of C. gigantea latex extract. The findings clearly demonstrate that the C. gigantea latex ethanolic extract exhibited a maximal inhibitory zone in a dose-dependent manner. Nonetheless, there was no discernible variation in the zone of inhibition levels between the 150mg and 300mg concentrations. The antifungal effectiveness of C. gigantea latex extract on the C. albicans revealed a wider diameter of clearance than that of other strains. Furthermore, the zone of clearance attained by the latex extract of C. gigantea is similar to that of the common medication, Amphotericin B¹³.

Anti-diarrheal activity:

Rats were used to test the anti-diarrheal properties of a hydroalcoholic (50:50) extract of the aerial portion of Calotropis gigantea in a model of castor oil-induced diarrhea. The proportion of the longest charcoal-traversed length divided by the small intestine's overall length was used to calculate the gastrointestinal transit rate¹⁴

GENERAL USES.

Culinary uses:

The center of the calotropis flower is used in Java to produce sweetmeat. Flavoring comes from the inner section of the flower. The plant's bloom is used as a beverage with milk to treat asthma, coughs, and colds. Young shoots and leaves are prepared like vegetables. Tea is made by infusing fruits. In Nigeria and Benin, traditional cheesemaking uses calotropis extract.

Traditional medical uses:

Ayurvedic medicine is a conventional method of treatment. For this, a variety of plants are employed. This plant's roots are thoroughly crushed and then administered by pressing them hard over the area that has been bitten. This plant's latex is used to treat rheumatic symptoms such as gingivitis, swellings, rat bites, and tooth issues. Bronchial asthma is treated with flowers. This herb is used to treat leprosy in India. Use of madar root to treat diarrhea. Calotropis is a unique medicinal plant that is utilized for many purposes. Traditional uses of calotropis include treating common illnesses like fever, indigestion, nausea, vomiting, colds, and asthma. The entire dried herb is a beneficial depuravate and tonic. The blooms have a bitter and tonic quality¹⁵.

BIOLOGICAL SOURCE/ GEOLOGICAL SOURCE/ NATURAL HABITAT:

Throughout the country, Calotropis grows wild up to 900 meters (msl). It is somewhat tolerant of salt and resistant to drought. It prefers sandy, disturbed soils with 300–400 mm of mean annual rainfall⁹. Due to the dispersal of its seeds by wind and animals, it quickly becomes established as a weed along deteriorating roadsides, lagoon edges, and overgrazed natural grasslands. It frequently predominates in abandoned agricultural sites, where it prefers to be found, especially in areas with limited rainfall and disturbed sandy soils. It's said to be an indication of over cultivation. For C. gigantea, a wide, less competitive habitat is preferable. The plant of this species can be found in areas with overly drained soil where yearly precipitation can reach up to 2000mm and in desert habitats where rainfall is restricted to 150 to 1000mm.

TOXICITY:

Calotropis gigantea is the more toxic of the two and is said to be even more deadly than cobra venom. Belonging to the Asclepiadaceae family, these two plants share comparable physiological and chemical reactions. The poisonous principles are calcin, uscharin, calcotropin, calcotropage, and calcotoxin. Owing to its irritant, neurotoxic, and anticholinergic properties, milk can be toxic and can manifest in various deadly forms. Serum contains 3% quantities of gigantin, an exceedingly toxic toxin. In large enough quantities taken internally, madar juice and latex cause a burning sensation in the mouth, throat, and stomach along with an unpleasant, bitter taste. After these come dilated pupils, tetanic convulsion, salivation, stomatitis, vomiting, diarrhea, collapse, and death. Delirium can happen from time to time. It is impossible to determine the dosage at which someone will die. The deadly window is between 30 and 8 hours long¹⁶.

HERBAL SIGNIFICANCE

Herbal plants are essential to our daily well-being and daily lives. They have been in use from antiquity to the present. Another significant plant in herbal medicine is Calotropis gigantea. Because of its many medicinal qualities, Calotropis gigantea is well-known for being used in traditional medicine to treat a wide range of illnesses.

According to Chaudiere and Ferrari-Iliou (1999), free radicals produce oxidative damage to living cells, which is the pathogenesis of many chronic diseases, including Parkinson's, Alzheimer's, cancer, aging, cardiovascular, atherosclerosis, cataract, inflammatory, and other degenerative conditions. Numerous antioxidants, including vitamins, carotenoids, flavonoids, polyphenols, saponins, enzymes, and minerals, are found in medicinal plants. In addition to being safer, natural antioxidants have anti-viral, anti-inflammatory, anti-cancer, anti-mutagenic, and anti-tumor effects. The four types of polyphenolic chemicals that are most frequently detected in plant extracts are tannins, alkaloids, flavonoids, and phenols. Numerous phytochemicals, including terpenoids, alkaloids, steroids, saponins, and flavonoids, have been found in various portions of C. gigantea, particularly the leaves. It has various therapeutic qualities. It is vital to research various pharmacological activities and medical uses. Therefore, they must be evaluated scientifically at the molecular and biochemical levels in order to be understood.

Calotropis has great relevance in India because of its huge industrial uses and commercial worth. The uses are-

Biogas production

To substitute for petroleum products

Cleansing of water

Energy plantation

Fibers, fodder, latex or rubber, etc¹⁷.

CONCLUSION:

Calotropis procera, often known as arka, is a significant Ayurvedic medication. According to estimates from the World Health Organization, 80% of people on the planet who live in underdeveloped nations rely on herbal medicine for their fundamental medical needs. Since this plant probably has more medicinal qualities than are now understood, researchers are looking into its potential for use in medicine. Plants like Calotropis have a lot of potential. It helps with a variety of illnesses. It goes by many names, including swallows wort in English, alarka in Sanskrit, and madder in Hindi. It grows in sandy, alkaline, and dry soils in most of the world's warm regions. Calotropis is harvested because of its medicinal properties. Calotropis show antimicrobial, anti-malarial, anti-oxidant, antifungal and antiulcer activity. Hindus worship this plant. This has flavoring purposes. Calotropis gigantean thrives along roadsides and in dry, open waste areas. Protease enzyme, ascorbic acid, and fish toxin containing sulfur and nitrogen are present in calotropis latex. Calotropis flowers have cyclisadol and terpenes. Skin disorders and liver issues are treated with them. Bowstring fiber is produced by Calotropis. The stems of the calotropis plant are used to make fishing nets, carpets, and thread. When patients took caloroptopies for joint discomfort, there have been reports of lesion, eruption, and blisters as an adverse effect.

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Received on 17.12.2024 Revised on 04.01.2025

Accepted on 20.01.2025 Published on 28.02.2025

Available online from March 03, 2025

Asian J. Pharm. Res. 2025; 15(1):77-82.

DOI: 10.52711/2231-5691.2025.00013

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