1. INTRODUCTION:

Over centuries and decades, our ancestors used herbal plant or herbal product in different forms as therapeutic which can be traced back for at least 5000 years¹. In few decades, development of modern or allopathic medicine has somehow reduced the role of medicinal plants in favour of synthetic drugs. Even now for the discovery of number of modern drug has been based on secondary metabolites of medicinal plants which is used by indigenous people². According to World Health Organization (WHO) report, about 80% of the world population depends on the natural product of plants, animals, and microorganisms for their health due to minimal side effect and cost effective³. The use of metabolites of different parts of plants for therapeutic is well known in Indian medicine from Vedic Age and Ayurvedic medicines and saved many lives before modern synthetic medicine reached to the common people. In addition, there is a continuing consumer demand of microbiologically safe, natural and/or preservative-free foods and cosmetic products without any side effects⁴. Medicinal plants contain organic compounds via primary and secondary metabolic cycles of different paths, known as phytochemicals (phyto means plant in Greek) and are responsible for the defensive strength of the body which are basically alkaloids, carbohydrates, flavonoids, steroids, tannins, saponins, peptides, glycosides, resins and terpenoids.

India is rich source of medicinal plants and herbs; there are more than 10,000 medicinal plants of which more than 1800 medicinal plants are used in Ayurveda, 4700 in Traditional Medicinal Practice, 1100 in Siddha Medicinal System, 750 Unani, 300 in Homeopathy, 300 in Chinese System of Medicine and finally 100 in Allopathic System⁵. Besides the above, another system is existed termed as folk medicine which is similar to the Ayurvedic system, the medicinal practitioners of folk medicinal systems are also known in Eastern India as Kavirajes⁶. The factors responsible for the continues and extensive use of herbal remedies in different forms in India are their effectiveness, easy availability, low cost, comparatively less toxic effects and the shortage of practitioners of modern medicine in rural areas.

Amaranthaceae is group of flowering plants, annual or perennial herbs together with some shrubs or small trees or vines, often reddish, many salt loving plants (halophytes) which are adopted to salty soils. This family counts with some 70 genera and nearly 1000 species and is closely related to the Chenopodiaceae. The Amaranthaceae family is named after the genus Amaranth (Amaranthus). It includes some popular garden plants such as cockscomb, some species are used as vegetables such as Amaranthus hybridus, leaves used in spinach, pot herbs and troublesome weeds. About 8 genera and over 50 species of Amaranthaceae family have been reported from India. Some of the genera of Amaranthaceae family with higher number of reported species are listed below as - Alternanthera (200, alligator weed), Gomphrena (100, globe amaranth), Iresine (80, gizzard plant), Amaranthus (60, pigweed), and Celosia (60, Celosia). Some field identification characteristics of the Amaranthaceae family are – steams often succulent, and or joined; leaves alternate or opposite and simple; no stipules; flowers are small, pubescent, actinomorphic, bisexual or monoecious, dense inflorescence; sepals usually 3-5, free or fused basally, and surrounding the fruits; petals are absent; stemens as many as sepals, positioned on the inside of each sepal; ovary superior or half inferior, 1-3 fused carpel, one locule and one ovule, basal placentation; fruits are berry, capsule, or nutlet; seeds strongly curved. Amaranthaceae species containing highly arid habitats which are grows in very salty soils. This family include extremely high seed production plants – ranging between 13,000 and 50,000 seeds per plant, depending on the richness of the soil⁷ and a fruit dispersal mechanism involving the whole plant, e.g. tumbleweed.

Some species of Amaranthaceae family are used as foods preservatives, natural food colors, and nutritions and in traditional folk medicine for the treatment of several diseases such as infections, inflammation, fever, antioxidants, aphrodisiac, analgesic, etc. The chemical analyses of Amaranthaceae plants done of researcher suggested that these are source of phenolic acids, aurones, betacyanins, betalains, betaxanthins, chromoalkaloids, ecdysteroids, flavonoids, protoalkaloids, saponins, steroids, and triterpenes^8-15. Therefore, the species of the Amaranthaceae family are having antioxidant activity due to the presence of phenolic compound which has capacity to scavenge free radicals, protect against lipid peroxidation and quench reactive oxygen species^10,16-19. Hence, members of this plant family (containing betaxanthins and betalains) are used in the extraction of natural pigments as food colorants and antioxidants^8,10,17. Many species of this family have red inflorescence, fruits, and vegetable parts due to presence of betalains pigments (it is class of nitrogen containing pigments). In some species, the red color is due to presence of flavonoid pigments which has similar color even though they have different chemical structures.

The plants of the Amaranthus family can be identified from the tropics to cool temperate regions. Nativity of the Amaranthaceae are tropical and subtropical areas of Central America, Africa and Australia²⁰, Amaranthus tricolor is main species grows predominantly in Asia, Amaranthus dubious is cultivated in the Caribbean land while Amaranthus cruentus is grows predominantly in Africa and some of the Amaranthus species as grain crops are present in South America.

The plant genus Celosia of Amaranthaceae family (genus of annual or perennial herbs, edible and ornamental plants), consisting of about 60 species (Caryophyllales) worldwide, is native to subtropical and temperate zones of Africa, South America, and South East Asia. The flowers of the species of Celosia genus is of edible and ornamental plants. The generic name is derived from the Greek word kelos, meaning "burned," and refers to the flame-like flower heads. These are commonly known examples are wool-flowers, brain celosia or cockscombs, if the flower heads are crested by fasciation; it is called as Velvet flower.

Celosia argentea is a smooth annual herb type plant and routinely used as leafy vegetable²¹ in the rainforest zone of Africa. In India and China, it is known as a troublesome weed. It is a herbaceous plant and is known for its very bright colors and traditional uses²². This is plant of tropical origin; they grow best in full sunlight and should be placed in a well drained area. The wild form of Celosia argentea (sometimes referred to as C. trigyna) is a potherb throughout the savanna area of tropical Africa. The common names of Celosia argentea as semen celosiae, celosia, silver cock’s comb, cock’s comb, quail grass, woolflower in English. In India, locally it has different names as per regions and culture or traditional uses in different names as sitivara, vitunnaka, sunishannaka (Sanskrit), indivara, survali, safed murga (Hindi), annesoppu, and kanne hoo (Kannada)²³.

2. SCIENTIFIC CLASSIFICATION:

Kingdom	: Plantae (Angiosperms)
Super division	: Spermatophyte
Division	: Eudicots / Magnoliophyta
Class	: Core eudicots / Magnoliopsida
Order	: Caryophyllales
Family	: Amaranthaceae (flowering plants)
Subfamily	: Amaranthoideae and Gomphrenoideae
Genus	: Celosia (184 scientific plant, 51 species are accepted) and Lithophila
Species	: C. argentea
Binomial name	: Celosia argentea L., Amaranthus Cristatus
Synonyms	: Celosia cristata, Semen celosiae.

3. VERNACULAR NAMES:

English : Common coxcomb, Crested coxcomb, Feather coxcomb

Telugu : Gurugu, Panchechettu

Hindi : Sufaid murga, Indivara, Survali, Laal Murga

Sanskrit : Vitunnaka, Sitivara, Sunishannaka

Panjabi : Srwali

Marathi : Kombda

Kannada : Kanne Hoo

Chinese : Bairihong, Ye ji guan huo, Guo weicao, Ji guan huo

French : Amarantecrete de coq, Celosieargentee, Celociecrete de coq

4. DESCRIPTION:

Celosia argentea L. is fast growing, erect, coarse, simple or branched and smooth annual herb, 0.4 – 2 m in height with many ascending branches and brilliant colored bedding plants. Steam and branches of herb are strongly ridged and often sulcate, quite glabrous²⁴.

Leaves are alternate, lanceolate-oblong to narrow linear, entire, 4 to 14 cm long, acute to obtuse, shortly mucronate with the excurrent midrib, glabrous, bitter taste and odour, light green; lamina of the leaves from the centre of the main stem 2-15 x 0.1-3.2 cm, tapering below into an indistinctly demarcated, slender petiole; upper and branch leaves smaller, markedly reducing; leaf axils often with small leaved sterile shoots.

Inflorescence dense (rarely laxer below) many-flowered spike, 2.5-20 x 1.5-2.2 cm, small, silvery to pink colored, 8 to 12 mm long, conical at first but becoming latter cylindrical in full flower, more flowers at the ends of stem and branches, sulcate peduncle up to 20 cm long, which often lengthens during flowering. The bracts and bracteoles lanceolate or the lower deltoid towards the base of the spike deltoid having 3-5 mm long hyaline with more or less aristate with the excurrent midrib, persistent after the fall of the flower. Perianth segments are 6-10 mm long, narrowly oblong -elliptic, acute to rather blunt, shortly mucronate with the excurrent midrib, with 2-4 lateral nerves ascending more than halfway up the centre of each segment, margins widely hyaline. Filaments very delicate, 5-6 mm long with free 2.5- 3 mm part, the free part subequalling or exceeding the staminal sheath, sinuses rounded with no or very minute intermediate teeth, both anthers and filaments creamy to magenta. Stigmata 2-3, very short, the filiform style 5-7 mm long; ovary 4-8-ovulate. Capsule 3-4 mm, ovoid to almost globular. Roots are cylindrical, white with characteristic odor and having bitter test. The length of roots ranges from 12–15 cm in length and 2–3 cm in breadth.

Semen Celosiae is splendent oblate seed of C. argentea plant, with a diameter of 1.25–1.5 mm, lenticular, shining, black or reddish-black surface, middle-eminence, hilum in latero-scoop, testa very finely reticulate and with its seed coat thin and crumbly. Semen Celosiae is the most important part of herbal medicine in C. argentea, but due to the equivocal profile, coloration, and texture, it is hard to distinguish the Semen Celosiae from Semen Cristata. However, it is noted that, seeds are most important part for medicine.

5. OCCURRENCE:

Celosia argentea plant is known worldwide, its use for food. These plants can be found growing wildly insubtropics and warm temperate zones - W-E Nepal: Bhutan, Cambodia, China, Japan, Korea, India, Laos, Malaysia, Myanmar, Philippines, Russia, Thailand, Vietnam; Tropical Africa. C. argentea is an important cultivated vegetable herb in the rainforest zone of Tropical Africa region. The wild form, referred to as C. trigyna is a potherb throughout the savanna area of tropical Africa. Celosia argentea, a weed grows in rainy season throughout hilly and dry area of India and other tropical regions of the world mainly in Sri Lanka, Yeman, Indonesia, America and West indies²⁴. Early, it grows slowly but flowering may occurs within 6-7 weeks from sowing. It grows best in areas where temperature is in the range 25 – 30⁰C, but can tolerate 20 – 40⁰C but not survival below 5⁰C.

6. CULTIVATION:

Celosia argentea in India mainly grow as weed wildly and now it cultivated in Tirunelveli. Now most of the hot and malnourished regions of the equatorial zone cultivated the species of celosia species plants as vegetable and flowering plants in gardens. It can be planted well in humid areas or during monsoon season and it grows in the wet season. C. argentea is a simple plant needs moderate soil moisture for its proper growth²⁴. C. argentea was cultivated for cut flower production in Israel²⁵, Japan and Netherlands, and the local environmental conditions in the tropical zone is suitable for their growth.

7. TRADITIONAL AND PHARMACOLOGICAL USES:

Let food be the medicine and medicine be the food is the lifestyle of people nearly 2500 years ago. But in traditional societies, nutrition and healthcare both are strongly interconnected and therefore many plants have been consumed both as food and for medicinal purpose^26a,b.

Celosia argentea plant shows different physiological effects because of different bioactive compounds present in it and therefore is widely used to cure several disorders such as fever, diarrhea, piles, bleeding nose, mouth sores, itching, wounds, jaundice, gonorrhea, and has different pharmacological activity such as immunological activity, cytoprotective, inflammation, antioxidant, haematological, antidiarrheal, anticancer, antimitotic activity, hepatoprotective, antimetastatic, antioxidant, antibacterial, antifungal, antidiarrhead activity, gynaecologic disorders, anti-urolithiatic, growth activity and also as disinfectant^26c,27; the dry powder of seeds are useful in diarrhea, aphrodisiac, reduce the inflammations, strength the liver, gonorrhea, clearing the vision and healing diseases of the eye; burnt leaves are stypice (Unani). The dried plant is considered antiscorbutic and cooling in China.

1. Pawra Tribe of Satpura Hills, Maharashtra, India was used Celosia argentea for the treatment of white discharge. Whole plant dry powder (local name – Rukada) approximately 20 g is given with cup of milk during night for 7 days²⁸. The leaves are used as a vegetable in Philippines, Moluccas and West Tropical Africa because of good source of protein, carbohydrate, and minerals.

2. In Indian folk medicines, it is used for diabetes²⁹, seeds are used for the treatment of jaundice, diarrhea, gonorrhea, wounds and fever; in Shri Lanka, leaves are used for inflammations, fever and itching; in China, flowers and seeds used in treatment of gastroenteritis and leucorrhea, profuse uterine bleeding and in Antilles, decoction of flowers used for phthisis^30a; in USA, rural Honduras practice C. argentea for encouraging lactation and its decoction for hemorrhage^30b; in Riau province, Sumatra (Indonesia) antibacterial assay of extracts of 114 species were tested and C. argentea was found to have activity against cough and jaundice^30c; in Vietnam, C. argentea plant is used as hemostatic herb^30d; in screening of Taiwanese crude flower extract of C. argentea was found antibacterial effect against Streptococcus mutants^30e, and also flowers of the plant are used against snakebite^30f. The leaves and flowers are used as edible and are grown for such use in Africa and Southeast Asia^30g.

3. Celosia argentea roots along with other plants sample powder in water is used to treat inflammation in Ogun State, Nigeria³¹. Bruised stems and leaves of Celosia argentea are applied as poultice for infected sores, boils, and skin eruptions.

4. Poultice of leaves, smeared with honey, used as cooling application to inflamed areas and painful affections such as buboes and abscesses.

5. Celosia argentea seeds powder where used to treat eye diseases (redness and swelling) and mouth sores in China and Japan³². It is used to treat photophobia, and frequent lacrimation with intense headache. It is acts as principal, ministerial, adjunctive or messenger drug.

6. Whole plant and flowers are used as antidote for snake poison^30f. This plant exhibits good quantity of micronutrients like Mg, Ca, S, P, K and Fe and toxic elementals show their concentrations below permissible limit therefore used as supplementary food for deficiency of minerals like iron (Fe), magnesium (Mg) and calcium (Ca)³³.

7. Celosia argentea used for treatment of constipation, 7 to 9 cm piece of fresh root is crushed and soaked in half glass of water for 4 - 5 hours and this water is admistered to the patient once a day for two days. Also, the curry of fried leaves is used instead of root extract in most of region of tribe³⁴. The powder of root of Celosia argentea used for treatment of stomachache, half spoon of powder is administrated for adult and half of its is used for children in single dose³⁴.

8. In folk practices, Semen celosiae, the seeds, leaf and steam of Celosia argentea has been traditionally used for treatment of diabetes, aphrodisiac, cataracts, keratitis, iridocyclitis, caligo corneae, gastrointestinal disorders, antipyratic and sarcoptidosis³⁵. The report suggests that it is also useful in the therapeutics of jaundice, inflammation, metrrorhagia, gonorrhoea, and the healing of wounds (alcoholic extract) and injuries^35-37. Decoction of the seeds with sugar is prescribed against dysentery of human and animals. Crude ethanol extract of Semen celosiae, the seeds of Celosia argentea possessed antipyretic, antispasmodic, anticancer, diuretic and antibacterial activities. The water extract of Semen celosiae, the seeds of Celosia argentea shows most significant protective effect on CCl₄-induced liver injury in rats³⁸. An acidic polysaccharide from the Semen Celosiae, is a potent anti-hepatotoxic agent for chemical and immunological liver injury models in animals³⁸. Celosian is also an immunostimulating agent in addition to its antihepatotoxic effects³⁶.

9. Ethanol extract of Celosia argentea L. (Amaranthacea) shows remarkable hepatoprotective activity against paracetamol induced liver injury in rat at the dose of 250 and 500 mg/kg which is judged from the serum marker enzyme³⁹.

10. The seed paste is used to cure ovarian and uterine diseases^40-41.

11. The use of Celosia argentea Linn aqueous flower extract as a natural indicator in acid base titration was studied⁴². An equivalence point obtained by the flower extract was coincident with the equivalence points obtained by standard indicators expected in weak acid against weak base titration. This becomes best indicator for all type of acid-base titration because of economy, simplicity and availability.

12. Anti-metastatic and immunomodulating activities^43a,b of the water extract of seeds of Celosia argentea plant showed that administration of seed extracts for 7 days before tumor inoculation significantly inhibited liver metastasis caused by intraportal injection of colon 26-L5 carcinoma cells in a dose-dependent manner^43a. The 70% ethanol extract and water extract of aerial part of plant were screened for delayed type hypersensitivity, neutrophil adhesion test, and cyclophosphamide induced myelosuppression to assess the effect on immunity in Swiss albino mice at the dose of 50 and 100 mg/kg^43b.

13. Anti-diabetic activity of alcoholic extract of seeds and roots separately of Celosia argentea Linn is studied in rats and results reported that chronic administration of the extract directly significantly reduced the blood glucose in alloxan-induced diabetic rats for two weeks and also prevented a decrease in their body weight²⁹.

14. Anti-microbial activity of ethanolic extract of Celosia argentea root on different microorganisms (bacteria) is studied and the extract showed significant antimicrobial activity especially against E. coli and S. aureus⁴⁴ while plant seed oil n-hexane extract showed antifungal activity against Aspergillus fumigatus, Candida tropicalis and Trichophyton mentagrophytes^45a. The leaves, stem and root extract in aqueous ethanol of Celosia argentea were subjected for antimicrobial study; the leaf extract shows antifungal activity and anti bacterial activity, stem extract and root extract had only antibacterial activity and no antifungal effect and bactericidal at the same concentration for all bacterial strains with the exception of Escherichia coli^45b.

15. Ethanolic extract of Celosia argentea plant showed a remarkable hepatoprotective activity against paracetamol induced hepatotoxicity³⁹.

16. Flavonoid fraction from Celosia argentea Linn leaves are shows significant dose dependent anti-inflammatory activity in rat paw edema and cotton pellet induced chronic inflammatory models⁴⁶.

17. Three new triterpenoid saponins, named celosin E, celosin F and celosin G, together with a known compound cristatain were isolated from the seeds of Celosia argentea L. and shows in vitro antitumor and anti-inflammatory activities⁴⁷.

18. Ethanolic extract of Celosia argentea (seed) showed significant anti urolithiatic activity⁴⁸.

19. Phenols (epigallocatechin) present in aqueous extract of leaves of C. argentea were showing anti-inflammatory⁴⁶ and anti-oxidant properties. Aqueous extract shows cadmium-induced oxidative stress in the animals, with the best result at the dose of 400 mg/kg⁴⁹.

20. Semen Celosiae can diffuse the papillae and is not for application in patients with glaucoma. There is no more side effects were recorded in related literature and the investigation of its related toxicity was lacking²⁹.

21. Semen Celosiae can diffuse the papillae, and is not for application in patients with glaucoma, and liver and kidney dysfunction^50a,b. No more side effects were recorded in related literature. In general, C. argentea is a safe medicinal product even in larger dosages.

8. CHEMICAL CONSTITUENTS:

Phytochemical screening of steams, leaves, and roots yielded starch, protein, tannin, flavonoids, saponins, fat, sugar, proteins. The total ash content of steams, leaves, and roots is 16.2%, 16% and 12.6%; from which insoluble ash content is 6.3%, 6.5% and 5.6% respectively. The study suggested that, protein and flavonoid content is higher in leaf while carbohydrate content is higher in root. Therefore, this plant is used as vegetable in most of Tribes. A variety phytoconstitutents^43a,51a-b are isolated from the C. argentea L which includes flavonoids – Isoflavones and latlancuayin; glycosides; phenols – Lutin, epigallocatechin, gallic acid, caffeic acid, rosmarinic acid, quercetin; tannins; triterpenoid saponins - celosin A-G, celosin I-II and celosin H-J together with a known compound cristatain; Cycpeptide – morodin, celogentin A –K and celogenamide A; betalains - 2-descarboxy betandin, amaranthin, isoamaranthin, betalimic acid, miraxanthin V, (S)-Tryptophan, (S)-Tryptophan-BX, 3-methoxytyramine-BX; lyciumin-A methylate; lyciumin-C methylate; Fatty acid – arachic acid, arachidonic acid, linolenic acid, hexadecanoic acid, palmitoleic acid, octadecanoic acid, octadecanoic monoenoic acid, oleinic acid, linoleic acid; solanine; β-sitosterol; betaxanthins; a and β-gamachaconines. This plant is good source of minerals because of their higher amount such as Ca – 178.08 mg, P – 38.01 mg, K – 62.34 mg, Na – 35.25 mg, Mg – 39.64 mg, Fe – 15.25 mg, Zn – 7.25 mg, and Cu – 3.75 mg per 100 g of sample with trace amount of Cr, Mn, Ni, and Pb.

The phytochemical contents extracted is depends on medium and condition such as - aqueous extract shows presence of alkaloids, carbohydrates, glycosides, tannins, protein, amino acids, steroids; methanolic extract shows presence of alkaloids, carbohydrates, glycosides, tannins, protein, amino acids, and steroids; while Chloroform extract shows presence of carbohydrates, tannins and petroleum ether extract shows presence of alkaloids, carbohydrates, glycosides, protein and amino acids.

A new three bicyclic moroidin type peptides, Celogentin A, B and Celogentin C antimiotic along with moroidin, were extracted in methanol from the seeds of Celosia argentea. The celogentin C is four times more potent for inhibitory activity than moroidin. Moroidin is isolated from the seeds of C. argentea in methanol, which is a unique bicyclic peptide originally isolated from Laportea moroides (Labiatae)^52b, remarkably inhibits the tubulin polymerization⁵³ and studied their microtubule activity^52a.

Betaxanthins are the conjugation products of betalamic acid with different amino acids or amines; in Celosia argentea varieties, three immonium conjugates of betalamic acid with dopamine (miraxanthin-V or dopamine-betaxanthin, B₁), 3-methoxytyramine (3-methoxytyramine-betaxanthin, B₂) and (S)-tryptophan [(S)-tryptophan-betaxanthin, B₃]. These betaxanthins were isolated in aqueous methanol from Celosia argentea (yellow and orange-red fluorescence genotypes) besides the known betalamic acid and amaranthine/isoamaranthine (A₁/A₂). They are used as colourant properties in foods⁵⁴.

The amaranthin, a characteristic pigment is characterized from extract of red inflorescences of common cockscomb (Celosia argentea var. cristata) were compared and proved to be qualitatively identical to those of extracted from orange red inflorescence of feathered amaranth (Celosia argentea var. plumosa). It is fragmented in two parts in mass spectrum as betanin and betanidin⁵⁵. Comparative analyses of the pigments of yellow and orange inflorescences of C. argentea var. cristata (common cockscomb) and Celosia argentea var. plumosa (feathered amaranth) gave identical betalain patterns with the presence of three betaxanthins, two of them being new structures⁵⁵.

A new cyclic 17-membered nonapeptide, celogenamide A, has been isolated along with lyclumins A and C methylates from the methanol extract of seeds of Celosia argentea, and the structure including absolute stereochemistry was determined by chemical means and using extensive 2D NMR and LC-MS methods⁵⁶.

Two new oleanolic acid saponins; celosin A and celosin B, along with stigmasterol, β-sitosterol, β-daucosterol, hexacosoic acid, palmitic acid and stearic acid were isolated from the ethanolic extract of Semen celosiae, the seeds of Celosia argentea⁵⁷.

9. CONCLUSION:

C. argentea has been widely used in traditional medicine (generally seeds; Semen Celosiae) with a long history of India and China. It is reputed for the treatment of eye related issues and diseases. It induces hyperpyrexia of the liver, hepatic asthenia, heat in blood and used to cure several disorders such as fever, diarrhea, piles, bleeding nose, mouth sores, itching, wounds, jaundice, gonorrhea, and has different pharmacological activity such as immunological activity, cytoprotective, inflammation, antioxidant, haematological, anticancer, antimitotic activity, hepatoprotective, antimetastatic, antioxidant, antibacterial, antifungal, anti-diarrhead activity, gynaecologic disorders, anti-urolithiatic, anti-diabetes, immunomodulatory, growth activity anti-infection, anti-oxidant agent, and also as disinfectant among other plant samples. Till further study is urgently needed to gain a better understanding and formulation of C. argentea to provide better service for clinical use. C. argentea contains different secondary metabolites in which saponins, cyclic-peptides, phenols, and minerals are the main pharmacological active agents and triterpenoid saponins, Cycpeptide and betalains are the promising targets for further studies due to their bioactivities. Some of the researcher studies the pharmacological effects and the mechanisms of bioactive molecules for the treatment on particular disease have been performed, but complete understanding remains elusive. But till the pathways of their distribution, absorption, metabolism, and excretion by the human and animals are almost nonexistent and need to be urgently studied and clarified by pharmacokinetic studies. So far the studies are significant but limited to the level of active fractions or crude extracts and separation of bioactive molecules. Therefore, proper and systematic study of more promising bioactive chemical class of compounds or individual compounds should be done by using bioactivity-guided isolation strategies or by using different modeling strategies. The possible mechanism of action and potential synergistic or antagonistic effects of mixtures of bioactive compounds derived from C. argentea also need to be evaluated by integrating pharmacological, pharmacokinetic, bioavailability-centered, and physiological approaches. This is one of the plant which does not have any serious side effects or marked toxicity have been reported so far, but further relative systematic toxicity, storing ability and safety evaluation studies are still needed to assure safety for biological applications as herbal and allopathic medicine.

10. CONFLICTS OF INTEREST:

The authors declare no conflicts of interest.

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