TREATMENT OF VARIOUS DISEASES BY CARISSA SPINARUM L. – A PROMISING SHRUB

TREATMENT OF VARIOUS DISEASES BY CARISSA SPINARUM L. - A PROMISING SHRUB

Amreen Fatima*¹, Prem Prakash Singh ¹, Parul Agarwal ¹, Raghuveer Irchhaiya ¹, Shashi Alok ¹ and Amita Verma ²

Institute of Pharmacy, Bundelkhand University, Jhansi, Uttar Pradesh, India

Department of Pharmaceutical Sciences, Faculty of Health Sciences, Sam Higginbottom Institute of Agriculture, Technology and Sciences-Deemed University ², Allahabad, Uttar Pradesh, India

ABSTRACT: Carissa spinarum L.  is  a  small  spinous  evergreen  shrub  growing throughout  India  in  dry  regions.The plant used locally in Indian and Chinese system of medicines to cure various diseases. Carissa spinarum has also been used in the Ayurvedic medical system because of its therapeutic effects against liver disease, epileptic disease, microbial disease, cytotoxic, viral diseases.The isolated metabolites and crude extract have exhibited a wide of in vitro and in vivo pharmacological effect, including antioxidant, antimicrobial, antiviral, anticonvulsant, anticancer, antiarthritic, antihelmintic, cytotoxic activity. A chemical study of this plant was then initiated, and this led to the isolation of 12 compounds, including a coumarin, two cardiac glycosides and nine lignans. These isolated compounds were evaluated for several biological activities, including antiherpetic, cytotoxic, antioxidant and antibacterial effects.A shrub, Carissa spinarum have emerged as a good source of the traditional medicines for the treatment of inflammation, arthritis, microbial infection, epilepsy, viral infection, cancer disease. Pharmacological results have validated the use of this species in the traditional medicines. Some bioassays are difficult reproduce because the plant materials used have not been well identified; therefore analytical protocol and standardization of extracts should be established prior to biological evaluation. Root, stem and leaf of this shrub should receive more attention. Expansion of research materials would provide more opportunities for the discovery of new bioactive principles from the Carissa spinarum.

Carissa spinarum,   Karaunda, Pharmacological studies, Medicinal properties

INTRODUCTION: Plants and their secondary metabolic constituents have a long history of use in modern medicine and in certain systems of traditional medicine, and are the sources of important drugs such as atropine, codeine, digoxin, morphine, quinine and vincristine ¹. 

India is sitting on a gold mine of well-recorded and well-practiced knowledge of traditional herbal medicine. But, unlike China, India has not been able to capitalize on this herbal wealth by promoting its use in the developed world despite their renewed interest in herbal medicines ².

Plant-derived substances have recently become of great interest owing to their versatile applications. Medicinal plants are the richest bio resource of drug of traditional systems of medicine, modern medicines, neutraceuticals, food supplements, folk medicines, pharmaceutical intermediates, and chemical entities for synthetic drug ³.

Plant profile:

Synonyms: C. diffusaRoxb, C. ovata, C. brownii, C. edulis, C. opaca.

Family: Apocynaceae – the oleander family

Common names: Currant Bush, Conker berry, Bush Plum, Burrum Bush, Wild Karaunda ⁴.

Taxonomical Hierarchy ⁵:

Kingdom        :           Plantae

Subkingdom  :          Viridaeplantae

Phylum           :           Tracheophyta

Class               :           Magnoliopsida

Subclass          :           Asteridae

Order              :          Gentianales

Family                        :           Apocynaceae

Genus             :           Carissa

Species            :           Spinarum

Vernacular names ^{6, 7}:

Andhra Pradesh:         Vaka, kalivi, kalli;

Bengal             :           Karamacha;

Gujarat                        :           Karmarda;

Karnataka        :           Karekayi, garji, kavali;

Maharashtra    :           karavada, karanda, karwant;

Himachal Pradesh:     karondhu, garna, kharnu;

Hindi               :           Karunda;

Sanskrit           :           Karamarda, avighna;

Tamil Nadu     :           Kalakkay, kalachedi.

Botanical studies:

Distribution: Thorny bushes of C. spinarum L. are found commonly growing in the forests and wastelands up to elevations of 1,500 meters. They are highly drought-resistant. They bear small fruits which are eaten by all and are also offered for sale at many places.

This shrub is found wild in most parts of India, especially in the dry foothills of the Punjab, the sub-Himalayan tract up to 4,000 feet in the trans-Indus territory and also on the coast of the southern Andaman (Fig. 1) Carissa spinarum L. ⁸.

FIG: 1 CARISSA SPINARUM L.

Morphology: An erect thorny shrub, with forked branches, 2-3 meters in height; wood, very hard; bark, light brown to green, can be stripped off longitudinally by hand, exposing the white to light-green wood underneath; thorns, 3.2 cm long, brown to greenish at the base and deep brown towards the tip.

Leaves ovate, 4.5 cm long, 2.5 cm broad, leathery, venation, reticulate pinnate; margin, entire; petiole 3 mm long; leaves exuding white latex, when plucked from the stem.

Flowers, short-stalked, sweetly scented, bisexual, complete, bracteates, cyclic, actinomorphic, their color varying between white and camellia rose 622; inflorescence, terminal or a corymbs cymes, with about 10 flowers; calyx, polysepalous, with 5 sepals, green, companulate, 2 to 3 mm, long; corolla, tubular at the base, dilated at the top, five-lobed, glabrous, white, the dilation of corolla 8 to 9 mm; androecium, with 5 stamens, each 2 to 3 mm long, inserted near the neck of the tubular portion of the corolla; gynoecium, one, superior, 7 to 8 mm long, with a spindle-shaped stigma. Fruit, an ovoid berry, 9 mm in length, 6 mm in diameter, 642 mg in weight, 586 microlitres in volume; fruit color, hyacinth blue 40; pulp, scarlet 19/2; juice, shrimp red 616/3.

Seeds lanceolate, 5 to 6 mm in length, 4 mm in diameter, black, each 28 mg in weight, 42 microlitres in volume ⁸.

The flowering and fruiting season: Generally, the flowering takes place during April and May. In some cases, it might start even by the end of July. The peak flowering season, however, was observed to occur by the middle of May. The small fruits take a lot of time to develop and mature. They start ripening from November and continue to do so till the end of January. Mature fruits were also observed on some bushes as late as April. These fruits were, probably, the outcome of the July blossoming ⁸.

Yield: The average yield of medium-sized bush is C. spinarum L. was found to be 272 grams.

Chemical Constituents:

Chemical composition of the fruit: The fresh fruits contain acids, sugars, reducing sugars, non-reducing sugars, tannins, pectin and vitamin C. carissol (an epimer of α-amyrin), lupeol, oxalic, tartaric, citric, malic, malonic and glycolic acids, glycine, alanine, phenyl alkaline, cerine, glucose and galactose.

Chemical composition of the Root: Carissone, carindone, carinol, odoroside H, digitoxigenin, glucose and D- digitalose.

CARISSONE       CARINOL            CARINDONE

Chemical composition of the Seed: Fatty acids, viz., palmitic, stearic, oleic, arachidic, linoleic acids.

Chemical composition of the Leave: Triterpene alcohol, ursolic acid.

Chemical composition of the Flower: myrcene, limonene, camphene, canene, dipentene, farnesol, nerolidol, dihydrojasmone, α-terpeneol, citronellal, β-ionone, nerylacetate, linalool and geranyl acetate ⁹.

Medicinal properties: The roots of C. spinarum L. are reported to be many medicinal uses. They are ground and put into the wounds of cattle to kill worms. It is also used in combination with the roots of some other medicinal plants to treat rheumatism by the mundas (a tribe) of Chhota Nagpur. It is a strong purgative and is used as one of the ingredients in some purgative preparations. A large dose of the roots of C. spinarum L.  may even prove fatal owing to profuse purging. The roots also act as a repellent in the case of snakes, when the roughly ground powder of the roots mixed with water is poured into the holes of snakes ⁸.

The medicinal uses, commercial uses, edible uses and other uses of C. Spinarum whole plant are given in Table 1. ¹⁰.

TABLE 1: THE MEDICINAL USES, COMMERCIAL USES, EDIBLE USES AND OTHER USES OF C. SPINARUM WHOLE PLANT

Dessert quality: The fruits are eaten along with the seeds. They are sweet in taste and of fairly good quality.

Utilization: As stated earlier, the small fruits of C. spinarum L. are commonly eaten and are also offered for sale at certain places. As it is evident from the chemical composition of the fruit, it is highly nutritious and is a very good source of protein. The content of total soluble solids is very high and indicates the possibility of this wild fruit being dehydrated and processed. Research should be taken up in this direction.

The bushes of this wild plant are thorny and are very effective as a fence and are mainly used in the villages for this purpose. These bushes are very hardy and drought-resistant and can grow even on very poor and rocky soils. Therefore they can be used for afforestation in soil conservation. The leaves are fairly rich in tannins (9-15 per cent) and constitute a promising tanning material, particularly in combination with other tanning stuffs, such as the twigs and bark of Emblica officinalis Gaertn ⁸.

Family Apocynaceae: Trees, shrubs, or vines, rarely sub shrubs or herbs, with latex or rarely watery juice. The Leaves simple, opposite, rarely whorled or alternate, pinnately veined; stipules absent or rarely present. Inflorescences cymose, terminal or auxiliary, with bracteoles. Flowers are bisexual, 5- [or 4]-merous, actinomorphic. Calyx 5- or rarely 4-partite, quincuncial, basal glands usually present.  Corolla 5- or rarely 4-lobed, salver form, funnel form, urceolate, or rarely rotate, lobes overlapping to right or left, rarely valvate.

Stamens 5 or rarely 4; filaments short; anthers mostly sagittate, free or connivent into a cone adherent to pistil head, dehiscing longitudinally, base rounded, cordate, sagittate, or prolonged into an empty spur; pollen granular; disc ring like or cup-shaped, 2-5-lobed, or absent. Ovaries superior, rarely half-inferior, connate or distinct, 1- or 2-locular; ovules (1 or) 2-numerous per locule Style 1; pistil head capitates, conical, or lampshade – shaped, base stigmatic, apex 2-cleft and not stigmatic.

Fruit a berry, drupe, capsule, or follicle. Seeds with or without coma; endosperm thick and often horny, scanty but sometimes absent; embryo straight or nearly so, cotyledons often large, radical teretes.

Fruit type is highly diversified in the family, and it is diagnostic of many genera. Genera 1-4 produce 1, 2-celled berries from a flower; genus 5 produces 2, 1-celled berries from a flower; 6 and 7 produce mostly fleshy follicles containing deeply indented seeds with ruminate endosperm; 8 has follicles and winged seeds; 9 produces follicles and seeds with 2 comas; 10-12 have follicles with globose seeds; 13-18 have drupes mostly with fleshy mesocarp; 19 has samaroid fruit; 20 has spiny capsules with seeds winged all around; and 21-44 have free or fused follicles and comose seeds. Double flowers are known only from cultivated forms of Nerium oleander, Tabernaemontana divaricata, and Wrightia religiosa.

Plants of the Apocynaceae are often poisonous and are rich in alkaloids or glycosides, especially in the seeds and latex. Some species are valuable sources of medicine, insecticides, fibers, and rubber. About 155 genera and 2000 species distributed primarily in the tropics and subtropics, poorly represented in the temperate regions. Of the 44 genera and 145 species present in China, one genus and 38 species are endemic, and nearly 95% of the taxa grow in the southern in the southern and southwestern portions of the country ¹¹.

Genus Carissa: Shrubs are climbers, or small trees, mostly spiny, branches dichotomous. Leaves opposite; petiole 2-3 mm. Cymes terminal or auxiliary, dichotomous, pedunculate, usually many flowered. Flowers are 5- [or 4]-merous, Calyx without gland or rarely with many basal gland inside. Corolla salver form, tube cylindrical, dilated at stamina insertion, lobes overlapping to left or to right. Stamens included in throat; anthers lanceolate, obtuse or apiculate, base not appendage; disc absent. Ovary are 2-loculed; ovules 1-4 in each locule, rarely numerous, biseriate. Style are fili form; pistil head narrowly oblong or fusi form, apex shortly 2-cleft. Berries are 1- [or 2]-loculed. Seeds are 2 or more, peltate; endosperm fleshy; cotyledons ovate, radicle inferior. About 30 species: tropics and subtropics of Africa, Asia, and Australia; four species in China ¹².

Species spinarum: A bushy shrub or tree with rigid spreading branches armed with straight thorns. This evergreen plant found throughout the hotter parts of India and sub-Himalayan region. It is also observed in Andaman Islands.

Light grey fibrous barks, white or pink fragrant flowers in clusters. Berries dark purple or black. It can be cultivated in gardens, mostly as hedges for its fragrant flowers and edible berries. Berries make good tarts, syrups, jellies or a cooked preserve. Flowers are used for personal adornment.

Leaves are used in tanning industry and as fodder for sheep and goats. It is also suitable for rock gardens and fencing ¹⁰.

Pharmacological studies done so far on Carissa spinarum L.: The pharmacological studies done so far on Carissa spinarum L. are given in Table 2.

TABLE 2: THE PHARMACOLOGICAL STUDIES DONE SO FAR ON CARISSA SPINARUM L.

Toxicity: There was no mortality amongst the graded dose groups of animals and they did not show any toxicity of behavioral changes at a dose level of 2000mg/kg. This finding suggests that the ERCS is safe in or non-toxic to rats and hence doses of 100, 200 and 400 mg/kg, p.o were selected for study ^{13, 14, 16}.

The evaluation of acute toxicity for the Carissa edulis extract at the therapeutic oral dose of 250 mg/kg in uninfected male and female Balb/C mice. The results indicate that there was no significant difference in the mean weights of mice given an oral dose of extract at 250mg/kg and the control that were given no drug in both sexes of mice ²⁷.

The median lethal dose (LD₅₀) of the Carissa edulis extract in mice was found to be 282.8 mg/kg body weight administered intraperitoneally. At 1000 mg/kg dose there was 100% mortality and the minimum dose that killed a rodent was 100 mg/kg. The oral LD₅₀ value for Carissa edulis was above 5000 mg/kg ¹⁵.

 CONCLUSION: The present review discusses the pharmacological aspect of the shrub C. spinarum and especially provides a detail analysis of the literature published since the year 1771. Glycosides, flavonoids, saponins, triterpenoids, steroids, tannins and other phenolic compounds are commonly occurred in this species. Pharmacological studies carried out on crude extracts and pure metabolites provided pragmatic documents for its traditional uses, and have revealed this shrub to be a valuable source for medicinally important molecules.

Throughout our literature review, we observed that C. spinarum were inclined to dissimilar pharmacological functions. The C. spinarum possesses potent antimicrobial and nutritional evaluation. The C. spinarum is good treatment of Hepatoprotective, helmintic and cytotoxic diseases. The toxicity of C. spinarum shows no mortality amongst the dosed group of animals and they did not show any toxicity or behavioral changes at a dose level of 2000mg/kg. This finding probably suggests that the C. spinarum is relatively safe in or non-toxic.

Expansion of research materials would provide more chances for discovery of new bioactive principle from the C. spinarum.

ACKNOWLEDGEMENT: The authors are thankful to the authorities of Bundelkhand University, Jhansi, for providing support to the study and other necessary facilities like internet surfing, library and other technical support to write this review article.

REFERENCES:

1. Tyler VE: Public Health Nutrition. Edition 3, 2000, 447–452.
2. Kamboj VP: Current science. 2000, 35.
3. Ncube NS, Afolayan AJ and Okoh AI: Assessment techniques of antimicrobial properties of natural compounds of plant origin: current methods and future trends. African Journal of Biotechnology 2008; 7(12): 1797-1806.
4. www.somemagneticislandplants.com.au/index.../72-carissa-spinarum
5. Altera MP: L Publication, 1771, 559.
6. Trivedi PC: Book Review: Indian Medicinal Plants. IndianJournal of Traditional knowledge 2009; 8(4): 1-2.
7. Kirtikar KR and Basu BD: Indian Medicinal Plants. Edition 2, 1980: 1548-1549.
8. Parmar C and Kaushal MK: Carissa spinarum. In: Wild Fruits. Kalyani Publishers, New Delhi, India. 1982: 15–18.
9. Sharma PC, Yelne MB and Dennis TJ: Database on Medicinal Plants Used In Ayurveda. Edition 3, 2005: 369-377.
10. www.floracafe.com/Search_PhotoDetails.aspx?Photo=Top&Id...
11. Bingtao LI, Antony JM, Leeuwenberg DJ and Middleton: "Apocynaceae" in Flora of China. Published by Science Press (Beijing) and Missouri Botanical Garden Press 2012; 16: 143.
12. Bingtao LI, Antony JM, Leeuwenberg DJ and Middleton: "Carissa" in Flora of China. Published by Science Press (Beijing) and Missouri Botanical Garden Press 2012; 16: 146.
13. Hegde K, Issac C and Joshi AB: Antiarthritic activity of Carissa spinarum root extract in freund’s adjuvant induced polyarthritis in rats. Pharmacology online 2010; 2: 713-718.
14. Hegde K, Satyanarayana D and Joshi AB: Evaluation of anticonvulsant activity of Carissa spinarum root extract. RJPS 2011; 1(1): 64-68.
15. Ya’u J, Yaro AH, Abubakar MS, Anuka JA and Hussaini IM:  Anticonvulsant activity of Carissa edulis (Vahl) (Apocynaceae) root bark extract. Journal of etnopharmacology 2008; 120: 255-258.
16. Hegde K and Joshi AB: Hepatoprotective and antioxidant effect of Carissa spinarum root extract against CCl4 and paracetamol-induced hepatic damage in rats. Bangladesh J Pharmacol 2010; 5: 73-76.
17. Khan MR, Sahreen S and Khan RA: Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl₄-induced damage in rat. BMC Complementary and Alternative Medicine 2011; 11: 48.
18. Khan MR, Sahreen S and Khan RA: Evaluation of antioxidant activities of various solvent extracts of Carissa opaca fruits. Food Chemistry 2010; 122: 1205–1211.
19. Rao JM, Rao RJ, Kumar, US, Reddy SV and Tiwari AK: Antioxidant and a new germacrane sesquiterpene from Carissa Spinarum. Natural Product Research 2004; 19(8): 763-769.
20. Harwansh RK, Garabadu D, Rahman MA and Garabadu PS: In vitro antihelmintic activity of different extracts of root of Carissa spinarum. IJPSR 2010; 1(10): 84-88.
21. Sanwal R and Chaudhary AK: Wound healing and antimicrobial potential of Carissa spinarum L. in albino mice. Journal of Ethnopharmacology 2011; 135: 792–796.
22. Sarla S, Subhash C and Alok KS: Nutritional evaluation, antimicrobial activity and phytochemical screening of wild edible fruit (Carissa opaca). International Research Journal of Pharmacy 2011; 2(12): 217-221.
23. Ibrahim H, Oyi RA, Ehinmidu JO, Musa KY and Bright NT: Antimicrobial activity of the water extracts of the leaves and fruits of Carissa edulis Vahl (Apocynaceae). Journal of Medicinal Plants Research 2010; 4(11): 1028-1032.
24. Nedi T, Mekonnen N and Urga K: Diuretic effect of the crude extracts of Carissa edulis in rats. Journal of Ethnopharmacology 2004; 95: 57-65.
25. El-Fiky FK, Abou-Karam MA and Afify EA: Effect of Luffa aegyptiaca (seeds) and Carissa edulis (leaves) extracts on blood glucose level of normal and streptozotocin diabetic rats. Journal of Ethnopharmacology 1996; 50: 43-47.
26. Zia M, Bibi Y, Nisa S and Chaudhary FM: Antibacterial activity of some selected medicinal plants of Pakistan. BMC complementary and alternative medicine 2011; 11: 52.
27. Tolo FM, Rukunda GM, Muli FW, Njagi ENM, Njue W, Kumon K, Mungai GM, Mathaura CN, Muli JM, Keter LK, Oishi E and Kofi-Tsekpo MW: Anti-viral activity of the extracts of a Kenyan medicinal plant Carissa edulis against herpes simplex virus. Journal of Ethnopharmacology 2006; 104: 92-99.
28.  Tolo FM, Rukunga GM, Muli FW, Ochora J, Eizuru Y, Muthaura CN, Kimani CW, Mungai GM and Kofi-Tsekpo MW: In vitro antiviral activity of aqueous extracts of Kenyan Carissa edulis, Prunus Africana and Melia azedarach against human cytomegalovirus. African Journal of Health Sciences 2007; 14: 143-148.
29. Tolo FM, Rukunga GW, Muli FW, Ochora JM, Irungu BN, Muthaura CN, Wanjiku CK, Mungai GM, Ngoc Q, Hashimoto K and Asakawa Y: The antiviral activity of compounds isolated from Kenyan Carissa edulis (Forssk.) Vahl. Journal of Medicinal Plants Research 2010; 4(15): 1517-1522.
30. Kebenei JS, Ndalut PK and Sabah AO: Anti-plasmodial activity of Nortrachelogenin from the root bark of Carissa edulis (Vahl). International Journal of Applied Research in Natural Products 2011; 4(3): 1-5.
31. Koffuor GA, Sam GH, Dadzeasah PE, Owiafe EO and Asante-Gvapong A: Erythropoietic effects of the ethanolic root bark extract of Carissa edulis in phenylhydrazine-induced anemic Sprague-dawley rats. Research Journal of pharmacology 2012; 6(2): 20-24.
    

    ---

    How to cite this article:

    Fatima A, Singh PP, Agarwal P, Irchhaiya R, Alok S and Verma A: Treatment of various diseases by Carissa spinarum L. - A promising shrub. Int J Pharm Sci Res 2013: 4(7); 2489-2495. doi: 10.13040/IJPSR. 0975-8232.4(7).2489-95

    ---