Remarkable Advances in the Pharmacology of Carissa carandas

Swami Gaurav¹, Nagpal Navneet², Rahar Sandeep², Singh Preeti³, Singla Shivali⁴, Nagpal Manisha A² and Kapoor Reni⁵

¹CT Institute of Pharmaceutical Sciences, Jalandhar, India

²BIS college of Pharmacy, Moga, India

³Saroj Institute of Management and Technology, Lucknow, India

⁴Geetanjali Institute of Pharmacy, Udaipur, India

⁵Akal College of Pharmacy, Sangror, India

ABSTRACT:

Carissa carandas L. is known as Bengal Currant or Christ’s thorn, Karanda, kerenda (Malay), karaunda (India), nam phrom or namdaeng (Thailand), caramba (Philippines), kalakai (Tamil), and ci huang guo (Chinese). As per ethanopharmacology, Carissa carandas fruits are eaten to treat liver dysfunction, to break fever, to counteract the putrefaction of blood and roots are use in promote digestion. A remarkable advance in the pharmacology of Carissa species (Carissa carandas) show the antibacterial, scavengers of free radicals and inhibitors of xanthine oxidase, antioxidant, cardiotonic and blood pressure, anti convulsant activity, hepatoprotective, analgesic and anti-inflammatory activity. According to herbal and ayurveda system Carissa carandas also useful in the hypoglycemic conditions.

KEYWORDS: Carissa carandas, Hypoglycemic, Hepatoprotective, Blood pressure.

INTRODUCTION:

Carissa carandasL. (Arduina carandas[Linnaeus] K. Schumann, Damna-canthus esquirolii H. Léveillé) is a spiny treelet that grows up to 5m tall and is native to India and cultivated in Taiwan, India, Indonesia, Malaysia, Burma, Sri Lanka, Thailand, and the Pacific Islands. Its fruits, which can be eaten raw, are also made into jelly, or used for pies. The stems are up to 5cm long and show numerous spines, which are woody, simple or forked. The leaves are decussate, simple, and exstipulate. The petiole is 5mm long. The blade is light green, oblong, broadly ovate to oblong, 3cm – 7cm 1.5cm – 4.5cm. The base of the blade is broadly cuneate to round and the apex is shortly apiculate. The blade shows 5–8 pairs of secondary nerves. The inflorescences are terminal, usually 3-flowered cymes that are up to 2.5cm long. The flowers are fragrant. The calyx has five lobes, which are 2.5–7mm long, with many basal glands inside. The corolla is white or pale rose, the corolla tube is about 2cm long, puberulent inside, and develops five linear contorted 1cm-long acute lobes. The fruits are reddish-purple, 3cm 2.3cm – 6cm 3.7cm – 4.3cm 3cm, 1.5cm –2.5cm 1cm – 2cm, ellipsoid to grape-like (Figure 1)

ETHNOPHARMACOLOGY

In Cambodia, Laos, and Vietnam, the fruits are eaten to treat liver dysfunction, to break fever, and to counteract the putrefaction of blood. The roots are bitter and used to promote digestion. The juice expressed from the roots is applied externally to calm itching. The plant is known to produce pentacyclic triterpenoids, including carissin and lignans.⁴ Vohra and De reported some levels of cardioactivity from this plant.5 A remarkable advance in the pharmacology of Carissa species has been provided by the work of Lindsay et al.⁶ They isolated from the wood of Carissa lanceolata R. Br. a series of quinones with antibacterial activity — carindone, carissone, and ehydrocarissone (Figure 2).

Dehydrocarissone inhibited the growth of both Staphylococcus aureus and Escherichia coli with Minimum Inhibition Concentration (MIC) values inferior to 0.5mg/mL and about 2mg/mL against the Gram-negative bacillus Pseudomona aeruginosa. Taylor et al.⁷ made the interesting observation that a plant classified in the genus Carissa inhibits the survival of Herpes Simplex Virus (HSV), Sindbis virus, and poliovirus.⁸ Are carindone, carissone, and dehydrocarissone involved here? Does Carissa carandas L. have antiviral principles?

Note that the plant has probably some level of antidiabetic activity since oral administration of ethanolic extracts of leaves from Carissa edulis lowered blood glucose both in normal and streptozotocin (STZ) diabetic rats.^1-3

1. Scavengers of free radicals and inhibitors of xanthine oxidase:

Ethanolic and aqueous extracts of Carissa carandas from apocynaceae demonstrate 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals have scavenging activity. Inhibitory effects towards the invitro reaction of the hypoxanthine and xanthine oxidase (XO) were also carried out in the presence of plant extract, aglycones quercetin, kaempferol and apigenin along with allopurinol.

Table1: DPPH radical scavenging activity by plants extracts.

Scientific name	Family	Used part	IC₅₀ value (µg/ml)
Carissa carandas	Apocynaceae	Fruit
Aqueous			>100
Ethanol:water (4:1)			90
Ethanol:water (1:1)			>100

The xanthine oxidase inhibition activity of plant extracts of Carissa carandas had 50% xanthine oxidase inhibition with more than 100 µg/ml.

Two new compounds, the sesquiterpene glucoside and (6S,7R,8R)-7a-[β-glucopyranosyl)oxyl]lyoniresinol were isolated from the stem of Carissa carandas, together with three known lignans. The structures of the isolated compounds were determined on the basis of spectroscopic evidence.

2. Antioxidant activity:

Antioxidants are vital substances which possess the ability to protect the body from damages caused by free radical induced oxidative stress. The antioxidant activities of various extracts from different organs of Carissa carandas were screened for by using ferric thiocyanate (FTC) and thiobarbituric (TBA) methods. All the extracts showed strong antioxidant activities as compared to BHT (a commercial antioxidant) towards the autooxidation of linoleic acids.

The identification of major flavonoid content of carissa carandas was made based on the co-chromatography comparison with authentic markers, rf values, colours, ultra violet and mass spectrum analyses. The major compound in the extract was tentative identified as apigenin 6-C-rhamnosil-7-O-rhamnoside.

Table 2: Identification of flavonoid glycosides in Carissa carandas.

Flavonoids	*Hydrolysis*		Colour		Rf values			HPLC retention time
Flavonoids	Aglycone	Sugar	UV	UV + NH₃	BAW	15% HOAc	H₂O	HPLC retention time
Pelargonidin 3-O-glucoside	Pelargonidin	glucose	Yellow	Bright yellow	44	42	0	15.5
Chrysoeriol 7-O-glucoside	Chrysoeriol	glucose	Yellow	Yellow	38	11	0	10.8
Quercetin 3-O-methyl 7-O-glucoside	Quercetin 3-O-methyl	glucose	Orange	Bright Orange	33	7	0	15.6
Apigenin 6-C-rhamnosil 7-O-rhamnoside	Apigenin 6-C-rhamnoside	rhamnose	Deep purple	Brightgreenish yellow	70	70	60	22.8

After 4 hours hydrolysis treatment, apigenn 6-C-rhamnose and rhamnose were identified. The UV spectrum analysis of this compound revealed the absence of NaOAc shift indicating that the 7-hydroxyl was substituted by the rhamnose. The minor components found in the extract are Pelargonidin 3-O-glucoside. Chrysoeriol 7-O-glycoside and Qurercetin 3-O-methyl-7-O-glucoside.^{6- 9}

3. Antidiabetic activity:

Different kinds of medicinal plant used in the herbal formulation of the antidiabetic formulations (e.g Amree pluse tablets (Aimil pharmaceutical, new Delhi), D-400 ) The ayurveda system ^(3,
4) has defined the antidiabetic effects of the Carissa carandas .

Meaning: Unripe and ripe both verities of Carissa carandas are heavy in digestion and used as the anti-thirst, Produces heat, used in anorexia and initiates the RAKT, PITTA (heat) and KAPHA (water), Ripe fruit are sweet, used in anorexia, light in digestion and used in the PITTA and VATA Dash disorders.

According to ayuraveda Vata known as the vatik prameha, it is further divide into four types: vasameha, mejajamehe, lasicameha, oozumeha. Oozumeha ⁽³⁾ also has known as the medhumeha i.e. Diabetic mellitus.

Meaning: karamard is described in ayuraveda as “GRAHI” substrance. Grahi means which has appetizer and diagestive properties and is liquid absorber, it is known as “Deravshosak”.^{(10, 11)}

4. Cardiotonic and Blood pressure:

The alcoholic extract of the root of Carissa carandas L. has been reported to posses cardiotonic activity and to produce a perceptible decrease in the blood pressue in normal anaesthetizedcats. Chemical studies have led to the isolation of possibly anew cardioactive substarnce; glucosides of odoroside H, a new terpenoid carindone besides carissone, lupeol, ursolic acid and its methyl ester. A recent investigation of the pharmacological activity of the extract showed an increase in free histamine in the guinea pig lung and a pronounced decrease in blood pressure at 1 mg/kg dose which lasted for 4-5 hr. on fractionation of extract, the hypotensive activity was found to be localized in the C6H6-soluble fraction which prompted further examination of its constituents.

As per ayuraveda the alcoholic extract of root stem and leaf of Carissa carandas showed positive inotropic activity on hypodynamic guniapig heart and isolated papillary muscle preparation of cat.^{(2, 12)}

5. Anti convulsant activity:

The phytochemical screening of the extract revealed the presence of small quantities of alkaloids, flavonoids, saponins and large amounts of cardiac glycosides, triterpenoids, phenolic compounds and tannins. Based on the present state of knowledge of the chemical constituents of the extract, it is not possible to attribute with certainty its anticonvulsant effect to one or several active principles among those detected in the screening. However, triterpenic steroids and triterpenoidal saponins are reported to possess anticonvulsant activity in some experimental seizure models such as MES and PTZ27, 28. Some alkaloids, monoterpenes, flavonoids also have protective effects against PTZ, picrotoxin and NMDLA-induced convulsions

It can be concluded from the study that the anticonvulsant effects of the ethanolic root extract of C. carandas may be via non-specific mechanisms. ⁽¹³⁾

6. Hepatoprotective activity:

Oral pretreatment with ethanolic extract of the root of V. carandas showed significant hepatoprotective activity against CCl4 and paracetamol induced hepatotoxicity by decreasing the activities of serum marker enzymes, bilirubin and lipid peroxidation and significant increase in the levels of uric acid. Glutathione, super oxide dimetase, catalase and protein are in a dose dependent manner, which was confirmed by decrease in total weight of the liver and histopathological examination. It was concluded that promising hepatoprotective activities of C. carandas root extract. ⁽¹⁴⁾

7. Analgesic and anti-inflammatory activity:

The ethanolic (50% v/v) extracts of Carissa carandas were examined for anti-inflammatory and analgesic activities in experimental animals. Carissa carandas (50-200 mg/kg) caused a dose dependent inhibition of swelling caused by carrageenin significantly in cotton pellet induced granuloma in rats (P< 0.05 to P< 0.001). there was a significant increase in the analgesy meter induced pain in rats. The extracts of Carissa carandas resulted in an inhibition of stretching episodes and percentage protection was 16.05-17.58% respectively in acetic acid induced writhing.⁽¹⁵⁾

CONCLUSION:

In the present review extract from various parts of Carissa carandas show advance pharmacology activities i.e. antibacterial, scavengers of free radicals and inhibitors of xanthine oxidase, antioxidant, cardiotonic and blood pressure, anti convulsant activity, hepatoprotective, analgesic and anti-inflammatory activity and it also useful in the hypoglycemic conditions. It was concluded that Carissa carandas can be very useful in the various herbal formulations as a novel potential herbal drug.

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Received on 27.01.2010

Accepted on 26.03.2010

Research Journal of Pharmacognosy and Phytochemistry. 2(3): May-June 2010, 177-180