MURRAYA KOENIGI-A BOON IN DIFFERENT PATHOLOGICAL CONDITIONS

Since very long period of time medicinal plants or their bioactive compounds have been utilized by majority of world population particularly in developing countries for primary and traditional healthcare system. At present scenario, people are more interested to use herbal drugs because they are considered as safe and inexpensive having no adverse effects. Different parts of the plants like roots, leaves, stem, bark, fruits and seeds have been used in treatment of different diseases and strengthening the immune system. Murraya koenigii, is a herb from mainly Asian origin, it has therapeutic applications such as in bronchial disorders, piles, vomiting, skin diseases, night blindness, dysentery, diarrhoea, bites of poisonous animals, bruises and eruption etc. The present review is an attempt for description of M. koenigii, its phytochemical constituents and various pharmacological activities.


INTRODUCTION
Murraya koenigii (family Rutaceae) is a herb having characteristic aroma and different potential medicinal values. It is deciduous shrub or tree up to 6 m in height and 15-40 cm in diameter with short trunk, thin smooth grey or brown bark and dense shady crown 1 . The most important chemical constitutents responsible for its intense characteristic aroma are P-gurjunene, Pcaryophyllene, P-elemene and O-phellandrene. The plant is rich source of carbazole alkaloids. Phytocompounds like koenimbine, koenine, mahanimbine, murrayazolidine, murrayazoline, murrayacine, girinimbine, mukoeic acid, etc. have also been isolated and characterized 2 . The stem of M. koenigii is an aromatic and more or less deciduous shrub or small tree upto 6 meters in height and 15 to 40 cm in diameter. The main stem is dark green to brownish. The bark of the stem can be peeled off longitudinally which exposes the white wood underneath. Flowers are small, white fragrant ebracteate, calyx deeply five cleft, pubescent 3 . Petals five, free, whitish, glabrous and with dotted glands. Fruits occur in close clusters, small ovoid or subglobose, glandular, thin pericarp enclosing one or two seeds having spinach green color 4 . Fresh leaves, dried leaf powder, and essential oil are widely used for flavouring soups, curries, fish and meat dishes, eggs dishes, traditional curry powder blends, seasoning and ready to use other food preparations. Bark and roots are used as stimulant and externally to cure eruptions and bites of poisonous animals 5 . It is traditionally used as a whole or in parts as anti-emetics, anti-diarrheal, febrifuge, blood purifier, antifungal, depressant, antiinflammatory, body aches, for kidney pain and vomiting. Green leaves are eaten raw for cure of dysentery, diarrhoea and for checking vomiting 6 . Leaves and roots are also used traditionally as bitter, anthelmintic, analgesic, curing piles, inflammation, itching and are useful in leucoderma and blood disorders 7 .

PHYTOCHEMISTRY
Murraya koenigii is a rich source of different organic compounds with diverse chemical composition.

Roots
Roots contains murrayanol, mukoenine-A, -B and C and murrastifoline -F. bis -2-hydroxy-3-methyl carbazole, bismahanine, bi koeniquinone-A and bismurrayaquinone A, Koenoline (1-methoxy-3hydroxylmethyl carbazole). Roots were also found to contain girinimbine 11 . Seeds Mahanimbine, girinimbine, koenimbine, isomahanine and mahanine were isolated form seeds of M. koenigii 12 . pharmacological activity profile of M. koenigii 1. Antioxidant and free radical-scavenging activity: Antioxidant activity has been reported by a number of workers. In a study antioxidative properties of the extract of M.koenigii leaves were done using different solvents. They were evaluated on the basis of oil stability index together with their radical scavenging ability against 1-1-diphenyl-2-picrylhydrazyl. The methylene chloride extract and the ethyl acetate soluble fraction of the 70 % acetone extract was prolonged 13,14 . 2. Cytotoxic Activity-In a study the alkaloid koenoline isolated from the root bark of M. koenigii is found to exhibit cytotoxic activity against KB cell culture system 15 . Carbazole alkaloids isolated from the stems are found to have significant effects in the growth of the human leukaemia cell line HL-60. Mahanine, pyrafoline-D and murrafoline-I (Carbazole alkaloids) showed significant cytotoxicity against HL-60 cells and cause a significant loss in mitochondrial membrane potential. The results obtained suggested it, s cytotoxic activity potential 16 .

Hypoglycemic activity
Leaves feeding produce hypoglycemia by increasing the hepatic glycogenesis as evident by increased activity of glycogen synthetase 17 . In a study a decrease in glycogenolysis and gluconeogenesis is reported and was evident form decreased activity of glycogen phosphorylase and gluconeogenic enzymes. A significant reduction in fasting blood sugar and postprandial blood sugar was observed by feeding (12 gm) leaves powder to non insulin dependent diabetes mellitus patients. The results obtained suggested it, s hypoglycemic activity potential 18 .

Antimicrobial and anti-fungal activity
In a study Murrayanine, girinimbine and mahanimbine isolated form stem bark showed anti fungal activity against human pathogenic fungi. 1-formyl-3 methoxy-6-methyl carbazole and 6,7-dimethoxy-1-hydroxy-3methyl carbazole were reported to possess antibacterial and anti fungal property. Extract containing murrayanol and or isomahanine is used as microbicide in variety of industries due to high safety, strong activity, little odor and without coloring effect 19 .

Anti-inflammatory activity
In a study stem bark of alcoholic extract in a dose of 1 gm/kg body weight showed protective effect against carrageenan-induced inflammation. Crude root extract also showed anti-inflammatory activity in rat model. The mast cell stabilization and antihistaminic effects of EEMK were suggested to be the probable mechanisms for its anti-inflammatory action and thus attains its

Immunomodulatory activity
In a study methanolic extract of M. koenigii showed significant increase in phagocytic index by rapid removal of carbon particles from blood stream. The extract also increased the antibody titre against ovalbumin and protection towards cyclophosphamideinduced myelosuppression in albino mice. Oral administration of the aqueous extract of leaves at doses of 250 and 500 mg/kg significantly enhanced the delayed-type hypersensitivity reaction induced by ovalbumin. The extract also potentiated the production of circulating antibody titre significantly in response to ovalbumin 21 .

Alzheimer disease therapy
In a study administration ethanolic extract of M. koenigii Leaves for 15 days produces significant dosedependent improvement of memory. The results also indicated to reduce the brain cholinesterase activity and total cholesterol level. Diet rich in M. koenigii leaves produced significant dose dependent improvement in the memory scores of young and aged mice and significantly reduced the amnesia induced by scopolamine (0.4 mg/kg, intraperitoneally) and diazepam (1 mg/kg, intraperitoneally) 22 .

Anti-obesity and anti-hyperlipidemic activities
In a study the dichloromethane and ethyl acetate extracts of Murraya koenigii leaves significantly reduced the body weight gain, plasma total cholesterol and triglyceride levels significantly. The observed antiobesity and antihyperlipidemic activities of these extract are correlated with the carbazole alkaloids, Mahanimbine. When it was given orally (30 mg/kg/day) significantly lowered the body weight gain. These findings demonstrate the excellent pharmacological potential of mahanimbine to prevent obesity 23 . 9. Anti-amnesic and wound-healing activity-In a study aqueous extract of M. koenigii accelerates the wound-healing process by decreasing the surface area of the wound. Aqueous extract of leaves showed marked reduction in wound area in comparison with the control group from 4 th day onwards in albino rats by excision wound model 24 .

Kidney protective activity
In a study aqueous extract of leaves produced a significant dose-dependent decrease in serum urea and creatinine levels (P<0.001), and a marked increase in the levels of plasma antioxidant capacity (P<0.01) in diabetic rats, compared with the control (non-diabetic) subjects. Histological studies of the kidneys of these animals showed comparable tissue regeneration by the aqueous extract 25 .

Antipyretic activity
In a study ethanolic extract of leaves of M. koenigii was investigated for antipyretic activity in rats using yeast-induced pyrexia model. Ethanolic extract at a single dose of 300 mg/kg produced significant antipyretic activity (P<0.01) in albino rats as compared with the standard drug paracetamol 26 .

Anti-ulcer activity
Antiulcer activity of aqueous and solvent ether extracts of Murraya koenigii was studied in reserpine induced gastric ulcer model in albino rats. Aqueous and solvent ether extracts of Murraya koenigii effective in gastric ulceration and suggested as protective as ranitidine. The extract dose of Murraya koenigii 200-400 mg/kg produced significant inhibition of gastric secretion. The results obtained suggested that the extract possesses significant antiulcer activity 27 .

Anti-trichomonal activity
In an earlier study carbazole alkaloids and their derivatives from M. koenigii leaves showed antitrichomonal activity against Trichomonas gallinae. Girinimbine and girinimbilol with IC50 values of 1.08 and 1.20 mg/mL were the most active. Acetylation of girinimbilol and mahanimbilol improved their activities to 0.60 and 1.08 mg/Ml 28 . 14. Anthelmintic activity Ethanolic and aqueous extracts from M. koenigii leaves were investigated for their anthelmintic activity against Pheretima posthuma. Both the extracts exhibited significant anthelmintic activity at concentration of 100 mg/mL. The alcoholic extract produced more significant anthelmintic activity than petroleum ether extract 29 .

Cosmetic use
Hyaluronidase inhibitors are extracted from M. koenigii and are formulated in a cream base. M. koenigii extract is included in a skin-lightening cosmetic for its moisturizing, antioxidant and hyaluronidase inhibitory activity. Herbal composition containing M. koenigii stem extract as one of the ingredient showed skin lightening and rough skin improving effect. M. koenigii was studied for sun protection 30,31 .

Anti-diarrhoeal activity
In a study bioactive alkaloids like, kurryam and koenimbine obtained from fractionated n-hexane extract of the seeds of M. koenigii were showed inhibitory action in reference to castor oil-induced diarrhoea and prostaglandin E2-induced enter pooling in strain of Wistar rats in charcoal meal test in Wister rats, these compounds were found to exhibit significant reduction in gastrointestinal motility and play mandate role in studying the modulatory role in disease progression 32 17. Anti-cancer Activity Intraperitoneal inoculation of Dalton's Ascitic Lymphoma cells in the mice produced an enormous increase in the cancer cell count which indicated that there is progression of cancer in the animals 33