A REVIEW STUDY OF MEDICINAL USES OF MANJISHTHA ( RUBIA CORDIFOLIA )

Dr. BhanuPratap Singh, Dr. Om PrakashDadhich and Dr. Deepa. 1. MD Scholar, Dept. of ShariraKriya, National Institute of Ayurveda, Jaipur, Rajasthan. 2. Professor & HOD, Dean Academic, Dept. of ShariraKriya, National Institute of Ayurveda, Jaipur, Rajasthan. 3. M.D. (ShariraRachana), Medical Officer, Rajasthan. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


Morphological description:-
Origin and habitat 7 :-It is a deciduous climber with weak flexible stem upto 10 feet high and .25 inch diameter. Basal portion of stem is usually persistant and often softly woody. Branches are quadrangular, remoeselyscabrid or glabrous. Leaves 4 inch whorl, two often larger and with longer petioles, long, ovate, acute, base cordate, scabrid or smooth strong basal nerves. Flowers are less than 1 inch in diameter, dark red or pinkish brown, in terminal cymose, leafy panicles. Fruits are globose, dark purple or black fleshy, succulent, with red juice. Geographical distribution-It is commonly occurring throughout the hilly regions of india, ascending to 8000 ft. Frequently in the himalayan region of country from the north west frontier eastwards on the himalaya and south to ceylon and the malay, also in china, japan, java and tropical africa 8 . It occurs throughout india (dehradun, kashmir, nagpur, malva), nepal, shrilanka, iran, afghanistan. It is propagated by seeds and stem cutting.
Iridoids:-6-methoxygeniposidic acid is found along with manjistin, garancin and alizarin. Oleananestriterpinoid:rubiprasin a, b, and c along with arboranetriterpinoids, like rubiarbonol a, b, c, d, e and f have been isolated.
Bicyclic hexapeptides:-the compounds having antitumour activity have been isolated and identified chemically. Anthraquinones:-the colouring matter present in the roots of R. cordifolia is a mixture of purpurin (trihydroxyanthraquinone) and manjistin (xanthopurpurin-2-carboxylic acid). The roots contain small amounts of xanthopurpurin or purpuroxanthin and pseudopurpurin (purpurin-3-carboxylic acid). The plant also contains dihydromollugin, mollugin, rubilactone. Purpurin, belonging to the lipocalin family of proteins, is a fast dye for cotton printing and forms complexes with various metal ions. It is a glycosaminoglycan binding protein as well as a retinol binding protein.
Alizarin, or 1, 2-dihydroxyanthraquinone or mordant red, is the red dye originally derived from the root of the madder plant. In 1869, it became the first natural pigment to be duplicated synthetically. R. cordifolia yielded anthraquinones namely, 1-hydroxy-2 carboxy 3-methoxyanthraquinone, 1-hydroxy-2 methyl 6 or 7-methoxyanthraquinones. The other compounds were oleanolic acid acetate, β-sitosterol, and scopoletol. Ten fatty acids with saturated and unsaturated long chains were also identified.

1396
Traditional uses in different systems of herbal medicine:-In traditional korean system of medicine, the root is used to treat rheumatism, jaundiceand menstrual disorders. In philippine system, a decoction of root is drunk as a remedy for urinary disorders 13 . The natives of the republic of south africa take a decoction of the leaf or root for pleurisy and other inflammatory conditions of the chest. The stem is used in tibetan system of medicine in the treatment of blood disorders and spreading fever of kidneys and intestines 14 .
Unani system of medicine:-R. cordifolia has been prescribed for paralysis, dropsy, jaundice, amenorrhoea, urinary tract obstructions, skin disorders, menstrual disorders (excessive or painful bleeding), renal stone, urinary disorders and blood detoxification.
Chinese system of medicine:-roots help menstrual flow, promote blood circulation, promote urination, stop coughing blood or vomiting blood, nose bleeding. The plant is also useful in treatment of missing menses due to blood stasis, pain and inflammation caused by bleeding and blood circulation stasis, injuries from impacts and in jaundice and edema 15 . The herb is internally used for abnormal uterine bleeding, internal and external haemorrhage, bronchitis, and rheumatism 16 .
Ethnoveterinary usage:-R. cordifolia is used in the treatment of liver fluke, dysentery, maggots, wounds and intestinal worms in animals.
Pharmacological activity:-Anti-acne property:-The anti-acne activity of anthraquinone rich fraction of R. cordifolia in a gel formulation against propionibacterium acne, staphylococcus epidermidis, malassezia furfur is proved when compared with standard clindamycin gel 20 .

Anti-arthritic property:-
The anthraquinones rich fraction of ethanolic extract of R. cordifoliahas imperative anti-arthritic potential andshowed edema inhibition in induced arthritic model,which is similar to a standard non-steroidal antiinflammatory drug, aspirin 21 .
Anti-cancer property:-Anticancer activities of various fractions of R. cordifoliaroots extracts was demonstrated through in vitroand/orin bioassays based on animal models. The crude aqueousextracts demonstrated growth inhibitory activity onselected cancer cell lines as well as on normal humanmammary epithelial cells 22 .
Anti-convulsant activity:-In modern medicine, R. cordifoliawas reported to have anticonvulsant activity. Triterpenes inhibited seizures induced by maximum electric shock, electrical kindling and various chemoconvulsants in rats. Brain gaba and serotonin (5-ht) contents were raised by the compound proves its anticonvulsant property 23 .
1397 Anti-diabetic:-Alcoholic extract of root and leaf extracts were found to have promising antidiabetic activity against animal models. The extract of roots reduced the blood sugar level in alloxan treated diabetic rats, indicates that the extract has an extra pancreatic effect 24 . The aqueous root extracts was found to normalize hyperglycemia, hyper triglyceridemia, enhanced transaminases of liver and kidney, hypochromic microcytic anemia, and loss of body weight in streptozotocin -induced diabetic rat models 25 . Serum cholesterol and triglyceride level were decreased where as serum high density lipoprotein and protein levels were increased in diabetic rats 26 .
Anti-inflammatory activity:-Rubiacordifolia root extract has been used as anti-inflammatory agent because of the presence of rubimallin. It inhibited the lipoxygenase enzyme pathway, which catalyses the production of various inflammatory mediators such as leukotrienes that are involved in asthma, arthritis, and other inflammatory disorders, and the production of cumene hydroperoxides 27 .

Wound healing activity:-
The root extract of R. cordifoliawas reported as an effective wound healing principle in experimental models as wound healer 28 . Ethanolic extract and the hydrogel formulation of roots were found to be effective in the functional recovery and healing of wounds and also lead to histo-pathological alterations 29 .

Anti-microbial activity:-
The root extracts of R. cordifoliahave been studied for their antimicrobial activity against various pathogenic bacteria. Sitosterol and daucosterol possess antibacterial activity. Rubiacordone a reported to have considerable antimicrobial activity against gram +ve bacteria like bacillus subtilis, streptococcus faecalisand bacilluscereus 30 . The green synthesized silver nanoparticles using R. cordifoliaplant root extract was highly inhibiting the bacterial pathogens like vibrio alginolyticus,pseudomonas aeroginosa, shigellaspp, plesiomonasv and vibrio parahaemolyticus. They had highest antimicrobial effect against pseudomonasaeroginosaand plesiomonas shigelloides 31 .

Anti-oxidant activity:-
Rubiacordifoliacontains a wide variety of antioxidants like alizarin, hydroxyl anthraquinones and rubiadin which have been using in various medicaments. The study of in vivo antioxidant activity and its influence on ethanolinduced immuno-supression showed that the concurrent daily administration of madder prevented the decrease of humoral and cell-mediated immune response, phagocytosis index, leukocyte count, glutathione content etc., which were comparable with that of the combination of vitamin e and c 32 .
Anti-platelet activating effect:-In ayurvedic system, the plant is prescribed to cure blood related ailments. Partially purified fraction of the whole plant inhibits the action of platelet activating factor at its receptor level either by its blocking or by desensitization property 34 .
Anti-proliferative property:-Aqueous, ethanolic extract of root reported to have significant anti-proliferative effect. Mollugin found to be an active antiproliferative principle by bioassay-monitored fractionation. It did not exert cytotoxicity to human fibroblast cell line 35 .

Antistress and nootropic activity:-
Alcohollic extract enhanced brain υ-amino-n-butyric acid levels and decreased brain dopamine and plasma corticosterone levels 36 . The extract inhibited acidity and ulcers caused due to cold restraint stress.

Anti-ulcer activity:-
The effect of alcoholic extracts of roots of R. cordifoliaand its antiulcer potential on alcohol, ibuprofen, cold restraintstress and pyloric ligation-induced gastric lesionswas studied along with ranitidine, a standard drug 37 .

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Theextract showed substantial and significant protectionagainst gastric ulcers in all the models compared to ranitidine. Antiviral activity:the naphtha-hydroquinones are reported to have antiviral activity. 6-hydroxy group and a pyran or furan ring of furomollugin and mollugin strongly suppressed the secretion of hepatitis b surface antigen, in human hepatoma hep3b cells. The methanolic extracts of leaves have minimum inhibitory concentration of different virus using hel cell cultures and vero cell cultures 38 .

Diuretic activity 39, 40 :-
To substantiate the traditional claim, the hydroalcoholic root extract of R. cordifoliawas evaluated for its diuretic property and got positive results. The hydroalcoholic extract as well as the ethanol extract showed significant increase in urine volume and electrolyte excretion in a dose dependent manner compared with the reference drugs.
Gastroprotective activity:-Rubiacordifoliahas both gastroprotective and ulcer healing properties. Triterpenoids present in root extracts are potent antiulcer and antioxidant compound which can be clinically explored 41 .

Hepatoprotective activity:-
The quinone derivatives from R. cordifoliareported to have hepatoprotective effect on animal systems. Animal model studies proved that the methanolic extract protects the liver thioacetamide-induced hepatotoxicity 42 . The aqueous-methanol extract has found to be effective against acute and chronic hepatitis caused by the hepatitis b virus by interfering with the secretion of hepatitis b surface antigen in human hepatoma cells 43 .

Immuno-modulating activity:-
The alkaloids, cardiac glycosides, tannins, flavonoids and phenols present in R. cordifoliaare responsible for enhanced immuno-modulation. Ethanolic extracts of the whole plant were administrated to rats to test immunosuppressive activity and showed enhanced cell mediated and humoralimmuno-potentiating activity 44 . Hence R. cordifoliacan be utilized as a source of immunity enhancing drug.

Neuroprotection:-
Rubiacordifoliahas been reported to contain a wide variety of antioxidants and exhibited strong free radical scavenging properties against reactive oxygen and nitrogen species. The herb attenuate oxidative stress mediated cell injury during oxygen glucose deprivation and exert the above effects at both the cytosolic as well as at gene expression level and may be an effective therapeutic tool against ischemic brain damage 45 . The alcoholic extract decreases the neuro-degeneration and helps in memory retention activity 46 .
Radiation protection:-Oxidative stress induced by oxygen derived reactive oxygen species produces several adverse effects which are highly implicated in several degenerative diseases such as cancer. The therapeutic applications of r.Cordifoliaextract provide significant protection against radiation induced lipid peroxidation, hemopoietic injury and genotoxicity when administered intra-peritoneally before the radiation exposure 47 .

Calcium channel blocker(s) in R. cordifolia:-
The calcium channel antagonistic activity of a crude root extract of R. cordifolia was tested in isolated tissue preparations. The extract (0.1-3mg/ml) augmented spontaneous contractions of guinea pig atria, rabbit jejunum and rat uterus in a concentration-dependent manner.

Nephrotoxicity:-
The hydro-alcoholic extract of rubiacordifolia could decrease the intensity of cisplatin induced nephrotoxicity in swiss albino mice. The extract could significantly decrease the cisplatin induced nephrotoxicity as inferred from the tissue antioxidant status in the drug administered animals. Remarkable change was observed in serum creatinine and urea levels.

1399
Other uses:-Apart from its medicinal value, this plant has also been used as natural colorants in food, medicated oils, syrups etc. Root derived dye also used as textile and hair dye. Madder extracts is commonly used as a colorant for confections and soft drinks, because of its advantageous resistance to heat and light. The persuasive antioxidant activity of madder is effectively exploited in food industry as chemo-preventive agents. R. cordifoliacan be used as a single drug to cure chikungunya fever 48 . Leaf extract is used during cataract of eyes, conjunctivitis and also to clean the eyes. In patients with eczema, the topical application of the plant caused reduction in the severity of score and oedema, exudation and itching being significantly relieved.
Crude methanolic extract suppressed the spontaneous contractions of guinea-pig atria, rabbit jejunum and rat uterus in a concentration dependent manner. The indicated spasmolytic activity similar to that of verapamil, a standard ca++ channel blocker, suggests the presence of calcium channel like constituents in the plant, which may be responsible for the folkloric use of this plant for disintegration of urinary stones 49 . Psoriasis is a skin disease associated with hyper proliferation and aberrant differentiation of keratinocytes. The in vitro and in vivofindings together, the preclinical study confirms that ethanol fraction is a promising antipsoriatic agent.

Conclusion:-
Manjishtha is very important drug, which is described from ancient time. Acharya had already known the importance of manjishtha in the therapeutic management. Hence they used single or in combination in the form of churna, kwath, lepa, ghrita, taila etc. Used internally or externally to cure and prevent various diseases. The multiple benefits of rubiacordifoliamade it a true miracle of nature. Ithas several effects like anti-oxidant,antiinflammatory, anti-acne, anti-arthritic, anti-cancer, anti-convulsant, anti-diabetic, anti-microbial, anti-peroxidative, anti-proliferative, anti-stress, anti-ulcer, anti-viral, diuretic, gastroprotective, neuroprotective, immune modulating, radiation protective, hepatoprotectivewound healing etc. Properties.