Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 157

Pharma Science Monitor 8(2), Apr-Jun 2017

PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES Journal home page: http://www.pharmasm.com

A GOLD ORNAMENTAL –RUBIA CORDIFOLIA:A REVIEW Komal A. Kale*, Sonia J. Patell, Ankita B. Chaudhary, Nehal K. Gohil Department of Pharmacology. Shree Naranjibhai Lalbhai Patel College of Pharmacy, Umrakh, Bardoli.

ABSTRACT Indisputably the third millennium is witnessing the worldwide changes in healthcare. cordifolia () commonly known as Indian Madder is an important medicinal plant used in Indian traditional medicine for curing various diseases. The Phytochemical screening revealed that they were positive for anthraquinones, glycosides, flavonoids, steroids, phenols and saponins and were negative for alkaloids, tannins and quinones of all solvent extractions. It is an important medicinal plant being used for treatment of different ailments. KEYWORDS: Rubia cordifolia, phytochemicals, Indian Madder, Pharmacological actions, Ethno-medicinal.

INTRODUCTION The family Rubiaceae comprises about 450 genera and 6500 species and includes trees, shrubs and infrequently herbs. Rubia cordifolia L. is a perennial, herbaceous climbing plant, with very long , cylindrical, flexuous, with a thin red bark. Stems often have a long, rough, grooved, woody base. belonging to this family are known to contain substantial amounts of anthraquinones, especially in the roots. [1] The traditional therapeutic use of the plant has been for skin disorders and for anticancer activity. Furthermore, the anthraquinones of the Rubiaceae family exhibit some interesting in vivo biological activities, such as antimicrobial, antifungal, hypotensive, analgesic, and antimalarial, and antioxidant, anti-leukemic and mutagenic functions.

Komal et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 157-164 Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 158

Table 1: Taxonomical and morphological classification of Rubia cordifolia[2] Taxonomical classification Morphological classification Kingdom Plantae Plant Perennial herbaceous climber Division Magnoliophyta Roots Long, cylindrical, flexuous with a thin red bark Class Magnoliopsida Stem Very long, rough, grooved and woody base Order Branches Scandent, quadrangular, glabrous and shining Family Rubiaceae Arranged in four whorls, ovate Genus Rubia L. Fruits 4-6 mm in diameter, globose, purplish black when ripe

CHEMICAL CONSTITUTES[3] Quinones The plant contains quinines, mainly anthraquinone glycosides and include 1-hydroxy 2-methoxy nanthraquinone, 1, 4- dihydroxy-2- methyl-5-methoxy anthraquinone, 1, 3- dimethoxy 2- carboxy anthraquinone and rubiadin). Iridoids 6-methoxygeniposidic acid is found along with manjistin, garancin and . Oleananes triterpinoid Rubiprasin A, B, and C along with arborane triterpinoids, like rubiarbonol A, B, C, D, E and F.

R 8 O R1

R7 R2

R6 R3

R5 O R4

Komal et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 157-164 Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 159

Alizarin R1=R2=OH, R3=R4=H Purpurin R1=R2=R4=OH, R3=H Pseudopurpurin R1= R2=R4=OH, R3=COOH Xanthopurpurin R1= R3=OH, R2=R4=H Munjistin R1= R3=OH, R2=COOH, R4=H Rubiadin R1= R3=OH, R2=CH3, R4=H

Figure A: Structure of primary chromophores found in Rubia cordifolia[2]

Anthraquinones The coloring matter present in the roots of R. cordifolia is a mixture of purpurin (trihydroxy anthraquinone) 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. R. cordifolia yielded anthraquinones namely, 1- hydroxy-2 carboxy 3- methoxyanthraquinone, 1- hydroxy-2 methyl 6 or 7-methoxy- anthraquinones. The other compounds were oleanolic acid acetate, β-sitosterol, and scopoletol. Ethno-medicinal Importance of Rubia Cordifolia Manjisthadi Taila (oil) for headaches, ring worm and other fungal infections. Manjistadi Taila and Kadalipatra prevent formation of discoloration, eschar and contracture to the patient of burn in comparison of bactigauze. The leaves and stem is also used to cure mouth infection in babies and in the treatment of pneumonia. extract is applied on scabies and ringworm. Seed taken in vinegar and honey helps the swelling and hardness of spleen. Similarly manjistha and Glycyrrhiza glabra are pounded with sours applied as paste to treat fracture. The oil extract of whole plant is used to cure eczema. [4] PHARMACOLOGICAL ACTIVITES Anti-ulcer activity The effect of alcoholic extracts of roots of R. cordifolia and its antiulcer potential on alcohol, ibuprofen, cold restraint stress and pyloric ligation-induced gastric lesions was studied along with ranitidine, a standard drug. [5]

Komal et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 157-164 Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 160

The extract showed substantial and significant protection against gastric ulcers in all the models compared to ranitidine. In polyherbal formulations, the ulcerogenicity effect in rats showed significantly lesser ulcer effect even at very high dosage as compared to that of aspirin.[6] Anti-peroxidative activity Solvent free alcoholic extract of R. cordifolia showed antiperoxidative property in rat liver homogenate. The cumene hydroperoxide induced malondialdehydeformation accompanied by the reduced glutathione level even in the presence of above toxin.[7] Diuretic activity To substantiate the traditional claim, the hydroalcoholic extract of R. cordifolia was evaluated for its diuretic property and got positive results. [8, 9] 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. [10]

Gastroprotective activity The methanolic extract and the chloroform fraction showed reduction in ulcer index, lipid peroxidation, and increase in the mucin content, CAT and reduced glutathione in stomach tissue.[11] Anti-acne property Methanol extract of Rubia cordifolia inhibit proliferation of P. acne. [12] It is moderately effective against TNF alpha and show low activity against IL-8. It is regarded as astringent and useful in external inflammations like ulcers and skin diseases. [13] Anti-oxidant activity Alcoholic extract of root of Rubia cordifolia and its constituent rubiadin were found antioxidant property. [14, 15] Immuno-modulating activity Ethanolic extracts of the whole plant were administrated to rats to test immunosuppressive activity and showed enhanced cell mediated and humoral immuno-potentiating activity.[16] Neuroprotection Rubia cordifolia has been reported to contain a widevariety 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.[17]

Komal et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 157-164 Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 161

Anti-convulsant 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. [18] Wound healing activity The root extract of R. cordifolia was reported as an effective wound healing principle in experimental models as wound healer. [19] 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. cordifolia extract provide significant protection against radiation induced lipid peroxidation, hemopoietic injury and genotoxicity when administered intra- peritoneally before the radiation exposure. [20] Antiviral activity The naphthohydroquinones are reported to have antiviral activity. 6-hydroxy group and a pyran or furan ring of furomollugin and mollugin stronglysuppressed the secretion of hepatitis B surface antigen, in human hepatoma Hep3B cells. [21] Anti-arthritic property The anthraquinones rich fraction of ethanolic extract of R. cordifolia has imperative anti-arthritic potential and showed paw edema inhibition in induced arthritic model, which is similar to a standard non-steroidal anti-inflammatory drug, aspirin [22]. Anti-diabetic activity The extract of roots reduced the blood sugar level in alloxan treated diabetic rats, indicates that the extract has an extra pancreatic effect[23]. 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 [24]. The leaf extract decreased in the blood glucose level compared to the glibenclamide n normal fasted rat and alloxan-induced diabetic rats [25] CONCLUSION Rubia cordifolia is an ethnic plant that all the parts of which have been medicated. Roots of this plant having high medicinal value and are recognized as official.The reported phytochemicals

Komal et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 157-164 Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 162 and pharmacological studies support its traditional use and have now proven as source of several clinically important drug resources. It has been reported for the presence of glycosides, saponins, Anthraquinones, tannins, hexapeptides, quinones, and triterpenoids. Alkaloids are the lead molecules of therapeutic importance from the selected plants. These are heterocyclic Indole compounds which have proved to be having pharmacological properties. Sr.no. Biomarker Activity 1 Rubiadin Anti-oxidant 2 Triterpene Anti -convulsant 3 Napthohydroquiones Anti-viral 4 Bicyclic hexapeptides Anti-tumor

REFERANCES 1. M.Kannan, A.J.A.Ranjit Singh and M.Narayanan Phytochemistry and Ethanopharmacological Studies onRubia cordifolia Linn. (Rubiaceae)Ethnobotanical Leaflets 13: 338-342. 2009 2. Pankaj Bhatt, A. S. KushwahRubia cordifolia Overview: A New Approach to Treat Cardiac DisordersInt. J. Drug Dev. &Res., April-June 2013, 5(2): 47-54. 3. Rupali Patil, Mahalaxmi Mohan, Veena Kasture and Sanjay KastureRubia cordifolia: a reviewOriental Pharmacy and Experimental Medicine 9(1), 1-13. 4. Devi Priya M, E.A. Siril Traditional and Modern Use of Indian Madder (Rubia cordifolia L.): An Overview Int. J. Pharm. Sci. Rev. Res., 25(1), Mar – Apr 2014; Article No. 27, Pages: 154-164. 5. Kalra P, Datusalia AK, Sharma S, Antiulcer potential of Rubia cordifolia Linn. In experimental animals, Int. J. Green Pharm., 5, 2011, 149-154. 6. Gupta M, Shaw BP, Mukerjee A, Studies on Antipyretic-Analgesicand Ulcerogenic activity of polyherbal preparation in Rats andMice, Int. J. Pharmacol., 4, 2008, 88-94. 7. Tripathi YB, Sharma M, Shukla S, Tripathi P, Thyagaraju K,Reddanna P, Rubia cordifolia inhibits potato lipoxygenase, IndianJ. Exp. Biol., 33, 1995, 109-112. 8. Pawar AT, Divakar K, Chandrasekar SB, Goli D, Diuretic activity ofroot extract of Rubia cordifolia Linn., Pharmacologyonline, 1,2009, 597-603.

Komal et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 157-164 Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 163

9. Pawar AT, Anap RM, Ghodasara JV, Kuchekar BS, Protective effectof hydroalcoholic root extract of Rubia cordifolia inIndomethacin-Induced Enterocolitis in Rats, Indian J. Pharm. Sci.,73, 2011, 250-253. 10. Tripathi YB, Sharma M, Manickam M, Rubiadin, a newantioxidant from Rubia cordifolia, Indian J. Biochem. Biophys., 34, 1997, 302-306. 11. Deoda RS, Kumar D, Bhujbal SS, Gastroprotective effect of Rubiacordifolia Linn. On Aspirin plus Pylorus-ligated Ulcer, BMC Complem. Altern. M., 2011,e541624. 12. Gorle AM, Patil SS. Evaluation of antioxidant and antiacneproperty of Rubia cordifolia. Der Pharmacia Sinica. 2010; 1(3):59-63. 13. Jain A, Bansal E, Inhibition of Propionibacterium acnes-inducedmediators of inflammation by Indian herbs, Phytomedicine,2003;10: 34–38. 14. Joharapurkar A A, Zambad S P, Wanjari M M, Umathe S N. Invivo evaluation of antioxidant activity of alcoholic extract ofRubia cordifolia linn. And its influence on ethanol-inducedImmunosuppression. Indian Journal of Pharmacology. 2003; 35:232-236. 15. Tripathi Y B, Sharma M.The interaction of Rubia cordifolia withiron redox status: a mechanistic as pectin free radical reactions. Phylo medicine, Vol. 6(1), pp. 51-57. 16. Kannan M, Singh R, Narayanan, Phytochemistry andimmunopharmacological investigation of Rubia cordifolia Linn.(Rubiaceae), Pharmacologyonline, 3, 2009, 653- 662. 17. Rawal AK, Muddeshwar M, Biswas S, Effect of Rubia cordifolia,Fagonia cretica Linn. and Tinospora cordifolia on free radicalgeneration and lipid peroxidation during oxygen- glucosedeprivation in rat hippocampal slices, Biochem. Biophys. Res.Commun., 12, 2004a, 588-596. 18. Kasture VS, Deshmukh VK, Chopde CT, Anticonvulsant andbehavioral actions of triterpene isolated from Rubia cordifoliaLinn., Indian J. Exp. Biol., 38, 2000, 675-680. 19. Biswas TK, Mukherjee B, Roy JB, Plant medicines of Indian originfor wound healing activity: A review, Int. J. Low Extrem. Wounds,2, 2003, 25-39. 20. Tripathi YB, Singh AV, Role of Rubia cordifolia Linn. In radiationprotection, Indian J. Exp. Biol., 45, 2007, 620-625. 21. Ho LK, Don MJ, Chen FC, Yeh SF, Chen JM Inhibition of hepatitis Bsurface antigen secretion on human hepatoma cells componentsfrom Rubia cordifolia,. J. Nat. Prod., 59, 1996, 330-333.

Komal et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 157-164 Impact factor: 3.958/ICV: 4.10 ISSN: 0976-7908 164

22. Jaijesh P, Srinivasan KK, Kumar PB, Sreejith G, Ciraj AM, Anti-Arthritic property of the plant Rubia cordifolia Linn.,Pharmacologyonline, 1, 2008, 107-113. 23. Patil RA, Jagdale SC, Kasture SB, Antihyperglycemic, antistressand nootropic activity of roots of Rubia cordifolia Linn., Ind. J.Exp. Biol., 44, 2006, 987-992. 24. Baskar R, Bhakshu LM, Bharathi GV, Reddy SS, Karuna R, ReddyGK, Saralakumari D, Antihyperglycemic activity of aqueous rootextract of Rubia cordifolia in Streptozotocin- induced diabetic rats, Pharm. Biol., 44, 2006, 478-479 25. Viswanathaswamy AHM, Koti BC, Singh AK, Thippeswamy AHM Antihyperglycemic and antihyperlipidemic effect of Rubia cordifolia leaf extract on Alloxan-induced Diabetes, RJPS, 1, 2011, 49-52.

Komal et al. / Pharma Science Monitor 8(2), Apr-Jun 2017, 157-164