Rubia cordifolia L.

Last updated: 2016 Oct 14

Scientific Name

Rubia cordifolia L.

Synonyms

Dioscorea verticillata Lam., Galium cordifolium (L.) Kuntze, Rubia clematifolia Reinw. ex Miq., Rubia cordata Thunb., Rubia javana DC., Rubia pratensis (Maxim.) Nakai, Rubia pubescens (Nakai) Nakai, Rubia purpurea Decne., Rubia scandens Zoll. & Moritzi, Rubia secunda Moon [1]

Vernacular Name

English Indian madder [2], Bengal madder, madder , dyer’s madder [3]
China Chien tsao, ch’ien, ch’ien ts’ao, qian cao gen [3]
India Manjistha, akane, brtsod, chien-tsoa, farberwurzel, garance, manji, manjit, velmadata [4]
Indonesia Letah meong (Sundanese); kletak (Javanese) [2]
Philippines Kamagut, mankit (Igorot); pantig-pantig (Bagobo) [2]
Vietnam Thiên can [2]
Tibet Btsod, dama, dzoe, hana, mula, ny tze ka, rak da [3].

Geographical Distributions

Rubia cordifolia has an extremely large area of distribution, ranging from Africa through Central Asia to India, Japan, China, Indo-China, Malaysia (Sabah), the Philippines, parts of Indonesia (Sumatra, Java), and northern Australia. [2]

Botanical Description

R. cordifolia isan extremely variable species belongs to the Rubiaceae family. It is a climbing or creeping herb that can reach up to 10 m long. [2]

The stem is with long internodes, quadrangular, sometimes prickly or hispid and often hairless. [2]

The leaves are simple, in whorls of (2-)4(-8), with cordate to (narrowly) ovate leaf blade, measuring 2.5-10 cm x 1-4 cm, with 3-9-palmate veins, cordate or rounded at the base, acute or acuminate at the apex, entire and with smooth or retrorsely scabrid or hairy or strigose surface. The petiole is usually long, and measuring 5-8 cm but sometimes as short as 0.5 cm. [2]

The flowers are in axillary and terminal cymes, trichotomously branching, with long-peduncled panicles, measuring 3.5-4.5 mm in diametre, with variable color from greenish-white to purple-red and (4-)5-merous. The stamens are epipetalous. The ovary is inferior, 2-celled and with 2 styles. [2]

The fruit is a spherical or 2-lobed berry, 1-2-seeded, measuring 4-5 mm x 3.5-5 mm, and bluish-black but sometimes red or purple. [2]

The rootstock is perennial, with long roots, cylindrical and zigzags with thin red bark. [2]

Cultivation

The vast area over which R. cordifolia occurs indicates its adaptability. In Southeast Asia, it occurs mostly in humid areas, 500-2500 m above sea level, mostly in secondary vegetation. [2]

Chemical Constituent

R. cordifolia  has been reported to contain quinones (e.g. anthraquinone glycosides including rubiadin, 1-hydroxy 2-methoxy anthraquinone, 3-dimethoxy 2-carboxy anthraquinone), rubiprasin A, rubiprasin B, rubiprasin C, ruiearbonols, aborane triterpenoids, mangistin, alizarin, garancin, mollugin, and furomollugin. [5][6][7][8]

Plant Part Used

Stem, leaf, root. [4][9][10][11]

Traditional Use

R. cordifolia has been a major source of red pigment dye in Mediterranean, Africa and Asia. The root and stem decoction of R. cordifolia is used as natural food colourant, natural hair dye, and natural wool and cotton dyes. [9][10]

R. cordifolia was also very useful as a medicinal in Ancient Greece, Africa and Asia. [9][10]

R. cordifolia is thought to be very effective as a treatment for diseases of the stomach and intestines. In Uganda and Tanzania the leaves are used to treat general stomach discomfort as well as diarrhoea [9]. In order to treat general stomach pain, a decoction of the roots is ingested [11]. A popular application in Zimbabwe in order to treat diarrhoea is to pulverise R. cordifolia root and then ingest the pulp [12].

Numerous other applications of R. cordifolia include that of cough suppressant, liver protective [13], and poison antidote [9][11]. The root and leaves of R. cordifolia are chewed and then applied on snake spit wound area [14].

Another popular and purportedly effective role of R. cordifolia is that of being beneficial to the reproductive organs of both men and women. In South Africa, the juice of the root or the raw root itself has been used in order to treat erectile dysfunction. The plant itself is thought to have strong libido properties [9]. Sap from the entire R. cordifolia plant is used in enema form for numerous sexually transmitted diseases, specifically gonorrhea [15]. The root of R. cordifolia is a primary ingredient in a root cocktail used in order to treat scrotal swelling [16]. In order to reduce scarring of the umbilical cord after birth, the baby is bathed in the decoction of whole R. cordifolia plant. This usage primarily occurs in Uganda. [17]

R. cordifolia is found in many traditional Ayurvedic formulations including Asvagandhady Arista, Brhanmajisthadi, Candana Sava, Jatyadi Ghrta, Kvatha Curna, Manjisthadi Taila, Phala Ghrta and Pinda Taila [18]. The rasa (taste) of R. cordifolia is classified as kasaya (astringent), tikta (bitter) and madhura (sweet). R. cordifolia is particularly useful in treating disorders of the Kapha dosha, as it pacifies Kapha (the earth and water elements) and Vata (the air and space elements) while stimulating the Pitta dosha (the fire and water elements) [4].

The uses of R. cordifolia in Ayurveda cover a wide variety of ailments. It has been used for urinary tract disorders, urinary discharge, jaundice, skin depigmentation, menstrual disorders and certain kinds of paralysis [4]. Ayurvedic medicine also claims R. cordifolia as having antidiarrhoeal, painkiller, antiparasitic worms, and antifever activity. It has also been used to treat inflammation in the uterus, vagina, ear, eye and blood [18].

In Ayurvedic medicine, the powdered root of R. cordifolia is the most common form of this medicine [18]. A paste consisting of the powdered root of R. cordifolia and honey is used topically for several kinds of mild and moderate skin disorders [4].

Preclinical Data

Pharmacology

Cytotoxic and growth inhibitory activities

A new peptide prepared from a chloroform-methanol (10:1) - soluble portion of a methanol extract from R. cordifolia dried roots was evaluated for its cytotoxicity against P-388 leukemia cells, and showed IC50 value was 0.012 µg/mL [19]. In another study, the methanol extract of R. cordifolia dried roots showed cytotoxicity against P-388 leukemia cells and human nasopharynx carcinoma (KB), with IC50 value were 0.12 and 0.7 µg/mL respectively [20].

Methylene chloride fraction (methanol extract was further fractionated) of R. cordifolia roots through in vitro studies using the tetrazolium-based colorimetric assay (MTT assay) showed strong cytotoxicity against human colon cancer (HT-29) and human breast cancer (MCF-7) cell lines. It also showed DNA topoisomerase I and II inhibitory activities, measured by assessing the relaxation of supercoiled pBR 322 plasmid DNA. [21]

Aqueous extract of R. cordifolia roots showed growth inhibitory activity against a variety of cancer cell lines. At a 1:10 dilution, R. cordifolia extract exhibited 51-75% growth inhibitory activity on human lung carcinoma (A549), human pancreatic carcinoma (Panc-1), human breast adenocarcinoma (MCF-7), human prostate adenocarcinoma (PC-3) and human prostate carcinoma (LNCaP) cell lines with IC50 values determined from full dose response curve were 414, 420, 319, 183, and 71 µg/mL respectively. [22]

Antioxidant activity

The antioxidant activity of R. cordifolia was found to be in the form of regulating glutathione oxidation. Cumene hydroperoxide (CHP) was used as pharmacological tool for the study of lipid peroxidation which is measured in terms of malondialdehyde formation. Solvent free alcoholic extract of R. cordifolia studied in Albino rats liver homogenate showed that it prevented cumene hydroperoxide (CHP) induced malondialdehyde formation in the dose and time dependent manner. The effect of R. cordifolia on reduced glutathione (GSH) was also studied. Result indicated that the group treated with 1 mg/mL R. cordifolia extract showed reduction in the rate of lowering GSH content, whereby in normal condition, GSH content decreases after 20 minutes as a result of auto-oxidation. In the treated group, the normal GSH level was maintained for up to 40 minutes. [23]

Radioprotective activity

Alcoholic extract of R. cordifolia root showed radioprotective potential when studied by Swiss albino mice of strain A survival, hemopoietic cell protection and micronucleus assay. The LD50 value for the alcoholic root extract was found to be 1200 mg/kg body weight at 72 hour post irradiation. A significant radiation protection (67%) as assessed by increased animal survival was observed when R. cordifolia extract was administered intraperitoneally, 90 minutes prior to radiation exposure. The extract also inhibited radiation induced lipid peroxidation measured by the inhibition of thiobarbituric acid reactive substance (TBARS), whereby at a selected dose of 460 mg/kg body weight was effective in protecting the radiation induced suppression of endogenous colony forming units in spleen. A significant inhibition of radiation (2 Gy) induced micronuclei formation was observed when it was administered 90 minutes before irradiation. [24]

Antimicrobial activities

R. cordifolia has been the subject of laboratory studies on Hepatitis B, as it inhibits secretion of the Hepatitis B surface antigen. Furomollugin and mollugin compounds isolated from R. cordifolia roots strongly suppressed the secretion of hepatitis B surface antigen (HBsAg), both with IC50 of 2.0 µg/mL, in human hepatoma Hep3B cells while having little effect on the viability of the cells. Evaluation of structurally related derivatives of furomollugin and mollugin revealed that a 6-hydroxy group and a pyran or furan ring contribute to this suppressive effect. [25]

Methanol extract of R. cordifolia whole plant contained in 1 cm diameter impregnated disks applied to inoculated agar plate showed inhibition of 1.2-1.6 cm to Neisseria gonorrhoea, Neisseria meningitidis, Streptococcus pyogenes and Staphylococcus aureus. [15]

Hepatoprotective activity

Rubiadin, a major constituent isolated from ethanol extract of R. cordifolia roots was assessed against carbon tetrachloride (CCl4)-induced hepatic damage in Sprague–Dawley rats. Rubiadin at a dose of 50, 100 and 200 mg/kg was orally given once daily for 14 days. The markedly increased serum enzymatic activities of serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP) and γ-glutmyltransferase (γ-GT) due to carbontetrachloride treatment were dose dependently restored towards normal values. Meanwhile, the reduced activities of glutathione S-transferase and glutathione reductase were also restored towards normalization. Rubiadin also significantly prevented the increase of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl4 intoxicated rats in a dose dependent manner. [26]

Antistress activity

Alcoholic extract of R. cordifolia roots was studied on cold restraint induced stress. Alcoholic extract enhanced brain γ-amino-nbutyric acid (GABA) levels and lowered brain dopamine and plasma corticosterone levels. Stress ulcers were induced in Albino mice (NIN strain) by exposing them to restraint stress for 2 hours at temperature 4°C. R. cordifolia extract of (25, 50 and 100mg/kg) or diazepam (1mg/kg) was administered intraperitoneally 30 minutes before stress. The levels of dopamine, γ-amino-n-butyric acid (GABA), plasma 11-hydroxycorticosteroids, total acidity and the severity of ulcers were measured. In vehicle treated mice, cold restraint stress (CRS) increased ulcer index from 0.4 ± 0.06 to 1.34 ± 0.06. R. cordifolia extract (25, 50, and 100 mg/kg) significantly reduced ulcer index in a dose-dependent manner in mice under CRS. Diazepam (1 mg/kg) also decreased ulcer index in animals under CRS as compared to stress control animals. [27]

Anticonvulsant activity

An animal model also suggests that R. cordifiolia has anticonvulsant activity. Triterpene isolated from the acetone soluble part of petroleum ether extract of R. cordifolia roots and rhizomes was studied on convulsions induced by maximum electro shock (MES) and various chemoconvulsants in Albino rats (NIN strain) and Albino mice (NIN strain). The mice were pretreated with either R. cordifolia. The crystals of triterpene were suspended in 0.5% (w/v) carboxy-methylcellulose and were administered orally to the animals. The mice were pretreated with either triterpene crystals or vehicle or diazepam (2 mg/kg), 30 minutes before the administration of either pentylenetetrazol (80 mg/kg), strychnine (1 mg/kg), or an electric shock (42 mA for 0.2 second using corneal electrodes. The convulsions onset and the seizure incidences were recorded in case of chemoconvulsants, whereas the duration of tonic hind leg extension and convulsion incidences were observed in case of MES induced convulsions. Result showed that the triterpene crystals dose dependently inhibited the convulsion incidences and significantly delayed the onset of spasm and clonus in the pentylenetetrazol treated mice, but it failed to inhibit strychnine-induced seizures. In vehicle treated animals, the seizure incidences was 8/8 and the latency to spasm and convulsions were 58.0±5.4 and 108.4±7.5 seconds respectively. Animals pretreated with triterpene crystals at doses of 50 mg/kg and 100 mg/kg showed seizure incidences of 5/8 and 4/8 each, while latency to spasm were 104.7±8.2 seconds (p < 0.01) and 135.7±7.2 seconds (p < 0.001) respectively. The latency to convulsions for triterpene treated mice at doses of 50 mg/kg and 100 mg/kg were 164.6±12.4 seconds (p < 0.05) and 189.3±11.4 seconds (p < 0.01) respectively. In the MES test, the duration of tonic extensor phase declined dose dependently. Triterpene crystals at the dose of 200 mg/kg prevented the tonic extensor phase completely. [28]

Antihyperglycemia activity

The effect of alcoholic extract of R. cordifolia roots was also investigated on elevated blood glucose level in alloxan treated Albino mice (NIN strain). Mice were injected with alloxan (200 mg/kg) subcutaneously 24 hours before alcoholic extract of R. cordifolia (100, 200, or 400 mg/kg) were administered intraperitoneally. Alloxan increased blood glucose level from 65.40±9.53 to 147.20±8.21 mg/dL. Alcoholic extract of R. cordifolia (100, 200, and 400 mg/kg) reduced the blood glucose level significantly to 84.80±3.58, 77.75±3.30, and 108.8±7.83 mg/dL, respectively when measured 1 hour after the extract was given. [27]

Toxicity

No documentation

Clinical Data

No documentation.

Clinical findings

No documentation

Precautions

No documentation

Interaction & Depletion

Interaction with drug

Based on pharmacology as well, this herb should not be used by those being treated for Hepatitis B unless directed and monitored by a physician. [25]

Based on preliminary research and assumptions into the role of R. cordifolia in affecting GABA levels in the brain, this herb should not be used by those taking seizure medications. [28]

Interaction with other Herbs

No documentation

Contraindications

No documentation

Dosage

Dosage Range

1-3 g powder, 56-112 mL decoction 1-3 times per day or as directed. [4]

Most Common Dosage

No documentation.

Standardisation

No documentation.

Poisonous Management

No documentation.

Line drawing

17

Figure 1: The line drawing of R. cordifolia. [2]

References

  1. The Plant List. Ver1.1. Rubia cordifolia L. [homepage on the Internet]. c2013 [updated 2012 Mar 23; cited 2015 Dec 14]. Available from: http://www.theplantlist.org/tpl1.1/record/kew-180230
  2. Oyen LPA. Rubia cordifolia L. In: Lemmens RHMJ, Wulijarni-Soetjipto N, editors. Plant Resources of South-East Asia No. 3: Dye and tannin-producing plants. Wageningen, Netherlands: Pudoc, 1991; p. 112-113.
  3. Quattrocchi U. CRC world dictionary of medicinal and poisonous plants: Common names, scientific names, eponyms, synonyms, and etymology. Volume V R-Z. Boca Raton, Florida: CRC Press, 2012; p. 86.
  4. Kapoor, LD. CRC Handbook of Ayurvedic Medicinal Plants. Boca Raton, FL: CRC Press; 2001; p. 292.
  5. Gupta PP, Srimal RC, Verma N, Tandon JS. Biological activity of Rubia cordifolia and isolation of an active principle. Pharm Biol. 1999;37(1):46-49.
  6. Kannan M, Ranjit A, Narayanan M. Phytochemistry and ethanopharmacological studies on Rubia cordifolia Linn. (Rubiaceae). Ethnobot Leaflets. 2009;13:338-342.
  7. Qiao YF, Wang SX, Wu LJ, Li X, Zhu TR. [Studies on antibacterial constituents from the roots of Rubia cordifolia L.]. Yao Xue Xue Bao. 1990;25(11):834-839. Chinese.
  8. Chang LC, Chavez D, Gills J, Fong H, Pezzuto J, Kinghorn A. Rubiasins A–C, new anthracene derivatives from the roots and stems of Rubia cordifolia. Tetrahedron Lett. 2000;41(37):7157-7162.
  9. Schmelzer GH, Gurib-Fakim A, editors. Plant Resources of Tropical Africa 11(1): Medicinal plants 1. Wageningen, Netherlands: PROTA Foundation/Backhuys Publishers/CTA; 2008.
  10. Ferreira ES, hulme A, McNab H, Quye A. The natural constituents of historical textile dyes. Chem Soc Rev. 2004;33(6):329-336.
  11. Kokwaro JO. Medicinal plants of East Africa. Nairobi, Kenya: East African Literature Bureau, 1976; p. 181-182.
  12. Chinemana F, Drummond RB, Mavi S, de Zoysa I. Indigenous plant remedies in Zimbabwe. J Ethnopharmacol. 1985;14(2-3):159-172.
  13. Neuwinger HD. African traditional medicine: A dictionary of plant use and applications. Stuttgart, Germany: Medpharm Gmbh Scientific Publishers; 2000.
  14. Bussmann Rainer, WP Swartzinsky, W Aserat, P Evangelista. Plant use in Udo-Bulu and Demaro, Bale Region, Ethiopia. J Ethnobiol Ethnomed. 2011;7:28.
  15. van Puyvelde L, Geiser I, Rwangabo PC, Sebikali B. Rwandese herbal remedies used against gonorrhoea. J Ethnopharmacol. 1983;8(3):279-286.
  16. Gelfland M, Mavi S, Drummond RB, Ndemera B. The traditional medicinal practitioner in Zimbabwe: His principles of practice and pharmacopoeia. Gweru, Zimbabwe: Mambo Press, 1985; p. 411.
  17. Segawa P, Kasenene JM. Medicinal plant diversity and uses in the Sango bay area, Southern Uganda. J Ethnopharmacol. 2007;113(3):521-540.
  18. Pathania S, Daman R, Bhandari S, Singh B, Lal B. Comparative studies of Rubia cordifolia L. and its commercial samples. Ethnobot Leaflets. 2006;2006(1):19.
  19. Lee JE, Hitotsuyanagi Y, Kim IH, Hasuda T, Takeya K. A novel bicyclic hexapeptide, RA-XVIII, from Rubia cordifolia: structure, semi-synthesis, and cytotoxicity. Bioorg Med Chem Lett. 2008;18(2):808-811.
  20. Itokawa H, Ibraheim ZZ, Qiao YF, Takeya K. Anthraquinones, naphthohydroquinones and naphthohydroquinone dimers from Rubia cordifolia and their cytotoxic activity. Chem Pharm Bull (Tokyo). 1993;41(10):1869-1872.
  21. Son JK, Jung SJ, Jung JH, et al. Anticancer constituents from the roots of Rubia cordifolia L. Chem Pharm Bull (Tokyo). 2008;56(2):213-216.
  22. Shoemaker M, Hamilton B, Dairkee SH, Cohen I, Campbell MJ. In vitro anticancer activity of twelve Chinese medicinal herbs. Phytother Res. 2005;19(7):649-651.
  23. Pandey S, Sharma M, Chaturvedi P, Tripathi YB. Protective effect of Rubia cordifolia on lipid peroxide formation in isolated rat liver homogenate. Indian J Exp Biol. 1994;32(3):180-183.
  24. Tripathi YB, Singh AV. Role of Rubia cordifolia Linn. in radiation protection. Indian J Exp Biol. 2007;45(7):620-625.
  25. Ho LK, Don MJ, Chen HC, Yeh SF, Chen JM. Inhibition of hepatitis B surface antigen secretion on human hepatoma cells. Components from Rubia cordifolia. J Nat Prod. 1996;59(3):330-333.
  26. Rao GM, Rao CV, Pushpangadan P, Shirwaikar A. Hepatoprotective effects of rubiadin, a major constituent of Rubia cordifolia Linn. J Ethnopharmacol. 2006;103(3):484-490.
  27. Patil RA, Jagdale SC, Kasture SB. Antihyperglycemic, antistress and nootropic activity of roots of Rubia cordifolia Linn. Indian J Exp Biol. 2006;44(12):987-992.
  28. Kasture VS, Deshmukh VK, Chopde CT. Anticonvulsant and behavioral actions of triterpene isolated from Rubia cordifolia Linn. Indian J Exp Biol. 2000;38(7):675-680.