International Journal of Drug Development and Research

Keywords

Rubia cordifolia, Traditional uses, Phytochemical studies, Pharmacological actions, Recent activities, Cardioprotective approach.

INTRODUCTION

Ayurvedic materia medica mentioned Manjistha as detoxifying herb removing “ama/toxin” from the blood. Rubia denotes ‘red’ as their internal use imparts red color to breast milk and urine1. Roots of this plant having high medicinal value and are recognized as official2. In the ethnobotanical claims, roots of Rubia cordifolia mentioned for the treatment of jaundice used by the folk tribes of West Bengal and Uttaranchal. Manjistha stem describes as cure for snake bite and scorpion sting. It is also effective on non healing diabetic foot ulcer3. Manjistha having cooling effect in the body and therefore, traditionally used for chronic pyrexia and puerperal fever. It is a popular remedy for the relief of heat and itching in eczema, psoriasis, herpes, scabies and also reported successful in treatment of vitiligo when given with honey4. Manjistha has been reported for the presence of glycosides, saponins, anthraquinones, tannins, hexapeptides, quinones, triterpenoids5. Literature describes the beneficial effects of Rubia cordifolia in treatment of number of ailments including alzheimer, diabetes, cancer, acne, inflammation, allergy, enterocolitis, bacterial and viral infection. Other reported activities are immunomodulator, analgesic, diuretic, gastroprotective, hepatoprotective and nephroprotective. Rubia cordifolia show potent antioxidant activity against lead nitrate and radiation induced toxicity6, 7. Rubia cordifolia has been evaluated for its wound healing activity8. The leaves of this plant also studied for its antiviral and in-vitro free radical scavenging activity9. Apart from its medicinal value, Manjistha has also been used as natural food colorants and natural dyes. The coloring pigments present in the roots are purpurin and munjistin in major amounts. Madder root extract has investigated for its dying characteristics and yielded beautiful orange red to scarlet shades when applied onto the woolen yarn10.

TRADITIONAL USES:

Manjistha is an ayurvedic herb that is mentioned in Charaka and Sushruta. Charaka has categorized it as varnya, jvarahara, vishaghna. Sushruta has mentioned it pittasamsamana. Traditional uses of manjistha mentioned in ayurvedic materia medica are following:

Ayurvedic pharmacopoeia of India therapeutically indicate it for Yoni roga (menstrual disorder), Kustha (skin disease), Sarpavisa (snake bite), Visarpa (herpes virus), Aksi roga (eye disease), Arsa (haemorrhoids), Bhagna (Fracture)11.

According to the ancient ayurvedic text, Bhava Prakash, Manjistha is able to bind with amavisha (free radicals) and garavisha (xenobiotics) toxins which cause inflammation, skin disease, ulcers, among other problems. Manjistha in Sanskrit also termed as Jingi (vibrational energy) which helps to reestablish the intelligence of the tissues. A balanced combination of soma (cooling) and agni (heat) found in Manjistha. Agni allows the herb to penetrate into the cellular level of tissues and Soma helps to soak up the toxins and neutralize them.

Ayurvedic preparations:

Manjistha is an important ingredient of many ayurvedic formulations and preparations; Mahamanjisthadi kvatha, Manjisthadi taila, Manjistha arka, Manjistha malahara, Manjistha phanta, Septilin syrup etc.

Mahamanjisthadi kvatha: The herbal supplement used as blood purifier, immunomodulator, promotes skin health and complexion.

Septilin syrup: A polyherbal preparation containing Rubia cordifolia as one of the ingredient, tried in 40 children suffering from various upper respiratory tract infections. Very good response was seen in 34 (85%) children. Incidence of recurrences was minimal12

Body Revival: It is an Indian herbal formulation having suspension of Aegle marmelos, Acorus calamus, Rubia cordifolia, Saussurea lappa, Blumea lacera, Rumex vasicarius, Curcumas melo, Symplocos racemosa and honey. Investigation showed that Body Revival potentiates cardioprotection against isoproterenol induced myocardial ischemia and ADP or collagen induced human platelet aggregation13.

PHYTOCHEMICAL STUDIES:

Rubia cordifolia (Manjistha) basically known for its anthraquinones and naphthohydroquinones phytochemical constituents14. The major phytoconstituents of Rubia cordifolia reported include Rubiadin15, Rubicordone A16, Rubiasins AC17, Rubiatriol (triterpenoid)18, 6-methoxygeniposidic acid an iridoid glycoside19 and two pentacyclic triterpenoid- Rubicoumaric acid and Rubifolic acid20. Mollugin, furomollugin, dehydro-alpha-lapchone are isolated from chloroform fraction21.

The primary chromophores present in Rubia cordifolia are alizarin, purpurin, pseudopurpurin xanthopurpurin, munjistin, rubiadin. All of the chromophores share the base 9,10-anthraquinone structure but with different functional groups at carbons 1-4 (Fig. A)22.

Four naphthoic acid esters namely rubilactone, 3'- carbomethoxy-4'-hydroxy-naphtho[1',2'-2,3]furan, dihydromollugin and 3-carbomethoxy-2(3'- hydroxy)isopentyl-1,4-naphthohydroquinone-1-Obeta- D-glucoside were isolated from the roots of Rubia cordifolia23.

Identification of aroma compounds in Rubiae Radix (dried roots of Rubia cordifolia) done by gas chromatography. As a result of 43 components, accounting for 91.5% of total oil detected, in which mollugin (19.6%), furomollugin (17.4%), eugenol (12.7%), (E)-anethole (10.6%), 4-tert-butyl-2-phenyl phenol (9.9%), menthol (2.7%) are the main components24.

Biomarkers:

PHARMACOLOGICAL ACTIONS

RECENT ACTIVITIES:

1. Antibacterial activity of ethanolic extract of Rubia cordifolia evaluated against ESBL (Extended Spectrum Beta-Lactamase) producing urinary E.coli infection. Isolation of different E.coli strains done from urine samples of patients and all the isolates tested for different antibiotics and screened for their ESBL production. Total 7 different ESBL producing E.coli obtained and tested against the ethanolic extract of Rubia cordifolia using Kirby Bauer method and found to be inhibited variably by the extract. The plant can be a potential candidate as alternative antibacterial agent to combat drug resistant organisms49.

2. Methanolic extract of Rubia cordifolia showing ameliorative effect in N-nitrosodiethylamineinduced hepatocellular carcinoma in rats. Mitochondrial enzymes and respiratory chain enzymes, which decreased in Nnitrosodiethylamine treated rats, increased significantly in Rubia cordifolia treated rats. The levels of hydroxyl radicals and lipid peroxidation also decreased. Histological analysis of liver confirmed the prevention of pathological changes caused by Nnitrosodiethylamine, which suggest that Rubia cordifolia may be developed as an effective chemotherapeutic agent50.

3. Psoriasis is skin disorder characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes. Ethyl acetate (EA) fraction of Radix Rubiae inhibits cell growth and promotes terminal differentiation in cultured human keratinocytes which strongly suggest its antipsoriatic activity. Evaluation is done by cornified envelope (CE) formation assay showed that EA fraction of Radix Rubiae significantly accentuated the CE formation, a well-recognized marker of terminal differentiation, in cultured HEK and HaCaT cells in a dose and time dependent manner51.

4. Methanolic extract of Rubia cordifolia induced typical apoptosis in HEp-2 (Human laryngeal carcinoma) cell line through the elevation of reactive oxygen species generation. Inhibition of cell proliferation and lactate dehydrogenase release increased in a time and dose-dependent manner. Apoptotic effect of Rubia cordifolia extract (30 mg/ml) on HEp-2 cells confirmed by fluorescent and transmission electron microscopy based on morphological and ultrastructural changes52.

5. Alizarin, a natural hydroxyanthraquinone derived from root of Rubia cordifolia evaluated as an osteotropic drug for treatment of bone tumors because of its high affinity to bone. Antitumor activity of alizarin investigated on human cell lines representative for bone metastases from prostate cancer, breast cancer and for three human osteosarcoma cell lines. Alizarin induced a dose-dependent inhibition of cell growth over time in osteosarcoma and breast cancer cell lines, whereas in prostate cancer cell line, it appeared to be cytotoxic only at higher concentration. Studies found that alizarin acted through the inhibition of ERK phosphorylation and cell cycle arrest in the Sphase53.

CARDIOPROTECTIVE APPROACH:

Rubia cordifolia role in supporting heart health is evidenced by traditional and reported activities which show that it act as potent blood purifier, antioxidant, diuretic, calcium channel blocker, antiplatelet, antidiabetic, antiinflammatory, antistress, immunomodulator etc. Rubia cordifolia known for its antioxidant, antiinflammatory and potent blood purifier activities can play an important role to detoxify ischemia induced free radical generation. Diuretic activity of Rubia cordifolia could be an alternative therapy in the management of congestive heart failure (CHF) for rapid mobilization of edema fluid. Antistress, diuretic and vasodilating properties of Manjistha can play an important role in the management of hypertension. Rubia cordifolia inhibits platelet aggregation induced by PAF (Platelet Activating Factor) potentiate its therapeutic role in coronary artery disease. Antihyperglycemic and antihyperlipidemic effects of Manjistha direct its medicinal role in diabetic cardiomyopathy and diabetic macrovascular disease. Rubia cordifolia exhibits spasmolytic activity similar to that of verapamil suggestive of presence of calcium channel blocker(s) like constituents in this plant54 and therefore, indicates its possibility to treat arrhythmias result from calcium overload in ischemia-reperfusion condition.

CONCLUSION:

Today prescription of combination therapy (hypolipidemic, diuretic, calcium channel blocker, vasodilator, antiplatelet) are common in patients with cardiac dysfunction. Chances of drug interaction and adverse effect arise with combination therapy. Rubia cordifolia an individual plant with multiple activities that is essential to support heart health could become a new approach in the management of cardiac disorders and therefore, need research work to isolate cardiac biomarkers from this plant.

Tables at a glance

Table 1 Table 2 Table 3 Table 4

Figures at a glance

Figure A

References

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