Rubia Cordifolia L.) with Special Reference to Ayurvedic and Modern Aspect

Available Online at http://www.recentscientific.com International Journal of CODEN: IJRSFP (USA) Recent Scientific

International Journal of Recent Scientific Research Research Vol. 11, Issue, 04 (A), pp. 37958-37968, April, 2020 ISSN: 0976-3031 DOI: 10.24327/IJRSR Research Article

A COMPREHENSIVE REVIEW ON MANJISHTHA (RUBIA CORDIFOLIA L.) WITH SPECIAL REFERENCE TO AYURVEDIC AND MODERN ASPECT

Dr. Bharti Sadabal1*, Dr. T.A.Pansare2, and Dr Sachin Govindrao Tike3

1 PG Scholar (Dravyaguna) Govt. Ayurved College, Osmanabad, Maharashtra 413501 2Associate Professor (Dravyaguna), Govt. Ayurved College, Osmanabad, Maharashtra 413501 3Assistant Professor and Incharge H.O.D. Dept of Panchkarma Govt Ayurved College, Osmanabad

DOI: http://dx.doi.org/10.24327/ijrsr.2020.1104.5214

ARTICLE INFO ABSTRACT

Article History: Medicinal plants have an imperative role to preserve the disease free healthy human life. Manjishtha (Rubia cordifolia L.) belonging to Family Rubiaceae is traditional and medicinal standards towards Received 4th January, 2020 th a disease free population. It is frequently prescribed in various indigenous systems of medicine like Received in revised form 25 Ayurveda. In Ayurvedic classics various properties of Manjishtha such as varnya (beneficial for February, 2020 complexion), swarya (improves voice), jvarahara (reduces fever), vishaghna (detoxifies), Accepted 18th March, 2020 th kushthaghna (useful in skin disorders), raktavikarhar (beneficial in blood disorders), vranahar Published online 28 April, 2020 (wound healing), pramehaghna (useful in diabetes), shothahar (anti-inflammatory), yoni-netra and karnavikarhar (useful in uterine -eye and ear disorders), Arshoghna (cures piles) etc. are well Key Words: described. It is also a well known rasayana (rejuvenative). Acharya Sushruta has mentioned

Manjishtha, Rubia cordifolia, Manjishtha as pittasamsamana (which pacifies the pitta dosha). Manjishtha have valuable effects phytoconstituents, pharmacological resembling anti-carcinogenic, anti-acne, immunity-enhancing, anti-oxidant, anti-inflammatory, hepato-protective, cardio-protective, gastro-protective, neuro-protective, nephro-protective and many other pharmacological activities. Literature describes the luxurious effects of Rubia cordifolia to treat number of diseases including cancer, alzheimer, diabetes, acne, inflammation, allergy, enterocolitis and bacterial and viral infection. The phytochemical constituents like anthraquinones, glycosides, saponins, steroids, phenols, and flavonoids, alkaloids, tannins etc. were found as a major constituent in this plant. This review not only provides details about Ayurvedic information but it also gives a bird's eye view on the phytoconstituents and pharmacological properties of Manjishtha for future scope of research and for conservation of this valuable herb.

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INTRODUCTION and hepatoprotective and are extensively used against blood, urinary and skin diseases [5,6] . In prehistoric, Manjistha as an The interest of Public, academic and government in traditional efficient blood cleanser or purifier and hence is widely used medicines is growing exponentially because of the increased beside blood, urinary and skin diseases. [7] Externally, incidence of the adverse drug reactions and economic burden Manjistha was applied on major burns, mixed with honey on of the modern system of medicine[1]. The herbal medicines are freckles. It is a potent drug for persistent skin diseases like relatively safer than artificial drugs [2,3]. In Ayurveda, there are erysipelas, leucoderma, and inflammation also used to reduce a number of natural crude drugs that have the potential to treat fever and against blood disorders in Ayurveda. conventionally, different disorders, one of the important drug is Rubia it is used in many herbal formulations for various cosmetic cordifolia Linn. It is also known as Indian Maddar. It is a preparations because of its antiseptic, inflammatory, and perennial, herbaceous prickly climber with long and cylindrical galacto-purifier activity.[8] Root is used internally and root with a thin red bark, admired for its versatile action. It is externally to gain shine and glow of the skin and aids to distributed in the hilly area of Himalayas from Kashmir remove pimples, freckles and discoloration.[9] Apart from its eastwards and Nilgiris [4] .One of its very good actions is anti- medicinal value, Manjistha has also been used as natural food acne effect through anti-bacterial, anti-inflammatory, anti- colorants and natural dyes. Coloring pigments present in the oxidant and anti-androgen action. The roots and stems are well roots are munjistin and purpurin in large amounts. Madder root known source of Anthraquinones, it also been reported as extract has investigated for its dying characteristics and yielded antioxidant, anti-inflammatory, anticancer, immunomodulator

*Corresponding author: Dr. Bharti Sadabal PG Scholar (Dravyaguna) Govt. Ayurved College, Osmanabad, Maharashtra 413501 Dr. Bharti Sadabal, Dr. T.A.Pansare, and Dr Sachin Govindrao Tike., A Comprehensive Review on Manjishtha (Rubia Cordifolia l.) with Special Reference to Ayurvedic and Modern Aspect beautiful orange red to scarlet shades when applied onto the kushtha (skin diseases), raktadosha (bood related), visarpa woolen yarn.[10] Manjishtha contains active constituents like (erysipelas), vrana (wound), and prameha (diabetis). anthraquinones, glycosides, saponins, steroids, phenols, and flavonoids, alkaloids, tannins etc. which are responsible for its Dhanwantari nighantu [13] therapeutic efficacy. It exhibits various pharmacological Synonyms: Kalameshi, samanga, vikasa, aruna, manjuka, effects like anti-carcinogenic, anti-acne, immunity-enhancing, raktayashti, bhandi, yojanvalli, kshetrini, vijay, rakta, raktangi, anti-oxidant, anti-inflammatory, cardio-protective, gastro- vastrabhushana (used for the dueing of cloths), jingi, bhandi, protective, hepato-protective, neuro-protective, nephro- kala, gandali, and kalameshika. protective etc. The present paper is an endeavor to draw attention to Ayurvedic information, diverse pharmacological Guna karma- manjishtha is madhura and kashaya in rasa activities and medicinally active phytoconstituents of ushna in veerya and guru. It treats kapha, ugra vrana...... , Manjishtha and provide medicinal values of this valuable herb prameha, raktavikara, visha and netraroga. to scientific communities. The rich heritage of traditional drug, Madanpaal nighantu [14] ‘Manjishtha’ is evaluated in this review to provide broad and distinctive information which will be helpful to researchers and Synonyms: Manjishtha (A reputed drug for purifying blood), pharmaceutical industries to develop the pharma worth of this vijay,, rakta, raktangi, kalameshika, raktayashti, tamravalli wonder drug. (Coppry when half-dried), samanga, vastrabhushana(used for the dueing of cloths),, manjula (A reputed drug for purifying Vernacular Names blood), vikasa, bhangi, chadmika, jwaranashini (Act as anti- Sanskrit: Manjishtha, Viksa, Yojanvalli pyretic). Hindi: Manjith Guna and karma: madhura, kashaya and tikta in rasa and is Marathi: Manjit golden in colour. It is guru and ushna in property and wins Bengoli: Manjishtha over visha, kapha, shopha...., yonishool, netrashool, Gujarati: Manjith raktatisara, kushtha, rakta, visarpa, vrana, and prameh. Shaak Tamil: Manjitti of manjishtha has deepana property and possess madhura rasa Telgu; Tamravalli and wins over pitta and vata Kannd: Manjishtha Malayalum: Manjithi Kaidev nighantu:-[15]

English: Indian madder[11] synonyms: Raktangi, raktyashtika, chadmaka, manjula, bhandi, Ayurvedic Properties[11] bhandira, samanga, vikasa, vastrabhushana, tamramula, tamravalli , kalmeshi, jingi, yojanvalli. Rasa: Tikta (bitter), kashaya (astringent), madhur (sweet) Guna: Guru (heavy), ruksha (dry) Guna and karma: madhura, kashaya, and tikta in rasa, guru in Veerya: Ushna (hot) property, ushna in veerya and enhanceses voice quality. It use Vipaka: Katu (pungent) in ear and eye disorders, vaginal disorders, kapha, shotha, Dosha: Pacifies kapha and pitta visha, visarpa, prameha, kushtha, arsh (arsha)., vrana vikara, Karma: Varnaropana, Jwarhara,shothahar, kushthaghna. and raktavikar. Shaak of manjishtha is sweet in taste, laghu, snigdha and has agnideepak ...... property and wins over vaat Manjishtha in Nighantu`s and pitta. [12] Bhavprakash nighantu Description of plant Synonyms: Manjishtha (A reputed drug for purifying blood), It is a perennial, prickly climber with a stem, growing up to 12 vikasa (An extensive spreading climber)., jingi (An extensive m long. Leaves are highly variable, ovate lanceolate, 5-7 spreading climber), samang (It spreads in all directions)., nerved, 2-10 cm long and 2-5 cm broad, occurring in whorls of kalmeshika (Roots are black on completely druing), 4-6. Flowers are fragrant, minute, whitish or greenish yellow. mandukparni (It is spreading like Mandukaparni), bhandiri Fruit is minute, glabrous, 1-2 seeded, dark purplish or blackish (Colour resembling the blacked pot), bhandi, bhanditiki (An when mature. During August-October plant carries flower and extensive spreading climber), yojanvalli (An extensive fruit. Roots are perennial, long, cylindrical, and rusty brown in spreading climber)..., rasayani (A blood purifier which colour. [16] maintain normal health), kala (roots are black in colour), raktangi (The roots are red when fresh), raktangi, aruna (The Taxonomic Classification stem are red in colour), gandiri (Alleviates glandular Kingdom : Plantae swellings), manjusha (Purifies the blood and gives complexion Class : Dicotyledoneae to the body), and vastraranjini (Used for dyeing cloths). Subclass : Sympetalae Manjishtha possess madhura, tikta, and kashaya rasa. It Order : Rubiales enhances voice and improves complexion. It is guru and ushna Family : Rubiaceae in veerya and is used in dealing of visha (poison), kapha, Genus : Rubia shotha (imflamation), yoni (mestrual), netra (eye diseases), and Species : cordifolia. [17] karna (ear related diseases) , disorders, raktatisara (desentry), Availability of Manjishtha

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It occurs throughout India (Dehradun, Kashmir, Nagpur, dihydroxy-2- methyl-5-methoxy anthraquinone, 1,3- dimethoxy Malva, and Chitrakut), Nepal, Shrilanka, Iran, and Afghanistan. 2- carboxy anthraquinone and rubiadin [23].Also possesses It is propagated by seeds and stem – cutting[18]. According to different classes of bioactive compounds such as Raja Nighantu, Manjishtha has four types; Chola, Yojani, anthraquinones and their glycosides, naphthoquinones and Konchi and Sinhali[19]. Manjishtha has also three species like- glycosides, terpenes, bicyclic hexapeptides, iridoids [24]. Rubia Rubia cordifolia (Indian madder), Rubia akane (Asian madder) cordifolia yielded anthraquinones namely, 1hydroxy-2 carboxy and Rubia tinctoram (European or African madder) [20] 3-methoxy anthraquinone, 1hydroxy-2 methyl 6 or 7-methoxy- anthraquinones and other compounds oleanolic acid acetate, β- API Standards are as follows sitosterol, and scopoletin. Ten long chains saturated and Manjishtha- Rubia cordifolia Linn.[21] unsaturated fatty acids [25]. The roots of Rubia cordifolia produce two anthraquinones, namely cordifoliol and part used- Stem cordifodiol. On the basis of spectral data analyses and chemical Foreign matter: Not more than 2%, Appendix 2.2.2 reactions their structures have been established as 1-hydroxy-3- Total ash: Not more than 12%, Appendix 2.2.3 ethyl-9, 10 anthraquinones (1) and 1,8-dihydroxy-11,20 Acid –insoluble ash: Not more than 0.5%, Appendix 2.2.4 (15pentyl-naphthoquinone) phenanthrene (2) [26]. The roots of Alcohol-soluble extractive: Not less than 3%, Appendix 2.2.6 Rubia cardifolia provide several naphthoquinones and Water-soluble extractive : Not less than 17%, Appendix 2.2.7 [27]. hydroxyanthraquinones and their glycosides Other quinones Macroscopic and Microscopic Examination isolated were 4dihydroxy 2-methylanthraquinone, 4naphthoquinone, lucid primeveroside, 1, 5-dihydroxy 2methyl Stem: is quadrangular, divaricately branched, prickly-hispid, anthraquinone, 3-prenyl methoxy 1, ruberythric acid Cross section of the stem showed rectangular outline with anthraquinones, 2-methyl-1, 3, 6-trihydroxy-9, 130 single layered epidermis covered with cuticle and pyramidal 10anthraquinone and 2-methyl-1, 3, 6-trihydroxy-9, hairs. Hypodermis sclerenchymatous present at the corners of 10anthraquinone 3-Oα-rhamnosyl (1→2)-β-glucoside. the stem. The cortex is photosynthetic chlorenchymatous, 6Methoxy geniposidic acid (iridoids) is also found along with Phloem 4-6 layered, composed of sieve tubes and phloem man Justin, garancin, and alizarin [28]. The methanol extract of parenchyma. Cambium ring is represented by two layers. Rubia cordifolia roots contains 2 naphthoquinones [29]. The Secondary xylem is made up of vessels, tracheids, fibers and bicyclic hexapeptides RA-I and RA-II have been isolated from xylem parenchyma. vessels are large and uniformly arranged. chloroform/methanol extract of roots of Rubia Cardifolia [30]. Medullary rays are uniseriate. Recently two new bicyclic hexapeptides, allo RA-V and neo- Leaves: glabrous and rough 3.8-9 × 1.6-3.5 cm long, arranged RA-V, and one cyclic hexapeptide, O-Secora-V were isolated in whorls of four, ovate-lanceolate, 3-9 palmately veined. from Rubia cardifolia [31]. The plant also contain Lower leaves are larger than the upper. Leaf base is slightly dihydromollugin, Mollugin, rubilactone [32]. cordate. The margins are with minute white prickles. Leaf Traditional Therapeutic Uses section showed solitary layered epidermis, enclosed among cuticle and possesses pyramidal hairs. Palisade cells are single In ‘Charaka Samhita’ Manjistha is also mentioned in ten covered and closely filled, spongy cells multilayered and varnya [33] drugs and as Visaghna [34] Jvarahara.[35] the loosely arranged. In the lesser portion of the midrib 2-4 layers powdered dried roots and fruits we can give internally to cure prepared of collenchymatous cells. Vascular bundles are the skin diseases and disorders of spleen.[36] It is also given in collateral and closed, conjoint and definite in number. major burns, fractures and dysentery,[37] to improve complexion and to treat skin diseases and blood born diseases.[38,39] Petiole: 5-10 cm long with sharp, recurved prickles. Stipules Manjistha paste is used along with honey in Vyang.[40] It has absent or modified into leaves. The T.S. of the petiole showed properties of blood purifying agent and pigment stimulant, single layered epidermis with pyramidal hairs. Below the tonic and are used in skin and blood diseases.[41] Ayurvedic epidermis, 3-4 layers of sclerenchymatous cells were present. pharmacopoeia of India therapeutically indicate it for Yoni roga The cortical cells were made of thin-walled chlorenchyma. The (menstrual disorder), Kustha (skin disease), Sarpavisa (snake vascular bundle is 'C'- shaped. bite), Visarpa (herpes virus), Aksi roga (eye disease), Arsa Root: is long, cylindrical, flexuose, smooth and reddish. The (haemorrhoids), Bhagna (Fracture).[42] Formulations containing cross-section of roots showed an outer 5-7 layer of cork tissue, manjistha as main ingredient used for treating skin disease [43- which occasionally contains tannin. Phellogen is not distinct, 52] The roots are alterative, anodyne, antiphlogistic, astringent, Secondary cortical cells thin-walled, red in color and polygonal diuretic, expectorant, styptic and vulnerary.[53] in shape. Secondary xylem dish consists mainly of vessels and Ayurvedic Preparations tracheids. Vessels are abundant and distributed uniformly. Secondary phloem forms a wide zone of reddish color consists Manjistha is an important element of lots of ayurvedic of thin-walled, sieve elements and phloem parenchyma but formulations; Mahamanjisthadi kvatha, Manjisthadi taila, lacks phloem fibers. Cambium is distinct and lacks medullary Manjistha arka, Manjistha malahara, Manjistha phanta, Septilin rays. The whole portion of the root is red coloured indicates the syrup etc. Mahamanjisthadi kvatha: The herbal addition used as presence of anthraquinones [22]. blood purifier, immunomodulator, promotes skin health and skin texture. Septilin syrupis contains many herbal preparation Phytochemical Studies containing Rubia cordifolia as one of the constituent, tried in Rubia cadifolia has mainly anthraquinone, quinines glycosides 40 children suffering from various upper respiratory tract and include 1-hydroxy 2-methoxy anthraquinone, 1, 4- infections. Excellent response was seen in 34 (85%) children.

37960 | P a g e Dr. Bharti Sadabal, Dr. T.A.Pansare, and Dr Sachin Govindrao Tike., A Comprehensive Review on Manjishtha (Rubia Cordifolia l.) with Special Reference to Ayurvedic and Modern Aspect

Incidence of recurrences was minimal.[54] Body Revival: It is an effective antiproliferative action on HaCaT cells (IC (50) 0.9 Indian herbal formulation having suspension of Aegle microg/ml). The standardized EA fraction was formulated into marmelos, Acorus calamus, Rubia cordifolia, Saussurea lappa, local application like gel form and its keratinocyte-modulating Blumea lacera, Rumex vasicarius, Curcumas melo, Symplocos action was tested on mouse tail model. EA fraction dose- racemosa and honey. Investigation showed that Body Revival dependently increased the number and thi ckness of granular potentiates cardioprotection against isoproterenol induced layer and epidermal thickness on mouse tail skin, indicative of myocardial ischemia and ADP or collagen induced human the keratinocyte differentiation-inducing activity. Taking the in platelet aggregation[55] . vitro and in vivo findings together, the present preclinical study confirms that EA fraction is a promising antipsoriatic agent Pharmacological actions [64] warranting further development for to treat psoriasis. Anticarcinogenic activity Antibacterial Activity The root extract of Rubia cordifolia has potent anticancerous The antibacterial activity of the extracts of stem-bark, Rubia activity against MDA-MB-231 breast cancer cell lines using cordifolia and Lantana camara root-bark, prepared with Sulforhodamine B assay [56]. The administration of Mollugin in solvents of different polarity, was evaluated by the agar-well Mice showed inhibition of passive cutaneous anaphylaxis and diffusion method. Twelve bacteria, six each of gram-positive protection of mast cell degranulation and also showed and gram-negative strains, were used in this study. Chloroform inhibition against lymphoid leukemia (P338) [57]. The ethanolic and methanol extracts of R. cordifolia and L. camara was extract of Rubia cardifolia exhibited strong inhibition of human found to be more particular on the way to the gram-positive cervical cancer cell line thus can be a source of powerful strain, although gram-negative P. aeruginosa was also pharmacophore for treatment of disease like cancer [58]. The inhibited by the methanol extracts of both these plants in a dose presence of cyclic hexapeptides and quinones in Rubia dependent manner. R. cordifolia was significantly active cardifolia exhibited a momentous anticancer activity against against B. subtilis and S. aureus compared with streptomycin various proliferating cells [59]. The derivatives of RA-V like and penicillin G used as standards.[65] Alkyl ether and ester exhibit momentous effects against P388 lymphocytic leukemia, human nasopharynx carcinoma, and Comparative studies of Rubia cordifolia and its Commercial MM2 mammary carcinoma cells [60]. Several secondary plant Samples were done. It was carried out by comparing the metabolites were isolated from roots of Rubia cordifolia and authentic sample from its commercial samples keeping in mind rhizomes of G. glabra by using Cayman COX (ovine) the pharmacopoeial standards of Ayurveda. The quantitative inhibitory screening assay, few molecules showed potent COX- phytochemical studies of the drug samples are carried out by 2 inhibitory activity against cancer [61]. study the fraction of ash, extractive values and qualitative screening was carried out by Thin Layer Chromatography and Anti-tumour activity .[66] different biochemical tests Anti-tumour activity of RC-18, proved from Rubia cordifolia Anti Ulcer Effect was repeatedly tested in different sets of experiments on a spectrum of experimental murine tumours, viz. P388, L1210, The effect of Rubia cordifolia against experimentally induced L5178Y, B16 melanoma, Lewis lung carcinoma and sarcoma- gastric ulcer and compare activity with its fractions by 180. RC-18 exhibited significant increase in life span of ascites employing aspirin plus pylorus-ligated ulcer screening model leukaemia P388, L1210, L5178Y and a solid tumour B16 in wistar rats. The study confirmed that chloroform extract melanoma. However, it failed to show any inhibitory effect on showed the momentous activity at lower doses compared to solid tumours, Lewis lung carcinoma and sarcoma -180. parent extract. The mechanism can be attributed to decrease in Promising results against a spectrum of experimental tumours gastric acid secretary activity along with strengthening of suggest that RC-18 may lead to the development of a potential mucosal defensive mechanism by prostaglandin synthesis and anti-cancer representative.[62] antioxidant potential.[67]

Wound Healing Effect Hepatoprotective Activity

Wound Healing of a herbal formulation of Rubia cordifolia The hepatoprotective activity of an aqueous and methanol was done. emulsion formulation of herbal drug mixture of extract of Rubia cordifolia was investigated against R.cordifolia, C.asiatica, T.belerica, P.zeylanica, and acetaminophen and CCl4induced hepatic damage. W.somnifera was formulated. Animals were inspected daily up Acetaminophen created 100% death at a dose of 1 g/kg in mice to 20th days and healing was good and produces wound while pretreatment of animals with plant extract (500 mg/kg) contraction, period of epithelization and histological study. It reduced the fatality rate to 30%. Acetaminophen at a dose of shows, that there is contraction and new epithelization of 640 mg/kg produced liver damage in rats as manifested by the excision wound.[63] rise in serum levels of GOT and GPT to 1447±182 and 899±201 IU/L (n =10) respectively, compare with respective Anti-proliferating Property manage values of 97±10 and 36±11. Pretreatment rats through Roots of the Rubia cordifolia L. Ethyl acetate extract inhibits plant extract (500 mg/kg) lower significantly (p<0.005) the keratinocyte propagation in vitro and promotes keratinocyte respective serum GOT and GPT levels to 161±48 and 73±29.[68] segregation in vivo. Ethanolic extract of Radix Rubiae is fractioned sequentially with hexane, ethyl acetate (EA), n- butanol and water. EA fraction was found to possess most 37961 | P a g e International Journal of Recent Scientific Research Vol. 11, Issue, 04 (A), pp. 37958-37968, April, 2020

Anti-acne property dose dependent manner, which is comparable to that of phenylbutazone.[86] It also inhibited the lipoxygenase enzyme Methanol extract of Rubia cordifolia inhibit proliferation of P. pathway, which catalyses the production of various acne.[69] It is moderately effective against TNFalpha and show inflammatory mediators such as leukotrienes that are involved low activity against IL-8. It is regarded as astringent and useful in asthma, arthritis, and other inflammatory disorders and the in external inflammations like ulcers and skin diseases.[70]The production of cumene hydroperoxides.[87] Notable nitric oxide anthraquinone rich fraction of R.cordifolia in a gel formulation scavenging activity was exhibited in vitro by some extracts of showed The anti-acne activity against Propionibacterium acne, R.cordifolia.[88] A formulation of munjistin and purpurin from Staphylococcus epidermidis, Malassezia furfur when compared .[71] cell culture manifested to have and antproliferative action with standard Clindamycin gel .[89] during the rapid development of a model oedema Anti-oxidant activity Radioprotective Propertyz extract of root of Rubia cordifolia and its constituent rubiadin Radioprotective latent of alcoholic extract of root of Manjistha were found antioxidant property.[72],[73],[74] showed a significant radiation guard (67%) as assessed by Hydroxyanthraquinones were the prime antioxidant phenolic increased animal endurance when R. cordifolia extract was constituents of R. cordifolia.[75] The antioxidant properties of administered intra peritoneally before radiation exposure. R.cordifolia extract for protection Alcoholic against lipid Results suggest the alcoholic root extract provides protection peroxidation and reduced glutathione (GSH) content in rat liver against radiation-induced lipid peroxidation, hemopoietic homogenate compared with vitamin E and parabenzoquinone .[90] [76] injury and genotoxicity (PBQ). Nephrotoxicity Anti-microbial activity The hydro-alcoholic extract of Rubia cordifolia can reduce the Extract of R. cordifolia showed a good inhibitory activity strength of cisplatin induced nephrotoxicity in Swiss albino against P. acnes standardized culture. The evaluation was mice. The extract could significantly decrease the cisplatin carried out by both dilution method as suggested in MIC, there induced nephrotoxicity as inferred from the tissue antioxidant R. cordifolia extract was taken 600 μg/ml. The evidence of status in the drug administered animals. Remarkable change anti-acne activity of R.cordifolia was further supported by Cup- was observed in serum creatinine and urea levels. Lipid plate method.[77] Rubia cordifolia was effective against peroxidation in the kidney and liver tissues was also Klebsiella pneumonia. The root extracts of R. Cordifolia had considerably reduced in Rubia cordifolia extract treated studied for their antimicrobial activity against different animals.[91]An effective column-switching counter-current pathogenic bacteriaes. Sitosterol and daucosterol possess chromatography (CCC) protocol combining stepwise elution antibacterial activity. The root extracts constituents such as mode was successfully developed for simultaneous and anthraquinones and flavonoids suppressed the activity preparative separation of anti-oxidative components from ethyl phytopathogens of Gossypium.[78] Aldehyde aceate, acetate extract of traditional Chinese herbal medicine.[92] dihydromollugin and rubimallin reported to have significant .[79] Anti-Protective effect antibacterial activity against Klebsiella pneumonia Ethanolic extract inhibited s-Lactamase producing The hydro-alcoholic extract of roots of Rubia cordifolia Linn. uropathogenic E. coli.[80] The chloroform and methanol extracts Shows the protective effects (HARC) against ethylene glycol reported to have antibacterial activity against the grampositive induced urolithiasis and its possible underlying mechanisms strains, although gram negative Pseudomonas aeruginosa was using male wistar albino rats. Ethylene glycol feeding resulted also inhibited by the methanol extracts in a dose dependent in hyperoxaluria, hypocalciuria as well as increased renal manner. The aqueous extract is active against Bacillus subtilis excretion of phosphate. The greater than before calcium and and Staphylococcus aureus compared with streptomycin and oxalate levels and number of calcium oxalate crystals deposit penicillin G.[81] The ethanolic whole plant extract also showed in the kidney tissue of calculogenic rats was considerably same result.[82] Rubiacordone A reported to have considerable reverted by HARC treatment. The HARC supplementation also antimicrobial activity against Gram-positive bacteria like prevents the hurt of renal functions. The results indicate that Bacillus subtilis, Streptococcus faecalis and Bacillus cereus.[83] the HARC can protect against ethylene glycol induced The green urolithiasis as it reduced and prevented the growth of urinary stones. Therefore, HARC is supportive to prevent the repetition synthesized silver nanoparticles using R. cordifolia plant root of the disease as it showed its result on early stages of stone extract was highly inhibiting the bacterial pathogens enlargement. The mechanism underlying this effect is mediated resembling Plesiomonas shigelloides, Vibrio alginolyticus, possibly through an antioxidant, nephroprotection and its effect Pseudomonas aeroginosa, Shigella spp, and Vibrio on the urinary concentration of stone-forming constituents and parahaemolyticus. They had highest antimicrobial effect risk factors.[93] against Pseudomonas aeroginosa and Plesiomonas shigelloides.[84] The protective effect of Rubia cordifolia against lead nitrate- induced immune response impairment and kidney oxidative Anti-inflammatory activity damage was studied. Seventy-two adult male Swiss albino The aqueous extract of R. cordifolia showed anti-inflammatory mice were used for biochemical and immunological studies and effect in rats.[85] The anti-inflammatory action is because of the were divided into six groups of six mice each. Mice were presence of rubimallin. The aqueous extract showed anti- treated with lead nitrate (40 mg/kg, orally) either alone and or inflammatory activity in rats with carrageenan paw oedema in a in combination with RC (50 and 100 mg/kg body weight) daily 37962 | P a g e Dr. Bharti Sadabal, Dr. T.A.Pansare, and Dr Sachin Govindrao Tike., A Comprehensive Review on Manjishtha (Rubia Cordifolia l.) with Special Reference to Ayurvedic and Modern Aspect for 40 days. Lead nitrate administration induced a significant defensive mechanism by prostaglandin synthesis and (P<0.001) increase in LPO, whereas a significant (P<0.001) antioxidant potential.The extract of Rubia cardifolia exhibited depletion of CAT and GSH in renal tissues. In addition, it also significant protection against gastric ulcers in all the models of showed a significant (P<0.001) reduction in macrophage yield, rats compared to ranitidine. In polyherbal formulations, the viability of macrophage, phagocyte index, serum ulcerogenic effect in rats showed significantly lesser ulcer immunoglobulin level, and PFC in kidney. However, result even at a very high dosage as compared to that of aspirin combination treatment with RC observed a significant [99]. (P<0.001) reversal of lead nitrate-induced toxicity on oxidative Antimutagenic activity stress and immunological parameters. The lead nitrate-induced Different root extracts of Rubia cordifolia and their immunosuppression is due to oxidative stress and RC can antimutagenic activity was estimated in Ames Histidine prevent the same by virtue of its in vivo antioxidant property.[94] reversion assay using Salmonella typhimurium against Anti-Adipogenic Activity: Anti-adipogenic activity of 2- mutations induced by direct-acting mutagen 4-nitro-o- carbomethoxy-2, 3-epoxy-3-prenyl-1, 4-naphthoquinone phenylenediamine (NPD) and against S9-dependent mutagen 2- (CMEP-NQ) isolated from the roots of Rubia cordifolia L., its Aminofluorene (2-AF) in TA98 tester strain of S. effects on cell viability, apoptosis, and adipogenesis in 3T3-L1 typhimurium.The root extract of Rubia cordifolia was preadipocytes were investigated.[95] fractionated into highly polar methanol extract (RME) and comparatively less polar chloroform extract (RCE). RME was Anti-HIV Activity found to be quite effective in inhibiting the mutagenicity of Various extracts prepared from medicinal plants, were chosen 2AF, i.e. indirect-acting mutagen, in comparison to the on the basis of similarity of chemical constituents with reported mutagenicity induced by direct-acting mutagen i.e. NPD. The anti-HIV compounds or on the origin of their traditional inhibitory activity against NPD was 41.69% and 58.21% at the convention as immunomodulators. Various extracts had maximum dose tested (2.5×103 μg/0.1 ml) during coincubation prepared via Soxhlet extraction and liquid-liquid partitioning. and preincubation mode of experiments, respectively. RME Ninety-two extracts were prepared from 23 plants. Anti-HIV significantly inhibited 2AF-induced histidine revertants by activity was measured in a human CD4+ T-cell line, CEM-GFP 70.71% and 71.70% respectively during coincubation and cells infected with HIV-1NL4.3 from the different 8 plants preincubation mode of experiments with IC50 of 500 μg/0.1 ml Nine extracts was prepared shows significantly reduced viral in the preincubation mode of the experiment. Chloroform production in CEM-GFP cells infected with HIV-1NL4.3. extract (RCE) reduced the mutagenicity of NPD by 59.04% in Aegle marmelos, Argemone mexicana, Asparagus racemosus, the preincubation mode of the experiment at the maximum Coleus forskohlii, and Rubia cordifolia demonstrated tested dose of 2.5×103 μg/0.1 ml with IC50 of 664 μg/0.1ml. promising anti-HIV potential.[96] RCE 134 completely inhibited the 2AF mutagenicity, as about 99% inhibitory effect was recorded in both coincubation and Neuroprotective Properties: R. cordifolia has been shown to preincubation mode of treatments [100]. exert cell/neuroprotective properties via preventing the depletion and increasing GSH (glutathione) levels by inducing Antiviral activity GCLC (c-glutamylcysteine ligase) expression, reducing oxidant The anti-rotaviral effect of Rubia cordifolia aerial part (RCAP) levels by direct scavenging, and decreasing iNOS expression. and its cytotoxicity toward MA-104 cells was evaluated using The protective ability may be attributed to the GSH and the WST-8 assay. Colloidal gold technique and real time vitamin C content of the herb.[97] Neuroprotective effect of polymerase chain reaction (qPCR) assay was use to verify the Rubia cordifolia Linn. was studied on β-amyloid Induced findings of the antiviral assay. Then, 4′,6-diamidino-2- cognitive dysfunction in Mice. Ethanolic extract of Rubia phenylindole (DAPI) staining method had consequently used to cordifolia administration significantly (P<0.01) reduced the β- explore the mode of death with the cells. It was revealed that amyloid induced cognitive and memory dysfunction. The both the possibility of MA-104 cells and the viral load were extract decreases the neurodegeneration and helps in memory reduced with increasing concentration of the extract. DAPI retention activity. The extract showed significant effects staining show that virus-induce apoptosis was the cause of the (P<0.05) in short term retention and increases long term low down cell viability and viral load, an outcome which was retention of memory in step-down inhibitory avoidance task accelerate with incubation in the aqueous herbal extract. The and an increase (P<0.05) in number of head dippings, line major compounds identified to exhibit this activities were crossings and rearings in the open field, and the water-maze Xanthopurpurin and Vanillic Acid. This study showed that test. The neuroprotective activity of the plant on alzheimer's RCAP extract effectively inhibited rotavirus multiplication by type dementia may be due to inhibition of AChE, MAO, free [101] .[98] promoting virus-induced apoptosis in MA-104 cells radical scavenging activity Diuretic activity Gastroprotective activity: The activity of Rubia cordifolia against experimentally induced gastric ulcer and compare Hydroalcoholic extract of roots of Rubia cordifolia in rats to activity with its fractions by employing aspirin plus pylorus- support its folklore claim. Four groups of rats were treated with ligated ulcer screening model in Wistar rats. The study vehicle (normal saline: 25 ml/kg), furosemide (20 mg/kg) and confirmed that chloroform fraction showed the significant two doses of extract (286 mg/kg and 667 mg/kg body weight) activity at lower doses compared to plant extract. The orally. Urine excreted was collected up to 5h post-treatment mechanism can be attributed to decrease in gastric acid and analyzed for urine volume, Na+, K+, Cl- and creatinine secretary activity along with strengthening of the mucosal content. The extract showed a significant (p<0.01) and dose 37963 | P a g e International Journal of Recent Scientific Research Vol. 11, Issue, 04 (A), pp. 37958-37968, April, 2020 dependent increase in urine volume and electrolyte excretion. spontaneous movements. When the tissues were pretreated with Both doses of extract showed less influence on creatinine plant extract (1 mg/mi) or verapamil (0.5 ug/ml) addition of clearance than furosemide. The result indicates that calcium failed to restore spontaneous contractions. These hydroalcoholic extract of roots of Rubia cordifolia possesses results Indicate that the plant extract exhibits spasmolytic potent diuretic activity [102]. activity similar to that of verapamil suggestive of the presence of calcium channel blocker like constituent(s) in this plant [109]. Anti-convulsant Activity: Triterpenes isolated from Rubia Cardifolia inhibited seizures induced by maximum electric Sexual Performance and Virility activity shock, electrical kindling and various chemoconvulsants in A number of herbal drugs including Rubia cardifolia have been rats. Brain GABA and serotonin (5-HT) contents were raised validated for their effect on sexual behavior and fertility and by triterpenes reveals its anticonvulsant property [103]. can, therefore, serve as the basis for the identification of new Immunity enhancing activity: The ethanolic extracts of the chemical leads useful in sexual and erectile dysfunction [110]. whole plant of Rubia Cardifolia were tested for many Anti-peroxidative activity immunity enhancing activity using a murine model. The active compound present in the extract enhanced both cell-mediated Solvent free alcoholic extract of R. cordifolia and humoral immunity. Administering the extracts to rats that showedantiperoxidative property in rat liver homogenate. The were given the immunosuppressive drug, phosphamidon cumene hydroperoxide induced malondialdehyde formation showed significant restoration in immunity [104]. accompanied by the reduced glutathione level even in the presence of above toxin.[111] Anti-ESBL (Extended Spectrum ß-Lactamase) activity: The study attempted to explore the antibacterial properties of Rubia Anti-platelet activating effect cordifolia, against ESBL (Extended Spectrum ß-Lactamase) In Ayurveda herb is prescribed to cure blood related producing urinary E.coli. Different E.coli strains were isolated component. Partially purified fraction of the whole plant from urine samples collected from patients using standard inhibits the action of platelet activating factor at its receptor methods. All the isolates were tested for different antibiotics level either by its blocking or desensitization property.[112] and screened for their ESBL production based on NCCLS guidelines. Total 7 different ESBL producing E.coli were Other relevant uses obtained. All the seven isolates were tested against the Separately from its medicinal value, this plant can also used as ethanolic extract of Rubia cordifolia using Kirby Bauer method a natural colourants in food, syrups, medicated oils, etc… Root and were found to be inhibited variably by the extract. Thus derived dye also used as cloth and hair dye. Madder extracts is suggests inhibitory properties of the extract against ESBL commonly used as a colorant for confections and soft drinks, producing E.coli [105]. because of its advantageous resistance to heat and light. The Nootropic and Anti-stress activity: The Alcoholic extract of convincing antioxidant activity of madder is successfully roots of Rubia cardifolia enhance brain ˠ-amino-n-butyric acid exploited in food business as chemo-preventive agents. R. (GABA) levels and decreased brain dopamine and plasma cordifolia can be used as a single drug to cure Chikungunya corticosterone levels. Acidity and Ulcers caused due to the cold fever.[113]Leaf extract is used during cataract of eyes, restraint stress were inhibited by the alcoholic extract. Animals conjunctivitis and also to clean the eyes. In patients with treated with alcoholic extract spent more time in open arm in eczema, the topical application of the plant caused reduction in elevated plus maze model, which antagonized scopolamine- the severity of score and oedema, exudation and itching being induced learning and memory mutilation [106]. significantly relieved. Crude methanolic extract suppressed the spontaneous contractions of guinea-pig atria, rabbit jejunum Cardioprotective activity: Nowadays combination therapy and rat uterus in a concentration dependent manner. The (hypolipidemic, diuretic, calcium channel blocker, vasodilator, indicate spasmolytic activity analogous to verapamil, a antiplatelet) are common in patients with cardiac dysfunction. criterion Ca++ channel blocker, suggest the attendance of Chances of drug interaction and adverse consequences arise calcium channel similar to constituent in the plant, that may be with combination therapy. Rubia cordifolia an individual plant [107]. liable for the folkloric use of this plant for disintegration of with multiple activities is essential to support heart health .[114] urinary stones DNA Topoisomerases I and II Inhibition by Anti-arthritic activity the constituents from the roots of R. cordifolia were established.[115] Psoriasis is a skin disease associated with hyper The ethanolic extract of Rubia cordifolia exhibits a significant proliferation and aberrant differentiation of keratinocytes. The anti-arthritic activity which was statistically similar to aspirin in vitro and in vivo findings together, the preclinical study [108]. confirms that ethanol fraction is a promising antipsoriatic Spasmolytic activity .[116] agent It can protect indomethacin-induced enterocolitis in The Crude extract of Rubia cordifolia suppressed the rats and may be beneficial in patients with inflammatory bowel spontaneous contractions of guinea- pig atria, rabbit jejunum diseases.[117] Wool dyed with extracts from madder also showed and rat uterus in a concentration dependent manner (0.1-3 improved insect resistance for carpet beetle.[118] mg/ml). In rabbit aorta, it inhibited 136 norepinephrine (10 uM) and KCl (80 mM) induced contractions. Replacement of CONCLUSION physiological salt solution with calcium free solution abolished Manjishtha is a widely and traditionally used medicinal plant the spontaneous movements of rabbit jejunum. However, the amongst all the thousands of medicinal herbs. It plays an addition of calcium (25 pg/mi) in the tissue bath restored the important role as a potent blood purifier, anti-oxidant, anti- 37964 | P a g e Dr. Bharti Sadabal, Dr. T.A.Pansare, and Dr Sachin Govindrao Tike., A Comprehensive Review on Manjishtha (Rubia Cordifolia l.) with Special Reference to Ayurvedic and Modern Aspect inflammatory, anti-stress, anti-microbial which helps to cure with Hindi commentary by edition 2004 chaukhamba acne and improve skin health. The pharmacological activities publication. 2004 pg 19 reported in the present review validate the great therapeutic 14. 14 . Vaidya panchanan pandit rams Prasad Madanpaal value of Manjishtha. It is an important source of chemical nighantu of shri Madanpaal with Hindi commentary, compounds such as anthraquinones, glycosides, saponins, khemraaj shriKrishna das publication Bombay edition steroids, phenols, flavonoids, alkaloids, tannins etc. These 2008. pg 40. compounds are accountable for various pharmacological 15. 15. Prof. Priyavrat Sharma and Dr. Guru Prasad Sharma activities like anti-carcinogenic, anti-acne, immunity- Kaidev nighantu of shri Kaidev chaukhamba enhancing, anti-oxidant, anti-inflammatory, cardio-protective, publications Varanasi 2006. gastro-protective, hepato-protective, neuro-protective, nephro- 16. 16. Sukh Dev: A selection of Prime Ayurvedic plant protective etc. The plant has a numerous traditional uses for drugs Ancient-Modern Concordance. New Delhi: ameliorating variety of diseases, which were additionally Anamaya publishers; 2006. supported by quite a lot of pharmacological and clinical studies 17. 17. A. Verma, B. Kumar, P. Alam, V. Singh, and S. K. detailing the definite bioactivity of extracts of the plant. Gupta, Rubia cordifolia –a review on pharmaconosy and Accordingly Manjishtha has a leading power for the phytochemistry, IJPSR, 7(7), 2016, 2720-2731. development of new good efficacy drugs in future. That's why 18. Sheth Ashok K. The herbs of Ayurveda - vol. 4, 1st the industrialists should come ahead with innovative concepts edition; 2005. p. 988. and steps towards the most excellent use of this potential 19. Dr Tripathi Indradeva. Raja Nighantu, Chowkhamba medicinal plant for the welfare of mankind. krishnadas academy Varanasi; 2010. p. 174. 20. Sheth Ashok K. The herbs of Ayurveda - vol. 4, 1st References edition; 2005. p. 988.

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How to cite this article:

Dr. Bharti Sadabal, Dr. T.A.Pansare, and Dr Sachin Govindrao Tike.2020, A Comprehensive Review on Manjishtha (Rubia Cordifolia l.) with Special Reference to Ayurvedic and Modern Aspect. Int J Recent Sci Res. 11(04), pp. 37958-37968. DOI: http://dx.doi.org/10.24327/ijrsr.2020.1104.5214

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