IJBPAS, September, 2016, 5(9): 2231-2238 ISSN: 2277–4998 NUPHAR LUTEUM – A REVIEW KAUR M1 *AND MUKHTAR HM2 1*Department of Pharmaceutical Sciences (Pharmacognosy), G.H.G Khalsa College of Pharmacy, Gurusar Sadhar- 141104 Ludhiana, Punjab, India 2Department of Pharmaceutical Sciences (Pharmacognosy), Shaheed Bhagat Singh College of Pharmacy, Patti, Tarn Taran, Amritsar, Punjab. India *Corresponding authors: E Mail address- [email protected]; phone number- 9478144239 Received 5th June 2016; Revised 26th July; Accepted 4th August 2016; Available online 1st Sept. 2016 ABSTRACT Nuphar luteum (Yellow Water-lily, Brandy-Bottle) synonym Nuphar lutea is an aquatic plant of the family Nymphaeaceae, native to temperate regions of Europe, northwest Africa, and Western Asia. It has been used in dysentery, gonorrhoea and leucorrhoea. The leaves and roots have been used as a poultice for boils and inflamed skin. Medicinal herb contains multitude of chemical compounds like alkaloids, anthraquinone glycosides, terpenoids, saponins, flavonoids, tannins and phenolic compounds, proteins, amino acids, carbohydrates, starch and vitamin C. Plant possesses anti-leishmanial activity, antineoplastic, anti- inflammatory, antifungal, and antibacterial activities. This review illustrates its major constituents, pharmacological actions substantiating the claims made about this plant in the traditional system of medicine. Keywords: Alkaloids, Anti-leishmanial, Nuphar luteum, Pharmacological. INTRODUCTION Genus Nuphar (Aiton) W.T.Aiton commonly known as Nuphar is genus of aquatic plants in the Spatterdock, Nuphar japonica DC, Nuphar family Nymphaeaceae, with a temperate to luteum( L.) Sm. Known as Yellow water- subarctic Northern Hemisphere lily, Nuphar polysepala Engelm known as distribution. There are seven known species great yellow pond-lily, Nuphar pumila of this genus such as Nuphar advena (Timm) DC. Commonly known as Least 2231 IJBPAS, September, 2016, 5(9) Kaur M *and Mukhtar HM Review Article water-lily, Nuphar sagittifolia(Walter) treat tuberculosis. An infusion of dried, Pursh commonly named as Arrow-leaved grated plant was taken for heart trouble [5]. water-lily and Nuphar variegata Engelm. TOXICOLOGICAL REPORTS ex Durand (the variegated pond-lily). The The use of natural plants as emergency number of species in the genus is still under food in Finland and northern Europe has review [1,2]. Nuphar lutea (Yellow Water- been described by Airaksinen MM et al. lily, Brandy-Bottle) is an aquatic plant of The chemical contents of the commonly the family Nymphaeaceae, native to used "pettu" (pine bark), lichen (Cetraria temperate regions of Europe, northwest islandica, Cladonia sp.) and water plants Africa, and Western Asia [3,4]. (Calla palustris, Menyathes trifoliata, Nymphea sp. and Nuphar luteum) are described and their toxicity after traditional pretreatments were studied in mice and rats. As 50% w/w mixture in normal food none of them were tolerated by mice. However, rats tolerated 25% of "pettu" and ash-treated C. islandica in 3-month tests Nuphar luteum plant rather well, although the body weight did ETHNOPHARMACOLOGY not increase as much as in controls. At the The root is astringent, demulcent and end of experiment in the lichen group, the anodyne. It has been used in dysentery, rats had proteinuria, and on autopsy some gonorrhoea and leucorrhoea. The leaves tubular changes were found probably due to and roots have been used as a poultice for high concentrations of lead in the lichen boils and inflamed skin, while an infusion and kidneys. All the rhizomes studied has been used as a gargle for oral and contain toxic compounds, but they, pharyngeal ulcers. It was an important particularly calla, would be nutritionally medicinal plant for Aboriginal peoples. valuable. Boiling poorly eliminated their Thompson peoples mixed dry powdered toxicity, but after baking at 180-200οC the leaves with grease to make an ointment for most toxic Nuphar and Calla were well infections, bites and swellings. Tsimshian tolerated as 25% mixture during a 6-week peoples boiled the heart of the rootstock test [6]. and ate it for bleeding lungs and as a contraceptive. Other groups used the root to 2232 IJBPAS, September, 2016, 5(9) Kaur M *and Mukhtar HM Review Article PHYTOCHEMICAL REPORTS hydroxythiobinupharidine sulphoxide, syn- The preliminary phytochemical screening 6,6'-dihydroxy thiobinupharidine of petroleum ether, chloroform and sulphoxide and anti-thiobinupharidine methanol extracts of rhizomes of Nuphar sulphoxide[10]. luteum showed the presence of different PHARMACOLOGICAL REPORTS chemical constituents. The phytochemical Anti-leishmanial activity screening of petroleum ether extract The extracts prepared from 522 plants showed the presence of anthraquinone and collected from various parts of the North cardiac glycosides whereas chloroform America by Jain S et al. were screened in extract along with anthraquinone and vitro against blood stage trypamastigote cardiac glycosides showed presence of forms of T. brucei. Active extracts were alkaloids, terpenoids and carbohydrates. further screened at concentrations ranging Maximum diversity of chemical from 10 to 0.4 μg/mL. Active extracts were constituents were present in methanol also investigated for toxicity in extract that includes alkaloids, Differentiated THP1 cells at 10 μg/mL anthraquinone glycosides, terpenoids, concentration. The results were computed saponins, flavonoids, tannins and phenolic for dose-response analysis and compounds, proteins, amino acids, determination of IC50/IC90 values. A carbohydrates, starch and vitamin C [7]. significant number (150) of extracts The dry rhizomes of Nuphar luteum have showed >90 % inhibition of growth of yeilded three sulphur containing alkaloids : trypomastigote blood forms of T. brucei in thiobinupharidine, neothiobinupharidine primary screening at 20 μg/mL and nuphaleine ( C30H42O4N2S)[8]. From concentration. The active extracts were the rhizomes of Nuphar luteum a new C15 further investigated for dose-response alkaloid, nuphacristine, has been isolated. inhibition of T. brucei growth. The The structure and stereochemistry of antitrypansomal activity of 125 plant nuphacristine have been established on the extracts was confirmed with basis of spectral analysis and chemical IC50 < 10 μg/mL. None of these active transformations [9]. Four new alkaloids extracts showed toxicity against were isolated from the rhizomes of Nuphar differentiated THP1 cells. Eight plants lutea. Their structures were established as extracts namely, Alnus rubra, Hoita syn-6-hydroxythiobinupharidine macrostachya, Sabal minor, Syzygium sulphoxide, syn-6'- aqueum, Hamamelis virginiana, Coccoloba 2233 IJBPAS, September, 2016, 5(9) Kaur M *and Mukhtar HM Review Article pubescens, Rhus integrifolia and Nuphar dependent cleavage of procaspase-9 and luteum were identified as highly potent paRp. Synergistic cytotoxicity of the active antitrypanosomal extracts with IC50 values mixture with cisplatin and etoposide was <1 μg/mL [11]. demonstrated. Overall, our results show Anti-cancer activity that NUP inhibits the NFκB pathway and Ozer J et al. screened thirty-four acts as a sensitizer to conventional methanolic plant extracts for inhibition of chemotherapy, enabling the search for its the constitutive nuclear factor κB (NFκB) specific target and application against activity by a NFκB-luciferase reporter gene cancer and inflammation [12]. assay. Strong inhibition of NFκB activity Yildirim AB et al., investigated was found in extracts of leaf and rhizome antibacterial and antitumor activities of 51 from Nuphar lutea L. synonym Nuphar different extracts prepared with 3 types of luteum. The inhibitory action was narrowed solvents (water, ethanol and methanol) of down to a mixture of thionupharidines 16 different plant species Ajuga reptans (A. and/or thionuphlutidines that were reptans) L., Phlomis pungens (P. pungens) identified in chromatography fractions by Willd., Marrubium astracanicum (M. one- and two-dimensional NMR analysis. astracanicum) Jacq., Nepeta nuda (N. Dimeric sesquiterpene thioalkaloids were nuda) L., Stachys annua (S. annua) L., identified as the major components of the Genista lydia (G. lydia) Boiss., Nuphar mixture. The Nuphar alkaloids mixture lutea (N. lutea) L., Nymphaea alba (N. (NUP) showed a dose dependent inhibition alba) L., Vinca minor (V. minor) L., of NFκB activity in a luciferase reporter Stellaria media (S. media) L., Capsella gene assay as well as reduction of nuclear bursa-pastoris (C. bursa-pastoris) L., NFκB subunits expression as tested by Galium spurium (G. spurium) L., Onosma western blots and immunohistochemistry. heterophyllum (O. heterophyllum) Griseb., Decreased DNA binding was demonstrated Reseda luteola (R. luteola) L., Viburnum in electro mobility shift assays. NUP lantana (V. lantana) L. and Mercurialis inhibited both inducible and constitutive annua (M. annua) L.) grown in Turkey was NFκB activation and affected the canonical conducted. Antibacterial activity was and alternative pathways. Suppression of evaluated with 10 bacteria including NFκB was not cell type specific. Induction Streptococcus pyogenes (S. pyogenes), of apoptosis by the alkaloid mixture was Staphylococcus aureus (S. aureus), demonstrated by time-dependent and dose- Staphylococcus epidermidis (S. 2234 IJBPAS, September, 2016, 5(9) Kaur M *and Mukhtar HM Review Article epidermidis), Escherichia coli (E. coli), the raw materials (18 plants) containing Pseudomonas aeruginosa