“Night Jasmine” (Nyctanthes Arbortristis Linn.)

Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035

International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 6 Number 6 (2017) pp. 1018-1035 Journal homepage: http://www.ijcmas.com

Original Research Article https://doi.org/10.20546/ijcmas.2017.606.118

Systemic Review on Anti-Sciatica Plant “Night Jasmine” (Nyctanthes arbortristis Linn.)

Ashwani Kumar*, Beenu Rathi, Vani Tyagi, Priyanka and Manisha

Department of Biotechnology and Microbiology, Shri Ram College Muzaffarnagar, UP-251001, India *Corresponding author

ABSTRACT

Ayurveda is one of the oldest systems of medicine that uses plants and their extracts for

treatment and managing of various diseased states. Nyctanthes arbortristis Linn (Oleaceae) K e yw or ds is an important large flowering shrub of tropical and subtropical regions of the world that

has been conventionally used to provoke menstruation, for treatment of scabies and other Nyctanthes skin infections, as hair tonic, chalogogue, laxative, diaphoretic, diuretic, in treatment of arbortristis (NAT), Phytochemistry, arthritis, malaria , bronchitis and as anthelmintic. Nyctanthes arbortristis is one of the most Pharmacology, useful conventional plants in India. The various parts of plant like fruits, leaves, seeds, Antioxidant, flowers, barks and stem have important phytochemicals and have some medicinal Silver Nanoparticle. importance for treatment and management of different disease states. Phytochemicals like flavanol glycoside, oleanic acid, essential oils, tannic acid, carotene, fried line, lupeol, Article Info glucose, benzoic acid present in various parts of plant which have significant

Accepted: hepatoprotective, antiviral, antifungal, antipyretic, antihistamine, anti-malarial, 17 May 2017 antibacterial, anti-inflammatory, antioxidant activities. The present review focus on Available Online: Chemical constituent, ecosystem And distribution, Biological behavior of important 10 June 2017 compounds, pharmacological action, Medicinal application. This review will be beneficial

for future research work and their Potential Development.

Introduction

Nyctanthes arbortristis Linn (Oleaceae) (Fig. name „arbortristis‟ meaning „the sad tree‟ is 1) is popularly known as „Night Jasmine‟ supposedly derived from dull looks of the tree (English) or „Harsingar‟ (Hindi) due to the during daytime (Suresh et al., 2010). detail that its flowers emit a very strong and pleasant fragrance during the whole night Nyctanthes arbortristis Linn is one of the (Siddiqui et al., 2006; Rout et al., 2007). The well-known medicinal plants. It is a common flowers start falling after midnight and by the wild hardy large shrub or small tree. It is day break, the plant appears dull. native of India, distributed wild in sub- Himalayan regions and southwards to The generic name „Nyctanthes‟ has been Godavari, Lalitpur Nepal. Nyctanthes coined from two Greek words „Nykhta‟ arbortristis Linn is commonly known as (Night) and „anther‟ (flower) (Vats et al., Night Jasmine or Parijata (Sandhar et al., 2009; Meshram et al., 2012). The specific 2011). Different parts of this plant are used in

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Indian systems of medicine for various be propagated by cutting as well as by seeds. pharmacological actions and are known to The seeds have been found to exhibit a poor possess various ailments by tribal people of germination rate because of phenolics India esp. Orissa and Bihar along with its use compounds leaching out of the imbibed seeds. in Ayurveda, Sidha and Unani systems of These inhibitory phenolics compounds were medicines. It is used in several ailments stored in per carp assisted by the seed coat. including sciatica, rheumatism, gout and other The speed of germination is improved by joint diseases (Sah and Verma, 2012). The either removing both the treating seeds with a flowers are used as stomachic, carminative, solution of antioxidants like astringent to bowel, ant bilious, expectorant, polyvinylpyrrolidine (PVP) or hair tonic and in the treatment of piles and polyvinylpolypyrrolidine (PVPP) prior to various skin diseases (Khatune et al., 2001) germination (Abhishek Kumar Sah and Vinod and in the treatment of ophthalmic purposes Kumar Verma, 2012). (Sasmal et al., 2007). Traditionally the powdered stem bark is given in rheumatic Leaves joint pain, in treatment of malaria and also used as an expectorant (Rouf, 2003). The Leaves are opposite, 5 -10 by 2.5 – 6.3 cm, leaves of Nyctanthes arbortristis Linn are ovate, acute or acuminate, entire or with a few used extensively in Ayurveda medicine for large distant teeth, short bulbous hairs the treatment of various diseases such as rounded or slightcuneate; main nerves few, sciatica, chronic fever, rheumatism, and conspicuous beneath; petiole 6cm long, hairy internal worm infections, and as a laxative, (Abhishek Kumar Sah and Vinod Kumar diaphoretic and diuretic (Tuntiwachwuttiku et Verma, 2012). Leaves are simple, etiolate and al., 2003). estipulate (Bhosale et al., 2009). The lamina is ovate with acute or acuminate apex, the Scientific classification margin entire or serrated, somewhat undulated, particularly near the base, the Kingdom: Plantae upper surface dark green with dotted glands, Order: Lamiales and the lower surface pale green and softly Family: Oleaceae pubescent. NAT venation is unicostate, Genus: Nyctanthes reticulate with an average of 12 lateral veins Species: N. arbortristis leaving the midrib. The petioles are about 5– 7.7–10 mm long with ad axial concavity Climate and soil (Biswas and Mukherjee, 2011) (Fig. 2).

Soil Flowers

Loamy, pH: 5.6–7.5. The plant requires Flowers of NAT are small, delightfully conditions varying from full sunlight to fragrant, sessile in pedanculate bracteates partial shade and require to be watered fascicles of 3 5; peduncles 4- angled, slender, regularly, but does not need overwatering. hairy, auxiliary and solitary and in terminal short dichotomous chimes; bracts broadly Cultivation and collection ovate or sub orbicular, 6- 10 mm long, aciculate, hairy on both sides; Calyx 6-8 mm It is often cultivated in gardens due to its most long, narrowly campanulate, hairy outside, agreeable and irregular aroma. The shrub can glabrous inside, truncate or obscurely toothed

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Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035 or lobed, ciliated. Corolla glabrous rather colour regions. Scaling off the bark by more than 13 mm long; tube 6-8 mm long, circular flakes. Inner bark is creamy white, orange colour, about equaling the limb; lobes soft and collapsed and non-collapsed phloem white, unequally obcordate, cineaste (Bhosale zone distinctly visible (Bhosale et al., 2009) et al., 2009) (Fig. 3). (Fig. 5).

Fruits Traditional uses

Fruits of NAT are a capsule of 1-2 cm CNS depressant activity showed in Seeds, diameter, long and broad, obcordate orbicular, leaves and flowers extract of plant compressed, 2-celled, separating into 2 flat 1- (advance).The Nyctanthes arbortristis showed seeded carpals, reticularly veined, glabrous activity against Encephalomyocarditis virus (Bhosale et al., 2009). (EMCV) and Semliki forest virus (SFV).

Macroscopic character of fruit: The fruit is Phytochemical and pharmacogical and flat, brown and heart cordite-shaped to tissue culture study of Nyctanthes rounded-capsule, around 2 cm in diameter arbortristis with two celled opening transversely from the apex, each containing a single seed. The leaves of Nyctanthes arbortristis L Microscopically fruit showed typical (Oleaceae) are used in Ayurveda medicine for character of fruit. In the epicarp epidermal the management of a range of diseases, but cells were compactly arranged, polygonal reports on its phytochemicals and cells with slightly anticlinical walls covered pharmacological properties are inadequate. by a thin cuticle followed by l,3 layers of Herein, we report purification of an collenchymas, Spongyparenchymatous tissue, antioxidative polysaccharide (F2) extracted sclerenchymatous sclerenchymatous fibers from its leaves by water. The presence of a and oil gland (Shinde et al., 2014) (Fig. 4). highly branched polysaccharide (75 kDa) containing esterified phenolics acids was Seed revealed by chemical, chromatographic and spectroscopic analyses. Particularly, ESMS The seed is compressed and is 1 per cell analysis of per acetylated oligomeric (Abhishek Kumar Sah and Vinod Kumar fragments derived by Smith degradation Verma, 2012) Seeds are exalbuminous, test provides important structural information on a thick; the outer layer of large transparent cells spectrum of glycerol tagged oligosaccharides. and heavily vascularised (Bhosale et al., This polysaccharide showed dose dependent 2009) phytosterols, phenolics compounds, free radical scavenging capacity as evidenced tannins, flavonoids, cardiac glycosides, by DPPH and Ferric reducing power assay. saponins and alkaloids all are found in seeds This pharmacologically active compound (F2) of N. arbortristis (Shibani Basu et al., 2016). formed a water soluble complex with bovine serum albumin over pH 4.0–7.4. Accordingly, Bark traditional aqueous extraction method provides a molecular entity that induces a Bark of N.arbortristis plant is dark gray or pharmacological effect: this could epitomize a brown in colour and rough and firm. Bark smart approach in phototherapeutic surface is dip pled due to scaling off of management (Ghosh et al., 2015). The circular barks and patchy due to gray brown cytotoxic compound Altersolanol A, an

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Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035 anthraquinone derivative was isolated from the dominant constituent. The cumulative PM0409092 a fungus of Nyctanthes percentage of these four odd-numbered arbortristis (family Oleaceae). It was alkanes also showed phenological variation identified as a Phomopsis sp. by DNA being highest during the fruit ripening stage amplification and sequencing of the ITS (average value 63.29%) followed by the region. The chemical structure of Altersolanol flowering stage (mean value 60.74%). The A was elucidated from its physicochemical values remained moderate on an average of properties, 2D NMR spectroscopy and other 54.31% for the rest of the year. This study spectroscopic data. The compound has in also confirms the xerophytic feature of the vitro cytotoxic activity against 34 human plant having higher proportion of longer cancer cell lines with mean IC50 (IC70) carbon chain n-alkanes greater than C31 values of 0.005 μg ml-1 (0.024 μg ml-1) (dominant peaks are of C33 and C35) (Biswas respectively. Altersolanol A, a kinase et al., 2014). An efficient tissue culture inhibitor, induces cell death by apoptosis technology has been designed for mass through the cleavage by Caspase-3 and -9 and multiplication of Nyctanthes arbortristis L. by by decreased anti-apoptotic protein preculturing nodal explants in thidiazuron expression. There are several previous reports (TDZ)-supplemented liquid Murashige and of the anticancer activity of Altersolanol A, Skoog (MS) media. Direct inoculation of but we report here an extensive study using nodal segments on semi-solid MS medium 36 cell lines which gives wider spectrum of augmented with various concentrations of results. This study confirms the cytotoxic TDZ (0.1 to 0.9 μM) produced shoots but potential of Altersolanol A isolated from the with low regeneration response and few endophyte Phomopsis sp (PM0409092) of the shoots per explant. Hence, nodal explants plant Nyctanthes arbortristis. The compound were pretreated with greater concentrations of exhibits in vitro cytotoxicity against 34 TDZ (5 to 100 μM) in liquid MS media for human cancer cell lines with mean IC50 different durations (4, 8, 12, and 16 days) (IC70) value of 0.005 μg ml-1 (0.024 μg ml-1). with the aim of improving shoot regeneration This is an in-depth report of Altersolanol A response from cultured explants. After against a panel of 34 human cancer cell lines pretreatment, explants were transferred to and extends observations from previous agar-solidified hormone-free MS medium. studies indicating that Altersolanol A can be Best response in terms of percent regeneration used for the development of (94%), number of shoots per explant (20.00 ± chemotherapeutics. Altersolanol A, a kinase 1.15), and greatest shoot length (7.23 ± 0.83 inhibitor, induces cell death by apoptosis cm) were obtained with nodal segments through the cleavage of Caspase-3 and -9 and pretreated in 75 μM TDZ for 8 days. by decreased anti-apoptotic protein Similarly, root induction was obtained from expression (Mishra et al., 2015). pulse-treated micro shoots for 24 h with 200 μM indole-3-butyric acid (IBA) followed by The present communication is a first-time their transfer to 1/2 MS medium which report on the analyses of n-alkane profile of produced an average of 5.50 ± 0.92 roots per epicuticular wax extracted from the mature micro shoot. The rooted plantlets were leaves of Nyctanthes arbortristis L. during a transplanted to soil with 80% success rate calendar year. The composition of n-alkanes (Jahan et al., 2011). revealed hentriacontane (n-C31), tritriacontane (n-C33), tetratriacontane (n- Rapid differentiation of multiple shoots was C35) and nonacosane (n-C29) as the major observed in 94% of nodal explants of one constituents with tritriacontane (n-C33) being year old Nyctanthes arbortristis L. plants. 1021

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Shoot bud induction and multiplication took general depression of spontaneous motor place on Murashige and Skoog (MS) medium activity, significantly increased supplemented with two cytokines, i.e. Benzyl pentobarbitone sleeping time though it had no adenine (BA) or Kinetin (KN) either alone or effect on righting reflex. Furthermore higher in combination with different auxins, indole- doses of the extract abolished CAR without 3-butyric acid (IBA), indole-3-acetic acid affecting motor coordination. Moreover the (IAA) or α-naphthalene acetic acid (NAA). extract exhibited hypothermic effect and Between different media, pH levels and protected guinea pigs from histamine aerosol. growth regulators tried, the optimum These activities are common to major condition for maximum regenerative response tranquilizers and support the usage of the was obtained on MS + Kn (2.5 μM) + N AA plant by Ayurveda physicians in (0.5 μM) media at 5.8 pH, forming cultures aforementioned conditions. In addition with 23.26 ± 0.89 number of shoots and 6.36 significant purgative activity was also ± 0.80 cm shoot length after 8 weeks of exhibited by the extract (Saxena et al., 2002). culture. Histological sections confirmed the On the occurrence of sclerosed palisade cells formation of multiple buds from nodal in the leaf of Nyctanthes arbortristis L explants. Rooting was achieved ex vitro by (Ananda Rao, 1947). dipping the basal ends of micro shoots in 200 μM IBA for 30 min followed by their Anti-microbial and inflammatory aspects transplantation in sterile soil rite. The of Nyctanthes arbortristis plantlets with well-developed shoot and root system were successfully established in To investigate the immunomodulatory garden soil and grown outside in a greenhouse activity of aqueous extract of Nyctanthes with a 80% survival rate (Jahan et al., 2011). arbortristis flowers (NAFE) with particular A carotenoid aglycone Ag-NY1 was isolated reference to splenocytes proliferation and from the orange coloured tubular calyx of induction of cytokines. Antibody titer was flowers of Nyctanthes arbortristis. The determined by tube agglutination and indirect elucidation of the structure through a detailed ELISA assay in four groups of mice-control, spectroscopic study revealed that the antigen alone, and NAFE-treated (400 and carotenoid molecule is Crocetin, which is the 800 mg/kg for 21 days) after immunization major aglycone present in the stigma of with Salmonella antigen while cellular Crocus sativus. The compound exhibited a immunity was studied in three groups of rats good membrane stabilizing activity as (control and NAFE-treated - 400 and 800 compared to the corresponding glycoside mg/kg) following DNCB application. crocin (Gadgoli and Shelke, 2010). The Splenocytes from untreated and NAFE- decoction of the leaves of Nyctanthes treated rats were stimulated using arbortristis Linn (Harsingar) is widely used in concanavalin-A (Con-A) and optical density Ayurveda system of medicine for the (OD) and stimulation index were determined. treatment of sciatica, arthritis, fevers, and Splenocytes from control rats were also various painful conditions and as laxative. In treated in vitro with NAFE (50-1600 μg/ml) the present investigation, the water soluble and Con-A to determine the effect on portion of the alcoholic extract of the leaves splenocytes proliferation. Interleukin-2 (IL-2) was screened for some CNS activities (viz. and IL-6 levels in splenocytes supernatant hypnotic, tranquilizing, local anesthetic, from control and NAFE-treated rats and hypothermic, anticonvulsant), antihistaminic following in vitro treatment of splenocytes and purgative activities. The extract produced with NAFE (50-1600 μg/ml) were determined

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Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035 using ELISA kits. Marked to a significant Active constituents mediated disruption of increase in antibody titer by both the methods plasma membrane was studied through in NAFE-treated mice and a significant flowcytometry by permeabilization of increase in skin thickness in rats after fluorescent dye Propidium Iodide (PI). challenge with DNCB, respectively suggested Antioxidant activity of the extract was humoral and cell-mediated immunostimulant determined using the DPPH stable radical. potential of NAFE. Significant increase in OD Molecular validation of fungal DNA from the and stimulation index following e x vivo and extract was observed using PCR in vitro exposure of splenocytes and amplification. In silicon analysis of its active sensitization with Con-A and significant constituents over Mala s1 was performed elevation in IL-2 and IL-6 levels in using HEX software and visualized through splenocytes supernantant was also observed Pymol. The anti-Malassezia potential of NAT after their ex vivo and in vitro exposure to leaf extracts reflected moderate MIC 1.05 NAFE. Humoral and cell-mediated μg/μl against M. globes, while least effective immunostimulant activity of NAFE seems to against M. restrict with MIC 1.47 μg/μl. A be mediated through splenocytes proliferation linear correlation coefficient R (2) = 0.866 and increased production of cytokines, was obtained in case of M. globes while especially IL-2 and IL-6 (Bharshiv, 2016). minimum was observed in M. restrict with R (2) = 0.732. The flow cytometric data reveal ~ Exploration of anti-Malassezia potential of 75 % cell death when treated with active Nyctanthes arbortristis L. and their constituent‟s β-Sit sterol and Calceolarioside application to combat the infection caused by A. The docking confirmations and the Mala s1 a novel allergen. Malassezia interaction energies between Mala s1 and the commensal yeasts along with multitude of active constituents (β-Sit sterol and antigens have been found to be associated Calceolarioside A) from extracts showed an with various skin disorders including effective binding which suggests Mala s1 as Pityriasis vesicular (PV). Amongst them Mala efficient allergen for site specific tagging this s1, a 37 kDa protein has been proved to be a study revealed that Nyctanthes arbortristis L major allergen reacting with a large panel of (NAT) extracts possess high anti-Malassezia sera. However, there exists no therapeutic potential which is driven mainly by disruption alternative to combat such problems in form of plasma membrane. Also in silicon of plant based natural compounds. The validation and molecular modeling studies purpose of this study is in the first place, to establishes Mala s1 as a novel allergen that determine the anti-Malassezia activity of could be a potential target in disease Nyctanthes arbortristis L (NAT) ethanolic treatment. Our results would also provide a leaf extract through turbid metric growth foundation for the development of new curves, disruption of plasma membrane and therapeutic approach using NAT extract as secondly, it aims to present in silicon lead compound with high antioxidant property validation of its active constituents over Mala as an added trait for skin care (Mishra et al., s1a novel allergen The antifungal 2016). susceptibility 50 % ethanolic extract of NAT was determined by broth micro dilution In order to search for new products that method according to CLSI guidelines. Further display antimalarial and immunomodulatory MICs and IC50 were determined mechanisms that complement direct spectrophotometrically using the software antiparasitic activity, a set of in vitro and in SoftMax® Pro-5 (Molecular Devices, USA). vivo experiments were designed to evaluate

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Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035 the effect of Nyctanthes arbortristis in of 250 mg/kg and 500 mg/kg of body weight. Plasmodium Bergheim infected mice. Three Both standard drugs and extract were extracts of N. arbortristis leaves from varying administered orally to the animals. Control concentrations of alcohol and water were received distilled water orally. Results considered for their potential to suppress showed that Nyctanthes arbortristis Linn. expression of pro-inflammatory mediators Had potent analgesic and anti-inflammatory from macrophages primed with lip activities (Kakoti et al., 2013). polysaccharide. The ethanolic extract, which lowered the pro-inflammatory mediators Nyctanthes arbortristis Linn (Oleaceae) is a [tumor necrosis factor (TNF), 13.52-55.83 %; well-known traditional medicinal plant used interleukin-6 (IL-6), 0-17.29 %; and NO, throughout the India as an herbal remedy for 39.37-81.63 %], was selected to be examined treating various infectious and non-infectious in malaria (P. Bergheim) infected mice. diseases. To evaluate the antioxidative Corroborating the in vitro results, it was activity of hydro-alcoholic extract of flower observed that the extract could normalize the in the lymphocytes exposed to oxidative TNF (78 %) and IL-6 (70.35 %) optimally at stress induced by H2O2. Isolated lymphocytes 1 g/kg, thus retarding the pathological process were treated in vitro with extract or in infected mice and increasing the mean extract+H2O2, and the level of reduced survival time from 10.6 to 15.6 days. There glutathione (GSH) as well as the activity of were no signs of toxicity in the acute oral glutathione-S-transferase (GST) and lactate toxicity test up to 2 g/kg (1)H NMR of the dehydrogenase (LDH) were measured. biologically active extract was obtained to Treatment of lymphocyte with flower extract ensure the presence of the compound of (50, 100, and 200 μg/ ml) significantly interest, i.e., iridoid glycoside. The quality increased the level of GSH and decreased the and the reproducibility of results were activity of GST. The LDH activity measured ensured by means of achieving characteristic in the cell-free medium decreased high-performance liquid chromatography significantly. Pre-treatment of lymphocyte fingerprint of the extract (Agrawal et al., with flower extract protects the lymphocyte 2013). from the H2O2 induced oxidative stress by significantly increasing the levels of GSH as Stem bark of Nyctanthes arbortristis Linn. compared to the cells treated only with H2O2. was extracted in methanol to evaluate their Pre-treatment also reduced the activity of analgesic and anti-inflammatory activities. LDH significantly as compared to the cells The analgesic activity was determined on treated only with H2O2. The LDH activity in Wister albino rats by hot plate method, tail cell-free medium is associated with flick assay, and tail immersion method using membrane damage, the decreased levels of Morphine sulphate as standard drug at a dose LDH activity reflects the reduced level of of 5 mg/kg of body weight and the results membrane damage due to H2O2. The present were expressed as mean increase in latency findings suggest the protective role of the after drug administration ± SEM. The anti- hydro-alcoholic extracts of the flower of inflammatory activity was assessed by Nyctanthes arbortristis against membrane Carrageenan-induced rat paw edema using damage induced by H2O2. The results also diclofenac sodium as standard drug at a dose suggest that the extract might be rich in of 100 mg/kg of body weight and expressed phytochemicals with antioxidant/radical in terms of mean increase in paw volume ± scavenging potentials, which might find SEM. Stem bark extract was given at a dose application in antioxidant therapy (Hussain

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Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035 and Ramtek, 2012). roots, flowers, and seeds, the seed extract was Larvicidal activity of crude chloroform, effective against the larvae of all the three dichloromethane and methanol extracts of the species with LC(50) values 65.2, 154.5, and leaves and roots of six Indian plants, Eagle 54.4 ppm, respectively, for A. stephensi, A. marvelous L., Balanites aegyptica L., aegypti, and C. quinquefasciatus. Among the Caltrops gigantic L., Murraya koenigii L., three plant species studied for mosquito Nyctanthes arbortristis L. and Plumbago larvicidal activity, C. ternatea was showing zeylanica L., were tested against the early the most promising mosquito larvicidal fourth instar larvae of Aedes aegypti L. and activity. The phytochemical analysis of the Anopheles stephensi. The larval mortality was promising methanolic extract of the seed observed after 24 h of exposure. All extracts extract was positive for carbohydrates, showed moderate larvicidal effects. However, saponins, terpenoids, tannins, and proteins. In the highest larval mortality was found in conclusion, bioassay-guided fractionation of methanol extracts of P. zeylanica roots and B. effective extracts may result in identification aegyptica roots against Ae. aegypti (LC50 of a useful molecule for the control of 169.61 mg/lit, 289.59 mg/lit) and An. mosquito vectors (Mathew et al., 2009). stephensi (LC50 222.34 mg/lit, 102.29 mg/lit), respectively. The methanol extracts of The flowers of Nyctanthes arbortristis plants were more effective than the other showed interesting antibacterial activity extracts. This is an ideal eco-friendly against some gram-positive and gram- approach aid for the control of mosquito negative microorganisms (chloroform and species Ae. Aegypti and An. stephensi (Patil et ethyl acetate extracts) and significant al., 2010). cytotoxic activity (petroleum ether, chloroform and ethyl acetate extracts) Screening of natural products for mosquito (Khatune et al., 2001). Nyctanthes arbortristis larvicidal activity against three major L (Oleaceae), a plant widely used in the mosquito vectors Aedes aegypti, Culex traditional medicinal systems of India, has quinquefasciatus and Anopheles stephensi recently been reported to possess resulted in the identification of three potential hepatoprotective, antileishmanial, antiviral plant extracts viz., Saraca indica/Asoka, and antifungal activities. In the present study Nyctanthes arbortristis and Clitoria ternatea strong stimulation of antigen specific and for mosquito larval control. In the case of S. non-specific immunity, as evidenced by indica/Asoka, the petroleum ether extract of increases in humoral and delayed type the leaves and the chloroform extract of the hypersensitivity (DTH) response to sheep red bark were effective against the larvae of C. blood cells (SRBC) and in the macrophage quinquefasciatus with respective LC(50) migration index (MMI), has been values 228.9 and 291.5 ppm. The LC (50) demonstrated in mice fed with 50% ethanolic values of chloroform extract of N. arbortristis extract of seeds, flowers and leaves of this leaves were 303.2, 518.2, and 420.2 ppm plant. against A. aegypti, A. stephensi, and C. quinquefasciatus, respectively. The methanol Maximum activity was found in the seeds in and chloroform extracts of flowers of N. which the active principle(s) appear to be arbortristis showed larvicidal activity against mainly associated with lipids. In flowers and larvae of A. stephensi with the respective LC leaves, however, the major activity was found (50) values of 244.4 and 747.7 ppm. Among in the aqueous fraction of the 50% ethanol the methanol extracts of C. ternatea leaves, extract. The immunostimulant substance(s)

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Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035 found in N. arbortristis L. are likely to play a The extract exhibited significant aspirin-like role in its antiamoebic, antileishmanial, antinociceptive activity but failed to produce antiviral and certain other activities (Puri et morphine-like analgesia. It was also found to al., 1994). possess antipyretic activity against brewer's yeast-induced pyrexia in rats. The extract also The leaves of Nyctanthes arbortristis, besides produced gastric ulcers following oral being used in the treatment of sciatica and administration for six consecutive days in arthritis, are advocated for various kinds of rats. Results of the present study tend to fevers and painful conditions by the Ayurveda substantiate the use of this plant in fevers and physicians. In the present study, the water- painful conditions by Ayurveda physicians soluble portion of an ethanol extract of the (Saxena et al., 1987). leaves was screened for analgesic, antipyretic and ulcerogenic activities.

Fig.1 Whole plant of Nyctanthes arbortristis

Fig.2 NAT leaves showing morphology

Fig.3 Flowers of Nyctanthes arbortristis

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Fig.4 Morphology of Nyctanthes arbortristis fruit

Fig.5 Plant having young bark of Nyctanthes arbortristis

Fig.6 Flow chart of properties of Nyctanthes arbortristis

Tissue Culture Study

Antitussives Phytochemical and and Antioxidant Properties Pharmacologic of al Analysis Nyctanthes arbortristis (Harsingar)

Anti microbial Ethno and medicinal and Inflammatory Botanical Clinical and

Study Bioactivity

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Nyctanthes arbortristis Linn (Harsingar) is observational study was conducted at M.A. widely used as a decoction in the Ayurveda Podar Hospital - Ayurveda (MAPH-A) after system of medicine for treatment of sciatica ethics committee approval. Administration of and arthritis, but it has not yet been screened a paste of 5 fresh leaves, thrice a day for a scientifically. In the present study, the water week was a standard practice for management soluble portion of the alcoholic extract of the of malaria at MAPH-A. Clinical activity of N. leaves of Nyctanthes arbortristis (NAT) was arbortristis was evaluated by monitoring screened for the presence of anti- pyrexia, parasitemia and morbidity score inflammatory activity. NAT inhibited the (MS) in twenty patients. In addition, immune acute inflammatory edema produced by and biochemical markers and organ functions different phlogistic agents, viz. carrageenin, were monitored for objective markers of formalin, histamine, 5-hydroxytryptamine and response. Student's paired-'t' test was applied hyaluronidase in the hindpaw of rats. The to assess statistical significance. Ten out of 20 acute inflammatory swelling in the knee joint patients showed both fever and parasite of rats induced by turpentine oil was also clearance, which was confirmed by significantly reduced. In subacute models, polymerase chain reaction. Remaining ten NAT was found to check granulation tissue patients had persistent but decreasing formation significantly in the granuloma parasitemia. Four of them needed chloroquine pouch and cotton pellet test. Acute and as a fail-safe procedure. Irrespective of the chronic phases of formaldehyde induced degree of parasitemia all the patients showed Arthritis was significantly inhibited. NAT decrease in MS. There was also an increase in was also found to inhibit the inflammation platelet count and normalization of plasma produced by immunological methods, viz. lactic acid. There was a good clinical Freund's adjuvant arthritis and PPD induced tolerability and an improvement in organ tuberculin reaction. Thus anti-inflammatory function. The inflammatory cytokines showed activity in leaves of Harsingar supports its use a reduction; particularly in TNF-α within a in various inflammatory conditions by the day. At the given dosage, N. arbortristis followers of the Ayurveda system of medicine showed disease-modifying activity; early (Saxena et al., 1984). clinical recovery with a decline of TNF-α and a gradual parasite clearance. Further studies Clinical and bioactive aspects of Nyctanthes with a standardized formulation for dose- arbortristis searching and optimizing the treatment schedule are needed in a larger sample size. An unceasing threat of drug resistance The process of trial registration had not begun continuously poses demand for new when the study was conducted in 2000 antimalarial drugs. A scientific assessment of (Godse et al., 2016). Safety evaluation of a traditionally used antimalarial plants through polyherbal formulation containing reverse pharmacology is crucial for a fast hydroalcoholic extracts of Hippophae track drug discovery. An Ayurveda plant salicifolia, Nyctanthes arbortristis, Ocimum Nyctanthes arbortristis Linn. - (Parijat) is tenuiflorum, and Reinwardtia indica in being used in clinical practice and had shown rodents (Kumari et al., 2016). antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical Boiled aqueous extract of flowers (AEF) from study. To further explore antimalarial Nyctanthes arbortristis L. are used in Sri potential of the plant through additional Lankan traditional Ayurvedic Medicine to objective markers. An open-labelled manage diabetes mellitus. AEF has widely

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Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035 been used as a folk medicine for the treatment fractions were studied for antiplasmodial of various ailments due to its therapeutic potency against 3D7 (CQ sensitive) and Dd2 activity. However, little is known concerning (CQ resistant) strains of P. falciparum and therapeutic activity of the extract as well as its subsequently subjected to bioassay guided underline mechanisms and safety. Diabetes is fractionation using reverse phase known to increase low-density cholesterol and chromatography to pursue the isolation of decrease high-density cholesterol thus active fractions. Harshringar crude leaves triggering coronary diseases. Hence, the extract and some of its RPHPLC purified primary objective of the present study is to fractions exhibited promising antiplasmodial investigate the hypoglycemic and potency against 3D7 and Dd2 strains of hypolipidemic activities of the AEF. AEF was P. falciparum. The present study has provided prepared and male mice (n = 9 group) were scientific validity to the traditional use of gavages either with 250, 500 and 750 mg/kg leaves extract of Harshringar against malaria of AEF or distilled water (DW). leading to the conclusion that this plant holds Subsequently, fasting and random blood promise with respect to antimalarial glucose concentrations were determined. To phytotherapy. This is the first scientific report investigate mechanisms of actions of AEF, of antiplasmodial activity of RPHPLC animals were orally administered with 500 fractions of Harshringar leaves extract against mg/kg or the vehicle (DW) and glucose P. falciparum strains (Kumari et al., 2012). tolerance was performed before and after glucose challenge. For further studies, in vitro The effect of the water soluble fraction of the alpha-amylase assay and glucose absorption ethanol extract of Nyctanthes arbortristis from the gastrointestinal tract were performed (NAT) on tumor necrosis factor-alpha (TNF- using 500 mg/kg of the extract. Additionally, alpha) level in plasma of arthritic and soluble glycogen content in the liver and skeletal protein A (SpA)-treated Balb/c mice has been muscles, a complete lipid profile assay, and studied. Oral administration of this fraction in toxicological and biochemical parameters arthritic mice showed a consistent depletion were conducted after a chronic study. of TNF-alpha from the host plasma. A similar Treatment with AEF did not induce any overt depletion of TNF-alpha in the plasma of SpA- signs of toxicity or hepatotoxicity. Results the treated mice has been observed. The extract present study indicated that AEF possess also reduces plasma interferon-gamma level hypoglycemic and hypolipdemic properties. but the plasma IgM and IgG levels are not Therefore, AEF could be used as an affected. The implications of these alternative medicine in management of observations are discussed in the light of diabetes mellitus (Rangika et al., 2015). management of TNF-alpha in clinical disorders (Paul and Saxena, 1997). Nyctanthes arbortristis (Harshringar, Night Jasmine) has been traditionally used in Ethno medicinal and botanical study of Ayurveda, Unani and other systems of Nyctanthes arbortristis medicine in India. The juice of its leaves has been used by various tribal populations of The global burden of bacterial infections is India in treatment of fevers resembling very high and has been exacerbated by malaria. This work reports the antiplasmodial increasing resistance to multiple antibiotics. activity guided fractionation of Harshringar Antibiotic resistance leads to failed treatment leaves extract. Crude ethanolic Harshringar of infections, which can ultimately lead to leaves extract and its RPHPLC purified death. To overcome antibiotic resistance, it is

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Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035 necessary to identify new antibacterial agents. that could yield the highest probability of In this study, a total of 662 plant extracts finding promising compounds responsible for (diverse parts) from 222 plant species (82 the antibacterial activities against a broad families, 177 genera) were screened for spectrum of bacterial species. Further antibacterial activity using the agar cup plate investigation of the phytochemicals from method. The aqueous and methanolic extracts these plants will help to identify the lead were prepared from diverse plant parts and compounds for drug discovery (Panda et al., screened against eight bacterial (two Gram- 2016). positive and six Gram-negative) species, most of which are involved in common infections To investigate the plants traditionally used for with multiple antibiotic resistance. The prevention of malaria in Cuttack, Gajapati and methanolic extracts of several plants were Koraput districts of Odisha state, eastern shown to have zones of inhibition ≥ 12 mm India. An ethnobotanical survey was carried against both Gram-positive and Gram- out among 20 traditional healers who were negative bacteria. The minimum inhibitory sampled based on recommendations of local concentration was calculated only elders and local non-government organizations. Data were collected through With methanolic extracts of selected plants, semi-structured interview. The study revealed those showed zone of inhibition ≥ 12 mm the use of 16 traditional plant species against both Gram-positive and Gram- belonging to 12 families for prevention of negative bacteria. Several extracts had malaria. Andrographis paniculata, minimum inhibitory concentration ≤ 1 Azadirachta indica, Nyctanthes arbortristis, mg/mL. Specifically Adhatoda vasica, Ocimum sanctum, Piper nigrum, Zingiber Ageratum conyzoides, Alangium salvifolium, officinale were the most commonly reported Alpena galangal, Andrographis paniculata, plants for their malaria prophylactic use by Anogeissus latifolia, Annona squamosa, A. the healers of three districts of Odisha. Most reticulate, Azadirachta indica, Buchanania of the remedies were used in decoction form. lanzan, Cassia fistula, Celastrus paniculatus, Findings of this study provide a lead to Centella asiatica, Clausena excavate, Cleome explore traditional plants for malaria viscosa, Cleistanthus collinus, Clerodendrum preventive potential through further pre- indicum, Croton roxburghii, Diospyros clinical and clinical studies (Nagendrappa et melanoxylon, Eleutherine bulbosa, Erycibe al., 2013). paniculata, Eryngium foetidum, Garcinia cowa, Helicteres isora, Hemidesmus indicus, Nyctanthes arbortristis (Oleaceae) is a Holarrhena antidysenterica, Lannea mythological plant; has high medicinal values coromandelica, Millettia extensa, Mimusops in Ayurveda. The popular medicinal use of elengi, Nyctanthes arbortristis, Oroxylum this plant are anti-helminthic and anti-pyretic indicum, Paederia foetida, Pterospermum besides its use as a laxative, in rheumatism, acerifolium, Punica granatum, Semecarpus skin ailments and as a sedative. Vitally, the anacardium, Spondias pinnata, Terminalia natives plant it in their home gardens to pass alata and Vitex negundo were shown to have on its medicinal usage to oncoming significant antimicrobial activity. The species generations. The present review encompasses listed here were shown to have anti-infective an ethnopharmacological evaluation focusing activity against both Gram-positive and on information on the chemical constituents, Gram-negative bacteria. These results may pharmacological actions and toxicology in serve as a guide for selecting plant species order to reveal the therapeutic potential and

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Int.J.Curr.Microbiol.App.Sci (2017) 6(6): 1018-1035 gaps requiring research involvement. The class of drugs has been introduced into the present review is based on searches in market for many years. Water decoction of Scifinder (®), Pubmed (National Library of the leaves of Nyctanthes arbortristis L. is Medicine) and books published on the subject used in Indian Ayurvedic system to alleviate a during the period 1933 to 2012. Nyctanthes wide range of diseases including cough. arbortristis is most important in local and Herein, we have isolated a carbohydrate traditional medicines especially in India for polymer (CP) containing fraction from its treating intermittent fevers, arthritis and leaves by aqueous extraction method. CP is a obstinate sciatica. Crude extracts and isolated branched polysaccharide containing, amongst compounds from the plant were shown to be others, 1,3-/1,3,6-linked galactopyranosyl, pharmacologically active against 1,5-/1,3,5-linked arabinofuranosyl and 1,2- inflammation, malaria, viral infection, /1,2,4-linked rhamnopyranosyl residues. Oral leishmaniasis and as an immunostimulant. administration of CP fraction in doses of 25 The major classes of biologically active and 50 mg kg-1 body weight significantly compounds are the iridoid glucosides inhibited the number of citric acid-induced including Arbortristoside A, B and C from the cough efforts in guinea pigs in a dose seeds active as anticancer, anti-leishmania, dependent manner. Remarkably, CP did not anti-inflammatory, anti-allergic, altered specific airway resistance of animals immunomodulatory and antiviral. Other significantly. Consequently, aqueous molecules; calceolarioside A, 4- extraction method provided a molecular hydroxyhexahydrobenzofuran-7one and β- entity, which exhibited the cough suppressive sitosterol from leaves have been reported to activity: this could symbolize an attractive be active as anti-leishmanial, anticancer and approach in phytotherapeutic treatment (Ghos anti-inflammatory, respectively. The crude et al., 2015). extracts have been found to be safe with an LD50 of 16gm/kg, while the LD50 of To investigate the in vitro antioxidant activity arbortristoside-An isolated from the seeds was and total phenolic content of the methanolic found to be 0.5g/kg. Mostly in-vitro or in leaf extract of Nyctanthes arbortristis L (NA). some cases in-vivo models provide some The sample was tested using five in vitro evidence especially in the treatment of antioxidant methods (1, 1-diphenyl-2-picryl inflammatory conditions like arthritis, fevers hydrazine radical scavenging activity related to malaria and protozoan diseases (DPPH), hydroxyl radical-scavenging activity especially leishmaniasis. The only clinical (-OH), nitric oxide scavenging activity (NO), study found, is for treating malaria, but with superoxide radical-scavenging activity, and crude extract only. Further, more detailed total antioxidant activity) to evaluate the in safety data pertaining to the acute and sub- vitro antioxidant potential of NA and the total acute toxicity, cardio and immunotoxicity phenolic content (Folin-Ciocalteu method). also needs to be generated for crude extracts The extract showed good free radical or pure compounds (Agrawal and Pal, 2013). scavenging property which was calculated as an IC50 value. IC50 (Half maximal inhibitory Anti tussives and antioxidant aspects of concentration) of the methanolic extract was Nyctanthes arbortristis found to be 57.93 μg•mL (-1) for DPPH, 98.61 μg•mL(-1) for -OH, 91.74 μg•mL(-1) The prevalence of cough is reflected in for NO, and 196.07 μg•mL(-1) for superoxide antitussives being one of the most widely radical scavenging activity. Total antioxidant used therapies in the world; however no new capacity of the extract was found to be (1198

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± 24.05) mg ascorbic acid for the methanolic Tyagi executive director, Sri Ram Colleges, extract. Free radical scavenging activity Muzaffarnagar, Uttar Pradesh, India for observed in the extracts of NA showed a providing necessary facilities and tools to concentration-dependent reaction. The in vitro carry out the research dissertation work for scavenging tested for free radicals was post graduate for M.Sc. biotechnology reported to be due to high phenolic content in students. the leaf extract. The leaf extract of NA showed the highest total phenolic content References with a value of 78.48 ± 4.2 equivalent mg TAE/g (tannic acid equivalent). N. Abhishek Kumar Sah and Vinod Kumar arbortristis leaf extract exhibited potent free Verma. 2012. Phytochemical and radical scavenging activity. The finding Pharmacological Potential of Nyc suggests that N. arbortristis leaves could be a tanthes arbortritis: A Comprehensive potential source of natural antioxidant Review, Int. J. Res. Pharmaceutical (Michael et al., 2013). Biomed. Sci., Vol. 3 (1) Agrawal, J., Pal, A. 2013. Nyctanthes Nyctanthes arbortristis (Harsingar) generally arbortristis Linn--a critical used in traditional system of medicine for ethnopharmacological review. J. various ailments are supported by various Ethnopharmacol., 146(3): 645-58. studies involving its pharmacological and Agrawal, J., Shanker, K., Chanda, D., Pal, A. clinical evaluations. The above article 2013. Nyctanthes arbortristis positively accepted and discovered phytochemicals affects immunopathology of malaria- study, antimicrobial, antioxidant, tissue infected mice prolonging its survival. culture, inflammatory, ethno medicine, Parasitol. Res., 112(7): 2601-9. botanical, clinical, bioactivity and Ananda Rao, T. 1947. On the occurrence of pharmacological activities of plants. sclerosed palisade cells in the leaf of Nyctanthes arbortristis is single source of Nyctanthes arbortristis L. Curr. Sci., metabolites such as alkaloids, phytosterols, 16(4):122. phenolics, tannins, flavonoids, glycosides and Bhosale, A.V., M.M. Abhyankar, S.J. Pawar, saponins which is obtained from basic Khan Shoeb, Naresh patil. 2009. extracts of various parts of plant and show Nyctanthes arbortristis: A valuable treatment for various diseases. This Pharmacognos tic Review, Res. J. review conclude that time has come to make Pharmacognosy Phytochem., 2: 91-97. good use of centuries old awareness of Bharshiv, C.K., Garg, S.K., Bhatia, A.K. Nyctanthes arbortristis through modern 2016. Immunomodulatory activity of approaches of drug development. This will aqueous extract of Nyctanthes provide support among scientist in exploring arbortristis flowers with particular more information about the valuable reference to splenocytes proliferation therapeutic potential of Harsingar plant to and cytokines induction. Indian J. establish the ancient Ayurvedic system with Pharmacol., 48(4): 412-417. authenticity. Biswas, I., Ukil, S., Mukherjee, A. 2014. Determination of n-alkane constituents Acknowledgement and their phenological variation in the epicuticular wax of mature leaves of We take this opportunity to acknowledge our Nyctanthes arbortristis L. Nat. Prod. sincere thanks to our respected Chairman Dr. Res., 8(5): 330-2. SC Kulshreshtha and owernable Dr. B.K. 1032

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How to cite this article:

Ashwani Kumar, Beenu Rathi, Vani Tyagi, Priyanka and Manisha. 2017. Systemic Review on Anti-Sciatica Plant “Night Jasmine” (Nyctanthes ar-bortristis Linn.). Int.J.Curr.Microbiol.App.Sci. 6(6): 1018-1035. doi: https://doi.org/10.20546/ijcmas.2017.606.118

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