Review Article Holoptelea integrifolia (Roxb.) Planch: A...

Review ArticleHoloptelea integrifolia (Roxb) Planch A Review ofIts Ethnobotany Pharmacology and Phytochemistry

Showkat Ahmad Ganie and Surender Singh Yadav

Department of Botany Maharshi Dayanand University Rohtak Haryana India

Correspondence should be addressed to Surender Singh Yadav ssyadavindiarediffmailcom

Received 14 February 2014 Accepted 9 April 2014 Published 18 May 2014

Academic Editor Ziad Daoud

Copyright copy 2014 S A Ganie and S S Yadav This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Holoptelea integrifolia (Ulmaceae) is a versatile medicinal plant used in various indigenous systems of medicine for curing routinehealthcare maladies It is traditionally used in the treatment and prevention of several ailments like leprosy inflammationrickets leucoderma scabies rheumatism ringworm eczema malaria intestinal cancer and chronic wounds In vitro and in vivopharmacological investigations on crude extracts and isolated compounds showed antibacterial antifungal analgesic antioxidantanti-inflammatory anthelmintic antidiabetic antidiarrhoeal adaptogenic anticancer wound healing hepatoprotective larvicidalantiemetic CNS depressant and hypolipidemic activities Phytochemical analysis showed the presence of terpenoids sterolssaponins tannins proteins carbohydrates alkaloids phenols flavonoids glycosides and quinines Numerous compoundsincluding Holoptelin-A Holoptelin-B friedlin epifriedlin 120573-amyrin stigmasterol 120573-sitosterol 1 4-napthalenedione betulinbetulinic acid hexacosanol and octacosanol have been identified and isolated from the plant species The results of several studiesindicated that H integrifolia may be used as an effective therapeutic remedy in the prevention and treatment of various ailmentsHowever further studies on chemical constituents and their mechanisms in exhibiting certain biological activities are needed Inaddition study on the toxicity of the crude extracts and the compounds isolated from this plant should be assessed to ensure theireligibility to be used as source of modern medicines

1 Introduction

Plants have been rich source of medicinal agents sincetime immemorial They have remained main components ofvarious traditional systems of medicine namely AyurvedaUnani Siddha Chinese and so forth Plant species hasremained a good source of anti-infective agents which arecost-effective and have fewer side effects [1] Recently theWHO (World Health Organization) estimated that 80 ofpeople worldwide rely on herbal medicines for some aspectsMany developing countries all over the world have intensifiedtheir efforts in documenting the ethnomedical data andscientific research on medicinal plants It is estimated thatthere are 250000 to 500000 species of plants on earth [2]There are about 47000 plant species in India out of which7500 plant species are of medicinal value only 800 plantspecies are used in the preparation of herbal drugs Soit is anticipated that plants can provide potential bioactive

compounds for the development of new ldquoleadsrdquo to combatvarious diseases A vast proportion of the available higherplant species have not yet been screened for biologicallyactive compounds drug discovery fromplants should remainan essential component in the search for new medicinesHerbal medicines have recently attracted much attentionas alternative medicines useful for treating or preventinglifestyle-related disorders but relatively very little knowledgeis available about their mode of action There has been agrowing interest in the analysis of plant products which hasstimulated intense research on their potential health benefits

2 Scope of Review

The review of H integrifolia was primarily needed to bridgethe gaps in between traditional uses and in vitro pharmaco-logicalbiological studies Previous reviews were based on

Hindawi Publishing CorporationBioMed Research InternationalVolume 2014 Article ID 401213 12 pageshttpdxdoiorg1011552014401213

2 BioMed Research International

RR

HHH

H

OO

S

R

S

S

SS

RS CH3

CH3

CH3

CH3CH3

CH3

CH3

(CH2)14

3HC

Figure 1 Holoptelin-A

simple ethnobotanical uses and few pharmacological activ-ities of the species Hence an attempt was made to updatethe complete information on botany phytochemistry andpharmacological activities of the species

The information provided was taken from differentsources like worldwide accepted scientific database Scopus(httpwwwscopuscom) Science Direct (httpwwwsci-encedirectcom) PubMed (httpwwwncbinlmnihgovpubmed) Springerlink (httpwwwspringercoin) GoogleScholar (httpscholargooglecoin) and Wiley (httpwwwonlinelibrarywileycom) thesis recognized books abstractsconference proceedings and nonimpact and nonindexedjournals The review highlighted the traditional uses of thespecies in Indian system of medicine (Table 2) secondarymetabolitesphytoconstituents isolated from various partsof the plant (Figures 1ndash10) along with proven biologicalactivity different biological activities reported on variousextracts and fractions of different plant parts (Table 3)The traditional uses reported biologicalpharmacologicalactivity isolated compounds and therapeutic application ofH integrifolia might be useful for scientists and researchersto find out new entities responsible for therapeuticactivity

3 Botany

31 Origin and Distribution The plant species originatedfrom Pacific Islands [3] It is distributed in temperate andtropical areas of northern hemispheres The plant is neu-tralized to the tropical regions of Asia including IndiaNepal Sri Lanka Indo-China Cambodia Laos MyanmarVietnam Burma and China [4] In India it is found inouter Himalayan region from Jammu eastward up to 2000 ftextending to Assam and Burma and in southwards fromBengal to Central Western and South India to dry region ofCeylon

HO

(R)(R)

HH (R)

(R)

(R)H

(S)

(S)(S)

(S)

(S)

CH3CH3

CH3CH3

CH3CH3

CH3CH3

Figure 2 Holoptelin-B

O

(S)HH

H

H

(S)

(R)

(R)(R)

(R)

(S)(S)

(S)

CH3

CH3

CH3

CH3CH3

CH3CH3

CH3

Figure 3 Friedlin

32 Taxonomic Status

Domain EukaryotaKingdom PlantaeDivision Magnoliophyta

BioMed Research International 3

(S)HH

H

H

(S)

(R)

(R)

(R)

(S)(S)(S)

(S)

(R)

RO

CH3

CH3CH3

CH3CH3

CH3CH3

CH3

Figure 4 Epifriedlin

HO

(R)(R) (R)

H

H

(R)

(R)

(R)

H

(S)

(S) (S)

CH3

CH3

CH3CH3

CH3CH3CH3

CH3

Figure 5 120573-amyrin

H

H

HO

H H

Figure 6 Stigmasterol

OH

Figure 7 Hexacosanol

OH

Figure 8 Octacosanol

HO

COOH

Figure 9 Betulinic acid

HO

CH2OH

Figure 10 Betulin

Class MagnoliopsidaOrder UrticalesFamily UlmaceaeGenus HolopteleaSpecies integrifolia

33 Plant Description The plant is a large deciduous treeup to 25m high Bark is 6ndash8mm thick whitish-grey smoothwith pubescent branchlets Leaves are simple alternate stip-ulate ovate or elliptic-ovate and acuminate in shape Thebark when cut and leaves when crushed emit an unpleasantodor Flowers are small greenish-purple and polygamousand found in short racemes or axillary fascicles In maleflowers there are 8 stamens and in bisexual flowers 5 stamensare present Ovary is superior unilocular compressed andstalked Style is very short (25ndash4mm long) with bifid stigmaFruits are one seeded samara light brown obliquely ellipticor orbicular winged and stalked indehiscent and 25ndash35 cmlong and 15ndash25 cm wide Flowering and fruiting are seen


Table 1 Vernacular names of Holoptelea integrifolia

Language Vernacular name

Hindi Papri Chilbil Kanju Banchilla BawalPoothigam Dhamna Begana Chirabil

English Indian elm Jungle cork tree Monkey biscuittree Indian beech tree

Sanskrit Chirivilva Pootikaranja UdakiryaHasthivaruni Markati Vayasi Karabhanji

Malayalam Aavil Njettaval AvalPunjabi Rajain Khulen ArjanTelugu Nemilinara Nali Thapasi Nemali PedaneviliKannada Kaladri Nilavahi Rahubija Thavasai RasbijaTamil Aya Ayil Kanci Vellaya Avil PattaiBengali Nata karanjaMarathi Ainasadada Vavala Vavli Papra BawalOriya Dhauranjan Turuda KaranjaGujarati Charal Charel Kanjo Waola Chirbil ChirmilKonkani VamvloBurmese Myaukseik PyaukseikNepali Sano pangroSiddha Iya

during the months of February-March Seeds are smallwhitish and kidney shaped

34 VernacularNames Holoptelea integrifoliahasmany com-mon names depending upon the languages spoken in aparticular region The names used in different languages arepresented in Table 1

35 Cultivation The plant is commonly cultivated by thetransplantation of nursery-raised seedlings In the nurseryseedlings are raised by sowing seeds in lines about 12ndash20 cmapart Transplantation is done when the seedlings are 10 cmin length at spacing of 225 times 225 cm The seedlings are keptin the transplant beds for two years and then planted in theseason of monsoon Fresh seeds are also sown directly at therate of 2 seeds per stake on the lines of 3m apart Continuouswatering is required in both cases

36 Diseases and Pests Generally the plant is disease freehowever some pests attack it Major pests of the tree arethe tree borers of the groups Bostrichidae BuprestidaeCerambycidae andPlatypodidae which commonly infest thestem and young leaves

4 Ethnomedicinal Uses

The plant Holoptelea integrifolia is used traditionally forthe treatment of inflammation gastritis dyspepsia colicintestinal worms vomiting wound healing leprosy dia-betes hemorrhoids dysmenorrhea and rheumatism [5]Bark and leaves are used as bitter astringent thermo-genic anti-inflammatory digestive carminative laxative

anthelmintic depurative repulsive and urinary astringent[6] Ethnomedicinally the leaves and stem bark of H inte-grifolia are used by tribal people for the treatment of variousailments (Table 2) The mucilaginous bark is boiled andthe juice squeezed out and applied to rheumatic swellings[7] Paste of the stem bark is externally applied to treatthe inflammation of lymph glands ringworm and scabiesDecoction of the leaves is used to regulate fat metabolismtreat ringworm eczema and cutaneous diseases [8] Stembark acts as an anti-inflammatory agent specifically for eyesStem bark paste is externally applied on forehead of thepatient suffering from common fever [9] Bark and leaf pasteof the plant are applied externally on the white patches orleucoderma Bark boiled in coconut oil andmixed with garlicis applied externally to eczema [10] For treatment of herpessimplex infection bark paste is applied over the affected partuntil it disappears Bark cut in the shape of a coin is tied onleft arm below the shoulder for treatment of malaria [11] It isalso used for the treatment of intestinal cancer [12] Leaf budmixed with lime juice is applied externally to affected areafor treatment of hair loss by infection [13] Bark groundedwith lemon juice and made into paste is used for weakness[14] Seeds are used especially on ringworm and dried fruitin polyurea and urinary disorders [15]

5 Pharmacology

H integrifolia is known to possess medicinal value in tra-ditional system and represented a wide range of pharmaco-logical properties Even though several traditional uses of Hintegrifolia are recognized a scientific validity and supportingevidence are a prerequisite for commercial exploitationTable 3 provides an overview on pharmacological propertiesof H integrifolia extracts as well as compounds isolatedfrom it In the proceeding text some of the available reportspertaining towards the important pharmacological potentialof H integrifolia extracts are being discussed

51 Antibacterial Activity Vinod et al [16] reported antibac-terial effect of hexane diethyl ether acetone and aqueousextracts of leaves of Holoptelea integrifolia against lactamresistant strain of Staphylococcus aureus The diethyl etherextract has shown the highest activity and the active principleresponsible for the present activity was found to be 1 4-naphthalenedione The MIC of the compound was found tobe 4mgmL

Padmaa and Durga [17] evaluated petroleum ether ben-zene chloroform methanolic and aqueous extracts of stembark of H integrifolia for antibacterial activity against Saureus Bacillus subtilis Escherichia coli and Pseudomonasaeruginosa Chloroform extract was found to be most effec-tive against all the test microorganisms The minimuminhibitory concentration for chloroform extract was found tobe 25 50 100 and 300 120583gmL against B subtilis S aureus Paeruginosa and E coli respectively

In the following year Ahmad et al [18] studied antibac-terial potential of chloroform leaf extract of Holoptelea inte-grifolia against various pathogenic microorganisms namely


Table 2 Ethnomedicinal profile of Holoptelea integrifolia

Diseasedisorderindication Part usedmode of application ReferenceLeprosy boils inflammation skin diseaseand scorpion sting Leaf is boiled in water and water bath is given [39]

Rickets Young leaf is applied on back bone and tied for 1 hr [40]

Headache Bark is made into a paste and applied [41]

Chronic wound Bark powder is applied [42]Leucoderma leprosy scabies and other skindiseases Leaf and bark [43]

Uncontrolled bleeding fresh wound Seeds are applied externally in the form of poulticeon the injured part

[44]

Rheumatism Mucilaginous bark is boiled juice is squeezed outand applied to swellings [7]

Ringworm eczema and cutaneous diseases Decoction of the leaves [8]

Common fever Stem bark paste is externally applied on forehead [9]

Eczema Bark boiled in coconut oil and mixed with garlic isapplied

[10]

Malaria Bark cut and tied on an arm [11]

Intestinal cancer Bark [12]

Herpes infection Leaf bud mixed with lime juice is applied externallyto affected area

[13]

Weakness Bark grounded with lemon juice and made into pasteis given

[14]

Polyurea and other urinary disorders Dried fruit is used [15]

Citrobacter freundii Micrococcus luteus Pseudomonas aerug-inosa and Pseudomonas fluorescence The antibacterial sen-sitivity was analyzed using disk diffusion method at vari-ous concentrations where zone of inhibition was comparedwith the standard drug cefotaxime The overall antibacte-rial activity of H integrifolia was found to be strongestagainst C freundii followed in descending order by Pfluorescence P aeruginosa and M luteus The minimuminhibitory concentration (MIC) for chloroform leaf extractwas found to be 1562 3125 3125 and 625mgmL againstC freundii P fluorescence P aeruginosa and M luteusrespectively Another group Joshi et al [19] demonstratedantibacterial and antitubercular activity of H integrifoliaagainst different Gram-positive and Gram-negative bacterialstrains and M tuberculosis H

37RV strain Alcoholic extract

showed moderate to good antibacterial and antitubercularactivity

52 Antifungal Activity Besides antibacterial H integrifoliahas a broad antifungal potential [20] The alcoholic leaf andstem extracts of H integrifolia were studied for antifungalactivity against five fungal strains namelyCandida tropicanaCandida krusei Candida albicans Aspergillus niger and Sac-charomyces cerevisiae using the agar well diffusion methodThe results indicated that C tropicana (MIC 39 120583gmL)is most sensitive to MSBE (methanolic stem bark extract)and S cerviceae (MIC 1562 120583gmL) and C tropicana (MIC1562 120583gmL) is most and equal sensitive organisms to MLE(methanolic leaf extract) Their MICs ranged from 1562 to

1250 120583gmL and 39 to 625120583gmL forMLE andMSBE respec-tively The lowest MMC (minimum microbicidal concen-tration) observed was 3904 120583gmL for C tropicana againstMSBE

Sahoo et al [21] screened the different leaf extracts ofHoloptelea integrifolia for antifungal activity against the testfungus Colletotrichum capsici The hydroethanolic extractof leaves was fractionated by differential solubility methodand only the petroleum ether extract was found to havefungitoxicity MIC of the active fraction was worked out(200 ppm) and at this concentration it was fungicidal innature The active fraction at MIC was able to withstandheavy inoculumdensity killed the test pathogen in 130 hrs ofexposure It could bemore effectively used at any pH between4 and 9 and may prove to be superior to other commercialfungicides The active fraction proved to be nonphytotoxicand it stimulated the rate of seed germination and seedlinggrowth of Capsicum annuum seeds

Ishnava et al [22] evaluated different fractions ofH inte-grifolia leavesfor antifungal activity The in vitro antifungalassay was performed by agar diffusion test and minimuminhibitory concentration (MIC) for hexane ethyl acetateand methanolic and aqueous fractions Among these ethylacetate extract exhibitedmaximumantifungal activity againstAlternaria sp Aspergillus parasiticus Aspergillus nidulansTrichoderma harzianum and Aspergillus flavus with MICranging from 80 to 40 ppm against Aspergillus nidulans andAlternaria sp respectively


Table 3 Pharmacological activities of various extracts of Holoptelea integrifolia

Activity Plant part Extract Experimental proceduresmodels References

Antibacterial

Leaves Hexane diethyl ether acetoneand aqueous

MIC (minimum inhibitoryconcentration) [16]

Stem bark Pet Ether benzene chloroformmethanolic and aqueous


Leaves Chloroform Disk diffusion assay [18]

Antifungal

Leaf and stem Methanolic Agar well diffusion method [20]

Leaves Hydroethanolic MIC (minimum inhibitoryconcentration) [21]

Leaves Hexane ethyl acetatemethanolic and aqueous

Agar diffusion test and MIC(minimum inhibitoryconcentration)

[22]

Anti-inflammatory

Leaves Aqueous Carrageenan-induced pawedema test [23]

Leaves Ethanolic

Carrageenan-induced pawedema dextran-induced pawedema histamine-induced pawedema serotonin-induced pawedema and cottonpellet-induced granuloma tests

[24]

Anthelmintic Stem bark Benzene chloroformmethanolic aqueous pet ether Dashrsquos method [25]

Bark Ethanolic and aqueous Time of paralysis and death assay [26]

Antioxidant

Stem bark EthanolicFTC (ferric thiocyanate) andTBA (thiobarbituric acid)methods

[27]

Leaves Methanolic 11diphenyl-2-picrylhydrazyl(DPPH) method [20]

Stem bark AqueousDPPH radical nitric oxidesuperoxide and reducing powerassays

[28]

Antidiabetic Leaves Ethanolic chloroform pt etherand aqueous Alloxan-induced diabetes model [29]

Leaves Methanolic and pet ether Alloxan-induced diabetes model [30]

Antidiarrhoeal Leaves EthanolicCastor oil and magnesiumsulphate-induced diarrhea micemodel

[32]

Adaptogenic Stem bark EthanolicForced swimming endurance testand chronic cold restraint stressmode

[34]

Anticancer

Leaves Ethanolic Doltonrsquos ascetic lymphoma(DAL) model [35]

Bark Ethanolic and pet etherDMBA- (dimethyl benz(a)anthracene-) induced breastcarcinoma assay

[36]

Bark Butanol hexane ethyl acetateand chloroform

MTT 3-(45-dimethylthiazole-2yl)-25-biphenyl-tetrazoliumbromide assay

[37]

Wound healing Stem bark andleaves Methanolic Excision and incision wound

model [20]

Antiulcer Leaves Methanolic Pylorus ligated ulcer model [45]

Analgesic Leaves Ethanolic ethyl acetaten-butanol and aqueous Tail flock method [46]

Hepatoprotective Leaves Methanolic Paracetamol-inducedhepatotoxicity assay [47]


Table 3 Continued

Activity Plant part Extract Experimental proceduresmodels ReferencesLarvicidal Leaves Acetone Standard WHO procedure [48]

Antiemetic Leaves Ethanolic Cisplatin-induced nausea model [49]

CNS depressant Leaves Methanolic Head dip Rota rod and tractiontests

[50]

Hypolipidemic Leaves and bark HydroalcoholicHMG-CoA reductase and LCAT(Lecithin cholesterol-acyltransferase) assays

[51]

53 Anti-Inflammatory Activity Anti-inflammatory activityof H integrifolia was reported by Sharma et al [23] Theactivity was analyzed by carrageenan- induced paw edematest in the male wistar strain rats weighing between 150and 200 gm The aqueous extract of H integrifolia at doses250 and 500mgkg was given to observe inhibition ofpaw edema which were comparable with indomethacin(10mgkg) used as a reference drugThe extract administeredorally produced a significant (119875 lt 005) dose-dependentinhibition of edema formation

In another report Kalpana and Upadhyay [24] investi-gated the anti-inflammatory properties of ethanolic extractof the leaves of Holoptelea integrifolia Planch A dose of 250and 500mgkg was given to observe percentage inhibitionof paw edema which were comparable with indomethacin(10mgkg) used as a reference drug The extract (500mgkg)exhibited maximum anti-inflammatory effect (3001 21723234 and 2962) with carrageenan dextran histamineand serotonin method respectively A significant percentageinhibition of paw edema by the extract as compared tostandard drug suggests its usefulness in acute and chronicanti-inflammatory models

54 Antihelminthic Activity Anthelmintics or antihelmin-thics are drugs that expel parasitic worms (helminths) fromthe body by either stunning or killing them They mayalso be called vermifuges (stunning) or vermicides (killing)The first report on antihelminthic activity of H integrifoliawas provided by Nadella and Paarakh [25] The activity ofdifferent stem bark extracts was evaluated against Pheretimaposthuma Among all the extracts tested methanolic andaqueous extracts showed better and dose-dependent activityin comparison with reference standard piperazine citrateMethanolic extract at 80mgmL showed shortest time ofparalysis (90 plusmn 089min) and death (3566 plusmn 081min) whencompared to piperazine citrate (334 and 556min resp at60mgmL)

In another study Kaur et al [26] comparatively stud-ied the anthelmintic potential of ethanolic and aqueousextract of H integrifolia bark using Eisenia fetida In thebioassay time of paralysis (119875) and time of death (119863)of the worms were determined at various concentrations(10 25 50 and 100mgmL) The bioassay revealed that theethanolic and aqueous extract significantly demonstratedparalysis and also caused death of worms especially at higherconcentration The ethanolic extract showed shortest time

of paralysis (626 plusmn 008min) and death (1673 plusmn 021min)at 100mgmL The results were comparable with standardpiperazine citrate (295 plusmn 009 amp 710 plusmn 011min resp at10mgmL)

55 Antioxidant Activity An antioxidant is a molecule thatcan terminate chain reactions by removing free radical inter-mediates and inhibit other oxidation reactions Holopteleaintegrifolia possess antioxidants which are responsible forthe scavenging activity through various mechanisms In onestudy Saraswathy et al [27] screened ethanolic crude extractof stem bark of Holoptelea integrifolia for its antioxidantactivity using 120572-tocopherol as standard antioxidant The freeradical scavenging activity of the extract was evaluated bytwo different methods ferric thiocyanate and thiobarbituricacid methods at a concentration of 002 and comparedwith vitamin E In FTC method the control showed highestabsorbance value (083) followed by extract (029) standardvitamin E (028) on day 5 however in TBA method thecontrol had the highest absorbance value (035) followed byH integrifolia (008) and Vitamin E (0075) Thus ethanolicextract exhibited significant in vitro antioxidant activity byinhibiting the oxidation of linoleic acid in both FTC and TBAmethods

In another study the methanolic extract of leaves (MLE)and stem bark (MSBE) of H integrifolia was screened forantioxidant activity by 11-diphenyl-2-picrylhydrazyl (DPPH)using HPLC method and total phenolic content was alsoestimated MSBE was found to be most potent antioxidantand had more phenolic content than the MLE The higherphenolic content of MSBE might have contributed to higherantioxidant activity of MSBE [20]

Recently Srivastava et al [28] evaluated the in vitroantioxidant potentials and phenolic content of aqueousextract of H integrifolia stem bark The activity was deter-mined by different methods namely DPPH radical nitricoxide superoxide and reducing power assays The DPPHradical scavenging activity ranged from 1314 to 5517comparable to standard ascorbic acid (2256ndash9368) TheIC50

value of plant extract for scavenging free radicals was7710 7495 and 8678 120583gmL by DPPH nitric oxide andsuperoxide assays respectively The total phenolic contentwas found to be 6173 plusmn 023mg GAEg

56 Antidiabetic Activity Mamatha [29] studied the effectof different extracts namely ethanolic petroleum ether


aqueous and chloroform of Holoptelea integrifolia leaves fortheir antidiabetic activity by using alloxan-induced diabetesmodels using albino rats The study indicated that ethanolicchloroform and aqueous extracts had more significant (119875 lt001) antidiabetic activity (1783 plusmn 2916 1927 plusmn 409 and1950 plusmn 289 resp) in acute as well as prolonged treatment(1627 plusmn 147 1729 plusmn 505 and 1809 plusmn 228 resp) compared tocontrol (2107 plusmn 324) The results were comparable with ref-erence standard glibenclamide (17018 plusmn 258 1598plusmn 253)Petroleum ether extract did not show significant (119875 lt 005)activity at 7th hour in acute study (2077 plusmn 442) compared todiabetic control

Sharma et al [30] screened methanolic and petroleumether extract of leaves of H integrifolia for antidiabeticactivity Diabetes in the test animal (male wistar albino rat)was induced by a toxic glucose analogue AlloxanThe activitywas compared with a standardglibenclamide The petroleumether extract at 100 and 200mgkg and methanolic extractat 200mgkg concentration showed significant antidiabeticactivity The activity may be due to presence of steroids andglycosides in the test extracts These phytocompounds maycause inhibition of ATP-sensitive potassium channels in pan-creatic beta cellsThis inhibition causes cell membrane depo-larization which causes voltage-dependent calcium channelsto open and increase in intracellular calcium in the beta cellswhich stimulates insulin release

Recently Sharma et al [31] studied antidiabetic activityof stem bark extract of H integrifolia in alloxan-induceddiabetic rats The treatment was continued for three weeks toestimate blood glucose level body weight and lipid profileThe blood glucose level decreased gradually in the animalstreated with the bark extract (250 and 500mgkg bw) orallyThe prevention of loss of body weight in diabetic animalswas found to be significant on day 15 in the animals of bothtreatment groups

57 Antidiarrhoeal Activity Report on antidiarrheal potentialof Holoptelea integrifolia was provided by Shrinivas et al[32] The ethanolic leaf extract of H integrifolia was studiedagainst diarrhea inmice induced by castor oil andmagnesiumsulphate In the experiment the test extract at the dosesof 250 and 500mgkg reduced the total number of faecesas well as the total number of diarrhoeic faeces in a dose-dependentmanner On the other hand in the gastrointestinalmotility test the extract at the same doses retarded signif-icantly (119875 lt 001) the intestinal transit of charcoal mealin mice when compared to the control atropine sulphate(5mgkg)

58 Adaptogenic Activity Adaptogens or adaptogenic sub-stances are a new class of metabolic regulators whichincreases the ability of an organism to adapt to environmentalfactors and to avoid damage from such factors [33]

Many herbs have been reported to possess adaptogenicagents H integrifolia is one such a plant which has adap-togenic activity Kumar et al [34] reported the adaptogenicactivity of ethanolic stem bark extract of H integrifoliain comparison with Withania somnifera The activity was

analysed in female albinoWister rats using forced swimmingendurance test and chronic cold restraint stressmode at dosesof 250 and 500mgkg Both the doses of test extract were ableto increase the swimming endurance when compared withanimals who received normal saline

59 Anticancer Activity The effect of Holoptelea integrifoliaon daltonrsquos ascitic lymphoma in Swiss albino mice wasreported by Lakshmi et al [35]The ethanolic extract of leavesof H integrifolia has been tested for anticancer activity at thedose of 250 and 500mgkg bw The study was conductedto determine the effect of EHI on tumour volume tumourcell count viable tumour cell count mean survival time andincrease in life span The findings of the study suggestedthat the crude extract of test plant has potential anticanceractivity The extract increased the life span of DAL treatedmice and restored the hematological parameters as comparedwith the DAL bearing mice in a dose-dependent mannerSoujanya et al [36] observed anti-breast cancer activityof ethanolic extract of H integrifolia Planch against 712-dimethyl benz(a)anthracene induced breast carcinoma inexperimental rats In the study body weight of experimen-tal animals tumor burden tumor multiplicity and tumorvolume of breast were determined The extract administeredorally at doses of 250 and 500mgkg showed significant(119875 lt 005 001) dose-dependent inhibition of breast cancerformation The tumor multiplicity was found to be 1 pergroup inhibition of breast cancer formation by the testextract was almost the same as shown by standard drugtamoxifen

Recently Guo et al [37] observed antineoplastic (anti-cancerantitumor) activity of butanol hexane ethyl acetateand chloroform bark extracts of Holoptelea integrifoliaThe effect was studied on small cell lung cancer breastprostate and colorectal and hepatocellular cancer cell linesThe findings of the study showed that hexane and ethylacetate extracts had significant cytotoxic effects on breastand prostate cancer cells Interestingly hexane extract wasselectively over approx 2-fold more toxic in prostate cancercells 25-fold in colon cancer cells and 5-fold in breast cancercells Similarly ethyl acetate extract was selectively approx2- to 3-fold more toxic in all the cancer cells compared tonon-cancer HEK293 cells Specifically the IC

50value of only

2977 plusmn 117mgmLof ethyl acetate in prostate cancer cells wasover 3-fold highly toxic than HEK293

510 Wound Healing Activity Wound healing is a complexphenomenon including proliferation of both parenchymaland connective tissue cells synthesis of ECM (extracellu-lar matrix proteins) remodeling of connective tissue andparenchymal components and acquisition of wound strength[38]

The wound healing potential of H integrifolia wasobserved by Reddy et al [20] In the study two differentextracts of H integrifolia namely methanolic leaf (ML) andmethanolic stem bark (MSB) extracts were analyzed forwoundhealing potential in albino rats using twowoundmod-els excision wound model and incision wound model The


findings revealed that in excision wound model more than90wound healing was recorded in treated groups by 14 daysof post-surgery whereas only 6299 was observed in thecontrol group In incision model higher breaking strengthsand higher hydroxyproline content in treated groups sug-gested higher collagen redeposition than the control groupBesides the external application of these extracts on thewound prevented the microbes from invading the woundresulting in the protection of wound against the microbialinfections

511 Antiulcer Activity Peptic ulcer disease (PUD) is aserious gastrointestinal disorder that requires a well-targetedtherapeutic strategy Hemamalini et al [45] reported theantiulcer activity of H integrifolia leaves The activity oftest extract was evaluated using pylorus ligated ulcer modelin rats and compared with the standard omeprazole Themethanolic extract at 500mgkg per oral dose significantly(119875 lt 001) reduced the ulcer index (343 + 006) ulcerformation (6961) volume of gastric juice (385 + 008mL)free acidity (3467 + 088 EqL) and total acidity (6917 +101 EqL) in pylorus ligation- induced ulcer models in ratsThe ulcer curative ratio of methanolic extract was almostcomparable to that of standard

512 Analgesic Activity An analgesic (informally known aspainkiller) is any member of the diverse group of drugs usedto relieve pain and to achieve analgesia

Various medicinal herbs have been reported to haveanalgesic potential However the first study towards theanalgesic activity of Holoptelea integrifolia was observed byRizwani et al [46] In the study different fractions of HIntegrifolia leaves were evaluated for analgesic activity inmice by tail flick method At the dose of 500mgkg the testextracts were found to have a significant (119875 lt 005) anal-gesic activity when compared to standard diclofenac sodium(50mgkg) Maximum effect was established at 150min afterdrug administration The maximum analgesic activity wasshown by ethanolic extract and followed in descending orderby ethyl acetate 119899-butanol and aqueous extract

513 Hepatoprotective Activity Hepatoprotection or antihep-atotoxicity is the ability to prevent damage to the liverRecently Hemamalini and Sathya [47] reported the hep-atoprotective activity of methanolic extracts of Holopte-lea integrifolia against CCl

4induced hepatotoxicity In the

study effect of test extract at a dose of 500mgkg onthe levels of serum marker enzymes Alanine Transaminase(ALT) Aspartate Transaminase (AST) Alkaline Phosphatase(ALP) and Total Bilirubin (TB) was determined The studyshowed that methanolic extract (500mgkg) exhibited asignificant protective effect by altering the serum levelsof AST ALT ALP and total bilirubin These observationswere supported by histopathological studies Simultaneoustreatment of methanolic extracts of H integrifolia with CCl

4

showed less damage to the hepatic cells as compared tothe rats treated with CCl

4alone Histological changes such

as steatosis (fatty change fatty degeneration or adipose

degeneration) inflammatory infiltrations and perivenularfibrosis were observed in CCl

4treated (toxic) control group

The test extract prevented these histological changes furtherindicating its hepatoprotective activity

514 Mosquito Larvicidal Activity The first study relatedto larvicidal activity of Holoptelea integrifolia was reportedby Singha et al [48] The effect of acetone extract fromH integrifolia leaves was evaluated on larval mortality ofCulex vishnui after 24 48 and 72 h of exposure with fiveconcentrations of crude extract (01 02 03 04 and 05)The study showed that themortality rate of all larval instars at05 concentration was significantly higher (119875 lt 005) thanat 01 02 03 and 04 concentrations Highest mortalitywas observed at 400 ppm concentration of acetone extractHigher mortality rate was also recorded in 72 h bioassaythan those in 24 and 48 h The results of regression analysisrevealed that the mortality rate (119884) was positively correlatedwith the period of exposure (119883) The log probit analysis(95 confidence level) revealed that LC

50values gradually

decreased with the exposure period

515 Antiemetic Activity An antiemetic is a drug that iseffective against vomiting and nausea Effect of ethanolicextract of leaves ofH integrifolia on cisplatin-induced nauseausing a rat model was investigated for antiemetic activity byShrinivas et al [49] Cisplatin at 3mgkg dosewas selected fortesting the antinausea activity of extract Cisplatin-inducedpica decreased significantly when animals were pretreatedwith H integrifolia extract at doses of 250 and 500mgkg

516 CNS Depressant Activity Hemamalini et al [50]ob-served the CNS (central nervous system) depressant activityof the methanolic leaf extract of Holoptelea integrifolia inSwiss albino mice A daily dose of 250mgkg of extractwas administered to the animals for 15 days after whichvarious CNS experiments such as exploratory behavior andmuscle relaxantwere recorded and comparedwith the controlanimals The findings revealed that the test extract causedsignificant reduction in exploratory behavioral pattern inhead dip test and reduction in muscle relaxant activity inrota rod and traction testsThese findings confirmed the CNSdepressant activity in tested animal models

517 Hypolipidemic Activity Hypolipidemic or antihyperlipi-demic agents are lipid-lowering drugs that are used in thetreatment of hyperlipidemias The leaf and bark paste ofHoloptelea integrifolia is traditionally used for the treatmentof obesity in Asian countries Based on the fact Subhashand Augustine [51] investigated the hypolipidemic effectof H integrifolia and its mechanism in diet-induced obeserat model In the study body weight serum lipids andlecithin cholesterolacyltransferase (LCAT) apolipoproteinsHMG-CoA reductase and faecal fat content were estimatedafter oral administration The findings of the study showedthat the test extract markedly lowered body weight serumlipids HMGR activity and apo B and increase high-densitylipoprotein-cholesterol and apoA1 concentrationsThe faecal


Table 4 Qualitative phytochemical screening of Holoptelea integrifolia

Solvent Plant part Reducing sugar Protein Phenol Alkaloid Steroid Triterpenoid Flavones Tannin Saponins Reference

Pt Ether Leaf + + minus minus + minus + + minus

[8]

Stem minus minus minus minus + minus minus + minus

Benzene Leaf minus minus minus minus + minus + + minus

Stem minus + minus minus + minus + + minus

Chloroform Leaf minus + minus minus + minus minus minus minus

Stem minus + + minus + minus + minus minus

Methanol Leaf minus + minus + + minus minus minus minus

Stem minus + + + + + + + minus

D Water Leaf minus minus + minus minus + minus + minus

Stem minus minus minus minus minus + minus + minus

Acetone Leaf + + + + + minus + + + [18](+) present and (minus) absent

analysis showed a remarkable increase in faecal lipids whichindicates the ability to inhibit intestinal fat absorptionPresence of a compound 3-(7-ethoxy-4-methyl-2-oxo-2H-chromen-3-yl) propanoate (C1) in the test extract couldbe responsible for the present activitywhich might haveinhibited HMGR activity and block intestinal fat absorption

6 Phytochemistry

Holoptelea integrifolia the versatile medicinal plant is theunique source of various types of compounds having diversechemical structure The plant species contains wide rangeof phytochemicals such as terpenoids sterols saponinstannins proteins carbohydrates and alkaloids [18 52] Inaddition H integrifolia also contains flavonoids phenolscardiac glycosides coumarins and quinines [53] Thequalitative phytochemical screening of H integrifolia ispresented in Table 4 Many compounds were isolated fromthe plant and proven to be biologically active Holoptelin-A(Figure 1) Holoptelin-B (Figure 2) friedlin (Figure 3)epifriedlin (Figure 4) 2-aminonaphthoquinone 120573-sitosterol120573-D-glucose 120573-amyrin (Figure 5) stigmasterol (Figure 6)and hederagenin have been isolated from heart wood andbark while hexacosanol (Figure 7) octacosanol (Figure 8)120573-sitosterol and 120572-amyrin were isolated from leaves [28]Sadasivan et al [16] isolated an antibacterial compound1 4-naphthalenedione from diethyl ether leaf extractof H integrifolia Recently Ahmad et al [54] isolatedtwo medicinal pentacyclic triterpenoids betulinic acid(3120573-Hydroxy- lup-20(29)-en-28-oic acid) (Figure 9) andbetulin (Lup-20(29)-ene-3120573 28-diol) (Figure 10) frommethanolic bark extract These isolated compounds wereidentified as betulinic acid and botulin respectivelyon the basis of detailed spectroscopic analysis and theircomparisons with the data reported in the chemicalliterature for these components The distinguishable positionin 13C-NMR of betulin was found at C-17 = 478 ppm andC-28 = 608 amp 606 whereas in the betulinic acid the valueof the same carbon signals depicted in the spectrum was

at 563 amp 5626 and 1805 amp 17962 due to the attachment ofCH2OH and COOH respectively Betulinic acid has valuable

biological potential such as inhibitors of HIV-1 entry HIV-protease or of reverse transcriptase (RT) whereas betulinhad significant anticancer effect on adenocarcinoma cervixcarcinoma hepatoma and breast cancer

7 Conclusion

It is evident from the available literature that Holoptelea inte-grifolia leaves are themost investigated part of the plant Leafand stem bark has been a promising agent for the treatmentof skin diseases like leucoderma scabies ringworm andeczema The biological studies such as antimicrobial anti-helminthic antidiabetic anti-inflammatory and antioxidantactivities were noticeable in crude extracts of various parts ofthe plant In parallel to above observations pure compound1 4-napthalenedione was marked for antibacterial activityagainst120573-lactam resistant strain of Staphylococcus aureusThedetailed study of pharmacology bioassay guided isolationof active principles and mechanism of action may help tounderstand the relation between pharmacological effects andtraditional uses of H integrifolia There are many areas towork in this plant for its full recognition Factors such asgeographical and seasonal variation play an important rolein the authentication of the chemical constituents responsiblefor the activity which also can be an area of interestThus it ismandatory to fill the huge gap of insufficient knowledge andawareness among pharmacologists as well as researchers tohold the position of this plant in providing better medicinalvalues to the society This can be fulfilled only by generatinginterest among research community through writing reviewsand carrying out research on different aspects of this plantspecies

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper


Acknowledgment

Financial assistance from University Grants CommissionNew Delhi and Haryana State council for Science and Tech-nology (HSCST) Department of Science and TechnologyGovernment of Haryana is thankfully acknowledged

References

[1] S H Samsam and F Moatar Natural Medicines and PlantsMashal Publications Tehran Iran 1991

[2] R P Borris ldquoNatural products research perspectives from amajor pharmaceutical companyrdquo Journal of Ethnopharmacol-ogy vol 51 no 1ndash3 pp 29ndash38 1996

[3] A Singh ldquoExotic floristic diversity of the Varanasi district ofUttar Pradesh Indiardquo Indian Journal of Plant Sciences vol 1 pp73ndash84 2012

[4] V D Bambhole and G G Jiddewar ldquoAntiobesity effect of Irisversicolor andHoloptelea integrifolia in ratsrdquo Sachitra Ayurvedavol 37 pp 557ndash561 1985

[5] P KWarrier V P K Nambiar andC Ramakutty IndianMedic-inal Plants A Compendium of 500 Species Orient Longman1995

[6] N D Prajapati S S Purohit and A K Sharma A Handbook ofMedicinal Plants A Complete Source Book Agrobias JodhpurIndia 2003

[7] K M Nandkani Indian Materia Medica Popular PrakashanMumbai India 1976

[8] J K P Benjamin and P K S Christopher ldquoPreliminary phyto-chemical and pharmacognostic studies ofHoloptelea integrifoliaRoxbrdquo Ethnobotanical Leaflets vol 13 pp 1222ndash1231 2009

[9] V K Singh and Z A Ali ldquoFolk medicines in primary healthcare common plants used for the treatment of fevers in IndiardquoFitoterapia vol 65 no 1 pp 68ndash74 1994

[10] V H Harsha S S Hebbar V Shripathi and G R HegdeldquoEthnomedicobotany of Uttara Kannada district in KarnatakaIndia plants in treatment of skin diseasesrdquo Journal of Ethnophar-macology vol 84 no 1 pp 37ndash40 2003

[11] P Mahishi B H Srinivasa and M B Shivanna ldquoMedicinalplant wealth of local communities in some villages in Shimogadistrict of Karnataka Indiardquo Journal of Ethnopharmacology vol98 no 3 pp 307ndash312 2005

[12] J G Graham M L Quinn D S Fabricant and N RFarnsworth ldquoPlants used against cancermdashan extension of thework of Jonathan Hartwellrdquo Journal of Ethnopharmacology vol73 no 3 pp 347ndash377 2000

[13] M Parinitham G U Harish N C Vivek T Mahesh andM BShivanna ldquoEthnobotanical wealth of Bhadra wild life sanctuaryin Karnatakardquo Indian Journal of Traditional Knowledge vol 3pp 37ndash50 2004

[14] N Rajakumar and M B Shivanna ldquoEthno-medicinal appli-cation of plants in the eastern region of Shimoga districtKarnataka Indiardquo Journal of Ethnopharmacology vol 126 no1 pp 64ndash73 2009

[15] C P Khare Indian Medicinal Plants An Illustrated DictionarySpinger Science 2007

[16] N V Vinod M Haridas and C Sadasivan ldquoIsolation of 14-naphthalenedione an antibacterial principle from the leaves ofHoloptelea integrifolia and its activity against 120573-lactam resistantStaphylococcus aureusrdquo Indian Journal of Biochemistry andBiophysics vol 47 no 1 pp 53ndash55 2010

[17] P Padmaa and N Durga ldquoAntibacterial activity of differentextracts of stem bark of Holoptelea integrifoliardquo InternationalResearch Journal of Pharmacy vol 2 pp 111ndash113 2011

[18] S Ahmad R Sharma S Mahajan R Agnihotri and A GuptaldquoAntibacterial evaluation and preliminary phytochemical anal-ysis of the leaf extract of Holoptelea integrifoliardquo Journal ofPharmacy Research vol 5 pp 3823ndash3825 2012

[19] S D Joshi C S Hallikeri and V H Kulkarni ldquoEvaluation ofantibacterial and antitubercular activities of Holoptelea integri-folia (Roxb) Planch barkrdquo Universal Journal of Pharmacy vol02 pp 87ndash90 2013

[20] B S Reddy R K K Reddy V G M Naidu et al ldquoEvaluationof antimicrobial antioxidant and wound-healing potentials ofHoloptelea integrifoliardquo Journal of Ethnopharmacology vol 115no 2 pp 249ndash256 2008

[21] K K Sahoo V K Yadav and A R Saxena ldquoAntifungalproperties of Holoptelea integrifolia (Roxb) Planchrdquo Annals ofPlant Protection Sciences vol 18 pp 438ndash442 2010

[22] K B Ishnava K H Chauhan and C A Bhatt ldquoScreening ofantifungal activity of various plant leaves extracts from Indianplantsrdquo Archives of Phytopathology and Plant Protection vol 45no 2 pp 152ndash160 2012

[23] S SharmaK LakshmiA Patidar AChaudhary and SDhakerldquoStudies on anti-inflammatory effect of aqueous extract ofleaves of Holoptelea integrifolia Planch in ratsrdquo Indian Journalof Pharmacology vol 41 no 2 pp 87ndash88 2009

[24] Kalpana and A Upadhyay ldquoAnti-inflammatory evaluation ofethanolic extract of leaves of Holoptelea integrifolia PlanchrdquoScholars Research Library vol 1 no 2 pp 185ndash195 2010

[25] D Nadella and P M Paarakh ldquoEvaluation of anthelminticactivity of Holoptelea integrifolia (Roxb) Planchrdquo InternationalJournal of Research in Ayurveda and Pharmacy vol 1 pp 637ndash641 2011

[26] S Kaur B Kumar S Puri P Tiwari and K Divakar ldquoCom-parative study of anthelmintic activity of aqueous and ethanolicextract of bark of Holoptelea integrifoliardquo International Journalof Drug Development and Research vol 2 no 4 pp 758ndash7632010

[27] A Saraswathy D S Nandini and D Ramasamy ldquoAntioxidantheavy metals and elemental analysis of Holoptelea integrifoliaPlanchrdquo Indian Journal of Pharmaceutical Sciences vol 70 no5 pp 683ndash686 2008

[28] J Srivastava K N Dwivedi and H P Pandey ldquoAssessment ofantioxidant activity and total phenolic content of aqueous stembark extract of Holoptelea integrifolia Planchrdquo InternationalJournal of Pharmacy and Pharmaceutical Sciences vol 5 pp357ndash361 2013

[29] M K Mamatha Phytochemical investigation and antidiabeticactivity of Holoptelea integrifolia Planch [MS thesis] KLEUniversity Karnataka India 2009

[30] S Sharma P Khatri A Pandey V Jakhetia L Chaturvediand N Dwivedi ldquoAnti-diabetic screening of leaves extract ofHoloptelea integrifolia Roxbrdquo International Journal of Pharma-ceutical Research and Development vol 2 pp 66ndash71 2010

[31] J Sharma S C Sharma Y S Sarangdevot and B Vyas ldquoStudyof antidiabetic activity of the stem bark extract of Holopteleaintegrifolia (Roxb)rdquo Research Journal of Pharmacology andPharmacodynamics vol 4 pp 181ndash184 2012

[32] S Shrinivas K S Lakshmi and T Rajesh ldquoEvaluation ofantidiarrhoeal potentials of ethanolic extract of leaves ofHoloptelea integrifolia in mice modelrdquo International Journal ofPharmaceutical Research vol 1 no 3 pp 832ndash836 2009


[33] A Panossian G Wikman and H Wagner ldquoPlant adaptogensIII Earlier andmore recent aspects and concepts on their modeof actionrdquo Phytomedicine vol 6 no 4 pp 287ndash300 1999

[34] B Kumar S Puri J Debnath M Salhan M kaur and AMittal ldquoComparative pharmacological evaluation of adapto-genic activity ofHoloptelea integrifolia andWithania somniferardquoInternational Journal of Drug Development and Research vol 3no 1 pp 84ndash98 2011

[35] K S Lakshmi S S Sharma T Rajesh and V Chitra ldquoAnti-tumour activity of ethanolic extract of leaves of Holopteleaintegrifolia on Dalton1015840s ascitic lymphoma in Swiss albino micerdquoInternational Journal of Green Pharmacy vol 4 no 1 pp 44ndash472010

[36] J Soujanya P Silambujanaki and V Leela Krishna ldquoAnticancerefficacy ofHoloptelea integrifolia Planch against 7 12-dimethylbenz(a)anthracene induced breast carcinoma in experimentalratsrdquo International Journal of Pharmacy and PharmaceuticalSciences vol 3 no 5 pp 103ndash106 2011

[37] HGuoD SWang GH Rizwani et al ldquoAntineoplastic activityofHoloptelea integrifolia (Roxb) Planch bark extracts (in vitro)rdquoPakistan Journal of Pharmaceutical Sciences vol 26 pp 1151ndash1156 2013

[38] S C Ramzi K Vinay and R Stanley Pathologic Basis ofDiseases WB Saunders Philadelphia Pa USA 1994

[39] K K Khanna V Mudgal G Shukla and P K ShrivastavldquoUnreported ethnomedicinal uses of plants from Mirazapurdistrict Uttar Pradeshrdquo in Ethnobotany in South Asia J KMahalakshmi Ed Scientific Publishers Jodhpur India 1996

[40] K K Singh and A Prakash ldquoObservation on ethnobotany ofKol tribe of Varanasi district Uttar Pradeshrdquo in Ethnobotanyin South Asia J K Mahalakshmi Ed Scientific PublishersJodhpur India 1996

[41] D K Mishra G Somanta and T K Mishra ldquoEthnomedicineof the tribe Kharia of Midnapore district West Bengalrdquo inEthnobotany in South Asia J K Mahalakshmi Ed ScientificPublishers Jodhpur India 1996

[42] S Pawar and D A Patil ldquoEthnomedicinal uses of barks inJalgaon districtrdquoNatural Product Radiance vol 6 no 4 pp 341ndash346 2007

[43] H Singh Medicinal Plants and Their Local Uses in Sub-Himalayan Tract of Uttaranchal Medicinal Plants Ethnobotan-ical Approach Agrobios Jodhpur India 2006 edited by P CTrivedi

[44] M J Beg M Z Beg and S J Ali Ethnomedicinal Studieson Sub-Himalayan Forest of North Eastern Utter Pradesh inMedicinal Plants Ethnobotanical Approach Agrobios JodhpurIndia 2006 edited by P C Trivedi

[45] K Hemamalini S Suvidha A Bhargav and U VasireddyldquoEvaluation of anti-ulcer activity of methanolic extracts ofKigelia africana Sophara interrupta and Holoptelea integrifolialeaves in experimental ratsrdquo International Journal of CurrentPharmaceutical Research vol 4 pp 16ndash21 2012

[46] G H Rizwani S Mahmud H Shareef R Perveen and MAhmed ldquoAnalgesic activity of various extracts of Holopteleaintegrifolia (Roxb) Planch leavesrdquo Pakistan Journal of Pharma-ceutical Sciences vol 25 pp 629ndash632 2012

[47] K Hemamalini and S B Sathya ldquoHepatoprotective activityof Sophara interrupta and Holoptelea integrifolia against car-bontetrachloride induced hepatotoxicity in ratsrdquo InternationalJournal of Biology Pharmacy and Allied Sciences vol 2 pp 80ndash89 2013

[48] S Singha U Adhikari A Ghosh and G Chandra ldquoMosquitolarvicidal potentiality of Holoptelea integrifolia leaf extractagainst Japanese Encephalitis Vector Culex vishunirdquo Journal ofMosquito Research vol 2 pp 25ndash31 2012

[49] S Shrinivas K Ravindra M Aradhana and B Kailash ldquoEtha-nolic leaf extract of Holoptelea integrifolia Planch decreasescisplatin-induced pica in ratsrdquo Journal of Pharmacognosy vol7 no 16 pp 293ndash297 2008

[50] K Hemamalini L G Soujanya U Vasireedy and P PavanildquoCNS activity of the methanolic leaf extracts of Sophorainterrupta Bedd Kigelia pinnata Dc Holoptelea integrifoliaplants in experimental animal modelsrdquo International Journal ofPharmacy and Technology vol 3 pp 3785ndash3791 2011

[51] A K Subhash and A Augustine ldquoHypolipidaemic effects ofmethanolic extract of Holoptelea integrifolia (Roxb) Planchonbark in diet-induced obese ratsrdquo Applied Biochemistry andBiotechnology vol 169 no 2 pp 546ndash553 2013

[52] S Mahmud H Shareef M Ahmad S Gouhar and G HRizwani ldquoPharmacognostic studies on fresh mature leaves ofHoloptelea integrifolia (ROXB) Planchrdquo Pakistan Journal ofBotany vol 42 no 6 pp 3705ndash3708 2010

[53] S R Kumar C Venkateshwar G Samuel and R S Gan-gadhar ldquoPhytochemical screening of some compounds fromleaf extracts of Holoptelea integrifolia (Planch) and Celestrusemarginata (Grah) used by Gondu tribes at Adilabad districtAndhra Pradesh Indiardquo International Journal of EngineeringScience Invention vol 2 pp 65ndash70 2013

[54] M Ahmed G H Rizwani F V Mohammed I Mahmood VU Ahmed and S Mahmud ldquoTriterpenoid antioxidant agentsfound in Holoptelea integrifolia (Roxb) Planchrdquo InternationalJournal of Pharmaceutical Chemical and Biological Science vol3 pp 63ndash67 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of


StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of



Advances in Pharmacological Sciences

Tropical MedicineJournal of


Medicinal ChemistryInternational Journal of


AddictionJournal of



BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Autoimmune Diseases


Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of


Pharmaceutics


MEDIATORSINFLAMMATION

of


RR

HHH

H

OO

S

R

S

S

SS

RS CH3

CH3

CH3

CH3CH3

CH3

CH3

(CH2)14

3HC

Figure 1 Holoptelin-A

simple ethnobotanical uses and few pharmacological activ-ities of the species Hence an attempt was made to updatethe complete information on botany phytochemistry andpharmacological activities of the species

The information provided was taken from differentsources like worldwide accepted scientific database Scopus(httpwwwscopuscom) Science Direct (httpwwwsci-encedirectcom) PubMed (httpwwwncbinlmnihgovpubmed) Springerlink (httpwwwspringercoin) GoogleScholar (httpscholargooglecoin) and Wiley (httpwwwonlinelibrarywileycom) thesis recognized books abstractsconference proceedings and nonimpact and nonindexedjournals The review highlighted the traditional uses of thespecies in Indian system of medicine (Table 2) secondarymetabolitesphytoconstituents isolated from various partsof the plant (Figures 1ndash10) along with proven biologicalactivity different biological activities reported on variousextracts and fractions of different plant parts (Table 3)The traditional uses reported biologicalpharmacologicalactivity isolated compounds and therapeutic application ofH integrifolia might be useful for scientists and researchersto find out new entities responsible for therapeuticactivity

3 Botany

31 Origin and Distribution The plant species originatedfrom Pacific Islands [3] It is distributed in temperate andtropical areas of northern hemispheres The plant is neu-tralized to the tropical regions of Asia including IndiaNepal Sri Lanka Indo-China Cambodia Laos MyanmarVietnam Burma and China [4] In India it is found inouter Himalayan region from Jammu eastward up to 2000 ftextending to Assam and Burma and in southwards fromBengal to Central Western and South India to dry region ofCeylon

HO

(R)(R)

HH (R)

(R)

(R)H

(S)

(S)(S)

(S)

(S)

CH3CH3

CH3CH3

CH3CH3

CH3CH3

Figure 2 Holoptelin-B

O

(S)HH

H

H

(S)

(R)

(R)(R)

(R)

(S)(S)

(S)

CH3

CH3

CH3

CH3CH3

CH3CH3

CH3

Figure 3 Friedlin

32 Taxonomic Status

Domain EukaryotaKingdom PlantaeDivision Magnoliophyta


(S)HH

H

H

(S)

(R)

(R)

(R)

(S)(S)(S)

(S)

(R)

RO

CH3

CH3CH3

CH3CH3

CH3CH3

CH3


HO

(R)(R) (R)

H

H

(R)

(R)

(R)

H

(S)

(S) (S)

CH3

CH3

CH3CH3

CH3CH3CH3

CH3


H

H

HO

H H


OH


OH


HO

COOH


HO

CH2OH

Figure 10 Betulin

















5 Pharmacology












[44]





[10]




[13]


[14]












Antibacterial






Antifungal





[22]

Anti-inflammatory


Leaves Ethanolic


[24]



Antioxidant


[27]



[28]




[32]


[34]

Anticancer



[36]



[37]


model [20]





Table 3 Continued




[50]


[51]





















50value of only












4








50values gradually









[8]












6 Phytochemistry




7 Conclusion





Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


(S)HH

H

H

(S)

(R)

(R)

(R)

(S)(S)(S)

(S)

(R)

RO

CH3

CH3CH3

CH3CH3

CH3CH3

CH3


HO

(R)(R) (R)

H

H

(R)

(R)

(R)

H

(S)

(S) (S)

CH3

CH3

CH3CH3

CH3CH3CH3

CH3


H

H

HO

H H


OH


OH


HO

COOH


HO

CH2OH

Figure 10 Betulin

















5 Pharmacology












[44]





[10]




[13]


[14]












Antibacterial






Antifungal





[22]

Anti-inflammatory


Leaves Ethanolic


[24]



Antioxidant


[27]



[28]




[32]


[34]

Anticancer



[36]



[37]


model [20]





Table 3 Continued




[50]


[51]





















50value of only












4








50values gradually









[8]












6 Phytochemistry




7 Conclusion





Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of















5 Pharmacology












[44]





[10]




[13]


[14]












Antibacterial






Antifungal





[22]

Anti-inflammatory


Leaves Ethanolic


[24]



Antioxidant


[27]



[28]




[32]


[34]

Anticancer



[36]



[37]


model [20]





Table 3 Continued




[50]


[51]





















50value of only












4








50values gradually









[8]












6 Phytochemistry




7 Conclusion





Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of








[44]





[10]




[13]


[14]












Antibacterial






Antifungal





[22]

Anti-inflammatory


Leaves Ethanolic


[24]



Antioxidant


[27]



[28]




[32]


[34]

Anticancer



[36]



[37]


model [20]





Table 3 Continued




[50]


[51]





















50value of only












4








50values gradually









[8]












6 Phytochemistry




7 Conclusion





Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




Antibacterial






Antifungal





[22]

Anti-inflammatory


Leaves Ethanolic


[24]



Antioxidant


[27]



[28]




[32]


[34]

Anticancer



[36]



[37]


model [20]





Table 3 Continued




[50]


[51]





















50value of only












4








50values gradually









[8]












6 Phytochemistry




7 Conclusion





Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


Table 3 Continued




[50]


[51]





















50value of only












4








50values gradually









[8]












6 Phytochemistry




7 Conclusion





Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of











50value of only












4








50values gradually









[8]












6 Phytochemistry




7 Conclusion





Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of









4








50values gradually









[8]












6 Phytochemistry




7 Conclusion





Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





[8]












6 Phytochemistry




7 Conclusion





Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


Acknowledgment


References




























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




























Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of

Review Article Holoptelea integrifolia (Roxb.) Planch: A...

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Transcript of Review Article Holoptelea integrifolia (Roxb.) Planch: A...