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Journal of Ethnopharmacology 94 (2004) 1–23

Review

Passiflora: a review update

Kamaldeep Dhawana,∗, Sanju Dhawanb, Anupam Sharmaba Department of Drugs Control Administration, Government of Haryana State, Sector-6,

Panchkula 134109, Indiab University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India

Received 26 April 2002; received in revised form 12 February 2004; accepted 23 February 2004

Available online 19 June 2004

Abstract

This review describes the morphology, microscopy, traditional and folklore uses, phyto-constituents, pharmacological reports, clinicalapplications and toxicological reports of the prominent species of the genusPassiflora. Flavonoids, glycosides, alkaloids, phenolic com-pounds and volatile constituents have been reported as the major phyto-constituents of thePassiflora species. A few species ofPassiflorahave been used for curing various ailments, the most important beingPassiflora incarnata Linneaus which possesses significant CNS de-pressant properties. The studies performed by the authors with the newly isolated benzoflavone (BZF) moiety fromP. incarnata have beendiscussed. In the concluding part, various virgin areas of research on the species of this genus have been highlighted with a view to ex-plore, isolate and identify the medicinally important phyto-constituents which could be utilized to alleviate various diseases affecting themankind.© 2004 Elsevier Ireland Ltd. All rights reserved.

Keywords: Passiflora; P. incarnata; Passiflora edulis; Morphology; Flavonoids; Anxiolytics

1. Introduction

The genusPassiflora, comprising about 500 species, is thelargest in family Passifloraceae (the Passion flower family)(Hickey and King, 1988; Maout and Decaisne, 1876; Rendle,1959). The species of this genus are distributed in the warmtemperate and tropical regions of the New World; they aremuch rarer in Asia, Australia, and tropical Africa. Severalspecies are grown in the tropics for their edible fruits, themost widely grown beingPassiflora edulis Sims (Passionfruit or purple granadilla) (McGuire, 1999). Many other aregrown outdoors in the warmer parts of the world or in theglasshouses for their exotic flowers.

2. Botany (morphology and microscopy)

The plants of genusPassiflora are shrubs and herbs,mostly climbers with auxillary tendrils. Stem herbaceous or

∗ Corresponding author. 1068 Sector-38-B, Chandigarh 160038, India.Tel.: +91-172-2691069; fax:+91-172-2582884.

E-mail address: [email protected] (K. Dhawan).

woody, generally climbing, very rarely arborescent. Leavesalternate, sometimes simple, entire, lobed or palmate,sometimes compound, imparipinnate; stipules germinate atthe base of petioles, rarely absent; tendril axillary, arisingfrom sterile pedicels. Flowers bisexual or unisexual, reg-ular. The large receptacle is often hollowed out like a cupor basin, and bears numerous filamentous or annular ap-pendages between the corolla and stamens, which may bebrightly colored and form a conspicuous corona of greatdiversity. Calyx of 3–5 free or basely connate, imbricatesepals. Corolla of 3–5 free or basely connate petals, rarelyabsent. Stamens 3–5 (10) inserted either at the bottom ofthe perianth, or at the base or top of gynophore; filamentssubulate or filiform, free or monoadelphous and sheath-ing the gynophore; anthers versatile, introrse, two-celled,dehiscence longitudinal. Ovary superior, more or less stip-itate, very rarely sessile, unilocular, of 3–5 united carpelscontaining several or many anatropous ovules on parietalplacentas. Styles equal in number to the placentas, coher-ing at the base, distinct at the top, spreading, simple orbranched, or 3–5 separate styles; stigmas clavate or peltate,sometimes sub-two-lobed; ovules numerous, anatropous,1–2 seriate, attached to 3–5 parietal linear placentas by

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2 K. Dhawan et al. / Journal of Ethnopharmacology 94 (2004) 1–23

longer or shorter funicles, enlarged into a cupule at theumbilicus. Fruit 1-celled, an indehiscent berry or a capsulewith 3–5 semi-placentiferous valves. Seeds numerous; fu-nicle dilated into a pulpy cupuliform or saccate aril; testacrustaceous, foveolate, easily separable from the membra-nous endopleura, which bears a longitudinal raphe. Embryostraight, occupying the axis of a fleshy dotted albumen;cotyledons foliaceous, flat; radicle cylindric, near the hilum,centrifugal. Pollination is effected by insects, in the attrac-tion of which the remarkable corona developments playan important part; the flowers are often strongly scentedand nectar is secreted on the receptacle. Extrafloral necto-ries occur on the leaf stalks. The taxonomy, morphology,growth form, site requirements and the related horticultureaspects ofP. incarnata have been extensively reviewed(McGuire, 1999). SincePassiflora is an exotic genus andmany of the species are cultivated for their beautiful orna-mental flowers, the information pertaining to the cultivationand gardening aspects of the Passion flowers can be gath-ered from thePassiflora Society International (Schappert,1999).

The microscopic aspects ofPassiflora were describedfirst by Solereder in 1908 (Solereder, 1908). In his work,it has been observed that there is an absence of anatomicalcharacters distinctive of the genus and common to all itsmembers. It is characteristic of the mature leaves that nospecial type of the arrangement of the neighbouring cellsaround the guard-cells can be detected, i.e., stomata areanomocytic in nature. The leaves of most of the mem-bers of the genusPassiflora are dorsiventral in structure.However,Passiflora mooreana Hook. andPassiflora retic-ulata Engl. have centric or almost centric structure. Themesophyll shows only a few special features. The mid-dle layers of spongy tissues contain thickened and pittedcells; inPassiflora arborea Spreng. andPassiflora citrifoliaMast., numerous spicular cells, with an irregular courseoccur in the mesophyll. The epidermal cells have straightor undulated lateral walls. In many species ofPassiflora,the epidermis of leaf and stem is characterized by cuticu-lar protuberances, whilst in other sections these structuresare only of isolated occurrence, e.g., inPassiflora spinosaMast. The stomata usually occur on the lower side of theleaf. The vascular bundles in the smaller veins are usuallyembedded. They may or may not be accompanied by scle-renchyma. Clusters of calcium oxalate are present in thetissue of the leaf and axis in the form of prisms and clustercrystals. InPassiflora caerulea Linn. spindle shaped bodiesoccur in the mesophyll-cells; these bodies are situated inthe cell-sap, and are probably of the nature of crystalloids.In the epidermis of the leaf ofPassiflora rotundifolia Linn.and Passiflora ichthyura Mast., sphaero-crystalline massesof unknown nature occur. Among internal secretory organsthe most noteworthy are the intercellular, spherical andapparently schizogenous secretory receptacles in the inte-rior of the leaf. The leaf has tanniniferous cells, which incertain species ofPassiflora are developed as tannin-sacs;

these mostly have wide lumina, often have thick walls andare frequently considerably elongated in vertical direction.In the species ofPassiflora both forms of trichomes occur,with walls of varying thickness. In species, viz.,Passifloraclathrata Mast.,Passiflora foetida Linn., Passiflora lepidotaMast. andPassiflora villosa Vell., the glandular trichomeshave a multi-seriate stalk, which is of variable lengthand, when long, sometimes contains a vascular bundle.The glandular head consists of multi-seriate core of elon-gated cells, which, as it were, forms the continuation ofthe stalk, and of a secretory palisade-like epidermis. Inaddition to the glandular trichomes, glandular spots arealso seen on the lower side of the leaf in some speciesof Passiflora. In a superficial section radially elongatedepidermal cells are observed at the periphery of the glan-dular spots; nearer the center these are adjoined by cells,the walls of which become more and more thickened andtheir luminae narrower, so that the actual glandular spotis enclosed by a rampart of thick-walled cells. These cellsthen pass over into the secretory tissue, the cells of whichhave a polygonal outline in the surface-view, but are seento be moderately elongated in a transverse section of theleaf. Several layers of these prismatic cells lie one aboveanother; finally, towards the interior of the leaf, they mergeinto a small-celled tissue filled with cluster crystals. Thelarge sessile or shortly stalked glands, which occur so fre-quently on the petioles, are merely a modification of theseglandular spots. The axis, even in the climbing forms, hasa normal structure. The formation of cork usually takesplace superficially, in the epidermis or in the subepidermallayer of cells. Transformation of the outermost layer ofcortical cells into the cork-cambium occurs in most speciesof Passiflora. The cork cells have thin walls. The spongycork of Passiflora suberosa Linn. consists of cells, whichare strongly elongated radially and are not suberized. Theprimary cortex frequently contains collenchymatous tissue.The pericycle includes isolated groups of bast-fibres or asclerenchymatous ring. Isolated groups of bast-fibres oc-cur in species ofPassiflora. The strongly thickened wallsof bast-fibres inPassiflora acerifolia Cham. et Schlecht.and Passiflora pulchella H.B.K. become violet on treat-ing a transverse section with chlor–zinc–iodine solution,while the network of middle-lamellae is stained yellow-ish. The wood ofPassiflora species is characterized byvariable breadth of medullary rays. Broad medullary raysoccur both in climbing species and in those which donot climb (Passiflora arborea Spruce). In the genusPas-siflora, which climbs by means of tendrils, especially inPassiflora spicata Mart., the diameter of vessels attains0.22 mm. The structure of the wall of the vessel, whereit is in contact with the parenchyma of the medullaryrays, varies. Wood parenchyma is scantily developed; thewood-prosenchyma may have either distinctly borderedor simple pits. The wood-prosenchyma with simple pitsis occasionally septate by means of delicate division-walls.

K. Dhawan et al. / Journal of Ethnopharmacology 94 (2004) 1–23 3

The British Herbal Pharmacopoeia (1983), UnitedStates Homoeopathic Pharmacopoeia 1981, Homoeo-pathic Pharmacopoeia of India 1974, PharmacopoeiaHelvetica 1987, Deutsches Arzneibuch 1997 Home-opathie 1981, Pharmacopee Francaise (1965)and manyof the herbal compendiums and Materia Medica con-tain monographs of only one species, i.e.,P. incarnataLinn. This species is also known by various other com-mon names, viz., Maypop, Maracuja, Passion Vine, Cark-ifelek, Zahril Aalaam and Prempushpi. However, in thePharmacopoeia of Brazil,Passiflora alata Dryand. isreported as the Passion flower instead ofP. incarnata(Farmacopeia Brasileira, 1959). The microscopic char-acteristics of leaf ofP. incarnata are also described inthe British Herbal Pharmacopoeia, 1983(British HerbalPharmacopoeia, 1983) and theDeutsches Arzneibuch 1997(DAB, 1997).

3. Ethno-pharmacology

The discovery of several thousands years old seeds ofPas-siflora from the archaeological sites at Virginia and NorthAmerica provides strong evidences of the pre-historic useof the fruits by the ancient ‘Red Indian’ people (Gremillion,1989). The early European travelers in North America notedthat Algonkian Indians in Virginia and Creek people inFlorida ate fruits ofPassiflora from cultivated as well as wildsources (Beverley, 1947). The then European settlers alsoconsumed the fruit and praised its flavor, thereby, suggest-ing the pre-historic consumption ofPassiflora as a fruit crop(Brickell, 1968). The use ofPassiflora as a medicine waslauded for the first time by a Spanish researcher Monardus inPeru in 1569 as the beautiful flowers ofPassiflora appearedto him to be symbolic of the passion of Christ (Taylor,1996). Various species ofPassiflora have been used exten-sively in the traditional system of therapeutics in many coun-tries. The extract ofPassiflora alata (fragrant granadilla)with aloes was reputed beneficial in atrophy of various parts(Felter and Lloyd, 1983). In Brazil, the said species, knownas ‘Maracuja’ has been put to use as an anxiolytic, seda-tive, diuretic and an analgesic (Oga et al., 1984). Passifloracaerulea (blue Passion flower), native of Brazil and intro-duced into Britain in 17th century, is the most vigorous andtender species having traditional use of its fruit as a seda-tive and anxiolytic (Hickey and King, 1988; Kirtikar andBasu, 1975; Rendle, 1959). Passiflora caerulea was usedmedicinally in Uruguay but no details are available (Wattand Breyer-Brandwijk, 1962). In West Indies, Mexico, theNetherlands and South America, the root has been used asa sedative and vermifuge. In Italy, the plant has been usedas an anti-spasmodic and sedative. In Mauritius, a tinctureand an extract of the plant had been used as a remedy forinsomnia due to various nervous conditions but not due to

pain. The root has been used as a diuretic and a decoctionof leaf as an emetic. In Argentine folk medicine, the aerialparts ofPassiflora caerulea are used as mild anti-microbialagents in diseases like catarrh and pneumonia (Anesini andPerez, 1993). Passiflora capsularis is a reputed emmena-gogue (Felter and Lloyd, 1983). Passiflora contrayerva is areputed counter-poison, deobstruent and cordial (Felter andLloyd, 1983). Passiflora edulis has been used as a sedative,diuretic, anthelmintic, anti-diarrheal, stimulant, tonic andalso in the treatment of hypertension, menopausal symp-toms, colic of infants in South America (Chopra et al.,1956; Kirtikar and Basu, 1975; Mowrey, 1993). In Madeire,the fruit of Passiflora edulis is regarded as a digestivestimulant and is used as a remedy for gastric carcinoma(Watt and Breyer-Brandwijk, 1962). In Nagaland (India),fresh leaves ofPassiflora edulis are boiled in little amountof water and the extract is drunk for the treatment ofdysentery and hypertension (Jamir et al., 1999). Fruits areeaten to get relief from constipation.Passiflora foetida leafinfusion has been used to treat hysteria and insomnia inNigeria (Nwosu, 1999). The plant is widely cultivated inIndia (Kirtikar and Basu, 1975). The leaves are applied onthe head for giddiness and headache; a decoction is givenin bilious-ness and asthma. The fruit is used as an emetic.In La Reunion, the leaves are considered emmenagogueand are also prescribed in hysteria. In Brazil, the herb isused in the form of lotions or poultices for erysipelas,and skin diseases with inflammation (Chopra et al., 1944).The Materia Medica Americana, a Latin work, publishedin Germany in 1787, mentions the use ofP. incarnata totreat epilepsy of the aged. An ancient report describes theuse of this plant in spasmodic disorders and insomnia ofinfants and the old (Bartram, 1995; CSIR, 1966a,b). Pas-siflora incarnata is a popular traditional European remedy(Handler, 1962) as well as a homoeopathic medicine(Rawat, 1987) for insomnia, anxiety, and has been used asa sedative tea in North America (Bergner, 1995). The planthas been used as analgesic, anti-spasmodic, anti-asthmatic,wormicidal and sedative in Brazil; as sedative and nar-cotic in Iraq; in diseased conditions like dysmenorrhea,epilepsy, insomnia, neurosis and neuralgia in Turkey; tocure hysteria and neurasthenia in Poland; in diarrhea, dys-menorrhea, neuralgia, burns, hemorrhoids and insomniain America (Taylor, 1996). P. incarnata has been usedfor morphine deaddiction in the traditional system ofmedicine in India (Lad, 2000; Vasudev, 1955). Passifloralaurifolia Linn. (yellow granadilla, Jamaica honeysuckle)is used to treat nervous heart palpitations in Trinidad(Raintree Nutrition, 1999). The juice of Passiflora mal-iformis Linn. is used for intermittent fevers in Brazil.Passiflora quadrangularis Linn. (giant granadilla) is usedthroughout the Caribbean as a sedative and for headaches.Leaf tea is taken for high blood pressure and diabetes(Seaforth et al., 1983). In Mauritius and Rodrigues, bath


of leaf-docoction ofPassiflora suberosa is used to treatskin diseases. Root decoction is used as an emmenagogneand is useful in hysteria (Fakim et al., 1993). In Cen-tral America, stems ofPassiflora pedunculata Mast., theaerial parts ofPassiflora sexflora Juss. andPassiflora vi-tifolia HBK have been used against snakebites (Morton,1981).

In view of the wide-spread traditional and ethno-pharma-cological reports on the members of genusPassiflora, a re-view of literature on the specific species ofPassiflora can bea sterling stuff which could glorify the magical healing po-tentials of the phyto-constituents reported from this genus;perhaps one of the oldest being put to use by the mankindduring the processes of scientific advancements towards there-exploration of our traditional heritages.

4. Phyto-constituents

Alkaloids, phenols, glycosyl flavonoids and cyanogeniccompounds are known in the genus. Literature survey hasrevealed that a number of reports are available onPassi-flora incarnata and Passiflora edulis, while only sporadicreports are there on other species ofPassiflora. Thus,Pas-siflora incarnata andPassiflora edulis have been dealt withas separate heads in the following passages, and the remain-ing species ofPassiflora have been presented in a tabularform.

4.1. Phyto-constituents of P. incarnata

4.1.1. FlavonoidsFlavonoids are reported to be the major phyto-constituents

of P. incarnata. These include apigenin (1), luteolin(2), quercetin (3), kaempferol (4) (Gavasheli et al.,1974), 6-�-d-allopyranosyl-8-�-xylopyranosyl-apigenin(Grandolini et al., 1997); C-glycosyl flavonoids vitexin(5), isovitexin (6) (Lutomski et al., 1981), orientin (7),isoorientin (8), schaftoside (9), isoschaftoside, isovitexin-2′′-O-glucopyranoside, isoorientin-2′′-O-gluco-pyranoside,2-glucosylapigenin, isoscoparin-2′′-O-glucoside, 2′′-O-glucosyl-6-C-glucosylapigenin, 6-�-d-glucopyranosyl-8-�-d-ribopyranosyl apigenin and swertisin (Chimichi et al.,1998; Congora et al., 1986; Geiger and Markham, 1986;Li et al., 1991; Proliac and Raynaud, 1988; Rahman et al.,1997). The greatest accumulation of flavonoids has beenreported to be in leaves and the highest concentration ofisovitexin was found to be between the pre-flowering andflowering stages (Menghini et al., 1993). During variousquantitative studies, it was observed that the ethanol freeliquid extract of P. incarnata contains higher contents offlavonoids as compared to the commercial preparations.Amongst various other species of the genus,Passiflora in-carnata contains highest content of isovitexin (Menghiniet al., 1993).

4.1.2. AlkaloidsP. incarnata contains simple indole alkaloids based on

�-carboline ring system namely harman (10), harmol (11),harmine (12), harmalol (13) and harmaline (14) (Poethkeet al., 1970). Content of harman (10) and harmine (12),determined by direct spectrofluorimetric methods on TLCplates, has been reported to be 10–20�g/100 ml in themedicinal fluid extract ofP. incarnata (Bennati, 1971).Recently, all types of�-carboline alkaloids have beenanalyzed quantitatively by HPLC with selective fluoro-metric detection (Tsuchiya et al., 1999). The vegetativeparts of green house grownP. incarnata contain 0.012and 0.007% of harman (10) and harmine (12), respec-tively, while the content of these alkaloids in the plantgrown in fields has been reported as 0.005% and nil,respectively (Lohdefink and Kating, 1974; Lutomskiand Nourcka, 1968; Rehwald et al., 1995).


4.1.3. Miscellaneous phyto-constituentsVarious other constituents which have been reported

from P. incarnata include�-benzo-pyrone derivative maltol(15) (Aoyagi et al., 1974), carbohydrates such as raffi-nose, sucrose,d-glucose andd-fructose (Gavasheli et al.,1975); essential oil containing hexanol (1.4%), benzylalcohol (4.1%), linalool (3.2%), 2-phenylethyl alcohol(1.2%), 2-hydroxy benzoic acid methyl ester (1.3%),carvone (8.1%), trans-anethol (2.6%), eugenol (1.8%),isoeugenol (1.6%),�-ionone (2.6%),�-bergamotol (1.7%)and phytol (1.9%) (Buchbauer and Jirovetz, 1992); vari-ous constituents responsible for typical odor ofPassifloraincarnata such as limonene, cumene,�-pinene, prez-izaene, zizaene, and zizanene (Buchbauer et al., 1992);twenty one amino acids (Gavasheli et al., 1974), and acyanogenic glycoside gynocardin (16) (Spencer and Seigler,1984).

4.2. Phyto-constituents of Passiflora edulis

4.2.1. GlycosidesFrom the methanol extract of air dried leaves, a cy-

clopropane triterpine glycoside, named Passiflorine (17)was isolated, chemically which was reported to be(22R),(24S)-22,28-epoxy-24-methyl-1�,3�,24,28-tetrahy-droxy-9,19-cyclo-9�-lanostan-4-oic acid �-d-glucosylester (Bombardelli et al., 1975). Passiflora edulis hasbeen reported to be rich in glycosides which includeflavonoid glycosides, viz., luteolin-6-C-chinovoside,luteolin-6-C-fucoside (Mareck et al., 1991); cyclopen-tenoid cyanohydrin glycosides passicapsin (18) and pas-sibiflorin (19) (Olafsdottir et al., 1989); cyanogenic gly-cosides passicoriacin (20), epipassicoriacin and epitet-raphyllin B (Seigler and Spencer, 1989) cyanogenic-�-rutinoside {(R)–mandelonitrile-�-l-rhamnopyranosyl-�-d-glucopyranoside} (21) (Chassagne and Crouzet, 1998)amygdalin (22), prunasin, mandelonitrile rhamnopyranosyl-�−d-glucopyranoside, sambunigrin (Chassagne et al.,1996); 6-O-�-l-arabinopyranosyl-�-d-glucopyranosidesof linalool, benzyl alcohol and 3 methyl-but-2en-1-ol(Chassagne et al., 1996); �-d-glucopyranoside and 6-O-�-l-rhamnopyranosyl-�-d-glucopyranoside of methyl salicy-late and�-d-glucopyranoside of eugenol (Chassagne et al.,1997).


4.2.2. Phenols4-Hydroxy-�-ionol, 4-oxo-�-ionol, 4-hydroxy-7,8-

dihydro-�-ionol, 4-oxo-7,8-dihydro-�-ionol, 3-oxo-�-ionol,isomeric 3-oxo retro-�-ionols, 3-oxo-7,8-dihydro-�-ionol,3-hydroxy-1,1,6 - trimethyl - 1,2,3,4- tetrahydronaphthalenevomifoliol and dehydrovomifoliol (Winterhalter, 1990),terpene alcohols linalool and�-terpeneol (Challier et al.,1990), terpene diols (E) and (Z)-2,6-dimethyl-octa-2,7-diene-1,6-diol, 2,6-dimethyl-octa-3,7-dien-2,6-diol, 2,6-dimethyl-1,8-octanediol, 2,6-dimethyl-octa-1,7-diene-3,6-diol, ionol derivatives oxygenated in position 3, and 2,5-dimethyl-4-hydroxy-3-(2H)-furanone (furaneol) have beenidentified (Chassagne et al., 1999). Two new ionones I andII were isolated (23, 24) (Naf et al., 1977) for the first timefrom Passiflora edulis.

4.2.3. AlkaloidsThe alkaloids reported to be present are harman (10),

harmine (12), harmaline (13) and harmalol (14) and the high-est concentration (0.12 mg%) of harman alkaloids is presentin the leaves (Lutomski and Malek, 1975; Lutomski et al.,1975).

4.2.4. Miscellaneous phyto-constituentsApart from glycosides, phenols and alkaloids, various

miscellaneous phyto-constituents reported fromPassifloraedulis include:

• Carotenoids: phytoene, phytofluene,�-carotene, neu-rosporene,�-carotene, lycopene, prolycopene, monoe-poxy-�-carotene,�-cryptoxanthin, �-citraurin, anther-axanthin, violaxanthin, neoxanthin (Mercadente et al.,1998), �-carotene,�-carotene,�-cryptoxanthin,�-apo-carotenol (Goday and Rodriguez, 1994).

• l-ascorbic acid (Wekesa et al., 1996).• Anthocyanins: cyanidin-3-O-�-glucopyranoside and

cyanidin-3-O-�-galactopyranoside (Chang and Su, 1998),cyanidin-3-glucoside, cyanidin-3-6′′-malonyl glucoside,pelargonidine-3-glucoside (Kidoey et al., 1997).

• γ-Lactones: �-hexa, �-deca and�-docecalacetone;�-hepta,�-octa and�-nona lactone (Nitz et al., 1990), fouralkylated�-lactones (Bernreuther et al., 1989).

• Flavor components: esters (Yamaguchi et al., 1983), 3-methyl-thiohexan-1-ol, 2-methyl-4-propyl-1, 3-oxathioneenantiomers (Mosandl and Heusinger, 1983), edulans Iand II (25, 26) (Whitfield et al., 1974).

• Volatile oil constituents: hexyl caproate and butyrate,and ethyl caproate and butyrate (95%) (Dawes and

Paul, 1961), limonene (Kuhlmann, 1984), 2-tridecanone(62.9%), (9Z)-octadecenoic acid (16.6%), 2-pentadecanone(6.2%), hexadecanoic acid (3.2%), 2-tridecanol (2.1%),octadecanoic acid (2%) and caryophyllene oxide (2%)(Arriaza et al., 1997).

• Amino acids: proline, aspartic acid, glutamic acid, serine,alanine (Fang and Ling, 1984).

• Carbohydrates: fructose, glucose, sucrose, maltose, lac-tose (Fang and Chang, 1981) and pectin (Simpson et al.,1984).

• Minerals: Na, K, Mg, Ca, Zn, Al, Mn, Fe (Nogueira et al.,1998).

• Enzyme cytoplasmic pyruvate kinase (Guo and Li, 1993).• Cycloartane triterpenes, cyclopassifloic acids A–D, and

their saponins, cyclopassiflosides I–VI (Yoshikawa et al.,2000), from the leaves and stems ofPassiflora edulis,which on further purification by silica-gel chromatogra-phy gave cyclopassifloic acids E–G and their saponins,cyclopassiflosides VII–XI (27), respectively (Yoshikawaet al., 2000).

5. Other Passiflora species and their phyto-constituents

Table 1 summarizes the phyto-constituents of variousother species ofPassiflora. The species have been arrangedin alphabetical order.


6. Pharmacological reports

Irrespective of the presence of a large variety of phyto-constituents in the genusPassiflora, only a few reportsregarding the pharmacological investigations on the plantsof this genus are available. Most of the pharmacologicalwork has been carried out on the CNS depressant effectsof various species. A group of Brazilian researchers haveperformed thorough pharmacological studies onPassifloraalata leaves using mice as the experimental animals (Ogaet al., 1984). The fluid extract from leaves ofPassifloraalata prepared according to the procedures described inthe French Pharmacopoeia, VIII edition (Pharmacopee

Francaise, 1965) was evaporated under reduced pressure at50◦C to yield a dry extract, which was further dissolvedin water for pharmacological studies. On intraperitoneal ad-ministration to mice at a dose of 150 mg/kg, thePassi-flora alata extract reduced amphetamine-induced sponta-neous motor activity, prolonged pentobarbital induced sleeptime at 150 mg/kg i.p., increased the onset time and survivalperiod on pentylenetetrazole-induced-seizures in the animalsat 75 and 150 mg/kg and also potentiated the analgesic effectat 75 and 150 mg/kg of the extract relative to indoprofen asa reference standard analgesic; all the pharmacological ef-fects being observed in dose-dependent manner. The LD50value of this extract was 456 mg/kg. Recently, the hydro-


Table 1Phyto-constituents of variousPassiflora species

Species Phyto-constituents

Passiflora adenopoda Moc. & Sesse Cyanogenic glycosides linamarin (28), lotaustralian (29) (Spencer et al., 1986)Passiflora alata Dryand. C-glycosyl flavonoids 2′′-xylosylvitexin and small amount of vitexin (5), isovitexin (6) and orientin (7)

(Ulubelen et al., 1982)Passiflora ambigua Linn. Flavonoid saponarin (Ulubelen et al., 1982)Passiflora apetala Linn. Cyanogenic glycoside Passibiflorin (19) (Olafsdottir et al., 1997)Passiflora biflora Domb. O- and C-glycosylflavones; 4′-O-rhamnosylswertisin, luteolin-7-O-neohesperidoside together with swertisin,

swertiajaponin, 4′-O-rhamnosyl-swertiajaponin, 2′′-O-rhamnosylisoorientin and 2′′-O-rhamnosylisovitexin(McCormick and Mabry, 1983); cyanogenic glycosides passibiflorin (19) and epipassibiflorin (Spencer andSeigler, 1985)

Passiflora bryonioides H.B.K. Flavone derivatives saponaretin, vitexin, apigenin-7-monoglucoside and two kaempferol-3-biosides (Poethkeet al., 1970)Alkaloid harman (10) (Poethke et al., 1970)

Passiflora caerulea Linn. A flavone chrysin (Speroni et al., 1996), cyanogenic glycoside sulphate tetraphyllin B-4-sulphate andepitetraphyllin B-4-sulphate (Seigler et al., 1982)

Passiflora calcarata Mast. Passiflorine (17) (Bombardelli et al., 1975)Passiflora capsularis Lam. Passicapsin (18); Cyanogenic bisglycoside 4-bi-vinosyltetraphyllin B (Fischer et al., 1982)Passiflora coactilis Linn. C-glycosyl flavones 4′-O-glucosyl-2′′-O-rhamnosyl orientin, 4′-O-glucosyl-2′′-O-rhamnosyl-vitexin, vitexin,

4′-O-glucosylvitexin, isovitexin (6), isoorientin (8), 4′-O-glucosyl orientin, 2′′-O-rhamnosyl orientin,scoparin, 2′′-O-rhamnosyl scoparin and 8-C-glucosyl-diosmetin (Escobar et al., 1983)

Passiflora coccinea Aubl. Cyanogenic glycoside passicoccin (30) (Spencer and Seigler, 1985)Passiflora cochinchinensis Spreng. Flavonoids naringin and apigenin-7-O-glucoside; Amino acids; Carbohydrates (Ma et al., 1982)Passiflora colinvauxii Linn. Cyanogenic glycoside passibiflorin (19) (Adsersen et al., 1993)Passiflora coriacea Fuss. Cyanogenic glycoside barterin (31) (Olafsdottir et al., 1989)Passiflora cyanea Mast. C-glycosyl flavonoid 2′′-xylosylvitexin and coumarin esculetin (Ulubelen et al., 1981)

Passiflora foetida Linn. Flavonoids pachypodol, 7,4′-dimethoxyapigenin, ermanin (32), 4′,7-O-dimethyl-naringenin,3,5-dihydroxy-4,7-dimethoxy flavanone (Echeverri and Suarez, 1985; Echeverri and Suarez, 1989)C-glycosyl flavonoids chrysoeriol, apigenin (1), isovitexin (6), vitexin (5), 2′′-xylosylvitexin, luteolin-7-�-d-glucoside, kaempferol (4) (Ulubelen et al., 1982); Cyanohydrin glycosides tetraphyllin A (33), tetraphyllin B(34), tetraphyllin B sulphate, deidaclin (35), volkenin (36) (Andersen et al., 1998); Fatty acids linoleic acidand linolenic acid (Hasan et al., 1980); alpha-pyrones named passifloricins (Echeverri et al., 2001)

Passiflora hybrida Nees A sulphate ester of tetraphyllin B (Jaroszewski and Fog, 1989)Passiflora indecora H.B.K. Cyanogenic glycoside passibiflorin (19) (Olafsdottir et al., 1997)Passiflora laurifolia Linn. Pantothenic acid, ascorbic acid (CSIR, 1966b)Passiflora lechenaultii DC Passiflorine (17) (Bombardelli et al., 1975)Passiflora lutea Linn. Cyanogenic glycosides linamarin (28), lotaustralin (29) and passibiflorin (19) (Spencer and Seigler, 1985)Passiflora menispermifolia H.B.K. Flavonoids vitexin (5), orientin (7), 6-hydroxy luteolin 6,7-dimethyl ether and luteolin-7-�-d-glycoside;

Coumarin esculetin (Ulubelen et al., 1981)Passiflora molliseria DC Ascorbic acid (Uzcategui, 1985)Passiflora mollissima Bayley Passiflorine (17); Volatile constituents: 30 alkane, alkene, aromatic and terpene hydrocarbons; 4 aldehydes;

11 ketones; 36 alcohols; 4 lactones, 5 fatty acids; 47 esters (Froehlich et al., 1989)Passiflora morifolia Mast. Cyanohydrin glucoside linamarin (28) (Olafsdottir et al., 1992)Passiflora oerstedii Mast. C-glycosyl flavonoid 2′′-xylosylvitexin; Sterols�-sitosterol and its 3−�-d-glucoside; Sugars–glucose,

fructose, galactose (Ulubelen et al., 1981)Passiflora palmeri Linn. Flavonoids quercetin-7, 3′-dimethyl ether, isoscoparin, isovitexin, apigenin-7-glucoside, vitexin (5),

chrysoeriol, isoscutellarein-8-methyl ether, quercetin (3), isorhamnetin, luteolin (2), isoorientin (8),luteolin-7-glucoside, selagin, 6-methoxy kaempferol, vicenin-2, 2′′-O-glucosyl vitexin, 2′′-O-rhamnosylvitexin and a flavone tricetin 4-methyl ether (Ulubelen et al., 1984)

Passiflora pavonis Mast. C-glycosyl flavones isovitexin (6), isoorientin (8), isoorientin-4′-�-d-glucoside, luteolin-7-�-d-glucoside(McCormick and Mabry, 1981)

Passiflora pendens Linn. Linamarin (28), lotaustralian (29), linustatin (37) and neolinustatin (38) (Spencer et al., 1986)Passiflora pittieri C-glycosyl flavonoids isovitexin, 2”-xylosyl vitexin, a mixture of vicenin-2, schaftoside (9) and

isoschaftoside, luteolin-7-O-glucoside and chlorgenic acid (Ulubelen et al., 1982)Passiflora platyloba Fuss. C-glycosides vitexin (5), isovitexin (6), isomollupentin (6-C-arabinosyl-apigenin),

isovitexin-7-rhamnosylglucoside and isomollupentin-7-rhamnosylglucoside (Ayanoglu et al., 1982)Passiflora quadrangularis Linn. Passiflorine (17) (Bombardelli et al., 1975); Triterpene glycoside quadranguloside (39) (Orsini et al., 1986),

oleanolic acid-3-sophoroside (Orsini et al., 1987)Monoterpenoids: (2E)-2,6-dimethyl-2,5 heptadienoic acid, (2E)-2,6 dimethyl-2,5 hepta dienoicacid-�-d-glucopyranosyl ester, (5E)-2,6-dimethyl-5,7-octadiene-2,3-diol and (3E)-3,7dimethyl-3-octene-1,2,6,7-tetrol (Osorio et al., 2000)

Passiflora racemosa Brot. Sulphate ester of tetraphyllin B (Jaroszewski and Fog, 1989)Passiflora sanguinolenta Mast& Linden Flavonoids isovitexin, luteolin-7-O-glucoside and 7-O-galactoside, xylosyl vitexin, apigenin (1),

apigenin-7-O-glucoside and luteolin (2) (Ulubelen and Mabry, 1983)


Table 1 (Continued )

Species Phyto-constituents

Passiflora serratifolia Linn. C-glycosyl flavonoids vitexin (5), isovitexin (6), orientin (7), 2′′-xylosyl vitexin and 2′′-xylosyl isovitexin(Ulubelen and Mabry, 1980)

Passiflora serratodigitata Linn. Serratin I (40) and its 7-�-glucoside; C-glycosylflavone 2′′-xylosylvitexin, 2′′-xylosylisovitexin, vitexin (5),isoorientin (8), vicenin and orientin (7) (Ulubelen et al., 1982)

Passiflora sexflora Fuss. Flavonoids 6-di-C-glycosylflavones, 6-mono-C-glycosylflavones, luteolin-7-O-glucoside, luteolin (2)(McCormick and Mabry, 1982)

Passiflora suberosa Linn. Cyanogenic glycosides passisuberosin (41), epipassisuberosin (Spencer and Seigler, 1987); Anthocyaninscyanidin-3-(6′′-malonylglucoside), 3-glucoside of cyanidin, delphinidin, petunidin, pelargonidin andanthocyanin acetylated with malonic acid (Kidoey et al., 1997)

Passiflora subpeltata Orteg. Cyanogenic glycoside barterin (31) (Olafsdottir et al., 1989)Passiflora talamansis Cyanogenic glycosides passibiflorin (19) and epipassibiflorin (Spencer and Seigler, 1985)Passiflora tetrandra Banks & Soland. 4-Hydroxy-2-cyclopentenone (Perry et al., 1991)Passiflora trifasciata Lem. Cyanogenic glycoside Passitrifasciatin (42) (Olafsdottir et al., 1991; Spencer and Seigler, 1985)Passiflora trinervia Poir. Flavonoids vitexin (5), isovitexin (6), luteolin-7-O-galactoside, esculetin, isoorientin (8) (Ulubelen and

Mabry, 1983)Passiflora vespertilio Ker-Gawl. Cyanohydrin glycosides passibiflorin (19) (Olafsdottir et al., 1997)Passiflora violacea Vell. Cyanohydrin glycoside linamarin (28) (Olafsdottir et al., 1988)Passiflora warmingii Mast. Cyanogenic glycosides linamarin (28), linustatin (21) (Fischer et al., 1982; Spencer et al., 1986);

Cyanohydrin glycoside barterin (31) (Olafsdottir et al., 1989)

ethanol extract of leaves ofPassiflora alata andPassifloraedulis have been evaluated at three dose levels (50, 100 and150 mg/kg) to confirm the anxiolytic effects in accordancewith the traditional reports of these two species, known as‘maracuja’ in Brazil (Petry et al., 2001).

The pharmacological effects of chrysin, a monoflavonoid,occurring in Passiflora caerulea were examined in mice(Wolfman et al., 1994). Chrysin, at a dose of 1 mg/kg in-duced significant anxiolytic behavior in mice by increasingthe number of entries as well as the time spent by mice inopen arms of the elevated plus maze apparatus. During acomparison between diazepam (6 mg/kg) and chrysin fortheir myorelaxant effects, chrysin did not exhibit myorelax-ant effect in the horizontal wire test even at the dose rangeof 0.6–30 mg/kg, suggesting that chrysin was an anxiolyticdevoid of sedative or muscle relaxant counter effects, un-like that of diazepam which exhibited a myorelaxant effect.Chrysin, a naturally occuring monoflavonoid inPassifloracaerulea was found to be a ligand for central as well asperipheral benzodiazepine receptors (Medina et al., 1990).When administered to mice by intracerebroventricular route,chrysin prevented the expression of tonic–clonic seizersinduced by pentylenetetrazole, also confirming thereby thepresence of benzodiazepine-like compounds inPassifloracaerulea. Aqueous extract ofPassiflora edulis has beenreported to exhibit non specific CNS depressant effects inmice, rats and healthy human volunteers, whereas, it wasalso noted that some samples ofPassiflora edulis had a“non-specific” CNS-depressant effect (Maluf et al., 1991).In another report on CNS depressant effects ofPassi-flora edulis, it was noted that the aqueous extract of theplant prolonged barbiturate-induced as well as morphine-induced sleep time in mice and also “partially” blocked theamphetamine-induced stimulant effects (Do et al., 1983).

Extract of Passiflora edulis has exhibited mild anti-fungalactivity against Microsporum gypseum, Chrysosporiumtropicum andTrichophyton terrestre (Qureshi et al., 1997).

Authors opine that the only one species, i.e.,Passiflora in-carnata also known as Passion flower, maypops, maracuja or‘prem-pushpi’ is perhaps, the one in the entire genus whichhas been used extensively as an anxiolytic and sedativethroughout the world since time immemorial. That is why,P.incarnata deserves to be described, identified and exploredproperly. In this part of the review, the maximum possiblepharmacological informations on this particular species hasbeen compiled. Maltol (15), a�-benzopyrone derivative, andethyl maltol were evaluated for their CNS-depressant effects(Aoyagi et al., 1974). Maltol and ethyl maltol, obtained bysublimation of 2N hydrochloric acid fraction ofP. incar-nata were reported to potentiate hexobarbital-induced sleep,inhibit pentylenetetrazole-induced convulsions and also de-creased amphetamine-induced hyperactivity in mice. Ethylmaltol was reported to be more potent as an anti-convulsantthan maltol, but comparatively less potent in decreasing thespontaneous motor-activity. The fluid extract ofPassifloraincarnata was studied for its neuropharmacolo-gical effectson rats (Speroni and Minghetti, 1988). The ethanolic extractfrom leaves and stems ofP. incarnata having a water con-tent of about 50%, was evaporated under reduced pressureat 45◦C to remove ethanol. Then water was added to reachhalf the volume of fluid extract at the start and the pH of thisaqueous solution was adjusted to 5.6. This solution was thenfreeze-dried and suspended in saline for pharmacologicalevaluations. On intraperitoneal injection, the extract signifi-cantly prolonged sleeping time at 80 and 160 mg/kg in mice,protected animals from convulsive effects of pentylenetetra-zole by causing an increase in the onset time and survivaltime in the PTZ-treated mice, decreased the amphetamine-


induced locomotor activity in a dose-dependent manner andalso increased the tail-flick latency in rats at 160 mg/kgdoses. However, the CNS depressant effect could not be as-cribed either to alkaloids or flavonoids present in the ex-tract. Lyophilized hydroalcoholic and aqueous extracts ofP.incarnata as well as the individual phyto-constituents viz.,maltol (15), flavonoids and harman (10–14) alkaloids wereassessed for their effects in mice (Soulimani et al., 1997).Fresh aerial parts ofP. incarnata were preserved in liquidnitrogen and ground at a low temperature (60◦C) to ob-tain a cryo-grinding. Thirty grams of the cryo-ground pow-der were added to 300 ml of (30%) ethanol and were leftto macerate for 12 h; a second maceration was performedat 35◦C for 12 h. After filteration, ethanol was evaporatedat low pressure at 35◦C and the extract was freeze-dried.An aqueous extract (10%, w/w) was prepared according tothe protocols described above, but ethanol was replaced bydistilled water. The aqueous extract showed sedative effectsat doses of 400 and 800 mg/kg, by decreasing the locomo-tor activity and also potentiated the induction of sleeping bypentobarbital in mice. The hydro-alcoholic extract did notshow such sedative effect. Instead, it enhanced locomotoractivity, suggestive of an anxiolytic effect at 400 mg/kg inmice. Though, these investigations confirmed the CNS de-pressant properties ofP. incarnata, yet, the exact mode ofaction of the extracts and the individual phyto-constituentscould not be understood in this extensive pharmacologicalexperimental study conducted by Soulimani et al. The recentpharmacological studies conducted by Zanoli et al. (Zanoliet al., 2000) have attributed the biological effects ofP. in-carnata to a flavonoid chrysin. Though, in these studies,the said authors have evaluated the flavonoid chrysin forits anxiolytic and sedative properties, it was not made clearwhether chrysin was isolated from the plant prior to attribut-ing the biological effects ofPassiflora incarnata to chrysinonly. In these studies, chrysin, when administered at a doseof 50 mg/kg in rats intra-peritonially, did not influence thepentobarbital-induced sleeping time in rats, decreased thelocomotor activity at 25 mg/kg and also exhibited anxiolyticactivity at a dose of 1 mg/kg which was manifested by theincreased latent-time spent in the light-dark compartmentmodel of anxiety.

During the exhaustive pharmacognostic and biologicalstudies on a few important plants of the genusPassiflora,authors have reported novel findings onP. incarnata whichmay throw some light over the earlier inconclusive andslightly contradictory reports onP. incarnata andPassifloraedulis. Aerial parts ofP. incarnata were procured from acultivated source Rati Ram Nursery, village Khurrampur,district Saharanpur, Uttar Pradesh, India and its authentic-ity was confirmed from the reference specific available atthe Forest Research Institute, Dehradun, Uttar Pradesh, In-dia, where a voucher specimen sample was also deposited(Number 1325/2000). Authentic specimen sample ofPassi-flora edulis was procured from the Medicinal Plants Gardenof the University Institute of Pharmaceutical Sciences, Pan-

jab University, Chandigarh, India. All the biological activ-ity studies were carried out at the Pharmacognosy ResearchLaboratory, University Institute of Pharmaceutical Sciences,Panjab University, Chandigarh, India. The studies were per-formed using mice (Swiss albino, both sexes), rats (Wistarrats, both sexes) and guinea pigs procured from the DiseaseFree Small Animal House of the Haryana Agriculture Uni-versity, Hissar, India and were housed at the standard labo-ratory conditions at the Central Animal House, Panjab Uni-versity, Chandigarh, India. All the experimental protocolsinvolving use of animals were approved by the InstitutionalEthical Committee of Panjab University, Chandigarh.

During a comparative study, onlyP. incarnata methanolextract exhibited significant anxiolytic activity at a doseof 125 mg/kg in mice, whereas,Passiflora edulis did notshow any significant anxiolytic activity in any of the ex-tracts/doses evaluated (i.e., petroleum ether, chloroform andwater) using the modified elevated plus-maze model of anx-iety, 2 mg/kg p.o. diazepam as a standard anxiolytic, andthe vehicle (comprising 66.6%, w/w, sucrose in water) as acontrol (Dhawan et al., 2001b). The petroleum ether, chloro-form, methanol and water extracts of the segregated leaves,stems, flowers, roots and the entire plant ofPassiflora in-carnata were evaluated for determining the relative anxi-olytic profiles of the segregated plant parts and the wholeplant respectively after making their suspension in the vehi-cle (simple syrup) using experimental animals mice and theelevated plus-maze model as the laboratory model for eval-uating anxiety. Only the methanol extract of leaves ofP. in-carnata exhibited significant anxiolytic activity (100 mg/kgp.o.) in mice, whereas, the petroleum ether, chloroform andwater extracts were found to be devoid of activity. Using el-evated plus-maze model of anxiety in mice, it was observedand reported that none of the extracts of roots ofP. incar-nata exhibited significant anxiolytic activity comparable tothat of the control (simple syrup) and the standard anxiolyticdose of diazepam (2 mg/kg) (Dhawan et al., 2001c). Themethanol extracts of leaves, stems, flowers, and whole plantexhibited anxiolytic effects at 100, 125, 200, and 300 mg/kg,respectively. These results show that roots and flowers ofP. incarnata act as natural adulterants by causing a signifi-cant increase in the anxiolytic dose. Therefore, separation ofthese parts is recommended prior to any pharmacological,phytochemical and standardization studies onP. incarnata.(Kumar, 2001). Subsequently, it has been reported that onlythe leaves ofP. incarnata should be used for performing bi-ological studies as the leaves contain the maximum concen-tration of the bioactive constitutents. The methanol extractof leaves were useful in suppressing SO2-induced cough inmice at 100 mg/kg p.o. dose, using suspension of codeinephosphate (10 and 20 mg/kg) in simple syrup (simple syrupbeing used as a control, as well as the vehicle) as a standardanti-tussive (Dhawan and Sharma, 2002a). Using a 7-daystreatment regimen, the same methanol extract of leaves ata dose of 100 mg/kg p.o. was found to possess significantspasmolytic properties as it prevented 10% ‘acetylcholine


chloride-induced dyspnoea’ in guine pigs which was eval-uated using an aerosol chamber with 1 kg/cm2 as the con-stant pressure. The anti-asthmatic properties of the methanolextract of leaves ofP. incarnata have been postulated dueto its influence over the�-adreno-receptors (Dhawan et al.,2003b). The methanol extract of leaves ofP. incarnata pos-sessed significant aphrodisiac properties in male mice as theextract treated male animals exhibited increased mountingbehavior in presence of non-estrous female mice, relative tothe control, i.e., simple syrup (Dhawan et al., 2002a). Allthese biological activites reported by the authors are in ac-cordance with the ethno-pharmacological reports regardingthe use ofP. incarnata in the traditional system of therapeu-tics.

A comparative study was performed taking the bioac-tive methanol extract of aerial parts ofP. incarnata andthe mother tincture preparations ofP. incarnata (30 ml) ofvarious reputed homoeopathic medicines, available in thelocal market, e.g., SBL Private Limited, Ghaziabad, India(SBL), Dr. Reckeweg & Co., Gmbh D-64625, Bensheim,Germany (DRCG), Dr. Willmar Schwabe India Pvt. Ltd.,NOIDA (DWSI), Dr. Willmar Schwabe, DHU-Arzneimittel,Germany (DWSG) and Bhandari Homoeopathic Laborato-ries, Ghaziabad (BHL) were procured from the local mar-ket (Dhawan et al., 2002c). Thirty ml quantity of these fivetinctures were dried under vacuum usingBuchi 461 Ro-tavapor and the solvent-free extracts ofP. incarnata werepreserved in a vacuum desicator. The market extracts werefurther subdivided into four doses, viz., 100, 200, 300 and400 mg/kg by suspending the dried extract in the vehiclecomprising simple syrup and 1% w/w of carboxymethylcel-lulose (CMC). The biological (anxiolytic) effects exhibitedby the marketed preparations were found to be different fromthat of the methanol extract ofP. incarnata being used bythe authors in the laboratory studies. All these preparationsexhibited the maximum anxiolytic activity in mice (on el-evated plus-maze apparatus) at different doses. It could beopined through this exercise that the inconsistancy in biolog-ical activity of plant preparations could be dealt with, onlyif the available pharmacopoeial monographs of a particularplant-derived medicine could be substantiated with the de-finate informations on certain vital finger-print parameters,i.e., leaf-constants, physico-chemical parameters, TLC pro-files, and reporting of a specific bioactive marker compound(Dhawan et al., 2001a).

The same extract, i.e., the bioactive methanol extract ofP. incarnata was further subjected to bioactivity-directedfractionation, chromatographic and partitioning methodsto reach at an almost pure fraction, which further exhib-ited significant anxiolytic activity at 10 mg/kg in miceusing diazepam as a standard anxiolytic on the elevatedplus-maze model of anxiety (Dhawan et al., 2001d). TheUV, LC–MS, GC–MS, IR,1H, 13C NMR characterizationstudies have confirmed the presence of a benzoflavone(BZF) moiety, never reported fromP. incarnata earlier, thathas been accounted for the CNS properties of this poten-

tial plant (Dhawan et al., 2001d,e,f; Dhawan, 2002). Thisphyto-moiety has basic structure comprising a benzene ringfused at 6, 7 position of a flavone compound. The completechemical structure of BZF phyto-moiety isolated from themethanol extract of aerial parts ofP. incarnata cannot bepublished due to patent considerations. The isolation of atri-substituted benzoflavone moiety as the main bioactivephyto-constituent ofP. incarnata is a significant break-through, which gives the authors a major leap forward notonly in understanding the mode of action ofP. incarnatabut also in exploring the unexplored virtues of the plant incountering the menace of substance/drug addiction.

In another study, the authors evaluated the effect of thebioactive fraction ofP. incarnata on the reversal of mor-phine tolerance and dependence in mice (Dhawan et al.,2001g,f). Mice were rendered tolerant and dependent onmorphine by administration of morphine sulfate (10 mg/kgp.o.) twice daily for 9 days. Concurrent co-administrationof BZF of P. incarnata (10–100 mg/kg) with morphine for9 days attenuated naloxone-precipitated withdrawal jumpson the 10th day. Co-administration of BZF during inductionphase (days 1–9) delayed the development of tolerance tothe analgesic effect of morphine, which was measured usingtail-flick analgesiometer. This particular study on morphinereversal effects ofP. incarnata is in accordance with theethno-pharmacological reports about the use of the plant ex-tract in morphine-deaddiction which mention the traditionaluse ofP. incarnata in morphine deaddiction in the traditionalsystem of medicine in India (Lad, 2000; Vasudev, 1955).

In the light of various reports (NicoNo, 2001), mention-ing the usefulness ofP. incarnata in tobacco addiction, stud-ies have been performed by using four doses (1, 5, 10 and20 mg/kg) of the bioactive BZF moiety isolated from aerialparts ofP. incarnata. In a 7-days experimental regimen, mice(n = 5) were given nicotine hydrogen tartrate (2 mg/kg), andcombinations of nicotine with four doses of BZF (NnP-1,NnP-5, NnP-10 and NnP-20) q.i.d., by s.c. route. At the endof the 7-days treatments, naloxone was given to all the micegroups to induce abrupt cessation of nicotine. Mice treatedwith 10 and 20 mg/kg dose of BZF concurrently with nico-tine, did not exhibit significant number of withdrawal jumpsrelative to the addict group (Nn group). It was evident thatmice receiving these two doses of the nicotine–Passifloracombination treatments (NnP-10 and NnP-20 groups) had nocraving, as the animals did not become dependent on nico-tine. Even an acute single administration of BZF moiety ofP. incarnata to the nicotine addict mice (N group) could af-ford prevention of nicotine-dependence-oriented withdrawal


effects at the highest dose of BZF (20 mg/kg) only, and thelower doses were almost inert (Dhawan et al., 2002d).

Mice were administered 10 mg/kg b.i.d. (twice a day) doseof �9-tetrahydrocannabinol (�9-THC), p.o. (per oral), for6 days to make them dependent upon cannabinoids. Concur-rently, the other groups of mice were administered�9-THCalong with 10 and 20 mg/kg b.i.d. doses of BZF orally for6 days. Upon measuring the locomotor activity during thetreatment regimen, it was reported that the mice receivingBZF and �9-THC together, developed significantly lesstolerance and dependence, relative to the mice receiving�9-THC alone. Upon administration of SR-141716A, a se-lective cannabinoid-receptor antagonist (10 mg/kg p.o.) toall the groups of mice on the 7th day, an artificial withdrawalwas produced due to an abrupt decline of�9-THC levels inmouse brain. However, the typical withdrawal effects likepaw tremors and head shakes, were significantly less in themice administered with�9-THC + BZF for 6 days. Uponadministration of 20 mg/kg dose of BZF to mice showingsevere symptoms of withdrawal due to administration of SR-141716A, there was a marked attenuation of the withdrawaleffects, thereby, suggesting the usefulness of BZF in the ex-pression of withdrawal effects of�9-THC. Thus, BZF whenadministered concurrently with�9-THC prevented the de-velopment of tolerance and dependence of cannabinoids inmice. Even an acute administration of BZF (20 mg/kg p.o.)significantly blocked the expression of withdrawal effectsin �9-THC-dependent mice (Dhawan et al., 2002e).

In the light of the established usefulness of the ben-zoflavone moiety in counteracting the withdrawal effectsof substances like morphine, cannabinoids and nicotine bythe authors, the bioactive benzoflavone moiety was given inmice treated with addictive dose (2 g/kg, bid for 6 days) ofethyl alcohol, in order to evaluate its effectiveness in coun-tering alcohol dependence and expression of the ethanol-withdrawal-induced hyper-anxiety (manifested in the formof increased locomotor activity) (Dhawan et al., 2002h). Ina 7 days regimen, different groups of mice were admin-istered vehicle, alcohol, and alcohol+ four doses (10, 20and 50 mg/kg of the benzoflavone moiety) ofPassiflora in-carnata; all treatments (chronic) being administered orally,twice daily for 6 days. Similarly, three other groups of micewere rendered addict upon alcohol by administration of theaddictive dose (2 g/kg, bid for 6 days) of ethyl alcohol, anda single acute administration of 10, 20 and 50 mg/kg doseof benzoflavone moiety was given on the 7th day. In both,chronic and acute administrations, the benzoflavone moietysignificantly prevented the expression of withdrawal effectsof alcohol as there was a significant decrease in anxiety-oriented behavior in mice that received benzoflavone moietyof P. incarnata. The chronic administration ofP. incarnatawith alcohol had better preventive effects than the singleacute treatment withP. incarnata in alcohol-dependent mice.

In light of the dependence and addiction-liabilities of ben-zodiazepines, a non-habit forming anxiolytic drug is the direneed of the hour. The BZF moiety which was earlier re-

ported to exhibit anxiolytic properties at 10 mg/kg p.o. dosein mice, was evaluated for its dependence-liabilities at threedoses (10, 50 and 100 mg/kg) upon a chronic 21-days treat-ment in mice. The three doses of BZF exhibited a normalambulatory behavior on 25th day after the treatment for 21days, confirming thereby, that BZF moiety had no addictionor dependence even upon a long-term use in mice. Even inthe case of diazepam, the BZF moiety prevented the develop-ment of diazepam-dependence and expression of withdrawaleffects when administered concurrently with 20 mg/kg p.o.dose of diazepam, for a period of 21 days. The ambulatoryactivity was used as the measure of physiological and phys-ical manifestation of chronic diazepam withdrawal-orientedrelapse of anxiety in the animals. The ambulatory activityof different co-treatments of 20 mg/kg diazepam and BZF(10, 50 and 100 mg/kg) revealed a dose-dependent preven-tive effect, as the 100 mg/kg dose of BZF afforded almostfull prevention of diazepam dependence in mice receivingthe combination treatments in the 21-days treatment regi-men (Dhawan et al., 2002f; Dhawan et al., 2003a).

To evaluate the androgenic and testosterogenic effects ofBZF and the flavonoid chrysin, authors performed studiesto describes the potential usefulness of bio-flavonoids forcountering the deleterious effects of aging upon the malesexuality in 2 years old rats. A flavone chrysin fromPassi-flora caerulea and the benzoflavone moiety (BZF) were ad-ministered to 2 years old male rats for a period of 30 days.After cessation of these treatments, there was a significantimprovement in the over-all sexual functions in male ratswhich were given the bio-flavonoids, relative to the control.The rats receiving chrysin (1 mg/kg) and BZF (10 mg/kg)exhibited increased libido, when they were allowed to in-teract with non-estrous female rats. Additionally, the ratsupon 30-days treatment with bio-flavonoids had increasedsperm count, greater fertilization potential as well as littersize, when they were allowed to interact with proven pro-estrous female rats of the similar strain. Between the two,BZF was more potent than chrysin, as an anti-aromataseagent and exhibited better effects upon sexual system of the2 years old rats. Plant flavonoids, thus, act as potent phyto-estrogens, and have tremendous clinical and therapeutic uti-lizations against physiological and biochemical effects ofaging (Dhawan et al., 2002b).

The BZF moiety was also found to be very useful inpreventing the chronic-drug-induced decline in libido, fer-tility and virility in male rats, in studies performed bythe authors. Separate groups of healthy male rats weregiven �9-THC (10 mg/kg p.o.), nicotine hydrogen tartrate(2 mg/kg, sub-cutaneously) or ethanol (3 g/kg p.o.), aloneas well as in combination with BZF (10 or 20 mg/kg p.o.)over a period of 30 days at a stretch. After 30-days treat-ment regimen, the THC-, ethanol- or nicotine-treated micehad a significant loss of libido (recorded by observing themounting behavior with non-estrous female rats), decreasein the sperm count, and also decrease in the number of im-pregnated pro-estrous female rats, relative to the rat-groups


which were given co-treatments of THC–BZF (Dhawanand Sharma, 2003), nicotine–BZF (Dhawan and Sharma,2002b) and ethanol–BZF. The results of these exhaustivestudies make the authors opine that BZF also prevents thedrug/substance induced decline in fertility, libido, etc.

Encouraged by the interesting results with the BZF moietyin counteracting the withdrawal-oriented dependence of var-ious substances of abuse, it was desirable to study the modeof action. Since, benzoflavone moieties are the strongestinhibitors (Aldrich Catalog, 1996) of the enzyme aromatase(a member of cytochrome P-450 family), they are very sig-nificant in the metabolism of sex-steroids (Kao et al., 1998;Kellis and Vickery, 1984). It is postulated that BZF inhibitthe metabolic conversion of androgens (testosterone) toestrogens, thereby increaseing free teststerone and decreas-ing free estrogen (Chen et al., 1997). The free teststeroneaccounts for the non-appearence of withdrawal effects ofsubstances like morphine, nicotine, cannabinoids, ethanoland even benzodiazepines. This hypothesis holds good inlight of the well-established fact that the sex-steroids (orneuro-steroids) are the pivotal body chemicals which areresponsible for symptoms like anxiety, depression, insom-nia, epilepsy, nervous fatigue and stress. Neuro-steroids arealso instrumental in our sexual behavior and performance(Crémoux, 2000; Leonard, 1985). Since, there are incon-trovertible evidences that chronic consumers of morphine,tobacco, cannabinoids and ethanol suffer from declinein libido, sexual fertility and virility due to severe fallin the plasma-testosterone levels, administration of BZFrestores the normal testosterone levels by stopping thearomatization of testosterone to estrogen (INFOFAX, 2001;INFOFAX, 2001; Kane, 2001). Secondly, BZF also facili-tates the body to produce more testosterone by eliminatingthe so called “negative feedback” loop, that otherwise re-duces natural testosterone production due to chronic treat-ment with drugs and substances like morphine, nicotine,cannabinoids and alcohol (Lee et al., 1994; Schwontkowski,1994). The mechanism that BZF might act by inhibiting theenzyme aromatase, thus, preventing the metabolic degra-dation of testosterone to estrogen, postulated by the authorhas been duly acknowledged as well as lauded recently(Dhawan, 2003).

A multi-component herbal preparationEuphytose that hasbeen used in France since 1927 for curing anxiety statescomprises powder extracts of the following herbs: 50 mgvalerian (Valeriana officinalis), 40 mg Passion flower (P.incarnata), 15 mg kola nut (Cola nitida), 15 mg guarana(Paullinia cupana), 10 mg hawthorn (Crataegus oxycantha),and 10 mg black horehound (Ballota foetida). The dosageof placebo or the formula was two tablets three times dailyfor 28 days (Bourin et al., 1997). The multi-center, double-blind, placebo-controlled general practice study of 182 out-patients randomized into two parallel groups, who after a7-days placebo treatment prior to active treatment contin-ued to show a score of over 20 in the 14-item Hamiltonanxiety scale (HAM-A). The Montgomery–Asberg depres-

sion rating scale was applied to exclude depressed patients.The results showed a significant decrease in the HAM-Ascale already on day 7, and on day 28 in scores of psy-chic anxiety (P = 0.025) and somatic anxiety (P = 0.011)compared to baseline, whereas, there were no significantchanges in the placebo group scores. Those scoring less than10 on the HAM-A scale at the end of the treatment period(‘cured’) numbered 23 (25.3%) in the placebo group versus39 (42.9%) in the formula group. Eighty-three percent (83%)of the formula group reported an improved social life ver-sus 65% in the placebo group. Mild adverse effects occurredin four patients in the formula group and 8 in the placebogroup. The ethanolic extract ofP. incarnata exhibited anti-inflammatory properties at a dose of 125–500 mg/kg in ratsagainst inflammations induced by cotton pallets, dextran andcarrageenin (Borrelli et al., 1996).

7. Toxicology

Though herbal products are generally regarded as safe,yet, on account of the occurrence of cyanogenic constituentsin Passiflora species, their toxicity can not be ruled out. Hu-man beings have the physiological ability to detoxify cyanidesatisfactorily, given an adequate protein diet (Jones, 1998).The United States FDA has reported 15 cases of toxicity oc-curring due to the consumption of multi-ingredient patentmedicinal products in whichPassiflora species formed oneof the constituent (USFDA, 2000). There have been reportsof erratic heart beat and tachycardia, severe headache, pul-monary emboli, hepatitis, diarrhoea, pneumonia, weaknessin upper extremities, intracerebral hemorrhage with diffi-culty in speaking, etc., which have been documented by theUSFDA. A stray case of death has also been reported due tothe consumption of a patent drugCybergenics HG 6 of L &S Research Corp. However, all these products were multi-ingredient formulations and the reported toxicities can notbe solely ascribed to Passion flower.

The unripe fruits ofPassiflora adenopoda have causedpoisoning due to the presence of HCN, which is producedin the pericarp and aril of the unripe fruits as well as inthe primary stem, petiole, bracts and stipules (Saenz andNassar, 1972). However, the ripe fruits were devoid ofHCN. Passiflora alata is reported to contain etiologic agentsof IgE-mediated occupational asthma and rhinitis (Giavinaet al., 1997). The plant is therefore a persistent risk forthe personals working with this species.Passiflora edulishas shown hepatobiliary and pancreatic toxicity in animalsand humans (Maluf et al., 1991). P. incarnata is listed as“safe herbal sedative” by the FDA of America (HerbClip,1996) and none of the available monographs ofP. incar-nata mention the toxicity or any contra-indication of thisplant. Since the physiological actions and the mode of CNSdepressant activity have not been well documented, it hasbeen advised to takeP. incarnata with caution when takenalong with other CNS depressants or stimulants (Felter and


Lloyd, 1983). A few individuals have experienced emesiswith this plant even at medicinal doses. Moderate doses actas anti-spasmodic or somewhat narcotic. Excessive doseshave produced spasms and even paralysis in animals. It hasbeen advised not to takeP. incarnata with procarbazineanti-neoplastic drugs, possibly to minimize CNS depression(Martin, 1978). The neuromuscular relaxing effects ofP.incarnata have been enhanced by the use of the aminogly-coside antibiotic like clindamycin. There has been a reportthat a 34 years old female patient developed severe nausea,vomiting, drowsiness and ventricular tachycardia followingself medication withP. incarnata (Fisher et al., 2000). Fivepatients have been reported to suffer altered consciousnessafter taking a herbal preparationRelaxir®, which is pre-pared fromP. incarnata (Solbakken et al., 1997). The ex-tract of the plant is being evaluated in Japan for its possibleteratogenic effects (Hirakawa et al., 1981). Herbal prepara-tions containingP. incarnata as one of the ingredients havecaused vasculitis in patients suffering from insomnia (Smithet al., 1993). Vitexin (5), a phyto-constituent present in var-ious Passiflora species has exhibited anti-thyroid activityduring in vivo and in vitro studies using rats as experimentalanimals (Gaitan et al., 1995). The popular American Maga-zineUS Pharmacist has discouraged the use ofP. incarnatain lactating mothers (US Pharmacist, 2001). Due to the pres-ence of passiflorine (17) and harmin alkaloids (10–14), theplant is reported as a general environmental toxic grass bythe University of California in theirEnvironmental Toxico-logical Newsletter (Environmental Toxicology Newsletter,1983). During the 9th meeting of the ComplementaryMedicines Evaluation Committee in 1998 at Melbourne, theharmful effects of harmala alkaloids inP. incarnata wereaccounted for their side-effects and the long-term prescrip-tion of harman alkaloids (10–14) was strictly prohibited inAustralia (CMEC9, 1998). A severe contra-indication ofP.incarnata with a synthetic MAO inhibitor drug Phenelzine(NARDIL®) has been highlighted (Miller, 1998).

8. Clinical applications

Amongst the 500 species of the genusPassiflora, P. in-carnata is the one which has extensive clinical applicationsthroughout the world. The worldwide clinical applicationsare evident from the fact thatPassiflora incarnata is anofficial plant drug inBritish Herbal Pharmacopoeia, 1983,Homoeopathic Pharmacopoeia of India 1974,United StatesHomoeopathic Pharmacopoeia 1981,Pharmacopoeia Hel-vetica 1987 and the pharmacopoeias of Egypt, France,Germany and Switzerland. The plant has also been de-scribed in theBritish Herbal Compendium 1992, theEu-ropean Scientific Cooperative on Phytotherapy (ESCOP)monographs 1997, Deutsches Arzneibuch (DAB) 1997,Deutsches Homo”pathisches Arzneibuch (DHAB) 1978,Bundesanzeiger (Banz). Monographien der KommissionE 1998 andAmerican Materia Medica 1983. Discovered

in 1569 in Peru,Passiflora incarnata was introduced intomedicine in 1840 by Dr. L. Phares of Mississippi. The useof this plant recently has been revived by Professor I.J.M.Goss of Georgia, having introduced it into Eclectic practice(Hoch, 1934).

In a non-randomized clinical observatory trial, Schellen-berg et al. (Schellenberg et al., 1993) pharmacologicallyevaluated a combination productBiral-neu® comprisingvalerian root and Passion flower (P. incarnata) extracts.For comparative purposes, 20 ambulatory patients diag-nosed with affective and psychosomatic disorders receivedeither the extract combination or the neuroleptic drugPropaphenin®. Central activity and vigilance were quanti-tatively controlled using EEG brain mapping. For clinicalimprovements, CIPS inventory was taken from a self-rating depression and anxiety scale. The combination ofthe plant extracts reduced occipital region central hyperac-tivity after 2 weeks, as evidenced by significant increases(P < 0.01) in selective alpha-power and theta-power. Forthose treated with the neuroleptic agent, the major powerincrease was found after 6 weeks. The anxiety and depres-sion index showed a similar decrease in all the patients. Theresearchers concluded that the combination product con-taining P. incarnata was more efficient thanPropaphenin®

has a remarkable position as a “herbal sedative” in theOTC market, yet its effectiveness has only been confirmedto a limited degree by controlled therapeutics and clinicalstudies (Schulz et al., 1997). The plant extract in combi-nation with the extracts of other herbs has been subjectedto double-blind, placebo-controlled studies in patients withanxiety related disorders (Bourin et al., 1997), dementiaand behavioral problems in aged patients (O’Brien, 1998).Two multiple crossover studies, each involving 12 adultfemale subjects, were performed to screen the acute seda-tive effects of extracts ofValeriana officinalis, Lavandulaangustifolia, P. incarnata, Piper methysticum, Mellisa of-ficinalis, Eschscholzia californica, Hypericum perforatumand Ginkgo biloba. Both studies were placebo-controlled,and a single dose of 10 mg diazepam was used as an activereference drug. All drugs were administered as a singledose. Prior to administration, as well as 2 and 3 h after ad-ministration, EEG was recorded from two leads (Fz–Cz andOz–T6) under vigilance-controlled and resting conditionsfor 5 min. Tiredness was rated by the subjects on a visualanalogue scale. The EEG was digitized and stored for lateranalysis of the absolute and relative power of seven facto-rially defined frequency bands. Under diazepam, the powerin the theta-frequency band decreased while it increased inthe beta-band. Some plant extracts increased power in thetheta-frequency band but had no effect on beta frequencyrange. Self-rated tiredness increased under diazepam andsome of the plant extracts but not with the placebo. Thesedative effects of plant extracts could be evaluated byquantitative EEG analysis and by self assessment (Schulzet al., 1998). The EEG patterns of rats under a chronic treat-ment withP. incarnata for 3 weeks supported the sedative


and CNS depressant effects of the plant (Sopranzi et al.,1990).

The clinical applications ofP. incarnata have been forcedchiefly upon the nervous system (Felter and Lloyd, 1983). Itproves specially useful in insomnia of infants and old peo-ple. The herb relieves nervous irritability resulting from pro-longed illness, menstrual disturbances and mental overwork.It calms the restlessness of typhoid fever. The sleep producedby P. incarnata is rich in REM sleep, resulting into freshnesson awakening. One of the earliest clinical applications of theplant was for the relief of tetanus. The drug is highly effectivein convulsions when given prior to an approaching attack.Passiflora incarnata is praised for its control over spasmsof childhood. Spasms due to meningeal inflammations havebeen controlled with it. The plant is useful in spasmodicdysmenorrhea, neuralgic pain, rectal pain or even cardiacpain. An aqueous extract has been lauded as an applicationover burns, hemorrhoids, painful ulcers and ulcerating car-cinomata. The double-blind clinical studies performed re-cently on 36 out-patients suffering from generalized anxietydisorders (GADs) has affirmed that efficacy of thePassi-flora incarnata extract (45 drops per day) was comparable tothat 30 mg per day dose of oxazepam (Akhondzadeh et al.,2001). A total of 65 opiates addicts were assigned randomlyto treatment withPassiflora extract plus clonidine tablet orclonidine tablet plus placebo drop during a 14-days double-blind clinical trial. All patients met the DSM IV criteria foropioid dependence. The fixed daily dose was 60 drops ofPassiflora extract and a maximum daily dose of 0.8 mg ofclonidine administered in three divided doses. The severityof the opiate withdrawal syndrome was measured on days 0,1, 2, 3, 4, 7 and 14 using the Short Opiate Withdrawal Scale(SOWS). Both protocols were equally effective in treatingthe physical symptoms of withdrawal syndromes. However,thePassiflora plus clonidine group showed a significant su-periority over clonidine alone in the management of mentalsymptoms. These results suggested thatPassiflora extractmay be an effective adjuvant agent in the management ofopiate withdrawal (Akhondzadeh et al., 2001).

Herpes Tincture containingP. incarnata, Astragalus mem-branous and Lomatium dissectum has been used in Ho-moeopathy as a treatment for various sexually transmitteddiseases and is also effective against HIV (Pizzorno andMurray, 1999). Dr. J. Lutomski has specifically lauded therole of P. incarnata preparations for sexual activity in fe-males, by stating “Die Bedeutung der Passionsblume in derHeilkunde” {the meaning of passion flower in medical sci-ence} (Lutomski et al., 1981). Passionflower preparationsare particularly useful in nervous manifestations of men-strual problems, menopause, and sexual activity, in females(Chevallier, 1996). That is why,P. incarnata extracts havebeen used as female-tonics and adaptogens. The plant is par-ticularily useful in “nerves” that are “on edge”. An averagedose of passionflower in a solid natural form is aproximately500 mg and there are no known or serious contradictions ofpassionflower, according to Dr. Taylor in his book,The Hon-

est Herbal (Tyler, 1993). The role ofPassiflora incarnata hasalso been appreciated in cancer patients (Payne, 2001). Thephobia, fear and anxiety on acount of cancer cause adrenalhormone release, the physiological effects of which includeactivation of adipocyte lipase (resulting in mobilization offree fatty acids) and partial inhibition of protein synthesis,i.e., the plasma amino acids which are readily utilized bynormal cells for protein synthesis are only partially used,resulting in an increase in the availability of amino acidsto meet tumor cell metabolic needs. It is vitally important,therefore, to provide the cancer patient with anxiolytic phy-tomedicine to minimize fear and anxiety related stress. Theextract ofP. incarnata alongwith other allied herbs is quiteuseful in ameliorating stress in cancer patients. This practiceis being adopted in Japan.The Dietary Supplement Health& Education Act of 1994 (DSHEA) has exempted herbslike passionflower, valerian, ginkgo and ginseng from thepurview of the Food & Drug Administration of the USA fortheir benefecial effects in the estrogen replacement therapy(ERT) in post-menopausal women (Ross et al., 2000).

Passiflora alata is reported to be official in thePharma-copoeia of Brazil (Reynolds, 1996). A liquid oral solutionof the plant in a dose of 5 ml thrice a day is recommendedin the insomnia, anxiety, dry cough, irritation of the respi-ratory mucosa, nervous disturbances of the menopause andsome painful conditions (Monteiro Da Silva Ltda, 2000).Spray-dried powders prepared from the 40% ethanolic ex-tractive solutions ofPassiflora edulis aerial parts, and Aerosil200® as an adjuvant, have been used in insomnia in Brazil(DeSouza et al., 2000).

9. Conclusions

Despite tremendous advancements in the field of medi-cal therapeutics, the studies conducted at the National Insti-tute of Mental Health, Bethesda, the USA (NIMH), revealthe alarming increase in CNS related disorders, the maintwo being anxiety and insomnia (Murray and Lopez, 2001;NIMH, 2001). A datum of the NIMH reports that anxietyrelated disorders will engulf every 7 out of 10 individualsin the USA alone, by 2020. Even in the developing coun-tries, where 4/5th of the planet’s people live, the next decadewill bring a dramatic change in the health-care needs ofthe people, as the anxiety-oriented disorders will replacetheir traditional enemies,i.e., the infectious diseases (Cherr,1999; Zal, 2000). Pharmaceutical options in the treatment ofanxiety have included the benzodiazepines, anti-depressants(MAO inhibitors and TCAs),�-blockers, azaspirones andsome anti-convulsants (O’Brien and Woody, 1986). Theseproducts, however, can cause serious problems of sedation,cognitive changes and addiction liabilities. The general pub-lic, in search of safe, cheap and effective treatment for theiranxiety, tension and stress, are starting to turn to nonphar-maceutical herbal products and other alternative medications(Newell et al., 1996). In view of the dire need of a safe,


effective and cheaper anxiolytic, various plants especiallyPassiflora incarnata have a great scope of clinical exploita-tion in the years to come. The plant has a long traditionaluse as an anxiolytic and sedative.

A perusal of literature on bioactivity ofPassiflora revealsthat researchers throughout the world have opined differ-ently and have postulated their own school of thought basedon their observations. The harmala alkaloids and flavonoidshave been reported as the main important constituents ofP. incarnata. The harmala alkaloids, due to their MAOenzyme inhibiting properties have been suggested to bethe main bioactive phyto-constituents (Bradley, 1992; NF,1926; Pletscher et al., 1959; Reynolds, 1996). The flavonoidchrysin (Zanoli et al., 2000) and a �-pyrone derivativemaltol (15) have also been accounted for their role in theCNS depressant activity of the plant (Aoyagi et al., 1974).In the latest reports, the sedative and anxiolytic activity ofP. incarnata has been attributed to the benzodiazepine andGABA receptors mediated biochemical processes in thebody (Simmen et al., 1999; Viola et al., 1998). The plant isreported to be a depressant to the motor side of the spinalcord, reducing arterial pressure and increasing rate of res-piration (Pletscher et al., 1959). Contrary to these reports,the exhaustive pharmacological work by Soulimani et al.(Soulimani et al., 1997), has ruled out the role of any ofthe known phyto-constituents inP. incarnata which couldhave been responsible for the sedative and anxiolytic ac-tivity of this plant. Authors, therefore, conclude that thereis no consensus of opinions between the various postulatedhypotheses pertaining to the bioactivity of this plant.

Authors attribute this lacuna to the confusing identity ofP. incarnata which has baffled the researchers and botanistssince 1843 (Hooker, 1843). Due to the similar morphologicand microscopic characteristics ofPassiflora incarnata andPassiflora edulis, the two plants have often been reportedas synonymous (Chakravarty, 1949; Jackson, 1895). Theconfounding resemblance ofPassiflora incarnata with Pas-siflora edulis which was first reported in 1843 even per-sists till date as is evident from a survey of the literature(Finzelberg, 1999; Kuntz, 1999; McGuire, 1999; RaintreeNutrition, 1999; Scheper, 1998; Vecchia, 1998). Passifloraedulis is mainly grown for its edible fruits (McGuire, 1999)and rarely finds mention in the reports as a potent hypno-sedative (Maluf et al., 1991). In fact, the two plants are somuch alike as to baffle even a plant taxonomist (Kumar,1999). Moreover, comparison would be possible only if wehave specimens of both the plants. Authors have establishedthe key differential parameters betweenP. incarnata andPassiflora edulis so as to properly identify the accurate plantout of these two identical species (Dhawan et al., 2001a;Dhawan et al., 2000). After establishing the correct identity,it has been possible to perform systematic pharmacologicalstudies on the proper bioactive plant, i.e.,P. incarnata andits un-imaginable virtues have been reported on account ofthe isolation of a tri-substituted benzoflavone moiety fromthe plant. The isolation of a BZF moiety fromP. incarnata

has been a significant breakthrough which makes us under-stand the inconclusive reports by earlier researchers. Thismoiety merits human trials and its exact and full chemicalidentity can not be disclosed here for our right to protectthe patent over it, though, the useful structure and the postu-lated mode of action of this tri-substituted BZF moiety hasbeen presented here for the interests and benefits of a reader.By way of several experimental studies, the anxiolytic, anti-tussive, anti-asthmatic and aphrodisiac effects ofP. incar-nata have been confirmed in the crude methanol extract ofthis plant. Further, a novel tri-substituted benzoflavone moi-ety has been isolated and reported which has exhibited itsusefulness in the addiction of morphine, ethanol, nicotine,cannabinoids and diazepam. This BZF moiety has also ex-hibited substance-induced decline in sexual parameters inmale animals, besides, exhibiting its own use as a virility-enhancing agent.

The plants over other species of Passiflora also havepromising scope for a future research.

Fluorine is a very common industrial pollutant that hassevere toxic effects also. Due to its strong electro-negativity,fluorine can form complex with biologically active sub-stances. Chrysin, reportedly present inPassiflora incarnatacan form complexes with metals due to its anti-oxidant ac-tivities. Chrysin as well as other flavonoids ofP. incarnataappear to exert a beneficial effect in chronic exposure to in-dustrial toxins including fluorine compounds (Liwiec et al.,2000). In an experimental study conducted by Liwiec et al.,the effect of flavonoid chrysin (20 mg/kg for 3 months) wasevaluated in rats intoxicated with NaF for a constant periodof 3 months. After 3 months, the various enzymes viz., as-partate aminotransferace (AspAT), alanine aminotranferace(AlAT), cholinesterase (ChE), alkaline-phosphatase (AP)and bilirubin concentrations in serum were measured. In-toxicated animals had higher levels of AspAT, AlAT andChE. This increase was suppressed by chrysin. AP ac-tivity was reduced in intoxicated animals. These findingssuggest the promising role of chrysin-enriched diet as asupportive-cum-preventive measure in exposure to fluorinecompounds.

Passiflora tetrandra which has got anti-bacterial activityagainstEscherihia coli, Bacillus subtilis andPseudomonasaeruginosa can also have potential to be another plant-derived antibiotic (Perry et al., 1991). The plant has alsoexhibited cytotoxicity to P-388 murine leukemia cells.Passicol consisting of polyacetylenic compounds has alsoexhibited anti-bacterial and anti-fungal activities (Nicollset al., 1973). This compound has been detected inPassifloracaerulea and Passiflora edulis. Thus, the above species ofPassiflora can offer newer anti-bacterial and anti-fungalagents, if worked upon. Ermanin (32) having deterrentactivity againstDione juno larvae has been isolated fromPassiflora foetida(Echeverri et al., 1991). Ermanin can be agood pesticide against such pests and insects. InPassifloraquadrangularis, the presence of angiotensin convertingenzyme inhibitor and aldose reductase enzyme inhibitor


has been reported (Okamoto and Yoshizawa, 1994). Theplant thus, can be a hunting ground for the discovery ofa novel anti-hypertensive agent. Recently, it has been ob-served that chrysin which is present in many species ofPassiflora has got testosterone boosting properties (JarrowFormulas Inc., 2000). Interestingly, Passion flower whensmoked with Lobelia has shown laudable result in de-addicting the nicotine/cigarette smokers (NicoNo, 2001;Viable Herbal Solutions, 2001). Passion flower is recog-nized as a dietary supplement and approved flavoring agentby the US government and the Council of Europe. Till1978, this herb enjoyed OTC status in the USA (Horatioet al., 1948). The genusPassiflorais a good source of bio-flavonoids, i.e., chrysin, apigenin, kaempferol, quercetin,apigenin, and genistein, etc., which have tremendous thera-peutic potentials as anti-oxidants, immuno-modulators, anti-anxiety agents and anti-carcinogens (Merken and Beecher,2001; Murcia et al., 2001). The benzoflavone moiety, beingthe strongest aromatase inhibitor, and various flavonoidsfrom other species ofPassiflora, can also be exploitedfor its postulted use in various mental disorders, espe-cially arising out of addiction of tobacco, opiates, cannabi-noids, alcohol, and synthetic anxiolytics (Brounstein, 1995;Capasso et al., 1998). Species ofPassiflora have also beenput to use as OTC preparations throughout the world insymptoms like andropause, menopause, as calming ther-apy for hyperactive-children, in case of severe anxiety dueto insomnia, restlessness and nervous edgy, and also invarious sexual dysfunctions in males as well as females(Aubert and Anthoine, 1985; Blumenthal et al., 1998;Chua, 2002; Cooper and Ritchie, 2000; EnvironmentalToxicology Newsletter, 1983; Foster and Dube, 1990;Fremerman, 1998; Gagiu et al., 1978; Grandolini et al.,1997; Hoffman, 1984; Holt and Comac, 1998; Incledon,2001; Jarrow Formulas Inc., 2000; Johnson, 1995; Lam,2001; Lycos, 2001; Marx, 2001; Melissa, 2000; Pelisseroet al., 1996). Our exhaustive pharmacological studies usingthe BZF moiety ofP. incarnata were also based on the vari-ous reports mentioning the use of extracts, tea, tincture, andeven tablets ofP. incarnata against various addiction-pronesubstances.

Thus, the various species ofPassiflora, besides their or-namental and exotic values, can prove to be useful sourcesof newer biological molecules which can be potent phyto-pharmaceuticals in the future. This genus is a boon and bless-ing and a panacea for the ailing masses. The varied thera-peutic uses described in our report provePassiflora true toits platonic name, i.e., passion of Christ.

Acknowledgements

The authors are grateful to the Council of Scientific andIndustrial Research, New Delhi, India for awarding SeniorResearch Fellowship to Kamaldeep Dhawan and ResearchAssociatship to Dr. Sanju Dhawan.

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