Passiflora incarnata / Passionflower

Nederlandse naam: Passiebloem (Maypop)
Herkomst: Verenigde Staten

Een winterharde passiebloem die zonder enige moeite in de tuin gehouden kan worden. Het is wel aan te raden om jonge planten nog even af te dekken met wat stro of een laagje bladeren, omdat deze nog wat kwetsbaar zijn. De bloemen variëren in kleur van bleekwit tot roze-achtig, paars. De passievruchten staan in de VS bekend als Maypop en zijn eetbaar. De plant groeit heel decoratief tegen een muur of schutting, het liefst zo veel mogelijk in de zon. 

Zaaibeschrijving:
Zaden 24 uur weken in sinaasappelsap en vervolgens zaaien in zaai- en stekgrond. Grond constant vochtig houden, afdekken met huishoudfolie of glas en op een warme en lichte plaats binnenshuis laten kiemen. Kieming kan enkele weken tot maanden duren.  

Werkzame bestanddelen:
Alkaloïden (0.025-0.032%) uit de harmaangroep als passiflorine, arbitine, yageine, loturine (harmaan), harmalol, harmine, harmaline en misschien harmol (discutabel); flavonoïden berekend als hyperoside (0.3-0.4%) met vitexine, isovitexine, kaempferol, quercetine en rutine; saponarine, oriëntine, iso-oriëntine, maltol, ethylmaltol, passicol, vetzuren, etherische oliën met meer dan 150 verschillende actieve componenten; alleen de wortel bevat cumarinen

Het werkzame alkaloïde dat men vroeger passiflorine noemde, heet tegenwoordig: 3-methyl-beta-carboline (harmaan). Het bezit een sedatieve en slaapbevorderende werking. De hoeveelheid alkaloïde aanwezig in de plant hangt sterk af van de grondsoort, de herkomst en de bereidingswijze van het product

Werkingsmechanisme
De passiebloem bezit sedatieve, hypnotische(slaapverwekkende), spasmolytische en pijnstillende eigenschappen. De ESCOP noemt als indicaties voor deze plant gespannenheid, rusteloosheid en geïrriteerdheid welke vaak optreden samen met inslaapproblemen.
Dierstudies toonden een sedatieve werking op het centrale zenuwstelsel aan. In hoge doses ingenomen, hebben passiebloem extracten een anticonvulsieve werking, in lage doses treedt een afname van de spontane motorische activiteit op. Eveneens constateerden onderzoekers een verlengde slaapperiode. Wetenschappers schrijven deze eigenschappen toe aan maltol en ethylmaltol. Harmane alkaloïden staan er om bekend een stimulerende invloed uit te oefenen op het centrale zenuwstelsel via het proces van mono-amino-oxidase (M.A.O.) remming. Men neemt aan dat de sedatieve werking van mantol en ethylmaltol deze stimulerende werking van de alkaloïden blokkeert, maskeert, remt of opheft. 
De alkaloïden hebben bovendien een spasmolytische invloed op het gladde spierweefsel en verlagen de bloeddruk. In Passiflora treft men tevens lage serotonineconcentraties aan hetgeen wellicht mede de ontspannende, kalmerende, stemmingsbevorderende en bloeddrukverlagende eigenschappen van de plant verklaart. Vervolgonderzoeken met droogextracten toonden naast genoemde eigenschappen ook een opvallende anxiolytische (angstremmende) werkzaamheid aan. In verschillende documenten wijzen auteurs op de fungicide en antibacteriële werkingen van de plant.

Praktijk
Passiflora wordt het meest gebruikt bij (in)slaapproblemen, spanning en onrust. Inname van gestandaardiseerde extracten (op 3.5-4% isovitexine flavonoïden) vergemakkelijkt het inslapen en verlengt de slaapperiode aanzienlijk (tot 40%).
Daarnaast is het extract geïndiceerd bij nervositeit, onrust, geïrriteerdheid en klachten daaruit voortvloeiend (spierkrampen, astmatische krampen, Irritable Bowel Syndrom, nerveuze tachycardie en hypertensie). Bij een hormonale disbalans heeft gebruik van extracten een harmoniserend en ontspannende effect. Extract kunnen derhalve geïndiceerd zijn bij menstruatieklachten en overgangsklachten. Van Hellemont stelt een combinatie van Crataegus oxyacantha met Passiflora voor bij hartkloppingen en tachycardie.

Contra-indicaties
Zowel de bestanddelen harman als harmaline versterken uteruscontracties. Gebruik tijdens zwangerschap en lactatieperiode is gecontra-indiceerd.

Bijwerkingen
De ESCOP waarschuwt dat bij inname van de plant of extracten daarvan sufheid kan optreden. De rijvaardigheid en het correct bedienen van machines kan beïnvloed worden. Als deze bijwerkingen optreden, dient men af te zien van deelname aan het verkeer of het bedienen van machines. Incidenteel treden overgevoeligheidsreacties op.




Passiflora monograph

Scientific Name(s): Passiflora incarnata L., occasionally P. lutea L. Family: Passifloraceae
Common Name(s): Passion flower ; passion fruit , granadilla (species with edible fruit); water lemon ; Maypop , apricot vine , wild passion flower ( P. incarnatus ); Jamaican honeysuckle ( P. laurifolia ).

Botany

The term “passion flower” connotes many of the approximately 400 species of the genus Passiflora , which are primarily vines. Some of the species are noted for their showy flowers, others for their edible fruit. Common species include P. incarnata , P. edulis , P. alata , P. laurifolia , and P. quadrangularis . Those with edible fruit include P. incarnata , P. edulis , and P. quadrangularis , the latter being one of the major species grown commercially for its fruit. 1 Passiflora species are native to tropical and subtropical areas of the Americas. In the United States, P. incarnata is found from Virginia to Florida and as far west as Missouri and Texas. The flowers of Passiflora have 5 petals, sepals, and stamens, 3 stigmas, and a crown of filaments. The fruit is egg-shaped, has a pulpy consistency, and includes many small seeds. 1 , 2

History

The passion flower was discovered in 1569 by Spanish explorers in Peru, who saw the flowers as symbolic of the passion of Christ and, therefore, a sign of Christ's approval of their efforts. This is the origin of the scientific and common names. 3 The folklore surrounding this plant possibly dates further into the past. The floral parts are thought to represent the elements of the crucifixion (3 styles represent 3 nails, 5 stamens for the 5 wounds, the ovary resembles a hammer, the corona as the crown of thorns, the petals representing the 10 true apostles, with the white and bluish-purple colors those of purity and heaven). 2 , 4 In Europe, passion flower has been used in homeopathic medicine to treat pain, insomnia related to neurasthenia or hysteria, and nervous exhaustion. Other indications have included bronchial disorders (particularly asthma), compresses for burns, inflammation, inflamed hemorrhoids, climacteric complaints, pediatric attention disorders, and pediatric nervousness and excitability. 5

Chemistry

Researchers have identified a number of constituents in different passion flower species. The official passion flower is considered to be P. incarnata , which is used for the drug. 6 Key constituents in P. incarnata include flavonoids, maltol, cyanogenic glycosides, and harman indole alkaloids. 2 Flavonoid content (2.5%) includes flavone di-C-glycosides shaftoside, isoshaftoside, isovitexin (found in highest concentration between preflowering and flowering stages in 1 report), 7 iso-orientin, vicenin, lucenin, saponarin, and passiflorine. 8 Free flavonoids include apigenin, luteolin, quercetin, and kamferol. 6 Another report confirms similar constituents by mass spectral analysis. 9 Flavonoid determination by high-performance liquid chromatography and other methods has been extensively reported. 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 The stability of dried extract also has been studied. 18 P. incarnata components include phenolic, fatty, linoleic, linolenic, palmitic, oleic, and myristic acids, as well as formic and butyric acids, 5 , 19 coumarins, phytosterols, essential oil, maltol (0.05%), 6 , 20 and harman and its derivatives (0.03%). Harmala alkaloids include harmine, harmaline, and harmalol. Quantitative determination of harman and harmin in P. incarnata also has been performed. 21

Comparative studies
Thin layer chromatographic methods to differentiate P. incarnata from P. edulis and P. caerulea have been described. 19 Quantitative analysis of different plant parts from P. incarnata and P. edulis indicate that P. edulis leaves have the highest alkaloid content, and that fruit rinds contain approximately 0.25% alkaloids. Seeds and root tissue have the lowest alkaloid content. These findings may have economic importance. P. edulis fruit rinds, by-products of passion fruit juice production, may provide an economical source of alkaloids. 22 Flavonoids from P. trinervia and P. sanguinolenta also have been reported. 23 A review of the chemical constitution of Passiflora species is available. 24

Passion Flower Uses and Pharmacology

Passion flower has been researched for its sedative and anxiolytic effects. 2 , 6 , 8 A 1986 survey of British herbal sedatives revealed passion flower as the most popular. Other popular species included Valeriana officinalis , Humulus lupulus , and Scutellaria lateriflora . 25 , 26 Martindale, The Extra Pharmacopoeia lists many multi-ingredient preparations from other countries. 27
The pharmacological activity of Passiflora is attributed primarily to the alkaloids and flavonoids. The harmala alkaloids inhibit monoamine oxidase, which may account for part of their pharmacologic effect. 20Sedative/anxiolytic

Animal data
Animal studies have shown that Passiflora extracts have a complex action on the central nervous system (CNS), inducing dose-dependent stimulation and depression. 28 A report describes CNS-receptor binding sites of P. incarnata . 29
Passiflora species exhibit sedative activity in animals 30 and anxiolytic activity in mice. 31 When given to rats, P. incarnata extract led to diminished general activity when tested in a 1-arm, radial maze. 32 In mice, P. incarnata 's sedative and anxiolytic properties were associated with aqueous extracts of aerial plant parts. 33 The sedative effect of Passiflora may require both the alkaloids and flavonoids to be present. 22 Mice injected subcutaneously with 400 mg/kg of maltol and ethyl maltol showed reduced spontaneous activity, bradycardia, hypothermia, relaxation of skeletal muscle, and diminished pinna, corneal, and ipsilateral flexor reflexes. An ethylene chloride-soluble fraction at 2 mg/mL reduced brain oxygen consumption and the effect with the acid-soluble fraction was greater. Maltol and ethyl maltol potentiated the sleep-inducing effect of hexobarbital and counteracted the convulsive effects of pentylene or strychnine. These findings indicate that maltol and ethyl maltol may mask the stimulant effects of harmala alkaloids. 20                                                        Passiflora teelt bij Marleenkruiden

Other Passiflora species exhibit similar effects. P. coerulea has sedative actions. 34 Constituent chrysin, isolated from this same species (a central benzodiazepine [BZ] ligand) has anxiolytic effects, due in part to this role as a partial agonist of central BZ receptors. 35 Tranquilizing effects have been seen with alkaloids from the harman group in P. edulis species. 36

Clinical data
Human studies of Passiflora species as a sedative/anxiolytic have been conducted. A case report using the plant in a combination natural product, Calmanervin , for successful sedation before surgery was reported. 37 In a multicenter, double-blind trial of 91 patients, Passiflora (in combination, Euphytose ) exhibited statistically significant differences when compared with placebo in the treatment of adjustment disorder with anxious mood. 38 A study of Passiflora in the combination product Compoz contradicts these last 2 studies. It was not possible to differentiate between aspirin or placebo when tested as a daytime sedative. However, the duration of this study was only 2 weeks. 39

Miscellaneous uses
Passion flower's ability to reduce anxiety makes it useful for asthma, palpitations, and other cardiac rhythm abnormalities, high blood pressure, insomnia, neurosis, nervousness, pain, and other conditions. 2 , 6 , 8 However, no clinical data is available to support any of these potential uses.
In vitro experiments have demonstrated that Passiflora kills a wide variety of molds, yeasts, and bacteria. Group A hemolytic streptococci are much more susceptible than Staphylococcus aureus , with Candida albicans being intermediate in susceptibility. The antimicrobial activity of Passiflora disappears rapidly from dried plant residues but fades more gradually in aqueous extracts. Addition of dextran, milk, or milk products has a stabilizing effect on dry Passiflora . 40 , 41 A later report describes the P. tetrandra component, 4-hydroxy-2-cyclopentenone, as having antipseudomonal actions. This constituent was also found to be cytotoxic to P388 murine leukemia cells. 42
Other uses of passion flower include herbal treatment for menopausal complaints 43 and as a flavored syrup to mask drug taste. 44

Dosage
No clinical trials of passion flower as a single agent have been reported; therefore, the typical daily dose of 4 to 8 g is not supported.

Pregnancy/Lactation
Use of passion flower is contraindicated during pregnancy because of the uterine stimulant action of its alkaloids harman and harmaline, and the content of the cyanogenic glycoside gynocardin. 45 , 46 , 47

Interactions
None well documented.

Adverse Reactions
Extracts produced no adverse effects in mice when administered intravenously. 40 Cyanogenesis from species P. edulis has been suggested. 48 The plant's known actions may reduce arterial pressure affecting circulation and increasing respiratory rate. 8 There are no controlled human trials using single herb preparations of Passiflora extracts before the mid-1990s. 49There have been cases of vasculitis 50 and altered consciousness in 5 patients taking the herbal product Relaxir , produced mainly from P. incarnata fruits. 51 Occupational asthma and rhinitis may occur from the species P. alata , which was substantiated by skin testing and Western blotting in vivo and in vitro studies. 52

Toxicology
Little information is available on the clinical toxicity of Passiflora . P. adenopoda fruits may produce some toxic effect. 53

Bibliography
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Passionflower is also known as passion vines,, in the genus Passiflora , belonging to the family Passifloraceae, native to southeastern parts of the America. The herb has been used in traditional medicine in treating nervous tension including anxiety, insomnia, seizures, sleep problems and hysteria.

Health Benefits 
1. Anti-Trichomonas vaginalis activity
In the investigation of saponins from Quillaja, Passiflora, and Ilex species and its effects on trichomonas vaginalis found that saponins from Passiflora alata and Quillaja saponaria presented the best anti-T. vaginalis activity (MIC = 0.025%). In addition, all samples induced erythrocyte lysis and LDH release. As far as we know, this is the first report demonstrating the potential anti-T. vaginalis activity of these saponins, according to "Anti-Trichomonas vaginalis activity of saponins from Quillaja, Passiflora, and Ilex species" by Rocha TD, de Brum Vieira P, Gnoatto SC, Tasca T, Gosmann G.(1)

2. Anxiety
In this study, 60 patients were randomized into two groups to receive either oral Passiflora incarnata (500 mg, Passipy IranDarouk) (n = 30) or placebo (n = 30) as premedication, 90 min before surgery. A numerical rating scale (NRS) used for each patient to assess anxiety and sedation before, and 10, 30, 60, and 90 min after premedication, found that administration of oral Passiflora incarnata as a premedication reduces anxiety without inducing sedation, according to "Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study" by Movafegh A, Alizadeh R, Hajimohamadi F, Esfehani F, Nejatfar M.(2)

3. Antidiabetic activity
In the identification of methanolic extracts of leaves of Passiflora incarnata and its effect (100 and 200mg/kg, for 15 days) to streptozotocin-induced diabetic mice orally, found that Methanolic extract (200mg/kg) produced a significant reduction in fasting blood glucose level in streptozotocin-induced diabetic mice. Significant differences were also observed in urine glucose level, oral glucose tolerance test, serum lipid profile and body weight of methanolic extract treated diabetic mice, when compared with diabetic, normal and standard drug treated mice. Histopathological studies of the pancreas showed comparable regeneration of the cells by extract which were earlier necrosed by streptozotocin, according to "Antidiabetic activity of Passiflora incarnata Linn. in streptozotocin-induced diabetes in mice" by Gupta RK, Kumar D, Chaudhary AK, Maithani M, Singh R.(3)

4. Sleep quality
In the investigation of Passiflora incarnata, a traditional herbal used as sedative, anxiolytic and a popular sleep aid used for the treatment of sleep disturbance, found that forty-one participants (18-35 years) were exposed to each treatment for a week, whereby they consumed a cup of the tea and filled out a sleep diary for 7 days, and completed Spielberger's state-trait anxiety inventory on the seventh morning. Ten participants also underwent overnight PSG on the last night of each treatment period. Of six sleep-diary measures analysed, sleep quality showed a significantly better rating for passionflower compared with placebo (t(40) = 2.70, p < 0.01). These initial findings suggest that the consumption of a low dose of Passiflora incarnata, in the form of tea, yields short-term subjective sleep benefits for healthy adults with mild fluctuations in sleep quality, according to "A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (passionflower) herbal tea on subjective sleep quality" by Ngan A, Conduit R.(4)

5. Opiates withdrawal
In the demonstration of clonidine plus passiflora extract vs. clonidine plus placebo in the outpatient detoxification of 65 opiates addicts, found that the passiflora plus clonidine group showed a significant superiority over clonidine alone in the management of mental symptoms. These results suggested that passiflora extract may be an effective adjuvant agent in the management of opiate withdrawal. However, a larger study to confirm our results is warranted, according to "Passionflower in the treatment of opiates withdrawal: a double-blind randomized controlled trial" by Akhondzadeh S, Kashani L, Mobaseri M, Hosseini SH, Nikzad S, Khani M.(5)

6. Anxiogenic and anticonvulsant effects
In the classification of five different extracts, prepared from a single batch of Passiflora incarnata, administered to CF-1 mice for 1 week in their drinking water prior to evaluation of their behavioral effects found that anticonvulsant effects against PTZ-induced seizures were seen in mice that received 2 of the 5 Passiflora extracts. Instead of the anxiolytic effects described by others, anxiogenic effects in the elevated plus maze were seen in mice receiving any of the 5 Passiflora extracts, according to "Passiflora incarnata L. (Passionflower) extracts elicit GABA currents in hippocampal neurons in vitro, and show anxiogenic and anticonvulsant effects in vivo, varying with extraction method" by Elsas SM, Rossi DJ, Raber J, White G, Seeley CA, Gregory WL, Mohr C, Pfankuch T, Soumyanath A.(6)

7. Antiradical activities
In the investigation of the aqueous and ethanolic extracts of passionflower and the influence of the flavonoids on the antiradical activity by DPPH* and ABTS* + methods, found that Passiflora extract has not only sedative but also antiradical activity. The ethanol extract catches free radicals more effectively than the water extract. The strongest antiradical effect among the investigated flavonoids (chlorogenic acid, hyperosid, isovitexin, caffeic acid, quercetin, luteolin, orentin, rutin, scutelarein, vicenin and vitexin) was predetermined by vicenin, isovitexin and orentin, according to "Antiradical activities of the extract of Passiflora incarnata" by
Masteikova R, Bernatoniene J, Bernatoniene R, Velziene S.(7)

8. Nicotine reversal effects
In the investigation of the Nicotine reversal effects of benzoflavone moiety (BZF) of the plant Passiflora incarnata Linneaus found that found that those mice treated with the two highest doses of BZF,in combination with nicotine (NP-10 and NP-20), showed significantly fewer nicotine-abstinence withdrawal jumps and normal ambulatory behaviour. BZF treatment prevented weight loss and resulted in normal performance in the swimming endurance test, which may be a measure of stress and/or depression. Similarly, acute administration of a single 20 mg/kg dose of BZF prevented some of the nicotine-withdrawal effects; lower doses were almost inert. These studies, although preliminary, suggest that the BZF may have value in treating nicotine addiction, according to "Nicotine reversal effects of the benzoflavone moiety from Passiflora incarnata Linneaus in mice" by Dhawan K, Kumar S, Sharma A.(8)

9. Drug/substance reversal effects
Administered concomitantly with nicotine, ethanol and delta-9-tetrahydrocannabinol for 30 days in male rats and benzoflavone moiety (BZF) effects in preventing the drug-induced decline in sexuality in male rats, found that BZF moiety isolated from P. incarnata is a tri-substituted derivative of alpha-naphthoflavone (7,8-benzoflavone), a well-known aromatase-enzyme inhibitor, the mode of action of BZF has been postulated to be a neurosteroidal mechanism vide in which the BZF moiety prevents the metabolic degradation of testosterone and upregulates blood - testosterone levels in the body, according to "Drug/substance reversal effects of a novel tri-substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linn.--a brief perspective" by Dhawan K.(9)

Side Effects
1. Passionflower may interact with other herbs and medication, including sedative and blood thinner medicine.
2. Do not use the herb in children or if you are pregnant or breast feeding without approval from the related field specialist.

Referenties PubMed
(1) http://www.ncbi.nlm.nih.gov/pubmed/22218924
(2) http://www.ncbi.nlm.nih.gov/pubmed/18499602
(3) http://www.ncbi.nlm.nih.gov/pubmed/22212504
(4) http://www.ncbi.nlm.nih.gov/pubmed/21294203
(5) http://www.ncbi.nlm.nih.gov/pubmed/11679027
(6) http://www.ncbi.nlm.nih.gov/pubmed/20382514
(7) http://www.ncbi.nlm.nih.gov/pubmed/19051605
(8) http://www.ncbi.nlm.nih.gov/pubmed/14578021
(9) http://www.ncbi.nlm.nih.gov/pubmed/14690874



Passionflower / Passiflora incarnata L.
Family: Passifloraceae 
by Gayle Engels, Josef Brinckmann
HerbalGram. 2016; American Botanical Council

Commonly known as passionflower, purple passion flower, or maypop, Passiflora incarnata is one of approximately 520 species in the family Passifloraceae. Species in this family are found primarily in Central and South America, and, less commonly, in North America, Australia, and Southeast Asia.1 Growing up to 25 feet in length, passionflower is an herbaceous vine that climbs using axillary tendrils, and it spreads aggressively by root suckers. It has deciduous (or evergreen, depending on the climate), three-lobed, dark green leaves that are whitish on the underside. Conspicuous, largely lavender corona flowers with showy pistils and stamens appear in spring through fall and are followed by yellow edible fruit (berries).2
Passiflora incarnata is native to the southeastern United States3 and is currently distributed from Florida west to Texas, north to southeastern Kansas, and east to Virginia,4 where it is cultivated in gardens and found in disturbed sites, along fences, by roadsides, in thickets, and on waste grounds.1 The northern limits of passionflower’s current range are an extension of its original habitat due to increasing anthropogenic effects (i.e., the influence of human activities on nature). Archeological evidence indicates, for example, that P. incarnata did not occur in Arkansas or Kentucky prior to the 1550s.4 In the 17th century, European colonizers brought P. incarnata to Europe, where it was introduced, domesticated, and is still cultivated today, particularly in Mediterranean France and Italy, where there are several certified organic farms growing passionflower for the herbal market.
While some of the material of commerce is obtained from cultivation in the United States and parts of southern Europe, much of the commercial supply of passionflower is still wild-collected in the southeastern United States. The entire vine, including stems, leaves, flowers, and fruits, is harvested by hand starting in the late spring (when it begins to flower) from disturbed areas, fields, and early successional habitats.5*
Although the second edition of the American Herbal Products Association’s Herbs of Commerce also lists other passionflower species — namely, P. caerulea (blue passionflower), P. coriacea (bat-leaf passionflower), P. edulis (purple granadilla or purple passionflower), P. foetida (stinking passionflower), and P. laurifolia (yellow granadilla or bay-leaf passionflower)6 — this article focuses on P. incarnata. 

HISTORY AND CULTURAL SIGNIFICANCE
Historically, various P. incarnata plant parts have been used as food or medicine by Native American tribes in the southeastern United States, including the Apalachee and Creek (both of Florida),7 Cherokee (Georgia, North and South Carolina, Tennessee, Virginia), Houma (Louisiana),8 and Powhatan (Virginia).9 Seeds of P. incarnata are often found among archaeobotanical artifacts at excavation sites (e.g., at the Early Historic North American archaeological period [17th century] Creek town of Fusihatchee in Alabama, and at several Apalachee sites in North Florida).7 According to archeological evidence, human use of P. incarnata began in the Late Archaic period (3,500-800 BCE) in North America. Seeds have been identified at Late Archaic period sites in Alabama and Tennessee; Early Woodland period (800 BCE-200 CE) sites in Georgia; Middle Woodland period (100 BCE-550 CE) sites in Alabama and Tennessee; Late Woodland period (550-1000 CE) sites in Alabama, Louisiana, and Tennessee; Mississippian/Protohistoric period (1000-1550 CE) sites in Alabama, Georgia, North and South Carolina, Tennessee, Mississippi, and Virginia; and Historic period (1550-1800 CE) sites in Georgia, North Carolina, and Tennessee.4

In his manuscript The Historie of Travaile Into Virginia Britannia, William Strachey, an English writer who served as the first Secretary of the Colony of Virginia in 1610, documented Algonkian food uses of wild passionflower fruits, which the indigenous referred to as “maracock,” in coastal Virginia.10 It has been suggested that the origin of one of passionflower’s common names “maypop” is an alteration of “maycock,” a name derived from the Powhatan (Virginia) name “mahcawq.” But the name may also refer to the sound made when the buds begin popping in the month of May, or to the popping sound that is made when the fruits are crushed or stepped on.7
The genus name Passiflora and the corresponding vernacular name “passionflower” originate from the Italian fiore della passione, a name given to the flower in a context of Christian symbology (objects associated with the crucifixion of Christ).4 This story can be traced back to 1605 CE at the start of the papacy of Pope Paul V (1552–1621), when a live P. incarnata plant was given to the pope and planted as a gift in his honor. First described in a treatise on New World flora written by the Italian Dominican monk Simone Parlasca and published in 1609,11 as well as in a 1619 publication by Neapolitan Dominican monk and druggist Fra Donato d’Eremita,12 the flower’s corona was represented as resembling the crown of thorns, the three styles being the nails of the cross, the three-lobed leaves the spear, and the five anthers representing the marks of the five wounds, among other correlations.13 Passionflower was first introduced into England in 1629 as a greenhouse plant later described in a folio (pamphlet) titled Six Numbers of Coloured Figures of Passion Flowers by Mary Lawrance.14

In 1838, W.B. Lindsay of Bayou Gros Tête, Louisiana, brought the clinical use of inspissated (thickened or congealed) passionflower juice to the attention of his friend David Lewis Phares of Newtonia, Mississippi, after having prescribed it for 30 years (since about 1808) with reportedly successful outcomes in cases of tetanus neonatorum.† In his early years of dispensing passionflower juice, Lindsay had attributed observed differences in dosage strength and efficacy to an incorrect assumption that preparations were being made from different species of Passiflora. He was later convinced that the medicines had all been made from P. incarnata but that the differences were due to dissimilarities in season of gathering, mode of preparation, and locality of growth. (For example, Lindsay believed that passionflower wild-collected on uplands and in Bayou Gros Tête made the strongest medicine, while passionflower collected near dikes or levees around New Orleans was inferior.) Later, in their clinical practices, both Phares and his son, J.H. Phares, reported success using passionflower juice to treat tetanus erectus in horses.14 D.L. Phares reportedly also carried out human trials, published in the New Orleans Medical Journal, using passionflower preparations made by Lindsay.
In the late 19th century, Isham Jabus Marshall Goss, MD (1819-1896), of Georgia introduced the use of passionflower into Eclectic medical practice. According to the 18th edition of King’s American Dispensatory (3rd Revision), published in 1898, specific indications for use of passionflower liquid extracts in the Eclectic system of medicine included “irritation of brain and nervous system with atony; sleeplessness from overwork, worry, or from febrile excitement, and in the young and aged; neuralgic pains with debility; exhaustion from cerebral fullness or from excitement; convulsive movements; infantile nervous irritation; nervous headache; tetanus; hysteria; oppressed breathing; cardiac palpitation from excitement or shock.”15

Traditional European uses of the plant include for anxiety, constipation, indigestion, insomnia, nervousness, and mild infections.1 In Poland, it has been used for hysteria and neurasthenia, while, in Turkey, in addition to insomnia, it has been used for epilepsy, painful menstruation (dysmenorrhea), neuralgia, and neurosis.1
Defined as the dried herbage of “Passiflora incarnata Linné” collected after some of the berries have matured, “Passiflora” entered the fourth edition of the National Formulary (NF IV) in 191616 and remained officinal through the fifth edition (NF V) until 1936. A monograph for “Tinctura Passiflorae” was also included in the NF V.17 The 20th edition of The Dispensatory of the United States of America, published in 1918, added monographs describing both “Passion Flower N.F.” and “Tinctura Passiflorae N.F.”18
In 1975, the US Food and Drug Administration (FDA) considered inclusion of “passion flower extract” as a sedative active ingredient in its proposal to establish a monograph for over-the-counter (OTC) nighttime sleep-aid and daytime sedative drug products. Although “passion flower extract” was a labeled active ingredient in marketed sedative drug products at that time, the FDA’s Advisory Review Panel on OTC Sedative, Tranquilizer and Sleep-Aid Drug Products was unable to find sufficient evidence to demonstrate that it induced sedation. The panel initially classified the use of passion flower extract in nighttime sleep-aid products as “irrational.”19 In 1978, while still included in the ongoing review of nighttime sleep-aid active ingredients, the FDA issued a tentative final order placing passion flower extract into Category II, meaning “nonmonograph” or “Not Generally Recognized as Safe and Effective” (not GRASE).20

Another eleven years passed before the FDA would issue its final rule in 1989, which classified passion flower extract as nonmonograph. OTC nighttime sleep-aid drug products containing passion flower extract could no longer be marketed unless the product was the subject of an approved New Drug Application (NDA). Existing passionflower drug products were then required to be phased out of the market.21 By the time the Dietary Supplement Health and Education Act (DSHEA) of 1994 was passed, passionflower-based products were transitioned from OTC drug to the newly established dietary supplement framework. In 2000, the FDA ruled that some OTC drug monograph claims would be acceptable as structure-function claim statements, including claims listed in its nighttime sleep-aid monograph (in particular, “for the relief of occasional sleeplessness,” because occasional sleeplessness is not a characteristic symptom of a disease).22 In this case, it turned out that certain passionflower-based dietary supplements could now be marketed with the same claim statement as when previously labeled and marketed as OTC sleep-aid drug products, provided that the notifying company had compiled a substantiation file containing sufficient levels of evidence to support the claim for its specific product.
In 1985, the German Commission E approved the use of passionflower herb, prepared as an herbal tea infusion or equivalent galenical preparation, as a nonprescription medicine for treating nervous restlessness.23 Since then, national labeling standards monographs of European Union (EU) member states, such as those of the German Commission E, have been superseded by monographs of the European Medicines Agency (EMA). In Germany, the aerial parts (herb) of P. incarnata remains classified as both medicine and food (depending on dose) and appears on List B in Germany’s List of Substances, meaning that restricted use in foods is recommended because pharmacological effects occur above a certain dose.24

A quality standards monograph for “Passiflorae Herba” first entered the European Pharmacopoeia (PhEur) in the 2000 supplement to the 1997 third edition25 and has remained official through the current ninth edition published in July 2016.26 In 2007, a comprehensive monograph (quality and therapeutics) for “Herba Passiflorae” entered volume three of the WHO Monographs on Selected Medicinal Plants.27 In the same year, the EMA published a labeling standards monograph (later superseded by a 2014 revised monograph),28 and the following year, Health Canada published its labeling standards monograph.29 Although a quality standards monograph for “Pasiflora, Parte Aérea” entered the Mexican Pharmacopoeia in 2013,30 remarkably there is not yet an official quality standards monograph available in the United States Pharmacopeia (USP) for this widely used medicinal plant that is native to the United States.
Currently, herbalists employ P. incarnata for its analgesic, antispasmodic, hypnotic, nervine, and hypotensive effects. It has proven useful as a sedative for intractable insomnia, for relieving nerve pain, and for addressing seizures and asthma associated with spasms and tension.31
An online retrospective survey of the use of herbal anxiolytics by college students published in 2012 revealed that passionflower was the most commonly used herbal dietary supplement for reducing anxiety. Of 235 students who responded, 85 (36.2%) used passionflower in the previous 12 months (of those 85 students, 55 used it less than 10 times, 19 used it monthly, nine weekly, and two daily).32 The most common reasons given for using an herbal dietary supplement were recommendation by friends or family (38%), ease of obtaining dietary supplement (36.3%), and lower cost compared to prescription drugs (23.1%).

CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES
In the United States, passionflower may be used as a natural flavoring substance, so long as the minimum quantity to produce the intended effect is used.33 (The FDA regulation specifically lists “passion flower [Passiflora incarnata L.],” but it may be safe to assume that passionflower fruit and extracts thereof are included in the scope of the regulation.) Passionflower is also permitted as a component of dietary supplement products, requiring FDA notification within 30 days of marketing if a structure-function claim is made and product manufacturing according to dietary supplement current good manufacturing practices (cGMPs).34
In Canada, passionflower is regulated as an active ingredient of licensed natural health products (NHPs) requiring pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD). Labels of licensed NHPs prepared from British or European pharmacopeial-quality passionflower may carry the claim statement “Traditionally used in Herbal Medicine as a sleep aid (in cases of restlessness or insomnia due to mental stress).”30 Additionally, passionflower is listed in the draft “Cognitive Function Products” monograph as a sedative active ingredient.35 At the time of this writing (September 2016), 547 licensed NHPs list P. incarnata as an ingredient, of which 543 products list it as a medicinal ingredient, and four NHPs list it as a non-medicinal ingredient.36

For herbal medicinal product companies in the EU, or in non-EU countries where the PhEur is an official compendium (e.g., Australia and Canada), there are quality standards monographs established by the European Directorate for the Quality of Medicines (EDQM) for “Passion Flower Herb” containing a minimum of 1.5% flavonoids (expressed as vitexin), and “Passion Flower Dry Extract” containing a minimum of 2.0% flavonoids (expressed as vitexin), which can be used as the basis for active ingredient specifications.29 Registered Traditional Herbal Medicinal Products (THMPs) composed of PhEur-quality passionflower and prepared as herbal teas, liquid extracts, or as solid dosage forms containing dry extract, may be labeled and marketed “for relief of mild symptoms of mental stress and to aid sleep.”28
For use in cosmetic products, the European Commission Health and Consumers Directorate lists “Passiflora Incarnata Extract” (extract of whole plant) for astringent function. “Passiflora Incarnata Flower Extract” is listed for skin-conditioning and skin-protecting functions, and “Passiflora Incarnata Water” (aqueous solution of the steam distillates obtained from passionflower) is listed for masking and skin-conditioning functions.37

MODERN RESEARCH
Passiflora incarnata herb contains 1-2.5% flavonoids (pharmacopeial quality contains minimum 1.5% flavonoids, expressed as vitexin), consisting almost exclusively of C-glycosyl flavones. The proportion of each individual flavonoid is, however, highly variable. For example, isovitexin-2”-O-glucoside is present at 0.1 to 0.8%, isoshaftoside at 0.05 to 0.5%, shaftoside at 0.02 to 0.61%, and isoorientin-2”-O-glucoside at 0.1 to 0.46%, and in some types swertisin is present (at about 0.3%). There are only small amounts of vicenin-2 and lucenin-2, and very low levels of orientin and vitexin. Passionflower also contains polysaccharides (especially arabinoglucan), free amino acids including gamma-aminobutyric acid (GABA), and trace amounts of harmala alkaloids.38 Wohlmuth et al. (2010) attribute the high variability of flavonoid levels in different samples to the existence of two distinct chemotypes. The type that contains swertisin is almost absent of shaftoside and isoshaftoside.39
In vivo and in vitro studies of P. incarnata show limited support of its anti-anxiety, antiasthmatic, anticonvulsant, antidiabetic, antiseizure, antitussive, and sedative properties.1,40-44
Passionflower is primarily used in combination with other herbs, and clinical evidence of its efficacy as a monopreparation is limited. There are, however, at least six clinical studies on P. incarnata alone for conditions including anxiety, sleep, and attention deficit hyperactivity disorder (ADHD).
In a randomized, single-blind study from 2013, 63 patients needing periodontal treatment were randomly assigned into one of three groups of 21 to test the efficacy of passionflower in reducing dental anxiety. One group was given 20 drops of passionflower extract (Pasipay, 30% hydroalcoholic extract with total flavonoid content of 4% w/w, including vitexin and rutin; Iran Darouk Pharmaceutical Co.; Tehran, Iran) the night before treatment and 20 drops following treatment. In the placebo group, the placebo drops were administered in the same way. The third group received no intervention. Patients filled out the Corah’s Dental Anxiety Scale, Revised (DAS-R) at the initial interview and following the intake of medication before periodontal treatment. The passionflower group experienced a significant reduction in anxiety following administration of the drops, from 12.09 ± 2.42 down to 8.47 ± 2.08 (P < 0.0001). There was no significant reduction in anxiety in the other two groups.45

A randomized, double-blind, placebo-controlled (RDBPC) prospective study published in 2011 investigated the effect of passionflower on preoperative anxiety. Forty-five minutes prior to receiving spinal anesthesia, 60 patients completed both parts of the State-Trait Anxiety Inventory (STAI) questionnaire to measure basic anxiety and induced anxiety. Sedation level and psychomotor function were also measured. Thirty minutes prior to receiving anesthesia, hemodynamics were measured via heart rate and systolic, diastolic, and mean arterial pressures, and the patients were randomly assigned to two groups. Patients received either passionflower syrup (700 mg/5 mL aqueous extract; Sandoz, Kocaeli, Turkey; no additional information provided) or placebo. All of the tests were performed again just prior to administration of anesthesia, and there was a statistically significant increase in STAI scores in the placebo group but no other statistically significant differences. The authors state that oral administration of P. incarnata suppresses the increase in anxiety before spinal anesthesia without affecting psychomotor function, sedation level, or hemodynamics.46

Another RDBPC study published in 2008 evaluated the efficacy of passionflower in reducing preoperative anxiety. Sixty patients scheduled for inguinal herniorrhaphy (surgical repair of a hernia in which a loop of the intestine has protruded through a weak area of the adominal wall) were randomly assigned into one of two groups. One group received 500 mg of Pasipay 90 minutes before surgery; the other received placebo. Each patient’s anxiety and sedation were assessed using a numerical rating scale (NRS) before taking medication and at 10, 30, 60, and 90 minutes after. Psychomotor function also was assessed upon arrival in the operating room and 30 and 90 minutes after tracheal extubation. The Pasipay group experienced significantly lower mean NRS scores over time (P < 0.001) with no other significant differences between groups. This suggests that oral administration of passionflower prior to surgery can reduce anxiety without inducing sedation.47

In 2001, a randomized, double-blind, controlled study compared the efficacy of passionflower to the conventional pharmaceutical sedative drug oxazepam in treating generalized anxiety disorder (GAD). Outpatients diagnosed with GAD (N = 36) at least six months prior to the study were randomly assigned to receive either 45 drops/day of Pasipay plus a placebo tablet or 30 mg/day oxazepam plus placebo drops for four weeks. Both Pasipay and oxazepam were effective in treating GAD, and while there were no significant differences between the two groups regarding total side effects, patients on oxazepam experienced significantly more problems related to impairment of job performance.48

One double-blind, placebo-controlled, repeated-measures study published in 2011 investigated the effects of passionflower tea on sleep. Healthy volunteers (N = 41) were recruited and provided information regarding their health and sleeping patterns. All had mild sleep difficulties and were not taking any medications or remedies other than contraception. Passionflower tea bags (2 g of dried P. incarnata leaves, stems, seeds, and flowers; Hilde Hemmes’ Herbal Supplies Pty. Ltd.; Ridgehaven, South Australia) or parsley tea bags (2 g of Petroselinum crispum [Apiaceae]; same producer) were provided with brewing instructions. Each participant drank one tea or the other each night for a week while keeping a sleep diary (which included a subjective report of their sleep, as well as the number and duration of naps, types and amounts of caffeine and alcohol consumption, and bedtime). Participants also completed the STAI questionnaire on the seventh morning. After a one-week washout period, participants switched to the other tea and repeated the process for another week. Additionally, 10 volunteers participated in overnight polysomnography (PSG) on the last night of each treatment period, the results of which were used to validate sleep diaries. Of the PSG and subjective sleep parameters analyzed, subjective sleep quality alone was significantly better in the passionflower group than in the placebo group. The authors opined that the small sample size limited the power of the statistical analysis. Furthermore, they stated that the passionflower tea dose was three times less than the recommended dosage and questioned if tea might not be the most effective way of administering passionflower. They also suggested that using volunteers with mild sleep issues rather than clinically diagnosed insomnia left little room for improvement and that their study may have been too short to observe significant improvement.49

Based on the German Commission E’s approval of passionflower for nervous restlessness and the British Herbal Compendium’s indication of passionflower for ADHD, researchers in 2003 conducted an eight-week, randomized, parallel group study on 34 children diagnosed with ADHD. One group was administered Pasipay (0.04 mg/kg/day, twice daily) and the other methylphenidate (1 mg/kg/day, twice daily). Patients were assessed by a child psychiatrist at baseline, 14, 28, 42, and 56 days. There were no significant differences between the two groups at baseline or during the course of the study, and both groups showed significant improvement over eight weeks of treatment. The methylphenidate group did experience more probable side effects than the Pasipay group, including decreased appetite (seven subjects vs. two subjects, respectively) and anxiety/nervousness (six subjects vs. no subjects, respectively). The authors suggest that passionflower may be an appropriate treatment for ADHD, especially in children who do not tolerate pharmaceutical stimulants, but that larger studies are needed to confirm their findings.50
One RDBPC study from 2001 investigated the efficacy of passionflower as an adjuvant to help with anxiety and insomnia during detoxification from opioids using clonidine. Male opioid addicts (N = 65) were randomly assigned to receive either 0.8 mg/day of clonidine plus 60 drops of “passiflora extract” (no further information provided) or 0.8 mg/day of clonidine plus 60 drops of placebo, three times per day in divided doses. Severity of opioid withdrawal syndrome was measured on days 0, 1, 2, 3, 4, 7, and 14 using the Short Opiate Withdrawal Scale (SOWS). Both groups experienced significant alleviation of physical withdrawal symptoms, but the passiflora-clonidine group experienced a significant reduction in mental symptoms starting on day 2, which was not the case in the clonidine-only group. The authors suggest that passiflora may indeed be an effective adjuvant in the management of opioid withdrawal but that further, larger studies are needed to confirm these results.51
As mentioned previously, passionflower is most often used in combination with other herbs, and there have been studies that have investigated the efficacy of these combinations. In a randomized, controlled trial published in 2013, NSF-3 (410 mg of polyherbal extract containing 80 mg of passionflower, 300 mg of valerian [Valeriana officinalis, Caprifoliaceae], and 30 mg of hops [Humulus lupulus, Cannabaceae]; M/s Tablets India; Chennai, India) performed as well as the conventional pharmaceutical sedative zolpidem in improving total sleep time, sleep latency, and insomnia index scores, and decreasing number of nightly awakenings.52
An Italian study published in 2011 showed that children taking 0.5 mL/kg body weight of Vagostabil Junior (containing California poppy [Eschscholzia californica, Papaveraceae] aerial parts dry extract titrated to 0.8% total alkaloids expressed as protopine, and passionflower aerial parts dry extract titrated at 4% minimum total flavonoids expressed as vitexin; Cristalfarma; Milan, Italy) had significantly improved sleep quality without adverse effects over the course of 14 days.53

FUTURE OUTLOOK
There are no known comprehensive reports available on the conservation status of wild P. incarnata in its native southeastern United States habitat. However, the passionflower vine thrives in human-disturbed areas, and its geographical distribution has expanded over time. In some places where it has been introduced outside of its native habitat, the species is considered invasive.8 Even within its geographical origin, the vines spread from its natural areas along edges of forested areas into agricultural fields, pastures, and citrus groves.5 According to Lockard and Swanson (1998), “Many farmers find this plant to be a nuisance and might very well accept your offers to harvest it.”54 For sustainable wild-collection, Lockard and Swanson recommend that harvesters should not disturb the roots, leave at least 10% of a passionflower vine patch unharvested in order to facilitate regeneration, and rotate patches rather than returning to the same patch year after year. Harvesting should be carried out “on sunny days, late in the morning after the dew has dried.”54
In recent decades, some herbal product companies have switched from wild-collected passionflower herb to material produced under controlled cultivation. One reason for this switch is that passionflower vines are climbers that attach to, and get tangled up with, other plants, particularly with other climbing vines. This can make it difficult for harvesters to completely separate out passionflower aerial parts and avoid unintentional adulteration with plant parts of non-target species.54 Furthermore, highly invasive Asian climbing vines, including kudzu (Pueraria montana var. lobata, Fabaceae) and precatory (Abrus precatorius, Fabaceae), now share habitat with P. incarnata vines in the southeastern US. Both kudzu and precatory are listed as noxious weeds in Category I of the Florida Exotic Pest Plant Council (FLEPPC) list of invasive plant species. Category I species are defined as “invasive exotics that are altering native plant communities by displacing native species, changing community structures or ecological functions, or hybridizing with natives.”55 Toxic precatory vine plant parts have been implicated in the past as potential adulterants to various wild-harvested materials.56 And for passionflower cultivated outside its native habitat, potential contamination with pyrrolizidine alkaloid (PA)-containing weeds (particularly in Europe) was identified in a May 2016 public statement by the EMA. The EMA listed “Passiflorae herba” among the top 10 herbal ingredients most likely affected by PA contamination and therefore made recommendations for risk management and quality control, including that farms should implement “significantly enhanced” good agricultural and collection practices (GACPs) to mitigate the risk.57
Although in recent years there have been occasional market shortages of certified organic passionflower of pharmacopeial quality, there is evidence that passionflower production is occurring increasingly through sustainable agricultural practices, along with very recently enhanced GACPs to avoid contamination with non-target weed species. Presently, the main source countries for certified organic cultivated passionflower are France and Italy, but organic cultivation is also increasing in the United States, especially at farms in Kentucky, Missouri, North Carolina, and California. Given that P. incarnata is not an endangered or threatened species in its native habitat (although potentially competing with highly invasive climbing vines), and that controlled cultivation is also increasing, it appears that increased global demand can be satisfied through sustainable production methods.
The use of passionflower herb (or extracts thereof) as an active ingredient of traditional herbal medicines, modern phytomedicines, and herbal dietary supplements is likely to continue to increase globally, as are sustainable production systems, whether through controlled cultivation or wild-harvesting. Some experts, however, have cautioned that care must be taken by companies to identify and select specific chemotypes in order to ensure reproducible quality and efficacy.39
 
–Gayle Engels and Josef Brinckmann
 
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22. Food and Drug Administration (FDA). Regulations on Statements Made for Dietary Supplements Concerning the Effect of the Product on the Structure or Function of the Body; Final Rule. Federal Register. 2000;65(5):1000-1050.
23. Blumenthal M, Busse WR, Goldberg A et al, eds. Klein S, Rister RS, trans. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston, MA: Integrative Medicine Communication; 1998.
24. Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (BVL). List of Substances of the Competent Federal Government and Federal State Authorities: Category “Plants and plant parts.” Cham Heidelberg New York Dordrecht London: Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (BVL); 2014:112.
25. European Pharmacopoeia Commission. Europäisches Arzneibuch Nachtrag 2000. Stuttgart/Eschborn: Deutscher Apotheker Verlag/Govi-Verlag — Pharmazeutischer Verlag GmbH; 2000.
26. European Pharmacopoeia Commission. European Pharmacopoeia Ninth Edition (PhEur 9.0). Strasbourg, France: European Directorate for the Quality of Medicines; 2016.
27. World Health Organization. WHO Monographs on Selected Medicinal Plants Volume 3. Geneva, Switzerland: World Health Organization; 2007.
28. Committee on Herbal Medicinal Products. Community herbal monograph on Passiflora incarnata L., herba. London, UK: European Medicines Agency; 2014.
29. Natural and Non-prescription Health Products Directorate. Passionflower. Ottawa, ON: Health Canada; 2008.
30. Comisión Permanente de la Farmacopea de los Estados Unidos Mexicanos. Farmacopea Herbolaria de los Estados Unidos Mexicanos (FHEUM), Segundo edición. México: Secretaría de Salud; 2013.
31. Hoffmann D. Medical Herbalism: The Science and Practice of Herbal Medicine. Rochester, VT: Healing Arts Press; 2003.
32. Birkett M. Use of anxiolytic natural products by college students. J Altern Complement Med. 2012;18(6):527-528.
33. US Food and Drug Administration (FDA). § 172.510 Natural flavoring substances and natural substances used in conjunction with flavors. Code of Federal Regulations, Title 21. Washington, DC: US Government Printing Office; 2016:57-60.
34. US Food and Drug Administration. 21 CFR Part 111 Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; Final Rule. Federal Register. 2007;72(121):34752-34958.
35. Natural and Non-prescription Health Products Directorate. Cognitive Function Products. Ottawa, ON: Health Canada; 2014.
36. Natural and Non-prescription Health Products Directorate. Licensed Natural Health Products Databases. Ottawa, ON: Health Canada; 2016.
37. European Commission Health & Consumers Directorate. Cosmetic Ingredients and Substances (CosIng) Database. Brussels, Belgium: European Commission; 2016.
38. Blaschek W (ed.). Wichtl — Teedrogen und Phytopharmaka — Ein Handbuch für die Praxis. 6. Auflage. Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft. 2016;472-475.
39. Wohlmuth H, Penman KG, Pearson T, Lehmann RP. Pharmacognosy and chemotypes of passionflower (Passiflora incarnata L.). Biological and Pharmaceutical Bulletin 2010;33(6):1015-1018.
40. Elsas S-M, Rossi DJ, Raber J, et al. Passiflora incarnata L. (passionflower) extracts elicit GABA currents in hippocampal neuron in vitro, and show anxiogenic and anticonvulsant effect in vivo, varying with extraction method. Phytomedicine. 2010;17:940-949.
41. Appel K, Rose T, Fiebich B, Kammler T, Hoffmann C, Weiss G. Modulation of the γ-aminobutyric acid (GABA) system by Passiflora incarnata L. Phyto Res. June 2011;25(6):838-843. doi: 10.1002/ptr.3352.
42. Traub M. Passionflower (Passiflora): An Overview of the Research and Clinical Indications. Brevard, NC: Gaia Herbs; 2012.
43. Nassiri-Asl M, Shariati-Rad S, Zamansoltani F. Anticonvulsant effects of aerial parts of Passiflora incarnata extract in mice: involvement of benzodiazepine and opioid receptors. BMC Complementary and Alternative Medicine. 2007;7:26.
44. Schulz H, Jobert M, Hübner WD. The quantitative EEG as a screening instrument to identify sedative effects of single doses of plant extracts in comparison with diazepam. Phytomedicine. December 1998;5(6):449.458.
45. Kaviani N, Tavakoli M, Tabanmehr MR, Havaei RA. The efficacy of Passiflora incarnata Linnaeus in reducing dental anxiety in patients undergoing periodontal treatment. J Dent Shiraz Univ Med Scien. 2013;14(2):68-72.
46. Aslanargun P, Cuvas O, Dikmen B, Aslan E, Yuksel MU. Passiflora incarnata Linneaus as an anxiolytic before spinal anesthesia. J Anesth. 2012;26:39-44.
47. Movafegh A, Alizadeh R, Hajimohamadi F, Esfehani F, Nejatfar M. Preoperative oral Passiflora incarnata reduces anxiety in ambulatory surgery patients: a double-blind, placebo-controlled study. International Anesthesia Research Society. June 2008;106(6):1728-1732.
48. Akhondzadeh S, Naghavi HR, Vazirian M. Shayeganpout A, Rashidi H, Khan M. Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. Journal of Clinical Pharmacy and Therapeutics. 2011;26:363-367.
49. Ngan A, Conduit R. A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (passionflower) herbal tea on subjective sleep quality. Phytother Res. August 2011;25(8):1153-1159.
50. Akhondzadeh S, Mohammadi MR, Momeni F. Passiflora incarnata in the treatment of attention-deficit hyperactivity disorder in children and adolescents. Therapy. 2005;2(4):609-614.
51. Akhondzadeh S, Kashain L, Mobaseri M, Hosseini SH, Nikzad S, Khani M. Passionflower in the treatment of opiates withdrawal: a double-blind randomized controlled trial. J Clin Pharm Ther. 2001;26:369-373.
52. Maroo N, Hazra A, Das T. Efficacy and safety of a polyherbal sedative-hypnotic formulation NSF-3 in primary insomnia in comparison to zolpidem: a randomized controlled trial. Indian J Pharmacol. January-February 2013;45(1):34-39.
53. Sannia A, Forti S, Cesarani A. Efficacy of complex herbal compound of Eschscholtzia californica and Passiflora incarnata (Vagostabil® Junior) on sleep disturbances during pediatric age [in Italian]. Minerva Pediatrica. December 2011;63(Suppl. 1, N. 6):1-6.
54. Lockard A, Swanson AQ. A Digger’s Guide to Medicinal Plants. Eolia, MO: American Botanicals; 1998.
55. FLEPPC. List of Invasive Plant Species. Florida Exotic Pest Plant Council; 2015.
56. Flaster T, Lassiter J. Quality control in herbal preparations: using botanical reference standards for proper identification. HerbalGram. 2004;63:35-37.
57. Committee on Herbal Medicinal Products. Public statement on contamination of herbal medicinal products/traditional herbal medicinal products with pyrrolizidine alkaloids: Transitional recommendations for risk management and quality control. London, UK: European Medicines Agency; 2016.



Passiflore
A l'origine, cette plante qui contient harmane, harmine, harmaline, harmol et harmalol pouvait être considérée comme une  drogue ayant un effet sédatif et hypnotique de par la présence de  ces alcaloïdes. Ces constituants sont proches de ceux que contient  Peganum harmala, une plante calmante mais toxique [4] !
Constatant l’effet sédatif d’un extrait de passiflore, Soulimani et al. en 1997 [5]  pensaient déjà à un éventuel effet des flavonoïdes. Aujourd’hui, c’est la vitexine  (flavonoïde) et ses métabolites qui seraient les principes actifs responsables de  l’effet sur le système nerveux central [3]. La vitexine et ses métabolites sont aussi  présents dans d’autres plantes comme l’aubépine, la réglisse, la salicaire, l’origan,  Rumex acetosa, le fenugrec, etc.

Parmi les nouvelles indications dérivant des effets sédatifs, on retiendra que la  passiflore faciliterait le sevrage aux diazépines, aux opioïdes, au tabac, à la nicotine, à l’alcool [1,2,6]. L’extrait de passiflore est un antagoniste de l’expression de la  sensibilisation locomotrice de la nicotine.
Le dernier symposium de Grasse, le Phyt’arom, a permis de découvrir un essai  d’extrait de myrtille contre la dégénérescence cognitive [7] et l’utilisation de l’hibiscus dans l’infection urinaire [8].
La phytothérapie est en perpétuel renouveau. De nouveaux principes actifs, de  nouveaux modes d’action, de nouvelles indications, quelques fois aussi la survenue  d’effets secondaires, de contre-indications, de précautions d’emploi, etc. À l’heure où  les caisses réduisent ou suppriment des médications, la phytoaromathérapie apporte  des solutions. Faut-il encore qu’elle reste abordable au maximum de bourses.

Références
1. Akhondzadeh S, Naghavi HR, Vazirian M, et al. (2001) Passion flower in the treatment of opiates withdrawal: a double-blind randomized controlled trial. J Clin Pharm Ther 26: 369–73
2. Breivogel C, Jamerson B (2012) Passion flower extract antagonizes the expression of nicotine locomotor sensitization in rats. Pharm Biol 50: 1310–6
3. Bureau L (2013) Plénière Phyt’arom 2013
4. Hammiche V, Merad R, Azzouz M (2013) Plantes toxiques à usage médicinal du pourtour méditerranéen. Springer-France, 447 p
5. Soulimani R, Younos C, Jarmouni S, et al. (1997) Behavioural effects of Passiflora incarnata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J Ethnopharmacol 57:11–20
6. Tomczyk M, Zovko-Koncić M, Chrostek L (2012) Phytotherapy of alcoholism. Nat Prod Commun 7: 273–80
7. Lafaye S (2013) Intérêt d’un extrait de fruit rouge titré en anthocyanes dans une formulation nutraceutique pour retarder et/ou diminuer la dégénérescence cognitive liée à l’âge (Phyt’arom 2013)
8. Meyer M (2013) L’Utirose™, extrait d’Hibiscus (Hibiscus sabdariffa) contre les infections urinaires (Phyt’arom 2013)


Z Phytother 2014; 35(05): 215-218
Passionsblume 
Wirkmechanismus der Passionsblume aufgeklärt
Christine Hoffmann, Inga Trompetter, Gabriele Weiß

Der Mensch reagiert auf Stress von jeher gleich: Der Körper bereitet sich auf eine anstrengende Leistung vor, denn für unsere Vorfahren bedeutete Stress eine Lebensbedrohung durch Tiere oder feindlich gesinnte Menschen. Es gab nur zwei mögliche Verhaltensweisen – Kampf oder Flucht. Beide erfordern eine erhöhte Handlungsbereitschaft der Muskulatur, des Kreislaufs und des zentralen Nervensystems. Diese wird v.a. durch die Ausschüttung zweier Stresshormone erreicht: Adrenalin und Cortisol. Sie bewirken einen erhöhten Tonus der Skelettmuskulatur, eine Erhöhung des Blutdrucks, der Atemfrequenz und des Blutzuckerspiegels. Andere energiefordernde Prozesse wie Wachstum und Verdauung werden heruntergefahren.

Im ZNS wird unter Stress die Verarbeitung von Reizen im Großhirn reduziert. Veränderte Ausschüttungsmuster der Neurotransmitter Serotonin und Noradrenalin sorgen stattdessen für eine Nutzung von Reaktionsmustern des Stammhirns, weil eine kognitive Einschätzung der Situation viel zu lange dauern würde. Diese Stressreaktion ist heutzutage meist nicht mehr zeitgemäß. Die Vorbereitungen des Körpers sind nur dann sinnvoll, wenn es im Anschluss zu einer körperlichen Anstrengung kommt und dadurch die bereitgestellte Energie abgebaut wird.

Auf heutige Stressoren wie Zeitdruck, Überforderung und Mehrfachbelastung folgt aber meist keine körperliche Anstrengung. Die Stresshormone werden nur langsam wieder abgebaut. Längerfristige Erhöhungen haben negative Folgen: Adrenalin und Cortisol bewirken einen ständig erhöhten Blutdruck und die Freisetzung körpereigener Fette, die die Blutgefäße schädigen. Cortisol reduziert die Abwehr von Viren und Bakterien. Auch die Wirkung von Insulin wird durch Cortisol verringert. Die Bauchspeicheldrüse kann dies zwar kurzfristig durch eine vermehrte Ausschüttung von Insulin ausgleichen, auf Dauer wird die Produktion jedoch reduziert – das Diabetesrisiko steigt. Darüber hinaus werden in Stresssituationen die Verdauungsorgane schlechter durchblutet, was zu Obstipation und einem erhöhten Entzündungsrisiko führen kann. Im Unterschied zur Magen- Darm-Muskulatur wird die Skelettmuskulatur überbeansprucht. Chronische Verspannungen bis hin zu Haltungs- und Gelenkschäden sind die Folge.

Und die Psyche leidet immer mit: Chronischer Stress geht mit nervöser Unruhe, Schlafstörungen und Angst einher. Langfristig können Angststörungen, ein Burnout- Syndrom oder eine Depression entstehen.

#
Stress im Griff
Neben dem Erlernen von Entspannungstechniken und einem achtsamen Umgang mit den eigenen Ressourcen kann auch eine medikamentöse Therapie Stresssymptome wie nervöse Unruhezustände und ihre Folgen reduzieren. Das Problem: Häufig werden schon bei leichten bis mittelschweren Stresssymptomen Benzodiazepine eingesetzt. Diese Medikamente können bei einer Einnahme von über 4 Wochen eine Abhängigkeit verursachen. Laut der Deutschen Hauptstelle für Suchtfragen e.V. wurden im Jahr 2010 fast 10 Mio. Packungen Benzodiazepine verschrieben. Zwischen einem Drittel und der Hälfte dieser Packungen wurden nicht wegen akuter medizinischer Probleme, sondern zur Vermeidung von Entzugserscheinungen verordnet. In Deutschland sind zwischen 1,1 und 1,2 Mio. Menschen von Benzodiazepinen abhängig; das sind 80% aller Medikamentenabhängigen ([9]). Laut dem BKKLandesverband Bayern werden die volkswirtschaftlichen Folgen der Medikamentenabhängigkeit in Deutschland auf ca. 14 Mio. Euro im Jahr geschätzt. Die Benzodiazepinabhängigkeit ist die dritthäufigste Suchterkrankung in Deutschland ([17]).

Hier gibt es phytotherapeutische Alternativen. Bei Stresssymptomen wie nervöser Unruhe, Angst und Schlafstörungen ist der Einsatz von Arzneimitteln mit Extrakten aus dem Kraut der Passionsblume (Passiflora incarnata L.) sicher und Erfolg versprechend. Auch Extrakte aus Baldrianwurzel, Hopfenzapfen, Lavendelöl oder Melissenkraut sind mögliche Optionen.

#
Mit Passiflora incarnata gegen Stress

Die Passionsblume stammt aus Amerika. Sie wurde dort von den Ureinwohnern wegen ihrer essbaren Frucht, der Maracuja, angebaut. Die Azteken erkannten aber auch die beruhigenden Effekte des Krautes und nutzten es bei Schlaflosigkeit und Nervosität. Über die spanischen Eroberer gelangte dieses Wissen nach Europa. Spanische Missionare gaben der Passionsblume ihren Namen, weil sie in ihrer Blüte die Passion Christi versinnbildlicht sahen. Seit dem 20. Jh. ist Passionsblumenkraut in Europa eine offizinelle Arzneidroge ([4], [8]).

In der Monografie der Kommission E wird die Verwendung von Passiflora-incarnata-Kraut zur Behandlung von nervöser Unruhe empfohlen ([18]). Laut der ESCOP-Monografie wird es erfolgreich bei Anspannung, Ruhelosigkeit und Einschlafstörungen angewandt ([14]). Das Committee on Herbal Medicinal Products der European Medicines Agency (EMA) hat 2007 eine eigene Monografie herausgegeben; hier wird der Einsatz von Passionsblumen- Extrakt im Rahmen des „traditional use“ bei leichten Stresssymptomen und zur Schlafförderung empfohlen ([12]).

Erst im letzten Jahrzehnt wurden klinische Studien mit Passionsblumenkraut-Extrakt durchgeführt, die vielversprechende Ergebnisse zeigten:

> die Wirkung auf leichte Verlaufsformen der generalisierten Angststörung ist vergleichbar mit 15 mg Oxazepam/Tag ([3])
> präoperative Angstsymptome werden gemildert ([6], [20])
> es konnte eine positive Wirkung bei Kindern mit ADHS gezeigt werden ([2])
> positive Effekte wurden beim Opiatentzug beobachtet ([1]).
Die Pascoe pharmazeutische Präparate GmbH hat in einer aktuellen Studie einen Nachweis der pharmakologischen Wirkung des Passionsblumen-Arzneimittels Pascoflair® 425 mg mittels quantitativer Erfassung der elektrischen Hirntätigkeit erbracht. Das Studiendesign war einfach verblindet, randomisiert und placebokontrolliert. Sechzehn gesunde Erwachsene beiderlei Geschlechts im Alter von 30–70 Jahren wurden untersucht. Verglichen wurden die psychophysiologischen und kognitiven Auswirkungen bei Einmaleinnahme der Tageshöchstdosis (3 Tabletten à 425 mg Extrakt) gegen Placebo. Es konnten statistisch abgesicherte Veränderungen der EEG-Profile gezeigt werden – mit einem Wirkmuster, welches im Einklang mit den beruhigenden und entspannenden Effekten steht. Der Wirkeintritt zeigte sich bereits nach 30 Minuten mit zeitabhängiger weiterer Wirkungszunahme. Die maximale beruhigende Wirkung wurde nach 3 Stunden erreicht. Es gab keinerlei Leistungsminderung in Bezug auf Wachheit und Konzentration. Im Rahmen der Studie wurden keine unerwünschten Ereignisse mit kausalem Zusammenhang festgestellt. Arzt und Probanden beurteilten die Verträglichkeit zu 81,3% als „sehr gut“ (übrige Nennungen: „gut“) ([10]).

Alle aufgeführten Studien bestätigen den beruhigenden und angstlösenden Effekt von Passiflora-incarnata-Extrakt auf das zentrale Nervensystem; über den genauen Wirkmechanismus gab es aber bis vor einigen Jahren nur sehr wenige Erkenntnisse.

#
Wirkmechanismus aufgeklärt

Die Effekte der Passionsblume führten zur Annahme eines Einflusses auf den Stoffwechsel des Neurotransmitters gamma- Aminobuttersäure (GABA). GABA ist der wichtigste endogene inhibitorische Neurotransmitter. Niedrige GABA-Spiegel im zentralen Nervensystem werden mit nervöser Unruhe, Angst, Depression und Schlaflosigkeit in Zusammenhang gebracht.
GABA moduliert eine Reihe von Verhaltensmechanismen und physiologischen Abläufen: Schlaf, Ernährungsverhalten, Sexualverhalten, Schmerz, kardiovaskuläre Regulation, Thermoregulation und Stimmung. Chronischer Stress wirkt sich negativ auf das GABA-System aus, er reduziert die Zahl der GABAergen Interneuronen im Hippocampus und beeinträchtigt kognitive Prozesse. Es gibt 2 Arten von GABA-Rezeptoren: GABAA- und GABAB-Rezeptoren. An GABAA-Rezeptoren greifen auch Barbiturate und Benzodiazepine an. Deshalb ist GABA der wichtigste Angriffspunkt in der Behandlung von Angstzuständen und Schlafstörungen. Eine medikamentöse Aktivierung dieses Systems hat sehr schnelle Effekte zur Folge ([15]).

Aber auch bei Depressionen spielt GABA eine Rolle: Die GABA-Spiegel im Gehirn depressiver Personen sind niedrig und können durch medikamentöse Behandlung erhöht werden.

In vivo (Maus) konnten für einen Passionsblumen- Extrakt (Passiflorae herbae extractum siccum Ph. Eur.; Droge-Extrakt- Verhältnis 5–7:1, Extraktionsmittel 50% Ethanol (V/V): Pascoflair® 425mg) anxiolytische Effekte gezeigt werden; sie waren GABA-vermittelt und vergleichbar mit Diazepam ([16]). In einer Arbeit von 2010 konnte erstmals ein Nachweis des genauen Wirkmechanismus eines Passiflora-incarnata- Extraktes in vitro erbracht werden ([5]). Die Untersuchungen beinhalteten Bindungsstudien an den GABA-, Benzodiazepin- und Ethanol-Bindungsstellen des GABAA- Rezeptors und am GABAB-Rezeptor. Zusätzlich wurden Effekte auf die GABA- Wiederaufnahme, die GABA-Freisetzung und die GABA-Transaminase-Aktivität untersucht:

GABA-Wiederaufnahme und -Freisetzung
Der Passionsblumen-Extrakt zeigte eine potente Hemmung der GABA-Wiederaufnahme in Cortex-Synaptosomen der Ratte mit einer mittleren effektiven Konzentration (EC50) von 95,7 μg/ml und einer maximalen Hemmung von 97,5 ± 7,2% ([5]) (Abb. 2). Passionsblumen-Extrakt ist also ein GABA-Wiederaufnahmehemmer. Ein Effekt auf die kaliuminduzierte [3H]-GABA-Freisetzung wurde dagegen nicht beobachtet.

 Zoom ImageZoom Image Abb.2:Wirkung des Passionsblumen-Extraktes auf die GABA-Aufnahme in Rattencortex-Synaptosomen (Mittelwert ± CI95); nach (5).

#
GABA-Bindungsstelle am GABAA-Rezeptor
Der Passionsblumen-Extrakt konkurrierte konzentrationsabhängig mit der Bindung des GABA-Antagonisten [3H]-SR95531 an Rattenhirnmembranen. Die mittlere inhibitorische Konzentration (IC50) lag bei 101 μg/ml (Abb. 3). Eine Bindung an die GABA-Bindungsstelle ist daher mit hoher Wahrscheinlichkeit ein Teil des Wirkmechanismus der Passionsblume.

 Zoom ImageZoom Image Abb.3: Kompetitive Bindung des Passionsblumen-Extraktes an die GABABindungsstelle des Ratten-GABAA-Rezeptors (Mittelwert ± SEM); nach (5).

#
Benzodiazepin-Bindungsstelle am GABAA-Rezeptor
Der Passionsblumen-Extrakt hemmte die Bindung des Benzodiazepin-Antagonisten [3H]-Ro-15-1788 nur in sehr hohen Konzentrationen (IC50 = 944 mg/ml). Zusätzlich wurde die Bindung nicht durch die Anwesenheit von GABA moduliert, wie es für Referenzsubstanzen wie Diazepam bekannt ist. Diese Ergebnisse machen eine Bindung des Passionsblumen-Extraktes an die Benzodiazepin- Bindungsstelle des GABAA-Rezeptors sehr unwahrscheinlich. Dies könnte eine Erklärung dafür sein, warum Passionsblumen- Extrakte im Gegensatz zu Benzodiazepinen kein Abhängigkeitspotenzial haben.

#
Ethanol-Bindungsstelle am GABAA-Rezeptor
Der IC50-Wert für die kompetitive Hemmung des Passionsblumen-Extrakts an die Ethanol-Bindungsstelle des GABAA-Rezeptors war sehr hoch: 512 mg/ml. Eine Bindung an diese Bindungsstelle ist also auch wenig wahrscheinlich und liefert somit eine weitere Erklärung für das nicht vorhandene Abhängigkeitspotenzial.

#
GABAB-Rezeptor
Der Passionsblumen-Extrakt konkurrierte konzentrationsabhängig mit der Bindung des GABAB-Rezeptorantagonisten [3H]-CGP 5462 an Rattenhirnmembranen. Die IC50 lag bei 120 mg/ml; eine Bindung an diesen Rezeptor scheint also wahrscheinlich.

Weiterhin wurde in einer [35S]-GTP-gamma- S-Bindungsstudie ermittelt, dass der Passionsblumen-Extrakt ein Antagonist dieses Rezeptors ist: Die Messung der Bindung des GTP-Analogs Guanosin-5′-O-(3- [35S]thio)triphosphats ([35S]-GTPgammaS) an das G-Protein eines G-Protein-gekoppelten Rezeptors ist eine Methode zur Messung der agonistischen Wirkung einer Substanz am Rezeptor. Hat eine Substanz keine agonistische Wirkung, kann durch Zugabe eines potenten Agonisten eine antagonistische Wirkung ermittelt werden ([7]). Der Passionsblumen-Extrakt hatte eine niedrigere IC50 (31 mg/ml) im Antagonisten- als im Agonisten-Modus (115 mg/ml). Daher scheint der Passionsblumen-Extrakt ein Antagonist am GABAB-Rezeptor zu sein. Dies erklärt auch die antidepressive Wirkung von Passionsblumen-Extrakten, da in In-vivo-Studien für GABAB-Antagonisten ein antidepressiver Effekt beschrieben wurde ([22]).

In einer zusätzlichen Untersuchung zeigte der Passionsblumen-Extrakt antagonistische Effekte an Adenosin-A1- und Cannabinoid- Rezeptoren. Antagonisten des Adenosin- A1-Rezeptors wurden in vivo als potente Anxiolytika und kognitionsfördernde Substanzen beschrieben ([19]). Cannabinoid- Rezeptorantagonisten mildern in vivo Entzugssymptome ([21]). Ein solcher Effekt konnte für die Passionsblume auch klinisch bestätigt werden ([1]); die beobachtete antagonistische Wirkung könnte der verantwortliche Mechanismus sein.

Online
http://dx.doi.org/10.1055/s-0034-1371745

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