Passion flower vine (Passiflora incarnata/edulis) is by far one of the most well rounded herbs the Amazon rainforest has to offer. There are over 300 species of passionflower, and recent evidence suggests that many of them can be used interchangeably. That said, the preferred species are generally considered to be Passiflora incarnata, and Passiflora edulis.

Passionflower is traditionally used as a tea, but can also be used effectively as a herbal extract or tincture. Its benefits include analgesic, muscle relaxant, antibacterial, anti-depressant, anti-anxiety, promotes calmness, slows racing thoughts, aids in falling asleep, fights cancer, protects the heart, and lowers blood pressure.

Passionflower is a good addition to most herbal treatment plans, as it helps to reduce the stress involved with many different conditions. It works great as a sleep aid without being overly sedating.Perhaps its best use is to treat the type of insomnia associated with stress or racing thoughts before bed time. Passionflower is even gentle, and effective enough to use with children, and has shown promise in treating those with ADD or ADHD.

Indications:

[15]

• Alcoholism
• Anxiety
• General pain
• Headaches
• Hyperactivity in children
• Hysteria, insomnia (especially stress related)
• Seizures
• Menstrual  cramps
• Muscle cramps
• Nerve tonic
• Neuralgia
• Rapid heart beat
• As an antispasmodic
• Topical analgesic
• Diuretic
• Colic in infants
• Asthma
• Coughs
• Menopausal symptoms
• Hypertension
• Ischemia
• Epilepsy

MENOPAUSAL SYMPTOMS:

M. Miroddi et al. (2013) [8] Refers to a clinical study done on menopausal women, found that P. incarnata was able to exert beneficial effects on precocious menopause symptoms (vasomotor signs, insomnia, depression, anger, headaches, etc). The researchers in this study suggested that health professionals can use it as an alternative to hormone therapy.

OPIATE WITHDRAWAL SYMPTOMS:

A study done reviewing the clinical studies of Passiflora incarnata referred to a clinical double blind randomized trial vs placebo that investigated the effects of Passiflora incarnata on patients undergoing opiate withdrawal. This trial found that P. incarnata in combination with clonidine (commonly used pharmaceutical noted to have a better ability to treat physical symptoms of opiate withdrawal than mental), was able to reduce the mental symptoms of opiate withdrawal (insomnia, craving, dysphoria, anxiety, agitation, irritability) successfully. [8].

Traditional Uses:

The use of Passiflora spp. dates back through many years and many cultures. It has been used in Ayurvedic, Unani, and Siddha medical systems [12], as well as Native Americans, and various cultures in Central and South America.

Prehistoric use of Passiflora incarnata dates back to the late Archaic period (8000-2000B.C) in North America, and is hypothesized by ethnobotanists to have been a minor food plant for native Americans rather than a staple [8]. Medicinally, it is documented that the Cherokee indians have used, and continue to use Passiflora spp. root tea as a tonic for the liver, and for skin boils. The roots are also pounded and used topically as an anti-inflammatory [8], and as an analgesic [16]. In Brazil Passiflora incarnata has been used as an analgesic, anti-spasmodic, wormicide, and sedative. [8]. In some other areas of the Amazon, the fruit used as a heart tonic and to calm coughs. [15]. P. feotida decoction of leaves and fruit are used traditionally in various Amazonian medical systems for diarrhea, asthma, biliousness, Peruvian medical systems, have commonly used passion fruit juice for UTIs, and as a mild diuretic [15].

In the 1800s in North America, the leaf infusion was used as a sedative, for headaches, and general pain, as well as topically for bruises, headaches, and general pain. [15]. Since then, in canada, europe, and USA, it has been used for well over the last 200 years as a tranquilizer, and anxiolytic. It has also been used for colic, diarrhea, dysentery, menstrual difficulties, insomnia, neuralgia, eye disorders, epilepsy, convulsions, muscle spasms, and pain in these regions. [15].

Countries outside South America, have used this plant for its sedative properties and as a narcotic (Iraq), to treat hysteria and neurasthenia (Poland), diarrhea, dysmenorrhoea, neuralgia (Turkey, America), burns, haemorrhoids, insomnia, and to treat patients affected by opiate dependence (India) [8]. Sasikala. V et al., (2011) [12] noted its use in various cultures for treating itches. Passiflora spp. flower has been used medicinally as a sedative, anxiolytic, antispasmodic, hypotensive. P. edulis, P. quadrangularis have both been used, however P. incarnata demonstrates the strongest effects [14].

When passion flower was found in Peru by a spanish doctor named Monardes, he took note of the indigenous uses, and brought it back to the old world from where he came [15]. Once Passiflora reached Europe, it became widely cultivated and used for mild symptoms of mental stress, anxiety, and mild sleep disorder [8]. The greatest admiration from the Europeans was during the 16th, and 17th centuries due in part from its beautiful flowers, and partly because of the belief that passion flowers were thought to represent the passion of Christ [16] hence its common name, passion flower.

Botanical Description:

Passiflora is the largest genus in the Passifloraceae family, consisting of nearly 500 species [12], with the addition of nearly 400 artificial hybrids [16]. In fact of the nearly 500 species, the vast majority are found in Central, or South America, with a few species rarely occurring in North America, Southeast Asia, and Australia [8].  Colombia is particularly rich in Passiflora as it accommodates more than 100 species , and contains nearly all sections of the genus [16].

The majority of the species in the Passiflora genus are perennial climbers, though some are trees (subgenus Astrophea), shrubs, herbaceous plants, and annuals [16]. M. Miroddi et al (2013) [8] describes Passiflora incarnata as an evergreen climbing vine reaching a height of up to 6m. The stems are vining, glabrous, herbaceous, and include tendrils. The leaves are alternate, 3-lobed, serrulate, petiolate, and herbaceous. Passiflora flowers are hermaphrodite and are very characteristic in overall look, containing 5 petals, and 5 sepals, 3 styles, and 3 stamens (typically). Flowering time is usually june-july, and produces its ripe seeds by october or november. Pollination usually occurs via bees [8], or other flying insects [16]. Some other species of Passiflora that are not included in this article are pollinated by hummingbirds, or bats [16].

The leaves of passiflora vary dramatically in size, and shape, and to some extent color, within the genus. In fact, Passiflora as a genus contains the most diverse leaf shapes out of any other genus of plant [16]. In Central, and South America exists the Heliconius butterfly, it is these butterflies that are given responsibility for the dramatic differences of Passiflora leaves. These butterflies feed exclusively on passionflower leaves during its caterpillar stage, so passionflower has altered it leaves in ways to match the other plants of its surroundings so as not to be seen by the observant butterflies [16]. This leaf variation even occurs at different stages of the plants development. In some rainforest species for example, the leaf forms of younger plants often resemble that of plants growing on the rainforest floor, changing throughout the years to eventually imitate the foliage of canopy plants as it ages and grows up and into the rainforest canopy [16].

Passiflora fruit can be described as large, or small berries, with the amount of seeds contained varying greatly. Fruit has a thick pericarp, except in the case of P. feotida where the pericarp is instead thin and papery. Generally, the morphology of Passiflora fruit is very diverse [16].

P. Edulis and P. incarnata are found in the Amazon Rainforest, and are the most commonly used species medicinally [15]. In the united states, Belize, Brazil, Colombia, guatemala, and India, P. incarnata is grown on a large scale and has become the most economically important medicinal species. This emphasis has most likely been placed on P. incarnata due to traditional use and lack of bioprospecting [16], as few other species have been tested medicinally, and the ones that have, for the most part have shown very similar effects including P. edulis, P. feotida, P. quadrangularis, P. anata, P. setacea, P. nitida, and P. tenufila [6, 12, 16, 14]. In fact P. incarnata, P. edulis, P. nitida, P. laurifolia, P. quadrangularis, P. feotida, P. alata, and the common flower shop and garden center species P. caerula are all found in the same Subgenus (also called Passiflora but is considered sub genus) [16].

Habitat, Ecology, Distribution:

P. feotida (Stinking passion flower) is South American in origin and is one of the few annual species contained in the Passiflora genus [16].

P. incarnata prefers more temperate zones, and is native to the southern United States, and sports 6-8cm, fragrant flowers in a variety of colors [16].

P. edulis is native to Brazil, Paraguay, and northern Argentina, however has spread throughout most of the tropics and sub tropics worldwide [16].

In general, the majority of the Passiflora species can be found in lower North America, Central America, and South America, and is mostly found in the tropics [8].

Harvesting, Collection, Preparation:

Due to Passiflora’s relationship with the Heliconius butterfly, and its ever changing and deceptive leaf shape, it can often be very well camouflaged in its environment [16].

When collecting passion flower for medicine, it is important to consider what is being treated.

For fungal infections it may be best to damage the leaves a few hours or days before harvesting as this has been shown to increase the antifungal agents located in the plant (J. Nirner et al., 1972).

In accordance with taste, Livia de L de O Pineli et al., (2014) [6] noted that P. nitida stood out as particularly preferred in flavour and had high antioxidant activity as well. P. alata on the other hand, was the least preferred and had the most bitter flavour.

If the antioxidant effects are the desired effects, species choice will make a difference, P. edulis, P. setacea, P. nitida, P. tenufida,  all have high antioxidant levels, with P. malformis leaf aqueous extract shown to have the highest antioxidant profile [14].

Constituents:

The major phytochemicals contained within Passiflora spp. include Alkaloids, phenols, glycosides, flavonoids, passiflorins, polypeptides, and alpha-pyrones [12].

Taylor L. (2005) [15] listed in her book the following constituents: Alpha-alanine, apigenin, aribine, chrysin, citric acid, coumarin, cyclopassifloic acids A-D, cyclopassiflosides I-VI, diethyl malonate, edulan I, edulan II, flavanoids, glutamine, gynocardin, harmane, haraline, harmalol, harmine, harmol, homoorientin, isoorientin, isoschaftoside, isovitexin, kaempferol, loturine, lucenin-2, lutenin-2, luteolin, n-nonacosane, orientin, passicol, passiflorine, passifloric acid, pectin, phenolic acids, phenylalanine, proline, prunasin, quercetin, raffinose, sambunigrin, saponarin, saponaretin, saponarine, schaftoside, scopoletin, serotonin, sitisterol, and stigmasterol.

Other constituents include phenolic compounds, fatty acids (linoleic, linolenic, palmitic, oleic, and myristic acids), formic and butyric acids, coumarins, phytosterols, and essential oils [8]. About 294 volatile compounds have been identified in several passion fruit extracts [12]. Maltol has also been discovered in various Passiflora species, which has documented sedative effects, as well as the neurotransmitter serotonin [15].

Flavonoids represent 2.5% of P. incarnata with such examples as vitexin, isovitexin, orientin, isoorientin, apigenin, kaempferol, vicenin, lucenin, and saponarin [8]. An HPTLC method has been developed by Pereira et al. (2004) to quantitatively determine the flavonoid contents in the leaves of P. alata, P. edulis, P. caerulea, and P. incarnata. [8]. The flavonoid chrysin is of significant note (also found in propolis, and honey), and has been shown to exhibit significant anxiolytic effects [15], and has been the focus of many of the studies referred to in this paper, all of which have shown therapeutic value including: antioxidant, anti-inflammatory, anti-allergic, anti-diabetic, anti-estrogenic, antibacterial, and anti-tumor effects (E.R. Kasala et al., 2015).  Taylor, L. (2005) [15] notes that when flavonoids and glycosides were tested for sedative value separately, an opposite effect resulted. She reasons that only combined, as a whole plant do they produce sedative effects.

Harmane alkaloids (indole) are also present which are believed to be the cause of the antispasmodic and hypotensive effects. [15].

Passiflora contains cyanogenic glycosides as a way to defend itself against pests. These glycosides diminish in concentration as the leaves age [16]. On the outside of the blossom, extrafloral nectar glands produce a nectar that is deposited onto the petioles and leaves of the plant. It is this nectar that attracts ants, and wasps, which is thought to be in an attempt for passion flower to defend itself against the coevolved Heliconius caterpillar [16]. The author at this time does not know the chemical constituents of this nectar or its application medicinally.

Pharmacology on Dose:

A study done by Sasikala V. et al., (2011) [12] using the extraction of P .feotida, obtained the extract by using a method involving drying P. feotida in shade, powdering, extracting with petroleum ether and ethanol using a soxhlet apparatus. Then a hot water infusion, evaporation with rotary vacuum-evaporator, then finally underwent lyophilization. A dried extract was result. This requires experience and specialized machinery, but it outlines the concepts behind producing an extract of this plant.

Depending on what the desired effects of the manufactured extract is, various methods provide better extraction. For example, methanol extracts were found to contain the highest antioxidant content, with high phenolic, and antibacterial properties. (S.D. Ramaiya et al.,2014), however an infusion of Passiflora edulis was shown to have higher levels of TPs (total phenolics), and CTs (condensed tannins) than hydroalcoholic extracts [6], and even still, hydroalcoholic extracts of P. edulis  had higher levels of TFs (total flavonoids) [6]. So it is evident that depending on what the extract is to be used for, various extraction methods will provide a more concentrated medicine for various pathologies. The other factor to note is the effect of these various processes on the heat labile constituents of the plant. As an example, metanol may provide the best extraction of antioxidants, however cannot be consumed, therefore must be evaporated out before use. This process often requires heat and therefore may damage the heat labile constituents in the process, thus using a different, less efficient extraction solvent is perhaps better despite lowered extraction efficiency.

J. Nirner et al., (1972), noted that the antifungal activity provided by Passiflora spp, is increased when the living plant tissue is wounded. This is significant if the reason for using Passiflora  involves needing antifungal properties.

Passiflora extracts can be tailored greatly based on species choice, extraction method, aspects of how the plant was cultivated, and of course in what dose the plant is used.

For analgesic effects, an ethanol extract is found to be most effective at 200mg/kg [12].

A normal dose for the ethanol extract would be between 100 and 200 mg/kg 1-3 times per day. In sensitive individuals start at around 50mg/kg, and with less sensitive indiviuals up to 300mg/kg may be used.

Infusion – Standard preparation (1:20 dried herb:water) 250ml (1 cup) 2-3 times daily

Capsules/tablets – 2-3g, 2-3 times daily

Cultivation:

Passion flower of all species make great house or garden plants. The flower is spectacular, they are easy to grow, and the leaves, stems, and fruit can easily be harvested and used.Many species of Passiflora do well in container culture, and home environments, outdoors seasonally in northern climates, or all year in tropical climates. Passionflower plants will pretty much all do well in a general potting mix, or regular garden soil. Passiflora can grow in sandy, loamy, or clay soils but generally prefers well-drained soil. [8].

Due to the climbing nature of passion flower, a climbing aid such as a tree, or trellis may be needed.

In nature, 95% of all flowering plants have a symbiotic relationship with mycorrhizal fungi [16], and therefore it may be beneficial to inoculate with a commercial strain of endo- and ecto-mycorrhizal fungi when planting.

Passiflora incarnata is the most economically important of the Passiflora species, and is currently being cultivated on a large scale in Belize, Brazil, Colombia, Guatemala, India, United States [16], and in Australia. [8].

Pharmacology and Medical Research:

ANALGESIC

In a study done on the analgesic effects of P. feotida on mice, 200 mg/kg  of ethanol extract was found to be comparable in effectiveness to morphine sulphate (5mg/kg). [12]. This same study concluded that “it is very clear that P.feotida also has analgesic and anti-inflammatory activities for the pharmaceuticals”.

ANTIBACTERIAL

The antibacterial and antifungal compound Passicol, has reportedly been isolated from P. edulis providing distinct antibacterial effects against gram-positive, but not gram negative bacteria [14]. Gram negative bacteria include such examples as Staphylococci, Streptococci, Corynebacterium diphtheriae (responsible for diphtheria), Bacillus anthracis (Anthrax), and Pneumococci.

The seeds have been found to possess antifungal compounds in the form of protein (Passiflin), and peptide (Pe-AFP1) [14].

ANTICANCER

*See chemoprotective effects*

ANTICONVULSANT

Passiflora incarnata extract (containing amino acids), were found to contain high amounts of GABA, as well as providing the ability to induce direct GABA currents in CA1 hippocampal pyramidal neurons [13], thus providing evidence for anticonvulsant activity.

Marjan Nassiri-Asl et al., (2007) [7] found similar effects in their study on a hydro-alcoholic extract of Passiflora called Pasipay. They found that it was able to prolong the onset time of seizures, decrease the duration of seizures, and provide mortality protection.They concluded that Pasipay may be useful in the treatment of absence seizure due to its effect on GABAergic and opioid systems, however suggested more studies were needed in order to investigate the mechanisms involved.

In a separate study chrysin was considered responsible, and its anxiolytic actions were linked to the activation of GABAa in rats [10].

ANTIDEPRESSANT

Chrysin (5,7-dihydroxyflavone), is a flavonoid found in bee propolis, honey, Passiflora spp, and a variety of other plants. It is noted to produce antioxidant [6, 17], antinflammatory [17], antineoplastic, hypolipidemic, and antidepressent [1] activity.

In the pathophysiology of depression, several mechanisms are considered: oxidative stress (through reduced oxygen species, and glutathione in various brain regions), BDNF deficiencies, and inhibition of Na+,K+, ATPase activity [1]. CUMS (Chronic unpredictable mild stress) is an animal model developed to mimic the initiation and progress of clinical depression in humans, and may also be used in the evaluation of antidepressant therapies, through both behavioural, and biochemical testing in animals [1]. This study aimed at evaluating the effects of chrysin on female mice subjected to CUMS, through monitoring the changes in both NGF (Nerve growth factor), and BDNF (brain-derived neurotrophic factor) levels, and Na+, K+, -ATPase activity in the hippocampus and prefrontal cortex. The mice were given either a low dose (10 ml/kg), or high dose (20 mg/kg) of Chrysin dissolved in saline/propylene glycol solution (80:20), or fluoxetine (10 mg/kg) daily for 28 days, 30 minutes before stress was induced via various methods such as damp bedding for 12 hours, constant lighting for 36 hours, angled cages for 12-18 hours, electric shock foot, water and food deprivation, and others. After CUMS ended, mice were given behavioural tests (open field test, forced swimming test, sucrose preference test), blood samples were taken, and hippocampus and prefrontal cortex was dissected. It was found that all of the deleterious effects of the CUMS test were “significantly ameliorated” by the chrysin treated mice when compared to the control group, and was observed to produce antidepressant effects on the non stressed group of mice as well. The results were similar to the results obtained from the group treated with known antidepressant fluoxetine. Chrysins effect was noted to prevent the elevation of corticosterone levels, produce antioxidant activity, prevent inhibition of Na+,K+,ATPase activity, as well as up regulate NGF, and BDNF levels.

All of these results are consistent with current theories on the pathophysiology of depression, and mimic the results of currently used antidepressant pharmaceuticals (fluoxetine) (C. B. Filho et al., 2015). With the observation that chrysin treatment resulted in lowered corticosterone levels, it suggests that the antidepressant activity of chrysin is associated with the HPA axis in mice. [1]. One of the key biological abnormalities associated with a depressive disorder is in fact hyperactivity of the HPA axis (C. B. Filho et al., 2015).

ANTI-INFLAMMATORY

In a study done investigating the activity of chrysin on ischemia/reperfusion injuries in the mouse model [17], researchers found that mice pre-treated with chrysin, who were then subjected to an induced ischemia in the cerebral artery for one hour, followed by reperfusion, had reduced deficit scores, and infarct volumes compared to the control group. Researchers in this study suggest that the results were due to the anti inflammatory, and anti-oxidative effects of chrysin.

In a separate study, the ethanol extract of P. feotida (100 mg/kg) was found to possess “highly acute anti-inflammatory effect” in mice [12].

ANTIOXIDANT

Infusions of Passiflora edulis, P. setacea, P. nitida, P. tenufila, all had antioxidant profiles comparable or higher than that of green tea [6].

P. maliformis leaf methanol extract was shown to have the most significant source of TPC, and strongest antioxidant activity. For stem extracts, P. quadrangularis  methanol extract had the highest phenolic levels, and possessed the highest antioxidant activity [14].

ANTISPASMODIC

Passiflora spp, contains a group of harmane alkaloids [15], which have been the subject of many studies. This class of alkaloids has been shown to inhibit muscle contraction, through inhibition of different types of calcium channels in rabbit aorta [4]. This class of alkaloids is also hallucinogenic [4].

ANTITUSSIVE

A study done in 2002 with mice, suggested that a methanol leaf extract of passionflower was shown to be comparable to the cough suppressant action of codeine [2]. It may be possible that these actions are related to the strong antispasmodic activity of the harmala alkaloids contained within Passiflora spp.

ANXIOLYTIC

Passiflora contains the flavonoid chrysin which has significant anxiolytic effects [13, 15]. In fact, the anxiolytic effects of Passiflora incarnata are noted to be as effective as benzodiazepines such as oxazepam in the treatment of generalized anxiety disorder with less side effects (Clinical naturopathy: an evidence based guide to practice pg 192) [13].

CARDIOPROTECTIVE

Neha Rani et al, (2015) [9] demonstrated chrysins potential as a potent cardioprotective agent. They determined that these effects were most likely through PPAR-γ activation, modulation of MAPKs and TGF-β inhibition.

CHEMOPROTECTIVE

Chemoprevention, or chemoprotection, is the use of natural or synthetic chemicals to inhibit, reverse, or delay the process of carcinogenesis [3]. Chrysin has been the subject of multiple studies investigating these effects, and has been found to produce chemoprotective effects in the following cancer cell lines: Oropharyngeal, mammary, melanoma, anaplastic thyroid, pancreatic, liver, gastric, colon, cervical, melanoma, oesophageal, lung, colon, cervical, lung, rectal, glioma, esophageal squamous, leukemia, hepatocellular, neuroblastoma, squamous cell carcinoma, oral, and prostate [3].

Carcinogenesis takes place through a multistep process, beginning with a cellular transformation of normal cells into cancer cells. Which then proliferates, eventually leading to the establishment of metastatic lesions (E.R Kasala et al., 2015).

E. R. Kasala et al., (2015) [3] states that “In vitro and in vivo models have shown that chrysin inhibits cancer growth through induction of apoptosis, alteration of cell cycle and inhibition of angiogenesis, invasion and metastasis without causing any toxicity and undesirable side effects to normal cells” (page 214). These researchers go on further to say that ”extensive research over the years has made it clear that most chronic illnesses like cancer can only be cured by multi targeted, as opposed to mono-targeted therapy”. This information, along with other research demonstrating chrysins antioxidant [6], and antinflammatory [12] effects, suggest that Passiflora spp may well be a viable option during cancer treatment. Utilizing multiple mechanisms to treat and prevent the disease.

In a time where cancer is one of the leading causes of death in both the western world, and the third world [3], these effects offered by Passiflora spp. may very well be the source of a new standard in cancer treatment protocols.

HYPOTENSIVE

Contains harmane alkaloids [15]. One study found that harmalone and other harmane alkaloids were able to inhibit calcium channels in vascular and smooth muscle tissue, preventing contraction, thus providing hypotensive effects [4].

The antioxidant, and antiinflammatory profiles of Passiflora spp,  may also play an important role in this pathology.

NEUROPROTECTIVE

The flavonoid chrysin, was noted to have neuroprotective effects through anti inflammatory, and antioxidative activity, measured through induced ischemia/reperfusion injury in mice. [17] The result of this study also showed strong therapeutic possibility of chrysin on the treatment of ischemic stroke, however more research is needed in this area.

Another chemical, maltol, found in Passiflora spp. and is also formed in the natural thermal degradation of starch, has been shown to provide neuroprotective effects against oxidative stress in the brains of mice [18].

SEDATIVE

Passiflora spp contains maltol which has documented sedative effects, as well as naturally occurring serotonin [15].

Since the 1960s, benzodiazepines have been one of the most widely used hypnotic drugs. However it is well known and documented that these drugs also create dependency, tolerance, and rebound insomnia in patients (K. Shinomiya et al., 2005).

TOXICITY/ CONTRAINDICATIONS:

Passiflora spp. is classified by the FDA as “generally regarded as safe” [15]. To study toxicity of this plant, researchers tested an ethanol leaf extract of P .feotida, that was given to mice in doses of 2000 mg/kg with no mortality and no alteration in behaviour. [12]. Leslie Taylor., (2005) [15] also stated that Passiflora is generally regarded as safe for children and infants as well.

There may be an Interaction with barbiturates, benzodiazepines with Passiflora spp. There is a possibility for it to potentiate its effects, caution should be used as it may increase sedation. This effect may actually be beneficial, but needs more clinical study. [16].

Synergy:

Commonly combined with such herbs as valerian, hops, hypericum, Melissa officinalis [16].

References:

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