Traditional Uses of Passionflower

+ Historic Use

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].

+ Western Herbal Medicine

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.

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].

Passiflora spp. flower has been used medicinally as a sedative, anxiolytic, antispasmodic, hypotensive. Passiflora edulis, Passiflora quadrangularis have both been used, however Passiflora 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.

+ Traditional South American Medicine

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. 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].

Herb Details: Passionflower

+ 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].

+ 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 & Medical Research

+ Menopause

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

A study 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 psychiatric symptoms of opiate withdrawal (insomnia, craving, dysphoria, anxiety, agitation, irritability) successfully [8].

+ 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 sulfate (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].

+ 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.

A hydroalcoholic extract of passionflower (Pasipay) was found to be able to prolong the onset time of seizures, decrease the duration of seizures, and provide mortality protection. The researchers in this study 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 to investigate the mechanisms involved [7].

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], anti-inflammatory [17], antineoplastic, hypolipidemic, an antidepressant [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 behavioral, 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. The dose was given 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 behavioral tests (open field test, forced swimming test, sucrose preference test), blood samples were taken, and hippocampus and prefrontal cortex were dissected. It was found that all of the harmful 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 [1].

The results were similar to the results obtained from the group treated with known antidepressant fluoxetine. Chrysin effect was noted to prevent the elevation of corticosterone levels, produce antioxidant activity, prevent inhibition of Na+, K+, ATPase activity, as well as upregulate NGF, and BDNF levels.

All of these results are consistent with current theories on the pathophysiology of depression and mimic the effects of currently used antidepressant pharmaceuticals (fluoxetine). 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. One of the key biological abnormalities associated with a depressive disorder is in fact hyperactivity of the HPA axis [1].

+ 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 antioxidative effects of chrysin.

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

+ Antioxidant

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

P. maliformis leaf methanol extract was shown to have the most significant source of TPC and most potent 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. 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

GABAergic Activity

In vitro research involving Passiflora, extracts noted the presence of GABA in the extract, which produced a dose-dependent GABAA current in hippocampal slices of mice [13]. This suggests a plausible mechanism for the anxiolytic effects by upregulating the parasympathetic nervous system activity. The anxiolytic effects of passionflower extracts have also been noted to be present without inducing sedation [20].

Animal studies have shown that chrysin, a monoflavonoid from passion flower is a partial agonist of the benzodiazepine receptors [20], which are located on and modulate the GABAA receptors.

Na+, K+, ATPase Preservation

Other research investigating the effect of passionflower on Na+, K+, ATPase activity in the hippocampus noted a protective effect in the treatment group [1]. A reduction of this enzyme is noted to result from repeated exposure to stress hormones [22], resulting in atrophy and a reduction in the number of synapses in the hippocampus [23]. The inhibition of this enzyme is associated with excitotoxic and neuronal damage [1], which corresponds with the excitotoxic activity associated with anxiety [24].

+ Cardioprotective

One study demonstrated chrysin's potential as a potent cardioprotective agent [9]. These researchers determined that the 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 healthy cells into cancer cells. Which then proliferates, eventually leading to the establishment of metastatic lesions [3].

E. R. Kasala et al., (2015) stated 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" [3] (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 chrysin's antioxidant [6], and anti-inflammatory [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 anti-inflammatory profiles of Passiflora spp may also play an essential 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 the 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.

Phytochemistry

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

+ Summary Of Constituents

Passiflora contains: Alpha-alanine, apigenin, chrysin, citric acid (tricarboxylic acid), coumarin, cyclopassifloic acids A-D, cyclopassiflosides I-VI, diethyl malonate, edulan I, edulan II, flavanoids, glutamine, gynocardin, harmane (aka aribine), 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

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 [3].

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

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

+ Cyanogenic Glycosides

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. The author at this time does not know the chemical constituents of this nectar or its application medicinally.

+ Pharmacology on Dose:

Depending on what the desired effects of the manufactured extract are, various methods may provide better extraction. For example, methanol extracts were found to contain the highest antioxidant content, with high phenolic, and antibacterial properties [14], however, an infusion of Passiflora edulis was shown to have a higher total phenolic content, and condensed tannins than hydroalcoholic extracts, and even still, hydroalcoholic extracts of P. edulis had higher levels of total flavonoids [6].

The other factor to note is the effect of these various processes on the heat labile constituents of the plant. As an example, methanol may provide the best extraction of antioxidants, however, cannot be consumed, therefore must be evaporated before use. This process often requires heat and may hence damage the heat labile constituents in the process, thus using a different, less efficient extraction solvent is perhaps better despite lowered extraction efficiency.

The antifungal activity provided by Passiflora spp. was increased when the living plant tissue is wounded. This is significant if the reason for using Passiflora involves needing anti-fungal properties. [5].

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