Volume 2, Issue 2, May 2009                                                            INDUSTRY NEWS

        Passion Flo...
Volume 2, Issue 2, May 2009                                                      INDUSTRY NEWS

Several major references d...
Volume 2, Issue 2, May 2009                                                      INDUSTRY NEWS

that Passiflora contains a...
Volume 2, Issue 2, May 2009                                          INDUSTRY NEWS

Figure 3: Molecular structure of Ox...
Volume 2, Issue 2, May 2009                                                 INDUSTRY NEWS

clinical trial is needed. Such ...
Volume 2, Issue 2, May 2009                                              INDUSTRY NEWS

8). Burkard W, Kopp B, Krenn L, Be...
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Nmr Industry News Story Vol 2, Iss 2, May 09


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Passion Flowers: Exciting Results when Traditional Knowledge is Confirmed by Modern Science
By: Charles Spielholz, Ph.D., Medical Writer/Editor – Nutraceutical Medical Research, LLC
Published May 2009

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Nmr Industry News Story Vol 2, Iss 2, May 09

  1. 1. Volume 2, Issue 2, May 2009 INDUSTRY NEWS Passion Flowers: Exciting Results when Traditional Knowledge is Confirmed by Modern Science By: Charles Spielholz, Ph.D., Medical Writer/Editor – Nutraceutical Medical Research, LLC Published May 2009 N ow society has modern approaches to understanding the properties of passion flowers and, thus far, the results are very exciting. Recent research has indicated that several species of passion flowers that have been used traditionally exhibit anxiolytic (anti- anxiety) activity. The passion flower species most often used for this type of research is Passiflora incarnata (also known as maypop or the purple passion flower). Data have been collected both from clinical trials in humans and experimental procedures in rodents. In this article we are going to briefly review data showing that passion flowers, concentrating mostly on Passiflora incarnata, exhibit anxiolytic effects. We will then discuss directions for future research on this interesting and Passiflora incarnata (Purple Passion Flower), also known as Maypop promising flower. First discovered by Europeans in 1569 (by the Passion flowers, a genus of flowering plants which Spanish while exploring Peru), passion flowers exist mostly as vines, contain several hundred have been used by various Native American groups member species. The genus name is Passiflora. to alleviate the symptoms of a variety of conditions. The genus is native to the Americas, Asia and These conditions include what we now call anxiety, Australia; however species of passion flowers have insomnia, pain, hysteria and nervous exhaustion. been brought to other parts of the world both for European explorers adapted the traditional use of their beauty and their edible fruit. passion flowers for medicinal purposes. 1
  2. 2. Volume 2, Issue 2, May 2009 INDUSTRY NEWS Several major references discuss research on the Passiflora incarnata showed dose dependent anxiolytic and sedative effects of passion flowers changes in anxiety (9). It has also been shown that (1-3). One clinical study in which 60 patients were the extract from the leaves, stems and flowers randomized into two groups before (outpatient) exhibited anxiolytic activity whereas the roots did surgery showed that patients who received an oral not (10). dose of Passiflora incarnata 90 minutes prior to surgery scored significantly lower on clinical Additionally, it has been shown that not all species anxiety tests then patients who received placebo (4). of passion flower exhibit anxiolytic effects. Extracts A multicenter, double blind trial, using a from Passiflora incarnata exhibited anxiolytic combination of plant extracts including Passiflora properties while extracts from Passiflora edulis showed a statistical difference in comparison to (also known as passion fruit and maracuya) did not placebo for treatment of anxiety (5). Additional (11). Note that in addition to showing that the clinical data, with 36 patients, have shown that anxiolytic effects are specific to only certain species Passiflora incarnata not only is an effective of Passiflora, experiments of this sort also serve as approach for treatment of anxiety, but that it is may important controls helping to prove that the be as effective as the benzodiazepine oxazepam (6). anxiolytic effect is unique to just some species of Benzodiazepines are prescribed drugs with sedative, passion flowers, and not all species. hypnotic, anxiolytic, anticonvulsant and muscle Researchers have begun to isolate and analyze the relaxing properties. It must be noted that not all components of Passiflora and have made some studies have replicated these observations astounding observations. First, it has been shown statistically indicating that much larger clinical trials are required to completely understand the properties of Passiflora. Given the interesting clinical data indicating that Passiflora species, particularly Passiflora incarnata, exhibit anxiolytic properties, it is useful to review some of the experimental work done in rodents on this botanical. Experiments studying the anxiolytic effects of substances in animal models allow researchers to pinpoint the actions of these substances on the central nervous system. Early studies using Passiflora extracts have shown that Figure 1: Chrysin, a flavonoid present in extracts of Passiflora incarnata. Evidence indicates that chrysin may be the active there are a variety of dose-dependent actions as well anxiolytic agent of Passiflora incarnata. as binding sites in the central nervous system in rodents (7, 8). Mice treated with extracts from 2
  3. 3. Volume 2, Issue 2, May 2009 INDUSTRY NEWS that Passiflora contains a number of chemical receptor) indicating that the extract was functioning constituents including flavonoids, glycosides, through the GABAA receptor and not the serotonin maltol and indole alkaloids. The flavonoids show receptor (16). the most interesting properties in rodents and we will focus on one flavonoid in particular, chrysin. There is no evidence that extracts of Passiflora Chrysin is a naturally occurring flavonoid that is incarnata are addicting in humans, unlike the extracted from Passiflora incarnata and some other various benzodiazepines that the extracts appear to Passiflora species. mimic. Preliminary evidence in mice indicates that the extracts are non-addicting, but also may Evidence that a benzoflavone isolated from attenuate benzodiazepine dependence to a small Passiflora incarnata has anxiolytic properties in extent (12). In fact, one report suggests using mice has been reported (12, 13). Since chrysin is passion flower extract as an adjuvant during opiate isolated from Passiflora incarnata, several withdrawal (17). That report presented data investigations have examined the anxiolytic indicating patients who used a passion flower properties of chrysin in rodents. The results of those extract during opiate withdrawal suffered fewer studies indicate that chrysin does have anxiolytic mental symptoms of withdrawal then patients who properties in rats while another flavonoid, apigenin, did not use the extract. isolated from Matricaria chamomilla (camomile) and provided at equal doses, did not (14). It was also reported that the anxiolytic activity of chrysin Figures 2-5: show a comparison of different benzodiazepine derivatives. Note how similar the structures are to chrysin. was blocked by flumazepil, a competitive inhibitor of the benzodiazepine binding site on the GABAA receptor (14). This observation is consistent with the idea that chrysin’s anxiolytic properties function through the GABAergic receptor in the central nervous system. Another report showed that chrysin was as effective an anxiolytic agent as midazolam (a short acting benzodiazepine) and that the anxiolytic effect was inhibited by flumazepil (15). In another set of experiments performed in mice, an extract prepared from Passiflora incarnata exerted an anxiolytic effect equal to diazepam (Valium), another benzodiazepine (16). In this study, the anxiolytic effects of the extract were inhibited by flumazepil but not by WAY-100 635, an antagonist Figure 2: Molecular structure of Midazolam of the serotonin receptor (5-hydroxtryptamine 3
  4. 4. Volume 2, Issue 2, May 2009 INDUSTRY NEWS Figure 3: Molecular structure of Oxazepam Figure 5: Molecular structure of Diazepam The anxiolytic properties of the passion flower are exciting. Clinical data collected thus far indicates that Passiflora incarnata, the purple passion flower, exhibits anxiolytic activity. Experiments in rats and mice show extracts from the flowers, leaves and stems of Passiflora incarnata contain anxiolytic activity and that these extracts contain the flavonoid chrysin. Furthermore, it has been shown that chrysin possesses anxiolytic activity and that this property appears to function through the GABAA receptor. However, direct evidence showing that the chrysin in extracts of Plassiflora incarnata is the agent responsible for the anxiolytic effects that have been observed is not yet available. The evidence collected so far has allowed the German Commission E to approve the use of passion flower for nervous restlessness. Figure 4: Molecular structure of Flumazepil Now that modern approaches appear to be confirming traditional knowledge about Passiflora incarnata, what is the next step? First, a large scale 4
  5. 5. Volume 2, Issue 2, May 2009 INDUSTRY NEWS clinical trial is needed. Such a trial will show speak with a health care provider before using conclusively that the purple passion flower, passion flower. Passiflora incarnata, does indeed have clear anxiolytic properties. So far, clinical data collected indicates that the anxiolytic properties of Passiflora REFERE CES incarnata are non-addicting and have no effect on memory. Only one adverse event (18) has been 1) Chevallier A. Encyclopedia of Medicinal Plants. reported and, to date, there are no known toxic (1996) New York, NY: DK Publishing, 117. effects associated with use of passion flower. The 2) Bruneton J. Pharmacognosy, Phytochemistry, adverse event included nausea, vomiting and Medicinal Plants. (1995) Paris, France: Lavoisier nonsustained ventricular tachycardia; however, it is Publishing Inc., 284-285. not clear exactly what that patient was taking and if the patient might have been taking other 3) J. CRC Handbook of Medicinal Herbs. (1985) medications that were not reported to the physician. Boca Raton FL: CRC Press, 347. A large clinical trial will sort out and confirm these important observations. In addition, adverse effects 4) Movafegh A., Alizadeh R., Hajimohamadi F, would be understood and appropriate warnings Esfehani F, Nejatfar M. (2008) Preoperative oral could then be provided. Further studies using Passiflora incarnata reduces anxiety in ambulatory rodents as a model system will allow investigators patients: a double-blind, placebo controlled study. to determine exactly which molecules in Passiflora Anesth Analg. 106: 1728-1732. incarnata extracts are involved in the anxiolytic 5) Bourin M, Bougerol T, Guitton B, Broutin E. effects. This would then allow for quality exact (1997) A combination of plant extracts in the quality control to be used in preparing extracts for treatment of outpatients with adjustment disorder use commercially and also allow for optimal with anxious mood: controlled study vs placebo. dosages to be determined. Fundam Clin Pharmacol. 11:127-132. Currently, passion flower is commercially available 6) Akhondzadeh S, Naghavi HR, Varirian M, as capsules and as a liquid extract. Since passion Shaveganpour A, Rashidi H, Khani M. (2001) flower can cause sleepiness, one should not drink Passion flower in the treatment of generalized alcohol with passion flower. Manufacturers anxiety: a pilot double-blind randomized controlled currently advise users not to drive or operate trial with oxazepam. J Clin Pharm Ther. 26:363- machinery or heavy equipment while using passion 367. flower. Passion flower is not meant for people with low blood pressure. If a person is taking an MAO 7) Speroni E, Minghetti A. (1988) inhibitor or is pregnant or nursing, they should Neuropharmacological activity of extracts from Passiflora incarnata . Planta Med: 54:488-491. 5
  6. 6. Volume 2, Issue 2, May 2009 INDUSTRY NEWS 8). Burkard W, Kopp B, Krenn L, Berger D, apigenin and chrysin. Fitoterapia. 71: Suppl 1:S117- Schaffner W. (1997) Receptor binding studies in the S123. CNS with extracts of Passiflora incarnata . Pharm Pharmacol Lett. 7:25-26. 15) Brown E, Hurd NS, McCall S, Ceremuga TE (2007) Evaluation of the anxiolytic effects of 9) Grundmann O, Wahling C, Staiger C, chrysin, a Passiflora incarnata extract, in the Butterweck, V. (2009) Anxiolytic effects of a laboratory rat. AANA J. 75:333-337. passion flower (Passiflora incarnata L.) extract in the elevated plus maze in mice. Pharmazie. 64:63- 16) Grundmann O, Wang J, McGregor GP, 64. Butterweck V (2008) Aniolytic activity of a phytochemically characterized Passiflora extract is 10) Dhawan K, Kumar S, Sharma A. (2001) mediated via the GABAergic system. Planta Med. Anxiolytic activity of aerial and underground parts 74:1769-1773. of Passiflora incarnata. Fitoterapia. 72: 922-926. 17) Akhondzadeh S, Kashani L, Mobaseri M, 11) Dhawan K, Kumar S, Sharma A, (2001) Hosseini SH, Nikzad S, Khani M. (2001) Passion Comparative biological activity study on Passiflora flower in the treatment of opiates withdrawal: a incarnata and P. Edulis. Fitoterapia. 72: 698-702. double-blind randomized controlled trial. J Clin Pharm Ther. 26: 369-373 12) Dhawan K, Kumar S, Sharma A, (2001). Anti- anxiety studies on extracts of Passiflora incarnata 18) Fisher AA, Purcell P, LeCouteur DG. (2000) Linneaus. J Ethnopharmacol. 78:165-170. Toxicity of Passiflora incarnata L. J Toxicol Clin Toxicol. 38: 63-66. 13) Dhawan K, Dhawan S, Chhabra S (2003) Attenuation of benzodiazepine in mice by tri- substituted benzoflavone moiety of Passiflora incarnata Linneaus: a non-habit forming anxiolytic. J Pharm Pharm Sci. 6:215-222. 14) Zanoli P, Avallone R, Baraldi M (2000) Behavorial characterisation of the flavonoids 6