1. INTRODUCTION

The genus Passiflora consists of 500 species that are mostly found in warm and tropical regions. Passiflora comes from Latin word “Passio” that was first time discovered by Spanish discoverers in 1529 and was described as a symbol for “Passion of Christ”^{1, 2}. The passion flowers or passion vines (Passiflora) have a genus of about 400 species of flowering plants and the largest in the family of Passifloraceae^{3, 4}. They are mostly vines, with some being shrubs, and a few species being herbaceous. The species of this genus are distributed in the warm temperate and tropical regions of the world, but they are much rarer in Asia, Australia, and tropical Africa. The medical utility of very few species of Passiflora has been scientifically studied⁵.

Passionflower extracts have been classified into several categories of chemical activities like anxiolytic, spasmolytic, hypnotic, sedative, narcotic and anodyne (Ozarko, 2001)⁶. These extracts are part of a treatment that has successfully treated outpatients with adjustment disorder and anxious mood (Broutin et al., 1997)⁷. Many species have been found to contain beta-carboline harmala alkaloids with anti-depressant properties. The flower and fruit has only traces of these chemicals, but the leaves and the roots are often more potent and have been used to enhance the effects of mind-altering drugs. Once dried, the leaves can also be smoked. Passiflora quadrangularris is used by traditional healers for snake bites. Snake bites causes blood clotting and eventually burst blood vessels around the bite, this is known as haemorrhaging⁸.

Classification:

Botanical source: Passiflora incarnata L.

Family: Passifloraceae

Genus: Passiflora L.

Species: Passiflora incarnata L.

Identifying Characteristics:

The stems wiry; three-lobed leaves, serrate; pale pink flowers 5-7 cm across; fruits ovoids or globose, 3-5 cm long [Figures 1-3]⁹.

Figure 1:- Passion flower

Figure 2:- Whole Plant

Figure 3:- Fruits

Bioactive Compounds:

Chemical content of Passiflora species is also not well delineated. Investigators have differed on whether its sedative effects are due to indole alkaloids such as harmane, harmaline, and harmol; flavonoids such as apigenin, luteolin, and scopoletin; or an isolated trisubstituted benzoflavone. In addition, recently it was determined that Passiflora contains more gamma-amino butyric acid (GABA) than 20 other plants examined¹⁰. One of six alkaloids isolated from P. incarnata has been called "passiflorine," and is believed by some to be the plant's active compound, although the Agricultural Research Service's web site describes passiflorine as inactive. The Chemical Abstract Service's database's only similar entry is "passiflorin," a steroid-like molecule found in P. edulis stems and leaves that is not an alkaloid. Passionflower extracts consist of fresh or dried aerial parts of P. incarnata or P. alata, collected during the flowering and fruiting period. Botanical identity is confirmed by thin-layer chromatography, microscopic and macroscopic examination, and organoleptic evaluation. Extracts contain 0.825% apigenin and luteolin glycosides, vitexin, isovitexin and their Cglycosides, kaempferol, quercetin, and rutin; indole alkaloids (0.01%), mainly harman, harmaline, harmine; coumarin derivatives; cyanogenic glycosides (gynocardin); amino acids (including GABA); fatty acids (linoleic and linolenic); gum; maltol; phytosterols (stigmasterol); sugars (sucrose); and a trace of volatile oil^{11, 12, 13, 14, 15, 16}.

1. Chrysin:

C15H10O4 (5, 7-dihydroxy-2-phenyl-(9CI)

Chrysin is a naturally occurring flavone chemically extracted from the blue passion flower (Passiflora caerulea). Chrysin acts as an aromatase inhibitor supplement to bodybuilders and athletes. It has been shown to induce an anti-inflammatory effect, most likely by inhibition of COX-2 expression via IL-6 signaling¹⁷. In rodent in vivo studies, chrysin was found anxiolytic^{18, 19}. In herbal medicine, it is recommended as a remedy for anxiety, but there are no controlled data in humans’ available²⁰. Chrysin exhibited an anxiolytic effect, which was showed by an increase in locomotor activity in rats when injected at 1 mg/kg. This effect was linked to GABA benzodiazepine receptors in the brain because the anxiolytic effect was blocked by an injection of Flumazenil, which is a benzodiazepine antagonist²¹. Chrysin and apigenin have been shown to inhibit the growth of breast carcinoma cells²², human thyroid cancer cells²³ and human prostate tumors²⁴. Apigenin is considered anti-mutagenic because it reduces the effects of mutagens in rats²⁵.

2. Benzoflavone:

The β-Naphthoflavone, also known as 5, 6-benzoflavone, is a potent agonist of the aryl hydrocarbon receptor and an inducer of detoxification enzymes as cytochromes P450 (CYPs) and uridine 5'-diphosphoglucuronosyltransferases (UGTs)²⁶. β -Naphthoflavone is a putative chemopreventive agent²⁷.

3. Harmala alkaloids:

C13H12N2O (7-Methoxy-1-methyl-9H-pyrido [3, 4-b] indole)

The passiflora family contains small amounts of harmala alkaloids, harmane (passaflorine), and possibly harmine (telepathine), harmaline, harmol, and harmalol. The presence of the last four in P. incarnata is disputed²⁸ because they are contained in only very small amounts (0.01% or less) ²⁹.

Furthermore, they have been identified as stimulants and monoamine oxidase inhibitors^{30, 31, 32} which would give antidepressant rather than sedative effects. Wild rue (Peganum harmala) which contains significant amounts of these substances (and after which they were named) is used therapeutically as a stimulant rather than a sedative. The harmala alkaloid which is the active principle in passiflora might also be a cause for concern for kidney toxicity, as these substances are toxic to the kidneys³³.

Extracts of the aerial parts of P. incamata L. contain the beta-carbolines: harman, hamun, hannalin, harmol, and harmalol, along with an aroma compound, maltol³⁴. Beta-carbolines, like those of P. incamata L., induce voluntary ethanol intake in rats³⁵. Some people may be interested in the fact that harman has been identified in beer; wine³⁶ and cigarette smoke³⁷. Beta-carbolines have been found to prevent neuron damage to the brain mitochondria of dopamine induced mice by acting as an antioxidant and scavenging hydroxyl radicals³⁸. Harman and related compounds are mutagenic and have become more mutagenic after nitrosarion occurs in the acidic conditions of the stomach. Harman acts as a vasorelaxant (something that reduces inflammation or edema), it functions by releasing GABA, serotonin and noradrenaline³⁹.

4. Glycosides

Orientin:

Glycosides are molecules in which a sugar is bound to a non-carbohydrate moiety, usually a small organic molecule. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides which can be activated by enzyme hydrolysis⁴⁰.

Leaf and stem material of P. edulis contain the new cyanogenic glycosides (2R)–α-allopyranosyloxy-2-phenylacetonitrile and (2S)–α-Dallopyranosyloxy-2-phenylacetonitrile , along with smaller amounts of (2R)–prunasin, (2S)-sambunigrin. Many different types of glycosides are present in passion flower such as apigenin, homoorientin, 7-isoorientin, isoshaftoside, isovitexin, kaempferol, lucenin, luteolin, norientin, passiflorine (named after the genus), quercetin, rutin, saponaretin, saponarin, shaftoside, vicenin and vitexin. In some cases this glycoside occurs with simple β-D-glucopyranosides: tetraphyllin A, deidaclin, tetraphyllin B, volkenin, epivolkenin and taraktophyllin. P. citrine contains passicapsin, a rare glycoside with the 2, 6- dideoxy- β -D-xylo-hexopyranosyl moiety, while P. herbertiana contains tetraphyllin A, deidaclin, epivolkenin and taraktophyllin, P. discophora tetraphyllin B and volkenin, and P. xviolacea tetraphyllin B⁴¹. Some other glycosides present in Passiflora are the hydrocarbon nonacosane and the anthocyanidin pelargonidin-3-diglycoside⁴².

Passiflora morifolia extracts contain the cyanohydrins glycoside and linamarin⁴³. Linamarin causes an increase of lactic acid and total cholesterol in the liver and brain in addition to the depletion of brain phospholipids in rabbits⁴⁴.

Isoorientin:

(Luteolin-8-C-glucoside)

Orientin is a flavone, a chemical flavonoid-like compound found in the passion flower, the Açai palm and Anadenanthera peregrina. Orientin is also reported to be in millets. Isoorientin (or homoorientin) is the luteolin-6-Cglucoside. It can be isolated from the passion flower, Vitex negundo, the Açaí palm and Swertia japonica⁴⁵.

Other organic compounds:

Passion flower contains many alkaloids, flavonoids as well as many organic compounds such as organic acids. This genus is rich in formic, butyric, linoleic, linolenic, malic, myristic, oleic and palmitic acids as well as phenolic compounds, and the amino acid α-alanine. Some species contain ester such as ethyl butyrate, ethyl caproate, n-hexyl butyrate and n-hexyl caproate which give the fruits their flavor and appetizing smell. Sugars, contained mainly in the fruit, are mostly d-fructose, d-glucose and raffinose. Among enzymes, Passiflora was found to be rich in catalase, pectin methyl esterase and phenolase. Apart from glycosides, phenols and alkaloids, various miscellaneous phyto-constituents which were also reported to be in P. edulis include, Edulans I and II⁴⁶ and pectins⁴⁷.The pectin fractions contain mainly sugars (83 - 85%, w/w). However, non-sugar components such as nitrogen-containing material (3 -8%, w/w) and ash (5 - 7%, w/w) are also present in these fractions⁴⁸.

Pharmacology:

Cannabinoids reversal:

The newly reported benzoflavone (BZF) moiety from the plant P. incarnata (Linn) has been evaluated in light of traditional reports on the use of this plant in breaking down cannabis addiction. In the modern or allopathic system of therapeutics, there has been no suitable remedy to combat the severe withdrawal effects of various cannabis products, including marihuana, marijuana, bhang, hashish, ganja, etc., the world-wide consumption of which has attained alarming proportions especially among the younger generation. It has been reported that the BZF of P. incarnata, when administered concurrently with cannabinoids, prevented the development of tolerance and dependence of cannabinoids in mice. Even an acute administration of the BZF significantly blocked the expression of withdrawal effects in cannabinoid dependence. So these studies suggested that the BZF may have beneficial role in cannabinoids reversal⁴⁹.

Nicotine reversal:

Some of the pharmacological studies on the BZF moiety also confirmed that the BZF moiety isolated from P. incarnata was very effective in countering the menace of addiction‑prone substance nicotine in laboratory animals. In light of various reports mentioning the usefulness of P. incarnata in tobacco addiction, studies have been performed by using the bioactive BZF moiety isolated from the aerial parts of P. incarnata. So these studies, although preliminary, suggested that the BZF may have value in treating nicotine addiction⁵⁰.

Alcohol Withdrawal:

A BZF moiety has been reported recently to be responsible for the multifarious CNS effects of P. incarnata Linn. In the light of the established usefulness of the BZF moiety in counteracting the withdrawal effects of substances like cannabinoids and nicotine by the authors, the bioactive BZF moiety has been tested in mice treated with an addictive dose of ethyl alcohol, in order to evaluate its effectiveness in countering alcohol dependence. The chronic administration of P. incarnata with alcohol had better preventive effects than the single acute treatment with P. incarnata in alcohol‑dependent mice. These results suggested that the treatment of P. incarnata extract could be used as safe and alternative drug for alcohol withdrawal⁵¹.

Anticonvulsant Activity:

The current therapeutic treatment of epilepsy with modern antiepileptic drugs (AEDs) is associated with side effects, dose-related and chronic toxicity and teratogenic effects, and approximately 30% of the patients continue to have seizures with current AEDs therapy. Natural products from folk remedies have contributed significantly in the discovery of modern drugs and can be an alternative source for the discovery of AEDs with novel structures and better safety and efficacy profiles. Evidence for anticonvulsant activity of P. incarnata in the clonic seizure of the pentylenetetrazole model has been tested. As the protective effects of P. incarnata in clonic seizure, it suggests that it could be useful for treatment of absent seizure. Furthermore, the important role of benzodiazepine receptor in the effects of P. incarnata should be considered⁵².

Antimicrobial activity:

In Passiflora species, many of the chemical components of passion flower (passicol) have antimicrobial activity^53,54,55.The ethanol leaf extracts exhibited variable degrees of antibacterial activity against P. putida, V. choleraeand moderate activity was noted in S. flexneri and S. pyogenes respectively. The acetone extracts exhibited strong to moderate activity against V. cholerae followed by P. putida, S. flexneri and S. pyogenes. The ethanol fruit extracts showed moderate activity against the bacterial pathogens namely V. cholerae, P. putida, S. pyogenes and S. flexneri. Among the two parts tested, the leaf extracts exhibited better antibacterial activity than the fruits⁵⁶. The earlier reports focused on the antibacterial properties of Passiflora species by different methods. Antibacterial activity of Passiflora which has got activity against Pseudomonas tetrandra, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa.

Antioxidant activity:

P. nitida leaf and P. palmeri stem extracts were characterized by a high antioxidant power that correlates with high catechin and odiphenol contents and shows antimicrobial activity. However, P. foetida leaf extracts, which also show high antimicrobial activity, have a low antioxidant power and low amounts of o-diphenol and catechin. P. tenuifila leaves show very high amounts of flavones and total phenols, but intermediate levels of antioxidant activity, probably due to the lower contribution of o-diphenols and gallocatechins relative to the phenol content⁵⁷. The antioxidant activity of leaf and stem extracts of P. edulis was determined using the 1, 1-diphenyl- 2-picrylhydrazyl (DPPH) free radical scavenging assay⁵⁸. DPPH offers a convenient and accurate method for titrating the oxidizable groups of natural or synthetic anti-oxidants⁵⁹. The crude extracts (leaf and stem) of P. edulis were mixed with 95% methanol to prepare the stock solution (10 mg/100 mL).

Anti-inflammatory activity:

The aqueous leaves extract of Passiflora species exhibited potent anti-inflammatory action in the experimental model in vivo⁶⁰. The aqueous leaves extract of P. edulis possess a significant anti-inflammatory activity on mice⁶¹. The systemic administration of P. edulis exhibited pronounced anti-inflammatory actions, characterized by inhibition of leukocyte influx to the pleural cavity and associated with marked blockade of myeloperoxidase, nitric oxide, TNF-α and IL-1α levels in the acute model of inflammation caused by intra pleural injection of mice. In one experiment, P. edulis was more effective in suppressing the TNF-α and IL-1α levels than dexamethasone⁶². P. edulis therefore, may be a source of new therapeutic candidates with a spectrum of activity similar to the current anti-inflammatory steroids such as dexamethasone.

Anti-tumor activity:

Fruit’s decoction of different passiflora species has been evaluated for the inhibition of activity of gelatinase matrix metalloproteinases (MMP-2 and MMP-9). Two metallo-proteases were involved in the tumour invasion, metastasis and angiogenesis. Water extract of P. edulis, at different concentrations was inhibited by the enzymes⁶³.

Congestive heart failure:

An extract containing passion flower and hawthorn has been studied as a possible treatment for shortness of breath and difficult use of exercise in patients with congestive heart failure. Although, the results are promising, the effects of passion flower alone are unclear. The high quality human research of passion flower alone compared to prescription drugs used for this condition is needed before a strong recommendation can be made⁶⁴.

Clinical Applications:

Allergies few reports of the use of passion flower products on allergic reactions, asthma, irritated sinuses, skin rashes, and skin blood vessel inflammation (vasculitis) have been reported in the available literature. It is believed that some reactions may have been caused by impurities in combination products, not by passion flower itself⁶⁵.

Side effects and warnings:

Passion flower is generally considered to be a safe herb with few reported serious side effects. In cases of side effects, the products being used have rarely been tested for contamination, which may have been the cause. Cyanide poisoning has been associated with passiflora fruit, but this has not been proven in human studies. Rapid heart rhythm, nausea, and vomiting have been reported. Side effects may also include drowsiness /sedation and mental slowness. Patients should be cautious when driving or operating heavy machinery. Passion flower may theoretically increase the risk of bleeding and affect blood tests that measure blood clotting⁶⁶. There is a reported case of liver failure and death of a patient taking a preparation of passion flower with kava. Caution should be applied in taking any kava-containing products, as kava has been associated with liver damage. It has been suggested that the cause of the liver damage is less likely related to the presence of passion flower.

Uses:

Traditional uses:

The uses here are based on tradition or scientific theories of Passiflora species. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. These traditional uses includes alcohol withdrawal, antibacterial, anti-seizure, anti-spasm, aphrodisiac, asthma, attention deficit hyperactivity disorder (ADHD), burns (skin), cancer, chronic pain, cough, drug addiction, Epstein-Barr virus, fungal infections, gastrointestinal discomfort (nervous stomach), Helicobacter pylori infection, hemorrhoids, high blood pressure, menopausal symptoms (hot flashes), nerve pain, pain (general), skin inflammation, tension and wrinkle prevention⁶⁷.

Industrial uses:

A number of species of Passiflora are cultivated outside their natural range because of their beautiful flowers. P. incarnatea L. commonly used in many herbal remedies is well known for its sedative properties, while several other species are cultivated for the production of fruit juice (P. edulis, P. quadrangularis, P. ligularis)⁶⁸. Passicol can also be produced from fruit rinds of the purple passion fruit, which are waste products from the manufacture of passion fruit juice. The resulting rich juice, which has been called a natural concentrate, can be sweetened and diluted with water or other juices (especially orange or pineapple), to make cold drinks. In South Africa, passion fruit juice is blended with milk and an alginate; in Australia the pulp is added to yogurt.

CONCLUSION:

Species of Passiflora are commonly found throughout world. These studies place this indigenous drug as a novel candidate for bio-prospection and drug development for the treatment of such diseases as anxiety, insomnia, convulsion, sexual dysfunction, cough, cancer and postmenopausal syndrome. The medicinal applications of this plant and countless possibilities for investigation still remain in relatively newer areas of its function. A comprehensive account of the chemical constituents is given in this review. Various types of preparations, extracts and individual compounds derived from this species have been found to possess a broad spectrum of pharmacological effects on several organs such as the brain, blood, cardiovascular and nervous systems as well as on different biochemical processes and physiological functions including proteosynthesis, work capacity, reproduction, and sexual function. Hence, phytochemicals and minerals of these plants will enable to exploit its therapeutic use.

REFERENCES:

1. Kinghorn GR. Passion, stigma, and STI. Sex Transm Inf 2001; 77:370‑5.

2. Dhawan K, Dhawan S, Sharma A. Passiflora: A review update. J Ethnopharmacol 2004; 94:1-23.

3. Montanher A, Zucolotto SM, Schenkel E, Frode T (2007). Evidence of anti-inflammatory effects of Passiflora edulis in an inflammation model. J. Ethnopharmacol., 109: 281-288.

4. Beninca J, Montanher A, Zucolotto S, Schenkel E, Frode T (2007). Evaluation of the AntiInflammatory Efficacy of Passiflora Edulis. Food Chem., 104: 1097-1105.

5. Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M (2001). Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. J. Clin. Pharm. Therapeut., 26-5: 363-367.

6. Ozarko G (2001). Passiflora. www.icon.com.au.

7. Broutin M, Bugerol T, Guitton B, Broutin E (1997). A combination of plant extracts in the treatment of outpatients with adjustment disorder with anxious mood: controlled study versus placebo. Fundamental Clin. Pharmacol., 11- 2: 127-132.

8. A. G. Ingale and A. U. Hivrale (2010). Pharmacological studies of Passiflora sp. and their bioactive compounds. African Journal of Plant Science Vol. 4(10), pp. 417-426.

9. The Wealth of India. A Dictionary of Indian Raw Materials and Industrial Products. CSIR; 7:278-9.

10. Carratu B, Boniglia C, Giammarioli S, Mosca M, et al. Free Amino Acids in Botanicals and Botanical Preparations. Journal of Food Science 2008; 73(5):C323–C328.

11. Bradley, P.R. (ed.). 1992. British Herbal Compendium, Vol. 1. Bournemouth: British Herbal Medicine Association.

12. Bruneton, J. 1995. Pharmacognosy, Phytochemistry, Medicinal Plants. Paris: Lavoisier Publishing.

13. ESCOP. 1997. 'Passiflorae herba.' Monographs on the Medicinal Uses of Plant Drugs. Exeter, U.K.: European Scientific Cooperative on Phytotherapy.

14. Newall, C.A., L.A. Anderson, J.D. Phillipson. 1996. Herbal Medicines: A Guide for Health-Care Professionals. London: The Pharmaceutical Press.

15. Wichtl, M. and N.G. Bisset (eds.). 1994. Herbal Drugs and Phytopharmaceuticals. Stuttgart: Medpharm Scientific Publishers.

16. Leung, A.Y. and S. Foster. 1996. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics, 2nd ed. New York: John Wiley & Sons, Inc.

17. Woo KJ, Jeong YJ, Park-kwon TK (2004). Chrysin induced apoptosis is mediated through caspase activation and akt inactivation in U937 leukemia cell. Biochem. Biophys. Res. Commun. 325-334: 1215-1222.

18. Brown E, Hurd NS, McCall S, Ceremuga TE (2007). Evaluation of the anxiolytic effects of chrysin a Passiflora incarnata extract in the laboratory rat. AANA. J., 75(5): 333–337.

19. Wolfman C, Viola H, Paladini A, Dajas F, Medina JH (1994). Possible anxiolytic effects of chrysin a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol. Biochem. Behav., 47-1: 1-4.

20. Balch PA (2002). Prescription for herbal healing: an easy to use A to Z reference to hundreds of common disorders and their herbal remedies. Avery, New York, ISBN 0-89529-869-4.

21. Zand RS, Jenkins DJ, Diamandis EP (2000). Steroid hormone activity of flavonoids and related compounds. Breast Cancer Res. Treatments, 62(1): 35-49.

22. Yin F, Giuliano AE, Law RE, Van Herie AJ (2001). Apigenin inhibits growth and induces G2/M arrest by modulating cyclin CDK regulators and ERK MAP kinase activation in breast carcinoma cells. Anticancer Res., 21-1A: 413-420.

23. Yin F, Giuliano AE, Van Hearle AJ (1999). Growth inhibitory effects of flavonoids in human thyroid cancer cell lines. Thyroid, 9(4): 369-376.

24. Knowles LM, Zigrossi DA, Tauber RA, Hightower C, Milner JA (2000). Flavonoids suppress androgen-independant human prostate tumor proliferation. Nutr. Cancer, 38-1: 116-122.

25. Nagasugi T, Nakashima M, Komai K (2000). Antimutagens in gaiyou (Artemisia argyi levl. et vant.) J. Agric, Food Chem., 48(8): 3256-3266.

26. Chlouchi A, Girard C, Bonet A, Viollon AC, Heyd B, Mantion G, Martin H, Richert L (2007). Effect of chrysin and natural coumarins on UGT1A1 and 1A6 activities in rat and human hepatocytes in primary culture. Planta Med., 73(8): 742-747.

27. Izzotti A, Bagnasco M, Cartiglia C, Longobardi, M, Camoirano A, Tampa E, Lubet RA, De FS (2005). Modulation of multigene expression and proteome profiles by chemopreventive agents. Mutat. Res., 11-59(11-2): 212-223.

28. Bennati E (1968). New Encyclopaedia of Botanical Drugs and Preparations Saffron Walden. Boll. Chim. Farm, pp. 107-716.

29. Lawrence (1989). The Lawrence Review of Natural Products Facts and Comparisons, Herbal Diuretics (Monograph), p. 1–2.

30. Fernandez D, Arriba A, Lizcano JM, Balsa MD, Unzeta M (1994). Inhibition of monoamine oxidase from bovine retina by betacarbolines. J. Pharm. Pharmacol., 46-10: 809-13.

31. Rommelspacher H, May T, Salewski B (1994). Harman (1- methyl-betacarboline) is a natural inhibitor of monoamine oxidase type A in rats. Eur. J. Pharmacol., 252(1): 51-59.

32. Ergene E, Schoener EP (1993). Effects of harmane (1-methyl-betacarboline) on neurons in the nucleus accumbens of the rat. Pharmacol. Biochem. Behav., 44(4): 951-957.

33. Hagiwara A, Sano M, Asakawa E, Tanaka H, Hasegawa R, Ito N (1992). Enhancing effects of harman and norharman on induction of preneoplastic and neoplastic kidney lesions in rats initiated with NethyI-N-hydroxyethylnitrosamine. Jpn. J. Cancer Res., 83-9: 949-955.

34. Soulimani R, Younos C, Jannouni S, Bousta D, Misslin R, Mortier F (1997). Behavioural effects of Passiflora incaranata L. and its indole alkaloid and flavonoid derivatives and maltol in the mouse. J. Ethnophannacol., 57-61: 11-20.

35. Baumn SS, Hill R, Rommelspacher H (1996). Harman induced changes of extracellular concentrations of neurotransmitters in the nucleus accumbens of rats. Eur. J. Pharmacol., 1-2: 75-82.

36. Bosin TR, Faull KF (1988). Harman in alcoholic beverages: pharmacological and lexicological implications Alcohol. Clin. Exp. Res., 12-5: 679-682.

37. Totsuka Y, Ushiyama H, Ishihara J, Sinha R, Goto S, Sugimara T, Wakabayashi K (1999). Quantification of the comutagenic beta carbolines nonharman and Harman in cigarette smoke condensates and cooked foods. Cancer Lett., 143-152: 139-143.

38. Lee KG, Shibamoto T (2000). Antioxidant properties of aroma compounds isolated from soybeans and mung beans. J. Agric. Food Chem., 48(9): 4290-4293.

39. Dolzhenko AT, Komissarov IV (1987). Characteristics of the presynaptic action of barman and its derivatives compared to benzodiazepine tranquilizers. Farmakol Toksikol., 50(2): 13-16.

40. Brito AM (2007). Synthesis and Characterization of Glycosides. Springer, ISBN 978-0-387-26251-2.

41. Jaroszewski JW, Olafsdottir ES (2002). Cyanohydrin glycosides of Passiflora: distribution pattern a saturated cyclopentane derivative from P. guatemalensis and formation of pseudocyanogenic α-hydroxyamides as isolation artifacts. Phytochem., 59-65: 501-511.

42. Duke JA (2008). Phytochemical and Ethnobotanical Databases –Passiflora spp. http://www.ars-grin.gov/duke.

43. Jaroszewski JW, Rasmussen AB, Rasmussen HB, Olson CE, Jorgensen LB (1996). Biosynthesis of cyanohydrin glucosides from unnatural nitriles in intact Passiflora morifolia and Tunera angustifolia. Phytochem., 42-43: 649-654.

44. Padmaja G, Panikkar KR (1989). Intermediary metabolic changes in rabbits administered linamarin or potassium cyanide. Indian J. Exp. Biol., 27-37: 635-639.

45. Linda D, Lloyd W, Rooney LW (2006). Sorghum and millet phenols and antioxydants. J. Cereal Sci., 44: 236-251.

46. Dhawan K, Dhawan S, Sharma A (2004). Passiflora: a review update. J. Ethnopharmacol., 94: 1-23.

47. Pinheiro ER, Silva IMDA, Gonzaga LV, Amante ER, Reinaldo FT, Ferreira, MMC, Amboni RDMC (2008). Optimization of extraction of high ester pectin from passion fruit peel (Passiflora edulis flavicarpa) with citric acid by using response surface methodology. Bioresour. Technol., 99-113: 5561-5566.

48. Yapo BM, Koffi L (2008). Dietary fiber components in yellow passion fruit rind a potential fiber source. J. Agric. Food Chem., 56-14: 5880-5883.

49. Dhawan K, Kumar S, Sharma A. Reversal of cannabinoids (delta 9‑THC) by the benzoflavone moiety from methanol extract of Passiflora incarnata Linn in mice: A possible therapy for cannabinoid addiction. J Pharm Pharmacol 2002; 54:875-81.

50. Dhawan K, Kumar S, Sharma A. Nicotine reversal effects of the benzoflavone moiety from Passiflora incarnata Linn in mice. Addict Biol 2002; 7:435-41.

51. Dhawan K, Kumar S, Sharma A. Suppression of alcohol‑cessationoriented hyper-anxiety by the benzoflavone moiety of Passiflora incarnata Linn. in mice. J Ethnopharmacol 2002; 81:239-44.

52. Nassiri-Asl M, Shariati-Rad F, Zamansoltani F. Anticonvulsant effects of arial parts of Passiflora incarnata extract in mice: Involvement of benzodiazepine and opioid receptors. BMC Complement Altern Med 2007; 7:26.

53. Nicolls JM (1970). Antifungal activity in Passiflora species. Ann. Bot. (London). 34: 229-337.

54. Birner J, Nicoll JM (1973). Passicol an antibacterial and antifungal agent produced by Passiflora plant species: preparation and physicochemical characteristics. Antimicrob. Agent Chemother., 3: 105-109.

55. Nicolls JM, Birner J, Forsell P (1973). Passicol an antibacterial and antifungal agent produced by Passiflora plant species: qualitative and quantitative range of activity. Antimicrob. Agents Chemother., 3: 110-117.

56. Afolayan AJ, Meyer JJM (1997). The antimicrobial activity of 3, 5, 7-trihydroxy flavones isolated from the shoots of Helichrysum aureonitens. J. Ethnopharmacol., 57: 177-181.

57. Bendini A, Cerretani L, Pizzolante L, Toschi TG (2006). Phenol content related to antioxidant and antimicrobial activities of Passiflora spp. Extracts. Eur. Food Res. Technol., 223: 102-109.

58. Blois MS (1958). Antioxidant determinations by the use of a stable free radica Nature, 26: 1199-1200.

59. Cao G, Sofic E, Prior RL (1997). Antioxidant and prooxidant behavior of flovonoids: structure activity relationships. Free radical Biol. Med., 22: 759-760.

60. Beninca J, Montanher A, Zucolotto S, Schenkel E, Frode T (2007). Evaluation of the AntiInflammatory Efficacy of Passiflora Edulis. Food Chem., 104: 1097-1105.

61. Vargas AJ, Geremias DS, Provensi G, Fornari PE, Reginatto FH, Gosmann G, Schenkel EP, Frode TS (2007). Passiflora alata and Passiflora edulis spray dried aqueous extracts inhibit Inflammation in mouse model of pleurisy. Fitoterapia, 78: 112-119.

62. Montanher A, Zucolotto SM, Schenkel E, Frode T (2007). Evidence of anti-inflammatory effects of Passiflora edulis in an inflammation model. J. Ethnopharmacol., 109: 281-288.

63. Puricelli L, Aicab ID, Sartorb L, Garbisa S, Caniato R (2003). Preliminary evaluation of inhibition of matrix metalloprotease MMP-2 and MMP-9 by Passiflora edulis and P. foetida aqueous extracts. Fitoterapia, 74: 302-304.

64. Capasso A, Sorrentino L (2005). Pharmacological studies on the sedative and hypnotic effect of Kava kava and Passiflora extracts combination. Phytomed., 12(1-2): 39-45.

65. Giavina-Bianchi PF, Castro FF, Machado ML (1997). Occupational respiratory allergic disease induced by Passiflora alata and Rhamnus purshiana. Ann. Allergy Asthma Immunol., 79-5: 449-454.

66. Kapadia GJ, Azuine MA, Tokuda H (2002). Inhibitory effect of herbal remedies on 12-O-tetradecanoylphorbol-13-acetate-promoted Epstein Barr virus early antigen activation. Pharmacol. Res., 45-53:213-220.

67. Dhawan K, Kumar S, Sharma A (2002). Reversal of cannabinoids (delta9-THC) by the benzoflavone moiety from methanol extract of Passiflora incarnata Linneaus in mice: a possible therapy for cannabinoid addiction. J. Pharm. Pharmacol., 54(6): 875-881.

68. Bendini A, Cerretani L, Pizzolante L, Toschi TG (2006). Phenol content related to antioxidant and antimicrobial activities of Passiflora spp. Extracts. Eur. Food Res. Technol., 223: 102-109.

Received on 29.10.2015 Accepted on 16.11.2015

Asian J. Pharm. Res. 5(4): October- December, 2015; Page 195-202

DOI: 10.5958/2231-5691.2015.00030.1