Passiflora: a review update.

This review describes the morphology, microscopy, traditional and folklore uses, phyto-constituents, pharmacological reports, clinical applications and toxicological reports of the prominent species of the genus Passiflora. Flavonoids, glycosides, alkaloids, phenolic compounds and volatile constituents have been reported as the major phyto-constituents of the Passiflora species. A few species of Passiflora have been used for curing various ailments, the most important being Passiflora incarnata Linneaus which possesses significant CNS depressant properties. The studies performed by the authors with the newly isolated benzoflavone (BZF) moiety from P. incarnata have been discussed. In the concluding part, various virgin areas of research on the species of this genus have been highlighted with a view to explore, isolate and identify the medicinally important phyto-constituents which could be utilized to alleviate various diseases affecting the mankind.

Drug/substance reversal effects of a novel tri-substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linn.--a brief perspective.

The present work is a mini-review of the author's original work on the plant Passiflora incarnata Linn., which is used in several parts of the world as a traditional medicine for the management of anxiety, insomnia, epilepsy and morphine addiction. A tri-substituted benzoflavone moiety (BZF) has been isolated from the bioactive methanol extract of this plant, which has been proposed in the author's earlier work to be responsible for the biological activities of this plant. The BZF moiety has exhibited significantly encouraging results in the reversal of tolerance and dependence of several addiction-prone psychotropic drugs, including morphine, nicotine, ethanol, diazepam and delta-9-tetrahydrocannabinol, during earlier pharmacological studies conducted by the author. In addition to this, the BZF moiety has exhibited aphrodisiac, libido-enhancing and virility-enhancing properties in 2-year-old male rats. When administered concomitantly with nicotine, ethanol and delta-9-tetrahydrocannabinol for 30 days in male rats, the BZF also prevented the drug-induced decline in sexuality in male rats. Because the BZF moiety isolated from P. incarnata is a tri-substituted derivative of alpha-naphthoflavone (7,8-benzoflavone), a well-known aromatase-enzyme inhibitor, the mode of action of BZF has been postulated to be a neurosteroidal mechanism vide in which the BZF moiety prevents the metabolic degradation of testosterone and upregulates blood - testosterone levels in the body. As several flavonoids (e.g. chrysin, apigenin) and other phytoconstituents also possess aromatase-inhibiting properties, and the IC50 value of such phytomoieties is the main factor determining their biochemical efficacy, by altering their chemical structures to attain a desirable IC50 value new insights in medical therapeutics can be attained, keeping in view the menace of drug abuse worldwide.

Antiasthmatic activity of the methanol extract of leaves of Passiflora incarnata.

The methanol extract of the leaves of P. incarnata was evaluated for its antiasthmatic effects against acetylcholine chloride (Ach)-induced-bronchospasm in guinea-pigs at doses of 50, 100 and 200 mg/kg. Using a 7-day treatment regimen, significant prevention of dyspnoea-related-convulsions was noted in the animals treated with a 100 mg/kg dose of this extract. No preventive effect was exhibited by the 50 mg/kg dose and at a higher dose, i.e. 200 mg/kg, the preventive effects against Ach-chloride-induced-dyspnoea were also reduced. This may be due to defective alpha-adrenoceptor function reported after excessive or continuous administration of an alpha-receptor agonist.

Attenuation of benzodiazepine dependence in mice by a tri-substituted benzoflavone moiety of Passiflora incarnata Linneaus: a non-habit forming anxiolytic.

PURPOSE: A tri-substituted benzoflavone moiety (BZF) recently isolated from the methanol extract of aerial parts of the plant Passiflora incarnata Linneaus had exhibited encouraging results in countering the dependence produced by addiction-prone substances like morphine, nicotine, cannabinoids and ethyl alcohol, during the studies performed by the authors. Since the BZF moiety had exhibited significant anxiolytic properties at 10 mg/kg p.o. dose in mice, therefore, it was desirable to evaluate this potential phyto-moiety (BZF) for its own dependence-liabilities It was also deemed viable to evaluate BZF moiety for its possible usefulness in countering the dependence-liabilities associated with the chronic use of benzodiazepines keeping in light their tremendous clinical use in the management of anxiety and insomnia. METHODS: Different groups of mice were administered BZF alone (10, 50 or 100 mg/kg, p.o.), and concomitantly with diazepam (20 mg/kg, p.o.) in a 21-days treatment regimen, followed by no treatments for the next 72-hours. The withdrawal effects in the form of ambulatory behavior of the treated animals were recorded on the 25th day using an Actophotometer. RESULTS: The BZF-alone (three doses) treated mice exhibited a normal ambulatory behavior on 25th day. Mice groups receiving co-treatments, i.e., BZF-diazepam concomitantly, also exhibited a normal ambulatory behavior in a dose-dependent manner, i.e., the higher dose of BZF (100 mg/kg) being more effective in countering the withdrawal effects of chronically administered diazepam than the lower doses (10 or 50 mg/kg). CONCLUSIONS: The studies revealed that the chronic administration of the BZF moiety (three doses), did not exhibit any dependence-liability of its own, even upon an abrupt cessation. Additionally, the BZF co-treatments with diazepam also prevented the incurrence of diazepam-dependence, which might be because of the aromatase enzyme inhibiting properties associated with the BZF moiety.

Aphrodisiac activity of methanol extract of leaves of Passiflora incarnata Linn in mice.

The aphrodisiac properties of the methanol extract of leaves of Passiflora incarnata Linn. have been evaluated in mice by observing the mounting behaviour. The methanol extract of P. incarnata exhibited significant aphrodisiac behaviour in male mice at all doses, i.e. 75, 100 and 150 mg/kg. Amongst these, the highest activity was observed with the 100 mg/kg dose when the mountings were calculated about 95 min after the administration of the test extracts.

Restoration of chronic-Delta 9-THC-induced decline in sexuality in male rats by a novel benzoflavone moiety from Passiflora incarnata Linn.

1 The present study comprised treatment of healthy male rats with Delta(9)-tetrahydrocannabinol (THC, 10 mg kg(-1), p.o.), and combinations of THC with benzoflavone moiety (BZF, 10 and 20 mg kg(-1), p.o.) isolated from Passiflora incarnata Linneaus, over a period of 30 days. 2 Upon 30-days chronic administrations, the THC-treated male rats had a significant loss of libido (mounting behaviour with non-oestrous female rats), decrease in sperm count, and number of impregnated pro-estrous female rats. 3 Co-administration of BZF (10 and 20 mg kg(-1) p.o.) afforded significant protection against the chronic-THC-induced decrease in libido, mating performance and fertility during 30-day experimental regimen. The 20 mg kg(-1) dose of BZF exhibited better results. 4 Upon discontinuation of THC, treatment with BZF (10 and 20 mg kg(-1) p.o.) also facilitated the early restoration chronic-THC-induced decline in libido, sperm count and sexual fertility within 7 days.

Prevention of chronic alcohol and nicotine-induced azospermia, sterility and decreased libido, by a novel tri-substituted benzoflavone moiety from Passiflora incarnata Linneaus in healthy male rats.

Excessive long term consumption of alcohol and nicotine have serious detrimental effects upon the libido, fertility, and sperm count in male species. The present work describes the beneficial effects of a novel tri-substituted benzoflavone moiety (BZF) isolated from Passiflora incarnata Linneaus, the phyto-chemical isolation, spectroscopic elucidation, and multifarious biological activities of which have recently been reported by the authors. The BZF moiety has been reported to increase libido, sperm count, and sexual fertility in 2 years old male rats at 10 mg/kg, po dose, in the one of our previous studies. Presently, the BZF moiety has been evaluated against chronic ethanol- and nicotine-induced decrease in libido, sexual fertility and mating efficiency in healthy male rats. The male rats were given ethanol (3 g/kg, po) A, nicotine (2 mg/kg, sc) N, alcohol-nicotine combinations (AN) alone, and also with 10 mg/kg po dose of BZF (concurrent administrations). These treatments were given for 30 days. At the end of treatments, it was observed that rat groups A, N, and AN had no libido (evaluated by mounting behaviour), declined sperm count, and consequently no mating efficiency or fertility (upon pairing with pro-estrus female rats). However, the rats which were given 10 mg/kg BZF along-with nicotine (NP group), alcohol (AP group), and alcohol-nicotine combination (ANP) exhibited significant libido-oriented mounting behaviour, increased sperm count (significantly comparable to the control group), and increased fertilization potential. The rats having decreased sperm count, libido and fertilization potential due to chronic administration of alcohol, nicotine and alcohol-nicotine combinations, i.e., rats of A, N, and AN groups were again subdivided and were given 10 mg/kg BZF for 7 days. This treatment confirmed that BZF speeds up the restoration of sexuality in rats upon cessation of the administration of substances like alcohol, nicotine and alcohol-nicotine combinations, which have severe detrimental effects upon male sexuality, fertility and vigour. BZF, the strongest inhibitor of aromatase enzyme, when administered concurrently with substances like alcohol and nicotine restores sexual virility, libido and vigour in male rats by maintaining the blood-testosterone levels to be high.

Comparative anxiolytic activity profile of various preparations of Passiflora incarnata linneaus: a comment on medicinal plants' standardization.

OBJECTIVES: Mother tincture preparation of Passiflora incarnata from five reputable manufacturers of homeopathic medicines were compared to the bioactive fraction of methanol extract of P. incarnata (standard) for their anxiolytic activity in mice using the elevated plus-maze model of anxiety. MATERIALS AND METHODS: The extracts of P. incarnata were further subdivided in four doses, i.e., 100, 200, 300, and 400 mg/kg, suspended in a vehicle, and administered orally to groups of mice. Methanol extract of P. incarnata (125 mg/kg, orally) was taken as a standard. Anxiolytic activity was measured using the elevated plus-maze model. All treatments were given orally. Forty-five (45) minutes after the treatments, mice were placed on the center of the elevated plus-maze and the number of entries in open arms were measured for 5 minutes. SUBJECTS: Studies were performed with Swiss albino mice. RESULTS: The dried mother tincture preparations exhibited maximum anxiolytic activity at 300 mg/kg (SBL); 400 mg/kg (DWSI and DWSG); 200 mg/kg (DRCG), and nil (BHL) respectively, with reference to anxiolytic activity exhibited by the methanol extract of aerial parts of P. incarnata (125 mg/kg). CONCLUSIONS: To ensure uniformity and consistency of the biologic effects exhibited by plant-derived phytopharmaceuticals, uniform standards are required globally. The monographs on P. incarnata mention standardization of the plant using any known flavonoid as the chemical marker and the marker compound was not the one responsible for the plants multifarious biologic effects. The recent report of a trisubstituted benzoflavone compound (BZF) as the main bioactive phytoconstituent of P. incarnata made it feasible to resort to biologic standardization of this plant using BZF as the biomarker compound. The biologic standardization would ensure bioequivalence of the medicinal preparations of P. incarnata. These studies also recommend the incorporation of leaf constants, ash values, extractive values, thin layer chromatography profile (vital "fingerprints" specific for a plant), and the quantitative assay by determining the bioactive BZF moiety in pharmacopoeias in order to ensure uniform biologic results and standards of P. incarnata because the plant currently has tremendous usefulness. The herbal pharmacopoeias, which are still in their "infancy," can be strengthened by incorporating the appropriate bioactive constituents that need to be identified by using modern technological procedures. Once the appropriate bioactive constituent(s) are established and authenticated, their qualitative and quantitative assay procedures can be developed. Reporting the vital fingerprint parameters of the plant and incorporation of assay procedures of the bioactive phytomoiety in the official monographs of medicinal plants, will certainly strengthen the herbal pharmacopoeias. This is perhaps the most important scientific approach that would ensure uniform standards and bioequivalence of plant-medicines - a need to revive faith in the healing potentials of plant-derived medicines.

Antitussive activity of the methanol extract of Passiflora incarnata leaves.

The methanol extract of the leaves of Passiflora incarnata (100 and 200 mg/kg, p.o.) exhibited significant antitussive activity on sulfur dioxide-induced cough in mice, the cough inhibition (39.4 and 65.0%, respectively) being comparable to that of codeine phosphate (10 and 20 mg/kg, p.o., respectively).

Reversal of cannabinoids (delta9-THC) by the benzoflavone moiety from methanol extract of Passiflora incarnata Linneaus in mice: a possible therapy for cannabinoid addiction.

The newly reported benzoflavone moiety from the plant Passiflora incarnata Linneaus has been evaluated in light of traditional reports on the use of P. incarnata 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. Mice were given a 10-mg-kg(-1) twice-daily dose of delta9-tetrahydrocannabinol (delta9-THC) by mouth for six days to make them dependent upon cannabinoids. Concurrently, other groups of mice were administered delta9-THC along with a 10- or 20-mg-kg(-1) twice-daily dose of the benzoflavone moiety from P. incarnata orally for 6 days. Upon measuring locomotor activity during the treatment regimen, it was noticed that the mice receiving the P. incarnata extract and delta9-THC together developed significantly less tolerance and dependence, relative to the mice receiving delta9-THC alone. Upon administration of SR-141716A, a selective cannabinoid-receptor antagonist (10 mg kg(-1), p.o.) to all the groups of mice on the 7th day, an artificial withdrawal was produced due to an abrupt decline of delta9-THC levels in mouse brain. However, the typical withdrawal effects like paw tremors and head shakes were significantly less in the mice given delta9-THC+P. incarnata benzoflavone moiety for 6 days. Upon administration of 20 mg kg(-1) of the P. incarnata benzoflavone moiety to mice showing severe symptoms of withdrawal due to administration of SR-141716A, there was a marked attenuation of withdrawal effects, thereby suggesting the usefulness of the benzoflavone moiety in delta9-THC withdrawal. Thus, the benzoflavone moiety of P. incarnata, when administered concurrently with delta9-THC, prevented the development of tolerance and dependence of cannabinoids in mice. Even an acute administration of the benzoflavone moiety (20 mg kg(-1), p.o.) significantly blocked the expression of withdrawal effects in delta9-THC-dependent mice.

Suppression of alcohol-cessation-oriented hyper-anxiety by the benzoflavone moiety of Passiflora incarnata Linneaus in mice.

A benzoflavone moiety has been reported recently to be responsible for the multifarious CNS effects of Passiflora incarnata Linneaus. In the light of the established usefulness of the benzoflavone moiety in counteracting the withdrawal effects of substances like morphine, cannabinoids and nicotine by the authors, the bioactive benzoflavone moiety (BZF) has been tested in mice treated with an addictive dose (2 g/kg, bid for 6 days) of ethyl alcohol, in order to evaluate its effectiveness in countering alcohol dependence. In a 7-day regimen, different groups of mice were administered vehicle, alcohol and alcohol+three doses (10, 20 and 50 mg/kg of the benzoflavone moiety) of P. incarnata; all treatments (chronic) being administered orally, twice daily for 6 days. Similarly, three other groups of mice were rendered addicts upon alcohol by administration of the addictive dose (2 g/kg, bid for 6 days) of ethyl alcohol, and a single acute administration of 10, 20 and 50 mg/kg dose of benzoflavone moiety was given on the 7th day. In both, chronic and acute administrations, the benzoflavone moiety prevented significantly the expression of withdrawal effects of alcohol as there was a significant decrease in anxiety oriented behavior in mice that received benzoflavone moiety of P. incarnata. The chronic administration of P. incarnata with alcohol had better preventive effects than the single acute treatment with P. incarnata in alcohol-dependent mice.

Nicotine reversal effects of the benzoflavone moiety from Passiflora incarnata Linneaus in mice.

A benzoflavone moiety (BZF) has recently been reported to be liable for many of the biological effects of the plant Passiflora incarnata Linneaus. In light of various reports mentioning the usefulness of P. incarnata in tobacco addiction, studies have been performed using four doses (1, 5, 10 and 20 mg/kg) of the bioactive BZF moiety isolated from the aerial parts of P. incarnata. In a 7-day experimental regimen, mice (n = 5) were given nicotine hydrogen tartrate (2 mg/kg), and combinations of nicotine with four doses of BZF (NnP-1, NnP-5, NnP-10 and NnP-20) q.i.d. by the s.c. route. At the end of the 7 days of treatment, naloxone was given to the mice from all groups to induce a nicotine withdrawal syndrome. The mice that had been treated with 10 and 20 mg/kg dose of BZF concurrently with nicotine showed a significantly fewer number of withdrawal jumps relative to the group treated with nicotine alone (Nn group). Separately, in a 14-day treatment regimen, mice (n = 10; for the N group, n = 12) were administered nicotine (2 mg/kg) and combinations of nicotine with four doses of BZF (NP-1, NP-5, NP-10, NP-20 groups) q.i.d. by the s.c. route. Spontaneous physical and behavioural signs of nicotine dependence were observed 3 hours after cessation of treatments on the 14th day. Mice administered with combinations of nicotine and 5, 10 and 20 mg/kg doses of BZF (i.e. NP-5, NP10 and NP-20 groups), exhibited less intensity and severity of withdrawal effects compared to the mice treated with nicotine alone. Those mice treated with the two highest doses of BZF,in combination with nicotine (NP-10 and NP-20), showed significantly fewer nicotine-abstinence withdrawal jumps and normal ambulatory behaviour. BZF treatment prevented weight loss and resulted in normal performance in the swimming endurance test, which may be a measure of stress and/or depression. Similarly, acute administration of a single 20 mg/kg dose of BZF prevented some of the nicotine-withdrawal effects; lower doses were almost inert. These studies, although preliminary, suggest that the BZF may have value in treating nicotine addiction.

Beneficial effects of chrysin and benzoflavone on virility in 2-year-old male rats.

This work describes the potential usefulness of bioflavonoids for countering the deleterious effects of aging on male sexuality in 2-year-old rats. A flavone chrysin from Passiflora caerulea Linn. and a benzoflavone moiety (BZF) recently isolated from Passiflora incarnata Linn. were administered to 2-year-old male rats for a period of 30 days. After cessation of these treatments, there was a significant improvement in overall sexual functions in the rats given bioflavonoids, compared with control rats. The rats receiving chrysin (1 mg/kg) and BZF (10 mg/kg) exhibited increased libido when they were allowed to interact with nonestrous female rats. Additionally, both treated groups had increased sperm count, greater fertilization potential, and greater litter size when they were allowed to interact with proven proestrous female rats of a similar strain. BZF was more potent than chrysin as an antiaromatase agent and exhibited better effects on the sexual system of the 2-year-old male rats. Plant flavonoids have great potential for clinical and therapeutic applications against the physiological and biochemical effects of aging.

Correct Identification of Passiflora incarnata Linn., a Promising Herbal Anxiolytic and Sedative.

Passiflora incarnata Linn. and Passiflora edulis Sims are the two important plants of the family Passifloraceae that have often been reported as synonymous because of their identical morphological and microscopic characteristics. P. incarnata is a popular sedative and anxiolytic, whereas, P. edulis is rarely reported to possess significant central nervous system depressant activity. P. edulis, as the name of the species reflects, is mainly grown for edible purposes. During a survey of literature on the genus Passiflora, it was noticed that in many references the two plants are mentioned synonymously. The designation by Sir William J. Hooker in 1843, followed by the citation of P. edulis as the synonym of P. incarnata in Index Kewensis of 1895, not only substantiated the controversial identity but also caused confusion to researchers. The prevailing confusion might have led to improper selection of the bioactive plant, thereby accounting for inconclusive and contradictory pharmacological reports on either of the two plants. In this work, we establish key identification parameters to differentiate P. incarnata from P. edulis. Various leaf constants such as vein-islet number, vein-termination number, stomatal number, and stomatal index are different for the two species. Physicochemical parameters such as ash values and extractive values and the thin layer chromatography profile of the petroleum ether extract of P. incarnata and P. edulis are also distinct and different. Various clinical uses of P. incarnata for anxiety and allied diseases are discussed.