Papaver rhoeas / Klaproos

Overview:
Poppy flowers, Papaver rhoeas L. [Fam. Papaveraceae], also known as corn poppy, corn rose, and flores rhoeados, are found wild in grain fields and along roadsides and highways in Eastern Europe, North Africa and Asia. Corn poppy is the source of the familiar poppy seeds used in baking. The German Commission E monograph for red-poppy petals indicates their use for treating respiratory complaints, disturbed sleep, and as a sedative and for the relief of pain. However, it also notes that the effectiveness in the conditions indicated has not been established. Poppy flowers are also used as a source of food colouring and for enhancing the flavour of herbal teas. Traditionally, poppy blossoms were used to make syrup of red poppy, which was believed to promote sleep, relieve minor aches and pains as well as respiratory irritations such as coughs, colds, and bronchitis. Instructions for preparing the medicinal syrup were listed in the British Pharmacopoeia as early as 1885 and 1898. An ethanolic aqueous extract of Papaver rhoeas petals evaluated for its behavioral and pharmaco-toxicological effects in mice was found to produce a sedative effect at a dosage of 400 mg/kg, which corresponds to a dosage that is much larger than that recommended for poppy flowers used traditionally by humans. Chemical analysis showed that the petals contained anthocyanins, whereas no alkaloids were detected. The lethal dosage in mice was approximately five times the amount found to be sedative, that being 2g/kg (LD10). Behavioral and pharmacological studies of the ethanolic and aqueous extract showed that the plant extract reduced locomotory, exploratory and postural behaviors of mice. These behavioral and pharmacological effects were found to be more pronounced when the solvent used for extraction was 10% ethanol and was not antagonized by benzodiazepines, opioids, dopaminergic and cholinergic compounds (flumazenil, naloxone, sulpuride and atropine).

Active Ingredients:
Poppy flowers contain: Anthocyanin glycosides, especially those with cyanidin as the aglycone, in particular mecocyanin ( = cyanidin 3-sophoroside), and others. Up to 12% isoquinoline alkaloids of which up to 50% is rhoeadine. The flowers also contain mucilage and many ubiquitous substances.

Suggested Amount:
Tea: Brew 2 teaspoons of the drug in boiling water, steep for 10 minutes, then strain. To dissolve phlegm, drink one cup three times per day. To sweeten add honey. 1 teaspoon = 0.8 grams

Drug Interactions:
None known.

Contraindications:
None known.

Side Effects:
There are reported cases of allergic contact urticaria from poppy flowers; it is recommended to use gloves for harvesting the fresh flowers. When pure poppy flowers are used as a tea, even the maximum therapeutic dosage recommended for an adult human (1.6-5 grams per day), causes no risk of toxicity, other than possible rare allergic reactions. The fresh flowers are reported to cause poisoning (stomach pain and vomiting) in children. When taken in large doses, poppy flowers cause convulsions and coma in cattle, cramps in rats, and stimulates respiration in rabbits. The toxicological effect of the alcoholic and aqueous plant extract administered intraperitoneally was determined in mice and the large dosages required to illicit toxicity indicated that the plant is safe when consumed in recommended dosage for humans. The toxicological results obtained indicated that 2g/kg is LD10 (lethal dosage that causes death in 10% of animals tested) and 4g/kg is LD50.

References:
  • Gamboa PM, Jauregui I, Urrutia I, Gonzalez G, Barturen P, Antepara I. 1997. Allergic contact urticaria from poppy flowers (Papaver rhoeas). Contact Dermatitis. 1997 Sep; 37(3): 140-1.
  • Pfeifer S, Hanus V. 1965. [On the alkaloids from Papaver rhoeas L.] Pharmazie. 1965 Jun; 20(6): 394. German.
  • Pfeifer S. 1965. [On the occurrence of glaudine in opium and Papaver rhoeas L.] Pharmazie. 1965 Apr; 20(4): 240. German.
  • Soulimani R, Younos C, Jarmouni-Idrissi S, Bousta D, Khalouki F, Laila A. 2001. Behavioral and pharmaco-toxicological study of Papaver rhoeas L. in mice. J Ethnopharmacol 2001 Mar 3; 74(3): 265-74.
  • Wichtl M and NG Bisset (eds). 1994. Poppy Flowers. In Herbal Drugs and Phyto-pharmaceuticals. (English translation by Norman Grainger Bisset). CRC Press, Stuttgart, pp. 419-420. 


Basic Clin Neurosci. 2016 Jul; 7(3): 195–202.
Papaver Rhoeas L. Hydroalcoholic Extract Exacerbates Forced Swimming Test-Induced Depression in Mice


According to the World Health Organization report, depression is the second leading debilitating factor in humans after cardiovascular diseases and leads to enormous socioeconomic losses (Beck & Alford, 2009). This disease has a complex pathophysiology, and more importantly, a large overlap exists between this disease and stress (Drevets, Price, & Furey, 2008; MacDonald, 1997; Mann, 2005). The main factors underlying the incidence and persistence of this disease include brain monoamine receptors dysfunction, reduced secretion and synthesis of monoamines such as norepinephrine, and possibly brain cells’ secondary monoamine receptors dysfunction (Berton & Nestler, 2006; Blier & de Montigny, 1994; Drevets, Price, & Furey, 2008; MacDonald, 1997; Mann, 2005). Recent studies have shown that increased cortisol and its damaging effect on neurogenesis through reduced nerve growth factor, disruption of endogenous opioid activity, and changes of GABA (gamma-aminobutyric acid) or glutamate activities, reduced cytokine activity in the brain, steroid activities in the brain, and abnormal circadian period can affect the incidence of depression (Caspi et al., 2003; Dantzer, O’Connor, Freund, Johnson, & Kelley, 2008; Drugan et al., 2013; Pariante & Lightman, 2008; Raison, Capuron, & Miller 2006; Southwick, Vythilingham, & Charney, 2005). Although many studies have been conducted on the synthesis of new antidepressants, the latest findings indicate that less than half of the depressed patients have recovered after using these drugs (Nestler et al., 2002). As a result, research on antidepressant chemicals of herbal origin is expanding across the world now (Drew & Myers, 1997). Research on medicinal plants, especially for the treatment of psychiatric and nervous disorders, is very important. A study on depressed people showed that more than 57% of those with major depression experienced better results with using herbal medications than conventional treatments (Drew & Myers, 1997; Sarris, 2007).

In previous studies conducted by the same research group, Papaver rhoeas L. hydroalcoholic extract was shown to reduce the metabolic effects of stress in mice (Mirzaei, Lotfi Kashani, Behzadi, & Sahraie, 2013). Previous studies also examined the effect of the extract of this plant on withdrawal syndrome (Pourmoteabbed et al., 2004), conditioned place preference (Sahraei et al., 2006b), and behavioral sensitization (Sahraei et al., 2006a) in mice. Papaver rhoeas (PR) is a 25–90 cm tall herbaceous plant with red flowers that grows in various parts of the country. This plant contains various alkaloids, such as rhoeadine, rhoeadic acid, papaveric acid, mechoic acid, mucilage, and sugar (Zargari, 1994; El & Karakaya, 2004; Gürbüz, Üstün, Yesilada, Sezik, & Kutsal, 2003; Hillenbrand, Zapp, & Becker, 2004; Pfeifer, 1965; Schaffer, Schmitt-Schillig, & Muller, 2005; Winkler & Awe, 1961; El-Masry, El-Ghazooly, Omar, Khafagy, & Phillipson, 1981; Kalav & Sariyar, 1989; Soulimani, Younos, Jarmouni-Idrissi, Bousta, Khalouki, & Laila, 2001). Historically, this plant was brewed and used to relieve insomnia and reduce inflammation (Zargari, 1994). It also has sedative and mucus relief effects, and is referred to as “harmless opium” due to small amount of morphine in its extract (Zargari, 1994).

Given the anti-opioid (Zargari, 1994), antidopaminergic, and anticholinergic (Saeed-Abadi et al., 2012) effects of PR extract and the role of these agents in the incidence of depression, the present study set out to examine the effect of the extract of this plant on forced swimming test (FST) stress-induced depression in mice. Since the incidence of depression is more frequent in females than in males, the study also made comparisons between genders. Finally, as hypothalamic-pituitary adrenal activity is recognized the main cause of depression (Pariante & Lightman, 2008), this study also investigated the effect of this extract on the activation of the aforementioned system’s functions by measuring plasma corticosterone concentrations (Krishnan & Nestler, 2011; Lucki, 1997).

The present study investigated the effect of Papaver rhoeas L. hydroalcoholic extract on reducing depression caused by FST-induced stress in male and female mice. Results of this study showed that the administration of this extract reduced depression in mice (longer mobility of mice in water), which was comparable to the effect of fluoxetine as a standard antidepressant. Administration of the extract also increased plasma corticosterone concentration, which is the main glucocorticoid hormone secreted by the mice adrenal gland during stress. The PR extract did not affect the mice mobility. Therefore, the antidepressant effect of the extract may not be due to the inhibition of hypothalamic-pituitary-adrenal stress system or stimulation of movements in the animals.

In pathophysiological terms, the reduced concentration of neurotransmitters such as serotonin, norepinephrine, and dopamine cause depression, and all approved antidepressants increase the activity of at least one of these chemical transmitters (Berton & Nestler, 2006; Nestler et al., 2002; Southwick, Vythilingham, & Charney, 2005). Results of the present study, in which the administration of Papaver rhoeas L. hydroalcoholic extract reduced depression in mice, could indicate that the extract of this plant increases at least one of the neurotransmitters involved in depression such as serotonin, dopamine, or norepinephrine (Beck & Alford, 2009). Researchers have shown that depression is directly associated with stress and increased glucocorticoids secretion into the blood (Drugan et al., 2013). However, in the present study, administration of Papaver rhoeas L. extract increased the secretion of this hormone, which shows that the depression-inhibiting effect of the extract has not been due to the inhibition of corticosterone secretion (the main glucocorticoid secreted in mice).

The present study also showed that the effect of the extract was not due to its involvement in the mice motor activity. Numerous studies have been conducted on the various effects of PR extract, and the present study also showed that the extract of this plant has major depression-inhibiting effects. Previous studies have shown that PR extract has immense effects on numerous animal models, including physical and mental morphine-dependence (Pourmotabbed et al., 2004; Sahraei et al., 2006b), morphine responsiveness and behavioral tolerance (Sahraei et al., 2007), and tolerance to the analgesic effects of morphine (Shams et al., 2008). Recent studies, however, have shown the effect of this plant in inhibiting the metabolic effects of stress in male mice (Mirzaie et al., 2013). This extract also boosts memory and inhibits memory loss due to stress in mice (Mirzaie et al., 2013).

All these studies indicate the beneficial effects of the PR extract. The effective compounds in Papaver rhoeas L. hydroalcoholic extract to reduce depression have not identified yet. However, previous researchers have shown that the extract contain anthocyanin, which might reduce depression through interactions with dopamine receptors and their subsequent inhibition (Sahraei et al., 2007). It should be noted that presynaptic dopamine D2 receptors are positioned on dopamine terminals, and their inhibition increases the release of dopamine, which is an effective neurotransmitter in reducing depression (MacDonald, 1997; Mann, 2005). To better understand the effect of this extract, the interaction between the extract and dopamine system is suggested to be examined.

The majority of studies conducted on Papaver rhoeas indicate the presence of papaveric acid, papaverine, and muconic acid in its extract, which are among the most effective compounds on brain neurotransmitters. Previous studies have also shown the anti-glutamate effects of the PR extract (Saeed-Abadi et al., 2012). Since the inhibition of glutamate is currently considered one of the best ways to reduce depression, it appears that the effect of this extract is at least partially caused by this mechanism. Furthermore, this extract also has antiopioid and anticholinergic effects that might have been influential as well. Although the anti-anxiety effect of the extract was not examined in the present study, it might be helpful to study this particular effect to better understand the effects of this plant.

In the present study, a slight difference was observed between the male and female mice in their response to this extract, which might indicate gender differences in stress-induced depression and treatment. Previous studies have shown the greater sensitivity of the female brain to stress compared to the male brain, which might be the reason for this difference. The difference in responsiveness was also observed with fluoxetine. No comprehensive research has yet been conducted on this topic, though a review seems essential.

In this study, the PR extract did not appear to have any inducing or inhibiting effect on the mice’s motor activity in either gender. Previous studies did not report any motor-activity effect for the extract either, and in our previous study, the extract showed no effect on the animals’ mobility in and of itself (Sahraei et al., 2006a; Sahraei et al., 2007). The extract therefore appears to be unable to affect animals’ motor activity function, an effect which is easily discernible with morphine (Sahraei et al., 2006a). The important point is the fluoxetine effect in increasing motor activity in female mice compared to male mice. This effect of fluoxetine has not yet been reported, but it might be due to the ability of fluoxetine in increasing extracellular dopamine concentration in the brain (Ettehadi et al., 2013), even though the center of this increase does not properly match the motor control center.

The present study showed that the extract is capable of stimulating plasma corticosterone concentration increase in male and female mice, which was not the case with fluoxetine. Our previous study also confirmed the effect of the extract on increasing the plasma corticosterone concentration in mice (Saeed-Abadi et al., 2012; Mirzaie et al., 2013). Although several studies directly refer to the increasing effect of glucocorticoid hormones due to stress and their effect on the incidence of mental fatigue, reduced brain monoamines, and depression (Pariante & Lightman, 2008), the present study showed that this extract does not exacerbate the inducing effects of stress on depression; instead, it inhibits this effect. Yet, the presence of compounds that affect dopaminergic, acetylcholine, glutamate, and opioid systems in the extract indicates that the extract induces different effects in different parts of the body, which results in reducing depression.

To recapitulate, with a 15% to 25% prevalence, depression is one the most common psychiatric disorders. It appears that the significant reducing effect of Papaver rhoeas L. hydroalcoholic extract on depression in mice can guide researchers in the quest for finding herbal antidepressants. It should be noted, however, that the present study investigated the short-term administration of the hydroalcoholic extract of this plant, and it is recommended for future studies to examine the long-term use of this extract. Since this extract could effectively reduce depression, it is suggested that its constituent parts be isolated through phytochemical techniques and its effective components be used in the preparation of more effective antidepressants.

References
  1. Beck T. A., Alford B. A. (2009). Depression: Causes and treatment. Pensilvania, USA: University of Pennsylvania Press.
  2. Berton O., Nestler E. J. (2006). New approaches to antidepressant drug discovery: Beyond monoamines. Nature Reviews Neuroscience, 7 (2), 137– 151. [PubMed]
  3. Blier P., De Montigny C. (1994). Current advances and trends in the treatment of depression. Trends in Pharmacological Sciences, 15 (7), 220– 226. [PubMed]
  4. Caspi A., Sugden K., Moffitt T. E., Taylor A., Craig I. W., Harrington H., et al. (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science, 301 (5631), 386– 389. [PubMed]
  5. Dantzer R., O'Connor J. C., Freund G. G., Johnson R. W., Kelley K. W. (2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nature Reviews Neuroscience, 9 (1), 46– 56. [PMC free article] [PubMed]
  6. Drevets W. C., Price J. L., Furey M. L. (2008). Brain structural and functional abnormalities in mood disorders: Implications for neurocircuitry models of depression. Brain Structure and Function, 213 (1–2), 93– 118. [PMC free article] [PubMed]
  7. Drew A. K., Myers S. P. (1997). Safety issues in herbal medicine: Implications for the health professions. Medical Journal of Australia, 166 (10), 538– 541. [PubMed]
  8. Drugan R. C., Morrow A. L., Weizman R., Weizman A., Deutsch S. I., Crawley J. N., et al. (1989).Stress-induced behavioral depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy. Brain Research, 487 (1), 45– 51. [PubMed]
  9. El-Masry S., El-Ghazooly M. G., Omar A. A., Khafagy S. M., Phillipson J. D. (1981). Alkaloids from Egyptian Papaver rhoeas. Planta Medica, 41 (1), 61– 64. [PubMed]
  10. El S. N., Karakaya S. (2004). Radical scavenging and iron-chelating activities of some greens used as traditional dishes in Mediterranean diet. International Journal of Food Sciences and Nutrition, 55 (1), 67– 74. [PubMed]
  11. Ettehadi H., Mojabi S. N., Ranjbaran M., Shams J., Sahraei H., Hedayati M., et al. (2013). Aqueous Extract of Saffron (Crocus sativus) Increases Brain Dopamine and Glutamate Concentrations in Rats.Journal of Behavioral and Brain Science, 3, 315– 9.
  12. Gürbüz İ., Üstün O., Yesilada E., Sezik E., Kutsal O. (2003). Anti-ulcerogenic activity of some plants used as folk remedy in Turkey. Journal of Ethnopharmacology, 88 (1), 93– 97. [PubMed]
  13. Hillenbrand M., Zapp J., Becker H. (2004). Depsides from the petals of Papaver rhoeas. Planta Medica, 70 (4), 380– 382. [PubMed]
  14. Kalav Y. N., Sariyar G. (1989). Alkaloids from Turkish Papaver rhoeas. Planta Medica, 55 (5), 488.[PubMed]
  15. Krishnan V., Nestler E .J. (2011). Animal models of depression: Molecular perspectives. Current Topics in Behavior and Neuroscience, 7, 121– 47. [PMC free article] [PubMed]
  16. Lucki I. (1997). The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behavioural Pharmacology, 8 (6–7), 523. [PubMed]
  17. MacDonald T. M. (1997). Treatment of depression: prescription for success? Primary Care in Psychiatry, 3, 7– 10.
  18. Mann J. J. (2005). The medical management of depression. New England Journal of Medicine, 353(17), 1819– 34. [PubMed]
  19. Mirzaei P., Lotfi Kashani F., Behzadi S., Sahraei H. (2013). The effect of Papaver rhoeas distillate on learning, memory, corticosterone and anorexia in little laboratory mice under inescapable tension.Medical Science Journal of Islamic Azad Univesity, Tehran Medical Branch, 23 (1), 21– 29.
  20. Nestler E. J., Barrot M., DiLeone R. J., Eisch A. J., Gold S. J., Monteggia L. M. (2002).Neurobiology of depression. Neuron, 34 (1), 13– 25. [PubMed]
  21. Pariante C. M., Lightman S. L. (2008). The HPA axis in major depression: classical theories and new developments. Trends in Neurosciences, 31 (9), 464– 468. [PubMed]
  22. Pfeifer S. (1965). On the occurrence of glaudine in opium and Papaver rhoeas L. Die Pharmazie, 20(4), 240– 240. [PubMed]
  23. Porsolt R. D., Deniel M., Jalfre M. L. (1979). Forced swimming in rats: hypothermia, immobility and the effects of imipramine. European Journal of Pharmacology, 57 (4), 431– 436. [PubMed]
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  25. Pourmotabbed A., Rostamian B., Manouchehri G., Pirzadeh-Jahromi G., Sahraei H., Ghoshooni H., et al. (2004). Effects of Papaver rhoeas extract on the expression and development of morphine-dependence in mice. Journal of Ethnopharmacology, 95 (2), 431– 435. [PubMed]
  26. Raison C. L., Capuron L., Miller A. H. (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology, 27 (1), 24– 31. [PMC free article] [PubMed]
  27. Sahraei H., Shams J., Faghih-Monzavi Z., Zardooz H., Pashaei-Rad S., Pourmotabbed A., et al. (2007). Effects of Papaver rhoeas. Extract on the Development and Expression of Tolerance to Morphine-Induced Locomotor Activity in Mice. Pharmaceutical Biology, 45 (6), 475– 480.
  28. Sahraei H., Faghih-Monzavi Z., Fatemi S. M., Pashaei-Rad S., Salimi S. H., Kamalinejad M. (2006a).Effects of Papaver rhoeas extract on the acquisition and expression of morphine-induced behavioral sensitization in mice. Phytotherapy Research, 20 (9), 737– 741. [PubMed]
  29. Sahraei H., Fatemi S. M., Pashaei-Rad S., Faghih-Monzavi Z., Salimi S. H., Kamalinegad M. (2006b). Effects of Papaver rhoeas extract on the acquisition and expression of morphine-induced conditioned place preference in mice. Journal of Ethnopharmacology, 103 (3), 420– 424. [PubMed]
  30. Sarris J. (2007). Herbal medicines in the treatment of psychiatric disorders: A systematic review.Phytotherapy Research, 21 (8), 703– 716. [PubMed]
  31. Schaffer S., Schmitt-Schillig S., Muller W. E., Eckert G. P. (2005). Antioxidant properties of Mediterranean food plant extracts: Geographical differences. Journal of Physiology and Pharmacology,56 (1), 115– 124. [PubMed]
  32. Saeed-Abadi S., Ranjbaran M., Jafari F., Najafi-Abedi A., Rahmani B., Esfandiari B., et al. (2012).Effects of Papaver rhoeas (L.) Extract on Formalin-induced Pain and Inflammation in Mice. Pakistan Journal of Biological Sciences, 15 (21), 1041. [PubMed]
  33. Shams J., Sahraei H., Faghih-Monzavi Z., Salimi S. H., Fatemi S. M., Pourmatabbed A., et al. (2010).Effects of Papaver rhoeas extract on the tolerance development to analgesic effects of morphine in mice. Iranian Journal of Pharmaceutical Research, 7, 141– 7.
  34. Soulimani R., Younos C., Jarmouni-Idrissi S., Bousta D., Khalouki F., Laila A. (2001). Behavioral and pharmaco-toxicological study of Papaver rhoeas L. in mice. Journal of Ethnopharmacology, 74(3), 265– 274. [PubMed]
  35. Southwick S. M., Vythilingam M., Charney D. S. (2005). The psychobiology of depression and resilience to stress: Implications for prevention and treatment. Annual Review of Clinical Psychology,1, 255– 91. [PubMed]
  36. Winkler W., Awe W. (1961). On the structure of rhoeadine isomers isolated from Papaver rhoeas.Archiv der Pharmazie, 294, 301– 306. [PubMed]
  37. Zargari A. (1994). Medicinal plants. Tehran, Iran: Tehran University Press.


Natural Standard Referenties Papaver rhoeas

Mechanism of Action
Pharmacology:

Constituents: Corn poppy petals contain depsides, anthocyanins, p-hydroxybenzoic acid, protocatechuic acid, 2-(4-hydroxyphenyl)-ethanol, 2-(3,4-dihydroxyphenyl)-ethanol, flavonoids (kaempferol, quercetin, luteolin and hypolaetin), glycosides (3- O-beta- D-glucopyranosylquercetin (isoquercitrine), 3- O-beta- D-glucopyranosylkaempferol (astragaline), and 3-O-beta- D-galactopyranosylquercetin (hyperoside) (7;​9). No alkaloids have been detected in the petals (7).
In general, the corn poppy plant contains alkaloids, including its major alkaloid n-methylasimilobine, stylopine, coptisine, isocorydine, glaudine, rhoeadine, and rhoeadine isomers (10;​11;​12;​13).
  • Antioxidant activity: In in vitro studies, corn poppy has shown antioxidant properties, with the greens exhibiting a marked scavenging effect on H2O2 at 0.2g/mL (4;​5).
  • Antiulcerogenic effects: In an in vivo study in rats, which was confirmed by histopathological studies, corn poppy root's antiulcerogenic effect was statistically potent (95.6%) (6).
  • Iron-chelating activity: In in vitro study, corn poppy greens showed Fe2+ ion-chelating activities that were >70% (4).
  • Morphine dependence effects: In a study of animals with dependence on morphine, injection of a Papaver rhoeas water extract 30 minutes before morphine administration increased the jumping and decreased the diarrhea associated with the morphine (1). In two mouse studies by another author, a water-alcohol extract of Papaver rhoeas reduced the acquisition and expression of morphine-induced behavioral sensitization and reduced the acquisition but not the expression of morphine-induced conditioned place reference (2;​3).
  • Sedative effects: Ethanolic and aqueous extracts of Papaver rhoeas petals reduced locomotory, exploratory, and postural behavior of mice, which was more pronounced when the solvent used for extraction was 10% ethanol and was not antagonized by benzodiazepines, opioids, dopaminergic, or cholinergic compounds (flumazenil, naloxone, sulpuride, and atropine) (7). The authors also noted that the plant extract did not induce sleep in mice after treatment with an infrahypnotic dose of pentobarbital.
Referenties
  1. Pourmotabbed, A., Rostamian, B., Manouchehri, G., Pirzadeh-Jahromi, G., Sahraei, H., Ghoshooni, H., Zardooz, H., and Kamalnegad, M. Effects of Papaver rhoeas extract on the expression and development of morphine-dependence in mice. J Ethnopharmacol 2004;95(2-3):431-435.
  2. Sahraei, H., Faghih-Monzavi, Z., Fatemi, S. M., Pashaei-Rad, S., Salimi, S. H., and Kamalinejad, M. Effects of Papaver rhoeas extract on the acquisition and expression of morphine-induced behavioral sensitization in mice. Phytother Res 2006;20(9):737-741.
  3. Sahraei, H., Fatemi, S. M., Pashaei-Rad, S., Faghih-Monzavi, Z., Salimi, S. H., and Kamalinegad, M. Effects of Papaver rhoeas extract on the acquisition and expression of morphine-induced conditioned place preference in mice. J Ethnopharmacol 2-20-2006;103(3):420-424. 
  4. El, S. N. and Karakaya, S. Radical scavenging and iron-chelating activities of some greens used as traditional dishes in Mediterranean diet. Int J Food Sci Nutr 2004;55(1):67-74
  5. Schaffer, S., Schmitt-Schillig, S., Muller, W. E., and Eckert, G. P. Antioxidant properties of Mediterranean food plant extracts: geographical differences. J Physiol Pharmacol 2005;56 Suppl 1:115-124. 
  6. Gurbuz, I., Ustun, O., Yesilada, E., Sezik, E., and Kutsal, O. Anti-ulcerogenic activity of some plants used as folk remedy in Turkey. J Ethnopharmacol 2003;88(1):93-97. 
  7. Soulimani, R., Younos, C., Jarmouni-Idrissi, S., Bousta, D., Khalouki, F., and Laila, A. Behavioral and pharmaco-toxicological study of Papaver rhoeas L. in mice. J Ethnopharmacol 3-3-2001;74(3):265-274. 
  8. Gamboa, P. M., Jauregui, I., Urrutia, I., Gonzalez, G., Barturen, P., and Antepara, I. Allergic contact urticaria from poppy flowers (Papaver rhoeas). Contact Dermatitis 1997;37(3):140-141.
  9. Hillenbrand, M., Zapp, J., and Becker, H. Depsides from the petals of Papaver rhoeas. Planta Med. 2004;70(4):380-382. 
  10. El Masry, S., El Ghazooly, M. G., Omar, A. A., Khafagy, S. M., and Phillipson, J. D. Alkaloids from Egyptian Papaver rhoeas. Planta Med 1981;41(1):61-64.
  11. AWE, W. and WINKLER, W. [Alkaloids of corn poppy.]. Arch Pharm Ber.Dtsch.Pharm Ges 1957;290/62(8-9):367-376. 
  12. Pfeifer, S. [On the occurrence of glaudine in opium and Papaver rhoeas L.]. Pharmazie 1965;20(4):240. 
  13. WINKLER, W. and AWE, W. [On the structure of rhoeadine isomers isolated from Papaver rhoeas.]. Arch Pharm 1961;294/66:301-306. View 
  14. Franchi, G. G., Franchi, G., Corti, P., and Pompella, A. Microspectrophotometric evaluation of digestibility of pollen grains. Plant Foods Hum.Nutr 1997;50(2):115-126. 
Natural Standard Monograph (www.naturalstandard.com)


Phytother Res. 2006 Sep;20(9):737-41. Effects of Papaver rhoeas extract on the acquisition and expression of morphine-induced behavioral sensitization in mice. Sahraei H, Faghih-Monzavi Z, Fatemi SM, Pashaei-Rad S, Salimi SH, Kamalinejad M.
Department of Physiology and Biophysics, and Behavioral Sciences Research Center (BSRC), School of Medicine, Baqiyatallah, University of Medical Sciences, Tehran, Iran. h.sahraei@bmsu.ac.ir
In the present study, the effects of a water-alcohol extract of Papaver rhoeas on the acquisition and expression of morphine-induced behavioral sensitization in mice were investigated. The subcutaneous (s.c.) administration of morphine (50 mg/kg) induced locomotor activity in animals, whereas the drug did not show an effect at a dose of 5 mg/kg. On the other hand, intraperitoneal (i.p.) administration of the plant extract (25, 50 and 100 mg/kg) did not show any effect. The locomotor behavioral response was enhanced in mice pretreated with morphine (5 mg/kg, daily x 3 days) alone, indicating that sensitization had developed. Extract (25, 50 and 100 mg/kg, i.p.) administration, 30 min before each of the three daily doses of morphine decreased the development of sensitization. Moreover, intraperitoneal administration of the plant extract (25, 50 and 100 mg/kg) 30 min before the test reduced the expression of morphine-induced behavioral sensitization. The results indicate that administration of the extract of Papaver rhoeas reduced the acquisition and expression of morphine-induced behavioral sensitization in mice.

J Ethnopharmacol. 2004 Dec;95(2-3):431-5. Effects of Papaver rhoeas extract on the expression and development of morphine-dependence in mice.
Pourmotabbed A, Rostamian B, Manouchehri G, Pirzadeh-Jahromi G, Sahraei H, Ghoshooni H, Zardooz H, Kamalnegad M. Department of Physiology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
The problem of drug dependence still remains unresolved. In the present study, the effects of water-alcohol extract of Papaver rhoeas on the expression and acquisition of naloxone-induced jumping and diarrhea in morphine-dependent mice were investigated. Administration of three daily doses of morphine (12.5, 25 and 50 mg/kg) for three days in order to develop dependence to morphine caused a significant and dose-dependent increase in the number of jumping and diarrhea when the animals were challenged with naloxone (4 mg/kg). On the other hand, administration with the plant extract (25, 50 and 100 mg/kg) did not show any effect. Injection of extract (25, 50 and 100 mg/kg) 30 min before the naloxone administration in morphine-dependent mice decreased the number of jumping and diarrhea. Administration of extract (25, 50 and 100 mg/kg) 30 min before morphine injection increased the number of jumping but decreased the diarrhea. It could be concluded that the extract of Papaver rhoeas can ameliorate the withdrawal syndrome in morphine-dependent mice. Therefore, the extract might be useful to treatment of withdrawal signs in opioid addicts.

J Ethnopharmacol. 2001 Mar 3;74(3):265-74.vBehavioral and pharmaco-toxicological study of Papaver rhoeas L. in mice.
Soulimani R1, Younos C, Jarmouni-Idrissi S, Bousta D, Khallouki F, Laila A.
Erratum in J Ethnopharmacol. 2007 Nov 1;114(2):277. Khalouki, F [corrected to Khallouki, F].
A lyophilized ethanolic aqueous extract of Papaver rhoeas petals was evaluated for its behavioral and pharmaco-toxicological effects in mice and its chemical composition was studied using thin layer chromatography (TLC). In this study, chemical analysis by TLC showed that the petals contain some anthocyanins, whereas no alkaloids were detected. The toxicological effect of alcoholic and aqueous plant extract administered intraperitoneally was determined in mice. The toxicological results obtained indicated that 2000 mg/kg is LD10 and 4000 mg/kg is LD50. Behavioral and pharmacological studies of ethanolic and aqueous extract showed that the plant extract reduced locomotory, exploratory and postural behavior of mice. This was evaluated through two specific behavioral tests; a non-familiar environment test (the Staircase test) and a familiar environment test (Free exploratory test). These behavioral and pharmacological effects are more pronounced when the solvent used for extraction is 10% ethanol and is not antagonized by benzodiazepines, opioids, dopaminergic and cholinergic compounds (flumazenil, naloxone, sulpuride and atropine). The plant extract did not induce sleep in mice after treatment with an infrahypnotic dose of pentobarbital. This finding shows that the plant extract has a sedative effect at a 400 mg/kg dosage.



In de oude Nederlandse farmacopee wordt + Petala Rhoeados / Klaprozen als volgt beschreven

De bloembladen van Papaver Rhoeas, LiNN. Sp. PI. 507. 

Ten hoogste 5 cM. lang en 9 cM. breed; geen nagel; plaat  dwars-langwerpig, dikwijls met min of meer ingesneden voet 
en daardoor niervormig; rand gaaf; in verschén toestand  scharlakenrood, veelal met een purperzwarte hartvlek van  verschillenden vorm; gedroogd vuil-purperkleurig, dun, zeer ineengeschrompeld, vaak samengekleefd. 
In verschén toestand, reuk zwak verdoovend; gedroogd,  bijna reukeloos; smaak een weinig slijmerig, min of meer  bitter. 


Dodonaeus over de klaproos
1644 Vlaams: Heul (Wilden oft Roode), Klapperroosen (Kleyne), Kollebloemen (Kleyne)
1616 Latijn: Papaver erraticum minus
1554/1557: Clapperroosen, Coquelicoc, Coquelicoc (petit), Coquelicoq, Huel, Huel (rooden), Huel (wilden), Klapperrosen, Kornrosen, Lethe, Lethusa, Magle, Magsamen, Mancop, Moen, Olmag, Onitron, Opium, Oxytonon, Papaver, Papaver commune, Papaver erraticum, Papaver fluidum, Papaver nigrum, Papaver rhoeas, Papaver rubrum, Pavot, Pavot commun, Pavot noir, Ponceau, Prosopon
 
Tderde gheslacht wordt oock voor een soorte van Papaver sylvestre ghehouwen ende wordt in die Apoteke gheheeten Papaver commune ende Papaver nigrum. In Duytsch Huel ende schijnt te wesene een Papaver rhoeas/ dat es een vloeyende/ oft rijsende Huel want sijn saet onvloeyet hem alst rijp es/ dat aen den anderen Huel niet en doet/ als voorseyt es.




Groeiplaatsen.
Op zandige Velden, ook onder het Koorn. Bij Pietersbierum en elders in het voormaalig Vriesland, op de Akkers in Hierden bij Harderwijk, bij Bronkhorst en elders in het voormaalig Gelderland, bij Heemskerk in Noord-Holland, onder Bloemendaal aan een Duinwal bij het opgaan van den weg na Overveen.

Huishoudelijk Gebruik.
In hooge Weilanden als eene schadelijke Plant te houden. (Brugmans) Volgens Bulliard zou de Plant van gelijke eigenschap en gebruik zijn als de Papaver Rhoeas, Klaproozen; maar inzonderheid kan van de Bloemen zo wel als van die der Klaproozen, een sap gewonnen worden, dat rood verwt. De Nationaale Huish. Maatsch. (voormaals Oeconomische tak) heeft Ao. 1781. een Gouden Medaille toegeweezen aan J. Az. Kool voor deszelfs bericht, te vinden in de uitgegeeven Verhandelingen van den Oeconomischen Tak, Landbouw No 2; dat uit deeze en andere roode Papaver-Bloemen een vogt of tinctuur kan getrokken worden, waarmede de Kaas; in plaats van Tournesol, die uit Vrankrijk komt; op de Noord-Hollandsche wijze rood kan geverwd worden. Hiertoe moeten 2 1/2 lb Bloemen met eene hoeveelheid regenwater van 5 gewoone flessen een half uur gekookt, en de bladen vervolgens in een doek met de handen uitgewrongen worden; met welk vocht koud geworden zijnde, men de kaas als de gewoone roodkorste kaas kan verwen. Het vogt blijft 8 etmaalen goed, doch men kan het 3 maanden bewaaren, wanneer men in ieder fles een halven lepel voorloop doet, en dit wel doorschut, en boven een weinig oly giet tot bedekking van de lucht. De Bloemen mede goed voor de Beijen (Sw. Abh)



Etymologie: De namen van de klaproos

Klaprozen waren altijd erg bekende, ‘populaire’ planten. Dat bewijzen de vele (volks)namen, die trouwens op heel diverse kenmerken van de plant wijzen. Sommige spreken echt wel tot de verbeelding: stinkroos, kollebloem, rode kol, korepater, kankerbloem, rode koornbloem, klapper, weulverbloem, bloeddroppels der soldaten, donderbloem, oorlogsbloem, doodsbloem, maankop, rosewiet, korenheul, heulbloem, koornroos, …

De algemene naam ‘papaver’ zou afgeleid zijn van het Keltische ‘papapap’ dat ‘pap’ of ‘brij’ betekent en het Latijnse ‘verum’ dat ‘echt’ of ‘waar’ betekent. Dat slaat op de oude gewoonte om papaversap door de pap te roeren om zo huilende baby’s rustiger te maken of in slaap te krijgen. ‘Rhoeas’ komt misschien van het Griekse ‘rhuan’ of ‘rhyas’ wat ‘vallend’ betekent en wijst op het snel uitvallen van de bloemblaadjes. De naam kan ook afkomstig zijn van het Griekse ‘Rhodeos’ of ‘rood’ naar de rode kleur van de bloemen. 

Volgens de Duitse botanicus en arts Hieronymus Bock (1498-1554) werd de klaproos genoemd naar het klapperende of ratelende geluid dat de rijpe zaden maken in de zaaddozen als deze geschud worden. Een andere verklaring verbindt de naam met een oeroud kinderspelletje waarbij bloemblaadjes werden omgevouwen tot een soort zakje dat, als je er een klap op gaf, met een 
klappend geluid opensprong. Dit spelletje werd ook beschreven door de Duitse arts Leonhard Fuchs (1501-1566), als verklaring voor de Duitse naam ‘Clapperroose’. Het tweede deel ‘roos’ verwijst natuurlijk naar de bloemvorm en de rode kleur van vele rozen.

Een andere oude naam voor deze plant is ‘kollebloem’. In 1543 vermeldt Fuchs ‘Colle’ en ‘Colbloemen’, Dodoens noteert in 1618 ‘Collebloem’. Het woord ‘kol’ kan wijzen op de gelijkenis van de gladde doosvrucht met een kaal kopje. Maar omdat de ‘kollebloem’ meestal in het koren groeit, kan de naam ook een verbastering zijn van ‘korenbloem’. Dodoens noemt de grote klaproos ook ‘wilden heul’, waarbij ‘heul’ is afgeleid van het Middelnederlandse ‘oele’, ontstaan uit het Latijnse ‘oleum’. Zo verwijst de naam naar de olie die uit papaverplanten geëxtraheerd kan worden.
De naam ‘kankerbloem’ zou erop wijzen dat boeren haar een ‘kanker’ in het veld vonden, maar het volksgebruik meldt dat de bloem zowel tegen kanker zou helpen, maar ook kanker kon veroorzaken.
De naam ‘klaproos’ wordt ook verbonden met de eigenschap van de bloem om dicht te klappen bij regenweer. In Vlaanderen wordt ze ook wel ‘onweersbloem’ of ‘donderbloem’ genoemd. In Wallonië wordt dit ‘tonnoire’, naar ‘tonnerre’. In vroegere tijden probeerde men ook onweders te bezweren met behulp van de klaproos. Men plukte grote boeketten met donderbloemen om die in de kerk te laten zegenen. Kwam er nadien onweersdreiging opzetten, dan stak men de gezegende planten in brand. 

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