Datura metel L. (Solanaceae)

Synonyms

Datura alba, Datura fastuosa

Vernacular Names:

English: Devil’s Trumpet, Metel, Downy Thorn Apple
Tamil: Oomathai
Chinese: Yangjinhua

General Information

D. metel grows on waste land and river sand, especially in sunny positions. This plant originated from China but was naturalized in the Mediterranean. D. metel can also be found in East Asia or India. [1]

Description

D. metel is a shrub-like herb with large flowers. The plant can reach measuring 1.5m in large, alternate, dark green leaves and sometimes with purple stem. The fruit is in the form of a spiny capsule. The foliage has a rank smell, but the large, trumpet-shaped flowers have a sweet fragrance that emit especially in the mornings and evenings. They come in single and double forms, and a variety of colors, from white to yellow and light to dark purple. [2] The flowers are hermaphrodite (have both male and female organs) and are pollinated by insects. This plant prefers light (sandy) and medium soils, either dry or moist. D.metel can grow in very alkaline soil but is unable to grow in the shade. [1]

Plant Part Used

Barks, leaves, seeds. [1]

Chemical Constituents

The whole plant of D. metel contains scopolamine (hyoscine) and atropine which increased gradually with the progress of developmental growth, and are most pronounced when the plant is at the end of its reproductive stage. The scopolamine accumulation is highest in the root after 16 weeks. The root contains higher amount of atropine compared to the other parts. The aerial parts usually accumulated relatively higher amounts of scopolamine and relatively lower amounts of atropine as compared with the root of the plant. [3] The plant contains the alkaloids hyoscyamine, hyoscine and atropine. The total alkaloid content of the leaves is 0.426%, which is mainly atropine. The seeds contain 0.426% alkaloids, which is mainly hyoscyamine. The roots contain 0.35% hyoscyamine. [1]

A colourless crystalline constituent, daturilin has been obtained from the acid-insoluble fraction of the alcoholic extract of D. metel leaves. This compound has been identified as l-oxo-21,24S-epoxy-(20S,22S-witha-2,5,25-trienolide. [4] Three withanolide compounds were discovered from the leaves of D. metel. These compounds were recognized as withametelin C, D, and E. [5] The previous studies showed that the cultured callus of D. metel contained cholesterol and 5α-pregnane3β,20β-diol. It also demonstrated the present of C28 sterol 3β,24ξ-dihydroxy-ergosta-5,25-dienolide and the withanolide 12-deoxywithastramonolide in in vitro propagated shoots of D. metel. [6] The three new withanolide (22-hydroxyergostan-26-oic acid  -lactone) compounds named baimantuoluoline A, B, and C and the two known withanolides withafastuosin E and withametelin C were isolated from the fraction exhibiting activity for psoriasis from the flower of D. metel . The three new structures were determined as (5 ,6 ,7 ,12 ,15 ,22R)-6,7-epoxy-5,12,15-trihydroxy-1-oxowitha-2,24-dienolide (baimantuoluoline A), (5 ,6 ,15 ,22R)- 5,6,15,21-tetrahydroxy-1-oxowith-24-enolide (baimantuoluoline B), and (5 ,6 ,12 ,22R)-5,6,12,21-tetrahydroxy-27-methoxy-1-oxowitha-2,24-dienolide(baimantuoluoline C). [7][8]

A pyrrole derivative, which was isolated from the chloroform extract of D. metel leaves was characterized as 2'-(3,4-dimethyl-2,5-dihydro-1Hpyrrol-2-yl)-1'-methylethyl pentanoate. [9] The three new withanolide glycosides named daturametelins H, I, J, were isolated from the methanolic extract of the aerial parts of D. metel. This methanolic extract also contains other compound such as daturataturin A and 7,27-dihydroxy-1-oxowitha-2,5,24-trienolide. [10]

About ten new withanolides namely withametelins I, J, K, L, M, N, O, P, 12β-hydroxy-1,10-seco-withametelin B and 1,10-seco-withametelin B, together with seven known withanolides were isolated from methanol extract of the flowers of D. metel. The structures of these 10 new withanolides compounds were elucidated by means of spectroscopic methods, and the absolute stereochemistry of withametelins I was confirmed by single-crystal X-ray analysis. [11]

Traditional Use:

D. metel contains tropane alkaloids and are used as sedative, antispasmodic and mydriatic agents. [12] The whole plant, but especially the leaves and seed, have anaesthetic, hallucinogenic, antiasthmatic, antispasmodic, antitussive, bronchodilator, anodyne, hypnotic and mydriatic effects. It has a wide range of applications in India, including in the treatment of epilepsy, hysteria, insanity, heart diseases, and for fever with catarrh, diarrhea and skin diseases. A poultice of the crushed leaves is used to relieve pain. In China, the plant is used in the treatment of asthma. In Vietnam, the dried flowers and leaves are cut into small chips and used in antiasthmatic cigarettes. About 3 to 5g of the flower extract can be used as an anaesthetic through oral consumption which produces general anaesthesia within 5 minutes which lasted for about 5 to 6 hours. [1] The flower of the D. metel is used in the treatment of pain, chronic bronchitis and asthma. [13][14]

Pre-Clinical Data

Pharmacology

Antifungal activity

The antifungal activity using pathogenic species of Aspergillus were investigated in the hexane, chloroform, acetone and methanolic fractions of D. metel. In this study, the chloroform fraction was found to have antifungal activity compared to the other fractions. The minimum inhibitory concentration (MIC) of the chloroform fraction of D. metel L. was 625.0mg/mL against all the three species of Aspergillus, i.e. A. fumigatus, A. flavus and A. niger , using the microbroth dilution and percent spore germination inhibition assays. The MIC by disc diffusion assay was found to be 12.5mg/disc. These results showed that the chloroform fraction of D. metel, was 9.2 times less active than amphotericin B (a standard drug for aspergillosis treatment). Such an   observation was expected because of the used of crude extract in this study. Although the chloroform fraction of D. metel extract was less potent against aspergillosis compared to amphotericin B, its in vitro toxicity as studied by MTT assay using monocyte-macrophage mouse RAW cells was 117.8 times less toxic compared to the toxicity of amphotericin B. Based on these results, constituents in the chloroform extracts of D. metel showed potential for development into better drugs against pathogenic fungi. [15]

The methanolic extracts D. metel also possessed antifungal properties against pathogenic Aspergillus fumigatus, A. flavus and A. niger. The extract was solubilized in dimethyl sulfoxide (DMSO) and diluted with water to make final concentration as per requirement. The antifungal activity was investigated using disc diffusion, microbroth dilution and percent spore germination inhibition assays. The minimum inhibitory concentration of D. metel against A. fumigatus, A. flavus and A. niger are 0.062mg/disc for disc diffusion, 1.250mg/mL in microbroth dilution and percent spore germination inhibition. Based on the results, methanolic extract of D.metel also has significant antifungal activity towards pathogenic Aspergilli. [16]

The phytochemical investigation on the chloroform extract of the leaves of D. metel led to the isolation of a new pyrrole derivative, which was characterized as 2'-(3,4-dimethyl-2,5-dihydro-1Hpyrrol-2-yl)-1'-methylethyl pentanoate. This compound was found to be active against all the species tested; Candida albicans, Candida tropicalis, Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. The MIC of the compound against the various fungal species by microbroth dilution assay ranged from 21.87 to 43.75µg/mL. Since the compound showed 90% of growth inhibitions (MIC90) it can be explored further to develop new antimycotic drugs. [9]

The post-antifungal effect (PAFE) of the antifungal compound 2-(3,4-dimethyl-2,5-dihydro-1Hpyrrol-2-yl)-1-methylethyl pentanoate (DHP) on Aspergillus fumigatus was investigated. Aspergillus fumigatus is a ubiquitous pathogen that causes a variety of diseases, especially in immunocompromised patients, such as in cancer patients, the recipients of bone marrow transplant, solid-organ transplant recipients and HIV-infected patients. The conidia of A. fumigatus were exposed to DHP at concentrations of 1x and 4x MIC90 for variable times at 37 °C. Amphotericin B (AmB) acted as the control. Both DHP and AmB prolonged the lag phases of the turbidimetric growth curves. Both treatments delayed growth, with lag phases of 11 h upon treatment with a concentration of 4x MIC90 for 4 h. DHP inhibited the expression of three A. fumigatus secretory proteins of 18, 42 and 55kDa using the SDS-PAGE profiles.The proteins inhibited by DHP may represent important targets within the pathogen as well as crucial factors involved in the pathogenesis of A. fumigatus. One protein of 42 kDa was found to be a metalloprotease, which is an important virulence factor that is able to degrade collagen in human lungs. The other proteins could not be sequenced due to interference from their high level of glycosylation. Analysis of time-dependent antigenic profiles showed the early expression of high-molecular-mass antigens. High-molecular-mass antigens were first expressed within a time frame of 10 h in the cultures. Expression of low-molecular-mass antigens started after 24 h culture. The treatment of A. fumigatus with DHP inhibited the expression of low-molecular-mass antigens. The 18kDa antigen which was expressed along with the high-molecular-mass antigens within 10 h of incubation was also found to be inhibited by DHP. Although the mechanism whereby DHP inhibit these proteins is unknown, the observations may provide valuable information in understanding the role of therapeutic in the virulence of the pathogen, as well as the antigen-mediated responses caused by A. fumigatus. [17]

Hypoglycemic activity

The seeds of D. metel were investigated for hypoglycemic and antihyperglycemic activities in normal Wistar albino rats and diabetic rats. Normal rats were given the D. metel seed powder (suspended in 1% sodium CMC) in the form of mucilage at doses of 25, 50 and 75mg/kg body weight. After base line blood glucose estimation, the rats were made diabetic by injecting freshly prepared aqueous solution of alloxan monohydrate (110mg/kg, i.p.). Animals with blood glucose levels above 300 mg/dL were given the D.metel seed powder (25, 50 and 75mg/kg body weight, orally). The standard antidiabetic drug used was gliclazide (0.56mg/kg). The blood samples were collected at 0.5, 1, 2, 4, 6, 8, 12 and 24 h after drug administration. A dose-dependent hypoglycemia was observed in animals treated with D. metel seed powder. A significant reduction in blood glucose of 22.35, 31.89 and 34.26 % was seen at 8h with doses f 25, 50 and 5mg/kg body weight, respectively.  The dose dependent antihyperglycemic activity was also observed with D. metel in alloxan-induced diabetic rats. The percentage reduction of blood glucose was higher in the diabetic state compared to the normal state by all the three doses of D. metel where a significant reduction in blood glucose of 49.22, 64.07, and 68.14% was observed at 8 h with the doses of 25, 50 and 75mg/kg body weight, respectively. Gliclazide, (0.56mg/kg, p.o.) produced significant (59.9%) reduction in blood glucose compared to the diabetic control at the 8h. These results showed that seed powder of D. metel possessed blood glucose lowering effect in normoglycemic and in alloxan-induced hyperglycemic rats. Thus, the folk usage of the seeds of D. metel for controlling diabetes may be validated by this study and the seeds offer promise for the development of potent phytomedicine for diabetes. [18]

Xanthine oxidase inhibitory activity

The xanthine oxidase inhibitory activity was assayed for D. metel which is traditionally used for the treatment of gout and related symptoms by the indigenous people of India. More than 50% xanthine oxidase inhibitory activity (in vitro) was seen in the methanolic extracts of D. metel which was comparable with the standard antigout drug, allopurinol which showed 93.21% inhibition at 100µg/mL concentration with an IC50 value of 6.75µg/mL.Theaqueous and alcoholic hydro extracts of D. metel did not produce significant activity up to 100µg/mL concentrations. In general, the methanolic extract was found to be more active compared to the aqueous and alcoholic hydro extracts. The methanolic extract was then screened for acute toxicity. The animals were observed individually at least once during the first 24 hours(with special attention to the first 4 h) and daily thereafter for approximately a period of 14 days. No toxicity was seen in the animals up to maximum dosage of 2000mg/kg body weight with no changes in behaviour pattern and no signs or symptoms of toxicity or mortality. The methanolic extract was also screened for in vivo hypouricaemic activity against potassium oxonate-induced hyperuricaemia in mice, but it did not show significant activity compared to the methanolic extract of Coccinia grandis and Vitex negundo. [19] 

Bioactive lipids and radical scavenging potentia activity

The fatty acids and fat-soluble bioactive of the D. metel seeds were analyse using gas-liquid chromatography (GLC) and normal-phase high performance liquid chromatography (HPLC). The amounts of n-hexane extract were found to be between 5.50% and 12.6%. The amount of total lipid in D.  metel seeds was 55g/kg in weight.  The major fatty acid was linoleic acid followed by oleic, palmitic and stearic acids. The crude n-hexane extract was characterized by a relatively high amount of phytosterols. The total phytosterols (TL) content was recorded at a higher level in D. innoxia (1.67% of TL) followed by D. metel (1.34% of TL). The next major components were stigmasterol, β-sitosterol, lanosterol, ∆5-avenasterol and sitostanol. In this extract, γ-tocopherol was the major component present accounting for more than 80% of total tocopherols detected. When different extracts were compared for their radical scavenging activity (RSA) toward the stable 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, D. metel was able to quench only 40 % of DPPH radical, which was low compared to other Datura species. D.metel seeds contain a considerable amount of oil and maybe a good source of essential fatty acids and lipid-soluble bioactives. The presence of tocopherols and sterols may have medicinal importance for human being. [20]

Antiproliferative activity

The five compounds isolated from the the methanolic extract of the aerial parts of D. metel were tested for their antiproliferative activity towards the human colorectal carcinoma (HCT-116) cell line. The compounds were withanolide glycosides named daturametelins H, I, J, daturataturin A and 7,27-dihydroxy-1-oxowitha-2,5,24-trienolide. Only the nonglycosidic compound (7,27-dihydroxy-1-oxowitha-2,5,24-trienolide) exhibited the highest antiproliferative  activity in HCT-116 cells, with an IC50 value of 3.2±0.2µM. [10]

Toxicities

All parts of this plant are poisonous. [21] The plant is very poisonous, even an in small dose which is due to its toxic tropane alkaloid. [1][2]

A review on traditional Chinese herbal medicines and anaesthesia revealed that herbs such as D. metel can lead to toxicity due to the presence of anticholinergic substances such as scopolamine, hyoscyamine and atropine. The yypical features of toxicity include acute confusion, fever, tachycardia, hot flushed dry skin, dilated pupils, dry mouth, urinary retention, hallucinations, headache, delirium, rapid and weak pulse, convulsions, and coma. [13][14][21]

D. metel may cause neural toxicity due to anticholinergic poisoning.[14]

The great caution is advised since excess doses cause severe intoxication and death. The toxic dose is very close to the medicinal dose so this plant should only be used under the guidance of a qualified practitioner. [1]

Cytotoxicity activity

The withametelins I,J, K, L, M, N, O, P, 12β-hydroxy-1,10-seco-withametelin B and 1,10-seco-withametelin B, were isolated from the methanolic extract of D. metel. The cytotoxicity assays of these compounds were performed using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The withametelins I, K, L, and N exhibited cytotoxic activities against A549 (lung), BGC-823 (gastric), and K562 (leukemia) cancer cell lines, with IC50 values ranging from 0.05 to 3.5µM. Withamilin J showed moderate cytotoxic activity against BGC-823 and K562 but less cytotoxicity against A549 [11]

Genotoxicity and Mutagenicity Studies

No documentation 

Clinical Data

Clinical Trials

Adverse Effects in Human:

Acute confusion occurs one hour after drinking a D. metel herbal decoction for nasal congestion. Dilated pupils were noted on admission. The clinical diagnosis was anticholinergic poisoning due to ingestion 10 times of the recommended dose. [22]

Use in Certain Conditions

Pregnancy / Breastfeeding

No documentation

Age Limitations

Neonates / Adolescents

No documentation

Geriatrics

No documentation

Chronic Disease Conditions

No documentation

Interactions

Interactions with drugs

No documentation

Interactions with Other Herbs / Herbal Constituents

No documentation

Contraindications

Contraindications

No documentation

Case Reports

No documentation


Read More

  1) Botanical Info

  2) Poisonous

References

  1. Plants for A Future http://www.pfaf.org/database/plants.php?Datura+metel
  2. The Herb Society of Amerika http://www.herbsociety.org/promplant/dmetel.php
  3. Afsharypuor S, Mostajeran A, Mokhtary R. Variation of scopolamine and atropine in different parts of Datura metel during development Planta Med. 61:383-384, 1995
  4. SiddiquI S, Sultana N, Ahmad SS and Haider SI. A novel withanolide from Datura metel. Phytochemistry 26(9):2641-2643, 1987.
  5. Gufta M, Manickam M, Sinha SC, Sinha-Bagchi A. and Ray BA. Withanolides of Datura metel Phyrochemistry, 31(7): 2423- 2425, 1992
  6. Bratati De . Steroidal compounds from in vitro regenerated shoots of Datura metel. Fitoterapia, 74:14–17, 2003.
  7. Manickam M., Sinha-Bagchi A, Sinha SC, Gupta M, Rays AB. Withanolides of Datura fastuosa leaves. Phytochemistry, 34(3):868-870,1993.
  8. Yang B, Wang Q, Xia Y, Feng W, Kuang H. *Withanolide Compounds from the Flower of Datura metel L. Helvetica Chimica Acta. 90( 8):1522 – 1528, 2007.
  9. Dabur R., Chhillar A. K., Yadav V.,Kamal PK,Gupta J and Sharma G. L. In vitro antifungal activity of 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate,a dihydropyrrole derivative. Journal of Medical Microbiology, 54: 549-552, 2005.
  10. Ma L. Xie CM. Li J. Lou FC. Hu LH Daturametelins H, I, and J: three new withanolide glycosides from Datura metel L.Chemistry & Biodiversity. 3(2):180-6, 2006.
  11. Pan Y, Wang X, Hu X. Cytotoxic Withanolides from the Flowers of Datura metel J. Nat. Prod., 70:1127-1132, 2007.
  12. Nuhu H. Alakaloid content of the leaves of three Nigerian Datura species Nig. J. Nat. Prod. And Med.6:15-18, 2002.
  13. Kam P. C. A. and Liew S. Review Article. Traditional Chinese herbal medicine and anaesthesia Anaesthesia, , 57:1083–1089, 2002.
  14. Ko RJ. Causes, Epidemiology, and Clinical Evaluation of Suspected Herbal Poisoning Clinical Toxicology, 37(6),:697–708, 1999.
  15. Rajesh GLS. Studies on antimycotic properties of Datura metel. Journal of Ethnopharmacology 80:193-/197, 2002.
  16. Dabur R Singh H., Chhillar A.K. Ali M., Sharma GL.  Antifungal potential of Indian medicinal plants. Fitoterapia 75: 389–391, 2004
  17. Dabur R., Mandal K. and Sharma G. L. Post-antifungal effects of the antifungal compound2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate on Aspergillus fumigatus Journal of Medical Microbiology 56: 815–818, 2007.
  18. Murthy B. K., Nammi S, Kota M.K., Rao R.V.K, Rao NK.,. Annapurna A. Evaluation of  hypoglycemic and antihyperglycemic effects of Datura metel (Linn.) seeds in normal and alloxan-induced diabetic rats. Journal of Ethnopharmacology, 91: 95–98, 2004
  19. Umamaheswari M, AsokKumar K, Somasundaram A, Sivashanmugam T, Subhadradevi V, Ravi TK. Xanthine oxidase inhibitory activity of some Indian medical plants. Journal of Ethnopharmacology 109: 547–551, 2007
  20. Ramadan MZ, Zayed R, El-Shamy H. Screening of bioactive lipids and radical scavenging potential of some solanaceae plants Food Chemistry 103: 885–890, 2007.
  21. Poisonous Plant; Datura metal http://www.ces.ncsu.edu/depts/hort/consumer/poison/Daturme.html
  22. Chan TYK., Tam HP, Lai CK, Chan AYW. A Multidisciplinary Approach to the Toxicology Problems Associated with the Use of Herbal Medicines. The Drug Monit ,27(1): 53-57, 2005