Phytochemicals, Pharmacological Properties and Biotechnological Aspects of Highly Medicinal Plant: Datura stramonium

Plants are the backbone of the life on earth. They are essential resource for human wellbeing and among them Datura stramonium is one of highly important plants commonly known as Jimson weed. It is an annual herb found in temperate and sub-tropical areas. Its medicinal significance is mainly because of higher amounts of tropane alkaloids and traditionally used throughout the world. It possesses many phytoconstituents including alkaloids, flavonoids, amino acids, tannins, saponins, carbohydrates, terpenoids, steroidal glycosides and phenols. Various pharmacological activities i.e. anti-asthmatic, antimicrobial, antioxidant, anticancer and anti-inflammatory are exhibited by the plant. Secondary metabolites obtained from species of Datura genus produce tropane alkaloids which have influence on human nervous system and are used in medicines. Despite of its medicinal importance it is a potentially poisonous plant and known as plant hallucinogen. Its random use can cause restlessness and acute poisoning may lead to death. In global increasing energy demand scenario, Datura stramonium plant seeds oil is proved as an efficient source for biodiesel production. This paper will present an exclusive review with respect to the phytochemicals, ethno-medicinal, pharmacological and biotechnological aspects which will lay a solid foundation for further scientific research work to exploit the medicinal and industrial benefits of this plant.


Introduction
All over the world Datura stramonium is known to be a very important medicinal plant and hallucinogen. The various parts of the plant i.e. flowers, leaves, seeds and roots are used in many medical treatments so Datura stramoniumhas a very special place in Ayurveda. The plant Datura stramonium L. belongs to genus Datura and family Solanaceae. The word Datura is derived from Sanskrit word Dhutra which means "divine inebriation". It is a local plant of North America it was identified and scientifically described by a Swedish botanist Carl Linnaeus in 1753 [54,59]. Datura stramonium is cosmopolitan plant found in many plant communities [86].
Datura stramonium is an annual herb and its height could be upto 2-5 feet (60-120 cm), it is erect and has foul smell [73]. Many species of Datura are used very extensively because of their medicinal values as it contains more than 30 alkaloids [74]. Since 1925 for isolation and identification of total alkaloid contents in Datura a lot of researches are carried out and the phytochemical constituents of plant are scopolamine, atropine, hyoscyamine, and tropanes [6,9]. In Ayurveda the parts of the plant are used for curing skin disorders, asthma, jaundice, piles and diabetes [14]. It has antifungal, antibacterial, antiulcer, antispasmodic, larvicidal, antioxidant [12], antinociceptive [1], hypolipidemic [62], hypoglycemic and anti-rheumatoid [26] activities and used in traditional folklore medicine in the world.

Distribution
The origin of Datura stramonium is uncertain [13]. It is locally found in the areas of tropical climates such as India, Mexico, and South America [88]. It is found in the garbage dumps in the Europe [59]. It was brought in UK from various resources such as soybean waste and bird seed [69,73]. Jimson weed is the native plant of the most of temperate and subtropical areas so it is most probably originated in Central America. Although Datura stramonium is originated in America but it is commonly found in the cultivated fields of France [36].
Jimson weed is indigenously found in Middle East, Germany, France, United States, South America, Capsian region and Hungary [81]. Thorn apple is widely distributed in the temperate regions of the world [6]. In UK Jimson weed is infrequently found especially during the hot summers. Datura stramonium is found on most of the places as a weed ranging from roadsides to farm in India [74]. The plant is present in the gardens, pastures and wastelands of district Baghdad [3]. It is not only a native plant of South Africa but it is also found in many other parts of the world as it was used by Red Indians for a long period of time as euphoric agent, and it is also utilized as therapeutic agent in the great Britain since 1800's [82].

Anti-asthmatic Activity
Datura stramonium was studied with respect to asthma treatment and possible effects on prenatal development. When a mother will use this plant for asthma treatment then the fetus will be exposed to it, and this plant will cause a continuous release of acetylcholine which results in desensitization of narcotic receptors, this could ultimately causes permanent damage to the fetus. Therefore it is concluded that this African herbal remedy should be used carefully during pregnancy [60].

Antimicrobial Activity
The extracts prepared from leaves and branches of jimson weed exhibit anti-microbial activities. The methanolic extracts of datura showed the antimicrobial activity against Gram positive bacteria. A very little antimicrobial activity was also observed against Escherichia coli and Pseudomonas aeruginosa [78]. When the combined crude ethanolic extracts of Datura stramonium along with Terminalia arjuna, Withania somnifera were analysed for the antibacterial and antifungal activities, a potential antimicrobial activity was observed against Staphylococcus aureus, Bacillus subtilus, Escherichia coli, Klebsiella pneumonia, Micrococcus luteus and Candida albicans [23]. The petroleum ether extracts of the plant have antimicrobial activities against E. coli and Trachystemon orientalis [70].

Anti-rheumatic Activity
The infusion prepared from stem, branches and leaves exhibits anti-rheumatic potential [40].

Antibacterial Activity
The leaf extracts of Datura stramonium show antibacterial activity against various strains of bacteria including Klebsiela pnuomenae, Staphylococcus aureus, Escherichia coli, Gram positive and Gram negative bacteria [66]. It is reported that higher concentrations of ethanolic leaf extracts are required for antibacterial activity against Klebsiela pnuomenae, Staphylococcus aureus, Escherichia coli to inhibit the growth. The antibacterial substance retard the formation of peptidoglycan and cells become died due to osmotic shocks. Datura stramonium exhibited a very significant antimicrobial activity against Bacillus thuringiensis and Agrobacterium tumefacians with the zone of inhibition of 16 mm and 19 mm [17]. The antibacterial activity of methanolic extracts of thorn apple seeds reveals that it is very active against Gram positive as well as Gram negative bacteria. These extracts show highest zone of inhibition (20 mm) against E. coli followed by (17.50 mm) zone of inhibition against S. aureus (16 mm) zone of inhibition against P. aeruginosa and lowest zone of inhibition (15 mm) against B. subtili [87].

Nematicidal Activity
The leaf extracts of D. stramonium exhibits very efficient nematicidal activity [71].

Antifungal Activity
A concoction prepared from D. stramonium, Azadirachta indica, Calotropis giganta, cow manure methanol and water has the strong antifungal activity against Fusarium magniferae [83]. The extracts obtained from leaves and branches of jimson weed exhibit antifungal properties. Datura stramonium exhibited very high antifungal activity against Aspergillus flavus [25].
The anti-fungal activity was observed against the Fusarium oxysporium (the fungal pathogen of pigeon pea plant) when the leaf extracts of eight plants including Datura stramonium, Hyptis sauveolens, Withania somnifera, Lawsonia inermis, Adhotoda zylanica was applied. The ethanolic extracts of these plants both in vivo and in vitro showed the inhibition of spore formation and growth of the pathogen [39].

Anticancer Activity
Various human cancer cells derived from breast (MDA-MB231), head, neck (FaDu) and lungs (A549) were exposed to aqueous extracts of D. stramonium for 24-48 hours and parameters of clonogenic cell and oxidative stress were also accounted. It was observed that cancer cell lines were sensitive to cell killing induced by extracts of Datura with some viability of < 0.05 [2].

Antitumor Activity
The endophytic fungi was separated from jimson weed and MTT assay was used on human gastric tumor cell line BGC-823 to test the antitumor activity and the result was 100% growth inhibition. Agglutin (DSA lectin) isolated from Datura stramonium caused differentiation of C6 glioma cells which was irreversible. DSA also stalled the growth of four human glial tumor cells [23].

Antioxidant Activity
Flavonoids are polyphonic compounds. The content of flavonoids in the methanolic extracts of Datura stramonium was between 23.15-63.3 mg/g. It was observed that they have properties of free radical scavenging, inhibition of hydrolytic oxidative enzymes and they also exhibit anti-inflammatory activity and their role in human health care and nutrition is significant [47,62]. The methanolic extracts can decrease the activity of DPPH free radicals just like Gallic acid which is a standard antioxidant [87]. The aqueous extract of Datura stramonium has more potent antioxidant activity as compared to organic extract [24].

Vibriocidal Activity
Organic solvent and aqueous extracts of different parts of the six medicinal plants was analyzed against the strain of Vibrio cholera for the treatment of cholera and gastrointestinal diseases. The results revealed that just like other medicinal plants D. stramonium can also be served as broad spectrum vibriocidal agent [71].

Traditional Uses of Datura Stramonium
Jimson weed is used to cure the people having deafness, soothe insomniacs and to release the heat during fever. The plant is found in a 4,000 years old painting which indicated that it was used by the Huichol Indian along with peyote to converse the spiritual world. It is used in Delphi by the priests of Apollo to help them in their divination. In American medical journal it is mentioned that Datura stramonium is one of the best remedies for hydrophobia and there is other medicine having better results as compare to this plant. Datura and cannabis are used in combined form as smoke because it burns very easily [7]. British soldiers use it to treat respiratory problems. It is also used for the treatment of various diseases such as motion sickness, nausea and dizziness. It is used as an analgesic for bone setting. It is an important drug with respect to asthma treatment [44]. And for this purpose the leaves of the plant are smoked in cigarette or pipe. In India the plant is utilized in the various ethno veterinary practices by the Gujjar community. In Ethiopia students used it to increase their imagination power and to make their mind more receptive to leaning. The plant is used in ointments as craft witch in Europe. Many European countries use its seeds to brew beer. The various tribes of Mexico such as Opata and Seri use the plant non-religious rituals. The growing Datura The plant is known as Yangjinhua in China and the Chinese people use it in the treatment of various diseases such as asthma, pain, rheumatism convulsions [39]. The oil obtained by crushing the leaves of Datura stramonium is used for skin diseases, headache and dandruff and its stems and stalks are chewed for treatment of toothache and respiratory disorders in Kashmir valley [38]. The traditional uses of Datura stramonium in various parts of the world are listed in the table:

Medicinal Uses
Extracts of Datura stramonium are prepared various solvents including ethyl acetate, acetone, chloroform, dichloromethane, methanol and ethanol for medicinal purposes [52].

Medicinal Uses of Leaves of Datura Stramonium
The leaves are used for treatment of pain and for this purpose the roasted leaves are applied on the affected area of body. They are very effective to cure headache, earache the pain due to hemorrhoids and neuralgia. They are used in mind altering drugs because of the presence of scopolamine and hyoscymine. The problem of arthritis (rheumatism and gout) can be overcome by the treatment with vapors of the leaves infusion. The smoke of the burning leaves is used to cure bronchitis [16]. The leaves are used as repellents against mites and mosquito. It is a good remedy for heart problems including palpitation and hypertension. The leaves are used as poultice to overcome boils. It is very much effective for treatment of whooping cough and spasm of bladder the leaves of Datura along with tobacco leaves are used as anodyne. It can also be used to cure rattlesnake bite, swellings, sprains and tumors. It relieves the pain of sciatica and certain medicinal effect is also observed for Parkinson's disease [37,72].

Medicinal Uses of Seeds of Datura stramonium
The oil obtained from Datura is good stimulant for hair growth and can cure baldness. The fistules and abscesses are also alleviated by jimson weed seeds. Seeds of Datura have anthelmintic, analgesic and anti-inflammatory properties and therefore they are used to relieve toothache, fever due to inflammation and intestinal and stomach pain due to worms [32].

Protection in Organophosphate Toxicity
The terrorists use the organophosphate nerve agent and for the treatment of it atropine is required. For such treatment the hospital's entire atropine will be even insufficient. The plant jimson weed possesses atropine and it can be obtained simply by boiling the crushed seeds of the plant. So Datura stramonium could be used to cope up with organophosphate toxicity and it increases the survival chances [80].

Tropane Alkaloids as Essential Medicine
Species included in Datura genus i.e. D. stramonium, D. tatula and D. innoxia produce tropane alkaloids and these species are cultivated for their atropine, hyoscyamine, and scopolamine content because of their impact on human nervous system and they are used to treat neurological problems. Secondary metabolites obtained from plants specifically hyoscyamine (HS) exhibit vital role in stress adaptation. Harfi et al., established 343 independent hairy roots (HRs) lines of Datura and studied the production of hyoscyamine (HS). The results of GC/MS screening showed the production of 13 alkaloids [35]. Highly Medicinal Plant: Datura stramonium Srinivasan et al., engineered yeast (Saccharomyces cerevisiae) strains for de novo production of tropine that is known as a key intermediate in the biosynthetic pathway of medicinal tropane alkaloids and this effort would contribute to industrial fermentation of medicinal TAs [76].

Biodiesel Preparation
There is the worldwide scenario of increasing energy demand with increasing population trend. Witte et al., reported that in comparison to Jatrpha curcus beef tallow biodiesel the Datura stramonium oil's biodiesel has best kinetic viscosity [89]. Ashutosh investigated Datura Stramonium biodiesel and he reported that if pure Datura stramonium plant seeds oil is directly used in engine that would be ultimately ejected by converting it into biodiesel through trans-esterification, we can observe more viscosity consistency. Beside that its calorific values and cetane numbers were also same as that of diesel fuel [4].

Bioremediation
The plant is also used in bioremediation as it removes 2, 4, 6-trinitrotoluene (TNT) from explosive waste sites and convert it into other forms by nitroreduction [79].
Datura plant extracts are effective in reducing the toxicity of cypermethrin pesticide [14].

In Vitro Acaricidal and Oviposition Deterrent
Properties The combined leaf extracts of Datura stramonium were applied against acaricide susceptible (IVRI-I line) Semicarpus anacardium and resistant (IVRI-I line) Rhiphicephalus microplus and they inhibited the growth [46]. The ethanol extracts of leaves and seeds of Datura stramonium were investigated for acaricidal, repellent and oviposition deterrent properties against adult two-spotted spider mites under laboratory conditions. The extracts of leaf and seed were applied in 167.25 and 145.75 g/L concentrations respectively (using a Petri leaf disc -Spray tower method) and they caused 98% and 25% mortality among spider mite adults after 48 hours. So this result suggests that Datura stramonium can be used to control the two-spotted spider mites [46,48].

Larvicidal and Mosquito Repellent Activities
The ethanolic exracts leaves of Datura stramonium were examined for larvicidal and mosquito repellent activities against Aedesaegypti, Anopheles stephensi and Culexquinquefasciatus. For larvicidal activity the LD50 values were found to be 86.25, 16.07 and 6.25 mg/L against Aedesaegypti, Anopheles stephensi and Culex quinquefasciatus respectively. These extracts provided complete mosquito repellency of 2.7, 71.7 and 117.7 min against Aedesaegypti, Anopheles stephensi and Culex quinquefasciatus at higher concentration. Datura stramonium exhibits significant larvicidal effects against Tribolium castaneum by reducing the growth rate and food consumption [37]. The ethanolic extracts of Datura stramonium exhibit significant larvicidal and mosquito repellent activities against Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus [12].

Insectividal Activity
The extracts obtained from the powdered leaves, stem and seeds of Datura stramonium were used to check their ability to control the stored products from attack of Callosobruchus maculates and the results revealed that with the increase of concentration the mortality rate is increased [37].

Reservoir of Virus and Whiteflies
Tomato severe rugose virus (ToSRV) is very significant begomovirus whose transmission is carried out by whitefly Bemisia tabaci in tomato crops. Gorayeb et al., evaluated the role of Datura stramonium as alternative host of ToSRV and found that D. stramonium was mostly a good host for whitefly reproduction. As a result of viral infection improved performance of Bemisia tabaci Mediterranean (MED) cryptic species on host plant was also observed. It is concluded that Jimson weed has significant value for the pathosystem and its control must be encompassed in management practices [30].

Callus Induction
Callus induction and regeneration efficiency can be enhanced from embryo culture of Datura stramonium by adjusting carbon sources and concentration [3].

Beverage Industry
Datura stramonium is used in alcoholic beverages to increase the intoxication [37].

Toxicity
The extracts of the plant are potentionally poisonous and random use can cause restlessness and severe poisoning can lead to death. Since the earliest record of history the hallucinogenic properties of Datura stramonium are known [10]. Tropane alkaloids include atropine (dl-hyoscyamine) and scopolamine (i-hyoscine) [23]. Atropine and scopolamine act as the depressant of central nervous system and they affect the muscarinic cholinergic receptors [20]. Many cases of suicide attempts by eating and chewing of Datura have been reported. It is very toxic plant because of the presence of toxic tropane alkaloids. Once soldiers ate this plant in salad in the region of Jamestown (Virginia) in 1676 and they got died because of the poisoning of the plant and for that reason the plant got its name as Jimson weed. The plant has very bitter taste and the animals usually don't eat it. But if food resources are inadequate the cattle, sheep, goat and horses consume it and get poisoned. In fatal cases the body temperature become very abnormal, it may lead to coma and the ultimate result could be death. Toxicity symptoms include nervousness, bloat, anorexia, tenesmus, rumen atony, tremors, excitability and even death in most severe cases [50]. The plant is very harmful for cattle, human, horses, sheeps, pigs, mules and chicken. Jimson weed has constrained medicinal uses. Datura seeds are many times accidently or intentionally ingested by human beings [86].

Datura Stramonium Poisoning in Horses
In horses intoxication with thorn apple results in hyperthermia, tachycardia, polypnoea with dispnoea, acute gastric dilation, secondary intestinal gas accumulation, mydriasis, dry mucosae, lack of thirst, complete refusal of feed, urination and defecation [10].

Toxicological Evaluation of Datura Stramonium in Rats
A sub-chronic feeding study of 90 days was carried out in male and female rats by providing diet comprising of 0.5, 1.58 and 5.0% jimson weed seeds. The seeds contain 2.70 mg of atropine 0.66 mg of scopolamine per gram. The jimson weed seeds produced certain effects including decrease in body weight, serum albumin, serum calcium and increase in testes and liver weight, serum alkaline phosphate and blood urea nitrogen. There were more obvious affects in female rats as compared to male rats, as females showed decrease in serum proteins and cholesterol and increase in serum glutamic-pyruvic transaminase and chloride, red blood cells and hemoglobin. There were not seen any histological lesions at 0.5% concentration of jimson weed. More adverse physiological changes were observed at 0.5% concentration of jimson weed in rats [19].

Conclusion
Plants are very important for pharmacological research and drug development as their bioactive constituents can directly be used as therapeutic agents and precursors for drug development. This paper has directed towards various interesting findings of medicinal value of Datura stramonium. Apart from its toxicity and ornamental value it possesses various phytochemicals which prove it as potent chemotherapeutic agent. Various parts of the plant are used in Ayurveda to treat human ailments. Present review gives us broad information about the bioactive constituents, ethnopharmacology along with scientifically claimed medicinal uses of Datura stramonium. The plant shows various important pharmacological activities due to the presence of active chemical compounds.
The findings of this paper would be helpful for the development of new agents for medical application (i.e. especially drugs for asthma, diabetes, epilepsy) and agro-industries based on natural products derived from plants. The plant can be used as a biocontrol agent because of its insecticidal, fungicidal activities and can also be used in bioremediation. It can also be used for biodiesel preparation. Extracts of Datura could be of high value in grain storage C. maculatus especially when plants are available to farmers with little resources to meet the high cost of pesticides.
As it is potentially toxic plant, its adverse effects can be extremely harmful. Therefore despite of beneficial aspects, the risk -benefit ratio should always be taken into consideration before using. It should be used very carefully after the proper consultation of the specialized person and females using it for asthma treatment should stop its use during pregnancy. There is a need of further investigation and quantification of phytoconstituents and pharmacological profile.
This information will play an important role to understand pharmacological, medicinal and biotechnological aspects of this plant and will also direct the future research.