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41. Luo, W., Zhao, M., Yang, B., Ren, J., Shen, G., & Rao, G. (2011). Antioxidant and antiproliferative capacities of phenolics puried from phyllanthus emblica l. fruit. Food Chemistry,
126(1), 277–282.
42. Bhattacharya, A., Kumar, M., Ghosal, S., & Bhattacharya, S. (2000). Effect of bioactive tannoid principles of emblica ofcinalis on iron-induced hepatic toxicity in rats. Phytomedicine,
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43. Santoshkumar, J., Devarmani, M.S., Sajjanar, M., Pranavakumar, M., & Dass, P. (2013). A
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44. Chatterjee, A., Chattopadhyay, S., & Bandyopadhyay, S.K. (2010). Biphasic effect of phyllanthus emblica l. extract on nsaid-induced ulcer: An antioxidative trail weaved with immunomodulatory effect. Evidence-based Complementary and Alternative Medicine, 2011, 146808.
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Chapter 4
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Belladonna
SadiaJaved, AsmaraAhmad, MuhammadSajidHamidAkash,
KanwalRehman, andArwaA.Al-Huqail
4.1 Introduction
Belladonna is a perennial herbaceous plant that produces anunpleasant odor [1].
The scientic name of belladonna is Atropa belladonna belonging to heSolanaceae,
which is a widely distributed and famous botanical family [2]. The genus name
Atropa is derived from the Greek word “Atropos”, meaning inexorable, and the
specie name belladonna is an italic word that means beautiful lady. The genus
Atropa includes four species, each withve-lobed owers with analternative leaf
pattern [3, 4]. The plant is given this name because of its use as a beautifying agent
by women in Renaissance, Italy [5]. The common names of this plant are belladonna, deadly nightshade, gray morel, devil's herb, dwale, poison black cherry,
naughty man’s cherries, devil’s cherries, divale, and dwayberry [6].
Duringthe Middle Ages, the Atropa belladonna plant extract was employed by
women as eye drops that madetheir facial features attractive by dilating the pupils
of their eyes [7]. However, belladonna was no longer employed as acosmetic product due to its harmful effects on humans, including enhanced heart rate, blurred
vision, and ultimately results in blindness [4]. The Romans military people
S. Javed (*) · A. Ahmad
Department of Biochemistry, Government College University, Faisalabad, Pakistan
e-mail: sadiajaved@gcuf.edu.pk
M. S. H. Akash
Department of Pharmaceutical Chemistry, Government College University Faisalabad,
Faisalabad, Pakistan
K. Rehman
Department of Pharmacy, The Women University Multan, Multan, Pakistan
A. A. Al-Huqail
Department of Biology, College of Science, Princess Nourah bint Abdulrahman University,
Riyadh, Saudi Arabia
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
M. Zia-Ul-Haq etal. (eds.), Essentials of Medicinal and Aromatic Crops,
https://doi.org/10.1007/978-3-031-35403-8_4
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commonly employed the belladonna plant extract as abiological agent for intoxicating the food supply of their enemies. Likewise, the poison-tipped arrows were
made by the archers using the toxic paste of belladonna extract [8]. It has been
stated that recently more than 15,000 lethal cases related to exposure to greater
doses of belladonna alkaloids have occurred [9].
The Solanaceae are well known for their applications in the food industries, but
unfortunately, these are absurdly lethal due to the highercontents of alkaloids in
them. However, a subgroup of these plants is hallucinogenic and has medicinal
properties [2]. One of these plants is Atropa belladonna has been reported to
havebeen employed as anarcotic, pharmaceutical, haunting, and warfare agent for
many years in Europe [10–12].
The different parts of Atropa belladonna contain different amounts of tropane
alkaloids, which exhibit both therapeutic and toxic properties when applied as
herbal medicine [5]. This chapter will highlight the morphological characteristics,
agronomy, and diseases caused by pests’ attacks to belladonna. In addition, it will
also briey discuss the therapeutic applications of belladonna in the eld of
medicine.
4.2 Morphology
Atropa Belladonna has a height ranging from 1.5 to 2 m, abranched pubescent
stem, and large acute, ovate-lanceolate, and petiolate leaves of 8–15cm in length
[13]. As depicted in Fig.4.1, it has abell-shaped, purple-colored owers thatare
solitary, located in the axil between stem and leaves, and grow laterally [4]. At the
Fig. 4.1 Atropa belladonna
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time of fruiting, the calyx part of theower is campanulate and pubescent, having
alength of 3cm and beingseparated into ve ovate-lanceolate, acute sepals. The
corolla part, which helps in plants’ reproduction, is campanulate, tubular, and
hasve thin lobes at its upper terminal, with greenish-yellow shade at the bottom
end and blue-violet shade at the top end. There are ve stamens containing unequal
laments with rounded or ovate anthers that are placed at the base ofthecorolla [1].
Moreover, the fruits belladonna produces are spherical-shaped berries whose size
range is 13–18mm in diameter. These berries comprise numerous kidney-shaped
seeds with asweettaste and purple juice [4].
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4.3 Agronomy
Atropa belladonna starts ourishing in May, keeps healthy untilsummer, and blossoms again in the autumn [1]. The plant species are cultivated around the globe but
areparticularly native to Western Asia, North Africa, Europe, and occasionally as
ornamental plants in the United States. TheEastern Hemisphere has been known for
practicing the hallucinogenic effect of Atropa belladonna [5]. It requires moderate
climatic conditions, such as clear and sunny weather especially during the crop
harvesting season. It is unable to survive water-logged situations as the increased
level of humidity and constant dampness cause root deterioration [14].
The cultivation of belladonna can be carried out in several places, like wooded
hills, hedgerows, shady areas, quarries, grasslands, and slopes [15]. But the favorable soil conditions include shady, humid, well-drained, slightly acidic, nitried,
silty-loam to clayey-loam,and an abundant amount of humus-containing area with
an altitude of 400–2000 m [1]. Studies have demonstrated that it can grow
10–1800m inheight in shaded trees, in shear-cut open areas, specically in beech
and spruce forests [13].
Regarding the crop plantation, it is done either by thevegetative method via cutting the roots and shoots or by propagating the seeds. The seed propagation method
is the easiest and mostcost-effective approach. In this method, seeds are carefully
chosen from a plant with a high content of alkaloids. The germination of seeds is
enhanced by treating them either with ethanol for 3 min or with petroleum for 6min,
and then the seeds are disseminated in the nursery beds at the start of thespring
season. 15 to 40% of the germination occurred within 10–21days. Then, during the
month of August, the transplantation of germinating seedlings carrying 1–3 leaves
is carried out by planting them in the eld at a distance of 45–60cm. Moreover,
before plantation, farmyard manure, potassium oxide, and diammonium phosphate
are also applied to the cultivated land, whereas at the time of branching and picking,
nitrogen fertilizer is applied. However, during summer, irrigation of crops is done
every 10–15days [14].
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4.4 Pests andViruses Infecting Belladonna
The pests that mainly attack Atropa belladonna are ea beetles, Epitrix atropae,
Foudras, and Epitrix pubescens, Koch. The genus Epitrix is widely distributed and
comprises almost 180 species [16]. These small beetles mostly attack the plants of
Solanaceae and riddle the leaves of plants [17]. During the summer season, the ea
beetles oviposit in the soil, and within 7–8days, eggs hatch into larvae. Larvae
remain in the soil andare converted to pupa after about 1week. The other pests that
attack the belladonna are Psylliodes hyoscyami, L., and caterpillars of Barathra
(Mamestra) brassicae, L., and Heliothis peltigera, Schiff [18].
Studies also demonstrated that the members of theSolanaceae family are being
infected by several pathogenic viruses. Employing high-throughput sequencing
technologies, the International Committee on Taxonomy of Viruses (ICTV) has
identied six orders, 32 families, and 141 genera, containing 1901 species of plant
viruses. The mode of transmission of plant viruses may be vertical or horizontal,
depending on the viral species. The viruses attacking the Solanaceae plants use
insect vectors, especially aphids, as their mode of transmission. The viruses identied to infect belladonna are belladonna mottle virus (BeMV) and henbane mosaic
virus (HMV). BeMV is transmitted through Epitrix atropae, whereas HMV is transmitted via aphids [19].
4.5 Chemical Constituents
The principle chemical constituents of Atropa belladonna are 20 different types of
tropane alkaloids, including atropine, atropamine, apoatropine, belladonnine, cuscohygrine, 1-hyoscyamine, 6-β-hyoscyamine, norhyoscyamine, N-methylpyrroline,
N-methylpyrrolidine, scopolamine, and tropine [4, 15, 20]. l-hyoscyamine and atro-
pine are present in the highest amounts in leaves, stems, roots and fruits. They both
contribute 99% of the total alkaloid content present in the leaves [1, 3]. Out of the
total alkaloid complex, hycosamine was observed to contribute 87.6% in the leaves
and 68.7% in the roots [15]. The concentration of atropine in the fruit is 0.1%,
whereas in theroots it ranges between 0.4% and 0.6%. It has been observed that the
concentration of alkaloids varies from one plant to other due to varying environmental factors like geographical area, harvesting season, soil type,and climatic conditions [1]. The plan’s chemical defense system involves several alkaloids like
hyoscyamine, scopolamine, and atropine which help protect the plant against various abiotic and biotic stresses [15].
In order to identify the alkaloids present in the plant extract of belladonna, several separating techniques are being employed. These include capillary electrophoresis coupled to UV detection, high-performance liquid chromatography (HPLC)
coupled to UV detection, thin layer chromatography (TLC) coupled to UV detection, high-performance liquid chromatography-mass spectrometry (HPLC-MS) and
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gas chromatography-mass spectrometry (GC-MS), quadrupole coupled to time-ofight analyzers (Q-TOF), and high-resolution mass analyzers like Orbitrap [21].
The analysis carried out by GLC and GLC-MS showed that the roots of belladonna
plant contain 13 alkaloids while 7 alkaloids are distributed in other parts of the
plant [4].
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4.6 Biosynthesis ofBelladonna Alkaloids
The biosynthesis of tropane alkaloids is mainly carried out in the roots of belladonna, from where they are transported to thestem, leaves, and fruits. The key
enzyme involved in the formation of tropane alkaloids is S-adenosylmethionine
dependent Putrescine N-Methyltransferase (PMT) causes the methylation of a
diamine, putrescine, into N-methyl putrescine, which is a primary metabolite in
these biosynthetic reactions [22, 23]. The N-methyl putrescine, then converted to
tropinone through aseries of intermediate compounds like 4-methylaminobutanal,
N-methyl-pyrrolium cation, and hygrine. Then tropinone reductase I catalyzes the
conversion of tropinone into tropine [24]. Afterwards, the condensation reaction of
phenyl-lactate with tropine results in the synthesis of littorine, which undergoes
oxidation and enzymatic rearrangement to form hyoscyamine. Furthermore,
hyoscyamine- 6-hydroxylase catalyzes the conversion of hyoscyamine to scopolamine [4] (Fig.4.2).
4.7 Mechanism ofAction ofBelladonna Alkaloids
Belladonna tropane alkaloids work as competitive inhibitors of all the subtypes
(M1–M5) of muscarinic acetylcholine receptors (mAChRs) [25, 26]. These are Gprotein-coupled receptors, found in several parts of human body. M1 receptors are
excitatory in nature, found both in thecentral and peripheral nervous system, and
involve the excitation of theCNS, regulation of homeostasis, and gastric parietal
cells for secretion of gastric acid. TheM2 receptor has inhibitory function and
islocated in cardiac cells. The M3 subtype receptors are found in exocrine glands,
endothelium of thevascular system, and smooth muscles of the bronchi, gastrointestinal tract, and urinary system. These receptors seem to be involved in vasodilation, glandular secretions, and thecontraction of smooth muscles. Whereas M4 and
M5 receptors are mostly present in the CNS, controlling attention, numbness,
arousal, and memory [4].
The mechanism of action of tropane alkaloids is depicted in Fig.4.3. The afnity
of atropine molecules is stronger for bronchial, heart, and gastrointestinal muscles.
While scopolamine acts strongly on theiris and ciliary body and greatly inuences
the reduction of the bronchial, salivary, and sweat gland secretions [25, 26].
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Fig. 4.2 Biosynthetic pathway of belladonna alkaloids
4.8 Pharmacodynamics ofBelladonna
Belladonna alkaloids stimulate the CNS by functioning as antagonist of muscarinic
receptors present in the brain [26]. The lower concentration of tropine shows no
signicant effect, whereas hyoscyamine is effective even at low dosages. Atropine
also involves the stimulation of respiratory, vagal, and vasomotor centers located in
the medulla. Belladonna has asignicant effect on the cardiovascular system. It is
responsible for causing tachycardia, especially in adults. However, no noticeable or
consistent impact of belladonna alkaloid on blood pressure was observed [27]. The
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Fig. 4.3 Mechanism of action of belladonna alkaloids. (Modied from Ref. [4])
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mydriatic property of belladonna is being employed in ophthalmology. Additionally,
it helps to examine the retina and other deep eye structures [1].
Atropine also seems to be involved in the relaxation of all the visceral smooth
muscles receiving signals from parasympathetic motor neurons. It functions to relax
the stomach, intestine, and urinary system [28]. Belladonna Alkaloids are also able
to paralyze the nerves of the pharynx by controlling the reex action of swallowing.
The berries of belladonna are utilized in Moroccan culture as aphrodisiacs and
euphoria, and in students for improving memory [1].
4.9 Pharmacotherapeutic Role ofBelladonna
Atropa belladonna, being rich in tropane alkaloids, has a number of medicinal
applications. It possesses anticholinergic, antimicrobial, anti-inammatory, anticonvulsant, antispasmodic, analgesic, anesthetic, and mydriatic characteristics [1,
4]. Plant extracts are employed in several homeopathic and herbal drugs to treat
local inammation, headache, and scarlet fever [21]. It is also utilized as ananticholinergic agent in cough suppressants, as asedative and bronchodilator in asthma,
whopping cough, and chronic obstructive pulmonary diseases for prevention against
bronchospasm, andas ananalgesic agent in rheumatoid arthritis, Parkinson’s disorder, colic, and neuralgia. Moreover, it is also the fundamental part of plasters used
in the treatment of psychiatric disorders [15, 27, 29].
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