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Atropa belladonna L. is a dangerous and toxic plant, belonging to the Solanaceae botanical family. The leaves and fruits, dark berries with an unfortunate pleasant taste, are rich in alkaloids, and this is the reason for the great medical interest for its extracts and isolated components.
The name of the Genus derives from Atropos, the Fate of Greek mythology who cuts the thread of life, causing death. The plant was in fact well known by the Greeks and Romans for its poisonousness. This is evidenced by its use by the poisoner Locusta, responsible for the death of the emperor Claudius and in turn executed with the same belladonna. [1]
The name of the Species belladonna means “beautiful woman”, it derives from a Renaissance custom. Courtesans used to squeeze the juice of the berries into their eyes to make them more beautiful and brighter, causing mydriasis. These women tolerated the blurring of vision caused by the dilation of the pupils and sometimes it also had a social meaning, to find even unattractive men appreciable. [2]
The toxic effects of Belladonna manifest themselves even just by touching it, as the alkaloidsare absorbed by the skin. Man is so sensitive that he can poison himself by eating animals that have fed on it. Animals exhibit mild effects and can therefore survive and become a human’s last poisonous meal. [1]
Active molecules
The principle chemical constituents of Atropabelladonna are 20 different types of tropanealkaloids, including atropine, atropamine, apoatropine, belladonnine, cuscohygrine, 1-hyoscyamine, 6-β-hyoscyamine, norhyoscyamine, N-methylpyrroline, N-methylpyrrolidine, scopolamine (also known as hyoscine), and tropine. [3]
L-hyoscyamine and atropine 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. Out of the total alkaloid complex, hycosamine was observed to contribute 87.6% in the leaves and 68.7% in the roots. The concentration of atropine in the fruit is 0.1%, whereas in the roots it ranges between 0.4% and 0.6%. [4]
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. [4]
Tropanic alkaloids are heterocyclic organic bases containing a nitrogen (N) atom in reduced form. These molecules are obtained in plants from the amino acids through two main metabolic pathways of decarboxylation and reductive deamination. The tropane ring is obtained from the amino acid ornithine, while tropic acid is obtained from phenylalanine, through different enzymatic routes. The biosynthesis of tropane alkaloids is mainly carried out in the roots of Belladonna, from where they are transported to the stem, leaves, and fruits. [1]
Belladonna extracts
In the fresh drug, L-hyoscyamine is almost exclusively present, which is also the active form. In the dry drug we find the D and L forms of hyoscyamine in equal proportions, to form the racemate known generically as atropine. Drying leads to having 50% L-hyoscyamine and 50% D-hyoscyamine, it means a 50% reduction of the active compound in favor of the genesis of an inactive compound, i.e., the stereoisomer D; in fact, this results in a 50% reduction in source activity. [1]
Generally, alkaloids are extracted with few steps:
- Drug is chopped and pulverized.
- The pulverized drug is mixed with an aqueous acidic solution (maximum pH 2 to avoid decomposition).
- Filtration: a first aqueous extract is obtained with alkaloids in the form of a salified base mixed with hydrophilic impurities.
- Sodium bicarbonate or sodium hydrogen carbonate is added to the aqueous acid solution to raise the pH up to 7: the salified base is converted into free base.
- Liquid-liquid extraction in organic allows the separation of alkaloids free bases from the hydrophilic impurities remaining in the alkaline aqueous solution.
- By drying the organic solution, it is possible to obtain the dry extract.
Other methods consist of using freeze-dried extracts of Belladonna, percolation, or in vitro production. These techniques, especially the last one, could increase extraction yields. Analysis of Belladonna extracts is performed by the newest HPLC protocols. [1]
Pharmacodynamics of Belladonna
Belladonna alkaloids stimulate the Nervous System by functioning as antagonist of muscarinic receptors present in brain and autonomic effector nerves.
The affinity of atropine molecules is stronger for bronchial, heart, and gastrointestinal muscles. Atropine also involves the stimulation of respiratory, vagal, and vasomotor centers located in the medulla. That’s why atropine has a significant effect on the cardiovascularsystem. It is responsible for causing tachycardia, especially in adults. [5]
Scopolamine acts strongly on the iris and ciliary body and greatly influences the reduction of the bronchial, salivary, and sweat gland secretions. [5]
Pharmacotherapeutic role
Atropa belladonna extracts possess anticholinergic, antimicrobial, anti-inflammatory, anticonvulsant, antispasmodic, analgesic, anesthetic, and mydriatic characteristics. [4]
Passive mydriasis caused by atropine is used in Ophthalmology to examine the retina and other deep eye structures. At stomach level it can be used for the treatment of ulcers, gastritis, and coughs, for the inhibition of gastric secretion. At the intestinal level it allows the relaxation of the tone, in subjects suffering from constipation, in the treatment of muscle spasms and pyloric occlusion. [1]
It was observed that scopolamine quickly helps in relieving the symptoms of depression for a longer period of time by working as a non-selectivemuscarinic Acetylcholine Receptors Inhibitor (mAChRsI). [6]
The disproportion of neurotransmitters like acetylcholine or dopamine in the basal ganglia causes parkinsonism. Belladonna plant extracts seem to be quite effective in the management of parkinsonism primarily in the main symptoms: tremor, inflexibility, bradykinesia, and postural instability. Scopolamine works as an inhibitor of the acetylcholine receptor and thus helps to control the extreme salivation in Parkinson’s patients. [7]
The peripheral action of Belladonna alkaloids is directly on autonomic effector cells and not on nerve endings, producing in the eye, mydriasis, cycloplegia, and perhaps vasodilatation. This orally administered treatment action may tend to elevate the intraocular pressure. That is the reason why Belladonna extracts can be used in controlling symptoms in acute congestive Glaucoma patients. [8]
Quality and Safety of drugs
In drug discovery, the most important feature of natural products is their shelf-life, structural versatility, and a significant and beneficial role in curing several human diseases due to their safety and efficiency. There must be a good harmonization between the quality of raw materials, in process materials and the final products.
It has become essential to develop consistent and specific quality control methods using a combination of traditional and current instrumental methods. Standardization is an essential measurement for ensuring the quality control of herbal drugs. [9]
References:
- Marcello Nicoletti: Botanica Farmaceutica – Storia, attività ed impieghi delle piante medicinali, 2007.
- Kilmer, Frederick B. “Belladonna monographs.” Journal of the American Pharmaceutical Association, 1932.
- Javed, S., Ahmad, A., Akash, M.S.H., Rehman, K., Al-Huqail, A.A. (2023). Belladonna. In: Zia-Ul-Haq, M., Abdulkreem AL-Huqail, A., Riaz, M., Farooq Gohar, U. (eds) Essentials of Medicinal and Aromatic Crops, 2023.
- Cano Ortiz, A., Piñar Fuentes, J. C., & Cano, E. Some medicinal plants of interest for their content in alkaloids I. Biomedical Journal of Scientific & Technical Research, 2022.
- Prusakov, P. Belladonna alkaloids. Encyclopaedia of Toxicology, 2014.
- Anacker, C. New insight into the mechanisms of fast-acting antidepressants: What we learn from scopolamine. Biological Psychiatry, 2018.
- Maurya, V. K., Kumar, S., Kabir, R., Shrivastava, G., Shanker, K., Nayak, D., et al. Dark classics in chemical neuroscience: An evidence-based systematic review of belladonna. ACS Chemical Neuroscience, 2020.
- Ullman, Egon V.; Mossman, Frank D. Glaucoma and Orally Administered Belladonna. American Journal of Ophthalmology, 1950.
- Amiri, Mohaddeseh, et al. “Environmental impact assessment of total alkaloid extracted from the Atropa belladonna L. using LCA.” GeoloGy, ecoloGy, and landscapes, 2017.
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