napellus L.

Scientific Name: Aconitum napellus L. Synonyms: Aconitum laxum Rchb. Aconitum napellus var. paniculatum Regel, Aconitum occidentale Timb.-Lagr.f. ex Gáyer ,Aconitum sqarrosum Koch, Aconitum sqarrosum Koch ex Rchb. Delphinium napellus (L.) Baill. Aconitum laxum Rchb. Aconitum napellus var. aniculatum Regel, Aconitum occidentale Timb.-Lagr.f. ex Gáyer, Aconitum sqarrosum Koch, Aconitum sqarrosum Koch ex Rchb. Aconitum capsiriense (Jeanb. & Timb.-Lagr.) Gayer Aconitum compactum (Rchb.) Gáyer , Aconitum linneanum Gáyer , Aconitum lusitanicum (Rouy) Nyman, Aconitum meyeri Rchb. Aconitum occidentale , Aconitum vulgare Fourr. Nine are accepted by the Flora Europaea : Aconitum napellus subsp. napellus , Aconitum napellus subsp. corsicum (Gáyer) W. Seitz, Corsica, Aconitum napellus subsp. firmum (Rchb.) Gáyer, Aconitum napellus subsp. fissurae (Nyár.) W. Seitz, Aconitum napellus subsp. hians (Rchb.) Gáyer, Aconitum napellus subsp. lusitanicum Rouy, Aconitum napellus subsp. superbum (Fritsch) W. Seitz, Aconitum napellus subsp. tauricum (Wulfen) Gáyer, Aconitum napellus subsp. vulgare (DC.) Rouy & Foucaud, Family: : Aconitum : napellus Common Name: Monkshood, Blue Rocket, Friar's Cap, Auld Wife's Huid. Part Used: whole Plant Description: The are tall with the erect stem being crowned by racemes of large and eye-catching blue, purple, white, yellow or pink zygomorphic with numerous stamens. They are distinguishable by having one of the five petaloid sepals (the posterior one), called the galea, in the form of a cylindrical helmet; hence the English name monkshood. There are 2–10 petals, in the form of nectaries. The two upper petals are large. They are placed under the hood of the calyx and are supported on long stalks. They have a hollow spur at their apex, containing the nectar. The other petals are small and scale like or non-forming. The 3–5 carpels are partially fused at the base. Chemical Constituents: Alkaloids:, mesaconitine, hypaconitine, jesaconitine, aconine, napelline, picraconitine, malonic acid, succinic acid, itaconic acid, aconitic acid, sugars, starches, fats, and resin.

19 Structures of the chemical constituents isolated from Aconitum napellus

Hypaconitine Jesaconitine

Napelline Aconitic acid Actions of Herb: anti-diabetic, analgesic, sedative Medicinal Uses: It is used externally for gout, sciatica, and colds with fevers. A homeopathic preparation of A. napellus is used to treat nervous disorders resulting from strong emotions and trauma, as well as anxiety and fever. It is used in the treatment of fevers, inflammation, bronchitis, neuralgia. Side effects and Toxicity: A. napellus poisoning symptoms include numbing and burning wherever the plant matter touches the mucous membranes and inside of the mouth, tingling, twitching, and paralysis. Dizziness, nausea, and intense , weakness, sweating, breathing problems, problems are also observed. These symptoms are usually followed by respiratory and circulatory damage which often lead to loss of consciousness and death within less than an hour of initial consumption. Contraindications: Pregnancy and Lactation Preparations & Dosages Extractum Aconiti Radicis Fluidum, Fluid Extract of Aconite Root. Dose, one minim. Tinctura Aconiti Radicis, Tincture of Aconite Root. Dose, from one to ten minims. Specific Medicine Aconite.Dose, from one-twentieth to one-half minim.

20 Aconitine Crystalline. Dose, one five hundredth of a grain. Aconitine Amorphous. Dose, one one-hundred and thirty-fourth of a grain. Pharmacokinetics Absorption by route of exposure Absorption from the is rapid. Alkaloids can be absorbed after prolonged skin contact with aconite . Distribution by route of exposure After the ingestion or infusion of any part of the plant, the alkaloids are present in the blood and reach the target organs (heart and brain) within 30 minutes. Biological half-life by route of exposure No data available. Metabolism Aconite is rapidly metabolized by the liver in less than 24 h. Elimination by route of exposure Excretion of the alkaloids and metabolites occurs mainly through the urine and faeces. Physico-chemical specifications Alcohol content of A. napellus of five mother tinctures varies from 59.01 to 64.55% (Range 61 to 65%, standard deviation = 2.40), weight/ml varies from 0.859 to 0.884 g/ml (range = 0.890 to 0.925, SD = 0.00956). Specific gravity varies from 0.903 to 0.929 (range is 0.930 to 0.950 = according to GHP and SD = 0.00998) and pH varies from 5.06 to 6.099 (range = 5.0 to 7.0 and SD = 0.41367).

Foreign matter: maximum 5% Loss on Drying: minimum 60%, determined on 5 gm of finely cut drug, by drying in an oven at 105 °C for 2 hrs.

Figure: Microscopic Examination of Aconitum napellus Schneider, A. (1921). The Micro-analysis of Powdered Vegetable Drugs, 2nd ed.

21 Microscopic Evaluation: Epidermal cells (upper and lower) tabular with wavy vertical walls; stomata on lower surface only; upper cells larger and vertical walls less wavy; trichromes simple, single celled with warty markings. Few comparatively thin walled, nearly colorless, very porous, stone cells. Pollen grains oval. Thin-layer Chromatography Test solution: To 10ml mother tincture add 1 ml of ammonia and shake twice with 10ml of ether. Evaporate the combined ether layers to dryness, under reduced pressure. Dilute the residue in 0.5 ml of methanol. Reference solution: Dissolve 10 mg of aconitine and 5 mg of quinine in 10 ml of methanol Plate: TLC silica gel plate Mobile phase: diethylamine, ethyl acetate, toluene (10:20:70) Application: 20 µL as bands Development: over a path of 15 cm Drying: In air, then for 15 minutes at 100 °C Detection: Spray with potassium iodobisulphate solution 1/5 diluted in hydrochloric acid. Examine in daylight. Results: The sequence of zones present in the chromatograms obtained with the reference and the test solution is presented in table below.

Figure: Thin-lay er Chromatography of A. napellus . French Pharmacopoeia. 2009. Aconite for homoeopathic preparations High Performance Thin-layer Chromatography Samples preparation for HPTLC: 2ml of the tincture were mixed with 2 ml of water and 1 ml of diluted ammonia solution. The mixture has been put onto a kieselguhr cartridge and eluted twice with 8 ml of ether. The extract was evaporated to dryness under reduced pressure. The residue was dissolved in 0.5 ml of methanol.

Uhlemayr M, Papagiannopoulos M. Detection of the decomposition of aconitine in Aconitum napellus mother tincture V. 2a and identification of the main cleavage products using HPTLC-MS. International Symposium for High Performance Thin-layer Chromatography. 2011.

22 HPTLC method: The sample solutions were applied on a HPTLC silica gel 60 (20 × 10 cm) glass plate (Merck, Darmstadt, Germany) by ATS4 (CAMAG, Berlin, Germany). Using a mobile phase of cyclohexane/ethylacetate/ diethylamine (70:20:10 v/v/v) the plate was developed twice over a migration distance of 60 mm. For detection the plate was sprayed with a mixture of a solution of tartaric acid in water and the solution of iodine and iron-III-chloride in acetone. High Performance Liquid Chromatography Sample preparation for HPLC: The visible zones were marked on an underivatised plate at a matching Rf value and extracted with methanol (2 min, flow rate 0, 3 ml -1) using a TLC – MS – interface (CAMAG, Berlin, Germany). All sample solutions of the zones were separately collected in glass vials.:

Figure: HPTLC of tincture and reference solution showing the extracted zones Uhlemayr M, Papagiannopoulos M. Detection of the decomposition of aconitine in Aconitum napellus mother tincture V. 2a and identification of the main cleavage products using HPTLC-MS.International Symposium for High Performance Thin-layer Chromatography. 2011. Instrumentation for HPLC-MS analysis : The HPLC system described above was coupled with an LTQ Orbitrap XL (Thermo Fisher Scientific, Dreieich, Germany). Ionization was performed with a heated electrospray interface equipped with a metal needle kit. The conditions used for mass spectrometry were as follows: capillary voltage 35V, spray voltage 3.00 kV, tube lens 120 V. Nitrogen was used as drying gas. The capillary temperature was set at 300 °C. Collision-induced dissociation spectra (CID) were obtained with collision energy of 35 and an activation time of 30 mins. Full scan spectra from m/z 150-2000 were obtained in positive mode. Aconitine was used for the optimization of ionization parameters.

23 Table: LC/MS data of Aconitum napellus tincture

Table: LC/MS data of an aged reference solution of aconitine

A. napellus is used for the treatment of chronic rheumatoid arthritis. In Chinese herbal formulas A. napellus is often used for its effectiveness in the treatment of chronic rheumatoid arthritis after proper processing for detoxifying aconite. ( Tsung PK, Hsu HY. 1987. Arthritis and Chinese Herbal medicine. Long Beach, CA: Oriental Healing Arts Institute. Miller LG, Murray WJ. 2007. Herbal Medicinals – A Clinician’s Guide. Viva Books Private Limited). References Aconite.Review of Natural Products.Facts & Comparisons 4.0.2009. St. Louis, MO: Wolters Kluwer Health, Inc. Armitage, AM. 2000. Armitage's garden perennials a color encyclopedia. Portland, Oregon: Timber Press:19–20. Bisset NG. 1981. Arrow in China. Part II. Aconitum--botany, chemistry, and pharmacology. J Ethnopharmacol; 4(3):247-336. Chan TY (2009). Aconite poisoning. Clin Toxicol (Phila) 47 (4): 279–85. Chappuis, E. (2014). Aconitum napellus . IUCN Red List of Threatened Species. Version 2014.1.International Union for Conservation of Nature. Chisholm, Hugh, ed. (1911). Aconite. Encyclopædia Britannica (11th ed.). Cambridge University Press: 151–152. Chyka PA, Seger D, Krenzelok EP, Vale JA (2005). "Position paper: Single-dose activated charcoal". Clin Toxicol (Phila) 43 (2): 61–87. Datta, Subhash Chandra. 1988. Systematic botany. New Delhi: Wiley Eastern Ltd. Lin CC, Chan TY, Deng JF (2004). Clinical features and management of herb-induced aconitine poisoning. Ann Emerg Med 43 (5): 574–9. Moong FPI, Karenberg AI. 2002. Toxicology in the Old Testament: Did the High Priest Alcimus Die of Acute Aconitine Poisoning? Toxicological Reviews. 21(3): 151–156. Adis International. Roberts M F, and Michael W. 1998. Alkaloids biochemistry, ecology, and medicinal applications. New York: Plenum Press: 18. Schneider A. (1921) The Microanalysis of Powdered Vegetable Drugs, 2nd edition. The Extra Pharmacopoeia Martindale.1958. 24 th edition. London: The Pharmaceutical Press; 1:38. Watad AA, Kochba M, Nissim A, Gaba V. 1995. Improvement of Aconitum napellus micropropagation by liquid culture on floating membrane rafts. Journal Plant Cell Reports, 14(6): 345–348.

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