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Aconitum napellus (Monkshood)

Authors:
101
6Aconitum napellus
(Monkshood)
Karma Yeshi and Phurpa Wangchuk
DOI: 10.1201/b23017-8
CONTENTS
6.1 Introduction .......................................................................................................................... 101
6.2 Botanical Description ........................................................................................................... 102
6.2.1 Morphology ..............................................................................................................102
6.2.1.1 Leaves ........................................................................................................102
6.2.1.2 Flowers ....................................................................................................... 102
6.2.1.3 Roots .......................................................................................................... 102
6.3 Distribution ........................................................................................................................... 103
6.4 Phytochemical Constituents ................................................................................................. 104
6.5 Pharmacological Studies ...................................................................................................... 104
6.6 Toxic Response ..................................................................................................................... 107
6.6.1 Toxicity in Humans ................................................................................................... 107
6.6.2 Mechanism of Toxicity in Human ........................................................................... 108
6.6.3 Clinical Management ................................................................................................ 108
6.7 Traditional and Other Potential Uses .................................................................................... 109
6.8 Future Remarks .................................................................................................................... 109
Notes .............................................................................................................................................. 110
References ...................................................................................................................................... 110
6.1 INTRODUCTION
Aconitum genus belongs to the family Ranunculaceae, and members of this genus are known as
aconites. This genus has three subgenera: monotypic subgenus – Gymnaconitum, Lycoctonum, and
Aconitum. Gymnaconitum has only one annual species, Gymnaconitum gymnandrum Maxim, and it
is reported only in China (Utelli et al., 2000). Rest two subgenera have numerous species. The distin-
guishing feature between Aconitum and Lycoctonum is that the former is characterized by biennial
paired tuberous roots and the latter one by perennial rhizomes (Lauener & Tamura, 1978). Aconitum
species are mostly spotted in the cooler northern hemisphere regions of Asia, North America, Great
Britain, and Europe (Jamtsho et al., 2021; Stork & Marraffa, 2005). According to the Kew Royal
Botanic Gardens, the Aconitum genus has 324 accepted species (Novikov et al., 2021). Some coun-
tries have reported several Aconitum species; for instance, more than 200 species are reported from
China (Singhuber et al., 2009), 38 species from Nepal (Shyaula, 2011), 27 species from India (Abd,
2016), and 19 species from Bhutan (Jamtsho et al., 2021). Aconitum species are widely used in the
scholarly traditional medicine systems in Asian countries, including Nepal (16 species; Shyaula,
2011), India (18 species; Abd, 2016), Bhutan (two species; Jamtsho et al., 2021), and China (two spe-
cies; Singhuber et al., 2009). Aconitum is one of the most exploited medicinal plant genera in the
traditional medicine system and indigenous drug discovery history (Ali etal., 2021). The medicinal
102 Exploring Poisonous Plants
properties of Aconitum species are due to diverse classes of secondary metabolites, and alkaloids are
one of the main compounds. Carbon-19 (C-19) and C-20 diterpene alkaloids are most common in
aconites, constituting approximately 450 alkaloids (Ali et al., 2021). Many Aconitum species are also
poisonous (e.g., Aconitum ferox, Aconitum laciniatum, Aconitum violaceum, Aconitum chasman-
thum, Aconitum luridum, and Aconitum napellus) as they contain toxic diterpenoid alkaloids, includ-
ing aconitine, mesaconitine, and hypaconitine which cause cardiotoxicity (Qasem et al., 2022). Oral
ingestion (accidental or deliberate) is the most common route of exposure to Aconitum toxins, and it
can also enter the body through the mucous membrane and intact skin. Whether it is oral ingestion
or dermal contact, absorption of aconitine occurs rapidly within a few minutes (Stork & Marraffa,
2005). The half-maximal lethal dose (LD50) of aconitine in mice is 1.8 mg/kg via oral ingestion,
while in humans, it is about 1–2 mg (Fujita et al., 2007; Sato et al., 1979). This chapter discusses
A. napellus L. in depth, including taxonomy and distribution, ethnopharmacology, phytochemistry,
reported biological properties, and associated toxicities.
6.2 BOTANICAL DESCRIPTION
A. napellus, popularly known as monkshood or wolfsbane, is a perennial herb often grown as orna-
mental due to its attractive blue owers. Botanical descriptions for morphology and anatomy are
referred from Akbar (2020), Duffell (2009), and Munch and Crosbie (1929). A. napellus belongs to
the family Ranunculaceae (Grin, 2009; Heywood, 1978), and it has numerous common names. The
most popularly used names are given here. English: Aconite, Helmet ower, Blue rocket, Devils
helmet, Monk’s hood, Wolf’s bane; French: Aconit; German: Blauer eisenhut, Blauer sturm-
hat; Italian: Aconitonapello, Erba luparia; French: Aconit napel; Dutch: Blauwe monnikskap;
Spanish: Aconite, Anapelo, Stormhatt.
6.2.1 Morphology
A. napellus is a perennial herb (i.e., it has self-supporting stems) with an upright stem, round and
smooth, and grows up to 2 m (Figure 6.1a).
6.2.1.1 Leaves
The leaves are simple (i.e., lobed or unlobed but not separated into leaets). Usually, they are lobbed
into three or ve segments (further divided), and the edge of the leaf blade has teeth (Figure 6.1b).
The surface under the leaves has only a few hairs. Leaves are petiolate and arranged alternately (i.e.,
one leaf per node along the stem).
6.2.1.2 Flowers
The owers are blue to purple and usually bloom during May and July. They are bisexual and
bilaterally symmetrical (i.e., only one way to divide), stalked, and racemose (Figure 6.1a). Petaloid
sepals (or tepals) are ve – one uppermost is helmet shaped and beaked and nearly hemispherical;
the two laterals are roundish and internally hairy; and the lower two are oblong oval (Figure 6.1c).
6.2.1.3 Roots
Tuberous roots are either single or in clusters of two or more. The younger ones are smooth and yel-
lowish white internally, while matured or older ones are deep wrinkled by side branches or branches
and brown inside (Figure 6.2a, b). Root is obconical, measuring 4–10 cm long and 1–3.5 cm wide
at the crown. The internal anatomy of roots (cross section) shows a distinct stellate cambial zone
(Figure 6.2c).
103Aconitum napellus (Monkshood)
6.3 DISTRIBUTION
A. napellus is spotted in mountainous regions at elevations up to 3,000 m above sea level. But it
usually grows in lowland areas. A. napellus prefers moist/wet and nutrient-rich soils, which are
slightly acidic and in the shade. In terms of climatic conditions, it prefers places where the night
temperature remains below 7°C and precipitation about 1 m (Johnson, 2007). A. napellus is native
to Western and Central Europe (Duffell, 2009). It is also reported in some parts of Asia and in
Oceania. Figure 6.3 shows that A. napellus is reported in at least 15 countries globally.
FIGURE 6.2 Roots of Aconitum napellus: (a) fresh young roots, (b) dried old roots, and (c) T.S. of root show-
ing a distinct stellate cambial zone. (Adopted from Munch & Crosbie, 1929).
FIGURE 6.1 (a) Aconitum napellus in its natural habitat, (b) palmate leaf, and (c) petaloid sepal. (Adopted
and modied from Wikimedia.)
104 Exploring Poisonous Plants
6.4 PHYTOCHEMICAL CONSTITUENTS
A. napellus is widely studied for its phytochemical constituents in various plant parts. Lethal car-
diotoxin ‘aconitine’ was rst discovered from A. napellus in 1833 by P.L. Geiger (Qasem et al.,
2022). Like other poisonous aconites, the whole plant of A. napellus contains toxins but are more
concentrated in the roots. Phytochemicals isolated from A. napellus are mainly constituted of alka-
loids and avonoids. Diterpenoid alkaloids, including Aconitine, Mesaconitine, Hypaconitine, and
N-Deethylaconitine, are isolated from the root, pollen, and nectar of A. napellus (Arlandini et al.,
1987; Dustan & Ince, 1891; Jacquemart et al., 2019). Other alkaloidal compounds such as Aconine A
& B, Hypaconitine, Napelline A & B, Neoline A & B, Benzoylmesaconitine, Benzoylhypaconitine,
Acosepticine A & B, 6-O-Acetylacosepticine A, 6-Demethyldephatine A–C, Leucostine, Acoseptine,
and N-Acetylsepaconitine A were also isolated or identied from various parts of A. napellus
(Jacquemart et al., 2019). Flavonoids reported from A. napellus are isolated exclusively from owers
(Table 6.1). Aconitine acid, which is an organic acid, was reported from the aconite juice (Figure 6.4).
6.5 PHARMACOLOGICAL STUDIES
Crude extracts and individual isolated compounds from A. napellus have shown a few promising
biological activities, such as antidiabetic, neuroprotective, and anti-anxiety. Crude methanolic and
aqueous extracts from A. napellus at 100, 200, and 400 mg/kg in Wistar albino rats through MTT
Assay (in vitro) and alloxans-induced hyperglycaemic rats (in vivo) showed hypoglycaemic poten-
tial (Chhetree et al., 2010), thus suggesting the potential application of A. napellus as an alternative
treatment for diabetes (Shoaib, Salem-Bekhit, et al., 2020).
In a study by Shoaib et al. (Shoaib, Siddiqui, et al., 2020) on the neuroprotective role of crude
extract from A. napellus in streptozotocin-induced diabetic Sprague-Dawley rats, a detoxied chlo-
roform extract showed a signicant (p < 0.05) improvement in the myelination and degenerative
changes of the nerve bres besides behavioural improvement (locomotor activity). There were sig-
nicant decrease in TBARS (thiobarbituric acid reactive substance) and increased levels of catalase,
FIGURE 6.3 World map showing the countries where Aconitum napellus is reported. (Country names
and locations are labelled manually using information from the Australasian Virtual Herbarium homepage
(adopted from AVH, 2022).)
105Aconitum napellus (Monkshood)
FIGURE 6.4 Chemical structures of chief alkaloidal constituents of Aconitum napellus.
TABLE 6.1
Compounds Isolated and Identied from Various Parts of Aconitum napellus
Parts Used for
Isolation Alkaloids Reference
Pollen, and nectar Aconitine Dustan and Ince (1891), Jacquemart
et al. (2019)
Pollen Mesaconitine Jacquemart et al. (2019)
Root N-Deethylaconitine, Aconitine, Mesaconitine Arlandini et al. (1987)
Pollen Aconine A & B, Hypaconitine, Napelline B, Jacquemart et al. (2019)
Neoline A & B, Benzoylmesaconitine,
Benzoylhypaconitine, Acosepticine A & B,
6-O-Acetylacosepticine A,
6-Demethyldephatine A–C, Leucostine,
Acoseptine, N-Acetylsepaconitine A
Nectar 18-Demethylpubescenine Jacquemart et al. (2019)
Pollen and nectar 6-Demethyldephatine C, Napelline A Jacquemart et al. (2019)
Whole plant Neoline, Napeline, Isotalatizidine, Karakoline, Kiss et al. (2013)
Senbusine A & C
(Continued)
106 Exploring Poisonous Plants
TABLE 6.1 (Continued)
Compounds Isolated and Identied from Various Parts of Aconitum napellus
Parts Used for
Isolation Alkaloids Reference
Whole plant Chasmanine, 1,14-O-Diacetylneoline, Liu and Katz (1995)
Isotalatizidine, Delsoline, Delcosine,
Virescenine, Songorine, Songoramine,
12-Epinapelline, 15-O-Acetyl-12-Epinapelline
Seeds Karakoline, Leroyine, Neoline, Isotalatizidine, Liu and Katz (1995)
12-Epinapelline
Flavonoids
Flowers Quercetin 7-O-(6-Trans-Caffeoyl)-β-
Glucopyranosyl-α-Rhamnopyranoside-3-O-β-
Fico, Braca, Bilia, et al. (2001), Fico,
Braca, De Tommasi, et al. (2001),
Glucopyranoside; Kaempferol
7-O-(6-Trans-Caffeoyl)-β-Glucopyranosyl-α-
Rhamnopyranoside-3-O-β-Glucopyranoside;
Kaempferol-7-O-(6-Trans-p-Coumaroyl)-β-
Glucopyranosyl-α-Rhamnopyranoside-3-O-β-
Fico, Braca, Tommasi, et al. (2001),
Luis et al. (2006)
Glucopyranoside; Quercetin
3-O-(6-Trans-Caffeoyl)-β-Glucopyranosyl-
(12)-β-Glucopyranosyl-7-O-α-
Rhamnopyranoside;
Quercetin-3-Sophoroside-7-
Rhamnopyranoside; 3-O-[β-D-
Glucopyranosyl-(1
3)-(4-O-Trans-p-Coumaroyl)-α-L-
Rhamnopyranosyl-(1 6)-β-D-
Glucopyranosyl]-7-O-[β-D-
Glucopyranosyl-(1
3)-α-L-Rhamnopyranosyl]kaempferol;
3-O-[β-D-Glucopyranosyl-(1 3)-(4-O-Trans-
p-Coumaroyl)-α-L-Rhamnopyranosyl-(1
6)-β-D-Glucopyranosyl]-7-O- [β-D-
Glucopyranosyl-(1 3)-α-L-
Rhamnopyranosyl]quercetin;
7-O-[β-D-Glucopyranosyl-(1 3)-α-L-
Rhamnopyranosyl]quercetin; Quercetin
3-O-(6-Trans-Caffeoyl)-β-
Glucopyranosyl-(1 2)-β-Glucopyranoside-7-
O-α-Rhamnopyranoside; Kaempferol
3-O-(6-Trans-Caffeoyl)-α-
Glucopyranosyl-(1 2)-β- Glucopyranoside-
7-O-α-Rhamnopyranoside; Quercetin
3-O-(6-Trans-p-Coumaroyl)-β-
Glucopyranosyl-(1 2)-β-Glucopyranoside-7-
O-α-Rhamnopyranoside; Kaempferol
3-O-(6-Trans-p-Coumaroyl)-β-
Glucopyranosyl-(1 2)-β- Glucopyranoside-
7-O-α-Rhamnopyranoside;
Quercetin-3-Sophoroside-7-Rhamnopyranoside
Organic acids
Aconite juice Aconitic acid Ventre et al. (1946)
107Aconitum napellus (Monkshood)
superoxide dismutase, and reduced glutathione in rats treated with A. napellus chloroform extract
than in the diabetic control group (Shoaib, Siddiqui, et al., 2020).
Moreover, homoeopathic preparations from A. napellus (diluted as 12 and 30 cH in 30% cereal
alcohol) also demonstrated anxiolytic effects in Wistar albino rats when treated with 0.15 mL/day
for 10 consecutive days (Haine et al., 2021). Anxiolytic activity was measured by the widely used
elevated plus maze (EPM) model, where EPM is a wooden device with two closed arms and two
open arms perpendicular to each other. Closed arms have lateral and end walls but no walls in open
arms. The greater the permanence time and entries in the open arms, the better the anxiolytic action
of drugs. Diluted crude extracts of A. napellus (12 cH in 30% cereal alcohol) showed 39.5% ± 8.4%
entries and 15.4% ± 8.6% time (p < 0.05) in open arms, while rats treated with 30 cH dilutions
showed 38% ± 12% entries and 11% ± 10% time, which was better compared to 30% alcoholic stan-
dard drug diazepam (52% ± 15% entries and 24.3% ± 6.7% time in open arms), thus exhibiting its
anti-anxiety potential (Haine et al., 2021).
Compounds isolated from A. napellus are antioxidative, and particularly, they have free radical
scavenging potential. A avonol glycoside, quercetin 7-O-(6-Trans-Caffeoyl)-β-Glucopyranosyl-(1
3)-α-Rhamnopyranoside-3-O-β-Glucopyranoside, showed DPPH free radical scavenging anti-
oxidant activity with an IC50 value of 1.94 μM (Braca et al., 2003). Flavonol glycoside, quercetin
3-O-(6 -Trans-Caffeoyl)-β-Glucopyranosyl-(1 2)-β-Glucopyranoside-7-O-α-Rhamnopyranoside,
showed inhibition (58.9%) of coupled oxidation of β-Carotene and linoleic acid after 1 hour (Braca
et al., 2003). Two avonol glycosides from ethanolic extract of A. napellus sp. lusitanicum, querce-
tin 3-O-(6-Trans-Caffeoyl)-β-Glucopyranosyl-(12)-β-Glucopyranosyl-7-O-α-Rhamnopyranoside
and Quercetin-3-Sophoroside-7-Rhaamnopyranoside, also showed DPPH free radical scavenging
activity with EC50 values of 7.56 (better than standard compound – rutin, EC50 = 7.67 ug/mL) and
10.56 ug/mL, respectively (Luis et al., 2006). Ultrahigh diluted homoeopathic A. napellus (200 c or
1,000 c, i.e., 200th or 1,000th dilution, respectively) prepared under centesimal scale (1: 99 ratio –
one part of drug and 99 part of solvent) lowered baker’s yeast (20%) induced fever in rabbits signi-
cantly (p < 0.05), but the effect was lower than the standard drug paracetamol (p < 0.001) (Ahmad
et al., 2017). Flavonol glycosides from A. napellus sp. lusitanicum also showed cysticidal activity
against trophozoites of Acanthamoeba castellanii (Martin-Escolano et al., 2021).
6.6 TOXIC RESPONSE
A. napellus was a popular poison in Rome among the elites and was a good weapon for murder
by poisoning (Moog & Karenberg, 2002). The whole plant is poisonous, but the most toxic ones
are roots and seeds. A. napellus contains three major toxic steroid alkaloids, namely aconitine,
mesaconitine, and jesaconitine. Aconitine is the main alkaloid responsible for toxicity, and it is pres-
ent throughout the plant but more concentrated in roots and leaves. Aconitine is a C19-diester diter-
penoid alkaloid present in Aconitum spp., which is also named aconite of Wutou (Vo et al., 2017;
Zhang et al., 2020). Although aconitine-containing herbal medicines are well known for the treat-
ment of rheumatoid arthritis and pains (Li et al., 2010; Yu et al., 2020), for example, Fuzi, which is
considered ‘the chief of the hundred drugs’ in China, more than 5,000 cases of aconite poisoning
have been reported between 2001 and 2010 (Liu, 2019), and it has caused chiey polymorphous
ventricular arrhythmias (Chan, 2009; Lin et al., 2004).
6.6.1 ToxiciTy iN huMaNs
The minimum lethal dose of aconitine is 3–6 mg. One gram of fresh A. napellus may contain
2–20 mg of aconitine, which means a small amount of this plant can be lethal. Ingestion will
instantly cause a burning sensation in the mouth (or tingling, including lips, tongue, and throat)
within 10–20 minutes. Subsequently, within 2–6 hours after ingestion, it will cause nausea, saliva-
tion, weakness, violent emesis, generalized paraesthesia, and extreme pain. With more time passed
108 Exploring Poisonous Plants
by, possibly between 6 and 8 hours, a person will experience diarrhoea, cardiac rhythm distur-
bances, convulsions, skeletal muscle paralysis, and possibly death due to respiratory paralysis (Stork
& Marraffa, 2005).
6.6.2 MechaNisM of ToxiciTy iN huMaN
Aconitine is a voltage-gated sodium channel activator in the myocardium. Aconitine binds to the
α-subunit of voltage-gated sodium channels, causing a permanent opening of the channel (Fu etal.,
2006). Aconitine also inhibits sodium and potassium ATPase to generate a cardiotonic or car-
diotoxic effect (Wang et al., 2021), which results in a prolonged inux of sodium ions (Na+) and
slowing after depolarization (Friese et al., 1997) (Figure 6.5). A high concentration of intracellular
Na+ simultaneously activates the Na+-Ca2+ exchanger (NCX), causing the movement of Ca2+ from
extracellular to the cytoplasm (Fu et al., 2007). This increased inux or overload of intracellular
Ca2+-Na+ ion is responsible for aconitine‐induced proarrhythmic effects. Recent studies have also
shown the association of the arrhythmogenic properties of aconitine with the potassium channel.
Aconitine blocks the human ether-à-go-go-related gene channel (hERG), which is the primary repo-
larization potassium current that determines the action potential duration (APD) of cardiomyocytes
(Li et al., 2010). Aconitine either blocks hERG completely during the open state or develops low
afnity to the channel during the closed or resting state; either way, it prolongs the myocardial APD.
Aconitine also blocks Kv1.5 channels in atrial myocytes, which causes lengthening of its action
potential, thus prolonging the refractory period of atrial muscle (Li et al., 2010). All these events
collectively lead to aconitine-induced cardiotoxicity in humans.
6.6.3 cliNical MaNageMeNT
Decontamination by administering certain syrup and charcoal is a common home remedy. Syrup
of ipecac (a drug obtained from dried rhizome and roots of Carapichea ipecacuanha) is essentially
FIGURE 6.5 Overview of mechanism of aconitine-induced cardiotoxicity. Aconitine binds to α-subunit
of voltage-gated Na+ channel in the myocardium, causing it to open permanently and inhibiting the sodium
potassium ATPase (NKA), allowing prolonged inux of Na+ ions and delayed after depolarization. Elevated
intracellular Na+ ions concurrently activate Na+-Ca+ exchanger (NCX), which enhances the inux of Ca+ from
extracellular to cytoplasm. NA+ and Ca+ overloads together are responsible for proarrhythmia. (A gure was
adapted from Zhou et al. (2020, 2021) and modied in Biorender online software platform.)
109Aconitum napellus (Monkshood)
not advisable as it causes extensive vomiting, onsets symptoms rapidly, and has a risk of respiratory
paralysis. Gastric decontamination with activated charcoal may be suitable for substantial recent
ingestions. Monitoring and replacing uid and electrolytes lost from vomiting and diarrhoea is
essential during the treatment. After decontamination, a patient may or may not show symptoms but
observation for another 2–4 hours is recommended, as toxicity from aconite alkaloids is unpredict-
able due to alkaloid variability (Stork & Marraffa, 2005). Symptomatic patients should be referred
to the hospital. There is no specic antidote, and no specic laboratory tests are available (Stork &
Marraffa, 2005).
6.7 TRADITIONAL AND OTHER POTENTIAL USES
A. napellus, a European native species, closely resembles A. carmichaeli, and it is still used in
European homoeopathic preparations (Moog & Karenberg, 2002; Singhuber et al., 2009).
Traditionally, A. napellus has been used as an arrow poison for hunting due to its toxic nature.
European history recorded and believed that the wife (Julia Agrippina, 49–54 AD) of the Roman
emperor Claudius poisoned him with A. napellus (Moog & Karenberg, 2002). This species was
occasionally applied as poison to kill imprisoned criminals in European history (Shoaib, Salem-
Bekhit, et al., 2020). In Chinese medicine, A. napellus is used to prevent cold, general weakness,
and ‘Yang’ deciency, and it is used as an antidote for several poisons (Singhuber et al., 2009).
It is used in folklore medicine to manage facial paralysis, inammation, musculoskeletal pains,
pyrexia, gout, pericarditis (Chang & Whitaker, 2001), sciatica, and rheumatism (Venkataraghavan
& Sundareesan, 1981). A. napellus is used against sudden development of fever, particularly when a
person has been exposed to cold weather, freezing, dry wind, and fevers developed after a frighten-
ing or shocking experience (Loo, 2009). A. napellus is also used in Ayurvedic and Unani medicinal
preparations, and other polyherbal formulations are used to treat diabetes and a nerve tonic (Shoaib
et al., 2019). Aconite is considered helpful for improving subjective symptoms such as numbness,
cold sensations, and extreme or chronic pains (Wang et al., 2011), which are associated with diabetic
neuropathy. Aconite tubers contain toxins, including diterpenoid alkaloid aconitine (Kelly, 1990).
Therefore, prior to use, boil aconite tubers for several hours or even for a couple of days based on
the quantity used (Tang & Eisenbrand, 1992). In Ayurvedic medicine, shodhana method is widely
applied, where Aconitum tuber is treated with a cow or goat milk, and the goat milk treatment gives
less aconitine (Shoaib, Siddiqui, et al., 2020).
6.8 FUTURE REMARKS
A. napellus is native to Europe, and it is still used in European homoeopathic preparations.
A. napellus is known for its ornamental (due to its attractive blue ower) and medicinal values.
Traditionally, the plant was used chiey as arrow-head poison and poisoning captured criminals
in Europe, as its roots contain cardiotoxins – aconitine. Besides this, the plant is popular in
indigenous medicine systems, cluing Chinese traditional medicine, Indian Ayurvedic medicine,
Japanese herbal preparations, and European homoeopathic preparations for treating musculo-
skeletal pains. Numerous phytochemicals are isolated from different parts of A. napellus, and
among them, diterpenoid alkaloids and avonol glycosides are dominant constituents. Both crude
extracts and pure isolated compounds (a few avonol glycosides) have shown various pharmaco-
logical activities, including antipyretic, antidiabetic, antioxidant, anti-anxiety, and neuroprotec-
tive activities.
A. napellus (whole plant) contains toxic diterpenoid alkaloids; thus, proper detoxication
is necessary prior to use as 1 g of fresh A. napellus may contain 2–20 mg of aconitine (lethal
dose of aconitine in humans = 3–6 mg), and it can cause fatal symptoms and ultimately death.
Prolonged boiling of any plant parts or treating cow or goat milk can also reduce aconitine
content.
110 Exploring Poisonous Plants
Future studies may focus on investigating the biological activities of those unstudied compounds
isolated from A. napellus and investigating the levels of aconitine in any commercial herbal prod-
ucts containing A. napellus to ensure safety and prevent toxicities.
NOTES
Karma Yeshi, Center for Molecular Therapeutics, Australian Institute of Tropical Health and
Medicine (AITHM), James Cook University, Smitheld, Australia
Phurpa Wangchuk, Center for Molecular Therapeutics, Australian Institute of Tropical Health and
Medicine (AITHM), James Cook University, Smitheld, Australia
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... Aconite's propensity to induce irregular heart rhythms has also been linked to its anticholinergic effects, mediated through the vagus nerve. Furthermore, aconite also acts on the ventromedial nucleus in the hypothalamus which regulates the autonomic nervous system causing bradycardia and hypotension 6 . Toxicological analysis of aconite can be performed to detect the presence of aconitine or its metabolites using techniques such as liquid chromatography mass-spectrometry and immunoassays 8 . ...
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Introduction BhutaneseSowa Rigpa Medicine (BSM) uses two species of Aconitum in 25 important multi-ingredient formulations. The formulations are used for treating chronic parasitic, microbial infections, inflammatory conditions, bilious fever, or high fever related to bile disorders, including colds and flu. Some Aconitum species are toxic, and there is a need for stringent quality control measures. Materials and methods Aconitum orochryseum Stapf and Aconitum laciniatum (Bruehl) Stapf, were collected from Lingzhi, which is geographically located under Thimphu district, Bhutan, between the altitudes of 4000 4900 meters above sea level (masl), between July and September. Their comparative pharmacognostic properties were evaluated by: 1) using physicochemical parameters, such as foreign matter and moisture contents, total ash, acid-insoluble ash and alcohol-soluble extracts values and loss on drying of individual crude drugs; 2) developing a comparative High-Performance Thin Layer Chromatography (HPTLC) fingerprint, at Menjong Sorig Pharmaceuticals Corporation Limited (MSCPL), under the Ministry of Health, Bhutan and 3) conducting a literature review to identify the nature and toxicity of alkaloids present in two Aconitum species. Results Two Aconitum species possess distinct macro- and microscopic characteristic features (including colour, taste, smell, appearance, and shape). The physicochemical analysis and the HPTLC fingerprinting of their methanol extracts yielded adequate data to differentiate and validate these two species identities, before adding them to 25 essential traditional medicinal drugs (ETMDs) or polyherbal formulations in BSM. A literature review revealed that the two Aconitum species contain two distinct types of alkaloids. Conclusions Two Aconitum species could be differentiated based on their botanical features, macro- and microscopic characteristics, physicochemical values and HPTLC fingerprint profiles. These pharmacognostic properties can be used as quality control parameters to confirm the two species' identity, thereby ensuring the quality and safety of BSM.
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Aconitine (AC) is well‐known as the main toxic ingredient and active compound of Aconitum species, of which several aconites are essential herbal medicines of Traditional Chinese Medicine (TCM) and widely applied to treat diverse diseases for their excellent anti‐inflammatory, analgesic, and cardiotonic effects. However, the cardiotoxicity and neurotoxicity of AC attracted a lot of attention and made it a favorite botanic poison in history. Nowadays, the narrow therapeutic window of AC limits the clinical application of AC‐containing herbal medicines; overdosing on AC always induces ventricular tachyarrhythmia and heart arrest, both of which are potentially lethal. But the underlying cardiotoxic mechanisms remained chaos. Recently, beyond its cardiotoxic effects, emerging evidence shows that low doses of AC or its metabolites could generate cardioprotective effects and are necessary to aconite's clinical efficacy. Consistent with TCM's theory that even toxic substances are powerful medicines, AC thus could not be simply identified as a toxicant or a drug. To prevent cardiotoxicity while digging the unique value of AC in cardiac pharmacology, there exists a huge urge to better know the characteristic of AC being a cardiotoxic agent or a potential heart drug. Here, this article reviews the advances of AC metabolism and focuses on the latest mechanistic findings of cardiac efficacy and toxicity of this aconite alkaloid or its metabolites. We also discuss how to prevent AC‐related cardiotoxicity, as well as the issues before the development of AC‐based medicines that should be solved, to provide new insight into the paradoxical nature of this ancient poison.
Article
Aconitine (ACO), a main active ingredient of Aconitum, is well-known for its cardiotoxicity. However, the mechanisms of toxic action of ACO remain unclear. In the current study, we investigated the cardiac effects of ACO and mesaconitine (MACO), a structurally related analog of ACO identified in Aconitum with undocumented cardiotoxicity in guinea pigs. We showed that intravenous administration of ACO or MACO (25 μg/kg) to guinea pigs caused various types of arrhythmias in electrocardiogram (ECG) recording, including ventricular premature beats (VPB), atrioventricular blockade (AVB), ventricular tachycardia (VT), and ventricular fibrillation (VF). MACO displayed more potent arrhythmogenic effect than ACO. We conducted whole-cell patch-clamp recording in isolated guinea pig ventricular myocytes, and observed that treatment with ACO (0.3, 3 μM) or MACO (0.1, 0.3 μM) depolarized the resting membrane potential (RMP) and reduced the action potential amplitude (APA) and durations (APDs) in a concentration-dependent manner. The ACO- and MACO-induced AP remodeling was largely abolished by an INa blocker tetrodotoxin (2 μM) and partly abolished by a specific Na+/K+ pump (NKP) blocker ouabain (0.1 μM). Furthermore, we observed that treatment with ACO or MACO attenuated NKP current (INa/K) and increased peak INa by accelerating the sodium channel activation with the EC50 of 8.36 ± 1.89 and 1.33 ± 0.16 μM, respectively. Incubation of ventricular myocytes with ACO or MACO concentration-dependently increased intracellular Na+ and Ca2+ concentrations. In conclusion, the current study demonstrates strong arrhythmogenic effects of ACO and MACO resulted from increasing the peak INa via accelerating sodium channel activation and inhibiting the INa/K. These results may help to improve our understanding of cardiotoxic mechanisms of ACO and MACO, and identify potential novel therapeutic targets for Aconitum poisoning.
Article
Aconitum carmichaelii Debeaux is a widely used herbal medicine, which has anti-inflammatory and analgesic activities. However, due to its high toxicity, poisoning incidents often occur all over the world. To systematically understand the pharmacokinetics (PK) and tissue distribution of A. carmichaelii, 18 representative alkaloids, including 8 amine- (ADA), 4 monoester- (MDA) and 6 diester-type (DDA) diterpenoid alkaloids, were simultaneously quantified by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QQQ-MS) with dynamic multiple reaction monitoring (MRM) mode. PK results suggested that benzoylmesaconine, mesaconitine, 10-OH-aconitine and aconitine had lower bioavailability, which might relate to the substitution at C-3. In tissue distribution, alkaloids present higher concentrations in the liver, kidney, and only songorine, neoline and benzoyldeoxyaconine were detected in the brain. Moreover, the concentrations of extremely toxic DDAs in high-dose group were much higher than that of low-dose group, indicating that these DDAs might be the main reason for the toxicity of Aconitum. The results also suggested that benzoyldeoxyaconine and deoxyaconitine should be determined for the quality control of A. carmichaelii due to their high concentrations in both herbal extract and tissues. The systematic investigation into these 18 representative alkaloids could basically illuminate the PK and distribution of A. carmichaelii in rats, and provide some information for clinical studies.