Chemical Compounds, Pharmacological and Toxicological Activity of Brugmansia suaveolens: A Review

This study investigates updated information in different search engines on the distribution, phytochemistry, pharmacology, and toxicology of Brugmansia suaveolens (Solanaceae) using the extracts or chemical compounds at present. This plant has been used in traditional medicine in different cultures as a hallucinatory, analgesic, aphrodisiac, nematicide, sleep inducer, and muscle relaxant, as well as a treatment for rheumatism, asthma, and inflammation. The flowers, fruits, stems, and roots of the plant are used, and different chemical compounds have been identified, such as alkaloids, volatile compounds (mainly terpenes), coumarins, flavonoids, steroids, and hydrocarbons. The concentration of the different compounds varies according to the biotic and abiotic factors to which the plant is exposed. The toxic effect of the plant is mainly attributed to atropine and scopolamine, their averages in the flowers are 0.79 ± 0.03 and 0.72 ± 0.05 mg/g of dry plant, respectively. Pharmacological studies have shown that an aqueous extract exhibits the antinociceptive effect, at doses of 100 and 300 mg/kg i.p. in mice. On the other hand, the ethanolic extract at 1000 mg/L, showed a nematocidal activity in vitro of 64% against Meloidogyne incognita in 72 h. Likewise, it showed a 100% larvicidal activity at 12.5 mg/L against Ancylostoma spp. In another study, the lethal activity of shrimp in brine from an ethanolic extract showed an LC50 of 106 µg/mL at double serial concentrations of 1000–0 (µg/mL). Although there are pharmacological and phytochemical studies in the plant, they are still scarce, which has potential for the examination of the biological activity of the more than one hundred compounds that have been reported, many of which have not been evaluated.


Introduction
Brugmansia suaveolens (Humb. and Bonpl. ex Willd.) Bercht. and J.Presl is widely distributed in the world both as a spontaneous species and as an ornamental plant [1], mainly in areas with climates ranging from tropical and subtropical to temperate [2]. It belongs to the Solanaceae family, and according to The Plant List, 12 are recognized in this genus, including hybrids and a subspecies (Brugmansia arborea, B. × candida, B. × cubensis, B. × dolichocarpa, B. × insignis, B. longifolia, B. pittieri, B. × rubella, B. sanguinea, B. sanguinea subsp. vulcanicola, B. suaveolens, and B. versicolor) [1]. The objective Brugmansia suaveolens belongs to the group of woody plants [17], considered shrubs or small trees (Figure 1), with a length ranging from 1 to 6 m high. The petiole is 2-5 cm long; the leaf lamina, with the widest end below the middle part known as an elliptical 15-30 cm long and 5-12 cm wide; the corolla is formed by a tube with lobes of 25-30 cm long; and the basal half is a narrow tubular shape and abruptly expands to form extended lobes 10-15 cm long. The color of the flower is white or reddish. The fruit is narrow at the end and wide in the middle part, and is 20 cm long with a 2.5 cm diameter. Flowering begins in January and from April to November. It bears fruit from May to June and in October [3].
Plants 2020, 9,1161 3 of 14 widest end below the middle part known as an elliptical 15-30 cm long and 5-12 cm wide; the corolla is formed by a tube with lobes of 25-30 cm long; and the basal half is a narrow tubular shape and abruptly expands to form extended lobes 10-15 cm long. The color of the flower is white or reddish. The fruit is narrow at the end and wide in the middle part, and is 20 cm long with a 2.5 cm diameter. Flowering begins in January and from April to November. It bears fruit from May to June and in October [3].

Ethnobotany
Many of these species are mainly appreciated as ornamentals, because of their ease of cultivation and the production of their characteristic flower smell at dusk [3], reaching its maximum peak at 21:00 [22]. B. suaveolens is also used in traditional medicine [3], despite being documented in the literature that
widest end below the middle part known as an elliptical 15-30 cm long and 5-12 cm wide; the corolla is formed by a tube with lobes of 25-30 cm long; and the basal half is a narrow tubular shape and abruptly expands to form extended lobes 10-15 cm long. The color of the flower is white or reddish. The fruit is narrow at the end and wide in the middle part, and is 20 cm long with a 2.5 cm diameter. Flowering begins in January and from April to November. It bears fruit from May to June and in October [3].

Ethnobotany
Many of these species are mainly appreciated as ornamentals, because of their ease of cultivation and the production of their characteristic flower smell at dusk [3], reaching its maximum peak at 21:00 [22]. B. suaveolens is also used in traditional medicine [3], despite being documented in the literature that

Ethnobotany
Many of these species are mainly appreciated as ornamentals, because of their ease of cultivation and the production of their characteristic flower smell at dusk [3], reaching its maximum peak at 21:00 [22]. B. suaveolens is also used in traditional medicine [3], despite being documented in the literature that its greatest use is as a hallucinogenic in shamanic rituals in some populations of Latin America [6], among them being some ethnic groups from the Amazon of Peru and Ecuador [40]. In the Inga people of Colombia, it is used externally to ward off the evil spirits that cause insomnia [41]. However, the first instances of its medicinal use were the Spanish in colonial times, where these plants were used for the treatment of rheumatism, infections, and asthma [42].

Phytochemistry
Chemical studies of this medicinal species date back to 1996 [47]. Such studies were the first qualitative on groups of compounds, where they were identified as amines, carbohydrates [48], alkaloids, phenolic compounds, flavonoids, steroids, terpenoids, tannins, anthraquinone glycosides, saponins, and triterpenes. The quantification of the alkaloids (5.903 ± 0.01333 mg/g), phenolic compounds (3.435 ± 0.0110 mg/g), and flavonoids (9.945 ± 0.0256 mg/g) was also carried out from the ethanolic extract of the flowers [49]. The concentrations of such compounds can vary, as in living flowers, they show a continuous change in the profile of their volatile compounds, which depend on intrinsic (genetic) and external factors (light, temperature, and water stress). In the case of the cut flowers, they suffer faster deterioration and a loss of volatile compounds [22]. Other factors that also affect it are attacks from pathogens (viruses, bacteria, fungi, and nematodes) and herbivores. The Marvin program was used to draw the structures of organic chemical compounds [50].

Alkaloids
Tropane alkaloids have anticancer activity [51]. Therefore, this group should be more studied in this regard. However, chemically, it is one of the most studied, where 59 alkaloids have been identified in the mature flowers, as well as in the immature flowers and fruits, corolla, flowers, roots, and flower nectar ( Table 2 and Figure 3).

Volatile Compounds
In the flowers and leaves, 50 volatile compounds have been identified and most of these compounds are found in the flowers (Table 3 and Figure 4).

Phenolic Compounds, Coumarin, and Flavonoids
A glycosylated phenolic compound, a coumarin, and seven flavonoids have been identified, in the flowers and leaves (Table 4 and Figure 5).

Steroids
Three Steroids have been identified in the flowers and leaves (Table 5 and Figure 6).

Steroids
Three Steroids have been identified in the flowers and leaves (Table 5 and Figure 6).

Hydrocarbons
The presence of four hydrocarbons in B. suaveolens has been identified only in the flowers (Table 6  and Figure 7). (1) (2) (3) (4) Figure 7. Structure of the hydrocarbons from Brugmansia suaveolens.

Pharmacological Activity
Brugmansia suaveolens is reported in traditional medicine in many Latin American countries; however, the first studies are from 22 years ago [4]. As there are very few pharmacological investigations of the plant, this is still an opportunity for future investigations.

Antinociceptive
The aqueous extract of B. suaveolens flowers was administered at doses of 100 and 300 mg/kg i.p.

Hydrocarbons
The presence of four hydrocarbons in B. suaveolens has been identified only in the flowers (Table 6 and Figure 7).

Hydrocarbons
The presence of four hydrocarbons in B. suaveolens has been identified only in the flowers (Table 6  and Figure 7). (1)

Pharmacological Activity
Brugmansia suaveolens is reported in traditional medicine in many Latin American countries; however, the first studies are from 22 years ago [4]. As there are very few pharmacological investigations of the plant, this is still an opportunity for future investigations.

Antinociceptive
The aqueous extract of B. suaveolens flowers was administered at doses of 100 and 300 mg/kg i.p. They significantly inhibited (p < 0.05) the induced contortions and increased the percentage of inhibition by acetic acid to 0.6% (3.0 ± 0.8 and 94.9%, and 0.6 ± 0.5 and 99%, respectively). Diclofenac 5 mg/kg i.p (43.4 ± 3.5 and 25.8%) was used as a positive control. An increase in the latency time was observed in the formalin test (20 µ L of 2.5%); in the first phase (0-5 min), with a dose of 100 mg/kg (15.6 ± 4.2 s and 63.3%) and 300 mg/kg (0.3 ± 0.3 s and 98.6%) and diclofenac (43.6 ± 7.0 s and 0%), and the second phase (20-25 min) with a dose of 100 mg/kg (7.5 ± 2.8 s and 82.2%) and 300 mg/kg (0.0 ± 0.0 s and 100%) and diclofenac (7.0 ± 2.8 s and 69.6%) in male Swiss albino mice. An increase in the latency time was also

Pharmacological Activity
Brugmansia suaveolens is reported in traditional medicine in many Latin American countries; however, the first studies are from 22 years ago [4]. As there are very few pharmacological investigations of the plant, this is still an opportunity for future investigations.

Antinociceptive
The aqueous extract of B. suaveolens flowers was administered at doses of 100 and 300 mg/kg i.p. They significantly inhibited (p < 0.05) the induced contortions and increased the percentage of inhibition by acetic acid to 0.6% (3.0 ± 0.8 and 94.9%, and 0.6 ± 0.5 and 99%, respectively). Diclofenac 5 mg/kg i.p (43.4 ± 3.5 and 25.8%) was used as a positive control. An increase in the latency time was observed in the formalin test (20 µL of 2.5%); in the first phase (0-5 min), with a dose of 100 mg/kg (15.6 ± 4.2 s and 63.3%) and 300 mg/kg (0.3 ± 0.3 s and 98.6%) and diclofenac (43.6 ± 7.0 s and 0%), and the second phase (20-25 min) with a dose of 100 mg/kg (7.5 ± 2.8 s and 82.2%) and 300 mg/kg (0.0 ± 0.0 s and 100%) and diclofenac (7.0 ± 2.8 s and 69.6%) in male Swiss albino mice. An increase in the latency time was also observed in the hot plate and tail dip tests [9].
In another study of the aqueous extract of flowers of B. suaveolens on the probable antinociceptive mechanism of the 300 mg/kg dose, a mechanism on benzodiazepine receptors was found. Flumazenil (5 mg/kg, i.p.) was used as an antagonist [57].

Antimicrobial
The antibacterial activity of the aqueous extract of B. suaveolens flowers against Bacillus thurigiensis was evaluated in one study and showed no activity [58].

Nematicide
The ethanolic extract of flowers at a concentration of 1000 mg/L, showed a 64% in vitro nematocidal activity against Meloidogyne incognita within 72 h. [49]. In another study of the ethanolic extract of aerial parts (flowers, and flowers and stems), a 100% larvicidal activity at a dilution of 12.5 mg against Ancylostoma spp was shown [59].

Muscle Relaxer
Brugmansia suaveolens ethanol extract inhibits rabbit smooth muscle contractility at 100% at a concentration of 75.5 g/mL [4].

Toxicity
There are several factors (climatic and seasonal) that can increase or decrease the concentration of the alkaloids associated with the toxicity of the plant. It has been documented that it has been involved in poisoning in many parts of the world, and other species, such as B. candida, B. sanguinea, and B. × candida, are considered toxic in some places like Mexico, especially their seeds. It is documented that an intake of 4 to 5 g of raw leaf, or just a seed, can cause a child to die [3]. Among the most toxic compounds are atropine and scopolamine, and their averages in the flowers are 0.79 ± 0.03 and 0.72 ± 0.05 mg/g of dry plant, respectively; these concentrations will increase if the plant is fertilized with organic fertilizer (6 kg/m 2 per year) [44]. In another study, a scopolamine concentration of 149.80 ± 6.01 µg/mL was determined in the flower nectar [37]. The plant parts that are the most involved in poisoning are flowers (77.5%), leaves (13.4%), fruits (4.5%), stem (2.3%), and root (2.3%) [60].