By Nicolas Vasquez C.
Acmella oleracea (L.) R.K.Jansen (Asteraceae) has in recent years become poular both as a garden plant and as a plant with medical properties. However, there has been some confusion about what it is called and it had also been assigned to the genus Spilanthes [e.g. S. acmella var. oleracea (L.) C.B.Clarke] or Bidens [e.g.. Bidens oleracea (L.) Cav. ex Steud.]. There are more doubts than certainties about the historical origin of A. oleracea, but it is well known for its uses against “toothache” in different parts of the world. The most studied group of compounds of this plant are the N-alkylamide and spilanthol is one of the major active principles of Acmella. Different traditional medicinal uses of the plant are being studied in in vitro and in vivo models with some promising findings. There have been few toxicological assessments in Acmella oleracea and in general, the results show a good safety profile of this plant; nevertheless, caution is required. There is a lack of clinical trials evaluating the efficacy of Acmella oleracea, however, one clinical trial evaluated the efficacy of the plant as local anesthetic.
Introduction
From mundane to spiritual uses, this plant has been part of traditional culture. Its characteristic pungent and strong taste has given it a space in the kitchens around the world, often consumed as tea, but as a condiment in some communities of northern Brazil (Nomura et al., 2013), in salads in the United States and added to steamed vegetables, soups, and meats in India. One of its most widespread uses is in horticulture as an ornamental plant (Hind and Biggs, 2003). However, some ancient native people have used the plant for religious festivals (Dubey et al., 2013).
Synonyms of Acmella oleracea (L) R.K Jansen include: Spilanthes acmella var. oleracea (L.) C.B.Clarke, Spilanthes oleracea var. fusca (Lam.) DC, and Bidens oleracea (L.) Cav. ex Steud. among others (The Plant List, 2010). Acmella oleracea (Asteraceae – daisy family; Bosch, 2004) are often confused taxonomically with members of the genus Spilanthes due to the similar morphological and phytochemicals characteristics; therefore, there is an overlapping of a large list of botanical names (Paulraj, Govindarajan and Palpu, 2013). In fact, most of the Acmella species were previously considered as part of the genus Spilanthes (Bosch, 2004). However, there are morphological and chromosomal differences. The genus Acmella has rayed heads and no pappus, whereas Spilanthes has discoid heads, this taxonomic character is considered reliable for species identification. At a chromosomal level, Spilanthes has 16 chromosomes, whereas , Acmella has 12 to 13 (Paulraj, Govindarajan and Palpu, 2013).
A. oleracea is an annual herb (60 to 90 cm tall) with erect stems, not usually rooting at nodes; the leaves are opposite, petiolate, petiole 20-60 mm long, flattened, with margin dentate. Inflorescence of solitary, terminal and axillary pedunculate capitula (Bosch, 2004; Hind & Biggs 2003). In the tropics the flowering period is throughout the year, but in 
temperate areas, when cultivated it is in early summer. Its propagation is usally performed through seeds rather than cuttings (Bosch, 2004; Hind & Biggs 2003).
It is largely grown for ornamental and medicinal properties. It was first described botanically from a cultivated specimen and is only known from cultivation of after being naturalized in humid places. The oldest recorded cultivation is from St. Vincent in 1791. The recorded distribution of this species is northern South America, USA, Haiti, India, South Africa, and East Africa, and apparently, it has become naturalized also in this part of Africa (Hind & Biggs 2003).
Some of its common names are: “toothache plant” and “agriao do Para”, “jambu”, “para-cress” (Portuguese origin) and in French as “Brede mafane”. Other names are “eye ball” and “spot plant” (because of its similarity to the eye), “salad cress”, and “spilanthes plant” (Hind & Biggs, 2003).
History and Uses
Even today, the origin of A. oleracea (L) R.K Jansen is unknown. There is a scarcity of records of the plant from the wild, but one hypothesis postulates that this is due to a long period of cultivation of Acmella alba (L’Hér.) R.K. Jansen in South America (Bosch, 2004). Collections in Brazil and Peru support this hypothesis (Hind & Biggs, 2003). According to this idea, after a long period of cultivation, A. oleracea have may spread in the tropics, but also, there is a possibility that the Portuguese may have introduced the plant to the Indian Ocean Islands, and then, around 1900, it spread to Africa by Indian laborers (Bosch, 2004).
A. oleracea’s traditional uses and applications have been explored in medicine, dental care, and cosmetics. In some parts of the world, the application of the whole plant has been employed to treat medical conditions, such as snake bites, but it has also been explored for cosmetics purposes, such as in anti-wrinkle preparations (Prachayasittikul et al., 2013). Its leaves and flowers have been used to treat rheumatism, fever, tuberculosis, malaria and as a diuretic. Its main traditional use around the world is as an anti-toothache agent, receiving the well-deserved name of “toothache plant” (Prachayasittikul et al., 2013). It is usually, the leaves that have been used as a local anesthetic, an antifungal agent, and particularly in Brazilian’s folk medicine, to treat prostate cancer (Duke, Bogenschutz-Godwin and Ottesen, 2009).
Phytochemistry
A. oleracea contains many different natural products (phytochemicals) such as phytosterols, essential oils, sesquiterpenes, flavonoid glucoside, and other bioactive metabolites. However, the major compounds are N-alkylamides (lipophilic nitrogen cmpounds generally including a poly-unsaturated aliphatic fatty acid chain and a shorter substituent at the nitrogen side), which, when chewed, provide a pungent taste, numbness of the area and increased salivation (Prachayasittikul et al., 2013). N-alkylamides, are the most studied compounds in Acmella, with a strong evidence for traditional anesthetic and anti-inflammatory uses (Nascimento et al., 2013).
An important N-alkylamide compound is spilanthol, which in 1945 was first isolated from an ethanol extract of A. oleracea (studied under the name of Spilanthes acmella, a synonym) (Prachayasittikul et al., 2013). It is an N-isobutylamide, with insecticidal properties, a strong pungent taste, and may produce astringency and local anesthetic effects. Its concentration is higher in flower head and roots of A. oleracea (Dubey et al., 2013).
Another interesting group of compounds are rhamnogalacturonans, pectic polysaccharides, that are in the primary cells wall of the plant. These compounds are not unique to A. oleracea , other plants have it with a slightly different structure. They show gastroprotective activities, highlighting the pharmacological importance of polysaccharides (Nascimento et al., 2013; Nomura et al., 2013).
PHARMACOLOGY
Antinociceptive effects:
Due to the traditional use of A. oleracea as an anti-toothache treatment, an in vivo animal study was performed in 2013, to assess the pain relief properties (antinociceptive) of an ethanol extract from the flowers of A. oleracea (L.) R.K. (EEAO). The model used was orofacial nociception test, giving a systemic dose of EEAO to mice. The results indicated that the extract had antinociceptive activity, particularly, in the orofacial region. This could be due to the inhibition of orofacial nociceptors (pain receptors), through modulation or blockade of specific receptors (TRPV1 and TRP1) (Nomura et al., 2013).
An aqueous extract of A. oleracea (called Spilanthes acmella) was assessed – in an animal model- to test its analgesic activity. The results showed that it significantly suppresses the acetic acid-induced writhing response compared to the control in a doses-dependent manner, but it was less intense than the standard drug (aspirin). This result suggests the effect is through peripheral pain inhibition mechanism (Chakraborty et al., 2004).
Another experiment, performed in guinea pigs, showed a significant local anesthetic property of the aqueous extract of ‘S. acmella MURR’. The research suggests that this activity could be explained by the presence of alkylamides (Chakraborty et al., 2010), but since Spilanthes acmella (L.) Murr is an unresolved name in this case (as in others, it is not really clear what species has been studied).
Diuretic effects:
Among other uses of A. oleracea, is its most commonly used as a diuretic. In 2004 Ratnasooriya et al. performed an experiment whereby rats were hydrated and then assessed for the amount of urine produced, after being given different concentrations of fresh cold-water flower extract (CWE) of ‘Spilanthes acmella’. The results showed that highest dose had a significant increase in diuresis, its effect was seen within an hour and lasted up to five hours. The effect compared favourably with a commonly used diuretic (furosemide) (Ratnasooriya et al., 2004). However, this dose – 1500 mg/kg of the cold water extract – is physiologically implausible and one myst be concerned about the relevance of such data.
To investigate the effect at a molecular level Gerbino et al. (2016) treated slices of kidneys from rats and cell lines models with 100 mg/ml of spilanthol. These slices express two important transporters involved in the process of urine concentration: Na+-K+-2Cl–—cotransporter or AQP2. Spilanthol has a substantial diuretic effect, increasing potassium and sodium in the urine. This, suggests that it is mimicking the effect of furosemide affecting the intracellular pathway of the above-mentioned carriers, positioning this compound as a possible diuretic drug to develop (Gerbino et al., 2016).
Gastroprotective effects:
In 2013 (Nascimento et al.) isolated from A. oleracea through aqueous extraction a polysaccharide, rhamnogalacturonan. As part of the experiment, hemorrhagic lesions (produced by ethanol) were generated in the gastric mucosa of rats; after this polysaccharide was administered orally. The results showed a dose-dependent effect, reducing the ethanol-induced gastric lesions, and revealing that this polysaccharide generates a gastroprotective activity in this type of lesions.
There are several possible mechanisms that could explain these anti-ulcer properties; it may act as a gastric protector, decrease the secretion of acids and pepsin, and increase mucosal secretion and/or the impact of scavenging radicals ((Nascimento et al., 2013).
Anti-inflammatory activity:
To measure the anti-inflammatory effect of ‘Spilanthes acmella’, an ethanolic extract of leaves was used and compared to aspirin. Albino rats were used to evaluate acute, subacute and chronic inflammation. Both the extract (ag 500 mg/kg, per oral) and aspirin demonstrated significant anti-inflammatory activity at all three stages, however, aspirin gave highest anti-inflammatory activity (Barman et al., 2009).
It has been suggested that some flavonoids from A. oleracea have anti-inflammatory effects. It is known that prostaglandins, involved in the last phase of acute inflammation, are the target for those compounds. Adding to this, flavonoids have antiproliferative activity, which is reflected in a decrease in granuloma (a type of inflammation) contents (Barman et al., 2009).
Antimalarial effects:
In India and Africa, S. acmella has been part of the traditional treatment of malaria. Some studies have shown that spilanthol and acetylenic N-alkylamide, have antimalarial activity against Plasmodium falciparum. Both compounds present good antimalarial activity (IC 50 between 5.8 and 41.4 µg /ml), spilanthol being the most potent (Prachayasittikul et al., 2013). An interesting point to note is that when S. acmella has been regenerated through an in vitro technique, it has higher active content compared with the same species grown as a normal crop. Therefore it has been suggested that S. acmella has the potential to provide a drug for the treatment and prevention of malaria (Prachayasittikul et al., 2013).
| SOME PHARMACOLOGICAL PROPERTIES OF ACMELLA OLERACEA | |||
| PHARMACOLOGICAL ACTIVITY | PLANT EXTRACT* | EXPERIMENTAL MODEL | REFERENCES |
| Antinociceptive activity | Ethanol extract from the flowers of A. oleracea (L.) R.K. | Orofacial nociception test | Nomura et al., 2013 |
| Analgesic activity | Aqueous extract of Spilanthes acmella | Acetic acid-induced writhing response | Chakraborty et al., 2004 |
| Local anesthetic activity | Aqueous extract of S. acmella MURR | Intracutaneous wheal method | Chakraborty et al., 2010 |
| Diuretic activity | Fresh cold-water flower extract (CWE) of Spilanthes acmella | Uniform water load | Ratnasooriya et al., 2004 |
| Diuretic activity | Isolate sphilanthol from methanol plant extract of A. oleracea | Mouse Kidney slices and cell lines models | Gerbino et al., 2016 |
| Gastroprotective activity | Isolate rhamnogalacturonan from A. oleracea’s aqueous extraction | Ethanol-induced gastric lesions | Nascimento et al., 2013 |
| Anti-inflammatory activity | Ethanolic extract from the leaves of Spilanthes acmella | Acute, subacute and chronic inflammation model | Barman et al.,2009 |
| Antimalarial effects | Isolate spilanthol and acetylenic N-alkylamide from EtOH extract of S. acmella | Plasmodium falciparum model | Prachayasittikul et al., 2013 |
* – In this table, as throughout the text, we use the botanical name used in the original publication, and in general these are synonyms of A. oleracea. If there are serious doubts, this is indicated.
Safety
The toxicology of A. oleracea has been studied in different animals, but principally in zebrafish, rats (albino and Wistar rats) and against mosquitos (different species). In the embryo of Zebra fish, the highest concentration (20% v/v) of Spilanthes acmella Murr. (an unresolved name) was tested but revealed no lethal effect. This opened the possibility to feed animals with crude plant extract (1% v/v) without lethal, sublethal or malformation effect (Dubey et al., 2013). Also, regards to fishes, it is important to mention that S. acmella was included at the FDA poisonous plant database and listed as an Indian fish poison (Paulraj, Govindarajan and Palpu, 2013).
In the second group of test animals, an aqueous extract of S. acmella was assessed in albino rats for 24 hours, revealing no adverse effects or mortality. On the other hand, in Wistar rats, were injected low (50 to150 mg/kg) and high (100 to 150 mg/kg) doses of hexane extract of S. acmella, showing in the highest full tonic-clonic convulsions in a dose-dependent manner (Paulraj, Govindarajan and Palpu, 2013).
Finally, due to spilanthol and N-alkylamides, Spilanthes acmella has insecticidal properties against different species of mosquitos. The extract of spilanthol taken from the flower heads is particularly active against Plutella xylostella (a moth), being considered as one of the most potent compounds against these insects (Dubey et al., 2013). Spilanthol, even in low doses, and some extracts were also effective against some insect vectors of parasites including Aedes aegypti and Culex quinquefasciatus including significantly affects on eggs and pupae, particularly, the nervous system (Dubey et al., 2013).
There is a potential of allergic reactions, and very little seems to be known about it (Dubey et al., 2013).
Clinical Evidence
Effectiveness and safety of the A. oleracea have been evaluated in buccal mucosa as a topical anesthetic (De Andrade et al., 2013). A clinical dental trial was performed with 29 volunteer adults (between 18 and 24 years) who were evaluated twice during one week in a double-blind study. Benzocaine (as anesthetic control) and Acmella ointment (in 15% and 30%) was applied randomly on either one of the two sides of the mouth with 15 minutes between the first and the second application. The ointment was made through hydrodistillation of fresh flowers from Pará (Spilanthes acmella (L.) Murray, a taxonomically unresolved name). After some minutes, a needle was inserted in any side of the volunteer’s mouth pain was assessed on a visual analog scale.
The results of the study showed no statistically significant difference between the Acmella ointment (at both doses) and the benzocaine, showing its anesthetic effect for the needle puncture. Nevertheless, in the same article, it is mentioned how the topical application can also produce an anesthetic placebo effect. Use of A. oleracea ointment, revealed no adverse effects.
Final Words
The monograph has revealed some of the main points to be considered about A. oleracea (L) R.K Jansen and its uses. The plant has been used traditionally in different ways highlighting its effect for dental pain, as a diuretic, antiinflamatory, anesthetic, and antimalarial. In vivo and in vitro studies have given scientific support to these traditional uses, however, more research is necessary in terms of methodology, where the species used are clearly identified, and thus avoiding taxonomic misunderstanding. Importantly, this overview also highlights that certain studies were conducted with botanically poorly defined material or an irrelevant doses, highlighting the need for a more rigorous assessment of this species in terms of its current evidence.
Especially, clinical and toxicological studies are needed to be able to advance in the evaluation of the efficiency and safety of this plant. In this sense, some animal experiments have shown a safe profile, but other have described that, at high doses, extracts of the plant can produce convulsions. Besides, the insecticidal property should be studied in more detail with respect to their potential. Finally, A. oleracea has revealed interesting and promising effects which should encourage further study of this plant.
© Nicolas Vasquez C. 2017. All rights reserved.
Nicolas Vasquez C., MSc Medicinal Natural Products and Phytochemistry 2016-2017 (student), Research Cluster “Biodiversity and Medicines”/ Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, Univ. London, 29 – 39 Brunswick Sq., London WC1N 1AX.
DISCLAIMER
In this essay, we do not intend to advise or recommend herbs for medicinal or health use. This information is for educational purposes only and should not be considered as a recommendation or an endorsement of any particular medical or health treatment. The use of any such product should be based on the appropriate advice of a health care professional or based on the information available in the patient information leaflets (i.e. for THR products). The information provided should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.
Bibliography
Barman, S., Sahu, N., Deka, S., Das, S. (2009) ‘Anti-inflammatory and analgesic activity of leaves of Spilanthes acmella (ELSA) in experimental animal models’. Pharmacologyonline, 1, pp. 1027–1034.
Bosch, C.H., 2004. Acmella oleracea (L.) R.K.Jansen. [Internet] Record from PROTA4U. Grubben, G.J.H. & Denton, O.A. (Editors). PROTA (Plant Resources of Tropical Africa / Ressources végétales de l’Afrique tropicale), Wageningen, Netherlands. <http://www.prota4u.org/search.asp>. Accessed 15 June 2017.
Chakraborty, A., Devi, R. K., Rita, S., Sharatchandra, K., Singh T.I. (2004) ‘Preliminary studies on antiinflammatory and analgesic activities of Spilanthes acmella in experimental animal models’. Indian Journal of Pharmacology, 36(3), pp. 148-50.
Chakraborty, A., Devi, B., Sanjebam, R., Khumbong, S., Thokchom, I. (2010) ‘Preliminary studies on local anesthetic and antipyretic activities of Spilanthes acmella Murr. in experimental animal models’. Indian Journal of Pharmacology, 42(5), pp. 277–279.
De Andrade, L. C., Rotta, I. W., Chaves, S. R., Uchida, D. T., Gazim, Z. C., Ferreira, F. B. P., Jacomassi, E. and Boleta-Ceranto, D. D. C. F. (2013) ‘Effectiveness of Acmella oleracea for topical anesthesia on buccal mucosa’, Revista Odonto Ciencia, 28(3), pp. 61–65.
Dubey, S., Maity, S., Singh, M., Saraf, S. A. and Saha, S. (2013) ‘Phytochemistry, pharmacology and toxicology of Spilanthes acmella: A review’, Advances in Pharmacological Sciences, 2013. doi: 10.1155/2013/423750.
Duke, J., Bogenschutz-Godwin, M., Ottesen, A. (2009). ‘Duke’s Handbook of Medicinal Plants of Latin America’. Boca Raton, Fl, USA: CRC Press, pp.13 ̶ 14.
Gerbino, A., Schena, G., Milano, S., Milella, L., Franco Barbosa, A., Armentano, F., Procino, G., Svelto, M. and Carmosino, M. (2016) ‘Spilanthol from Acmella oleracea lowers the intracellular levels of cAMP impairing NKCC2 phosphorylation and water channel AQP2 membrane expression in mouse kidney’, PLoS ONE, 11(5), pp. 1–22. doi: 10.1371/journal.pone.0156021.
Hind, N. and Biggs, N. (2003) ‘Plate 460. Acmella Oleracea Compositae’, Curtis’s Botanical Magazine, 20(1), pp. 31–39. doi: 10.1111/1467-8748.00368.
Nascimento, A. M., De Souza, L. M., Baggio, C. H., Werner, M. F. D. P., Maria-Ferreira, D., Da Silva, L. M., Sassaki, G. L., Gorin, P. A. J., Iacomini, M. and Cipriani, T. R. (2013) ‘Gastroprotective effect and structure of a rhamnogalacturonan from Acmella oleracea’, Phytochemistry. Elsevier Ltd, 85, pp. 137–142. doi: 10.1016/j.phytochem.2012.08.024.
Nomura, E. C. O., Rodrigues, M. R. A., Da Silva, C. F., Hamm, L. A., Nascimento, A. M., De Souza, L. M., Cipriani, T. R., Baggio, C. H. and De Paula Werner, M. F. (2013) ‘Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice’, Journal of Ethnopharmacology. Elsevier, 150(2), pp. 583–589. doi: 10.1016/j.jep.2013.09.007.
Paulraj, J., Govindarajan, R. and Palpu, P. (2013) ‘The Genus Spilanthes Ethnopharmacology, Phytochemistry, and Pharmacological Properties: A Review’, Advances in Pharmacological Sciences, 2013, p. 22. doi: http://dx.doi.org/10.1155/2013/510298.
Prachayasittikul, V., Prachayasittikul, S., Ruchirawat, S., Prachayasittikul, V. (2013) ‘Review article : High therapeutic potential of Spilanthes acmella ’:, EXCLI journal, 12, pp. 291–312.
Ratnasooriya, W. D., Pieris, K. P. P., Samaratunga, U. and Jayakody, J. R. A. C. (2004) ‘Diuretic activity of Spilanthes acmella flowers in rats’, Journal of Ethnopharmacology, 91(2–3), pp. 317–320. doi: 10.1016/j.jep.2004.01.006.
The Plant List, 11/02/2012. Acmella oleracea (L.) R.K.Jansen. (Online) Available from: http://www.theplantlist.org/tpl1.1/record/gcc-142218?ref=tpl1 (Accessed 15/06/2017).
Images
[1]Vine vera reservatoral skin care. Ingredient Spotlight: Acmella Oleracea Extract. 2015. (Online) Available from: http://vineveracosmetics.com/2015/09/18/ingredient-spotlight-acmella-oleracea-extract/ (Accessed 22/03/2017)
[2]PubChem. 2017. Spilanthol. (Online) Available from: https://pubchem.ncbi.nlm.nih.gov/compound/5353001#section=Top (Accessed 10/06/2017)
[3]Top tropical, Acmella Oleracez. 2017. (Online) Available from: https://toptropicals.com/catalog/uid/acmella_oleracea.htm (Accessed 22/03/2017)