Spilanthes acmella

• How It Works

  Spilanthes, also known as the “toothache plant”, may have numbing and pain-relieving effects, but human data are lacking.

  Spilanthes is an herbaceous plant that belongs to the daisy family. It is recognized in traditional medicine throughout Asia and South America for a variety of properties including anti-inflammatory, diuretic, and aphrodisiac effects. The leaves are used as food sources. The flowers of Spilanthes have earned it the name “toothache plant” for their numbing and pain-relieving effects.

  Spilanthes has also been noted to stimulate taste and improve saliva flow. Therefore, whether it could help side effects from cancer treatments such as dry mouth, mouth sores and inflammation, or changes in taste sensation may be of interest to researchers. However very few studies have been conducted and none of them have yet been done in humans.

• Purported Uses

  Toothache or gum infections
  Studies in the lab suggest that Spilanthes may protect against certain bacterial and dental infections, but there are no human data.

  Sore throat or sore mouth
  Studies in the lab suggest that Spilanthes may have a numbing effect and reduce inflammation, but studies have not yet been conducted in humans.

  Inflammation and wound healing
  Animal studies suggest that compounds in Spilanthes may protect against or possibly heal ulcers.

• Do Not Take If
  • You are using a diuretic (water pill) for blood pressure or for swelling: Animal studies show Spilanthes can promote urination and may increase the risk of adverse effects.
  • You have prostate cancer: Animal studies show that Spilanthes stimulates male hormone production, especially at high doses. This may affect the actions of the drugs used to treat prostate cancer.
  • You are pregnant: Animal studies suggest the potential for birth defects with high doses of this botanical.
• Side Effects

  In general, human data are lacking.

  Case Report

  Painful lip swelling: In a 42-year-old healthy man who presented to the emergency department. The suspected cause was an appetizer of “Szechuan buttons” ingested several days earlier, in the absence of any other explanation.

• Special Point

  Spilanthes, an herbaceous plant that grows in tropical and subtropical regions, should not be confused with jambu madu or wax jambu, which are names for the wax apple fruit tree that is widely cultivated in Southeast Asia.

• Scientific Name

  Spilanthes acmella, Spilanthes oleracea, Acmella oleracea, Acmella uliginosa

• Clinical Summary

  Spilanthes acmella is an herbaceous plant that belongs to the family Asteraceae. It is used in traditional medicine throughout Asia and South America, where it is known as Jambu. The leaves are used for culinary purposes, and the flowers have been used for their numbing and pain-relieving properties, earning the plant such common names as the toothache plant. In addition, it has been noted to relieve stomatitis, have taste-activating properties, and to induce a salivary response.

  In vitro and animal studies suggest that Spilanthes, related species, and their compounds have antimicrobial ^{(2) (3) (10)}, antinociceptive ^{(8) (9) (11)}, anti-inflammatory ⁽⁶⁾, gastroprotective ^(12) (13), and taste-activating ⁽⁴⁾ properties. Spilanthol and acmellonate, compounds derived from this plant, are associated with reduced toothache pain and increased saliva secretion ⁽¹⁾. Other experimental studies suggest diuretic ^(7) (18) and aphrodisiac ^(5) (19) effects.

  In vitro, a hydroethanolic extract of S. acmella produced cytotoxic effects in tumor cell cytoskeletons ⁽¹⁶⁾. In murine models of 5-fluorouracil-induced intestinal mucositis, spilanthol from A. oleracea reduced inflammation ⁽²⁰⁾. However, human data are lacking.

• Purported Uses
  • Gum infections
  • Inflammation
  • Sore throat
  • Stomatitis
  • Toothache
  • Wound healing
• Mechanism of Action

  Antinociceptive effects with this botanical have been attributed to anti-inflammatory properties ⁽¹¹⁾ and engagement of opioid receptors ⁽⁹⁾. Compounds that induce the tingling sensation associated with topical application or chewing of jambu include spilanthol, and to a lesser degree acmellonate ⁽⁴⁾. Taste-activating alkamide compounds that induce a salivary response have also been identified ⁽⁴⁾. Spilanthol is among the most active alkamides isolated from aerial parts of A. oleracea to demonstrate insecticidal ⁽¹⁴⁾ and acaricidal ⁽¹⁵⁾ activity.

  In animal models, spilanthol isolated from S. acmella reduced inflammatory responses via nuclear factor kappa-B inactivation ⁽⁶⁾. Potential mechanisms for gastroprotective effects with rhamnogalacturonan, a polysaccharide isolated from A. oleracea, include protectively binding to the mucosal surface, increasing mucus synthesis, scavenging radicals, and diminishing secretions of acid and pepsin ⁽¹²⁾. Other research suggests that rhamnogalacturonan promotes the restoration of epithelial continuity via epithelial cell proliferation and enhances mucin production to promote gastric ulcer healing ⁽¹³⁾.

  In vivo studies suggest potential teratogenic activity in embryos may be due to various spilanthol metabolites ⁽²¹⁾. An animal study found that an S. acmella ethanolic flower extract, rich in alkylamides, affected male sexual functioning by increasing levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) ⁽⁵⁾, with the effect being significant and lasting at high doses.

• Contraindications

  Patients with androgen-sensitive prostate cancer: In an animal study, an alkylamide-rich S. acmella ethanolic flower extract increased levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) ⁽⁵⁾.

  Pregnant women: In vivo studies suggest the potential for teratogenic effects with high doses of a hydroethanolic extract of A. oleracea ⁽²¹⁾.

• Adverse Reactions

  In general, human data are lacking.

  Case Report

  Painful lip swelling: In a 42-year-old healthy man who presented to the emergency department. The suspected cause was an appetizer of “Szechuan buttons” ingested several days earlier, in the absence of any other explanation  ⁽²²⁾.

• Herb-Drug Interactions
  • Cytochrome P4502E1 (CYP2E1) substrates: In vitro studies suggest spilanthol significantly inhibits CYP2E1 ⁽¹⁷⁾. Clinical relevance has yet to be determined, although drugs in this class include those used in general anesthesia such as isoflurane and sevoflurane. 
  • Antiandrogen drugs (bicalutamide, flutamide, abiraterone): In animal studies, S. acmella may increase testosterone levels ⁽⁵⁾. Clinical relevance has yet to be determined.
  • Diuretics: In animal studies, S. acmella has loop diuretic activity ⁽⁷⁾, and may have additive effects with other diuretic drugs.
• References

  1. Dubey S, Maity S, Singh M, et al. Phytochemistry, Pharmacology and Toxicology of Spilanthes acmella: A Review. Adv Pharmacol Sci. 2013;2013:423750.

  2. Spelman K, Depoix D, McCray M, et al. The traditional medicine Spilanthes acmella, and the alkylamides spilanthol and undeca-2E-ene-8,10-diynoic acid isobutylamide, demonstrate in vitro and in vivo antimalarial activity. Phytother Res. Jul 2011;25(7):1098-1101.

  3. Sathyaprasad S, Jose BK, Chandra HS. Antimicrobial and antifungal efficacy of Spilanthes acmella as an intracanal medicament in comparison to calcium hydroxide: An in vitro study. Indian J Dent Res. Sep-Oct 2015;26(5):528-532.

  4. Ley JP, Blings M, Krammer G, et al. Isolation and synthesis of acmellonate, a new unsaturated long chain 2-ketol ester from Spilanthes acmella. Nat Prod Res. Jul 20 2006;20(9):798-804.

  5. Sharma V, Boonen J, Chauhan NS, et al. Spilanthes acmella ethanolic flower extract: LC-MS alkylamide profiling and its effects on sexual behavior in male rats. Phytomedicine. Oct 15 2011;18(13):1161-1169.

  6. Wu LC, Fan NC, Lin MH, et al. Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-induced inflammatory mediators. J Agric Food Chem. Apr 9 2008;56(7):2341-2349.

  7. Ratnasooriya WD, Pieris KP, Samaratunga U, et al. Diuretic activity of Spilanthes acmella flowers in rats. J Ethnopharmacol. Apr 2004;91(2-3):317-320.

  8. Chakraborty A, Devi BR, Sanjebam R, et al. Preliminary studies on local anesthetic and antipyretic activities of Spilanthes acmella Murr. in experimental animal models. Indian J Pharmacol. Oct 2010;42(5):277-279.

  9. Ong HM, Mohamad AS, Makhtar N, et al. Antinociceptive activity of methanolic extract of Acmella uliginosa (Sw.) Cass. J Ethnopharmacol. Jan 7 2011;133(1):227-233.

  10. Lagnika L, Amoussa AM, Adjileye RA, et al. Antimicrobial, antioxidant, toxicity and phytochemical assessment of extracts from Acmella uliginosa, a leafy-vegetable consumed in Benin, West Africa. BMC Complement Altern Med. 2016;16(1):34.

  11. Nomura EC, Rodrigues MR, da Silva CF, et al. Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice. J Ethnopharmacol. Nov 25 2013;150(2):583-589.

  12. Nascimento AM, de Souza LM, Baggio CH, et al. Gastroprotective effect and structure of a rhamnogalacturonan from Acmella oleracea. Phytochemistry. Jan 2013;85:137-142.

  13. Maria-Ferreira D, da Silva LM, Mendes DA, et al. Rhamnogalacturonan from Acmella oleracea (L.) R.K. Jansen: gastroprotective and ulcer healing properties in rats. PLoS One. 2014;9(1):e84762.

  14. Moreno SC, Carvalho GA, Picanco MC, et al. Bioactivity of compounds from Acmella oleracea against Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and selectivity to two non-target species. Pest Manag Sci. Mar 2012;68(3):386-393.

  15. Castro KN, Lima DF, Vasconcelos LC, et al. Acaricide activity in vitro of Acmella oleracea against Rhipicephalus microplus. Parasitol Res. Oct 2014;113(10):3697-3701.

  16. Pacheco Soares C, Lemos VR, da Silva AG, et al. Effect of Spilanthes acmella hydroethanolic extract activity on tumour cell actin cytoskeleton. Cell Biol Int. Jan 2014;38(1):131-135.

  17. Raner GM, Cornelious S, Moulick K, et al. Effects of herbal products and their constituents on human cytochrome P450(2E1) activity. Food Chem Toxicol. Dec 2007;45(12):2359-2365.

  18. Gerbino A, Schena G, Milano S, et al. Spilanthol from Acmella Oleracea Lowers the Intracellular Levels of cAMP Impairing NKCC2 Phosphorylation and Water Channel AQP2 Membrane Expression in Mouse Kidney. PLoS One. 2016;11(5):e0156021.

  19. da Rocha CF, de Medeiros Souza Lima Y, Carvalho HO, et al. Action of the hydroethanolic extract of the flowers of Acmella oleracea (L.) R.K. Jansen on the reproductive performance of Wistar females rats: A popular female aphrodisiac from the Amazon. J Ethnopharmacol. Mar 25 2018;214:301-308.

  20. de Freitas-Blanco VS, Monteiro KM, de Oliveira PR, et al. Spilanthol, the Principal Alkylamide from Acmella oleracea, Attenuates 5-Fluorouracil-Induced Intestinal Mucositis in Mice. Planta Med. Feb 2019;85(3):203-209.

  21. de Souza GC, Matias Pereira AC, Viana MD, et al. Acmella oleracea (L) R. K. Jansen Reproductive Toxicity in Zebrafish: An In Vivo and In Silico Assessment. Evid Based Complement Alternat Med. 2019;2019:1237301.

  22. Mumtaz S, Ravi-Shankar K, Swati M, et al. Spilanthes acmella flowers and painful swelling of the lips. Br J Oral Maxillofac Surg. Apr 2019;57(3):295-296.