Spilanthol, the Principal Alkylamide from Acmella oleracea, Attenuates 5-Fluorouracil-Induced Intestinal Mucositis in Mice

Abstract

Mucositis is one of the commonest side effects in cancer patients undergoing treatment with radiotherapy and/or chemotherapy, and it currently lacks appropriate and effective treatment. , a species of flowering herb from South America, contains spilanthol, an alkylamide that has several pharmacological properties, including anesthetic, analgesic, and anti-inflammatory activities. Therefore, the purpose of this work was to evaluate the effect of spilanthol in intestinal mucositis in Swiss mice induced by 5-fluorouracil (5-FU), an antineoplastic agent administered systemically for the treatment of many different cancers. The repeated administration of 5-FU resulted in intestinal mucositis and consequent decreased food intake, together with weight loss, in all the animals. Daily administration of spilanthol significantly lowered the severity of intestinal mucositis, reducing histopathological changes and increasing the villus height in the animals treated with spilanthol at a dosage of 30 mg/kg (p< 0.0044) compared to a group exposed only to 5-FU. A decrease of myeloperoxidase activity was also observed in the animals treated with 30 mg/kg of spilanthol (p < 0.05), although several pro-inflammatory cytokines were not quantifiable in any group. In conclusion, the data demonstrated that spilanthol effectively reduced inflammation in a mouse model of intestinal mucositis induced by 5-FU, and that the compound might be a promising therapeutic candidate for the prevention and treatment of this condition.

Acmella oleracea extract increases collagen content and organization in partially transected tendons

“…Huang et al (2018) evaluated the effects of spilanthol on the expression of iCAM‐1 and mediators associated with inflammation in the epithelial cells of human lungs, and their results suggested that spilanthol exerts anti‐inflammatory effects by inhibiting the pro‐inflammatory cytokines COX‐2 and iCAM‐1, thereby leading to the inhibition of NF‐κB and MAPK signaling pathways. A study conducted by de Freitas‐Blanco et al (2019) demonstrated the anti‐inflammatory effect of spilanthol on induced intestinal mucositis in mice.…”

“…The Acmella oleracea (L.) R. K. Jansen, synonym Spilanthes acmella (L.) L., popularly known as jambu, belongs to the Asteraceae family and is native to the Amazon region. A. olleracea is very useful in folk medicine for the treatment of diseases in the mouth, throat, and teeth, rheumatism, anemia, and influenza, among others, because of bioactive compounds such as spilanthol (de Freitas‐Blanco et al, 2019; Neves et al, 2019). The chemesthetic sensation in the oral mucosa after consumption of the plant is due to the presence of alkylamides, represented by a high concentration of spilanthol, which is responsible for its analgesic and anti‐inflammatory effects (Dallazen et al, 2018; de Freitas‐Blanco et al, 2019).…”

“…A. olleracea is very useful in folk medicine for the treatment of diseases in the mouth, throat, and teeth, rheumatism, anemia, and influenza, among others, because of bioactive compounds such as spilanthol (de Freitas‐Blanco et al, 2019; Neves et al, 2019). The chemesthetic sensation in the oral mucosa after consumption of the plant is due to the presence of alkylamides, represented by a high concentration of spilanthol, which is responsible for its analgesic and anti‐inflammatory effects (Dallazen et al, 2018; de Freitas‐Blanco et al, 2019). Certain in vivo and in vitro studies have described the anti‐inflammatory and antinociceptive effects of the extract obtained from A. oleracea or isolated spilanthol, and enhanced wound contraction in the skin of rats (Dallazen et al, 2020; Huang, Huang, Hu, Peng, & Wu, 2019; Cho, Bach, Kim, Vuong, & Cho, 2017; Yamane et al, 2016; Nomura et al, 2013).…”

A Review of the Chemistry and Biological Activities of Acmella oleracea (“jambù”, Asteraceae), with a View to the Development of Bioinsecticides and Acaricides

“…Among the main biological activities, the anesthetic one is the main reason why A. oleracea has been used since ancient times to relieve toothache [ 90 ]. To date, the anesthetic mechanism of action is well established, depending on N -alkylamide spilanthol [ 91 ], which increases the release of gamma-aminobutyric acid (GABA) [ 92 ]; interacts with transient receptor potential vanilloid type 1 (TRPV1) and TRPA1 receptors [ 93 ]; stimulates the synthesis of prostaglandins; activates the opioidergic [ 94 ], serotoninergic, and GABAergic systems [ 95 ]; and blocks the voltage-gated Na + channels [ 11 ].…”

Therapeutic effects and mechanisms of plant-derived natural compounds against intestinal mucositis

“…Spilanthol, a major alkylamide from Acmella oleracea , possesses narcose, analgesic, and anti-inflammatory actions ( Silveira et al, 2018 ). de Freitas-Blanco et al (2019 )assessed the effect of spilanthol on gut mucositis in Swiss murine elicited by 5-fluorouracil. Continuous dose of 5-fluorouracil led to gut mucositis and consequently decreased food ingestion and weight reduction.…”