Acaricidal activity of synthetic spilanthol derivative against ticks of medical and veterinary importance.

The ANESPSAT, a synthetic spilanthol derivative, and its nanoformulation were evaluated against Rhipicephalus microplus and Amblyomma sculptum ticks. ANESPSAT activity was compared with spilanthol and derivatives (ANESPE and others). The compound was synthesized in a gram-scale by a 2-step process, comprising a direct ester amidation and a Horner-Wadsworth- Emmons reaction. The nanoemulsions were produced by coarse homogenization followed by high-energy ultrasonication, in which hydrodynamic diameter, polydispersity index, and zeta potential remained stable. The spilanthol-eugenol hybrid derivatives did not show significant acaricidal activity. ANESPE killed 83% of the R. microplus larvae at 30 mg.mL-1, while ANESPSAT killed 97% at 0.5 mg.mL-1, showing to be the most active compound. Spilanthol and ANESPSAT had similar high mortality rates for tick larvae, with LC50 values of 0.10 and 0.14 mg.mL-1 for R. microplus larvae, and 0.04 and 0.48 mg.mL-1 for A. sculptum larvae, respectively. The efficacy of spilanthol was lower against R. microplus engorged females when compared with ANESPSAT, which was highly effective (>98%) against R. microplus engorged females. The nanoemulsion with ANESPSAT was effective against tick females, preventing egg laying and achieving 100% efficacy at 2.5 mg.mL-1. Spilanthol had only 59% efficacy at 10 mg.mL-1. The results suggest that ANESPSAT, a natural product derivative, could be used in novel formulations for tick management that might be safer and environmentally friendly.

The potential of Acmella oleracea as a nutraceutical source for the symptomatic treatment of Burning Mouth Syndrome.

This study analysed the phytochemical profile of Acmella oleracea extract and the molecular interactions of its main compounds with TRPV1 and CB2, target receptors in the Burning Mouth Syndrome (BMS) pathogenesis. The phytochemical profile of A. oleracea's floral buds extract treated with activated charcoal (TCEE) was analysed by High-Performance Liquid Chromatography (HPLC) coupled to Mass Spectrometry (LC-MS). The quantification of spilanthol was analysed by HPLC coupled to a Diode-Array Detector (HPLC-DAD). The phytochemical analysis revealed the presence of nine alkylamides and phenolic compounds. The TCEE showed a significant increase in spilanthol content compared to the crude extract (CEE), going from 28.33 mg/g to 117.96 mg/g. The molecular docking indicated a behaviour of the alkylamides as partial TRPV1 agonists and CB2 agonists and, for the first time, indicates the action of these compounds in the symptomatic management of BMS.

Jambu Flower Extract (Acmella oleracea) Increases the Antioxidant Potential of Beer with a Reduced Alcohol Content.

Craft beers with different sensory perceptions have received the attention of more demanding consumers. In this sense, the application of plant extracts as brewing adjuncts is being increasingly studied. Allied with these perspectives is the consumption of lower alcoholic beverages, which also represents the desire for a market niche that has been growing gradually. The present work aimed to produce craft lager beer with the addition of plant extract and reduced alcohol content by partial replacement of malt with malt bagasse. The physical-chemical analyzes of the beer produced showed that it was possible to reduce the alcohol content by 40.5% compared to the control sample. In addition, an extract of Acmella oleracea (Jambu) obtained by supercritical extraction was added to increase the beer's antioxidant capacity. The ABTS, DPPH, and ORAC methods evaluated the antioxidant capacity. These assays were performed again after six months of storage. The quantification and identification of the significant substance in the extract (spilanthol) were performed using Gas Chromatography (GC-FID), Thin Layer Chromatography (TLC), and Attenuated Total Reflectance Infrared Spectroscopy (FTIR-ATR). The results showed significant increases in antioxidant activity compared to the sample without extract. This positive aspect opens a perspective for using jambu flower extract as a prominent antioxidant adjunct in beer.

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

Acmella oleracea contains spilanthol as the main active compound, which possesses analgesic and anti-inflammatory effects that can favor tendon reorganization. To analyze the effect of A. oleracea on the content and organization of collagen in injured tendons, the calcaneal tendon of male Lewis rats was partially transected and treated at the site of injury with a topical application of 20% A. oleracea ointment (AO group) or with the ointment base without the plant extract (B group). The animals were euthanized 21 days after partial transection. Higher collagen concentration was observed in the AO group than in the B group, and morphological analysis using polarization microscopy showed higher birefringence in the AO group than in the B group, indicating higher collagen organization. No difference was observed in the number of fibroblasts, blood vessels, proteoglycan distribution, and maximum load between the B and AO groups. In conclusion, topical application of 20% A. oleracea ointment increased the molecular organization and content of collagen, thus indicating a potential application in tendon repair. Studies on the later phases of the tendon healing process are necessary to demonstrate the possible biomechanical changes after the application of A. oleracea ointment.

Chymase inhibition: A key factor in the anti-inflammatory activity of ethanolic extracts and spilanthol isolated from Acmella oleracea.

ETHNOPHARMACOLOGICAL RELEVANCE: Acmella oleracea (L.) R. K. Jansen (Asteraceae), known as jambú in Brazil, is used in traditional medicine as analgesic and for inflammatory conditions, characterized by the presence of N-alkylamides, mainly spilanthol. This bioactive compound is responsible for the above-described pharmacological properties, including sialagogue and anesthetic. AIM OF THE STUDY: This study aimed to characterize the anti-inflammatory effects of A. oleracea leaves (AOEE-L) and flowers (AOEE-F) extracts, including an isolated alkylamide (spilanthol), using in vitro and in vivo models. The mechanism underlying this effect was also investigated. MATERIALS AND METHODS: Extracts were analyzed by HPLC-ESI-MS/MS in order to characterize the N-alkylamides content. AOEE-L, AOEE-F (25-100 µg/mL) and spilanthol (50-200 µM) were tested in vitro on VSMC after stimulation with hyperglycemic medium (25 mM glucose). Their effects over nitric oxide (NO) generation, chymase inhibition and expression, catalase (CAT), superoxide anion (SOD) radical activity were evaluated. After an acute administration of extracts (10-100 mg/mL) and spilanthol (6.2 mg/mL), the anti-inflammatory effects were evaluated by applying the formalin test in rats. Blood was collected to measure serum aminotransferases activities, NO activity, creatinine and urea. RESULTS: A number of distinct N-alkylamides were detected and quantified in AOEE-L and AOEE-F. Spilanthol was identified in both extracts and selected for experimental tests. Hyperglycemic stimulation in VSMC promoted the expression of inflammatory parameters, including chymase, NO, CAT and SOD activity and chymase expression, all of them attenuated by the presence of the extracts and spilanthol. The administration of extracts or spilanthol significantly inhibited edema formation, NO production and cell tissue infiltration in the formalin test, without causing kidney and liver toxicity. CONCLUSION: Taken together, these results provide evidence for the anti-inflammatory activity of leaves and flowers extracts of jambú associated distinctly with their chemical profile. The effects appear to be associated with the inhibition of chymase activity, suppression of the proinflammatory cytokine NO and antioxidant activities.

Comparison of powdered and fresh jambu (Acmella oleracea).

Jambu, Acmella oleracea (L.), is a low-growing herb plant, with cylindrical, fleshy, decumbent and branched stem varying from 20 to 30 cm in height. It is an abundantly cultivated and consumed vegetable in the northern region of Brazil and usually consumed in preparations of typical foods of the Amazon region. So, this work aimed to compare the chemical composition and physical chemistry of powdered and jambu leaf mass. Acmella oleracea plants were selected, sanitized and their leaves were crushed (without adding water). The mass was dried in an oven with forced air circulation under different conditions of temperature (60, 70 and 80 °C) and relative humidity (13.09, 8.14 and 5.45%, respectively), in two layer thicknesses (0.5 and 1.0 cm). The physical, chemical, physicochemical parameters moisture content, water activity, ash, protein, lipids, pH, total titratable acidity and color were analyzed in powdered and fresh leaves. Contrast test was used to evaluate the interaction between the layer thicknesses at 5% level of significance. Considering the contrasts, the parameters total soluble solids, ash, protein and lipids do not differ from those in the fresh sample, demonstrating that these parameters are not modified or degraded with the drying conditions. The pH and color parameters differed from those of the fresh material, due to degradation, which can be linked to the rise in temperature sensitivity. The moisture content and water activity also differed and were reduced, contributing to conservation of the material. Contrast analysis made it possible to conclude that the physicochemical composition did not undergo modifications through the use of drying. In addition, a powdered material with reduced water activity was obtained.

Reproductive toxicity of the hydroethanolic extract of the flowers of Acmella oleracea and spilanthol in zebrafish: In vivo and in silico evaluation.

Hydroethanolic preparations of Acmella oleracea is used in the north of Brazil as a female aphrodisiac. Thus, the objective of this study was to evaluate the action of the hydroethanolic extract of Acmella oleracea (EHFAo) flowers (21.873 and 44.457 mg/kg) and spilanthol (3 mg/kg) administered orally on reproductive performance and effects on the embryonic development of zebrafish F1 generation. It was observed that in the groups in which males and females received EHFAo and spilanthol, the spawning was interrupted, whereas in the groups in which only the females were treated, spawning occurred during the 21 days. Thus, in the histopathological evaluation of the gonads, it was possible to observe that the percentage of mature cells in the spermatozoa and females was significantly reduced. Only the embryo groups in which parental generation was treated with EHFAo showed lethal and teratogenic effects. On the other hand, the parental groups treated with the spilanthol presented only the lethality. Spilanthol and some metabolites showed good oral availability and important toxicological properties. Thus, it is suggested that the treatment of parental generation of zebrafish with EHFAo and spilanthol caused severe changes in the gonads and on fertility. However, on the embryo, the most striking effects in the development were recorded in the groups in which the parental generation was treated with the EHFAo, while the spilanthol influenced the lethality of the embryos.

Acute Toxicity of the Hydroethanolic Extract of the Flowers of Acmella oleracea L. in Zebrafish (Danio rerio): Behavioral and Histopathological Studies.

Hydroethanolic preparations of the botanical species Acmella oleracea L. are used in the north of Brazil for the treatment of various diseases. However, few studies have been conducted to evaluate the toxicity of this species. The objective of this study was to evaluate the acute toxicity of the hydroethanolic extract of A. oleracea L. (EHFAo) flowers in zebrafish by immersion and oral administration. The extract was analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). EHFAo was administered orally (44.457, 88.915, 199.94, 281.83, and 448.81 mg/kg) and by immersion (250, 300, 350, 400, and 450 µg/L). Behavioral and histopathological analysis of gills, liver, intestine, and kidney were performed. The presence of (2E,6Z,8E)-N-isobutyl-2,6,8-decatrienamide (spilanthol) in EHFAo was identified by ultra-high-re.solution liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS). Treatment with EHFAo caused significant behavioral changes and death. The calculated median lethal dose (LD50) was 148.42 mg/kg, and the calculated median lethal concentration (LC50) was 320 µg/L. In the histopathological study, it was observed that upon oral treatment, the tissue alterations that compromised the normal functioning of the organism occurred with EHFAo doses of 88.915, 199.53, and 281.83 mg/kg, the intestine being the most affected. When the treatment was performed by immersion, the most toxic EHFAo concentrations according to the histopathological evaluation were 300, 350, and 400 µg/L, with the most affected organ being the gills. Finally, EHFAo in this study was shown to be more toxic to the liver, intestine, and kidneys when administered orally and to gills, liver, and kidneys when administered by immersion in water. Therefore, considering the results obtained and the chemical characteristics of the main phytochemical marker of EHFAo, spilanthol, it can be suggested that, depending on the dose, this compound can lead to histopathological damages in the organs highlighted in this study.

Water deficit on germination and vigour in seeds of the Jambu / Déficit hídrico na germinação e vigor de sementes d e jambu

Water availability influences plant metabolism during the various stages of development, especially in the period between germination and seedling emergence. The aim of this study was to evaluate the effect of water deficit during the germination process on seeds of A. oleracea. The experiment was carried out in a completely randomised design, with four replications of 50 seeds. The treatments were arranged in a 5 x 2 factorial scheme, with the first factor consisting of the osmotic potentials (-0.2, -0.4, -0.6, -0.8 and distilled water for the potential 0.0 MPa) and the second factor consisting of two lots of seed. The germination test was carried out on substrates moistened with solutions of mannitol and polyethylene glycol (PEG 6000) at the various potentials, in a Biochemical Oxygen Demand (BOD) germinator at a temperature of 30°C and under constant light. The test was evaluated daily for 14 days, considering the seeds that had a root length equal to or greater than two millimetres as having germinated. The variables under analysis were germination, germination speed index, seedling length and seedling dry weight. The germination process of A. oleracea is compromised at water potentials of -0.2 MPa and -0.4 MPa when submitted to PEG and mannitol respectively. Seeds from Lot 1 were more tolerant to the water deficit than were those from Lot 2.

A disponibilidade de água influencia o metabolismo vegetal nas diversas etapas do desenvolvimento, especialmente no período entre a germinação e a emergência das plântulas. Diante disso, objetivou-se avaliar o efeito do déficit hídrico durante o processo de germinação de sementes de A. oleracea. O experimento foi conduzido em delineamento experimental inteiramente casualizado, com quatro repetições de 50 sementes. Os tratamentos foram arranjados em esquema fatorial 5 x 2, com o primeiro fator constituído pelos potenciais osmóticos (-0,2; -0,4; -0,6; -0,8 e água destilada para o potencial 0,0 MPa) e o segundo dois lotes de sementes. Para isso, o teste de germinação foi realizado em substratos umedecidos com soluções de manitol e polietilenoglicol (PEG 6000) nos diversos potenciais, em germinador do tipo Biochemical Oxigen Demand (B.O.D.) sob a temperatura de 30 °C e luz constante. O teste foi avaliado diariamente durante 14 dias, sendo considerado como germinadas, as sementes que apresentavam extensão radicular igual ou superior a dois milímetros. As variáveis analisadas foram germinação, índice de velocidade de germinação, comprimento de plântulas e massa seca de plântulas. O processo germinativo de sementes de A. oleracea é comprometido a partir de potenciais hídricos de -0,2 MPa e -0,4 MPa, quando submetidas ao PEG e manitol respectivamente. As sementes provenientes do lote 1 mostraram-se mais tolerantes ao déficit hídrico que as do lote 2.

Distinct mechanisms underlying local antinociceptive and pronociceptive effects of natural alkylamides from Acmella oleracea compared to synthetic isobutylalkyl amide.

Acmella oleracea (jambu), is used as ingredient for food and in folk medicine to relief toothache. Jambu edible flowers are rich in alkylamides, mainly spilanthol, which are responsible to evoke chemesthetic sensations. This study aimed to investigate the local effects promoted by the intraplantar injection of the hexanic fraction (HF) rich in alkylamides from jambu flowers and compare to synthetic isobutylalkyl amide (IBA). Swiss male mice were intraplantarly administrated with HF and IBA (0.1-30 µg/20 µL), and the underlying mechanisms associated to the antinociceptive (0.1 µg) and pronociceptive (30 µg) effects were evaluated in chemical and sensorial tests. HF and IBA at 0.1 µg promoted analgesia in neurogenic and inflammatory phases of formalin test, against glutamate-induced nociception and independent of the activation of endogenous opioidergic system and dependent of TRPV1 modulation, whereas only HF reduced both nociception and mast cell degranulation in hindpaw induced by compound 48/80. However, both potentiated the TRPA1-mediated nociception. In contrast, HF and IBA (30 µg)-evoked nociceptive behaviors were reduced by the activation of opioidergic system, by TRPA1 antagonist and TRP nociceptive fibers desensitization. In addition, 30 µg IBA-evoked nociception by activation of TRPV1, and 30 µg HF by mast cell degranulation. Furthermore, on the contrary of IBA, HF elevated both mechanical and thermal paw threshold. Altogether, these results indicate that alkylamides could elicited dual effects, adding new evidences and mechanisms for these opposite actions in different doses. Although further research is needed, we confirmed that alkylamides displays local analgesic and/or anesthetic effects.

Effects of Acmella oleracea methanolic extract and fractions on the tyrosinase enzyme

Abstract The aim of the current study is to evaluate the effect of Acmella oleracea (L.) R.K. Jansen, Asteraceae, methanolic extract, hexane (84.28% spilanthol) and dichloromethane (approximately 100% spilanthol) fractions on the tyrosinase enzyme. The dehydrated jambu extract was obtained through maceration using methanol. The extract residue was solubilized in MeOH/H2O (8:2) and subjected to liq.–liq. partition in organic solvents. Both the extraction and the partition procedures were conducted with three replicates. The analyses were performed using GC–MS, 1H and 13C NMR. The hexane fraction provided samples containing 84.28, 82.91 and 62.83% spilanthol in repetitions 1, 2 and 3, respectively. The dichloromethane fraction showed 88.55% spilanthol in repetition 1, and approximately 100% spilanthol in repetitions 2 and 3. The jambu extract as well as the hexane fraction (84.28% spilanthol) were able to activate the oxidizing activity of the tyrosinase enzyme for L-DOPA. The dichloromethane fraction (approximately 100% spilanthol) showed stronger inhibition effect on the tyrosinase enzyme in the first 10 min. The results raise the interest in study in spilanthol formulations for topical use, since it may prevent and/or slow skin hyperpigmentation or depigmentation processes. Furthermore, spilanthol may be used to control the enzymatic browning in fruits and vegetables.

Spilanthol: occurrence, extraction, chemistry and biological activities

Abstract Spilanthol (C14H23NO, 221.339 g/mol) is a bioactive compound that is found in many different plants that are used as traditional remedies throughout the world. It is present in Heliopsis longipes and several species in the genus Acmella, including A. oleracea L., also known as paracress and jambu. Its leaves and flowers have sensory properties (pungency, tingling, numbing, mouth-watering) that make it a popular spice and ingredient in several Brazilian dishes. Spilanthol can exert a variety of biological and pharmacological effects including analgesic, neuroprotective, antioxidant, antimutagenic, anti-cancer, anti-inflammatory, antimicrobial, antilarvicidal and insecticidal activities. So, the aim of this review is to present a literature review on the spilanthol that describes its occurrence, chemistry, extraction and biological activities.

Distinct growth and extractive methods of Acmellaoleracea (L.) R.K. Jansen rising different concentrations of spilanthol: An important bioactive compound in human dietary.

Acmella oleracea, commonly known as jambú, is a great source of spilanthol, a secondary metabolite responsible for different kind of biological activities, such as the antioxidant, antimicrobial, cytotoxic and anti-inflammatory bioactivities. The purpose of this work was to evaluate spilanthol content in A. oleracea plants obtained from three different cultivation conditions - in vitro, acclimatized and in field - and compare two different extraction techniques: maceration and microwave assisted extraction (MAE). Therefore, A. oleracea nodal segments were cultured on Murashige and Skoog medium. After 30days, developed plants were transferred to ex vitro conditions and successfully acclimatized. From all types of culture, the whole plant as well as the flowers, leaves, stems and roots were used, separately, to obtain ethanolic extract (75%) but only the micropropagated whole plant was used on the factorial design 24-1 on the microwave-assisted extraction. All the samples were quantified by HPLC-DAD and analyzed by CG-MS. Results show that the different acclimatized plant parts are the richest in spilanthol content, followed by the in vitro culture and, finally, field material. The MAE was able to extract the highest amount of spilanthol from in vitro whole plant (3.09%) compared to the classical maceration extract (0.98%) and, furnished good crude extracts yields under an optimized study accurately explained by the mathematical model. The antibacterial assay presented a negative result using in vitro samples and bacteria inhibition with field samples against Staphylococcus aureus (ATCC 29213) and Staphylococcus epidermidis (ATCC 12228) standard strains.

Influência da adubação com nitrogênio e fósforo na produção de Jambu, Acmella oleracea (L) R. K. Jansen / Influence of the fertilization with nitrogen and phosphorus in the production of jambu (Acmella oleracea (L) R. K. Jansen)

Com o objetivo de avaliar a influência de doses de nitrogênio e fósforo na cultura do Jambu, foi instalado experimento na fazenda experimental da APTA Polo Vale do Ribeira utilizando-se sementes da cultivar Nazaré. Os tratamentos foram conduzidos em blocos casualizados em esquema fatorial 4 x 4, e quatro repetições dos seguintes tratamentos: quatro doses de nitrogênio, (0; 37,5; 75 e 112,5 kg ha-1 N), quatro doses de fósforo (0; 75; 150 e 300 Kg ha-1 de P2O5). O solo foi inicialmente preparado recebendo calagem e adubação de plantio conforme recomendação em função da analise de solo. Após essas operações foi feito o transplante das mudas no espaçamento de 0,50 x 0,50 m e aplicado os tratamentos. A área útil da parcela foi de 1,0 m x 1,0 m. Foram analisadas as massas frescas e secas de folhas e flores, e o número de flores. A produção de matéria fresca e seca das folhas e flores foi influenciada pela adubação. Houve efeito das doses de nitrogênio, que proporcionaram aumento linear em todas as variáveis analisadas e, para a adubação fosfatada, a dose com 75 Kg ha-1 de P2O5 proporcionou a maior produção do número de flores e na massa fresca e seca das flores.

The objective of this work was to evaluate the influence of the use of nitrogen and phosphorus in the culture of jambu. The experiment was initiated at the experimental farm of the agency APTA Polo Vale do Ribeira, using the Nazaré cultivar. The experimental design was complete randomized with fourlevelsof nitrogen (0, 37.5, 75 and 112.5 kg ha-1 N) and phosphorus (0, 75, 150 and 300 Kg ha-1P2O5),and four reapplications. After soil preparation, liming and fertilization, seedlings of jambu were transplanted at a spacing of 0.50 x 0.5 m. The experimental plot was 1.0 x 1.0 m. Fresh and dry mass of leaves and flowers and number of flowers were analyzed. The production of fresh and dry leaves and flowers were influenced by fertilization. Thelevelsof nitrogen affected the outcome, as theyprovided a linear increase in all variables, and the phosphorus level of 75 kgha-1 P2O5 caused the highest average production in the number of flowers and in the fresh and dried mass of flowers.

Antinociceptive effects of ethanolic extract from the flowers of Acmella oleracea (L.) R.K. Jansen in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazil, Acmella oleracea (L.) R.K. Jansen, popularly known as "jambu", has been used by some communities from Amazon region to treat toothache. In this study we examined the antinociceptive effect of the ethanolic extract obtained from the flowers of Acmella oleracea (EEAO) in animal models of nociceptive (chemical and thermal) and neuropathic (partial sciatic nerve ligation) pain. MATERIALS AND METHODS: Adult male mice were treated by intraperitoneal route (i.p.) with EEAO before the induction of nociceptive response by formalin, capsaicin and cinnamaldehyde, thermal heat hyperalgesia (hot plate test) and mechanical allodynia (traumatic sciatic nerve injury). Acute toxicity and non-specific sedative effects were evaluated. RESULTS: EEAO (10, 30 and 100 mg/kg) reduced both neurogenic and inflammatory phases of the formalin- and also capsaicin- and cinnamaldehyde-induced orofacial nociception. Interestingly, EEAO at 100mg/kg (i.p.) also reversed capsaicin-induced heat hyperalgesia assessed as the latency to paw withdrawal in the hot plate test. Also in the hot plate test, paw withdrawal latency was increased by EEAO (100 mg/kg) and this response was only partially reversed by naloxone. Furthermore, EEAO (100 mg/kg) also reduced mechanical allodynia caused by partial sciatic nerve ligation for 3 h. The estimated LD50 value was 889.14 mg/kg and EEAO did not alter the locomotion of animals in the open-field test. CONCLUSION: Taken together, our data show that EEAO produces prevalent antinociceptive effects and does not cause adverse effects. The presence of N-alkylamides, including spilanthol, suggests that the therapeutic effect of EEAO is related to its highest anesthetic activity.

Efecto antiinflamatorio y toxicidad aguda del extracto etanólico de Acmella oleracea (L.) R. K. Jansen (Botoncillo) en ratones albinos / Anti-inflammatory effect and acute toxicity of the ethanolic extract of Acmella oleracea (L.) R. K. Jansen (Buttonhole) in albino mice

La especie vegetal Acmella oleracea (L.) R.K. Jansen (Botoncillo) es utilizada en la medicina popular por sus propiedades antiinflamatorias, anestésica dental, antiespasmódicas, también empleada para tratar diabetes y afecciones hepáticas. Los objetivos de la investigación fueron evaluar el efecto antiinflamatorio vía oral y vía tópica además de la toxicidad aguda vía oral del extracto etanólico de Acmella oleracea (L.) R.K. Jansen (Botoncillo) en ratones albinos. Las partes aéreas de Acmella oleracea (L.) R.K. Jansen (Botoncillo), fueron extraídos por maceración en etanol al 70%. EI efecto antiinflamatorio del extracto etanólico se evalúo utilizando el modelo de edema auricular inducido por TPA (13-acetato de 12-tetradecanoilforboi). La determinación de la toxicidad aguda se realizó por vía oral, bajo el método de Lorke. Para la determinación del efecto antiinflamatorio vía oral, se evaluaron dosis crecientes del extracto etanólico 300mg/Kg, 600mg/Kg, 900mg/Kg, 1200mg/Kg y para la vía tópica 0.5mg/oreja, 2.5 mg/oreja y 5 mg/oreja; las cuales fueron evaluados en el modelo inflamatorio. Los resultados mostraron que las dosis de extracto administrado por vía oral y tópica redujeron la inflamación de las orejas tratadas de los ratones albinos, con un porcentaje de inhibición de 35.21%, 48.09% para las dosis de 900 mg/Kg y 1200 mg/Kg respectivamente, administrados vía oral y para la vía tópica se tuvieron porcentajes de inhibición del 38.28% y 70.71% para las dosis de 2.5mg/Oreja y 5mg/Oreja respectivamente; comparando con el fármaco patrón lndometacina solo la dosis de 5mg/Oreja de extracto aplicado vía tópica superó el porcentaje de inhibición de inflamación. El extracto tuvo una respuesta dosis dependiente frente a la inflamación inducida por TPA. La determinación de la toxicidad aguda se realizó en dos fases por vía oral en ratones albinos de acuerdo al método de Lorke, obteniéndose una DL50 de 3800 mg/Kg de peso. En conclusión este estudio confirma el efecto antiinflamatorio atribuido a la planta Acmella oleracea (L.) R.K. Jansen (Botoncillo) y también valida su uso en la medicina popular y respecto a la toxicidad aguda la especie vegetal es ligeramente tóxica.