Research

Spilanthes Acmella (Toothache Plant)

35 peer-reviewed studies curated from PubMed and Semantic Scholar.

0
Meta-analyses
0
Systematic reviews
4
RCTs
31
Other studies
RCTs (11%)
Observational (6%)

Studies

Sorted by quality and recency

2022·Cureus·Nabnita Patnaik, Kumar Guru Mishra, Nihar Ranjan Pradhan

Randomized, Triple-Blinded, Placebo-Controlled Trial of SA3X (Spilanthes acmella) for the Management of Erectile Dysfunction.

RCTn = 448Sexual Health

Randomized, triple-blinded, placebo-controlled trial of SA3X (Spilanthes acmella) in 448 men with erectile dysfunction. SA3X significantly improved Men's Sexual Health Questionnaire scores, International Index of Erectile Function scores, and duration of penile erection compared to placebo. SA3X was safe with no serious adverse effects.

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2022·Maedica·Nabnita Patnaik, Kumar Guru Mishra, Nihar Ranjan Pradhan

Effect of SA3X (Spilanthes acmella) Supplementation on Serum Testosterone Levels in Males with Erectile Dysfunction - A Parallel Double-Blind Randomized Controlled Trial.

RCTn = 215Mens Health Sexual Health

A double-blind placebo-controlled RCT conducted in Hyderabad, India, with 215 male participants with erectile dysfunction and low testosterone levels. The study found that SA3X supplementation significantly increased serum testosterone levels and improved erectile function, as measured by MSHQ and IIEF scores, with effects maintained even after discontinuation of the intervention.

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2024·International journal of cosmetic science·Sanela M Savic, Nebojsa D Cekic, Tanja M Ilic, et al

Preliminary safety and in vivo efficacy of Acmella oleracea extract-loaded glycolipid emulsion serum-Effects on ocular irritation, dermal absorption, and facial skin biophysical and microrelief properties.

RCTSkin Hair Health

The study evaluated a glycolipid emulsion serum containing Acmella oleracea extract for its stability, safety, and efficacy as a topical anti-aging product. The serum showed no ocular irritation or systemic absorption and improved skin hydration, smoothness, and reduced roughness and wrinkles in human volunteers.

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2025·Journal of dental anesthesia and pain medicine·Michael Henrique Araujo Monteiro, Josilanny Araujo de Souza Alencar, Victor Augusto Benedicto Dos Santos, et al

Efficacy of lidocaine-prilocaine combined with amitriptyline orin a liposomal cream for topical anesthesia: a randomized crossover clinical trial.

RCTn = 40

Randomized crossover clinical trial comparing the anesthetic efficacy of lidocaine and prilocaine combined with either amitriptyline or jambu extract for topical anesthesia of the buccal and palatal mucosa. Formulations with amitriptyline showed relevant clinical potential, while jambu extract demonstrated intermediate efficacy. None of the formulations achieved significant pulpal anesthesia.

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2022·Cureus·Nabnita Patnaik, Kumar Guru Mishra, Nihar Ranjan Pradhan

Evaluation of Serum Testosterone Levels Following Three Months of SA3X (Spilanthes acmella) Supplementation.

Observationaln = 326Mens Health

Observational study of 326 men with erectile dysfunction supplemented with SA3X (Spilanthes acmella) for three months. Significant increases in serum testosterone levels were observed by the end of the second and third months. The change in testosterone levels was lower in participants with diabetes, hypercholesterolemia, and substance abuse history, but higher in those on phosphodiesterase-5 inhibitors.

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2021·Journal of family medicine and primary care·Nihar Ranjan Pradhan, Kumar Guru Mishra, Nabnita Patnaik, et al

Evaluation of effects of Spilanthes acmella extract on muscle mass and sexual potency in males: A population-based study.

Observationaln = 240Physical Performance Sexual Health

Longitudinal study of 240 male participants consuming SA3X capsules containing Spilanthes acmella extract. Significant increases in muscle mass and sexual activity were observed over 3 weeks and 2 months, suggesting the herb's potential as a muscle gainer and aphrodisiac.

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2026·Scientific reports·Kunat Suktham, Suvimol Surassmo, Raweewan Thiramanas, et al

Comparative evaluation of ultrasound-assisted extraction and micelle-mediated extraction of bioactive compound from Acmella oleracea.

StudyInflammation

The study compares ultrasound-assisted extraction (UAE) and micelle-mediated extraction (MME) for isolating IBDTA from Acmella oleracea. UAE achieved the highest extraction efficiency, while MME-extracted product exhibited the highest anti-inflammatory activity. Both methods are suitable for industrial applications in pharmaceutical, nutraceutical, and cosmeceutical industries.

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2022·Planta medica·Mirosława Grymel, Roman Mazurkiewicz, Sylwia Bajkacz, et al

Extraction, Purification, Quantification, and Stability of Bioactive Spilanthol from Acmella oleracea.

Study

The paper focuses on the extraction, purification, quantification, and stability of spilanthol from Acmella oleracea. It describes methods for isolating spilanthol, quantifying its concentration using HNMR, and ensuring its stability for long-term storage. Spilanthol is noted for its anti-inflammatory, antioxidant, analgesic, antifungal, and bacteriostatic properties, as well as its use in anti-aging cosmetics.

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2022·Pakistan journal of pharmaceutical sciences·Aqsa Afzal, Nisar Hussain Shah, Irshad Hussain, et al

Preparation of Spilanthes acmella based emulgel: Antimicrobial study and evaluation.

StudySkin Hair Health

The study developed an herbal emulgel using Spilanthes acmella extract for treating bacterial skin infections. The emulgel showed significant antibacterial activity against S. aureus, P. aeruginosa, and E. coli, with high antioxidative activity and promising drug delivery characteristics.

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2021·International journal of cosmetic science·Sanela M Savic, Nebojsa D Cekic, Sasa R Savic, et al

'All-natural' anti-wrinkle emulsion serum with Acmella oleracea extract: A design of experiments (DoE) formulation approach, rheology and in vivo skin performance/efficacy evaluation.

StudySkin Hair Health

The study describes the design and evaluation of an emulsion serum containing Acmella oleracea extract for anti-wrinkle effects. Rheological and stability properties were assessed, and in vivo evaluations showed noticeable reduction in skin wrinkles after 2 weeks of application, indicating beneficial effects on facial lines.

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2026·Journal of molecular histology·Edvaldo Mendes Silva, Cínthia Rio Branco da Silva, Janaína Ribeiro Costa, et al

Anti-hyperplastic effects of Acmella oleracea flower and leaf extracts in prostate cell lines and in spontaneously hypertensive rats.

Animal studyMens Health

The study investigated the effects of Acmella oleracea flower and leaf extracts on prostate hyperplasia using human prostate cell lines and a spontaneously hypertensive rat model. Both extracts attenuated prostatic hyperplasia, with the flower extract showing a more pronounced reduction in epithelial proliferation and stromal remodeling.

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2025·International journal of molecular sciences·Israel Hurtado-Díaz, Rubicela Teta-Talixtacta, Antonio Bernabé-Antonio, et al

GC-MS-Identified Alkamides and Evaluation of the Anti-Inflammatory, Antibacterial, and Antioxidant Activities of Wild.

In vitroInflammation Immunity

The study conducted a chemical analysis of the toothache plant using GC-MS and evaluated the antioxidant, anti-inflammatory, and antibacterial activities of its ethanolic extracts. The dichloromethane fractions of the aerial parts and root extracts showed significant inhibition of nitric oxide and TNF-α production, indicating strong anti-inflammatory potential. The extracts also demonstrated antibacterial activity, particularly against resistant strains, likely due to the presence of alkamides such as spilanthol.

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2025·Plants (Basel, Switzerland)·Marta Ferrati, Beatrice Bartolini, Giulio Lupidi, et al

Assessment of the-Alkylamide Content and Volatile Profiles in Two Cultivars of(L.) R.K. Jansen Grown in Aquaponics.

Study

The study assessed the alkylamide content and volatile profiles of two jambù cultivars grown in aquaponic and hydroponic systems. It found that aquaponics yielded plants with high alkylamide content, comparable to hydroponics, supporting the feasibility of eco-friendly cultivation methods.

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2025·Microbial pathogenesis·Aline G Silva, Renata P Costa, Yohana P Calegari-Alves, et al

Spilanthol from Acmella oleracea (L.) R. K. Jansen induces metabolic alterations and impair an important virulence factor in Cryptococcus neoformans.

In vitroImmunity

The study investigates spilanthol from Acmella oleracea for its antifungal properties against Cryptococcus neoformans. Spilanthol induced metabolic and morphological alterations, oxidative stress, and suppressed the virulence factor urease, suggesting potential as a novel therapeutic strategy.

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2025·International journal of biological macromolecules·Júlia Bertolini Fajardo, Mariana Hauck Vianna, Ana Barbara Polo, et al

Development and in vitro biological characterization of chitosan films loaded with the Acmella oleracea leaves extract for wound healing application.

In vitroSkin Hair Health

The study developed chitosan films incorporating methanol-based extract of Acmella oleracea for wound healing applications. The films showed significant swelling capacity, moisture content, structural homogeneity, non-toxicity, strong free radical scavenging, anti-inflammatory effects, suppressed bacterial growth, and increased cell migration in vitro.

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2024·Archives of dermatological research·Rabia Oztas Kara, Bahar Sevimli Dikicier, Berna Solak, et al

Investigation of the in-vitro lethal effect of spilanthol on demodex and finding the most effective dose.

In vitron = 70

In vitro study investigating the anti-demodex potential of spilanthol, derived from Spilanthes Acmella, by determining the minimal effective dose. Spilanthol at concentrations of 3%, 4%, and 5% showed similar acaricidal effects to 5% permethrin, with no additional effect at higher doses.

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2024·Journal of ethnopharmacology·Júlia Bertolini Fajardo, Mariana Hauck Vianna, Ana Barbara Polo, et al

Insights into the bioactive potential of the Amazonian species Acmella oleracea leaves extract: A focus on wound healing applications.

In vitroSkin Hair Health Inflammation

The study characterized the phytochemical composition of Acmella oleracea leaves extract and investigated its antioxidant, anti-inflammatory, antimicrobial, and wound healing potential. The extract showed strong anti-inflammatory and antioxidant activities, reduced biofilm adhesion, and enhanced fibroblast migration, indicating promising applications in wound treatment.

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2024·Journal of ethnopharmacology·Danilo de Souza Costa, Rayssa A Cajas, Carla Monteiro Leal, et al

Efficacy of spilanthol and Acmella oleracea (L.) R. K. Jansen (Asteraceae) extract against Schistosoma mansoni infection.

In vitro

The study evaluated the antiparasitic properties of Acmella oleracea extract and spilanthol against Schistosoma mansoni. In vitro and in vivo assays showed that both substances caused mortality of adult schistosomes and reduced worm burden in murine models. Spilanthol also significantly decreased egg burden and reduced hepato- and splenomegaly.

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2024·Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas·C A Priante-Silva, B H Godoi, R F Menegon, et al

Antitumor activity of membranes associated with Acmella oleracea extract.

In vitro

The study developed a biomaterial from chitosan and Acmella oleracea extracts to evaluate its antitumor activity against the HEp-2 tumor cell line. The chitosan membranes exhibited cytotoxic action, significantly reducing cell density and mitochondrial activity, and preventing wound closure in cell monolayers.

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2024·Frontiers in pharmacology·Antimo Fusco, Michela Perrone, Federica Ricciardi, et al

Combiningandextracts: a novel pharmacological approach in inflammatory vestibulodynia.

Animal studyInflammation

Animal study inducing vulvodynia-like symptoms in female mice using CFA, followed by treatment with Acmella oleracea and Boswellia serrata extracts. The combination significantly reduced vulvar hypersensitivity, spinal microgliosis, and neuronal overexcitation, suggesting potential for treating vulvodynia-associated pain.

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2024·Veterinary parasitology·Luis Adriano Anholeto, Guilherme Andrade Brancaglion, Danilo Martins Dos Santos, et al

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

In vitro

The study evaluated the acaricidal activity of ANESPSAT, a synthetic spilanthol derivative, and its nanoformulation against Rhipicephalus microplus and Amblyomma sculptum ticks. ANESPSAT showed high efficacy, killing 97% of R. microplus larvae at 0.5 mg/mL and achieving over 98% efficacy against engorged females. The nanoemulsion with ANESPSAT prevented egg laying and achieved 100% efficacy at 2.5 mg/mL.

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2023·Gels (Basel, Switzerland)·Aqsa Afzal, Syed Nisar Hussain Shah, Hina Javed, et al

Extract-Based Natural Oils Loaded Emulgel for Anti-Microbial Action against Dermatitis.

In vitroSkin Hair Health

The study developed a herbal emulgel containing spilanthol and olive oil for treating bacterial skin infections. The F4 formulation showed 100% antibacterial activity and produced the greatest zone of inhibition among all formulations.

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2023·Evidence-based complementary and alternative medicine : eCAM·Emanuelle T Rodrigues, Paulo Peretti, Roberto M Bezerra, et al

Pharmacological Characteristics of the Hydroethanolic Extract of(L) R. K. Jansen Flowers: ADME/ToxandAntihypertensive and Chronic Toxicity Evaluation.

Animal study

The study evaluated the pharmacological characteristics of the hydroethanolic extract of jambu flowers, focusing on ADME/Tox and antihypertensive effects in male spontaneously hypertensive and Wistar rats. Spilanthol was identified as the major compound. The extract was found safe at 100 mg/kg with no significant impact on blood pressure or toxic effects.

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2023·Natural product research·Mayra Suelen da S Pinheiro, Daniele A Moysés, Natasha C R Galucio, et al

Cytotoxic and molecular evaluation of spilanthol obtained from(L.) R. K. Jansen (jambu) in human gastric cancer cells.

In vitro

The study evaluated the effects of hydroethanolic extract of jambu and its active compound spilanthol on gastric cancer cells. Both the extract and spilanthol exhibited cytotoxicity against cancer cells, and molecular docking showed spilanthol's inhibitory potential for JAK1 and JAK2 proteins.

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2023·Phytotherapy research : PTR·Serena Boccella, Consalvo Mattia, Michela Perrone, et al

Synergistic effects of Boswellia serrata and Acmella oleracea extract combination for treating neuropathic pain in a preclinical model of spared nerve injury.

Study

The paper studies the synergistic effects of a combination of Boswellia serrata and Acmella oleracea extracts for treating neuropathic pain in a preclinical model of spared nerve injury.

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2022·Brazilian journal of biology = Revista brasleira de biologia·M Leite, H Tercya, B G Nascimento, et al

Anesthesia or seizure-like behavior? The effects of two Amazonian plants, Acmella oleracea and Piper alatabaccum in zebrafish (Danio rerio).

Animal study

The study tested crude ethanolic extracts from Acmella oleracea and Piper alatabaccum for anesthesia in zebrafish. While A. oleracea leaf extract showed potential for fish anesthesia, the flower extract and P. alatabaccum leaf extract induced seizure-like behavior and even death in some fish, highlighting potential neurotoxic effects.

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2022·Fitoterapia·Jorge Luiz Dallazen, Bruna Barbosa da Luz, Daniele Maria-Ferreira, et al

Local effects of natural alkylamides from Acmella oleracea and synthetic isobutylalkyl amide on neuropathic and postoperative pain models in mice.

Animal studyInflammation

The study evaluated the local effects of alkylamides from Acmella oleracea and synthetic isobutylalkyl amide on neuropathic and postoperative pain models in mice. Intraplantar administration of the hexanic fraction (HF) rich in alkylamides reduced mechanical and cold allodynia, as well as improved digital gait parameters. HF was effective on both neuropathic and postoperative pain, while IBA only partially reduced mechanical allodynia.

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2022·Journal of pharmaceutical and biomedical analysis·Maria Bellumori, Beatrice Zonfrillo, Valentina Maggini, et al

Acmella oleracea (L.) R.K. Jansen: Alkylamides and phenolic compounds in aerial parts and roots of in vitro seedlings.

In vitro

The study evaluated alkylamides and phenolic compounds in aerial parts and roots of Acmella oleracea seedlings grown in vitro. Spilanthol was prevalent in the aerial parts, especially in seedlings from regenerating lines, while roots showed higher total phenols.

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2021·Neurochemistry international·Wilasinee Suwanjang, Waralee Ruankham, Banthit Chetsawang, et al

Spilanthes acmella Murr. ameliorates chronic stress through improving mitochondrial function in chronic restraint stress rats.

Animal studyStress Brain Health

The study investigated the effects of Spilanthes acmella Murr. extract on mitochondrial dynamics in chronic restraint stress rats. The extract reduced mitochondrial fission protein expression and induced HSP60, MnSOD, and ATPsynthase in the hippocampus, reversing depressive symptoms in the forced swim test.

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2021·Medical mycology·Rodrigo L Fabri, Jhamine C O Freitas, Ari S O Lemos, et al

Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis.

In vitroWomens Health Inflammation

The study evaluated the antifungal activity of spilanthol against Candida albicans, a multidrug-resistant fungal strain. Spilanthol showed significant inhibitory effects on yeast cell membrane and cell wall integrity, reducing fungal growth and biofilm proliferation. Infected rats treated with spilanthol showed reduced fungal burden and inflammation, suggesting its potential for treating vulvovaginal candidiasis.

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2021·Microscopy research and technique·Selma Delgado de Souza Moro, Lucas de Oliveira Fujii, Luis Felipe Rodrigues Teodoro, et al

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

Animal studyJoint Bone Health

Animal study on the effect of Acmella oleracea extract on collagen content and organization in partially transected tendons of male Lewis rats. Topical application of 20% A. oleracea ointment increased collagen concentration and organization, suggesting potential for tendon repair.

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2025·Plants (Basel, Switzerland)·Ana Paula de Souza E Silva, Flávia Cristina Seabra Pires, Maria Caroline Rodrigues Ferreira, et al

Antiarrhythmic Effects of Supercritical Extract ofin Rats: Electrophysiological Evidence and Cardioprotective Potential.

Animal studyHeart Health

The study evaluated the electrophysiological and antiarrhythmic effects of a supercritical extract of spilanthol in rats. The extract showed dose-dependent antiarrhythmic effects, maintaining sinus rhythm and reducing heart rate and R-R interval, comparable to lidocaine.

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2025·Nutrients·Valentina Ferrara, Beatrice Zonfrillo, Maria Bellumori, et al

Neuroprotective Potential ofAerial Parts and Root Extracts: The Role of Phenols and Alkylamides Against Neuropathic Pain.

Animal studyBrain Health

The study investigated the neuroprotective potential of aerial parts and root extracts containing spilanthol, phenolic acids, and glycosylated flavonoids against chemotherapy-induced neuropathic pain. Both extracts reduced mortality and cytotoxicity, enhanced SOD activity, and alleviated neuropathic pain in mice, suggesting their potential in alleviating chemotherapy-induced neuropathy.

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2024·International journal of cosmetic science·Wang Feifei, Su Wenrou, Sun Jinyue, et al

Anti-ageing mechanism of topical bioactive ingredient composition on skin based on network pharmacology.

In vitroSkin Hair Health

The study investigates the anti-ageing mechanism of a composition containing eight ingredients, including Spilanthol from Acmella oleracea extract, using network pharmacology and in vitro experiments. The composition promotes fibroblast proliferation, collagen and elastin production, and inhibits ROS in skin cells, suggesting potential anti-wrinkle effects.

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2023·Chemistry & biodiversity·Maria Beatriz Viana Dos Santos, Douglas Costa Gontijo, Maria Fernanda Alves do Nascimento, et al

In Vitro and in Vivo Antimalarial Activity, Cytotoxicity and Phytochemical HRMSProfile of Plants from the Western Pará State, Brazilian Amazonia.

In vitro

The study assessed the in vitro antiplasmodial activity and cytotoxicity of ethanol extracts from 11 plants against chloroquine-resistant Plasmodium falciparum and in vivo antimalarial activity against Plasmodium berghei in mice. Acmella oleracea, Siparuna krukovii, and Trema micrantha showed significant parasite growth inhibition, with A. oleracea being the most promising for antimalarial phytomedicine development.

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