Therapeutic Potential of Solenopsis invicta Venom: A Scoping Review of Its Bioactive Molecules, Biological Aspects, and Health Applications

Abstract

Solenopsis invicta, a South American ant species from the Formicidae family (subfamily Myrmicinae), has recently established a stable settlement in Europe, raising public health concerns due to its venomous stings. The venom of S. invicta is rich in bioactive molecules, particularly piperidine alkaloids such as solenopsin A and peptides (Sol 1-4). These compounds have been implicated in various health applications, including antimicrobial, anti-inflammatory, and antitumour activities. While previous reviews have focused on the ecological and allergenic risks posed by S. invicta, this scoping review aims to evaluate the potential therapeutic uses of S. invicta venom by summarizing existing scientific evidence and providing a novel synthesis of recent research on its bioactive components. Furthermore, this study, by describing the unique biological aspects of S. invicta, provides an overview of its direct impact on public health, highlighting new findings on the venom's role in inhibiting bacterial biofilm formation and modulating cancer growth pathways through gene regulation. A search of databases (PubMed, Scopus, Science Direct, and Cochrane Library) identified 12,340 articles, from which 11 studies met the eligibility criteria. These studies included seven microbiological investigations and four studies on tumour cell lines and animal models. The findings suggest that S. invicta venom could inhibit biofilm formation, combat fungal infections, and suppress tumour growth. However, further research, including clinical trials, is required to fully elucidate the safety and efficacy of these bioactive molecules in human medicine, for their potential use in drug discovery to counteract several diseases, including cancer.

Keywords: RIFA; Solenopsis invicta; angiogenesis; antimicrobial; cancer; candida; drug discovery; head and neck squamous cell carcinomas (HNSCCs); tumour; venom.

Figure 1

Solenopsis invicta worker. The workers exhibit pronounced polymorphism [20], with lengths ranging from 1.5 mm to 4 mm, while the queens measure between 6 mm and 8 mm in length. The ant is identifiable by its reddish-brown colour with darker tones on the gaster and the presence of a stinger at the end of its gaster. Solenopsis invicta accumulates venom in its poison sac and convoluted gland, located within the abdomen, primarily near the stinger [21] (https://www.shutterstock.com/it/image-photo/red-imported-fire-ant-solenopsis-invicta-181051103 (access on 21 June 2024)) (in millimetre scale, 10 ≅ 1 mm).

Figure 2

Native Mediterranean ant species: Workers in a row of Crematogaster scutellaris on the trunk of Ailanthus altissima; photo taken by Mario Dioguardi and Diego Sovereto at the soil surrounding University of Foggia Dental Clinic, Italy. The impact on the ecosystem results in reduced native biodiversity with the potential to displace native ant species [34,35] and attacks other invertebrates [36], reducing their populations. This invasive species can also alter the physical and chemical properties of soils through structural modifications and nutrient accumulation during nest construction [37]. Moreover, they can cause damage to human infrastructure in urban areas, affecting sidewalks, cables, and wires.

Figure 3

Red imported fire ant (Solenopsis invicta): the bite and puncture lesion are highlighted. The area appears erythematous with the presence of edema (https://www.shutterstock.com/it/image-photo/red-imported-fire-ant-bite-solenopsis-1039911532 (access on 21 June 2024)). (In cementers scale, 1 ≅ 1 cm).

Figure 4

(A): Trans-2-Meth-6-undecyl piperidine (solenopsin A), (B): trans-2-methyl-6-tridecylpiperidine (solenopsin B), (C): trans-2-methyl-6-pentadecylpiperidine (solenopsin C); the figures of the molecules were obtained via the use of the online software https://chemicalize.com/app/calculation on 16 June 2024 starting from the IUPAC formula.

Figure 5

The entire selection and screening procedures are described in the PRISMA flowchart. The search was carried out from 1 September 2023 to 10 October 2023, with a final update of the records identified on 1 July 2024; in the yellow boxes, the number of records identified on EBSCO, Web Of Science, and LILACS as of 3 March 2024 are reported; in the grey boxes, the records identified on Google Scholar (using the keyword: Solenopsis invicta AND cancer) and on OPENGREY. DANS EASY Archive using the keyword “solenopsis” are reported.

Figure 6

Mechanistically, solenopsin has an in vitro selective inhibitory effect on AKT at concentrations of 20–30 μM; furthermore, it is hypothesized that solenopsin interrupts the interaction between IRS1 and the p85 regulatory subunit of PI3K and that it inhibits the activation of PDK1. IRS1 (insulin receptor substrate 1), PI3K (phosphoinositide 3-kinase), PDK1 (phosphoinositide-dependent kinase-1), AKT (protein kinase B), FOXO1A (Forkhead box protein O1).

Figure 7

Heatmap of relative abundance %. Data were extracted and estimated from Figure 2 of the study by Das et al. (2018) [101] using Python 3.13.0 and JupyterLab. These values pertain to the proteins “Sol i 2w,” “Sol i 4,” “Sol i 2q,” and “Sol i 2X1” found in the poison sacs of workers, queens, and alates.

Figure 8

Heatmap of relative abundance %. Data were extracted and estimated from Figure 3b and information reported in the study by Cai et al. (2022) [103]. The heatmap was generated using the extracted data with Python 3.13.0 and JupyterLab, and it pertains to the proteins and peptides in the Solenopsis invicta sample.