Correction: Casili et al. Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC). Cancers 2023, 15, 2796.

In the original publication [...].

Rebalancing NOX2/Nrf2 to limit inflammation and oxidative stress across gut-brain axis in migraine.

Migraine is one of the most common neurological illnesses, and it is characterized by complicated neurobiology. It was confirmed the influence of inflammation and oxidative stress in migraines and also in distal organs such as the intestine. Indeed, the constant bidirectional communication between the Central Nervous System (CNS) and the gastrointestinal (GI) tract, known as the gut-brain axis, has become an attractive target involved in different human disorders. Herein, we explored the role of NADPH oxidase 2 (NOX2) in nitroglycerin (NTG)-induced migraine in mice models to discover the mechanism by which, during migraine attack, oxidative stress is sustained within trigeminal neurons and GI. Considering the inverse relationship between NOX2 and Nrf2, Nrf2 upregulation seems to be a promising approach to decrease NOX2 expression and consequently limit oxidative stress and inflammation spread in neurological and non-neurological diseases. With this aim, we exploited tempol's Nrf2-inducer ability to better understand the involvement of Nrf2/NOX2 axis in migraine and associated GI comorbidities. Behavioral tests confirmed that tempol, in a dose-dependent manner, moderated clinical signs of migraine and abdominal pain. Moreover, we demonstrated that the decrease in migraine-related symptomatology was strongly linked to the modulation of Nrf2/NOX2 signaling pathway in the brain and colon. In the brain, the rebalancing of Nrf2/NOX2 prevented neuronal loss, decreased glia reactivity while inhibiting NF-κB and NLRP3 inflammasome activation. In the colon, Nrf2 upregulation and consequent NOX2 decrease reduced the histological damage, mast cells infiltration as well as tumor necrosis factor (TNF)-α and interleukin (IL)-1ß release. Furthermore, the attenuation of inflammation and oxidative stress led to the restoration of the intestinal barrier through TJs replacement. Taken as a whole, data suggested that the regulation of Nrf2/NOX2 balance is a successful way to reduce neurological and related intestinal impairments during migraine and could be of relevance for migraine-like attacks in humans.

Efficacy of an oral suspension containing xyloglucan and pea proteins on a murine model of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most common foregut disease, affecting about 20% of the adult population. Esophageal epithelial barrier plays a fundamental role in the pathophysiology of GERD; however, pharmacological therapies mainly aim to reduce the acidity of the gastroesophageal environment rather than to protect esophageal tissue integrity. This study aims to evaluate the efficacy of an oral solution containing xyloglucan and pea proteins (XP) in reestablishing gastroesophageal tissue integrity and biochemical markers. To induce GERD, C57BL/6 mice were alternatively overfed and fasted for 56 days and then treated with XP, sodium alginate, omeprazole, or omeprazole+XP twice daily for 7 days. Gastric pain and inflammatory markers were evaluated after 3 and 7 days of treatment. After sacrifice, the esophagi and stomachs were surgically removed for macroscopic and histological examination. Gastric pain was significantly reduced at days 3 and 7 by XP, omeprazole, and omeprazole+XP, while alginates were ineffective at day 3. XP was able to diminish gastric macroscopic damage and demonstrated the same efficacy as omeprazole in reducing esophageal damage. XP significantly reduced histological damage, with an efficacy comparable to that of omeprazole, but superior to alginates. Inflammatory markers were significantly reduced by XP, with superior efficacy compared with alginates at day 7. Interestingly, XP was also able to significantly increase gastric pH. This study demonstrated that XP restored gastric homeostasis, improved esophageal integrity, and decreased inflammation and pain with a similar efficacy to omeprazole and greater than alginates.

Evaluation of the nutraceutical Palmitoylethanolamide in reducing intraocular pressure (IOP) in patients with glaucoma or ocular hypertension: a systematic review and meta-analysis.

Intraocular pressure (IOP) positively correlates with both normal and high-tension glaucoma. To date, IOP targeting remains the validated pharmacological approach in counteracting glaucoma progression as well as in halting vision loss. Among the different adjuvant compounds, evidence highlighted the potential effectiveness of Palmitoylethanolamide (PEA), an endogenous fatty acid amide. Thus, a systematic review of the literature was conducted, thoroughly evaluating PEA treatment regimen in decreasing IOP in patients with eye disorders. We checked for articles across the scientific databases Pubmed (MEDLINE), Embase (OVID), and Web of Science from the inception to 30 August 2023, and a total of 828 articles were recovered. Six of these studies (199 patients) were included in the systematic review after the study selection process, and three studies for meta-analysia. Overall, PEA showed significant efficacy in reducing IOP in patients, this encourages its clinical use in glaucoma as well as across different forms of eye disorders.

bFGF-like Activity Supported Tissue Regeneration, Modulated Neuroinflammation, and Rebalanced Ca2+ Homeostasis following Spinal Cord Injury.

A spinal cord injury (SCI) is a well-defined debilitating traumatic event to the spinal cord that usually triggers permanent changes in motor, sensory, and autonomic functions. Injured tissue becomes susceptible to secondary mechanisms caused by SCIs, which include pro-inflammatory cytokine release, the activation of astrocytes and microglia, and increased neuronal sensibility. As a consequence, the production of factors such as GFAP, IBA-1, TNF-α, IL-1ß, IFN-γ, and S100-ß slow down or inhibit central nervous system (CNS) regeneration. In this regard, a thorough understanding of the mechanisms regulating the CNS, and specifically SCI, is essential for the development of new therapeutic strategies. It has been demonstrated that basic fibroblast growth factor (bFGF) was successful in the modulation of neurotrophic activity, also promoting neurite survival and tissue repair, thus resulting in the valuable care of CNS disorders. However, bFGF therapeutic use is limited due to the undesirable effects developed following its administration. Therefore, the synthetic compound mimetic of bFGF, SUN11602 (with chemical name 4-[[4-[[2-[(4-Amino-2,3,5,6-tetramethylphenyl)amino]acetyl]methylamino]-1-piperidinyl]methyl]benzamide), has been reported to show neuroprotective activities similar to those of bFGF, also demonstrating a good pharmacokinetic profile. Here, we aimed to investigate the neuroprotective activity of this bFGF-like compound in modulating tissue regeneration, neuroinflammation, and Ca2+ overload by using a subacute mouse model of SCI. SUN11602 (1, 2.5, and 5 mg/kg) was administered orally to mice for 72 h daily following the in vivo model of SCI, which was generated by the extradural compression of the spinal cord. The data obtained demonstrated that SUN11602 treatment considerably decreased motor alteration and diminished the neuroinflammatory state through the regulation of glial activation, the NF-κB pathway, and kinases. Additionally, by controlling Ca2+-binding proteins and restoring neurotrophin expression, we showed that SUN11602 therapy restored the equilibrium of the neuronal circuit. Because of these findings, bFGF-like compounds may be an effective tool for reducing inflammation in SCI patients while enhancing their quality of life.

An RNAi-Mediated Reduction in Transcription Factor Nrf-2 Blocks the Positive Effects of Dimethyl Fumarate on Metabolic Stress in Alzheimer's Disease.

The prevalence of obesity is rapidly rising around the world, and this will have a significant impact on our society as it is believed to be one of the leading causes of death. One of the main causes of these occurrences is added sugar consumption, which is associated with a higher risk of obesity, heart disease, diabetes, and brain illnesses such as Alzheimer's disease (AD). To this purpose, excess sugar might worsen oxidative damage and brain inflammation: two neuropathological signs of AD. Dimethyl fumarate (DMF) is an orally accessible methyl ester of fumaric acid with putative neuroprotective and immunomodulatory properties. In addition, DMF stimulates the nuclear factor erythroid 2-related factor 2 (Nrf-2), a key regulator of the antioxidant response mechanism in cells. The aim of the current study was to assess the potential therapeutic benefits of DMF in an in vitro model of metabolic stress induced by high and low sugar levels. We discovered that DMF reversed the negative impacts of high and low glucose exposure on the viability and oxidative stress of SH-SY5Y cells. Mechanistically, DMF's actions were mediated by Nrf-2. To this end, we discovered that DMF boosted the expression of the Nrf-2-regulated genes heme-oxygenase-1 (HO1) and manganese superoxide dismutase (MnSOD). More importantly, we found that inhibiting Nrf-2 expression prevented DMF's positive effects. Our combined findings suggest that DMF may be a valuable support for treatments for metabolic diseases.

Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC).

Oral squamous cell carcinoma (OSCC) is a commonly occurring head and neck cancer and it is characterized by a high metastasis grade. The aim of this study was to evaluate for the first time the effect of BAY-117082, a selective NLRP3 inflammasome inhibitor, in an in vivo orthotopic model of OSCC and its role in the invasiveness and metastasis processes in neighbor organs such as lymph node, lung, and spleen tissues. Our results demonstrated that BAY-117082 treatment, at doses of 2.5 mg/kg and 5 mg/kg, was able to significantly reduce the presence of microscopic tumor islands and nuclear pleomorphism in tongue tissues and modulate the NLRP3 inflammasome pathway activation in tongue tissues, as well as in metastatic organs such as lung and spleen. Additionally, BAY-117082 treatment modulated the epithelial-mesenchymal transition (EMT) process in tongue tissue as well as in metastatic organs such as lymph node, lung, and spleen, also reducing the expression of matrix metalloproteinases (MMPs), particularly MMP2 and MMP9, markers of cell invasion and migration. In conclusion, the obtained data demonstrated that BAY-117082 at doses of 2.5 mg/kg and 5 mg/kg were able to reduce the tongue tumor area as well as the degree of metastasis in lymph node, lung, and spleen tissues through the NLRP3 inflammasome pathway inhibition.

Neuroprotective effects of GSK-343 in an in vivo model of MPTP-induced nigrostriatal degeneration.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic nigrostriatal neurons, which causes disabling motor disorders. Scientific findings support the role of epigenetics mechanism in the development and progression of many neurodegenerative diseases, including PD. In this field, some studies highlighted an upregulation of Enhancer of zeste homolog 2 (EZH2) in the brains of PD patients, indicating the possible pathogenic role of this methyltransferase in PD. The aim of this study was to evaluate the neuroprotective effects of GSK-343, an EZH2 inhibitor, in an in vivo model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degeneration. Specifically, nigrostriatal degeneration was induced by MPTP intraperitoneal injection. GSK-343 was administered intraperitoneally daily at doses of 1 mg/kg, 5 mg/kg and 10 mg/kg, mice were killed 7 days after MPTP injection. Our results demonstrated that GSK-343 treatment significantly improved behavioral deficits and reduced the alteration of PD hallmarks. Furthermore, GSK-343 administration significantly attenuated the neuroinflammatory state through the modulation of canonical and non-canonical NF-κB/IκBα pathway as well as the cytokines expression and glia activation, also reducing the apoptosis process. In conclusion, the obtained results provide further evidence that epigenetic mechanisms play a pathogenic role in PD demonstrating that the inhibition of EZH2, mediated by GSK-343, could be considered a valuable pharmacological strategy for PD.

The Transcription Factor Nrf2 Mediates the Effects of Antrodia camphorata Extract on Neuropathological Changes in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a disorder that is characterized by progressive and selective neuronal injury and cell death. Recent studies have provided accumulating evidence for a significant role of the immune system and neuroinflammation in PD pathogenesis. On this basis, many scientific articles have highlighted the anti-inflammatory and neuroprotective properties of Antrodia camphorata (AC), an edible fungus containing various bioactive compounds. This study aimed to evaluate the inhibitory effect of AC administration on neuroinflammation and oxidative stress in a murine model of MPTP-induced dopaminergic degeneration. AC (10, 30, 100 mg/kg) was administered daily by oral gavage starting 24 h after the first administration of MPTP, and mice were sacrificed 7 days after MPTP induction. In this study, treatment with AC significantly reduced the alteration of PD hallmarks, increasing tyrosine hydroxylase expression and reducing the number of alpha-synuclein-positive neurons. In addition, AC treatment restored the myelination process of neurons associated with PD and attenuated the neuroinflammatory state. Furthermore, our study demonstrated that AC was able to reduce the oxidative stress induced by MPTP injection. In conclusion, this study highlighted that AC could be a potential therapeutic agent for the treatment of neurodegenerative disorders such as PD.

The Role of miR-128 in Neurodegenerative Diseases.

Several neurodegenerative disorders are characterized by the accumulation of misfolded proteins and are collectively known as proteinopathies. Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) represent some of the most common neurodegenerative disorders whose steady increase in prevalence is having a major socio-economic impact on our society. Multiple laboratories have reported hundreds of changes in gene expression in selective brain regions of AD, PD, and HD brains. While the mechanisms underlying these changes remain an active area of investigation, alterations in the expression of noncoding RNAs, which are common in AD, PD, and HD, may account for some of the changes in gene expression in proteinopathies. In this review, we discuss the role of miR-128, which is highly expressed in mammalian brains, in AD, PD, and HD. We highlight how alterations in miR-128 may account, at least in part, for the gene expression changes associated with proteinopathies. Indeed, miR-128 is involved, among other things, in the regulation of neuronal plasticity, cytoskeletal organization, and neuronal death, events linked to various proteinopathies. For example, reducing the expression of miR-128 in a mouse model of AD ameliorates cognitive deficits and reduces neuropathology. Overall, the data in the literature suggest that targeting miR-128 might be beneficial to mitigate the behavioral phenotype associated with these diseases.

Role of Basic Fibroblast Growth Factor in Cancer: Biological Activity, Targeted Therapies, and Prognostic Value.

Cancer is the leading cause of death worldwide; thus, it is necessary to find successful strategies. Several growth factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), and transforming growth factor beta (TGF-ß), are involved in the main processes that fuel tumor growth, i.e., cell proliferation, angiogenesis, and metastasis, by activating important signaling pathways, including PLC-γ/PI3/Ca2+ signaling, leading to PKC activation. Here, we focused on bFGF, which, when secreted by tumor cells, mediates several signal transductions and plays an influential role in tumor cells and in the development of chemoresistance. The biological mechanism of bFGF is shown by its interaction with its four receptor subtypes: fibroblast growth factor receptor (FGFR) 1, FGFR2, FGFR3, and FGFR4. The bFGF-FGFR interaction stimulates tumor cell proliferation and invasion, resulting in an upregulation of pro-inflammatory and anti-apoptotic tumor cell proteins. Considering the involvement of the bFGF/FGFR axis in oncogenesis, preclinical and clinical studies have been conducted to develop new therapeutic strategies, alone and/or in combination, aimed at intervening on the bFGF/FGFR axis. Therefore, this review aimed to comprehensively examine the biological mechanisms underlying bFGF in the tumor microenvironment, the different anticancer therapies currently available that target the FGFRs, and the prognostic value of bFGF.

Inhibition of LRRK2 Attenuates Depression-Related Symptoms in Mice with Moderate Traumatic Brain Injury.

Moderate traumatic brain injury (mTBI) has been associated with emotional dysregulation such as loss of consciousness, post-traumatic amnesia and major depressive disorder. The gene Leucine-rich repeat kinase 2 (LRRK2) is involved in protein synthesis and degradation, apoptosis, inflammation and oxidative stress, processes that trigger mTBI. The aim of this study was to investigate the role of LRRK2 in reducing depression-related symptoms after mTBI and to determine whether inhibition of LRRK2 mediated by PF-06447475 could have antidepressant effects. Moderate traumatic brain injury was induced by controlled cortical impact (CCI) and mice were treated with PF-06447475 at doses of 1, 2.5 and 5 mg/kg once daily for 14 days. We performed histological, immunohistochemical and molecular analyses of brain tissue 24 days after mTBI. Furthermore, the tissue changes found in the hippocampus and amygdala confirmed the depression-like behavior. PF-treatment with 06447475 significantly reduced the histological damage and behavioral disturbances. Thus, this study has shown that mTBI induction promotes the development of depression-like behavioral changes. LRRK2 inhibition showed an antidepressant effect and restored the changes in the copper/glutamate/N-methyl-D-aspartic acid receptor (Cu/NMDAR) system.

Recent Emerging Immunological Treatments for Primary Brain Tumors: Focus on Chemokine-Targeting Immunotherapies.

Primary brain tumors are a leading cause of death worldwide and are characterized by extraordinary heterogeneity and high invasiveness. Current drug and radiotherapy therapies combined with surgical approaches tend to increase the five-year survival of affected patients, however, the overall mortality rate remains high, thus constituting a clinical challenge for which the discovery of new therapeutic strategies is needed. In this field, novel immunotherapy approaches, aimed at overcoming the complex immunosuppressive microenvironment, could represent a new method of treatment for central nervous system (CNS) tumors. Chemokines especially are a well-defined group of proteins that were so named due to their chemotactic properties of binding their receptors. Chemokines regulate the recruitment and/or tissue retention of immune cells as well as the mobilization of tumor cells that have undergone epithelial-mesenchymal transition, promoting tumor growth. On this basis, this review focuses on the function and involvement of chemokines and their receptors in primary brain tumors, specifically examining chemokine-targeting immunotherapies as one of the most promising strategies in neuro-oncology.

Effect of a combination of pea protein, grape seed extract and lactic acid in an in vivo model of bacterial vaginosis.

Bacterial vaginosis (BV) is a common vaginal dysbiosis characterized by a malodorous discharge and irritation. The imbalance of the vaginal microbiota plays a key role in the development of BV. It has been demonstrated that Gardnerella vaginalis (GV), a facultative anaerobic bacillus, is involved in BV. Due to the rising number of antimicrobial-resistant species, recurrence of BV is becoming more frequent in women; thus, alternative treatments to antibiotics are needed. Natural substances have recently shown a great efficacy for the treatment of vaginal dysbiosis. Thus, this study aimed to investigate the beneficial effect of a product containing pea protein (PP), grape seed extract (GS) and lactic acid (LA) in an in vivo model of Gardnerella vaginalis-induced vaginosis by intravaginal administration of GV suspension (1 × 106 CFU/20 µL saline). Our results demonstrated that the product containing PP, GS and LA significantly reduced GV proliferation. More specifically, it significantly preserved tissue architecture and reduced neutrophil infiltration, inflammatory markers and sialidase activity when used both as a pre- or a post-treatment. Moreover, the product displayed strong bioadhesive properties. Therefore, our data suggested that the product containing PP, GS and LA could be used as alternative preventive or curative treatment for the management of BV.

Evaluation of the Efficacy of Xyloglucan, Pea Protein and Opuntia ficus-indica Extract in a Preclinical Model of Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by epidermal gene abnormalities, epidermal barrier defects and inflammation. Corticosteroids are considered to be standard treatments, but often come with side effects and lose efficacy with long-term use. Alternative treatments targeting the epidermal barrier defect are needed to manage the disease. Film-forming substances such as xyloglucan, pea protein and Opuntia ficus-indica extract (XPO) have generated interest for their ability to restore skin barrier integrity and may pose an alternative approach to disease management. Thus, the aim of this two-part study was to evaluate the barrier-protective properties of a topical cream containing XPO on the membrane permeability of keratinocytes exposed to inflammatory conditions and compare its efficacy to dexamethasone (DXM) in an in vivo model of psoriasis-like dermatitis. XPO treatment significantly reduced S. aureus adhesion, subsequent skin invasion and restored epithelial barrier function in keratinocytes. Furthermore, the treatment restored the integrity of keratinocytes, reducing tissue damage. In mice with psoriasis-like dermatitis, XPO significantly reduced erythema, inflammatory markers and epidermal thickening with a superior efficacy to dexamethasone. Given the promising results, XPO may represent a novel steroid-sparing therapeutic for epidermal-related diseases such as psoriasis, thanks to its ability to preserve skin barrier function and integrity.

Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial-Mesenchymal Transition.

Oral squamous cell carcinoma (OSCC) is a common human tumor, that originates from buccal mucosa and the tongue, associated with a high mortality rate. Currently, the treatment for OSCC involves surgery, chemotherapy and radiotherapy; however, survival outcomes for OSCC patients remain poor. For this reason, it is necessary to investigate new therapeutic strategies to counteract the progression of OSCC. In this study, we aimed to evaluate the role of dimethyl fumarate (DMF) in modulation of OSCC progression, both in vitro and in an in vivo orthotopic xenograft model. In vitro results revealed that DMF was able to reduce the expression of anti-apoptotic factors as BCL-2 and increased the expression of pro-apoptotic factors as Bax, Caspase-3 and BID. DMF appears to be involved in the modulation of oxidative stress mediators, such as MnSOD and HO-1. Furthermore, DMF showed to reduce the migratory ability of tumor cells and to modulate the expression of markers of epithelial-mesenchymal transition (EMT), as N-cadherin and E-cadherin. The in vivo study confirmed the data obtained in vitro significantly decreasing tumor mass and also reducing oxidative stress and apoptosis. Therefore, based on these results, the use of DMF could be considered a promising strategy to counteract oral cancer progression.

Overview on Common Genes Involved in the Onset of Glioma and on the Role of Migraine as Risk Factor: Predictive Biomarkers or Therapeutic Targets?

Gliomas are relatively rare but fatal cancers, and there has been insufficient research to specifically evaluate the role of headache as a risk factor. Nowadays, gliomas are difficult to cure due to the infiltrative nature and the absence of specific adjuvant therapies. Until now, mutations in hundreds of genes have been identified in gliomas and most relevant discoveries showed specific genes alterations related to migraine as potential risk factors for brain tumor onset. Prognostic biomarkers are required at the time of diagnosis to better adapt therapies for cancer patients. In this review, we aimed to highlight the significant modulation of CLOCK, BMLA1 and NOTCH genes in glioma onset and development, praising these genes to be good as potentially attractive therapeutic markers for brain tumors. A improved knowledge regarding the role of these genes in triggering or modulating glioma maybe the key to early diagnosing brain tumor onset in patients affected by a simple headache. In addition, investigating on these genes we can suggest potential therapeutic targets for treating brain tumors. These considerations open up the possibility of personalized treatments that can target each brain tumor's specific genetic abnormality.

Protein Kinase Inhibitors as a New Target for Immune System Modulation and Brain Cancer Management.

High-grade brain tumors are malignant tumors with poor survival and remain the most difficult tumors to treat. An important contributing factor to the development and progression of brain tumors is their ability to evade the immune system. Several immunotherapeutic strategies including vaccines and checkpoint inhibitors have been studied to improve the effectiveness of the immune system in destroying cancer cells. Recent studies have shown that kinase inhibitors, capable of inhibiting signal transduction cascades that affect cell proliferation, migration, and angiogenesis, have additional immunological effects. In this review, we explain the beneficial therapeutic effects of novel small-molecule kinase inhibitors and explore how, through different mechanisms, they increase the protective antitumor immune response in high-grade brain tumors.

The Pivotal Role of Protein Phosphatase 2A (PP2A) in Brain Tumors.

Protein phosphatase 2A (PP2A) is a highly complex heterotrimeric Ser/Thr phosphatase that regulates many cellular processes. PP2A is dysregulated in several human diseases, including oncological pathology; interestingly, PP2A appears to be essential for controlling cell growth and may be involved in cancer development. The role of PP2A as a tumor suppressor has been extensively studied and reviewed. To leverage the potential clinical utility of combination PP2A inhibition and radiotherapy treatment, it is vital that novel highly specific PP2A inhibitors be developed. In this review, the existing literature on the role of PP2A in brain tumors, especially in gliomas and glioblastoma (GBM), was analyzed. Interestingly, the review focused on the role of PP2A inhibitors, focusing on CIP2A inhibition, as CIP2A participated in tumor cell growth by stimulating cell-renewal survival, cellular proliferation, evasion of senescence and inhibition of apoptosis. This review suggested CIP2A inhibition as a promising strategy in oncology target therapy.

A New Approach for the Treatment of Recurrent Vulvovaginal Candidiasis with a Combination of Pea Protein, Grape Seed Extract, and Lactic Acid Assessed In Vivo.

BACKGROUND: Vulvovaginal candidiasis (VVC) is considered the second most common vaginal infection. Up to 8% of women in various populations experience more than three or four episodes within one year, which is regarded as recurrent vulvovaginal candidiasis (RVVC). Current therapies involve antifungal drugs that provide static effects but do not prevent recurrences due to increased antimicrobial resistance; thus, alternative therapies to antifungals are needed to prevent RVVC. METHODS: A murine model of Candida albicans-induced RVVC was performed to evaluate the efficacy of a topical product containing pea protein (PP), grape seed extract (GS), and lactic acid (LA) to treat recurrent infections. Mice were inoculated with three separate vulvovaginal infections of 5 × 104 cells/mL C. albicans, and histological evaluation, a myeloperoxidase (MPO) assay. and an ELISA kit for Prostaglandin E2 (PGE2) on vaginal tissues were performed. RESULTS: The data obtained highlighted that the combination of PP, GS, and LA significantly preserved vaginal tissue architecture and prevented vaginal inflammation, proving its efficacy for the management of RVVC. Moreover, the combination of PP, GS, and LA notably increased azole efficacy by adding a new mechanism of action when administered concomitantly. CONCLUSION: Taken together, results demonstrated that the treatment with a combination of PP, GS, and LA is able to reduce the adhesion of C. albicans.