Respiratory and food allergy conditions are increasing internationally and the most commonly used drugs in these conditions are antihistamines, products that can interfere as histamine receptor antagonists. In accordance with the need to test new principals capable of developing fewer side effects, we preliminarily studied the therapeutic antihistamine effect in vitro and in vivo of an innovative nutraceutical blend based on Quercetin, Perilla frutescens, Boswellia serrata, Blackcurrant, Parthenium, Helichrysum, Lactobacillus acidophilus and Bifidobacterium animalis. The in vitro test demonstrated the interaction between the examined mixture and a rat leukemia cell line (RBL-2H3) widely used as a model simulating mast cells in immunological and allergological studies; this pre-clinical test demonstrated a statistically significant reduction in cell histamine degranulation (about 30%). The in vivo test demonstrated instead that the mixture interferes up to 30% in the development of histamine wheal. In addition, during the in vitro test, we also tested the effect of the mixture on allergic inflammation, so we evaluated the interference of the mixture on TNF alpha levels, determining a reduction in tested concentrations of about 13%.

The primary pathogenic mechanism of Type I hypersensitivity reactions involves histamine-mediated activation of the H1 receptor (H1R) and the subsequent signaling of the phospholipase C β-inositol trisphosphate (PLCβ-IP₃) pathway. The present study evaluates the in vitro efficacy of a novel nutraceutical mixture—Quercetin, Perilla frutescens, Boswellia serrata, Blackcurrant, Parthenium, Helichrysum, Lactobacillus Acidophilus (L. acidophilus) and Bifidobacterium animalis (B. animalis)—in modulating HRH1 gene expression and the activation of the intracellular second messenger inositol trisphosphate (IP₃). Quantitative PCR (qPCR) analysis revealed that the mixture downregulated HRH1 expression by approximately 33% (p < 0.05) compared to the control group. Furthermore, ELISA assays demonstrated that the mixture significantly reduced IP₃ release by 10.30% (p < 0.05 vs. positive control). These results indicate that the nutraceutical mixture exerts its effects by modulating the H1R-PLCβ-IP₃ pathway through the reduction in both H1 receptor gene expression and IP₃ release. These findings suggest a potential mechanism of action involving the modulation of the histamine H1 receptor. Consequently, the mixture emerges as a promising candidate for further investigation into the H1R-IP₃ activation cascade.

Background: Neurological diseases are pathologies that affect the central nervous system, such as Alzheimer’s disease and other forms of dementia. A correlation between cognitive decline and energy metabolism has been identified, and the potential to treat mental deterioration through the integration of natural mixtures into therapeutic strategies has gained increasing interest. Objective: Given the close relationship between hypometabolism and cognitive impairment, this study investigated the metabolic effects of a mixture containing medium-chain triglycerides, omega-3 fatty acids, and choline bitartrate in a human neuronal cell model, with relevance to cognitive decline. This was achieved by comparing the synergistic effects of the combined ingredients with the effects of the individual ingredients on energy metabolism (ATP) in a human neuronal model. Methods: Starting from the maximum non-toxic concentration common to both the mixture and individual components (1.563 mg/mL), the selected cell model (SH-SY5Y) was incubated for 24 h with decreasing concentrations of the mixture to evaluate ATP levels and to identify the optimal concentration (0.391 mg/mL). The cell viability results of the mixture were compared with the dose–response curves generated from cells treated with the individual components at equivalent concentrations to those present in the mixture. Results: A statistically significant increase (p<0.05) was observed in ATP content following treatment with the mixture compared to the individual active ingredients. Conclusion: The pre-clinical results demonstrate that a mixture containing medium-chain triglycerides, omega-3 fatty acids, and choline bitartrate exerts a synergistic effect on cellular energy metabolism, enhancing ATP production in a neuronal model. This formulation supports energy metabolism and may be beneficial for patients suffering from neurodegenerative diseases.