{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:36:00Z","timestamp":1787582160409,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Global Pharmacies Partner"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>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 \u03b2-inositol trisphosphate (PLC\u03b2-IP3) pathway. The present study evaluates the in vitro efficacy of a novel nutraceutical mixture\u2014Quercetin, Perilla frutescens, Boswellia serrata, Blackcurrant, Parthenium, Helichrysum, Lactobacillus Acidophilus (L. acidophilus) and Bifidobacterium animalis (B. animalis)\u2014in 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 &lt; 0.05) compared to the control group. Furthermore, ELISA assays demonstrated that the mixture significantly reduced IP3 release by 10.30% (p &lt; 0.05 vs. positive control). These results indicate that the nutraceutical mixture exerts its effects by modulating the H1R-PLC\u03b2-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.<\/jats:p>","DOI":"10.3390\/cimb48090854","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:20:43Z","timestamp":1787577643000},"page":"854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical In Vitro Evaluation of an Innovative Nutraceutical Mixture Modulating the Histamine H1 Receptor\u2014Preliminary Data"],"prefix":"10.3390","volume":"48","author":[{"given":"Franco","family":"Frati","sequence":"first","affiliation":[{"name":"Private Independent Researcher, 20123 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0378-8935","authenticated-orcid":false,"given":"Carlo","family":"Cavaliere","sequence":"additional","affiliation":[{"name":"Department of Sense Organs, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Frati","sequence":"additional","affiliation":[{"name":"Clinic of Otolaryngology (ENT), University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7289-513X","authenticated-orcid":false,"given":"Giulio","family":"Torello","sequence":"additional","affiliation":[{"name":"TL Pharma Consulting, 65129 Pescara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Colasante","sequence":"additional","affiliation":[{"name":"TL Pharma Consulting, 65129 Pescara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Caputo","sequence":"additional","affiliation":[{"name":"Science Department Global Pharmacies Partner, 20123 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Scquizzato","sequence":"additional","affiliation":[{"name":"Science Department Global Pharmacies Partner, 20123 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Masieri","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Sciences, Sapienza University, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1111\/all.15889","article-title":"Nomenclature of Allergic Diseases and Hypersensitivity Reactions: Adapted to Modern Needs: An EAACI Position Paper","volume":"78","author":"Jutel","year":"2023","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alska, E., Doligalska, A., Napi\u00f3rkowska-Baran, K., Dolina, M., Osi\u0144ska, K., Pilichowicz, A., Wojtkiewicz, A., Kaczor, J.J., Szymczak, B., and Bartuzi, Z. 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