**Protective Effects of PollenAid Plus Soft Gel Capsules' Hydroalcoholic Extract in Isolated Prostates and Ovaries Exposed to Lipopolysaccharide**

**Annalisa Chiavaroli 1, Simonetta Cristina Di Simone 1, Alessandra Acquaviva 1, Maria Loreta Libero 1, Claudia Campana 1, Lucia Recinella 1, Sheila Leone 1, Luigi Brunetti 1, Giustino Orlando 1, Nilofar 1, Irene Vitale 1, Stefania Cesa 2, Gokhan Zengin 3,\*, Luigi Menghini 1,\* and Claudio Ferrante <sup>1</sup>**


**Abstract:** Pollen extract represents an innovative approach for the management of the clinical symptoms related to prostatitis and pelvic inflammatory disease (PID). In this context, the aims of the present work were to analyze the phenolic composition of a hydroalcoholic extract of PollenAid Plus soft gel capsules, and to evaluate the extract's cytotoxic effects, in human prostate cancer PC3 cells and human ovary cancer OVCAR-3 cells. Additionally, protective effects were investigated in isolated prostate and ovary specimens exposed to lipopolysaccharide (LPS). The phytochemical investigation identified catechin, chlorogenic acid, gentisic acid, and 3-hydroxytyrosol as the prominent phenolics. The extract did not exert a relevant cytotoxic effect on PC3 and OVCAR-3 cells. However, the extract showed a dose-dependent inhibition of pro-inflammatory IL-6 and TNF-α gene expression in prostate and ovary specimens, and the extract was effective in preventing the LPS-induced upregulation of CAT and SOD gene expression, which are deeply involved in tissue antioxidant defense systems. Finally, a docking approach suggested the capability of catechin and chlorogenic acid to interact with the TRPV1 receptor, playing a master role in prostate inflammation. Overall, the present findings demonstrated anti-inflammatory and antioxidant effects of this formulation; thus, suggesting its capability in the management of the clinical symptoms related to prostatitis and PID.

**Keywords:** Graminex pollen; hydroalcoholic extract; phenolic compounds; inflammation; oxidative stress; gene expression; TRPV1
