{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:46:09Z","timestamp":1790984769990,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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\u2019s 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-\u03b1 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.<\/jats:p>","DOI":"10.3390\/molecules27196279","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T01:41:58Z","timestamp":1664156518000},"page":"6279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Protective Effects of PollenAid Plus Soft Gel Capsules\u2019 Hydroalcoholic Extract in Isolated Prostates and Ovaries Exposed to Lipopolysaccharide"],"prefix":"10.3390","volume":"27","author":[{"given":"Annalisa","family":"Chiavaroli","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5041-3848","authenticated-orcid":false,"given":"Simonetta Cristina","family":"Di Simone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8776-1413","authenticated-orcid":false,"given":"Alessandra","family":"Acquaviva","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8133-5691","authenticated-orcid":false,"given":"Maria Loreta","family":"Libero","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8688-9549","authenticated-orcid":false,"given":"Claudia","family":"Campana","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Recinella","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Brunetti","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giustino","family":"Orlando","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4254-4140","authenticated-orcid":false,"given":"Nilofar","family":"Nilofar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Vitale","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8649-0017","authenticated-orcid":false,"given":"Stefania","family":"Cesa","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry and Technology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6548-7823","authenticated-orcid":false,"given":"Gokhan","family":"Zengin","sequence":"additional","affiliation":[{"name":"Department of Biology, Science Faculty, Selcuk University, Konya 42130, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7346-7395","authenticated-orcid":false,"given":"Luigi","family":"Menghini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-9407","authenticated-orcid":false,"given":"Claudio","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Botanic Garden \u201cGiardino dei Semplici\u201d, \u201cG. d\u2019Annunzio\u201d University, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jep.2005.07.007","article-title":"Studies on antibacterial, anti-inflammatory and antioxidant activity of herbal remedies used in the treatment of benign prostatic hyperplasia and prostatitis","volume":"103","author":"Steenkamp","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_2","first-page":"1364297","article-title":"Evidence for the Use of Complementary and Alternative Medicine for Pelvic Inflammatory Disease: A Literature Review","volume":"2022","author":"Wang","year":"2022","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.jep.2017.06.034","article-title":"Anti-inflammatory effect of Man-Pen-Fang, a Chinese herbal compound, on chronic pelvic inflammation in rats","volume":"208","author":"Zhang","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Orlando, G., Chiavaroli, A., Adorisio, S., Delfino, D., Brunetti, L., Recinella, L., Leone, S., Zengin, G., Acquaviva, A., and Angelini, P. (2021). Unravelling the Phytochemical Composition and the Pharmacological Properties of an Optimized Extract from the Fruit from Prunus mahaleb L.: From Traditional Liqueur Market to the Pharmacy Shelf. Molecules, 26.","DOI":"10.3390\/molecules26154422"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ferrante, C., Chiavaroli, A., Angelini, P., Venanzoni, R., Angeles Flores, G., Brunetti, L., Petrucci, M., Politi, M., Menghini, L., and Leone, S. (2020). Phenolic Content and Antimicrobial and Anti-Inflammatory Effects of Solidago virga-aurea, Phyllanthus niruri, Epilobium angustifolium, Peumus boldus, and Ononis spinosa Extracts. Antibiotics, 9.","DOI":"10.3390\/antibiotics9110783"},{"key":"ref_6","unstructured":"Cai, T., Gallelli, L., Cione, E., Verze, P., Palmieri, A., Mirone, V., Bonkat, G., Wagenlehner, F.M., and Johansen, T.E.B. (2021). The efficacy and tollerability of pollen extract in combination with hyaluronic acid and vitamins in the management of patients affected by chronic prostatitis\/chronic pelvic pain syndrome: A 26 weeks, randomized, controlled, single-blinded, phase III study. Minerva Urol. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Csik\u00f3s, E., Horv\u00e1th, A., \u00c1cs, K., Papp, N., Bal\u00e1zs, V.L., Dolenc, M.S., Kenda, M., Glava\u010d, N.K., Nagy, M., and Protti, M. (2021). Treatment of Benign Prostatic Hyperplasia by Natural Drugs. Molecules, 26.","DOI":"10.3390\/molecules26237141"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4303","DOI":"10.1002\/jsfa.7729","article-title":"Biological and therapeutic properties of bee pollen: A review","volume":"96","author":"Denisow","year":"2016","journal-title":"J. Sci. Food Agric."},{"key":"ref_9","first-page":"297425","article-title":"Bee Pollen: Chemical Composition and Therapeutic Application","volume":"2015","author":"Olczyk","year":"2015","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e13635","DOI":"10.1111\/jfbc.13635","article-title":"Synergic effect of bee pollen and metformin on proliferation and apoptosis of granulosa cells: Rat model of polycystic ovary syndrome","volume":"46","author":"Naseri","year":"2022","journal-title":"J. Food Biochem."},{"key":"ref_11","first-page":"201","article-title":"Antibacterial Activity of Honey and Beebread of Different Origin Against S. aureus and S. epidermidis","volume":"45","author":"Venskutonis","year":"2007","journal-title":"Food Technol. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"927","DOI":"10.2298\/ABS1203927K","article-title":"The antimicrobial activity of honey, bee pollen loads and beeswax from Slovakia","volume":"64","author":"Chlebo","year":"2012","journal-title":"Arch. Biol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/ptr.2103","article-title":"Antinociceptive and antiinflammatory activities of pine (Pinus densiflora) pollen extract","volume":"21","author":"Choi","year":"2007","journal-title":"Phytother. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/ptr.5655","article-title":"An Hydroalcoholic Chamomile Extract Modulates Inflammatory and Immune Response in HT29 Cells and Isolated Rat Colon","volume":"30","author":"Menghini","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kaur, P., Sandhu, K.S., Bangar, S.P., Purewal, S.S., Kaur, M., Ilyas, R.A., Asyraf, M.R.M., and Razman, M.R. (2021). Unraveling the Bioactive Profile, Antioxidant and DNA Damage Protection Potential of Rye (Secale cereale) Flour. Antioxidants, 10.","DOI":"10.3390\/antiox10081214"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00217-019-03345-6","article-title":"Reflectance colorimetry: A mirror for food quality\u2014A mini review","volume":"246","author":"Cairone","year":"2020","journal-title":"Eur. Food Res. Technol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Locatelli, M., Macchione, N., Ferrante, C., Chiavaroli, A., Recinella, L., Carradori, S., Zengin, G., Cesa, S., Leporini, L., and Leone, S. (2018). Graminex Pollen: Phenolic Pattern, Colorimetric Analysis and Protective Effects in Immortalized Prostate Cells (PC3) and Rat Prostate Challenged with LPS. Molecules, 23.","DOI":"10.3390\/molecules23051145"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1093\/infdis\/jiab067","article-title":"Etiology and Diagnosis of Pelvic Inflammatory Disease: Looking Beyond Gonorrhea and Chlamydia","volume":"224","author":"Mitchell","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1404813","DOI":"10.1155\/2018\/1404813","article-title":"Oral Fosfomycin for the Treatment of Acute and Chronic Bacterial Prostatitis Caused by Multidrug-Resistant Escherichia coli","volume":"2018","author":"Zhanel","year":"2018","journal-title":"Can. J. Infect. Dis. Med Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/iju.13549","article-title":"Oral administration of cernitin pollen extract (Cernilton\u00ae) for 30 days might be useful to avoid unnecessary biopsy in prostate biopsy candidates: A preliminary study","volume":"25","author":"Togo","year":"2018","journal-title":"Int. J. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.eururo.2009.05.046","article-title":"A Pollen Extract (Cernilton) in Patients with Inflammatory Chronic Prostatitis\u2013Chronic Pelvic Pain Syndrome: A Multicentre, Randomised, Prospective, Double-Blind, Placebo-Controlled Phase 3 Study","volume":"56","author":"Wagenlehner","year":"2009","journal-title":"Eur. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"120","DOI":"10.5534\/wjmh.2017.35.2.120","article-title":"The Clinical Efficacy of Pollen Extract and Vitamins on Chronic Prostatitis\/Chronic Pelvic Pain Syndrome Is Linked to a Decrease in the Pro-Inflammatory Cytokine Interleukin-8","volume":"35","author":"Cai","year":"2017","journal-title":"World J. Men\u2019s Health"},{"key":"ref_23","first-page":"558","article-title":"Overexpression of cyclooxygenase-2 in squamous cell carcinoma of the urinary bladder","volume":"7","author":"Shirahama","year":"2001","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Moita, E., Gil-Izquierdo, A., Sousa, C., Ferreres, F., Silva, L.R., Valent\u00e3o, P., Dom\u00ednguez-Perles, R., Baenas, N., and Andrade, P.B. (2013). Integrated Analysis of COX-2 and iNOS Derived Inflammatory Mediators in LPS-Stimulated RAW Macrophages Pre-Exposed to Echium plantagineum L. Bee Pollen Extract. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059131"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ab.2016.10.021","article-title":"Assessment of lipid peroxidation by measuring malondialdehyde (MDA) and relatives in biological samples: Analytical and biological challenges","volume":"524","author":"Tsikas","year":"2017","journal-title":"Anal. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.jpsychires.2021.10.021","article-title":"Lipopolysaccharide exacerbates chronic restraint stress-induced neurobehavioral deficits: Mechanisms by redox imbalance, ASK1-related apoptosis, autophagic dysregulation","volume":"144","author":"Kwatra","year":"2021","journal-title":"J. Psychiatr. Res."},{"key":"ref_27","first-page":"e13980","article-title":"Cinnamaldehyde and eugenol protect against LPS-stimulated oxidative stress and inflammation in Raw 264.7 cells","volume":"45","author":"Peker","year":"2021","journal-title":"J. Food Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1111\/1750-3841.14198","article-title":"Antitumor Perspectives of Oleuropein and Its Metabolite Hydroxytyrosol: Recent Updates","volume":"83","author":"Imran","year":"2018","journal-title":"J. Food Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"136085","DOI":"10.1016\/j.neulet.2021.136085","article-title":"Chlorogenic acid alleviates neurobehavioral disorders and brain damage in focal ischemia animal models","volume":"760","author":"Shah","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1677\/erc.1.00535","article-title":"The role of fibroblast growth factors and their receptors in prostate cancer","volume":"11","author":"Ozen","year":"2004","journal-title":"Endocr.-Relat. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1113\/JP277452","article-title":"Bladder overactivity and afferent hyperexcitability induced by prostate-to-bladder cross-sensitization in rats with prostatic inflammation","volume":"597","author":"Funahashi","year":"2019","journal-title":"J. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sipos, L., V\u00e9gh, R., Bodor, Z., Zaukuu, J.-L.Z., Hitka, G., B\u00e1z\u00e1r, G., and Kovacs, Z. (2020). Classification of Bee Pollen and Prediction of Sensory and Colorimetric Attributes\u2014A Sensometric Fusion Approach by e-Nose, e-Tongue and NIR. Sensors, 20.","DOI":"10.3390\/s20236768"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3390\/foods4030487","article-title":"Infant Milk Formulas: Effect of Storage Conditions on the Stability of Powdered Products towards Autoxidation","volume":"4","author":"Cesa","year":"2015","journal-title":"Foods"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Recinella, L., Chiavaroli, A., Masciulli, F., Fraschetti, C., Filippi, A., Cesa, S., Cairone, F., Gorica, E., De Leo, M., and Braca, A. (2021). Protective Effects Induced by a Hydroalcoholic Allium sativum Extract in Isolated Mouse Heart. Nutrients, 13.","DOI":"10.3390\/nu13072332"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.foodres.2018.04.028","article-title":"Crocus sativus L. stigmas and byproducts: Qualitative fingerprint, antioxidant potentials and enzyme inhibitory activities","volume":"109","author":"Menghini","year":"2018","journal-title":"Food Res. Int."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Orlando, G., Leone, S., Ferrante, C., Chiavaroli, A., Mollica, A., Stefanucci, A., Macedonio, G., Dimmito, M.P., Leporini, L., and Menghini, L. (2018). Effects of Kisspeptin-10 on Hypothalamic Neuropeptides and Neurotransmitters Involved in Appetite Control. Molecules, 23.","DOI":"10.3390\/molecules23123071"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"303","DOI":"10.4103\/0976-500X.119726","article-title":"How to calculate sample size in animal studies?","volume":"4","author":"Charan","year":"2013","journal-title":"J. Pharmacol. Pharmacother."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6279\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:38:21Z","timestamp":1760143101000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":38,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27196279"],"URL":"https:\/\/doi.org\/10.3390\/molecules27196279","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]}}}