PAOLA MINOSI

PhD Graduate

PhD program:: XXXIV


supervisor: Maura Palmery
advisor: Stefano Pieretti

Thesis title: Pharmacological characterization of new compounds and herbal derivatives for pain and inflammation treatment

Introduction: Despite the availability of several analgesic and anti-inflammatory options, the effective treatment of pain and inflammation is still a challenge for clinicians, and the balance between efficacy and safety aspects remains both crucial and difficult. Thus, the identification of new potential targets which may affect pain and inflammatory processes is becoming an urgent clinical and therapeutic need. This scientific project derives from a close collaboration with various national and foreign research groups, in order to establish an efficient and highly multidisciplinary approach to investigate the pharmacological profile of new compounds and herbal derivatives with significant antinociceptive and antinflammatory effects to be used for the treatment of pain and inflammation. Materials and Methods: The research approach involves the in vivo studies of natural (ammonium glycyrrhizinate; rubiscolin-6 and soymorphin-6) and non-natural compounds (C-terminal amides derivatives of rubiscolin-6 and soymorphin-6; six analogues of endomorphin-2 and DAPEA; two compounds obtained in silico studies; a series of lonidamine with high CB1 receptor affinity and new pH-sensitive formulation of niosomes containing Polysorbate 20 derivatized by Glycine and loaded with ibuprofen) using murine models of pain and inflammation. All experiments were carried out using male CD-1 mice weighing 25 g. Results: The results suggest the potential use of ammonium glycyrrhizinate for clinical treatment of pain and/or inflammatory-related diseases, included diabetic peripheral neuropathy. The results obtained by in vivo studies testing two natural compounds, rubiscolin-6 and soymorphin-6, and their C-terminal amides derivatives, show that rubiscolin-6 was able to increase the nociceptive threshold to thermal stimuli after supraspinal administration, but was ineffective after subcutaneous administration, in an experimental paradigm of chemical-induced nociception as the formalin test. On the other hand, instead, its derivatives (rubiscolin-6 C-amide) centrally administered demonstrates a strong antinociceptive effect higher than rubiscolin-6, and it is effective after subcutaneous administration. Both soymorphin-6 and its derivative soymorphin-6 C-amide induced a robust antinociceptive effect after central administration in tail flick test but both peptides have not been able to change the behavioral response to chemical-induced nociception in the formalin test. The in vivo antinociceptive profile of new six tetrapeptide models containing α-amino-γ-lactam of Freidinger in position 2 and 3, as analogues of endomorphin-2 (EM-2) and DAPEA, revealed that one of them (peptide A2D) exhibited a strong antinociceptive effect in vivo after intracerebroventricular administration, performing better than the parent compounds EM-2 and DAPEA. Peptide A3D is also able to produce antinociceptive effect both in the acute and in the inflammatory phase of the formalin test. The in vivo results obtained from two compounds (tripeptides 6 and 11) derived from previous in silico studies revealed their ability to induce an antinociceptive effect after intracerebroventricular and subcutaneous administrations in the tail flick and formalin tests, respectively. Subsequently, it was analyzed the in vivo orexant/anorexant and antinociceptive profile of a series of lonidamine joined Leu-, tert/Leu- and Val-amino acids with different C-terminal functional groups (LONI 1-4,11) as novel compounds with high CB1 receptor affinity and selectivity with different biological activity depending on the C-terminal substitution and amino acid residues and endowed with activities. The results demonstrated that LONI2 and LONI4 were able to inhibit food intake (anorexant effect) consistent with an inverse agonism at CB1 receptors. On the other hand, LONI11, an agonist towards cannabinoid receptors CB1 and CB2, proved to carry out a significant orexant an antinociceptive effect at the central and periphery levels. Finally, a new pH-sensitive formulation of niosomes containing Polysorbate 20 derivatized by Glycine and loaded with ibuprofen (NioIbu) was in vivo tested, using models of pain and inflammation. The results demonstrated that NioIbu, administered 2h before testing, reduced nociception, whereas the free form of ibuprofen was ineffective. Conclusion: In conclusion, these findings create prospects for conducting clinical studies with the compounds presented, which show in fact their effectiveness for chronic pain and inflammation control.

Research products

11573/1549244 - 2021 - Ammonium Glycyrrhizinate Prevents Apoptosis and Mitochondrial Dysfunction Induced by High Glucose in SH-SY5Y Cell Line and Counteracts Neuropathic Pain in Streptozotocin-Induced Diabetic Mice
Ciarlo, Laura; Marzoli, Francesca; Minosi, Paola; Matarrese, Paola; Pieretti, Stefano - 01a Articolo in rivista
paper: BIOMEDICINES (Basel: MDPI) pp. 608- - issn: 2227-9059 - wos: WOS:000665496600001 (12) - scopus: 2-s2.0-85107755534 (13)

11573/1566244 - 2021 - Selective MOR activity of DAPEA and Endomorphin-2 analogues containing a (R)-γ-Freidinger lactam in position two
Della Valle, A.; Stefanucci, A.; Scioli, G.; Szucs, E.; Benyhe, S.; Pieretti, S.; Minosi, P.; Sturaro, C.; Calo, G.; Zengin, G.; Mollica, A. - 01a Articolo in rivista
paper: BIOORGANIC CHEMISTRY (Academic Press Incorporated:6277 Sea Harbor Drive:Orlando, FL 32887:(800)543-9534, (407)345-4100, EMAIL: ap@acad.com, INTERNET: http://www.idealibrary.com, Fax: (407)352-3445) pp. 105219- - issn: 0045-2068 - wos: WOS:000703502700005 (4) - scopus: 2-s2.0-85111599634 (4)

11573/1487666 - 2021 - Soy-enriched bread, a pilot study to determine its beneficial effects in menopause
Giustarini, Daniela; Ricci, Comasia; Ceccarelli, Ilaria; Pieretti, Stefano; Andre, Paolo; Migliorini, Silvia; Massai, Lauretta; Minosi, Paola; Casini, Ilenia; Aloisi, Anna Maria - 01a Articolo in rivista
paper: PHYSIOLOGY & BEHAVIOR (Elsevier Science Limited:Oxford Fulfillment Center, PO Box 800, Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000, 011 44 1865 843699, EMAIL: asianfo@elsevier.com, tcb@elsevier.co.UK, INTERNET: http://www.elsevier.com, http://www.elsevier.com/locate/shpsa/, Fax: 011 44 1865 843010) pp. - - issn: 0031-9384 - wos: (0) - scopus: (0)

11573/1546607 - 2021 - Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity .
Minosi, P; Dimmito, Mp; Stefanucci, A; Pieretti, S; Mollica, A - 04f Poster
conference: 40° Congresso Nazionale SIF. SIF - SOCIETÀ ITALIANA DI FARMACOLOGIA (Modalità telematica)
book: Pharmadvances Vol. 3 (No. 1) 217; 2021 March - ()

11573/1546610 - 2021 - Pharmacological activities of plant-derived opioid peptides rubiscolin-6, soymorphin-6 and their c-terminal amide derivatives.
Minosi, P; Dimmito, Mp; Stefanucci, A; Sturaro, C; Calò, G; Pieretti, S; Mollica, A - 04f Poster
conference: 40° Congresso Nazionale SIF. SIF - SOCIETÀ ITALIANA DI FARMACOLOGIA (Modalità telematica)
book: Pharmadvances Vol. 3 (No. 1) 216; 2021 March - ()

11573/1546606 - 2021 - A novel identification system for potentially counterfeit medical devices based on the visual analysis through evaluation sheet .
Minosi, Paola; Pieretti, Stefano; Marletta, Marcella - 04f Poster
conference: 40° Congresso Nazionale SIF. SIF - SOCIETÀ ITALIANA DI FARMACOLOGIA (Modalità telematica)
book: Pharmadvances Vol. 3 (No. 1) 218; 2021 March - ()

11573/1566246 - 2021 - In silico identification of tripeptides as lead compounds for the design of kor ligands
Stefanucci, A.; Iobbi, V.; Della Valle, A.; Scioli, G.; Pieretti, S.; Minosi, P.; Mirzaie, S.; Novellino, E.; Mollica, A. - 01a Articolo in rivista
paper: MOLECULES (Basel: MDPI Berlin: Springer, 1996-) pp. 4767- - issn: 1420-3049 - wos: WOS:000690105400001 (15) - scopus: 2-s2.0-85112261896 (15)

11573/1438779 - 2020 - Acupuncture decreases pain and MIF salivary levels in men and women
Ilaria, Ceccarelli; Luana, Paulesu; Bao Tian Fu, ; Pieretti, Stefano; Li, Xu; Rong Zhen Tan, ; Chen, Yi; Xue, Yang; Minosi, Paola; Roberta, Romagnoli; Anna Maria Aloisi, - 01a Articolo in rivista
paper: INTERNATIONAL JOURNAL OF COMPLEMENTARY & ALTERNATIVE MEDICINE (Edmond OK: MedCrave Group, 2015-) pp. - - issn: 2381-1803 - wos: (0) - scopus: (0)

11573/1438773 - 2020 - Plant-derived peptides rubiscolin-6, soymorphin-6 and their c-terminal amide derivatives: pharmacokinetic properties and biological activity
Stefanucci, A.; Dimmito, M. P.; Tenore, G.; Pieretti, S.; Minosi, P.; Zengin, G.; Sturaro, C.; Calo, G.; Novellino, E.; Cichelli, A.; Mollica, A. - 01a Articolo in rivista
paper: JOURNAL OF FUNCTIONAL FOODS (Elsevier ltd) pp. - - issn: 1756-4646 - wos: WOS:000579501700035 (21) - scopus: 2-s2.0-85089438717 (23)

11573/1317375 - 2019 - Flavonoid-statins interactions
Aiello, Paola; Minosi, Paola; Peluso, Ilaria; Palmery, Maura - 04f Poster
conference: 2nd Conference on Innovations in Food Science & Human Nutrition (Londra)
book: 2nd Conference on Innovations in Food Science & Human Nutrition (IFHN-2019) - ()

11573/1317376 - 2019 - Oxidative stress biomarkers
Aiello, Paola; Minosi, Paola; Peluso, Ilaria; Palmery, Maura - 04d Abstract in atti di convegno
conference: 2019 Annual Conference on Genetics (Vienna)
book: Archives of Applied Medicine - ()

11573/1333302 - 2019 - “Glycyrrhizic Acid attenuates the cytotoxicity induced by high glucose in neuroblastoma cell line”
Ciarlo, Laura; Marzoli, Francesca; Minosi, Paola; Di Giannuario, Amalia; Matarrese, Paola; Pieretti, Stefano - 04f Poster
conference: 39° Congresso Nazionale della Società Italiana di Farmacologia (Firenze)
book: Libro dei Poster - ()

11573/1333297 - 2019 - Opportunity to Analyze Laboratory Mice Behavior by Tracking Systems based on UHF RFID Technology: pros and cons
Cirillo, E.; Minosi, P.; Marzoli, F.; Sergi, I.; Colella, R.; Patrono, L.; Catarinucci, L.; Pieretti, S. - 04b Atto di convegno in volume
conference: 2019 IEEE International Conference on RFID Technology and Applications (RFID-TA) (Pisa)
book: IEEE Xplore - (978-172810589-5)

11573/1313507 - 2019 - Discovery of orexant and anorexant agents with indazole scaffold endowed with peripheral antiedema activity
Dimmito, Marilisa P.; Stefanucci, Azzurra; Pieretti, Stefano; Minosi, Paola; Dvorácskó, Szabolcs; Tömböly, Csaba; Zengin, Gokhan; Mollica, Adriano - 01a Articolo in rivista
paper: BIOMOLECULES (Basel: MDPI) pp. - - issn: 2218-273X - wos: WOS:000489102800104 (19) - scopus: 2-s2.0-85072269583 (20)

11573/1296383 - 2019 - Long-Lasting Anti-Inflammatory and Antinociceptive Effects of Acute Ammonium Glycyrrhizinate Administration: Pharmacological, Biochemical, and Docking Studies
Maione, Francesco; Minosi, Paola; Di Giannuario, Amalia; Raucci, Federica; Giovanna Chini, Maria; De Vita, Simona; Bifulco, Giuseppe; Mascolo, Nicola; Pieretti, Stefano - 01a Articolo in rivista
paper: MOLECULES (Basel: MDPI Berlin: Springer, 1996-) pp. - - issn: 1420-3049 - wos: WOS:000476700300107 (24) - scopus: 2-s2.0-85068994181 (29)

11573/1343196 - 2019 - Long-lasting, antinociceptive effects of pH-sensitive niosomes loaded with ibuprofen in acute and chronic models of pain
Marzoli, F.; Marianecci, C.; Rinaldi, F.; Passeri, D.; Rossi, M.; Minosi, P.; Carafa, M.; Pieretti, S. - 01a Articolo in rivista
paper: PHARMACEUTICS (Basel: MDPI, 2009-) pp. 62- - issn: 1999-4923 - wos: WOS:000460799900014 (15) - scopus: 2-s2.0-85063235010 (16)

11573/1333303 - 2019 - “The arylpiperazinylalkyl pyridazinone ET1 as a potent antinociceptive agent after oral administration in mice”
Marzoli, Francesca; Maione, Francesco; Colucci, Mariantonella; Minosi, Paola; Di Giannuario, Amalia; Raucci, Federica; Mascolo, Nicola; Paola Giovannoni, Maria; Pieretti, Stefano - 04f Poster
conference: 39° Congresso Nazionale della Società Italiana di Farmacologia (Firenze)
book: Libro dei Poster - ()

11573/1333301 - 2019 - “Long-lasting antinociceptive effects of Ammonium Glychirrizinate in mice”
Minosi, P; Raucci, F; Di Giannuario, A; Chini, Mg; De Vita, S; Bifulco, G; Maione, F; Mascolo, N; Pieretti, S - 04f Poster
conference: 39° Congresso Nazionale della Società Italiana di Farmacologia (Firenze)
book: Libro dei Poster - ()

11573/1317287 - 2019 - Association of antioxidant nutraceuticals and acetaminophen (paracetamol): Friend or foe?
Minosi, Paola; Aiello, Paola; Peluso And Maura Palmery, Ilaria - 04f Poster
conference: 2nd Conference on Innovations in Food Science & Human Nutrition(IFHN-2019) (Londra)
book: 2nd Conference on Innovations in Food Science & Human Nutrition(IFHN-2019) - ()

11573/1317285 - 2019 - Small molecules with anti prion activity
Mustazza, C; Sbriccoli, M; Minosi, P; Raggia, C. - 01g Articolo di rassegna (Review)
paper: CURRENT MEDICINAL CHEMISTRY (Bentham Science Publishers BV:PO Box 7917, Exec Ste Y 26, Saif Zone Sharjah Uae:011 971 6 5571132, EMAIL: benthams@emirates.net.ae, INTERNET: http://www.bentham.org, Fax: 011 971 6 5571134) pp. - - issn: 0929-8673 - wos: WOS:000580568500001 (8) - scopus: 2-s2.0-85089623309 (7)

11573/1333300 - 2019 - “Long lasting inflammatory effects of ammonium glycyrrhizinate: an integrated study of pharmacology and computational analysis”
Raucci, F; Minosi, P; Di Giannuario, A; Chini, Mg; De Vita, S; Bifulco, G; Maione, F; Mascolo, N; Pieretti, S - 04f Poster
conference: 39° Congresso Nazionale della Società Italiana di Farmacologia (Firenze)
book: Libro dei Poster - ()

11573/1300681 - 2019 - IL-17A neutralizing antibody regulates monosodium urate crystal-induced gouty inflammation
Raucci, Federica; Iqbal, Asif J.; Saviano, Anella; Minosi, Paola; Piccolo, Marialuisa; Irace, Carlo; Caso, Francesco; Scarpa, Raffaele; Pieretti, Stefano; Mascolo, Nicola; Maione, Francesco - 01a Articolo in rivista
paper: PHARMACOLOGICAL RESEARCH (Attuale:ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD, 24-28 OVAL RD, LONDON, ENGLAND, NW1 7DX Elsevier Science Limited:Oxford Fulfillment Center, PO Box 800, Kidlington Oxford OX5 1DX United Kingdom:011 44 1865 843000, 011 44 1865 843699, EMAIL: asianfo@elsevier.com, tcb@elsevier.co.UK, INTERNET: http://www.elsevier.com, http://www.elsevier.com/locate/shpsa/, Fax: 011 44 1865 843010) pp. - - issn: 1043-6618 - wos: WOS:000487565500011 (41) - scopus: 2-s2.0-85069702655 (47)

11573/1652001 - 2019 - Polypharmacy and Nutraceuticals in Veterans: Pros and Cons
Sciarra, Tommaso; Ciccotti, Mario; Aiello, Paola; Minosi, Paola; Munzi, Diego; Buccolieri, Cosimo; Peluso, Ilaria; Palmery, Maura; Lista, Florigio - 01b Commento, Erratum, Replica e simili
paper: FRONTIERS IN PHARMACOLOGY (Lausanne: Frontiers Media S.A., 2010-) pp. 994- - issn: 1663-9812 - wos: WOS:000485166900001 (6) - scopus: 2-s2.0-85073037195 (6)

11573/1308177 - 2019 - Polypharmacy and Nutraceuticals in veterans: 1 partners in crime?
Tommaso, Sciarra; Ciccotti, Mario; Aiello, Paola; Minosi, Paola; Diego, Munzi; Cosimo, Buccolieri; Peluso, Ilaria; Palmery, Maura; Florigio, Lista - 01b Commento, Erratum, Replica e simili
paper: FRONTIERS IN PHARMACOLOGY (Lausanne: Frontiers Media S.A., 2010-) pp. - - issn: 1663-9812 - wos: (0) - scopus: (0)

11573/1207806 - 2018 - Curcumin-loaded Poly (d,l-lactide-co-glycolide) nanovesicles induce antinociceptive effects after local administration in mice
Ciarlo, Laura; Francesca, Marzoli; Minosi, Paola; Amalia Di Giannuario, ; Pieretti, Stefano - 04f Poster
conference: NANOMEDICINE ROME 2018 (Istituto Superiore di Sanità)
book: Abstract Book ISBN 978-88-97987-19-2 © Editore VALMAR – Roma, 2018. - ()

11573/1207807 - 2018 - Enhanced antinociceptive and anti-inflammatory effects of ibuprofen encapsulated in niosomal vesicles
Marzoli, Francesca; Minosi, Paola; Ciarlo, Laura; Di Giannuario, Amalia; Carafa, Maria; Marianecci, Carlotta; Pieretti, Stefano - 04f Poster
conference: NANOMEDICINE ROME 2018 (Istituto Superiore di Sanità)
book: Abstract Book ISBN 978-88-97987-19-2 © Editore VALMAR – Roma, 2018. - ()

11573/1207808 - 2018 - Prolongation of local pain insensitivity by anesthetic lidocaine loaded pH-TW20 Gly niosomes: effects on nociception in murine models of pain
Minosi, Paola; Marzoli, Francesca; Ciarlo, Laura; Di Giannuario, Amalia; Carafa, Maria; Rinaldi, Ferderica; Pieretti, Stefano - 04f Poster
conference: NANOMEDICINE ROME 2018 (Istituto Superiore di Sanità)
book: Abstract Book ISBN 978-88-97987-19-2 © Editore VALMAR – Roma, 2018. - ()

11573/1207828 - 2018 - Design, synthesis and biological profile of mixed opioid agonist/N-VGCC blocker peptides
Stefanucci, Azzurra; Novellino, Ettore; Macedonio, Giorgia; Dimmito, Marilisa Pia; Mirzaie, Sako; Caldas Cardoso, Fernanda; Lewis, Richard; Zádor, Ferenc; Erdei, Anna I.; Dvorácskó, Szabolcs; Tömböly, Csaba; Benyhe, Sandor; Pieretti, Stefano; Minosi, Paola; Mollica, Adriano - 01a Articolo in rivista
paper: NEW JOURNAL OF CHEMISTRY ([London] : Royal Society of Chemistry, [1998]-) pp. 5656-5659 - issn: 1369-9261 - wos: WOS:000430996700002 (5) - scopus: 2-s2.0-85045537082 (5)

11573/1207814 - 2017 - Opioid receptor activity and analgesic potency of DPDPE peptide analogues containing a xylene bridge.
Stefanucci, A; Novellino, E; Mirzaie, S; Macedonio, G; Pieretti, S; Minosi, P; Szűcs, E; Erdei, Ai; Zádor, F; Benyhe, S; Mollica, A. - 01a Articolo in rivista
paper: ACS MEDICINAL CHEMISTRY LETTERS (USA: ACS Publications) pp. 449-454 - issn: 1948-5875 - wos: WOS:000399435700014 (13) - scopus: 2-s2.0-85017562729 (13)

11573/1207820 - 2016 - Antinociceptive effects of Curcumin-loaded PLGA vesicles
Di Giovannandrea, Rita; Marzoli, Francesca; Minosi, Paola; Di Giannuario, Amalia; Pieretti, Stefano - 04f Poster
conference: NANOMEDICINE VITERBO 2016 (Viterbo)
book: Abstract Book Nanomedicine 2016 - ()

11573/1207811 - 2016 - Gender differences in pain and its relief
Pieretti, S; Di Giannuario, A; Di Giovannandrea, R; Marzoli, F; Piccaro, G; Minosi, P; Aloisi, Am - 01g Articolo di rassegna (Review)
paper: ANNALI DELL'ISTITUTO SUPERIORE DI SANITÀ (Latest publisher: Roma: Istituto Superiore di Sanità Roma: Istituto poligrafico dello stato) pp. 184-189 - issn: 0021-2571 - wos: (0) - scopus: 2-s2.0-84979948929 (250)

© Università degli Studi di Roma "La Sapienza" - Piazzale Aldo Moro 5, 00185 Roma