Tanshinone IIA (TIIA) and cryptotanshinone (CRY) from Salvia miltiorrhiza Bunge were investigated for their inhibitory activity against the cyclooxygenase-2 (COX-2)/microsomal prosta-glandin E synthase-1 (mPGES-1)/endothelial prostaglandin 3 (EP3) pathway using in silico, in vitro, in vivo, and ex vivo assays. From the analysis of the docking poses, both diterpenoids were able to interact significantly with COX-2, 5-lipoxygenase (5-LO), platelet-activating factor receptor (PAFR), and mPGES-1. This evidence was further corroborated by data obtained from a cell-free assay, where CRY displayed a significant inhibitory potency against mPGES-1 (IC50 = 1.9 ± 0.4 µM) and 5-LO (IC50 = 7.1 µM), while TIIA showed no relevant inhibition of these targets. This was con-sistent with their activity to increase mice bleeding time (CRY: 2.44 ± 0.13 min, p ≤ 0.001; TIIA: 2.07 ± 0.17 min p ≤ 0.01) and with the capability to modulate mouse clot retraction (CRY: 0.048 ± 0.011 g, p ≤ 0.01; TIIA: 0.068 ± 0.009 g, p ≤ 0.05). For the first time, our results show that TIIA and, in partic-ular, CRY are able to interact significantly with the key proteins involved not only in the onset of inflammation but also in platelet activity (and hyper-reactivity). Future preclinical and clinical in-vestigations, together with this evidence, could provide the scientific basis to consider these compounds as an alternative therapeutic approach for thrombotic-and thromboembolic-based diseases.

In Silico, In Vitro, and In Vivo Analysis of Tanshinone IIA and Cryptotanshinone from Salvia miltiorrhiza as Modulators of Cyclooxygenase-2/mPGES-1/Endothelial Prostaglandin EP3 Pathway / Saviano, A.; De Vita, S.; Chini, M. G.; Marigliano, N.; Lauro, G.; Casillo, G. M.; Raucci, F.; Iorizzi, M.; Hofstetter, R. K.; Fischer, K.; Koeberle, A.; Werz, O.; Maione, F.; Bifulco, G.. - In: BIOMOLECULES. - ISSN 2218-273X. - 12:1(2022), p. 99. [10.3390/biom12010099]

In Silico, In Vitro, and In Vivo Analysis of Tanshinone IIA and Cryptotanshinone from Salvia miltiorrhiza as Modulators of Cyclooxygenase-2/mPGES-1/Endothelial Prostaglandin EP3 Pathway

Chini M. G.;Casillo G. M.;Fischer K.;Werz O.;Maione F.
;
2022

Abstract

Tanshinone IIA (TIIA) and cryptotanshinone (CRY) from Salvia miltiorrhiza Bunge were investigated for their inhibitory activity against the cyclooxygenase-2 (COX-2)/microsomal prosta-glandin E synthase-1 (mPGES-1)/endothelial prostaglandin 3 (EP3) pathway using in silico, in vitro, in vivo, and ex vivo assays. From the analysis of the docking poses, both diterpenoids were able to interact significantly with COX-2, 5-lipoxygenase (5-LO), platelet-activating factor receptor (PAFR), and mPGES-1. This evidence was further corroborated by data obtained from a cell-free assay, where CRY displayed a significant inhibitory potency against mPGES-1 (IC50 = 1.9 ± 0.4 µM) and 5-LO (IC50 = 7.1 µM), while TIIA showed no relevant inhibition of these targets. This was con-sistent with their activity to increase mice bleeding time (CRY: 2.44 ± 0.13 min, p ≤ 0.001; TIIA: 2.07 ± 0.17 min p ≤ 0.01) and with the capability to modulate mouse clot retraction (CRY: 0.048 ± 0.011 g, p ≤ 0.01; TIIA: 0.068 ± 0.009 g, p ≤ 0.05). For the first time, our results show that TIIA and, in partic-ular, CRY are able to interact significantly with the key proteins involved not only in the onset of inflammation but also in platelet activity (and hyper-reactivity). Future preclinical and clinical in-vestigations, together with this evidence, could provide the scientific basis to consider these compounds as an alternative therapeutic approach for thrombotic-and thromboembolic-based diseases.
2022
In Silico, In Vitro, and In Vivo Analysis of Tanshinone IIA and Cryptotanshinone from Salvia miltiorrhiza as Modulators of Cyclooxygenase-2/mPGES-1/Endothelial Prostaglandin EP3 Pathway / Saviano, A.; De Vita, S.; Chini, M. G.; Marigliano, N.; Lauro, G.; Casillo, G. M.; Raucci, F.; Iorizzi, M.; Hofstetter, R. K.; Fischer, K.; Koeberle, A.; Werz, O.; Maione, F.; Bifulco, G.. - In: BIOMOLECULES. - ISSN 2218-273X. - 12:1(2022), p. 99. [10.3390/biom12010099]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/876880
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