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Ginseng has been reported to have diverse pharmacological effects. One of the therapeutic claims for ginseng is to enhance sexual function. Ginsenosides are considered as the major active constituents. A steaming process can alter the ginsenoside profile of ginseng products. The structure–function relationship of ginsenosides in the treatment of erectile dysfunction (ED) has not been investigated yet. In this work, 15 different processed ginsengs are produced by steaming, and 13 major ginsensosides are quantified by liquid chromatography with UV detection, including Rg1, Re, Rf, Rb1, Rc, Rb2, Rf, Rk3, Rh4, 20S-Rg3, 20R-Rg3, Rk1, and Rg5. Their anti-ED activities are screened using hydrocortisone-induced mice model (Kidney Yang Deficiency Syndrome in Chinese Medicine) and primary corpus cavernosum smooth muscle cells (CCSMCs). A processed ginseng with steaming treatment at 120${}^{\circ }$C for 4h and five times possesses abundant ginsenosides Rk1, Rk3, Rh4 and Rg5 transformed via deglycosylation and dehydroxylation, and produces optimal activity against ED. The number of sugar molecules, structure of hydroxyl groups and stereoselectivity in ginsenosides affect their anti-ED activity. Among the 13 ginsenosides, Rk1, Rk3, Rh4 and Rg5 are the most efficient in decreasing intracellular calcium levels by inhibiting phosphodiesterase 5A (PDE5A) to reduce the degradation of cyclic guanosine monophosphate (cGMP) in CCSMCs. Rg5 also restrain hypoxia inducible factor-1$\alpha$ (HIF-1$\alpha )$ expression in hypoxia state, and increase endothelial nitric oxide synthase (eNOS) expression in isolated rat cavernous tissue. These observations suggest a role for steamed ginseng containing two pairs of geometric isomers (i.e., Rk1/Rg5 and Rk3/Rh4) in the treatment of ED.

As the only metabolizing enzyme for the degradation of second messenger cAMP and cGMP, phosphodiesterase (PDE) has been the clinical target of various human diseases. But the hydrolysis procedure of PDE is still unclear. To investigate the mechanism of PDE catalysis, three types of PDE (PDE4d, PDE5a and PDE10a) were selected and studied by using molecular dynamics (MD) simulation and quantum mechanics (QM) calculation methods. MD Simulation results indicate that different PDEs share a similar hydrolysis area in the active sites, and the phosphate parts of cyclic nucleotides take the same orientation and are partly surrounded by water molecules. Based on the statistical data of MD simulation, the QM calculation models were built. The calculation results indicate that in aqueous solution, the nucleophile hydroxide ion that attacks the phosphor atom of the cyclic nucleotide in the hydrolysis may migrate between the two metal ions in the active site. To help the ring-open reaction, it is the water molecule that provides proton to the O3′ atom of cyclic nucleotide, and generates another hydroxide ion complexed with the metal ion.