Phosphodiesterases (PDEs) have the function of hydrolyzing intracellular second messengers (cAMP, cyclic adenosine monophosphate or cGMP, cyclic guanosine monophosphate), degrading intracellular cAMP or cGMP, thereby terminating the biochemical effects of these second messengers. . cAMP and cGMP play important regulatory roles in cellular activities. The regulation of its concentration is mainly determined by the balance between the synthesis of adenylate cyclase and the hydrolysis of phosphodiesterase (PDEs). PDEs are widely distributed in humans and their physiological roles involve multiple research fields. In recent years, PDEs have attracted a lot of attention from many scholars as a new therapeutic target, and have become a new research hotspot. The clinical research of selective PDE 4 and PDE 5 inhibitors has received special attention.
 
cAMP and cGMP act as second messengers of neurotransmitters, hormones, light and odors, and act extensively on target organs in cells such as kinases, ion channels and various PDEs. When a foreign signal is transmitted through the membrane and causes a series of physiological reactions to activate the nucleotide cyclase (as shown in Figure 1), cAMP and cGMP are produced. The mission of the PDEs family is to inactivate the hydrolysis to 5-single. Monophosphate nucleoside 5 (AMP). The balance between the synthesis of nucleotide cyclase and the inactivation of hydrolysis of PDEs determines the concentration of second messenger cAMP and cGMP. It is worth noting that cGMP is not only hydrolyzed by PDEs, but also regulates some PDEs activities. For example, PDE2 can be stimulated by cGMP, while PDE3 can be inhibited by cGMP, and PDE4 is not sensitive to cGMP.

The anti-inflammatory mechanism of PDE4 inhibitors mainly involves [5,8,9]:1 inhibiting the release of various inflammatory mediators/cytokines and inhibiting the expression of IL-4 and IL-5 genes in TH 2 cells. 2 inhibit leukocyte activation (breathing burst) and inhibit leukocyte migration. 3 inhibit the expression or upregulation of cell adhesion factor (CAM). 4 Induces the production of cytokines with inhibitory activity, such as IL-6. 5 induce apoptosis. 6 stimulate the release of endogenous hormones and catecholamines.

Mechanism of action of PDE5 The mechanism of penile erection is complex and there is no unified understanding. Most researchers have now turned their attention from hemodynamics to neurotransmitters. Three neural mechanisms have been shown to be involved in the regulation of cavernosal smooth muscle and spiral arterial tone. That is, adrenergic, cholinergic, and non-adrenergic non-cholinergic (NANC). It is now believed that the NANC mechanism is the main mechanism of cavernous blood vessels and smooth muscle relaxation, and NO is the neurotransmitter of NANC. Penile blood vessels and cavernosal smooth muscle relaxation are key factors throughout the erectile physiology. Sildenafil acts through the NO/cGMP pathway. Under the stimulation of the pelvic nerve NANC nervous system, NO synthase (NOS) acts on the sulfhydryl nitrogen end of L-arginine to produce NO, which is permeable to the cell membrane due to its lipophilic properties. The guanylate cyclase (GC), which rapidly diffuses between adjacent cells and acts on the cells, binds to iron ions in the heme molecule to form a NO-GC complex. This complex binds to the porphyrin site of the enzyme, resulting in a change in conformation that activates GC and produces a large amount of cGMP in the cell. cGMP acts as a second messenger in the cell and produces a series of physiological responses that make the cavernous smooth muscle and Vasodilation. The cGMP transmits information while being inactivated by hydrolysis of PDE5 to 5-GMP. Sildenafil selectively inhibits the hydrolysis of cGMP by cDE5, thereby increasing the concentration of cGMP accumulation and greatly enhancing its vasodilation effect.