To investigate the therapeutic efficacy of Cynomorium songaricum Rupr. ( C . songaricum , Suo Yang) polysaccharide (CSP) against pulmonary hypertension (PH) and explore whether its effects are associated with modulation of the phosphodiesterase type 5-cyclic guanosine monophosphate-protein kinase G (PDE5-cGMP-PKG) signaling pathway using both in vivo rat models and in vitro cultures of rat pulmonary arterial smooth muscle cells (RPASMCs). A rat model of PH was established via monocrotaline (MCT) administration, followed by daily oral gavage of CSP at low, medium, and high doses for 28 consecutive days. Hemodynamic parameters, including right ventricular systolic pressure (RVSP), were measured using right heart catheterization (RHC). Meanwhile, right ventricular hypertrophy indices (RVHI) and electrocardiographic parameters underwent systematic evaluation. For the in vitro assays, RPASMCs were exposed to Cobalt (II) chloride (CoCl 2 ) to establish a hypoxia-like injury model and then treated with CSP to evaluate its effects on cell proliferation, migratory capacity, and intracellular cGMP content. In vivo , CSP treatment dose-dependently mitigated MCT-induced hemodynamic dysfunction (e.g., RVSP and mPAP, P < .001), alleviated pathological pulmonary vascular remodeling (WA% and WT%, P < .001), mitigated right ventricular hypertrophy secondary to pressure overload (RVHI, P = .015), and reversed abnormal electrocardiographic manifestations in PH rats (e.g., QTc, P = .007; QRS, P = .010). In vitro , CSP markedly inhibited the CoCl 2 -triggered excessive proliferation (CCK-8, P = .013; EdU, P = .003) and migration (Transwell and wound-healing assays, P < .001) of RPASMCs and simultaneously restored the reduction in intracellular cGMP levels induced by hypoxic exposure ( P = .008). CSP exerts remarkable therapeutic effects against PH, mainly by inhibiting phosphodiesterase 5 and restoring the cGMP-PKG signaling cascade. These findings provide preclinical support for further investigation of CSP as a potential therapeutic candidate for PH.
Wang et al. (Fri,) studied this question.