Cynomorium Songaricum (CS), a perennial succulent herb parasitic on the roots of on the roots of Nitraria L species, thrives in arid desert environments across Asia, Africa, and Europe (Cui et al., 2013). In traditional Chinese medicine, CS is known as “Suoyang” and has been historically prescribed for the treatment of male sexual dysfunction (H. P. Liu et al., 2012). Its traditional use is well-documented and has persisted for centuries as a valued nutritional and medicinal resource (J. Li et al., 2025a, Li et al., 2025b). Recent pharmacological studies have uncovered a broader range of bioactivities for CS, including potential therapeutic effects against Alzheimer's disease (Cheng et al., 2021), diabetes (Z.-Q. Shi et al., 2021), benign prostatic hyperplasia (Tao et al., 2019), and obesity (Chen et al., 2020). Despite its traditional application for enhancing male sexual function, the specific active compounds and their underlying mechanisms have not been fully elucidated. Our research identifies that polysaccharides from CS (CSP) are potent inhibitors of phosphodiesterase-5 (PDE5), a critical enzyme expressed in smooth muscle cells and a validated drug target for both erectile dysfunction (ED) (J. Feng et al., 2025) and pulmonary hypertension (PH) (Corbin, 2004).

Penile erection is a neurovascular process initiated by sexual arousal, which triggers parasympathetic nerve activity. This leads to the release of nitric oxide (NO) in the corpus cavernosum, elevating intracellular cyclic guanosine monophosphate (cGMP) levels. The accumulation of cGMP activates protein kinase G (PKG) (Zhao et al., 2025), which in turn promotes calcium ion efflux, leading to the relaxation of vascular smooth muscle and increased arterial blood flow into the penile cavernous sinuses. This process compresses the subtunical venules, reducing venous outflow and thereby raising intracavernosal pressure (ICP) to produce a rigid erection (Vanhoutte et al., 2017). PDE5 inhibitors (PDE5Is), such as sildenafil, vardenafil, tadalafil, and avanafil, are first-line oral therapies for ED and PH that function by preventing the degradation of cGMP (Bruzziches et al., 2013). However, due to the high homology among PDE enzyme family members, these inhibitors often lack specificity, leading side effects such as headaches, flushing, dyspepsia, and visual disturbances (Corona et al., 2016). Consequently, the development of novel PDE5Is with improved safety and specificity is a significant research priority.

Natural products are increasingly recognized as valuable sources for novel therapeutics due to their unique chemical structures and favorable safety profiles (Luo et al., 2024). For example, icariin, derived from the traditional Chinese medicine Epimedium, is known to exhibit PDE5 inhibitory activity (Dell’Agli et al., 2008). Similarly, flavonoids such us quercetin and kaempferol have also demonstrated PDE5 inhibition (Corbin, 2004). Guided by the traditional use of CS for male sexual disorders, this study confirms that CSP significantly inhibits PDE5 activity. As key constituents of natural products, polysaccharides have historically presented significant research challenges due to their high polarity and structural complexity; however, recent advancements in chromatography and target validation now enable their detailed structural characterization and mechanistic elucidation (T. Wang et al., 2025; Huang et al., 2025; Shui et al., 2025). Previous research has already established that CSP exhibits a range of bioactivities, such as antioxidant (M. Li et al., 2025a, Li et al., 2025b; F. Wang et al., 2016), immunomodulatory (J. Li et al., 2024), antiviral (Tuvaanjav et al., 2016), and anticancer effects (F. Yang et al., 2016; G. Shi et al., 2011).

In this study, we employed cellular and animal models to investigate the regulatory effects of CSP on PDE5-mediated biological functions. We also assessed its absorption and toxicity profiles. Our findings provide robust scientific evidence supporting the traditional medicinal use of CS and identify CSP as a promising new class of PDE5 inhibitors. These results highlight the potential of CSP as a safe, natural therapeutic agent for ED, warranting further investigation for its clinical potential.