Exploring extracts from Wendlandia Uvariifolia Subsp. Chinensis (Merr.) Cowan as natural phosphodiesterase type 5 inhibitors with preclinical anti-erectile dysfunction activity.

Wendlandia uvariifolia subsp. chinensis (Merr.) Cowan is a traditional medicinal plant used by the Li ethnic group in Hainan Province, China, for the treatment of herpes zoster. However, its pharmacological properties remain unclear. This study aimed to evaluate its phosphodiesterase type 5 inhibitory activity, identify the active components, and explore its therapeutic potential for erectile dysfunction. Through high-throughput screening of 1200 traditional Chinese herbal medicines, this plant was identified as a potential phosphodiesterase type 5 inhibitor. Bioactivity-guided fractionation and gas chromatography-mass spectrometry analysis identified the petroleum ether fraction as the most active fraction, while phytol, one of its identified constituents, inhibited phosphodiesterase type 5 in vitro with an IC₅₀ value of 2.5 ± 0.1 μmol/L. In H₂O₂-injured endothelial cells, petroleum ether fraction significantly restored nitric oxide production. In a paroxetine-induced erectile dysfunction rat model, the fraction improved sexual behavior parameters, restored NO/cGMP signaling, and alleviated pathological remodeling and fibrosis in the corpus cavernosum. In a diabetes mellitus-associated erectile dysfunction rat model, the fraction also improved corpus cavernosum architecture, increased smooth muscle content, and reduced fibrosis, although the increase in the intracavernous pressure/mean arterial pressure ratio did not reach statistical significance. Overall, the results suggest the preclinical anti-erectile dysfunction potential of petroleum ether fraction and support its further mechanistic, pharmacokinetic, safety, and translational evaluation.