Exploring Extracts from Wendlandia Uvariifolia Subsp. Chinensis (Merr.) Cowan as Natural PDE5 Inhibitors with Potent Anti-Erectile Dysfunction Activity

Wendlandia uvariifolia subsp. chinensis (Merr.) Cowan ( W. u. chinensis ) 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 (PDE5) inhibitory activity, identify the active components, and explore its therapeutic potential for erectile dysfunction (ED). Through high-throughput screening of 1200 traditional Chinese herbal medicines, this plant was identified as a potential PDE5 inhibitor. After activity evaluation and gas chromatography-mass spectrometry analysis, its petroleum ether fraction (PE) exhibited the strongest PDE5 inhibitory activity, and its main component, phytol, was identified as a novel PDE5 inhibitor with an unreported structural framework. PE could induce endothelial cells to produce nitric oxide in vitro (NO). PE significantly improved the sexual behavior indicators, hormone levels, and penile tissue of paroxetine-induced ED rats in vivo, while increasing the intracavernous pressure/mean arterial pressure (ICP/MAP) ratio and reducing fibrosis in diabetes-related ED (DMED) rats. This study confirms that the PE fraction of W. u. chinensis has potent PDE5 inhibitory activity, providing a basis for the development of natural therapeutic drugs for ED and herbal medicine.