Protective effects of Euphorbia heterophylla against testicular degeneration in streptozotocin-induced diabetic rats in relation to phytochemical profile

Background: Diabetes mellitus (DM) poses a major risk to human health due to an array of implications, one of which is a detrimental effect on the testicular and reproductive functions. Euphorbia heterophylla is widely recognized for its medicinal properties worldwide. Methods and findings: The objective of this study was to profile E. heterophylla ethanol extract (EH-EtOH) and elucidate its protective role in oxidative stress, relieving inflammatory action of hyperglycemia-induced testicular degeneration and restoring the normal histological structure with physiological properties of testicular tissue in streptozotocin (STZ)-induced DM. High-resolution ultra-performance liquid chromatography-mass spectrometry (UHPLC-ESI-Orbitrap-MS) analysis was employed to analyze the compounds present in EH-EtOH. The protective effect of EH-EtOH against testicular degeneration in the rat model of DM was evaluated by measuring improvements in blood glucose levels, body weight, testicular inflammation, oxidative damage, testicular microcirculation impairment, and apoptosis of testicular cells induced by STZ. The chemical profiling of EH-EtOH revealed the presence of 52 compounds, including phenolic acids, flavonoids, coumarins, phloroglucinols, and triterpenes. Notably, this study identified isovitexin-C-hexoside, isorhamnetin-O-hexoside, diosmetin, and halfordin for the first time in Euphorbia species. Treatment with EH-EtOH effectively mitigated the damage caused by STZ, as evidenced by restored testosterone (T4) levels and antioxidant capacity, reduced expression of pro-inflammatory cytokines, improved testicular microcirculation, and inhibition of apoptosis in the testes. Conclusions: These results emphasize the potential therapeutic effect of E. heterophylla on DM related to male infertility and reproductive dysfunctions via its antioxidant/angiogenetic /anti-apoptotic effect.