Melatonin ameliorates circadian rhythm disruption induced erectile dysfunction by inhibiting oxidative stress mediated pyroptosis via Nrf2/HO‑1 axis

experiments respectively proved that CRD increased oxidative stress of penile corpus cavernosum and HUVECs by reducing nuclear factor erythroid 2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1) production, while MT increased Nrf2/HO‑1 to inhibit the oxidative stress. Meanwhile, CRD promoted pyroptosis in penile corpus cavernosum and HUVECs by increasing NLR family pyrin domain containing 3 (NLRP3) activation, which was relieved by MT through the attenuation of oxidative stress. Moreover, the reactive oxygen species inhibitor (NAC) inhibited CRD‑induced pyroptosis of HUVECs to preserve normal function, which confirmed that MT alleviated NLRP3‑mediated pyroptosis to preserved CRD‑induced ED by reducing oxidative stress. In conclusion, it was demonstrated that CRD‑induced ED by triggering an oxidative stress‑pyroptosis cascade. Conversely, MT treatment effectively counteracts this pathology by activating the Nrf2/HO‑1 pathway to suppress oxidative stress, thereby attenuating NLRP3‑mediated pyroptosis and ultimately restoring erectile function. These results provide the first systematic evidence for the central role of the oxidative stress‑pyroptosis axis in CRD‑induced ED, establishing a solid theoretical foundation for MT as a promising therapeutic strategy for CRD‑related ED.