Nanoliposomal myricetin attenuates diabetic testicular tissue injury and cellular dysfunction via coordinated modulation of PI3K/AKT/mTOR/SREBP-1c, Nrf2/HO-1, NF-κB, and caspase signaling pathways.

BACKGROUND

Diabetes is known to cause severe disruptions in metabolic and reproductive health, often leading to testicular dysfunction and impaired fertility.

OBJECTIVES

In this study, we investigated the therapeutic potential of myricetin (MYR), a natural flavonoid, delivered in a nanoliposomal formulation (MYR-LNPs) to counteract diabetes-induced testicular damage in a rat model of type 2 diabetes mellitus (T2DM).

METHODS

Ninety adult male albino rats were assigned to six groups, including non-diabetic controls, diabetic controls, and treatments with either free MYR or MYR-LNPs. Diabetes was induced using the nicotinamide-streptozotocin (NA-STZ) model, and all interventions lasted eight weeks.

RESULTS

Our findings revealed that diabetes significantly disrupted body weight, glycemic balance, reproductive hormones, testicular weight, sperm quality, and antioxidant defense systems. It also elevated markers of oxidative stress, inflammation, and apoptosis, while impairing mitochondrial functions with downregulation of the PI3K/AKT/mTOR/SREBP-1c pathway. Notably, oral administration of MYR-LNPs effectively mitigated these adverse effects, restoring glucose homeostasis, reproductive hormone levels, sperm parameters, antioxidant enzyme activities, PI3K/AKT/mTOR/SREBP-1c signaling cascade, and testicular tissue architecture and cellular integrity to near-normal levels. The nanoliposomal formulation consistently outperformed the crude form of MYR, highlighting the advantages of nanoparticle delivery in enhancing bioavailability and therapeutic efficacy. Overall, our study demonstrates that MYR-LNPs provide a protective and restorative effect against diabetes-induced testicular tissue injury and cellular dysfunction, offering promising insights into natural, nanotechnology-based interventions for male reproductive health.

CONCLUSION

These results suggest that MYR, when delivered in a targeted nanoliposomal form, may serve as a potential therapeutic strategy to preserve testicular cellular homeostasis and fertility potential in diabetic conditions.