Hyperuricemia (HUA) is a metabolic disease characterized by high levels of uric acid (UA) in the blood and varying degrees of kidney damage. Desirable nanoliposomes should simultaneously exhibit efficient biocompatibility and effective drug delivery. However, they both usually require special structural properties. Herein, we propose a strategy to prepare nanoliposomes with varying rigidity by replacing cholesterol (CH) with phytosterol esters (PE). The results showed that the particle size of phytosterol esters naringenin nanoliposomes (PE-NAR) was 179.5 nm, and the encapsulation efficiency (EE) was 79.93%. In atomic force microscopy (AFM) tests, PE-NAR showed a 1-fold increase in rigidity compared to cholesterol naringenin nanoliposomes (CH-NAR). By observing the effects of naringenin nanoliposomes (NAR-NLs) on the physiological and biochemical indicators in HUA mice, we explore its impact on kidney damage and inflammatory pathways in HUA mice. The results show that NAR-NLs significantly inhibit UA levels and improve kidney damage. Compared to oral naringenin, NAR-NLs generally enhance the in vivo antioxidant effects of naringenin. Furthermore, high-rigidity PE-NAR downregulated the renal inflammatory factor interleukin-1β (IL-1β) to 6.67%, demonstrating the highest inhibitory effect. Further experiments have demonstrated that naringenin exerts a protective effect in kidney injury by inhibiting the activation of NLRP3 inflammasome and reducing oxidative stress within the body. In summary, by adjusting the rigidity of the nanoliposomes, the oral administration of naringenin can effectively improve the alleviation of HUA.

Gastric ulcer is a widespread disease caused by various etiologies. Dendrobium officinale flowers exert several health benefits owing to their rich flavonoid content. In this study, protective effects and possible action mechanisms of D. officinale flowers’ flavonoid enriched extract (DOFF) were assessed against gastric ulcer. The result of sodium nitrite-aluminum nitrate colorimetry showed that 52.34% of the total extractive was flavonoid, and ultra-high performance liquid chromatography time of flight mass spectrometer (UPLC-Q-TOF/MS) revealed the presence of 28 components in DOFF of which 14 belonged to flavonoids. In addition, in vivo assay revealed DOFF potential in reducing the formation of ethanol-induced gastric mucosal lesions, with drop-in ulcer index from 64.33 ± 8.76 to 32.00 ± 4.47. Similar results were revealed in human gastric mucosal epithelia cells, with cells viability to increase from 27.2% to 61.6% post DOFF administration. To analyzed the protect effect of DOFF, we used Western blotting and immunofluorometric assay to revealed the expression levels of key proteins in cell pathways. The results showed that DOFF (320 μg/mL) could increase the level of oxidation marker protein (HO-1), apoptosis regulatory protein (Bcl-2) and autophagy marker (LC3β) by 50.84%, 43.85%, and 59.21% compared with ethanol-treated group respectively. Further analyzed of the mitochondrial activity and apoptosis pathway, we found that DOFF appeared to mitigate against ethanol-induced gastric mucosal injury via AMPK/mTOR/ULK1 and PI3K/AKT autophagy signaling pathways.