Fig 2: A schematic illustration of W1302 alleviating learning impairments induced by hypoperfusion with hypertension through the NO-regulated NF-κB signaling pathway and mitochondrial function preservation. In this schematic diagram, SHR-2VO rats, a VaD model associated with spontaneous hypertension, significantly increase pIκB, pNF-κB, iNOS and TNF-α levels, which further damage mitochondrial function and increases oxidative stress. W1302 activated NO/cGMP and further inhibited the NF-κB signaling pathway, decreasing inflammatory factors such as TNF-α and iNOS levels, and protecting cells from mitochondria damage.

Fig 3: The effects of W1302 on NO production and activities of eNOS or iNOS in SHR-2VO rats. SHR-2VO rats: permanent occlusion of bilateral common carotid arteries in spontaneously hypertensive rats; WKY rats: age-matched Wistar Kyoto rats as non-hypertensive sham-operated control. (A,B) The nitric oxide assay kit for detecting the production of NO (n = 8). (C) EC50 value of cGMP production in SKN cells after 4 h of incubation with W1302 (n = 4). (D–G) eNOS and iNOS were analyzed by Elisa kits (n = 8). Data were expressed as mean ± S.E.M. # p < 0.05 vs. WKY rats and * p < 0.05, ** p < 0.01, vs. SHR-2VO rats.