| First Author | He Z | Year | 2022 |
| Journal | Phytomedicine | Volume | 98 |
| Pages | 153956 | PubMed ID | 35151213 |
| Mgi Jnum | J:351778 | Mgi Id | MGI:7664293 |
| Doi | 10.1016/j.phymed.2022.153956 | Citation | He Z, et al. (2022) Esculentoside A alleviates cognitive deficits and amyloid pathology through peroxisome proliferator-activated receptor gamma-dependent mechanism in an Alzheimer's disease model. Phytomedicine 98:153956 |
| abstractText | BACKGROUND: Alzheimer's disease (AD) is characterized clinically by cognitive deficits and pathologically by amyloid-beta (Abeta) deposition and tau aggregation, as well as the brain atrophy. Esculentoside A (EsA), a neuroprotective saponin, is isolated from Phytolacca esculenta and shows potent health-promoting effects in a variety of experimental models. However, there are minimal reports on the effects of EsA on triple transgenic AD mice. PURPOSE: The current research aimed at investigating the protective effects and underlying mechanisms of EsA on the mitigation of cognitive deficits and pathology in triple transgenic AD mice. METHODS: Triple transgenic AD mice (3 x Tg-AD) of 8 months old received intraperitoneal treatment of 5 or 10 mg/kg EsA for 8 consecutive weeks. Morris water maze test and open field test were made to evaluate the cognitive function and degree of anxiety of the mice. Liquid chromatography with tandem mass spectrometry analysis was performed to characterize and to quantify EsA in the blood and brain of mice. Immunofluorescence assay and Western blot were adopted to measure the levels of peroxisome proliferator-activated receptor gamma (PPARgamma) and key proteins in Abeta pathology, ER stress- and apoptosis-associated pathways. The combination of EsA with PPARgamma were theoretically calculated by molecular docking programs and experimentally confirmed by the bio-layer interferometry technology. RESULTS: Supplemental EsA could improve the cognitive deficits of 3 x Tg-AD mice. EsA penetrated the brain-blood barrier to exert a strong effect on AD mice, evidenced as decreasing Abeta generation, reducing the degrees of oxidative and ER stress, and mitigating neuronal apoptosis through the increase of PPARgamma expression. In the culture of primary neurons, addition of PPARgamma inhibitor GW9662 eliminated the effects of EsA on AD pathologies. Direct combination of EsA with PPARgamma were demonstrated by molecular docking programs and bio-layer interferometry technology. CONCLUSIONS: For the first time, these outcomes revealed that EsA could penetrate the brain-blood barrier to exert a strong effect on ameliorating cognitive deficits in 3 x Tg-AD mice and exert neuroprotective effects toward AD pathology via PPARgamma-dependent mechanism. |
