Typhae pollen attenuates atherosclerosis by enhancing vascular endothelium function and lipid metabolism

Abstract

Ethnopharmacological relevance: Atherosclerosis is a pathological condition characterized by the accumulation of lipid-rich lesions within the endothelial layer, and it remains a significant contributor to global morbidity and mortality. Typhae Pollen (TP) has been extensively used in the treatment of blood stasis. However, the potential protective effects and underlying mechanisms of TP in atherosclerosis remain poorly understood.

Aim of the study: To explore the protective effects and mechanisms of Typhae Pollen extract (TPEX) on atherosclerosis.

Materials and methods: We established atherosclerosis models in ApoE^-/- mice using high-fat diet (HFD), with continuous oral administration of TPEX at specified doses and intervals in vivo. To explore the underlying mechanisms of TPEX, we employed integrated network pharmacology and transcriptome analysis. In vitro, palmitic acid and H₂O₂ induced primary hepatic cells lipid accumulation and endothelial cells dysfunction model were employed to investigate the potential mechanisms of TPEX using Western blot, immunofluorescence, nuclear/cytoplasmic proteins isolation techniques.

Results: TPEX improved aortic lipid deposition and arterial injury, alleviated hyperlipidemia, and reduced liver damage in HFD-induced ApoE^-/- mice. Mechanistically, TPEX mitigated endothelial cell senescence through the p53/p21 signaling pathway, suppressed inflammation by inhibiting the translocation of p65 into the nucleus, and alleviated oxidative stress by preventing the nuclear translocation of NRF2 and modulating the NRF2/HO-1 pathway. Furthermore, TPEX reduced inflammation and regulated lipid metabolism via the NOD signaling pathway and the SREBPs signaling pathway in the liver.

Conclusion: TPEX alleviates atherosclerosis by regulating endothelial dysfunction, hepatic lipid metabolism, and inflammatory processes. These findings provide new insights into the protective role of TPEX in atherosclerosis, especially regarding endothelial dysfunction and hepatic lipid metabolism.

Keywords: Atherosclerosis; Endothelial dysfunction; Lipid metabolism; Typhae pollen; p53/p65/NRF2/NOD/SREBPs signal pathway.