Curcumin Alleviates Gastric Precancerous Lesions by Modulating YAP/TEAD Signaling Pathway

Curcumin (CUR), a major active compound in Curcuma longa Linn., exhibits various bioactivities, but its potential in treating gastric precancerous lesions (GPL) and the underlying mechanisms remain unexplored. To investigate the effect and possible mechanism of CUR on GPL both in vitro and in vivo, an N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced rat model of GPL and a malignant transformation model of human gastric epithelial cells (MC cells) were employed. The results showed that CUR treatment reversed intestinal metaplasia and dysplasia in GPL rats. Furthermore, CUR treatment led to decreased levels of gastrin 17 and increased levels of pepsinogen I (PG I) and prostaglandin E2 (PGE2) in the rat model. Compared to normal controls, GPL rats exhibited elevated levels of interleukin 1β (IL-1β), IL-4, IL-6, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ), along with decreased levels of IL-10. CUR treatment reduced the levels of IL-1β and IL-4. Immunohistochemical analysis revealed that protein expressions of Yes-associated protein 1 (YAP1) and TEA domain transcription factor 1 (TEAD1) were significantly upregulated in human GPL tissues, while p-YAP1 expression was downregulated. CUR treatment downregulated YAP1 and TEAD1, and upregulated p-YAP1 and apoptosis-related proteins both in vivo and in vitro. In conclusion, CUR could alleviate gastric mucosal inflammation and prevent the occurrence and progression of GPL, potentially via modulation of the YAP/TEAD axis in the Hippo signaling pathway.