Arctigenin inhibits high glucose-induced EMT and cell proliferation to alleviate benign prostatic hyperplasia companied with type 2 diabetes mellitus through MBOAT4/ acylated Ghrelin/GHS-R.

Benign prostatic hyperplasia (BPH) affects aging men worldwide. Type 2 diabetes mellitus (T2DM) and BPH are aging related progressive diseases. High glucose (HG) promoted epithelial mesenchymal transformation (EMT) glucose-dependently in BPH cells. Arctigenin has multiple therapeutic functions as anti-tumor and anti-inflammatory. The role of Arctigenin in BPH and mechanism remain to be investigated. We proposed to explore the therapeutic effect of Arctigenin on BPH accompanied with T2DM and the molecular mechanism. EMT-related markers such as E-Cadherin and Vimentin along with Ki67 and MBOAT4/(acylated) Ghrelin/GHS-R in samples from BPH patients with euglycemia or T2DM were measured and the role of Arctigenin in cell proliferation, migration and vascular-like networks formation of BPH and vascular endothelial cells in HG culture and db/db mice (T2DM) with BPH were explored. Our results demonstrated that positive EMT-markers, MBOAT4/(acylated) Ghrelin/GHS-R and cell proliferation were found in HG samples of BPH patients, HG-induced cells and db/db mice. Arctigenin suppresses cell proliferation, cell migration and EMT, angiogenesis formation and attenuates BPH in mice under normal or HG condition. Our study suggested that Arctigenin might alleviate BPH companied with type 2 diabetes mellitus by inhibiting Ghrelin-induced EMT and cell proliferation through regulating MBOAT4/(acylated) Ghrelin/GHS-R.