Hexahydrocurcumin mitigates angiotensin II-induced proliferation, migration, and inflammation in vascular smooth muscle cells

Luckika Panthiya; Jiraporn Tocharus; Waraluck Chaichompoo; Apichart Suksamrarn; Chainarong Tocharus

doi:10.17179/excli2023-6124

Hexahydrocurcumin mitigates angiotensin II-induced proliferation, migration, and inflammation in vascular smooth muscle cells

EXCLI J. 2023 Jun 5:22:466-481. doi: 10.17179/excli2023-6124. eCollection 2023.

Authors

Luckika Panthiya^{1

2}, Jiraporn Tocharus³, Waraluck Chaichompoo⁴, Apichart Suksamrarn⁴, Chainarong Tocharus^{1

5}

Affiliations

¹ Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
² Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand.
³ Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
⁴ Department of Chemistry and Center of Excellence of Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand.
⁵ Functional Food Research Center for Well-Being, Chiang Mai University, Chiang Mai 50200, Thailand.

Abstract

The proliferation and migration of vascular smooth muscle cells (VSMCs) play vital roles in the pathogenesis of atherosclerosis and hypertension. It has been proposed and verified that hexahydrocurcumin (HHC), a metabolite form of curcumin, has cardiovascular protective effects. This study examined the effect of HHC on angiotensin II (Ang II)-induced proliferation, migration, and inflammation in rat aortic VSMCs and explored the molecular mechanisms related to the processes. The results showed that HHC significantly suppressed Ang II-induced proliferation, migration, and inflammation in VSMCs. HHC inhibited Ang II-induction of the increase in cyclin D1 and decrease in p21 expression in VSMCs. Moreover, HHC attenuated the generation of reactive oxygen species (ROS), and the expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and matrix metalloproteinases-9 (MMP9) in Ang II-induced VSMCs. The proliferation, migration, inflammation, and ROS production were also inhibited by GKT137831 (NADPH oxidase, NOX1/4 inhibitor) and the combination of HHC and GKT137831. In addition, HHC restored the Ang-II inhibited expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). These findings indicate that HHC may play a protective role in Ang II-promoted proliferation, migration, and inflammation by suppressing NADPH oxidase mediated ROS generation and elevating PPAR-γ and PGC-1α expression. See also Figure 1(Fig. 1).

Keywords: angiotensin II; hexahydrocurcumin; inflammation; migration; proliferation; vascular smooth muscle cell.