Effects of Cnidium officinale, Pueraria lobata Ohwi, and Leonurus japonicus Extract on Vascular Endothelial Dysfunctions in Ovariectomized Rats and Molecular Mechanisms.

Menopause is the natural period of aging in women induced by ovary deterioration, resulting in estrogen deficiency. We evaluated the antioxidative and anti-inflammatory properties of Cnidium officinale, Pueraria lobata Ohwi, and Leonurus japonicus (CPL) extracts on vascular endothelial dysfunction. After treatment, CPL extracts decreased serum lipid profiles, serum vasoactive substances, tail temperatures, and cardiovascular risk indices. In ovariectomized rats, vasodilation significantly increased, with an increase in endothelial nitric oxide synthase (eNOS) in the CPL200 and CPL500 groups compared with the OVX group (p < 0.05). The extracts also significantly reduced vascular cell adhesion protein 1 (VCAM-1) in the CPL50, CPL100, and CPL200 groups compared with the OVX group (p < 0.05, p < 0.01, and p < 0.001, respectively). Intercellular adhesion molecule 1 (ICAM-1) was also reduced in the CPL100 and CPL200 groups compared with the OVX group (p < 0.001 and p < 0.0001, respectively); this was achieved through the downregulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inducible nitric oxide (iNOS), which resulted in the synthesis of nuclear factor erythroid 2-related factor 2 (NRF2) and eNOS in HUVECs. Our results show that CPL extracts could provide cardioprotective effects against vascular endothelium dysfunction by decreasing inflammation and upregulating vasodilation, ascertained by evaluating the antioxidant systems of ovariectomized rats. Further studies are needed to explore the long-term cardioprotective effects.