The Effect and Mechanism of Oleanolic Acid in the Treatment of Metabolic Syndrome and Related Cardiovascular Diseases

Abstract

Metabolic syndromes (MetS) and related cardiovascular diseases (CVDs) pose a serious threat to human health. MetS are metabolic disorders characterized by obesity, dyslipidemia, and hypertension, which increase the risk of CVDs' initiation and development. Although there are many availabile drugs for treating MetS and related CVDs, some side effects also occur. Considering the low-level side effects, many natural products have been tried to treat MetS and CVDs. A five-cyclic triterpenoid natural product, oleanolic acid (OA), has been reported to have many pharmacologic actions such as anti-hypertension, anti-hyperlipidemia, and liver protection. OA has specific advantages in the treatment of MetS and CVDs. OA achieves therapeutic effects through a variety of pathways, attracting great interest and playing a vital role in the treatment of MetS and CVDs. Consequently, in this article, we aim to review the pharmacological actions and potential mechanisms of OA in treating MetS and related CVDs.

Keywords: cardiovascular diseases; metabolic syndrome; oleanolic acid.

Figure 1

OA in the treatment of MetS and CVDs. Chemical structures of OA drawn according to [14]. COX: cyclooxygenase; eNOS: endothelial nitric oxide synthase; NO: nitric oxide; FFA: free fatty acid; EDHF: endothelium-derived hyperpolarizing factor. ↓ indicates inhibition; ↑ indicates promotion.

Figure 2

The molecular mechanisms of OA in treating MetS and CVDs: regulation of PPAR, PI3K/Akt, and NF-κB pathways. Information is derived from the references in Table 1 and Table 2. PPAR: peroxisome proliferator-activated receptor; C/EBPα: CCAAT/enhancer-binding protein α; UCP1: coupled protein 1; CPT1A: carnitine palmitoyltransferase 1A; ACC: acetyl-CoA carboxylase; FAS: fat synthesis factor; ACACA: acetyl-CoA carboxylase alpha; GLUT: glucose transporter; FATP-1: fatty acid transport protein-1; ACSL: long-chain acyl-CoA synthetase; Akt: protein kinase B; eNOS: endothelial nitric oxide synthase; IRS: insulin receptor substrate; PI3K: phosphatidylinositol-3-kinase; mTOR: mammalian target of rapamycin; GSK3: glycogen synthase kinase-3; GS: glycogen synthase; GP: glycogen phosphorylase; FoxO1/3a: forkhead box O1/3a; G6Pase: glucose-6-phosphatase; PEPCK: phosphoenolpyruvate carboxykinase; MAPK: mitogen-activated protein kinase; Ikk: IκB kinase; NF-κB: nuclear factor-κB; TNF-α: tumor necrosis factor α; IL-6: interleukin 6; MCP1: monocyte chemoattractant protein-1; GLUT: glucose transporter. ↓ indicates inhibition; ↑ indicates promotion.