Delphinidin-3- O-glucoside, an active compound of Hibiscus sabdariffa calyces, inhibits oxidative stress and inflammation in rabbits with atherosclerosis

Abstract

Context: Delphinidin-3-O-glucoside (DP) is a bioactive compound of Hibiscus sabdariffa L. (Malvaceae) (Roselle) calyces and exerts endothelial protection and lipid-lowering activities, which provided a basis for the prevention and treatment of cardiovascular diseases.

Objectives: To investigate the therapeutic effects of DP against atherosclerosis.

Materials and methods: A rabbit model of atherosclerosis (AS) was established by 12 weeks of a high-fat diet (HFD). The rabbits were divided into five groups: control, AS, simvastatin (4 mg/kg), and two DP groups (10 and 20 mg/kg). After treatment with DP or simvastatin by oral gavage for 12 weeks, the lipid profiles were measured. Histopathological assessment of the aorta was performed by H&E staining. Oxidative stress and inflammation-related markers were analyzed by ELISA kit and real-time RT-PCR.

Results: DP (20 mg/kg) decreased serum TG (2.36 ± 0.66 vs. 4.33 ± 0.27 mmol/L for the AS group), TC, LDL-C, and HDL-C (all p < 0.05). DP (20 mg/kg) also reduced lipid levels in the liver and aorta. DP (20 mg/kg) down-regulated the mRNA levels of IL-6, VCAM-1, and NF-κB and up-regulated the mRNA levels of GSH-PX and SOD1.

Conclusions: This study proved that DP alleviated the HFD-induced oxidative stress and inflammation in atherosclerosis rabbits. These results provided the scientific basis for developing novel therapies.

Keywords: Hypolipidemic effect; antioxidant effect; high-fat diet; inflammatory cytokines.

Figure 1.

Histological changes of the rabbit abdominal aorta (H&E) after 12 weeks of DP treatment (A), bar = 50 µm, 200× magnification. The molecular structure of delphinidin-3-O-glucoside (B).

Figure 2.

Serum levels of lipid profiles were declined by delphinidin-3-O-glucoside (DP). The serum levels of TG (A), TC (B), LDL-C (C), and HDL-C (D) were measured by commercial kits. Values are expressed as mean ± SD. ^##p < 0.01 vs. control (Con) group; *p < 0.05 vs. atherosclerosis (AS) group; **p < 0.01 vs. atherosclerosis (AS) group.

Figure 3.

Effects of delphinidin-3-O-glucoside (DP) treatment on lipid profiles: liver TG (A), liver TC (B), aorta TG (C), aorta TC (D). Values are expressed as mean ± SD. ^##p < 0.01 vs. control (Con) group; *p < 0.05 vs. atherosclerosis (AS) group; **p < 0.01 vs. atherosclerosis (AS) group.

Figure 4.

Effects of delphinidin-3-O-glucoside (DP) treatment on serum oxidative markers: MDA (A), CAT (B), GSH-Px (C), and SOD (D). Values are expressed as mean ± SD. ^##p < 0.01 vs. control (Con) group; *p < 0.05 vs. atherosclerosis (AS) group; **p < 0.01 vs. atherosclerosis (AS) group.

Figure 5.

Effects of delphinidin-3-O-glucoside (DP) treatment on serum inflammation markers: ICAM-1 (A), MCP-1 (B), VCAM-1 (C), CRP (D), IL-6 (E), and TNF-α (F). Values are expressed as mean ± SD. ^##p < 0.01 vs. control (Con) group; *p < 0.05 vs. atherosclerosis (AS) group; **p < 0.01 vs. atherosclerosis (AS) group.

Figure 6.

Effects of delphinidin-3-O-glucoside (DP) treatment on aorta inflammation markers: ICAM-1 (A), MCP-1 (B), VCAM-1 (C), CRP (D), IL-6 (E), and TNF-α (F). Values are expressed as mean ± SD. ^##p < 0.01 vs. control (Con) group; *p < 0.05 vs. atherosclerosis (AS) group; **p < 0.01 vs. atherosclerosis (AS) group.

Figure 7.

Delphinidin-3-O-glucoside (DP) up-regulated the mRNA expression of aortic SOD1 (A) and GSH-Px (B). Values are expressed as mean ± SD. ^##p < 0.01 vs. control (Con) group; *p < 0.05 vs. atherosclerosis (AS) group; **p < 0.01 vs. atherosclerosis (AS) group.

Figure 8.

Delphinidin-3-O-glucoside (DP) down-regulated the mRNA expression of aortic IL-6 (A), NF-κB (B), and VCAM-1 (C). Values are expressed as mean ± SD. ^##p < 0.01 vs. control (Con) group; *p < 0.05 vs. atherosclerosis (AS) group; **p < 0.01 vs. atherosclerosis (AS) group.