Key result
Polydatin and P. sibiricum polysaccharides reduce serum lipids and lipid accumulation in ApoE-/- mice.
Why the study?
Atherosclerosis involves inflammatory responses and oxidative stress, and the potential synergistic anti-atherosclerotic effects of polydatin and Polygonatum sibiricum polysaccharides via TLR4/MyD88/NF-κB inhibition were unclear.
Does the combination of polydatin and Polygonatum sibiricum polysaccharides reduce atherosclerosis in ApoE-/- mice?
Does the combination of polydatin and Polygonatum sibiricum polysaccharides reduce atherosclerosis in ApoE-/- mice?
The combination of polydatin and Polygonatum sibiricum polysaccharides attenuates atherosclerosis in ApoE-/- mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway.
May support preclinical testing of PD plus PSP in atherosclerosis; leaves open clinical translation pending human trials.
Objective. Atherosclerosis is a chronic inflammatory disease, which is closely related to hyperlipidemia, inflammatory responses, and oxidative stress. As natural products, polydatin (PD) and Polygonatum sibiricum polysaccharides (PSP) have remarkable pharmacological effects in anti-inflammatory, antioxidant stress, and lipid regulation. In this study, we sought to investigate whether the combination of polydatin and P. sibiricum polysaccharides play an anti-atherosclerotic role in alleviating inflammatory responses by inhibiting the toll-like receptor4 (TLR4)/myeloid differentiation factor88(MyD88)/nuclear factor-kappa B(NF-κB) signaling pathway. Methods. Thirty-two ApoE-/- mice were fed with a high-fat diet (HFD) starting at the age of 8 weeks. Mice were randomly divided into four groups; (1) model group, (2) PD (100 mg/kg) + PSP (50 mg/kg) group, (3) TAK-242 (3 mg/kg) (TLR4 inhibitor) group, (4) PD (100 mg/kg) + PSP (50 mg/kg) + TAK-242 (3 mg/kg) group. Eight age-matched wild-type C57BL/6J mice fed an ordinary diet were used as a control group. Blood lipid levels were measured with an automatic biochemical analyzer. The lipid accumulation and histopathological changes in the aorta and liver were observed by Oil Red O and hematoxylin and eosin (H&E) staining, respectively. ELISA was performed to measure the serum levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). Western blot analysis was performed to analyze the expression of key proteins in the TLR4/MyD88/NF-κB signaling pathway. Results. Compared with the model group, the combination of PD and PSP significantly inhibit serum lipids (low-density lipoprotein cholesterol, total cholesterol, and triglyceride) and cell adhesion molecules (VCAM-1, ICAM-1). Oil Red O staining indicated that the combination of PD and PSP decrease lipid accumulation in the aorta and liver. Moreover, H&E staining suggested that the combination of PD and PSP alleviate aortic intimal hyperplasia, inflammatory cell infiltration, and hepatic steatosis. Finally, the combination of PD and PSP inhibit the expression of TLR4, MyD88, and the phosphorylation level of NF-κB p65 protein in the aorta. Conclusions. Polydatin synergizes with P. sibiricum polysaccharides in preventing the development of atherosclerosis in ApoE–/– mice by inhibiting the TLR4/MyD88/NF-κB signaling pathway.
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Ye et al. (2022) studied Atherosclerosis (n=40). Polydatin and Polygonatum sibiricum polysaccharides vs. Model group (high-fat diet) was evaluated on Serum lipids, cell adhesion molecules, and lipid accumulation. The combination of polydatin and P. sibiricum polysaccharides significantly inhibited serum lipids, cell adhesion molecules, and lipid accumulation in ApoE-/- mice.
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