Ginsenoside Rb1 Enhances Plaque Stability and Inhibits Adventitial Vasa Vasorum via the Modulation of miR-33 and PEDF

Abstract

Background: Atherosclerosis is closely associated with proliferation of the adventitial vasa vasorum, leading to the atherosclerotic plaque progression and vulnerability. In this report, we investigated the role of Ginsenoside Rb1 (Rb1) on atherosclerotic plaque stabilization and adventitial vasa vasorum (VV) along with the mechanisms involved.Methods and Results: Apolipoprotein E-deficient (ApoE−/−) mice were fed with a high-fat diet for 20 weeks, and then Ginsenoside Rb1 (50 mg/kg/d, intraperitoneal) was given for 4 weeks. Rb1 treatment significantly inhibited adventitial VV proliferation, alleviated inflammation, decreased plaque burden, and stabilized atherosclerotic plaques in apoE−/− mice. However, the beneficial effects of Rb1 on atherosclerotic lesion was attenuated by overexpression of miR-33. The analysis from atherosclerotic plaque revealed that Rb1 treatment could result in an induction of Pigment epithelium-derived factor (PEDF) expression and reduction of the miR-33 generation. Overexpression of miR-33 significantly reverted the Rb1-mediated elevation of PEDF and anti-angiogenic effect.Conclusions: Ginsenoside Rb1 attenuates plaque growth and enhances plaque stability partially through inhibiting adventitial vasa vasorum proliferation and inflammation in apoE−/− mice. The anti-angiogenic and anti-inflammation effects of Rb1 are exerted via the modulation of miR-33 and its target gene PEDF.

Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases

“…Berberine exerted its protective effects on KD-induced apoptosis of human coronary artery endothelial cells by inhibiting oxidative and ER stress ( Xu et al, 2020 ). Endothelial cell apoptosis induced by ER stress is closely linked with plaque progression, which can contribute to unstable atherosclerotic plaques, perhaps in response to thrombosis in atherosclerosis ( Yang et al, 2021 ). Homocysteine increases damage to vascular endothelial cells, thereby reducing vasodilation factors released by endothelial cells and impairing vasodilation in the endothelium, resulting in vascular endothelial apoptosis and inducing oxidation ( Salvio et al, 2021 ).…”

Advances in the Bioactivities of Phytochemical Saponins in the Prevention and Treatment of Atherosclerosis

“…Furthermore, ginsenoside Rb1 promoted atherosclerotic plaque stability via facilitating anti-inflammatory M2 macrophage polarization, which is achieved partly by elevating the production of interleukin (IL)-4 and/or IL-13 and the phosphorylation of signal transducer and activator of transcription 6 (STAT6) [ 30 ]. Ginsenoside Rb1 attenuated plaque growth and enhanced plaque stability partially by inhibiting adventitial vasa vasorum proliferation and inflammation in ApoE −/− mice [ 31 ]. Ginsenoside Rb1 inhibited vascular calcification as a selective androgen receptor modulator as evidenced by exhibiting inhibitory effects on vascular smooth muscle cells (VSMCs) calcification through androgen receptor-mediated Gas6 transactivation and antagonistic effects in prostate cancer cells [ 32 ].…”

“…Glycyrrhizin (or glycyrrhizic acid) belongs to the pentacyclic triterpenoid saponins and is a component rich in glycyrrhiza, which is famous as beet root or as a herbaceous plant [ 17 ]. The glycyrrhizin-containing Chinese herb XinNaoKang effectively alleviated AS by improving cecal microbiota and lipid metabolism in atherosclerotic mice [ 31 ]. Glycyrrhizin is one of the major bioactive components of Ger-Gen-Chyn-Lian-Tang (GGCLT), an officially standardized mixture of Chinese herbal medicines.…”

Excessive Adventitial and Perivascular Vascularisation Correlates with Vascular Inflammation and Intimal Hyperplasia

“…Albeit VV are indispensable for vascular physiology, a mutual interconnection between angiogenesis and inflammation propelled the seminal research on their role in vascular disease. Studies on hypercholesterolemic animals found that growth of VV networks precedes the development of the atherosclerotic lesions [ 7 , 8 ], and VV expansion is intimately associated with neointimal remodeling [ 9 , 10 ], while anti-angiogenic therapies inhibited intimal hyperplasia (IH) [ 11 ] and plaque growth [ 12 , 13 , 14 ]. In addition to VV, murine and rat adventitia and perivascular adipose tissue include myeloperoxidase-positive (MPO + ) clusters indicative of vascular inflammation [ 15 , 16 , 17 , 18 , 19 ], yet an association between the development of MPO + clusters and VV sprouting remains elusive.…”