<i>Whitmania Pigra</i> Whitman Extracts Inhibit Lipopolysaccharide Induced Rat Vascular Smooth Muscle Cells Migration and their Adhesion Ability to THP-1 and RAW 264.7 Cells

Abstract

Aim: Atherosclerosis is a kind of chronic inflammatory disease. A crucial pathology change of atherosclerosis is the migration of activated VSMCs to the intima where they interact with leukocytes by expressing adhesion molecules, including intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, monocyte chemoattractant protein-1 (MCP-1) expressed by VSMCs plays an important role in recruiting monocytes and macrophages. Leech (Whitmania pigra Whitman) is a traditional Chinese medicine to treat cardiovascular diseases including atherosclerosis, however previous research has rarely reported the molecular mechanism for its curative effect. Thus, our study focuses on the effects of leech extracts on the expression of inflammatory factors, adhesion molecules and MCP-1 in rat VSMCs.Methods: In our present study, wound-healing assay and Boyden chamber model were applied to evaluate the anti-migration effect of LEE (Leech Enzyme Extracts) on LPS induced VSMCs. The anti-adhesion effect was assessed using DiI-labeled THP-1 and RAW264.7.Results: LEE suppressed LPS-induced VSMCs migration and decreased the chemotaxis and adhesive capacity of THP-1 and RAW264.7 to LPS-stimulated VSMCs. LEE also attenuated the upregulation of a variety of pro-atherosclerotic factors by inhibiting the phosphorylation of p38 MAPK. LEE was also observed to prevent NF-κB p65 nuclear localization using immune-fluorescent staining.Conclusions: In conclusion, LEE suppresses LPS-induced upregulation of inflammatory factors, adhesion molecules and MCP-1 in rat VSMCs mainly via inhibiting the p38 MAPK/NF-κB pathways, thus partly uncovered LEE's molecular mechanisms for its therapeutic effect on atherosclerosis.

Soluble Vascular Cell Adhesion Molecules May be Protective of Future Cardiovascular Disease Risk: Findings from the PREVEND Prospective Cohort Study

“…Though previous studies conducted in general population settings have failed to demonstrate any statistically significant association of VCAM-1 with CVD risk, an increased risk of CVD with elevated levels of VCAM-1 has been suggested, given that circulating levels of other soluble adhesion molecules (such as E-selectin, P-selectin, or ICAM-1) have been found to be positively and independently associated with CVD outcomes 16 , 19 – 24 ) . Indeed, the therapeutic effect of leech enzyme extract on atherosclerosis (a traditional Chinese medicine commonly used for treating CVD) has been shown to be manifested via inhibiting the expression of adhesion molecules such as ICAM-1 and VCAM-1 49 ) . The mechanistic pathways for the link between elevated VCAM-1 levels and its protective effect on the development of CVD are unclear, as increased expression of soluble adhesion molecules have been suggested to play a direct role in the pathogenesis of atherosclerosis 50 ) via endothelial dysfunction and inflammation.…”

Nutraceuticals for prevention of atherosclerosis: Targeting monocyte infiltration to the vascular endothelium

“…Although NF‐κB has a central role in monocyte adhesion to the vascular endothelium via transcription of inflammatory mediators, multiple lines of study suggest that MAPKs also play an important role in NF‐κB‐dependent and ‐independent adhesion events in early atherosclerosis. A recent study showed that Whitmania pigra Whitman suppresses the expression of adhesion molecules (e.g., ICAM‐1 and VCAM‐1), the phosphorylation of p38, and p65 nuclear localization (Li et al, 2017). Liu et al suggested that matrine downregulates IkBα phosphorylation, which inhibits the expression of adhesion molecules including VCAM‐1 and ICAM‐1 by suppressing MAPKs and p65 translocation from the cytosol to the nucleus (Liu et al, 2016).…”

Clinical Effect of Traditional Chinese Medicine Shenhuang Granule in Critically Ill Patients with COVID-19: A Single-Centered, Retrospective, Observational Study

“…Aconiti Lateralis Radix Praeparata shows a significant effect in rheumatoid arthritis by inhibiting the concentrations of IL-1β, TNF-α, and IFN-γ [18]. Whitmania pigra Whitman has been widely employed in decoction for the treatment of blood stasis syndrome for many years in China and its enzyme extracts suppress LPS-induced upregulation of inflammatory factors in rat vascular smooth muscle cells [19]. These pre-clinical and clinical studies indicated that some herbs of SHG could directly kill bacteria and inhibit viruses while other herbs could regulate inflammation response and maintain a balance between pro-inflammatory and anti-inflammatory mediators, with no serious adverse reactions observed [13][14][15][16][17][18][19].…”