Integrative Atherosclerosis Treatment: Harnessing Herbal and Synthetic HMGB1 Inhibitors

Human group box protein 1 (HMGB1) is a nuclear protein critical in various cellular processes. It is released in response to stress, infection, or tissue damage and acts as a danger signal, triggering immunological responses. Elevated HMGB1 levels are linked to various diseases, including atherosclerosis. This review investigated the role of HMGB1 in atherosclerosis and assessed the effectiveness of current and emerging treatment approaches that target HMGB1. Data was obtained from various indexed scientific databases. The inclusion and exclusion criteria were based on the relevance to atherosclerosis and HMGB1, the types of intervention (herbal, synthetic, and experimental compounds), the mechanism of action, and the outcome measured (inflammatory markers, cellular responses, and atherosclerotic plaque evolution). The findings present a promising future for atherosclerosis treatment, with herbal extracts, and experimental and synthetic compounds showing significant potential in preclinical studies. Herbal compounds like glycyrrhizin, ginsenosides, and mogrosides demonstrate anti-inflammatory and antioxidant properties. Synthetic drugs like metformin, statins, and sodium-glucose transporter inhibitors (SGLT2) show significant promise by modulating HMGB1 activity and related pathways. Additionally, monoclonal antibodies and specific inhibitors targeting toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), and receptors of advanced glycated endpoints (RAGE) show potential for reducing vascular inflammation. Atherosclerosis is a multifaceted condition that requires a comprehensive approach, including cholesterol-lowering therapy. However, to fully harness the potential of HMGB1-targeted treatments, further research and clinical trials are necessary. These trials will be crucial in developing HMGB1-targeted therapies as effective adjuvants to cholesterol-targeting compounds in managing cardiovascular diseases.