Systematic review on effectiveness of flavonoids against hypercholesterolemia: Insights from in-silico, in-vitro, and in-vivo studies

• Flavonoids from natural products reduce hypercholesterolemia anti-oxidant and anti-inflammatory. • Flavonoids identify the effectiveness through In-Silico, In-vitro, and In-vivo study. • Natural products specifically flavonoids maintaining high-density lipoprotein cholesterol level (good cholesterol), while lowering low-density lipoprotein cholesterol level (bad cholesterol), very-low-density lipoprotein cholesterol, total cholesterol, and triglyceride. • It shows evidence increasing anti-oxidant in DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, Glutathione peroxidase (GPx), and Superoxide dismutase (SOD) activities. Abnormal cholesterol levels have been linked to one of modifiable risk factor called hypercholesterolemia and attributable risk of developing cardiovascular disease (CVD). Flavonoids from natural products have shown beneficial to treat hypercholesterolemia and it is believed having minimal side effects. Nevertheless, the finding of these studies is still controversial to study the effectiveness of flavonoids against hypercholesterolemia through preclinical studies; in-silico, in-vitro, and in-vivo. As a result, we carried out a systematic review to identify the effectiveness and relationship between cholesterol level and flavonoids through three study of in-silico, in-vitro and in-vivo. A comprehensive search for all study design of flavonoids was carried out up to 2023 using pertinent keywords in databases in Pubmed, Hindawi and ScienceDirect. The results showed that flavonoids from different natural products considerable raised or maintaining serum high-density lipoprotein cholesterol (HDL-C) while lowering the blood cholesterol level of low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein (VLDL), total cholesterol (TC) and triglyceride (TG). Additionally, flavonoids showed evidence in increasing anti-oxidant activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH), Glutathione peroxidase (GPx), Superoxide dismutase (SOD) activities. Furthermore, flavonoids promote lowering lipid synthesis in 3T3-L1 adipocytes. Meanwhile, in-silico approaches show evidence of flavonoids interact with two human proteins 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and human pancreatic α-amylase (HPA) with binding energy values ranging from -7.3 to -9.5kcal/mol. The overall results confirm that flavonoids decrease the cholesterol level and risk of CVD. Hence, giving evidence that flavonoids is having potential in treating the hypercholesterolemia.